Aromatic prodrugs of propofol, compositions and uses thereof   

Disclosed herein are prodrugs of propofol, methods of making prodrugs of propofol, pharmaceutical compositions of prodrugs of propofol and methods of using prodrugs of propofol and pharmaceutical compositions thereof to treat or prevent diseases or disorders such as migraine headache pain and post-chemotherapy or post-operative surgery nausea and vomiting.

Propofol (2,6-diisopropylphenol), (1), is a low molecular weight phenol that is widely used as an intravenous sedative-hypnotic agent in the induction and maintenance of anesthesia and/or sedation in mammals. The advantages of propofol as an anesthetic include rapid onset of anesthesia, rapid clearance, and minimal side effects (Langley et al., Drugs 1988, 35, 334-372). Propofol may mediate hypnotic effects through interaction with the GABAA receptor complex, a heterooligomeric ligand-gated chloride ion channel (Peduto et al., Anesthesiology 1991, 75, 1000-1009.).

Propofol is rapidly metabolized in mammals with the drug being eliminated predominantly as glucuronidated and sulfated conjugates of propofol and 4-hydroxypropofol (Langley et al., Drugs 1988, 35, 334-372). Propofol clearance exceeds liver blood flow, which indicates that extrahepatic tissues contribute to the overall metabolism of the drug. Human intestinal mucosa glucuronidates propofol in vitro and oral dosing studies in rats indicate that approximately 90% of the administered drug undergoes first pass metabolism, with extraction by the intestinal mucosa accounting for the bulk of this presystemic elimination (Raoof et al., Pharm. Res. 1996, 13, 891-895). Accordingly, oral administration of propofol is of little therapeutic utility because of extensive first-pass metabolism.

Propofol has a broad range of biological and medical applications, which are evident at sub-anesthetic doses and include treatment and/or prevention of intractable migraine headache pain (Krusz et al., Headache 2000, 40, 224-230; Krusz, International Publication No. WO 00/54588). Propofol, when used to maintain anesthesia, causes a lower incidence of post-operative nausea and vomiting (“PONV”) in comparison to common inhalational anesthetic agents; numerous controlled clinical studies support the anti-emetic activity of propofol (Tramer et al., Br. J. Anaesth. 1997, 78, 247-255; Brooker et al., Anaesth. Intensive Care 1998, 26, 625-629; Gan et al., Anesthesiology 1997, 87, 779-784). Propofol also has anti-emetic activity when used in conjunction with chemotherapeutic compounds (Phelps et al., Ann. Pharmacother. 1996, 30, 290-292; Borgeat et al., Oncology 1993, 50, 456-459; Borgeat et al., Can. J. Anaesth. 1994, 41, 1117-1119; Tomioka et al., Anesth. Analg. 1999, 89, 798-799). Nausea, retching and/or vomiting induced by a variety of chemotherapeutic agents (e.g., cisplatin, cyclophosphamide, 5-fluorouracil, methotrexate, anthracycline drugs, etc.) has been controlled by low-dose propofol infusion in patients refractory to prophylaxis with conventional anti-emetic drugs (e.g., serotonin antagonists and corticosteroids).

Propofol may also be used to treat patients with refractory status epilepticus (Brown et al., Pharmacother. 1998, 32, 1053-1059; Kuisma et al., Epilepsia 1995, 36, 1241-1243; Walder et al., Neurology 2002, 58, 1327-1332; Sutherland et al., Anaesth. Intensive Care 1994, 22, 733-737). Further, the anticonvulsant effects of propofol have also been demonstrated in rat efficacy models at sub-anesthetic doses (Holtkamp et al., Ann. Neurol. 2001, 49, 260-263; Hasan et al., Pharmacol. Toxicol. 1994, 74, 50-53).

Propofol may also be used as an antioxidant (Murphy et al., Br. J. Anaesth. 1992, 68, 613-618; Sagara et al., J. Neurochem. 1999, 73, 2524-2530; Young et al., Eur. J. Anaesthesiol. 1997, 14, 320-326; Wang et al. Eur. J. Pharmacol. 2002, 452, 303-308). Propofol, at doses typically used for surgical anesthesia, has observable antioxidant effects in humans (De la Cruz et al., Anesth. Analg. 1999, 89, 1050-1055). Pathogenesis or subsequent damage pathways in various neurodegenerative diseases involve reactive oxygen species and accordingly may be treated or prevented with antioxidants (Simonian et al., Pharmacol. Toxicol. 1996, 36, 83-106). Examples of specific neurodegenerative diseases which may be treated or prevented with anti-oxidants include, but are not limited to, Friedrich\'s disease, Parkinson\'s disease, Alzheimer\'s disease, Huntington\'s disease, amyotrophic lateral sclerosis (“ALS”), multiple sclerosis (“MS”), Pick disease, inflammatory diseases and diseases caused by inflammatory mediators such as tumor necrosis factor (TNF) and IL-1.

A significant problem with the therapeutic use of propofol is its lack of appreciable solubility in water. Accordingly, propofol must be specially formulated in aqueous media using solubilizers or emulsifiers (Briggs et al., Anaesthesia 1982, 37, 1099-1101). For example, in a current commercial product (Diprivan®, Astra-Zeneca) an oil-in-water emulsion (the emulsifier is the lecithin mixture Intralipid®), is used to formulate propofol (Picard et al., Anesth. Analg. 2000, 90, 963-969).

One potential solution to the insolubility of propofol in aqueous solution, which avoids the use of additives, solubilizers or emulsifiers, is a water-soluble, stable propofol prodrug that is converted to propofol in vivo. (Hendler et al., International Publication No. WO 99/58555; Morimoto et al., International Publication No. WO 00/48572; Hendler et al., U.S. Pat. No. 6,254,853; Stella et al., United States Patent Application No. US2001/0025035; Hendler, U.S. Pat. No. 6,362,234; International Publication No. WO 02/13810; Sagara et al., J. Neurochem. 1999, 73, 2524-2530; Banaszczyk et al., Anesth. Analg. 2002, 95, 1285-1292; Trapani et al., Int. J. Pharm. 1998, 175, 195-204; Trapani et al., J. Med. Chem. 1998, 41, 1846-1854; Anderson et al., J. Med. Chem. 2001, 44, 3582-3591; Pop et al., Med. Chem. Res. 1992, 2, 16-21). A significant problem with existing propofol prodrugs is their stability under physiological conditions, which prevents release of therapeutically significant concentrations of propofol, particularly when the prodrug is orally administered. Thus, there is a need for propofol prodrugs, which are sufficiently labile under physiological conditions to provide therapeutically significant concentrations of propofol, particularly, when the prodrug is orally administered.

SUMMARY

These and other needs are met by providing prodrugs of propofol, methods of making prodrugs of propofol, pharmaceutical compositions of prodrugs of propofol and methods of using prodrugs of propofol and pharmaceutical compositions thereof to treat or prevent diseases or disorders such as migraine headache pain, neurodegenerative disorders and post-chemotherapy or post-operative surgery nausea and vomiting. In some embodiments, prodrugs of propofol and pharmaceutical compositions thereof are orally administered. In other embodiments, prodrugs of propofol are translocated across the gastrointestinal mucosa via interaction with transporter proteins expressed within enterocytes lining the gastrointestinal tract.

In a first aspect, a compound of structural Formula (I) is provided:

or pharmaceutically acceptable salts, hydrates, solvates or N-oxides thereof, wherein:

n is 0 or 1;

Y is selected from the group consisting of a bond, CR1R2, NR3, O and S;

A is CR4 or N;

B is CR5 or N;

D is CR6 or N;

E is CR7 or N;

G is CR8 or N;

R18 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxycarbonyl, aryl, substituted aryl, arylalkyl, carbamoyl, substituted carbamoyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, heteroaryl, substituted heteroaryl and heteroarylalkyl;

R1 and R2 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, heteroaryl, substituted heteroaryl and heteroarylalkyl;

R3 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, arylalkyl, cycloalkyl and heteroaryl;

R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl, substituted heteroaryl, heteroarylalkyl, hydroxyl and —W[C(O)]kZ(CR9R10)rCO2R11;

R5 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl, substituted heteroaryl, heteroarylalkyl, hydroxyl and —W[C(O)]kZ(CR9R10)rCO2R11;

R6 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl, substituted heteroaryl, heteroarylalkyl, hydroxyl and —W[C(O)]kZ(CR9R10)rCO2R11;

R7 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl, substituted heteroaryl, heteroarylalkyl, hydroxyl and —W[C(O)]kZ(CR9R10)rCO2R11;

R8 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl, substituted heteroaryl, heteroarylalkyl, hydroxyl and —W[C(O)]kZ(CR9R10)rCO2R11;

W is selected from the group consisting of a bond, CR12R13, NR14, O and S;

Z is selected from the group consisting of CR15R16, NR17, O and S;

k is 0 or 1;

r is 1, 2 or 3;

each of R9, R10, R11, R12, R13, R15 and R16 is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, heteroaryl, substituted heteroaryl and heteroarylalkyl;

R14 and R17 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, arylalkyl, cycloalkyl and heteroaryl;

with the provisos that:

at least one of A, B, D, E and G is not N;

one and only one of R4, R5, R6, R7 or R8 is —W[C(O)]kZ(CR9R10)rCO2R11;

and if k is 0 then W is a bond.

In a second aspect pharmaceutical compositions are provided, which generally comprise one or more compounds disclosed herein, and a pharmaceutically acceptable vehicle such as a diluent, carrier, excipient or adjuvant. The choice of diluent, carrier, excipient and adjuvant will depend upon, among other factors, the desired mode of administration. In some embodiments, the mode of administration is oral.

In a third aspect, methods for treating or preventing various diseases or disorders including, but not limited to migraine headache pain, post-chemotherapy or post-operative surgery nausea and vomiting and neurodegenerative disorders (e.g., epilepsy, Friedrich\'s disease, Parkinson\'s disease, Alzheimer\'s disease, Huntington\'s disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Pick disease) are provided. The methods generally involve administering to a patient in need of such treatment or prevention a therapeutically effective amount of a compound disclosed herein and/or pharmaceutical compositions thereof.

In a fourth aspect, methods for inducing and/or maintaining anesthesia or sedation in a mammal are provided. The methods generally involve administering to a patient in need of such anesthesia sedation induction and/or maintenance a therapeutically effective amount of a compound disclosed herein and/or pharmaceutical compositions thereof.

DETAILED DESCRIPTION

“Alkyl” by itself or as part of another substituent refers to a saturated or unsaturated, branched, straight-chain or cyclic monovalent hydrocarbon radical derived by the removal of one hydrogen atom from a single carbon atom of a parent alkane, alkene or alkyne. Typical alkyl groups include, but are not limited to, methyl; ethyls such as ethanyl, ethenyl, ethynyl; propyls such as propan-1-yl, propan-2-yl, cyclopropan-1-yl, prop-1-en-1-yl, prop-1-en-2-yl, prop-2-en-1-yl (allyl), cycloprop-1-en-1-yl; cycloprop-2-en-1-yl, prop-1-yn-1-yl, prop-2-yn-1-yl, etc.; butyls such as butan-1-yl, butan-2-yl, 2-methyl-propan-1-yl, 2-methyl-propan-2-yl, cyclobutan-1-yl, but-1-en-1-yl, but-1-en-2-yl, 2-methyl-prop-1-en-1-yl, but-2-en-1-yl, but-2-en-2-yl, buta-1,3-dien-1-yl, buta-1,3-dien-2-yl, cyclobut-1-en-1-yl, cyclobut-1-en-3-yl, cyclobuta-1,3-dien-1-yl, but-1-yn-1-yl, but-1-yn-3-yl, but-3-yn-1-yl, etc.; and the like.

The term “alkyl” is specifically intended to include groups having any degree or level of saturation, i.e., groups having exclusively single carbon-carbon bonds, groups having one or more double carbon-carbon bonds, groups having one or more triple carbon-carbon bonds and groups having mixtures of single, double and triple carbon-carbon bonds. Where a specific level of saturation is intended, the expressions “alkanyl,” “alkenyl,” and “alkynyl” are used. In some embodiments, an alkyl group comprises from 1 to 20 carbon atoms. In other embodiments, an alkyl group comprises from 1 to 10 carbon atoms. In still other embodiments, an alkyl group comprises from 1 to 10 carbon atoms.

“Alkanyl” by itself or as part of another substituent refers to a saturated branched, straight-chain or cyclic alkyl radical derived by the removal of one hydrogen atom from a single carbon atom of a parent alkane. Typical alkanyl groups include, but are not limited to, methanyl; ethanyl; propanyls such as propan-1-yl, propan-2-yl (isopropyl), cyclopropan-1-yl, etc.; butanyls such as butan-1-yl, butan-2-yl (sec-butyl), 2-methyl-propan-1-yl (isobutyl), 2-methyl-propan-2-yl (t-butyl), cyclobutan-1-yl, etc.; and the like.

“Alkenyl” by itself or as part of another substituent refers to an unsaturated branched, straight-chain or cyclic alkyl radical having at least one carbon-carbon double bond derived by the removal of one hydrogen atom from a single carbon atom of a parent alkene. The group may be in either the cis or trans conformation about the double bond(s). Typical alkenyl groups include, but are not limited to, ethenyl; propenyls such as prop-1-en-1-yl, prop-1-en-2-yl, prop-2-en-1-yl (allyl), prop-2-en-2-yl, cycloprop-1-en-1-yl; cycloprop-2-en-1-yl; butenyls such as but-1-en-1-yl, but-1-en-2-yl, 2-methyl-prop-1-en-1-yl, but-2-en-1-yl, but-2-en-1-yl, but-2-en-2-yl, buta-1,3-dien-1-yl, buta-1,3-dien-2-yl, cyclobut-1-en-1-yl, cyclobut-1-en-3-yl, cyclobuta-1,3-dien-1-yl, etc.; and the like.

“Alkynyl” by itself or as part of another substituent refers to an unsaturated branched, straight-chain or cyclic alkyl radical having at least one carbon-carbon triple bond derived by the removal of one hydrogen atom from a single carbon atom of a parent alkyne. Typical alkynyl groups include, but are not limited to, ethynyl; propynyls such as prop-1-yn-1-yl, prop-2-yn-1-yl, etc.; butynyls such as but-1-yn-1-yl, but-1-yn-3-yl, but-3-yn-1-yl, etc.; and the like.

“Acyl” by itself or as part of another substituent refers to a radical —C(O)R30, where R30 is hydrogen, alkyl, cycloalkyl, cycloheteroalkyl, aryl, arylalkyl, heteroalkyl, heteroaryl, heteroarylalkyl as defined herein. Representative examples include, but are not limited to formyl, acetyl, cyclohexylcarbonyl, cyclohexylmethylcarbonyl, benzoyl, benzylcarbonyl and the like.

“Alkoxy” by itself or as part of another substituent refers to a radical —OR31 where R31 represents an alkyl or cycloalkyl group as defined herein. Representative examples include, but are not limited to, methoxy, ethoxy, propoxy, butoxy, cyclohexyloxy and the like.

“Alkoxycarbonyl” by itself or as part of another substituent, refers to a radical —C(O)OR31 where R3 is as defined above.

“Aryl” by itself or as part of another substituent refers to a monovalent aromatic hydrocarbon radical derived by the removal of one hydrogen atom from a single carbon atom of a parent aromatic ring system. Typical aryl groups include, but are not limited to, groups derived from aceanthrylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, coronene, fluoranthene, fluorene, hexacene, hexaphene, hexylene, as-indacene, s-indacene, indane, indene, naphthalene, octacene, octaphene, octalene, ovalene, penta-2,4-diene, pentacene, pentalene, pentaphene, perylene, phenalene, phenanthrene, picene, pleiadene, pyrene, pyranthrene, rubicene, triphenylene, trinaphthalene and the like. In some embodiment, an aryl group comprises from 6 to 20 carbon atoms. In other embodiments, and aryl group comprises from 6 to 12 carbon atoms.

“Arylalkyl” by itself or as part of another substituent refers to an acyclic alkyl radical in which one of the hydrogen atoms bonded to a carbon atom, typically a terminal or sp3 carbon atom, is replaced with an aryl group. Typical arylalkyl groups include, but are not limited to, benzyl, 2-phenylethan-1-yl, 2-phenylethen-1-yl, naphthylmethyl, 2-naphthylethan-1-yl, 2-naphthylethen-1-yl, naphthobenzyl, 2-naphthophenylethan-1-yl and the like. Where specific alkyl moieties are intended, the nomenclature arylalkanyl, arylalkenyl and/or arylalkynyl is used. In some embodiments, an arylalkyl group is (C6-C30) arylalkyl, e.g., the alkanyl, alkenyl or alkynyl moiety of the arylalkyl group is (C1-C10) and the aryl moiety is (C6-C20). In other embodiments, an arylalkyl group is (C6-C20) arylalkyl, e.g., the alkanyl, alkenyl or alkynyl moiety of the arylalkyl group is (C1-C8) and the aryl moiety is (C6-C12).

“Carbamoyl” by itself or as part of another substituent refers to the radical —C(O)N(R32)R33 where R32 and R33 are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroarylalkyl, substituted heteroarylalkyl, heteroaryl or substituted heteroaryl, as defined herein.

“Compounds” refers to compounds encompassed by the generic formulae disclosed herein and includes any specific compounds within those formulae whose structure is disclosed herein. Compounds may be identified either by their chemical structure and/or chemical name. When the chemical structure and chemical name conflict, the chemical structure is determinative of the identity of the compound. Compounds disclosed herein may contain one or more chiral centers and/or double bonds and therefore, may exist as stereoisomers, such as double-bond isomers (i.e., geometric isomers), enantiomers or diastereomers. Accordingly, when stereochemistry at chiral centers is not specified, the chemical structures depicted herein encompass all possible configurations at those chiral centers including the stereoisomerically pure form (e.g., geometrically pure, enantiomerically pure or diastereomerically pure) and enantiomeric and stereoisomeric mixtures. Enantiomeric and stereoisomeric mixtures can be resolved into their component enantiomers or stereoisomers using separation techniques or chiral synthesis techniques well known to the skilled artisan. Compounds disclosed herein may also exist in several tautomeric forms including the enol form, the keto form and mixtures thereof. Accordingly, the chemical structures depicted herein encompass all possible tautomeric forms of the illustrated compounds. Compounds disclosed herein also include isotopically labeled compounds where one or more atoms have an atomic mass different from the atomic mass conventionally found in nature. Examples of isotopes that may be incorporated into the compounds disclosed herein include, but are not limited to, 2H, 3H, 11C, 13C, 14C, 15N, 17O and 18O. Compounds disclosed herein may exist in unsolvated forms as well as solvated forms, including hydrated forms and as N-oxides. In general, the hydrated, solvated and N-oxide forms are within the scope of the present disclosure. Certain compounds disclosed herein may exist in multiple crystalline or amorphous forms. In general, all physical forms are equivalent for the uses contemplated herein and are intended to be within the scope of the present disclosure. Further, it should be understood, when partial structures of compounds are illustrated, that brackets indicate the point of attachment of the partial structure to the rest of the molecule.

“Cycloalkyl” by itself or as part of another substituent refers to a saturated or unsaturated cyclic alkyl radical. Where a specific level of saturation is intended, the nomenclature “cycloalkanyl” or “cycloalkenyl” is used. Typical cycloalkyl groups include, but are not limited to, groups derived from cyclopropane, cyclobutane, cyclopentane, cyclohexane, and the like. Preferably, the cycloalkyl group is (C3-C10) cycloalkyl, more preferably (C3-C7) cycloalkyl.

“Cycloheteroalkyl” by itself or as part of another substituent refers to a saturated or unsaturated cyclic alkyl radical in which one or more carbon atoms (and any associated hydrogen atoms) are independently replaced with the same or different heteroatom. Typical heteroatoms to replace the carbon atom(s) include, but are not limited to, N, P, O, S, Si, etc. Where a specific level of saturation is intended, the nomenclature “cycloheteroalkanyl” or “cycloheteroalkenyl” is used. Typical cycloheteroalkyl groups include, but are not limited to, groups derived from epoxides, azirines, thiiranes, imidazolidine, morpholine, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, and the like.

“Heteroalkyl, Heteroalkanyl, Heteroalkenyl and Heteroalkynyl” by themselves or as part of another substituent refer to alkyl, alkanyl, alkenyl and alkynyl groups, respectively, in which one or more of the carbon atoms (and any associated hydrogen atoms) are independently replaced with the same or different heteroatomic groups. Typical heteroatomic groups which can be included in these groups include, but are not limited to, —O—, —S—, —O—O—, —S—S—, —O—S—, —NR34R35—, ═N—N═, —N═N—, —N═N—NR36R37, —PR38—, —P(O)2—, —POR39—, —O—P(O)2—, —SO—, —SO2—, —SnR40R41— and the like, where R34, R35, R36, R37, R38, R39, R40 and R41 are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl.

“Heteroaryl” by itself or as part of another substituent refers to a monovalent heteroaromatic radical derived by the removal of one hydrogen atom from a single atom of a parent heteroaromatic ring system. Typical heteroaryl groups include, but are not limited to, groups derived from acridine, arsindole, carbazole, β-carboline, chromane, chromene, cinnoline, furan, imidazole, indazole, indole, indoline, indolizine, isobenzofuran, isochromene, isoindole, isoindoline, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, perimidine, phenanthridine, phenanthroline, phenazine, phthalazine, pteridine, purine, pyran, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolizine, quinazoline, quinoline, quinolizine, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazole, xanthene, and the like. In some embodiments, the heteroaryl group is from 5-20 membered heteroaryl. In other embodiments, the heteroaryl group is from 5-10 membered heteroaryl. Preferred heteroaryl groups are those derived from thiophene, pyrrole, benzothiophene, benzofuran, indole, pyridine, quinoline, imidazole, oxazole and pyrazine.

“Heteroarylalkyl” by itself or as part of another substituent refers to an acyclic alkyl radical in which one of the hydrogen atoms bonded to a carbon atom, typically a terminal or sp3 carbon atom, is replaced with a heteroaryl group. Where specific alkyl moieties are intended, the nomenclature heteroarylalkanyl, heteroarylalkenyl and/or heteroarylalkynyl is used. In some embodiments, the heteroarylalkyl group is a 6-30 membered heteroarylalkyl, e.g., the alkanyl, alkenyl or alkynyl moiety of the heteroarylalkyl is 1-10 membered and the heteroaryl moiety is a 5-20-membered heteroaryl. In other embodiments, the heteroarylalkyl group is 6-20 membered heteroarylalkyl, e.g., the alkanyl, alkenyl or alkynyl moiety of the heteroarylalkyl is 1-8 membered and the heteroaryl moiety is a 5-12-membered heteroaryl.

“Parent Aromatic Ring System” refers to an unsaturated cyclic or polycyclic ring system having a conjugated π electron system. Specifically included within the definition of “parent aromatic ring system” are fused ring systems in which one or more of the rings are aromatic and one or more of the rings are saturated or unsaturated, such as, for example, fluorene, indane, indene, phenalene, etc. Typical parent aromatic ring systems include, but are not limited to, aceanthrylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, coronene, fluoranthene, fluorene, hexacene, hexaphene, hexylene, as-indacene, s-indacene, indane, indene, naphthalene, octacene, octaphene, octalene, ovalene, penta-2,4-diene, pentacene, pentalene, pentaphene, perylene, phenalene, phenanthrene, picene, pleiadene, pyrene, pyranthrene, rubicene, triphenylene, trinaphthalene and the like.

“Parent Heteroaromatic Ring System” refers to a parent aromatic ring system in which one or more carbon atoms (and any associated hydrogen atoms) are independently replaced with the same or different heteroatom. Typical heteroatoms to replace the carbon atoms include, but are not limited to, N, P, O, S, Si, etc. Specifically included within the definition of “parent heteroaromatic ring systems” are fused ring systems in which one or more of the rings are aromatic and one or more of the rings are saturated or unsaturated, such as, for example, arsindole, benzodioxan, benzofuran, chromane, chromene, indole, indoline, xanthene, etc. Typical parent heteroaromatic ring systems include, but are not limited to, arsindole, carbazole, β-carboline, chromane, chromene, cinnoline, furan, imidazole, indazole, indole, indoline, indolizine, isobenzofuran, isochromene, isoindole, isoindoline, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, perimidine, phenanthridine, phenanthroline, phenazine, phthalazine, pteridine, purine, pyran, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolizine, quinazoline, quinoline, quinolizine, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazole, xanthene, and the like.

“Pharmaceutical composition” refers to at least one compound disclosed herein and a pharmaceutically acceptable vehicle, with which the compound is administered to a patient.

“Pharmaceutically acceptable salt” refers to a salt of a compound disclosed herein, which possesses the desired pharmacological activity of the parent compound. Such salts include: (1) acid addition salts, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or formed with organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo[2.2.2]-oct-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, and the like; or (2) salts formed when an acidic proton present in the parent compound is replaced by a metal ion, e.g., an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic base such as ethanolamine, diethanolamine, triethanolamine, N-methylglucamine and the like.

“Pharmaceutically acceptable vehicle” refers to a diluent, adjuvant, excipient or carrier with which a compound is administered.

“Patient” includes humans. The terms “human” and “patient” are used interchangeably herein.

“Preventing” or “prevention” refers to a reduction in risk of acquiring a disease or disorder (i.e., causing at least one of the clinical symptoms of the disease not to develop in a patient that may be exposed to or predisposed to the disease but does not yet experience or display symptoms of the disease).

“Prodrug” refers to a derivative of a drug molecule that requires a transformation within the body to release the active drug. Prodrugs are frequently, although not necessarily, pharmacologically inactive until converted to the parent drug. A hydroxyl containing drug may be converted to, for example, to an ester, carbonate, acyloxyalkyl or a sulfonate prodrug, which may be hydrolyzed in vivo to provide the hydroxyl compound. Prodrugs for drugs with functional groups different than those listed above are well known to the skilled artisan.

“Promoiety” refers to a form of protecting group that when used to mask a functional group within a drug molecule converts the drug into a prodrug. Typically, the promoiety will be attached to the drug via bond(s) that are cleaved by enzymatic or non-enzymatic means in vivo.

“Protecting group” refers to a grouping of atoms that when attached to a reactive functional group in a molecule masks, reduces or prevents reactivity of the functional group. Examples of protecting groups can be found in Green et al., “Protective Groups in Organic Chemistry”, (Wiley, 2nd ed. 1991) and Harrison et al., “Compendium of Synthetic Organic Methods”, Vols. 1-8 (John Wiley and Sons, 1971-1996). Representative amino protecting groups include, but are not limited to, formyl, acetyl, trifluoroacetyl, benzyl, benzyloxycarbonyl (“CBz”), tert-butoxycarbonyl (“Boc”), trimethylsilyl (“TMS”), 2-trimethylsilyl-ethanesulfonyl (“SES”), trityl and substituted trityl groups, allyloxycarbonyl, 9-fluorenylmethyloxycarbonyl (“FMOC”), nitro-veratryloxycarbonyl (“NVOC”) and the like. Representative hydroxyl protecting groups include, but are not limited to, those where the hydroxyl group is either acylated or alkylated such as benzyl, and trityl ethers as well as alkyl ethers, tetrahydropyranyl ethers, trialkylsilyl ethers and allyl ethers.

“SMVT” refers to the sodium-dependent multivitamin transporter (SLC5A6). Genes encoding this transporter have been cloned from rat, human and rabbit tissue (see Prasad et al., J. Biol. Chem. 1998, 273, 7501-7506; Wang et al., J. Biol. Chem. 1999, 274, 14875-14883; Chatterjee et al., Am. J. Physiol. 1999, 277, C605-C613; Prasad et al., Arch. Biochem. Biophys. 1999, 366, 95-106).

“Substituted” refers to a group in which one or more hydrogen atoms are independently replaced with the same or different substituent(s). Typical substituents include, but are not limited to, -M, -R60, —O−, ═O, —OR60, —SR60, —S−, ═S, —NR60R61, ═NR60, —CF3, —CN, —OCN, —SCN, —NO, —NO2, ═N2, —N3, —S(O)2O−, —S(O)2OH, —S(O)2R60, —OS(O2)O−, —OS(O)2R60, —P(O)(O−)2, —P(O)(OR60)(O−), —OP(O)(OR60)(OR61), —C(O)R60, —C(S)R60, —C(O)OR60, —C(O)NR60R61—C(O)O−, —C(S)OR60, —NR62C(O)NR60R61, —NR62C(S)NR60R61, —NR62C(NR63)R60R61 and —C(NR62)NR60R61 where M is independently a halogen; R60, R61, R62 and R63 are independently hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl, or optionally R60 and R61 together with the nitrogen atom to which they are bonded form a cycloheteroalkyl or substituted cycloheteroalkyl ring; and R64 and R65 are independently hydrogen, alkyl, substituted alkyl, aryl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl, or optionally R64 and R65 together with the nitrogen atom to which they are bonded form a cycloheteroalkyl or substituted cycloheteroalkyl ring. Preferably, substituents include -M, -R60, ═O, —OR60, —SR60, —S−, ═S, —NR60R61, ═NR60, —CF3, —CN, —OCN, —SCN, —NO, —NO2, ═N2, —N3, —S(O)2R60, —OS(O2)O−, —OS(O)2R60, —P(O)(O−)2, P(O)(OR60)(O−), —OP(O)(OR60)(OR61), —C(O)R60, —C(S)R60, —C(O)OR60, —C(O)NR60R61, —C(O)O−, —NR62C(O)NR60R61, more preferably, -M, -R60, ═O, —OR60, —SR60, —NR60R61, —CF3, —CN, —NO2, —S(O)2R60, —P(O)(OR60)(O−), —OP(O)(OR60)(OR61), —C(O)R60, —C(O)OR60, —C(O)NR60R61, —C(O)O−, most preferably, -M, -R60, ═O, —OR60, —SR60, —NR60R61, —CF3, —CN, —NO2, —S(O)2R60, —OP(O)(OR60)(OR61), —C(O)R60, —C(O)OR60, —C(O)O−, where R60, R61 and R62 are as defined above.

“Transported by the SMVT transporter” refers to the translocation of a molecule across a membrane of a cell expressing the SMVT transporter. The translocation occurs through interaction with the transporter and is energized by cotransport of Na+ ions across the membrane.

“Treating” or “treatment” of any disease or disorder refers. In some embodiments, to ameliorating the disease or disorder (i.e., arresting or reducing the development of the disease or at least one of the clinical symptoms thereof). In other embodiments “treating” or “treatment” refers to ameliorating at least one physical parameter, which may not be discernible by the patient. In yet another embodiment, “treating” or “treatment” refers to inhibiting the disease or disorder, either physically, (e.g., stabilization of a discernible symptom), physiologically, (e.g., stabilization of a physical parameter), or both. In yet another embodiment, “treating” or “treatment” refers to delaying the onset of the disease or disorder.

“Therapeutically effective amount” means the amount of a compound that, when administered to a patient for treating a disease, is sufficient to effect such treatment for the disease. The “therapeutically effective amount” will vary depending on the compound, the disease and its severity and the age, weight, etc., of the patient to be treated.

Reference will now be made in detail to various embodiments of the invention. While the invention will be described in conjunction with these embodiments, it will be understood that it is not intended to limit the invention to those embodiments. To the contrary, it is intended to cover alternatives, modifications, and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims.

The compounds disclosed herein are prodrugs of propofol. In some embodiments, the compounds are orally administered. In some embodiments, the compounds are able to pass across the gastrointestinal tract. In other embodiments, prodrugs of propofol are translocated across the gastrointestinal mucosa via interaction with transporter proteins expressed within enterocytes lining the gastrointestinal tract.

In some embodiments, compounds of structural Formula (I) are provided:

or pharmaceutically acceptable salts, hydrates, solvates or N-oxides thereof, wherein:

n is 0 or 1;

Y is selected from the group consisting of a bond, CR1R2, NR3, O and S;

A is CR4 or N;

B is CR5 or N;

D is CR6 or N;

E is CR7 or N;

G is CR8 or N;

R18 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxycarbonyl, aryl, substituted aryl, arylalkyl, carbamoyl, substituted carbamoyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, heteroaryl, substituted heteroaryl and heteroarylalkyl;

R1 and R2 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, heteroaryl, substituted heteroaryl and heteroarylalkyl;

R3 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, arylalkyl, cycloalkyl and heteroaryl;

R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl, substituted heteroaryl, heteroarylalkyl, hydroxyl and —W[C(O)]kZ(CR9R10)rCO2R11;

R5 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl, substituted heteroaryl, heteroarylalkyl, hydroxyl and —W[C(O)]kZ(CR9R10)rCO2R11;

R6 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl, substituted heteroaryl, heteroarylalkyl, hydroxyl and —W[C(O)]kZ(CR9R10)rCO2R11;

R7 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl, substituted heteroaryl, heteroarylalkyl, hydroxyl and —W[C(O)]kZ(CR9R10)rCO2R11;

R8 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl, substituted heteroaryl, heteroarylalkyl, hydroxyl and —W[C(O)]kZ(CR9R10)rCO2R11;

W is selected from the group consisting of a bond, CR12R13, NR14, O and S;

Z is selected from the group consisting of CR15R16, NR17, O and S;

k is 0 or 1;

r is 1, 2 or 3;

each of R9, R10, R11, R12, R13, R15 and R16 is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, heteroaryl, substituted heteroaryl and heteroarylalkyl;

R14 and R17 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, arylalkyl, cycloalkyl and heteroaryl;

with the provisos that:

at least one of A, B, D, E and G is not N;

one and only one of R4, R5, R6, R7 or R8 is —W[C(O)]kZ(CR9R10)rCO2R11;

and if k is 0 then W is a bond.

In some embodiments of a compound of Formula (I), n is 0. In other embodiments of a compound of Formula (I), n is 1.

In still other embodiments of a compound of Formula (I), n is 1 and R18 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl and heteroaryl.

In the above embodiment, R18 is selected from the group consisting of hydrogen, alkyl and substituted alkyl. Preferably, R18 is selected from the group consisting of hydrogen and C1-4 alkyl. More preferably, R18 is hydrogen or methyl.

In the above embodiment, R18 is selected from the group consisting of hydrogen, aryl and substituted aryl. Preferably, R18 is selected from the group consisting of hydrogen, phenyl and substituted phenyl.

In the above embodiment, R18 is selected from the group consisting of hydrogen, arylalkyl and substituted arylalkyl. Preferably, R18 is selected from the group consisting of hydrogen, benzyl and substituted benzyl.

In still other embodiments of a compound of Formula (I), Y is a bond.

In still other embodiments of a compound of Formula (I), Y is CR1R2 and R1 and R2 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, arylalkyl, cycloalkyl and heteroaryl. Preferably, R1 and R2 are independently hydrogen or alkanyl. More preferably, R1 and R2 are independently hydrogen or methyl.

In still other embodiments of a compound of Formula (I), Y is NR3 and R3 is hydrogen or alkanyl. More preferably, R3 is hydrogen or methyl.

In still other embodiments of a compound of Formula (I), Y is O.

In still other embodiments of a compound of Formula (I), Y is S.

In still other embodiments of a compound of Formula (I), A is CR4. Preferably, R4 is selected from the group consisting of hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo, hydroxyl and —W[C(O)]kZ(CR9R10)rCO2R11. More preferably, R4 is hydrogen, C1-4 alkyl or —W[C(O)]kZ(CR9R10)rCO2R11. Preferably, R4 is —W[C(O)]kZ(CR9R10)rCO2R11 and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, arylalkyl, cycloalkyl and heteroaryl. Preferably, R9, R10, R12, R13, R14, R15, R16 and R17 are independently hydrogen or alkyl, and R11 is selected from the group consisting of hydrogen, C1-4 alkyl, phenyl, substituted phenyl, benzyl and substituted benzyl. More preferably, R9, R10, R12, R13, R14, R15, R16 and R17 are independently hydrogen or C1-4 alkyl, and R11 is hydrogen.

In still other embodiments of a compound of Formula (I), A is N.

In still embodiment of a compound of Formula (I), B is CR5. Preferably, R5 is selected from the group consisting of hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo, hydroxyl and —W[C(O)]kZ(CR9R10)rCO2R11. More preferably, R5 is hydrogen, C1-4 alkyl or —W[C(O)]kZ(CR9R10)rCO2R11. Preferably, R5 is —W[C(O)]kZ(CR9R10)rCO2R11 and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, arylalkyl, cycloalkyl and heteroaryl. Preferably, R9, R10, R12, R13, R14, R15, R16 and R17 are independently hydrogen or alkyl, and R11 is selected from the group consisting of hydrogen, C1-4 alkyl, phenyl, substituted phenyl, benzyl and substituted benzyl. More preferably, R9, R10, R12, R13, R14, R15, R16 and R17 are independently hydrogen or C1-4 alkyl, and R11 is hydrogen.

In still other embodiments of a compound of Formula (I), B is N.

In still other embodiments of a compound of Formula (I), D is CR6. Preferably, R6 is selected from the group consisting of hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo, hydroxyl and —W[C(O)]kZ(CR9R10)rCO2R11. More preferably, R6 is hydrogen, C1-4 alkyl or —W[C(O)]kZ(CR9R10)rCO2R11. Preferably, R6 is —W[C(O)]kZ(CR9R10)rCO2R11 and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, arylalkyl, cycloalkyl and heteroaryl. Preferably, R9, R10, R12, R13, R14, R15, R16 and R17 are independently hydrogen or alkyl, and R11 is selected from the group consisting of hydrogen, C1-4 alkyl, phenyl, substituted phenyl, benzyl and substituted benzyl. More preferably, R9, R10, R12, R13, R14, R15, R16 and R17 are independently hydrogen or C1-4 alkyl, and R11 is hydrogen.

In still other embodiments of a compound of Formula (I), D is N.

In still other embodiments of a compound of Formula (I), E is CR7. Preferably, R7 is selected from the group consisting of hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo, hydroxyl and —W[C(O)]kZ(CR9R10)rCO2R11. More preferably, R7 is hydrogen, C1-4 alkyl or —W[C(O)]kZ(CR9R10)rCO2R11. Preferably, R7 is —W[C(O)]kZ(CR9R10)rCO2R11 and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, arylalkyl, cycloalkyl and heteroaryl. Preferably, R9, R10, R12, R13, R14, R15, R16 and R17 are independently hydrogen or alkyl, and R11 is selected from the group consisting of hydrogen, C1-4 alkyl, phenyl, substituted phenyl, benzyl and substituted benzyl. More preferably, R9, R10, R12, R13, R14, R15, R16 and R17 are independently hydrogen or C1-4 alkyl, and R11 is hydrogen.

In still other embodiments of a compound of Formula (I), E is N.

In still other embodiments of a compound of Formula (I), G is CR8. Preferably, R8 is selected from the group consisting of hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo, hydroxyl and —W[C(O)]kZ(CR9R10)rCO2R11. More preferably, R8 is hydrogen, C1-4 alkyl or —W[C(O)]kZ(CR9R10)rCO2R11. Preferably, R8 is —W[C(O)]kZ(CR9R10)rCO2R11 and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, arylalkyl, cycloalkyl and heteroaryl. Preferably, R9, R10, R12, R13, R14, R15, R16 and R17 are independently hydrogen or alkyl, and R11 is selected from the group consisting of hydrogen, C1-4 alkyl, phenyl, substituted phenyl, benzyl and substituted benzyl. More preferably, R9, R10, R12, R13, R14, R15, R16 and R17 are independently hydrogen or C1-4 alkyl, and R11 is hydrogen.

In still other embodiments of a compound of Formula (I), G is N.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR17, r is 1, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR17, r is 2, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 1, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 2, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR17, r is 1, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR17, r is 2, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 1, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11 each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 2, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR15R16, r is 1, and each of R9, R10, R11, R15 and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11, R15 and R16 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR15R16, r is 2, and each of R9, R10, R11, R15 and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11, R15 and R16 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is NR17, r is 1 and each of R9, R10, R11, R14 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11, R14 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is NR17, r is 2 and each of R9, R10, R11, R14 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11, R14 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is O, r is 1, and each of R9, R10, R11 and R14 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, each of R11 and R14 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is O, r is 2, and each of R9, R10, R11 and R14 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, each of R11 and R14 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is CR15R16, r is 1, and each of R9, R10, R11, R14, R15, and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11, R14, R15 and R16 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is CR15R16, r is 2, and each of R9, R10, R11, R14, R15 and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11, R14, R15 and R16 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is N, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R6, R7 and R8 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is N, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R7 and R8 is independently hydrogen, C1-4-alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R5, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R7 and R8 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is N, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R5, R6 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6 and R8 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is N, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6 and R7 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R5, R6 and R7 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6 and R7 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is N, D is CR6, E is CR7, G is N, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R6 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R6 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R6 and R8 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR17, r is 1, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR17, r is 2, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 1, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, each of R5, R6, R7 and R8 is hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 2, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R5 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR17, r is 1, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR17, r is 2, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 1, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, each of R4, R6, R7 and R8 is hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 2, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, each of R4, R6, R7 and R8 is hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR15R16, r is 1, and each of R9, R10, R11, R15 and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11, R15 and R16 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR15R16, r is 2, and each of R9, R10, R11, R15 and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11, R15 and R16 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is NR17, r is 1 and each of R9, R10, R11, R14 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11, R14 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is NR17, r is 2 and each of R9, R10, R11, R14 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11, R14 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is O, r is 1, and each of R9, R10, R11 and R14 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, each of R11 and R14 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is —NR4, k is 1, Z is O, r is 2, and each of R9, R10, R11 and R14 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, each of R11 and R14 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is. NR14, k is 1, Z is CR15R16, r is 1, and each of R9, R10, R11, R14, R15 and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11, R14, R15 and R16 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is CR15R16, r is 2, and each of R9, R10, R11, R14, R15 and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R5 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11, R14, R15 and R16 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is N, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R6, R7 and R8 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is N, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R4, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R7 and R8 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is N, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R4, R6 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6 and R8 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is N, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6 and R7 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R4, R6 and R7 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6 and R7 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is N, B is CR5, D is CR6, E is CR7, G is N, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R6 and R7 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R6 and R7 is independently hydrogen or C1-4 alkyl. More preferably, R6 and R7 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is N, B is CR5, D is N, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R7 and R8 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is N, B is CR5, D is CR6, E is N, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R7 and R8 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is N, E is CR7, G is N, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R4 and R5 is independently hydrogen or C1-4 alkyl. More preferably, R4 and R8 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R5, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R4, R5, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R5, R7 and R8 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R5, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR17, r is 1, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R5, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R5, R7 and R8 are hydrogen. Preferably, R11 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R5, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR17, r is 2, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R5, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R5, R7 and R8 are hydrogen. Preferably, R11 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R5, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 1, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R5, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R5, R7 and R8 are hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R5, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 2, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R5, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R5, R7 and R8 are hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R5, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR17, r is 1, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R5, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R5, R7 and R8 are hydrogen. Preferably, R11 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R5, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR17, r is 2, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R5, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R5, R7 and R8 are hydrogen. Preferably, R16 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11,

each of R4, R5, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 1, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R5, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R5, R7 and R8 are hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R5, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 2, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R5, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R5, R7 and R8 are hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R5, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR15R16, r is 1, and each of R9, R10, R11, R15 and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R5, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R5, R7 and R8 are hydrogen. Preferably, R11, R15 and R16 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R5, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR15R16, r is 2, and each of R9, R10, R11, R15 and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R5, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R5, R7 and R8 are hydrogen. Preferably, R11, R15 and R16 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R5, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is NR17, r is 1 and each of R9, R10, R11, R14 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R5, R7 and R5 is independently hydrogen or C1-4 alkyl. More preferably, R4, R5, R7 and R8 are hydrogen. Preferably, R11, R14 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R5, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is NR17, r is 2 and each of R9, R10, R11, R14 and R17 is independently hydrogen or C1-7 alkyl. Preferably, each of R4, R5, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R5, R7 and R8 are hydrogen. Preferably, R11, R14 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R5, R7 and R8 is independently hydrogen, C1-4 alkyl, C11 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is O, r is 1, and each of R9, R10, R11 and R14 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R5, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R5, R7 and R8 are hydrogen. Preferably, each of R11 and R14 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R5, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is O, r is 2, and each of R9, R10, R11 and R14 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R5, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R5, R7 and R8 are hydrogen. Preferably, each of R11 and R14 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R5, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is CR15R16, r is 1, and each of R9, R10, R11, R14, R15 and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R5, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R5, R7 and R8 are hydrogen. Preferably, R11, R14, R15 and R16 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R5, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is CR15R16, r is 2, and each of R9, R10, R11, R14, R15 and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R5, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R5, R7 and R8 are hydrogen. Preferably, R11, R14, R15 and R16 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is N, B is CR5, D is CR6, E is CR7, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R7 and R5 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R5, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R7 and R8 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is N, D is CR6, E is CR7, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R4, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R7 and R8 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is N, B is CR5, D is CR6, E is CR7, G is N, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5 and R7 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R5 and R7 is independently hydrogen or C1-4 alkyl. More preferably, R5 and R7 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is N, B is CR5, D is CR6, E is N, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R5 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5 and R8 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is CR4, B is N, D is CR6, E is N, G is CR8, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R4 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4 and R8 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is a bond, A is N, B is CR5, D is CR6, E is CR7, G is N, R6 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5 and R7 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R5 and R7 is independently hydrogen or C1-4 alkyl. More preferably, R5 and R7 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R5, R6, R7 and R5 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR17, r is 1, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR17, r is 2, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 1, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 2, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR17, r is 1, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR7, r is 2, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 1, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 2, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR15R16, r is 1, and each of R9, R10, R11, R15 and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11, R15 and R16 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR15R16, r is 2, and each of R9, R10, R11, R15 and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11, R15 and R16 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is NR17, r is 1 and each of R9, R10, R11, R14 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11, R14 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is NR17, r is 2 and each of R9, R10, R11, R14 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11, R14 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is O, r is 1, and each of R9, R10, R11 and R14 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, each of R11 and R14 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is O, r is 2, and each of R9, R10, R11 and R14 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, each of R11 and R14 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is CR15R16, r is 1, and each of R9, R10, R11, R14, R15 and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11, R14, R15 and R16 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R4 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R5, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14; k is 1, Z is CR15R16, r is 2, and each of R9, R10, R11, R14, R15 and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R5, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11, R14, R15 and R16 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, each of R9, R10, R11, R12, R13, R14, R15, R16 and R17 is independently hydrogen or C1-4 alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR17, r is 1, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R9 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR17, r is 2, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 1, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, each of R5, R6, R7 and R8 is hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R5 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 2, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR17, r is 1, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R5, R6, R7 and R8 are hydrogen. Preferably, R11 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR17, r is 2, and each of R9, R10, R11 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 1, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R5 is independently hydrogen or C1-4 alkyl. More preferably, each of R4, R6, R7 and R8 is hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 2, and each of R9, R10 and R11 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, each of R4, R6, R7 and R8 is hydrogen. Preferably, R11 is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR15R16, r is 1, and each of R9, R10, R11, R15 and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11, R15 and R16 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR15R16, r is 2, and each of R9, R10, R11, R15 and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11, R15 and R16 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R9 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is NR17, r is 1 and each of R9, R10, R11, R14 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R9 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11, R14 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is NR17, r is 2 and each of R9, R10, R11, R14 and R17 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11, R14 and R17 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is O, r is 1, and each of R9, R10), R11 and R14 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, each of R11 and R14 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is O, r is 2, and each of R9, R10, R11 and R14 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, each of R11 and R14 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is CR15R16, r is 1, and each of R9, R10, R11, R14, R15 and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11, R14, R15 and R16 are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O, A is CR4, B is CR5, D is CR6, E is CR7, G is CR8, R5 is —W[C(O)]kZ(CR9R10)rCO2R11, each of R4, R6, R7 and R8 is independently hydrogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR14, k is 1, Z is CR15R16, r is 2, and each of R9, R10, R11, R14, R15 and R16 is independently hydrogen or C1-4 alkyl. Preferably, each of R4, R6, R7 and R8 is independently hydrogen or C1-4 alkyl. More preferably, R4, R6, R7 and R8 are hydrogen. Preferably, R11, R14, R15 and R16 are hydrogen.