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Compounds and methods of useRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Heterocyclic Carbon Compounds Containing A Hetero Ring Having Chalcogen (i.e., O,s,se Or Te) Or Nitrogen As The Only Ring Hetero Atoms Doai, Hetero Ring Is Six-membered Consisting Of One Nitrogen And Five Carbon Atoms, Polycyclo Ring System Having The Six-membered Hetero Ring As One Of The Cyclos, Bicyclo Ring System Having The Six-membered Hetero Ring As One Of The Cyclos, Plural Hetero Atoms In The Bicyclo Ring SystemCompounds and methods of use description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070032518, Compounds and methods of use. Brief Patent Description - Full Patent Description - Patent Application Claims
[0001] This application claims the benefit of U.S. Provisional Application No. 60/355,313, filed Feb. 7, 2002, which is hereby incorporated by reference. FIELD OF THE INVENTION [0002] This invention is in the field of pharmaceutical agents and specifically relates to compounds, compositions, uses and methods for treating cell proliferation-related disorders, cell death and apoptosis-related disorders. BACKGROUND OF THE INVENTION [0003] Identification of therapeutic agents effective in the treatment of neoplastic diseases or for the treatment of neurological disorders is the subject of significant research efforts. [0004] Protein kinases represent a large family of proteins which play a central role in the regulation of a wide variety of cellular processes and maintaining control over cellular function. A partial list of such kinases includes ab1, Akt, bcr-ab1, Blk, Brk, Btk, c-kit, c-met, c-src, CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, cRaf1, CSF1R, CSK, EGFR, ErbB2, ErbB3, ErbB4, Erk, Fak, fes, FGFR1, FGFR2, FGFR3, FGFR4, FGFR5, Fgr, FLK-4, flt-1, Fps, Frk, Fyn, Hck, IGF-1R, INS-R, Jak, KDR, Lck, Lyn, MEK, p38, PDGFR, PIK, PKC, PYK2, ros, tie, tie2, TRK, Yes, and Zap70. As such, inhibition of kinases has become an important therapeutic target. [0005] Cell proliferation is the rapid reproduction of cells, such as by cell division. The cell-cycle, which controls cell proliferation, is itself controlled by a family of serine-threonine kinases called cyclin dependent kinases (CDKs). The regulation of CDK activation is complex, and requires the association of the CDK with a member of the cyclin family of regulatory subunits. A further level of regulation occurs through both activating and inactivating phosphorylations of the CDK subunit. The coordinate activation and inactivation of different cyclin/CDK complexes is necessary for normal progression through the cell cycle. Both the critical G1-S and G2-M transitions are controlled by the activation of different cyclin/CDK activities. Loss of control of CDK regulation is a frequent event in hyperproliferative diseases and cancer. (T. Noguchi et al., Am. J. Pathol., 156, 2135-47 (2000)) As such, inhibition of CDKs has become an important target in the study of chemotherapeutics (A. Senderowicz and E. Sausville, J. Nat. Canc. Instit., 92, 376-87 (2000)). [0006] Kinases have also been implicated in diseases and disorders of the central nervous system. For example, patients suffering from stroke, Alzheimer's disease or Parkinson's disease would benefit from the inhibition of kinases. Cdk5 has been shown to be involved in Alzheimer's pathology (R. Maccioni, et al., Eur. J. Biochem., 268, 1518-27 (2001)) and with neuronal development (G. Paglini and A. Caceres, Eur. J. Biochem., 268, 1528-33 (2001)). [0007] Protein kinases also control programmed cell death, also known as apoptosis. Apoptosis is a ubiquitous physiological process used to eliminate damaged or unwanted cells in multicellular organisms. Disregulation of apoptosis is believed to be involved in the pathogenesis of many human diseases. The failure of apoptotic cell death has been implicated in various cancers, as well as autoimmune disorders. Conversely, increased apoptosis is associated with a variety of diseases involving cell loss such as neurodegenerative disorders and AIDS. As such, inhibition of apoptosis has become an important therapeutic target. Cdk5 has been shown to be involved in apoptosis pathology (A. Catania et al., Neuro-Oncology, 89-98 (April 2001)). [0008] Quinolinones are known in the art. U.S. Pat. No. 4,127,574, issued Nov. 28, 1978, describes 3-sulfonyl-quinolinones as anti-allergic agents. U.S. Pat. No. 4,547,511, issued Oct. 15, 1985, describes 3-carboxamide-quinolinones as pharmaceuticals. S. Ibrahim et al., Ind. J. Het. Chem., 4, 125-130 (1994) describe 1-methylquinolinones. A. Sayed et al., Acta Chim. Acad. Sci. Hung., 94, 131-39 (1977), describes the preparation of 1-alkylquinolinones. M. Abass, Synth. Commun., 30, 2735-57 (2000), describes the preparation of 1-methylquinolinones. WO01/70227, published 27 Sep. 2001, describes 3-heterocyclylquinolinones as GnRH antagonists. WO01/70228, published 27 Sep. 2001, describes 3-phenylquinolinones as GnRH antagonists. WO01/62252, published 30 Aug. 2001, describes 3-pyrrolopyridinyl-quinolinones as tyrosine kinase inhibitors. WO01/29025, published 26 Apr. 2001, describes 3-(2-indolyl)quinolinones as tyrosine kinase inhibitors. [0009] U.S. Pat. No. 5,252,584, issued Oct. 12, 1993, describes 4-hydroxy-quinolinones as NMDA antagonists. K. Ashok et al., Ind. J. Chem., 32B, 786-87 (1993), describe the preparation of 4-hydroxy-quinolinones. E. Mohamed et al., J. Ind. Chem. Soc, 69, 82-4 (1992), describe the preparation of 4-hydroxy-quinolinones. WO92/18483, published 29 Oct. 1992, describes 1-methyl-4-hydroxy-quinolinones as pharmaceuticals. WO01/28993, published 26 Apr. 2001, describes 6-(indazol-2-yl)-thieno[2,3-b]pyridones as kinase inhibitors. M. Rehwald et al., J. Prakt. Chem., 342, 371-78 (2000), describe preparation of heteroaryl pyridinium salts. G. Tenant et al., J. Chem. Soc., Perkin Trans. 1, 827-32 (1999), describe preparation of heterocyclyl-pyridinium salts. K. Gewald et al., Liebigs. Ann., 787-91 (1995), describe preparation of heterocyclyl-pyridinium salts. T. El-Emary et al., Pharmazie, 55, 356-58 (2000), describe the preparation of pyrazolo[3,4-b]pyridin-2-ones. S. Naruto, et al., Chem. Pharm. Bull., 30, 3421-23 (1982), describe the preparation of benzofuro[3,2-b]pyridin-2-ones. WO01/62251, published 30 Aug. 2001, describes 3-pyrrolopyridinyl-quinolinones as tyrosine kinase inhibitors. WO01/29025, published 26 Apr. 2001, describes 3-(2-indolyl)quinolinones as tyrosine kinase inhibitors. WO01/28993, published 26 Apr. 2001, describes 3-(2-benzimidazolyl)quinolinones as tyrosine kinase inhibitors. WO01/62252, published 30 Aug. 2001, describes 3-pyrrolopyridinyl-quinolinones. U.S. Pat. No. 5,643,932, issued Jul. 1, 1997, describes thiazoles as superoxide radical inhibitors. A. Doroshenko et al. Chem. Heterocycl. Cmpd., 33, 1177-84 (1998) describes spectral properties of thiazolyl-coumarin derivatives. [0010] However, compounds of the current invention have not been described as inhibitors of cell proliferation or apoptosis such as for the treatment of cancer or stroke. DESCRIPTION OF THE INVENTION [0011] A class of compounds useful in treating cell proliferative disorders, neurological disorders and apoptosis is defined by Formula I [0012] wherein A is O, S or NH; [0013] wherein D is CR.sup.1 or N; [0014] wherein E is CR.sup.2 or N; [0015] wherein F is CR.sup.3 or N; [0016] wherein G is CR.sup.4 or N; [0017] wherein J is selected from NR.sup.6, S, O, and CR.sup.1; [0018] wherein K is selected from NR.sup.6, S, O, and CR.sup.2; [0019] wherein L is selected from NR.sup.6, S, O, and CR.sup.3; [0020] wherein Q is selected from hydroxy, --N(R.sup.5).sub.2, --NR.sup.5C(O)R.sup.5, --(C.sub.1-C.sub.8)alkyl-OR.sup.5, --(C.sub.1-C.sub.8)alkyl-S(O).sub.nR.sup.5, --N(C.sub.1-C.sub.8-alkyl)-S(O).sub.nR.sup.5, --NHS(O).sub.nR.sup.5, aryl, a monocyclic or bicyclic, non-aromatic carbocyclic ring, heteroaryl and a monocyclic or bicyclic, non-aromatic heterocyclic ring; wherein the ring is unsubstituted or substituted with one or more groups selected from H, halo, aryl, alkynyl, alkenyl, --OR.sup.5, --N(R.sup.5).sub.2, --(C.sub.1-C.sub.8)alkyl-N(R.sup.5).sub.2, lower alkoxyalkyl, --O--C.sub.1-C.sub.2-alkyl-O--, --S(O).sub.nR.sup.5, cyano, (C.sub.1-C.sub.8)alkyl, lower cyanoalkyl, lower alkylaminoalkoxy, lower aminoalkoxyalkyl (C.sub.3-C.sub.10cycloalkyl, nitro, optionally substituted 4-7 membered heterocyclyl, optionally substituted phenoxyalkyl, optionally substituted heterocyclyloxyalkyl, --SO.sub.2NR.sup.5R.sup.5, --NR.sup.5SO.sub.2R.sup.5, --C(O)N(R.sup.5).sub.2, --CO.sub.2R.sup.5, --CO.sub.2NR.sup.5R.sup.5, --SO.sub.2NHC(O)R.sup.5, optionally substituted phenylalkyl, optionally-substituted heterocyclylalkyl, --NR.sup.5C(O)N(R.sup.5).sub.2, --NR.sup.5C(O)R.sup.5, --NR.sup.5CO.sub.2R and --C(O)R.sup.5; [0021] wherein W is an monocyclic aromatic or non-aromatic, heterocyclic ring that is unsubstituted or substituted with one or more groups selected from halo, aryl, cycloalkyl, --OR.sup.5, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, --N(R.sup.5).sub.2, --(C.sub.1-C.sub.8)alkyl-N(R.sup.5).sub.2, --SO.sub.2NR.sup.5R.sup.5, --(C.sub.1-C.sub.8)alkylSO.sub.2R.sup.5, --(C.sub.1-C.sub.8)alkylSO.sub.2--(C.sub.1-C.sub.8)alkyl-R.sup.5, (C.sub.1-C.sub.8)alkyl, C.sub.3-C.sub.10)cycloalkyl, nitro, cyano, optionally substituted 5-6 membered heterocyclyl, formyl, alkylcarbonyl, cycloalkylcarbonyl, heterocyclylcarbonyl, arylcarbonyl, --NR.sup.5SO.sub.2R.sup.5, --C(O)N(R.sup.5).sub.2, --C(O)NR.sup.5R.sup.5a, --CO.sub.2R.sup.5, optionally substituted phenylalkyl, optionally substituted heterocyclylalkyl, --NR.sup.5C(O)N(R.sup.5).sub.2, --NR.sup.5C(O)R.sup.5 and --NR.sup.5CO.sub.2R.sup.5; [0022] wherein Z is selected from H, --N(R.sup.5).sub.2, --SR.sup.5, --OR.sup.5, --C(R.sup.5).sub.3 and aryl; [0023] wherein n is 0, 1 or 2; [0024] wherein m is 0 or 1; [0025] wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently selected from H, --OR.sup.5, OR.sup.5a, halo, aryl, alkenyl, alkynyl, --NR.sup.5.sub.2, --(C.sub.1-C.sub.8)alkyl-N(R.sup.5).sub.2, --S(O).sub.n--NR.sup.5R.sup.5, --S(O).sub.nR.sup.5, (C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.10)cycloalkyl, nitro, cyano, optionally substituted 4-10 membered heterocyclyl, --C(O)R.sup.5, --NR.sup.5SO.sub.2R.sup.5, --C(O)N(R.sup.5).sub.2, --CO.sub.2R.sup.5, optionally substituted arylalkyl, optionally substituted 4-10 membered heterocyclylalkyl, --NR.sup.5C(O)N(R.sup.5).sub.2, --NR.sup.5C(O)R.sup.5 and --NR.sup.5CO.sub.2R.sup.5; wherein R.sup.1 and R.sup.2 may be joined to form a 5-10 membered saturated or unsaturated carbocyclic or heterocyclic, ring; wherein R.sup.2 and R.sup.3 may be joined to form a 5-10 membered saturated or unsaturated carbocyclic or heterocyclic ring; or wherein R.sup.3 and R.sup.4 may be joined to form a 5-10 membered saturated or unsaturated-carbocyclic or heterocyclic ring; [0026] wherein R.sup.5 is independently selected from H, lower alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkyl-alkyl, and lower haloalkyl; [0027] wherein R.sup.5a is alkylaminoalkyl; [0028] wherein R.sup.6 is selected from H, (C.sub.1-C.sub.2)alkyl, and a lone pair of electrons; [0029] wherein a solid line with a dashed line represents either a single or a double bond; [0030] wherein each alkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, alkynyl, alkynyl, and alkoxy moiety of any R.sup.1, R.sup.2, R.sup.3, R.sup.4, or R.sup.5 can optionally join with another R.sup.1, R.sup.2, R.sup.3, R.sup.4, or R.sup.5 to form a 3-7 membered ring; and [0031] wherein each alkyl, aryl, heteroaryl, cycloalkyl, alkynyl, alkynyl, heterocyclyl, and alkoxy moiety of any R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, Q and W is optionally substituted with one or more groups selected from halo, --NH.sub.2, --OH, --CO.sub.2H, (C.sub.1-C.sub.6)alkylamino, (C.sub.1-C.sub.6)alkyl, C.sub.1-C.sub.6)alkoxy, C.sub.1-C.sub.6)haloalkyl, di(C.sub.1-C.sub.6)alkylamino, (C.sub.1-C.sub.6)alkylamino-(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)hydroxyalkylamino, (C.sub.1-C.sub.6)alkylamino-(C.sub.1-C.sub.6)alkylamino, phenyl, and heterocyclyl; [0032] provided W is not pyridinium; further provided W is not dihydropyrazolyl or oxadiazolyl when Ar is aryl; further provided Z is not OH when Ar is aryl; further provided Z is not H when W is or pyrazol-3-yl, when Ar is phenyl and when Q is phenyl; further provided Q is not unsubstituted phenyl when W is thiazol-4-yl, when Z is H and when F is C--OCH.sub.3; further provided Q is not 3,4-dimethoxyphenyl when W is thiazol-4-yl, when Z is H and when R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are H; further provided Q is not 3,4-dihydroxyphenyl when W is thiazol-2-yl, when Z is H and when R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are H; further provided Z is not phenyl when Q is phenyl, when W is tetrahydropyrazinyl and when Ar is phenyl; and further provided Z is not phenyl when Q is phenyl, when W is pyrazol-3-yl or dihydro-isoxazol-3-yl and when Ar is phenyl; [0033] and pharmaceutically acceptable derivatives thereof. [0034] The invention also relates to compounds of Formula I wherein, [0035] preferably phenyl, thienyl, pyrimidinyl, pyridyl and thiazolyl, [0036] more preferably phenyl, [0037] wherein Ar is optionally substituted with one or more radicals selected from --OR.sup.5, halo, aryl, alkenyl, alkynyl, --NR.sup.5.sub.2, --(C.sub.1-C.sub.8)alkyl-N(R.sup.5).sub.2, --S(O).sub.n--NR.sup.5R.sup.5, --S(O).sub.nR.sup.5, (C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.10)cycloalkyl, nitro, cyano, optionally substituted 4-10-membered heterocyclyl, --C(O)R.sup.5, --NR.sup.5SO.sub.2R.sup.5, --C(O)N--(R.sup.5).sub.2, --CO.sub.2R.sup.5, optionally substituted arylalkyl, optionally substituted 4-10 membered heterocyclylalkyl, --NR.sup.5C(--O)N(R.sup.5).sub.2, --NR.sup.5C(O)R.sup.5 and --NR.sup.5CO.sub.2R.sup.5, [0038] preferably --OR.sup.5, chloro, fluoro, phenyl, C.sub.2-C.sub.6 alkenyl, --C.sub.2-C.sub.6 alkynyl, --N(R.sup.5).sub.2, --(C.sub.1-C.sub.6)alkyl-N(R.sup.5).sub.2, --S(O).sub.nNR.sup.5R.sup.5, --S(O).sub.nR.sup.5, (C.sub.1-C.sub.6)alkyl, (C.sub.3-C.sub.6)cycloalkyl, nitro, cyano, optionally substituted 4-6 membered heterocyclyl, --C(O)R.sup.5R, --NR.sup.5SO.sub.2R.sup.5, --C(O)N(R.sup.5).sub.2, --CO.sub.2R.sup.5, optionally substituted phenyl-C.sub.1-C.sub.6-alkyl, optionally substituted 4-6 membered heterocyclyl-C.sub.1-C.sub.6-alkyl, --NR.sup.5C(O)N(R.sup.5).sub.2, --NR.sup.5C(O)R.sup.5 and --NR.sup.5CO.sub.2R.sup.5, [0039] more preferably --OR.sup.5, chloro, fluoro, phenyl, --N(R.sup.5).sub.2, --(C.sub.1-C.sub.2)alkyl-N(R.sup.5).sub.2, --S(O).sub.n--NR.sup.5R.sup.5, --S(O).sub.nR.sup.5, (C.sub.1-C.sub.4) alkyl, (C.sub.1-C.sub.2)haloalkyl, hydroxy-(C.sub.1-C.sub.2)alkyl, hydroxy-(C.sub.1-C.sub.4)-alkylamino, (C.sub.1-C.sub.2)-alkylamino-(C.sub.1-C.sub.2)-alkylamino, (C.sub.1-C.sub.2)-alkylamino-(C.sub.1-C.sub.2)-alkoxy, optionally substituted (C.sub.3-C.sub.6)cycloalkyl, optionally substituted heterocyclyl selected from pyrrolidinyl, piperazinyl, piperidinyl, and morpholinyl, --C(O)R.sup.5, --NR.sup.5SO.sub.2R.sup.5, --C(O)N(O)R.sup.5).sub.2, --CO.sub.2R.sup.5, optionally substituted benzyl, optionally substituted 4-6 membered heterocyclyl-C.sub.1-C.sub.2-alkyl, --NR.sup.5C(O)R.sup.5 and --NR.sup.5CO.sub.2R.sup.5, [0040] even more preferably cyclopropylmethylamino, 3-hydroxypropylamino, 2-(piperidin-1-yl)ethylamino, 2-(pyrrolidin-1-yl)ethylamino, 2-(morpholin-4-yl)ethylamino, 3-(piperidin-1-yl)propylamino, 3-(pyrrolidin-1-yl)propylamino, 3-(morpholin-4-yl)propylamino, N-methyl-N-(2-piperid-1-ylethyl)amino, N-methyl-N-(2-pyrrolidin-1-ylethyl)amino, N-methyl-N-(2 morpholin-4-ylethyl)amino, ((2S)-2-amino-3-phenylpropyl)amino, 4-methylpiperazin-1-ylamino, 4-methylpiperazin-1-yl, 3-aminopyrrolidin-1-yl, (diethylamino)ethylamino, 3,5-dimethylpiperazin-1-yl, (1-piperidylmethyl)amino, (2-methylbutyl)amino, 2-(dimethylamino)ethoxy, 2-(methylamino)ethoxy, ((2R)pyrrolidin-2-yl)methoxy, ((2R)-1-methylpyrrolidin-2-yl)methoxy, 2-(piperid-1-yl)ethoxy, 2-(piperazin-1-yl)ethoxy, 2-morpholin-4-ylethoxy, hydroxy, benzyloxy, methoxy, chloro, fluoro, phenyl, amino, methylamino, diethylamino, aminomethyl, dimethylaminoethyl, aminosulfonyl, methylthio, methylsulfonyl, piperazinylsulfonyl, methyl, cyclopropyl, pyrrolidinyl, piperazinyl, 4-methylpiperazinyl, piperidinyl, morpholinyl, methylcarbonyl, phenylcarbonyl, piperidinylcarbonyl, trifluoromethyl, hydroxymethyl, hydroxyethyl, diethylaminocarbonyl, methoxycarbonyl, optionally substituted benzyl, piperazinylmethyl, 4-methylpiperazinylmethyl, piperidinylmethyl, and morpholinylmethyl; [0041] wherein A is O, S or NH, and [0042] preferably O; [0043] wherein D is CR.sup.1, or N; [0044] wherein E is CR.sup.2, or N; [0045] wherein F is CR.sup.3, or N; [0046] wherein G is CR.sup.4 or N; [0047] wherein J is selected from NR.sup.6, S, O, and CR.sup.1; [0048] wherein K is selected from NR.sup.6, S, O, and CR.sup.2; [0049] wherein L is selected from NR.sup.6, S, O, and CR.sup.3; [0050] wherein Q is selected from hydroxy, --N(R.sup.5).sub.2, --NR.sup.5C(O)R.sup.5, --(C.sub.1-C.sub.8)alkyl-S(O).sub.nR.sup.5, --N(C.sub.1-C.sub.8-alkyl)-S(O).sub.nR.sup.5, --NHS(O).sub.nR.sup.11, aryl, a monocyclic or bicyclic, non-aromatic carbocyclic ring, heteroaryl and a monocyclic or bicyclic, non-aromatic heterocyclic ring, [0051] preferably hydroxy, (R.sup.5).sub.2N--, R.sup.5-carbonyl-HN--, R.sup.5-carbonyl-N(CH.sub.3)--, phenyl-O--(C.sub.1-C.sub.2)alkyl, R.sup.5SO.sub.2--(C.sub.1-C.sub.6)alkyl-, --N(C.sub.1-C.sub.6-alkyl)-S(O).sub.nR.sup.5, substituted or unsubstituted phenyl, substituted or unsubstituted 5-6 membered heteroaryl, substituted or unsubstituted C.sub.3-C.sub.6 cycloalkyl, and substituted or unsubstituted non-aromatic heterocyclyl; [0052] more preferably --N(R.sup.5).sub.2, R.sup.5-carbonyl-HN--, R.sup.5-carbonyl-N(CH.sub.3)--, phenyl-O-methyl, R.sup.5S(O).sub.n--(C.sub.1-C.sub.3)alkyl, --N(C.sub.1-C.sub.3-alkyl)-S(O).sub.nR.sup.5, substituted or unsubstituted phenyl, benzodioxolyl, and substituted or unsubstituted 6-membered heteroaryl; [0053] even more preferably --N(R.sup.5).sub.2, R.sup.5 (O).sub.n--(C.sub.1-C.sub.3)alkyl, --N(C.sub.1-C.sub.3-alkyl)-S(O).sub.nR.sup.5, --NH--S(O).sub.nR.sup.11, substituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrazinyl, substituted or unsubstituted pyrimidinyl and substituted or unsubstituted pyridazinyl; [0054] particularly amino, 2-pyridylamino, 3-pyridylamino, 4-pyridylamino, phenylsulfonylamino, N-methyl-N-(2-pyridylsulfonyl)amino, N-methyl-N-(3-pyridylsulfonyl)amino, N-methyl-N-(4-pyridylsulfonyl)amino, N-methyl-N-(2-thienylsulfonyl)amino, N-methyl-N-(phenylsulfonyl)amino, 2-pyridylsulfonylmethyl, 3-pyridylsulfonylmethyl, 4-pyridylsulfonylmethyl, 2-thienylsulfonylmethyl, phenylsulfonylmethyl, 2-furylmethylsulfonylmethyl, 3-trifluoromethylbenzyl-sulfonylmethyl, methylsulfonylmethyl, tert-butyl-sulfonylmethyl, 4-fluorophenyl-methylsulfonylmethyl, 4-chlorophenyl-methylsulfonylmethyl, [0055] phenyl substituted with one or more substituents selected from H, hydroxyl, chloro, fluoro, methoxy, amino, aminomethyl, methylsulfonyl, methyl, cyano, trifluoromethyl, and pyrrolyl, unsubstituted pyridyl, and [0056] pyridyl substituted with one or more substituents selected from chloro, fluoro, --NH.sub.2, --OH, --CO.sub.2H, methylamino, methyl, ethyl, diethyl-amino, pyrrolidinyl, piperazinyl, piperidinyl, morpholinyl and azetidinyl; [0057] more particularly substituted or unsubstituted pyridyl; [0058] wherein the ring is unsubstituted or substituted with one or more groups selected from H, halo, aryl, alkynyl, alkenyl, --OR.sup.5, --N(R.sup.5).sub.2; --(C.sub.1-C.sub.8)alkyl-N(R.sup.5).sub.2, lower alkoxyalkyl, --S(O).sub.nR.sup.5, (C.sub.1-C.sub.8)alkyl, cyano, lower cyanoalkyl, lower alkylaminoalkoxy, lower aminoalkoxyalkyl (C.sub.3-C.sub.10)cycloalkyl, nitro, optionally substituted 4-7 membered heterocyclyl, optionally substituted phenoxyalkyl, optionally substituted heterocyclyloxyalkyl, --SO.sub.2NR.sup.5R.sup.5.sub.1--NR.sup.5SO.sub.2R.sup.5, --C(O)N(R.sup.5).sub.2, --CO.sub.2R.sup.5, --CO.sub.2NR.sup.5R.sup.5, SO.sub.2NHC(O)R.sup.5, optionally substituted phenylalkyl, optionally substituted heterocyclylalkyl, --NR.sup.5C(O)N(R.sup.5).sub.2, --NR.sup.5C(O)R.sup.5, --NR.sup.5CO.sub.2R.sup.5 and --C(O)R.sup.5; [0059] preferably H, halo, phenyl, (C.sub.2-C.sub.6)-alkynyl, (C.sub.2-C.sub.6)-alkenyl, --OR.sup.5, --N(R.sup.5).sub.2, --(C.sub.1-C.sub.8)alkyl-N(R.sup.5).sub.2, lower alkoxyalkyl, R.sup.5-sulfonyl, R.sup.5-sulfonyl-(C.sub.1-C.sub.6)-alkyl, (C.sub.1-C.sub.8)alkyl, cyano, lower cyanoalkyl, lower alkylaminoalkoxy, lower aminoalkoxyalkyl (C.sub.3-C.sub.10cycloalkyl, nitro, optionally substituted 4-7, membered heterocyclyl, optionally substituted phenoxyalkyl, optionally substituted heterocyclyloxyalkyl, --SO.sub.2NR.sup.5R.sup.5, --NR.sup.5SO.sub.2R.sup.5, --C(O)N(R.sup.5).sub.2, --CO.sub.2R.sup.5, --CO.sub.2NR.sup.5R.sup.5, --SO.sub.2NHC(O)R.sup.5, optionally substituted phenylalkyl, optionally substituted heterocyclylalkyl, --NR.sup.5C(O)N(R.sup.5).sub.2--NR.sup.5C(O)R.sup.5, --NR.sup.5CO.sub.2R.sup.5 and --C(O)R.sup.5; [0060] wherein W is a monocyclic, aromatic or non-aromatic, heterocyclic ring that is unsubstituted or substituted with one or more groups selected from halo, aryl, cycloalkyl, --OR.sup.5, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, --N(R.sup.5).sub.2, --(C.sub.1-C.sub.8)alkyl-N(R.sup.5).sub.2, --SO.sub.2NR.sup.5R.sup.5, (C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.10)cycloalkyl, nitro, cyano, optionally substituted 5-10 membered heterocyclyl, formyl, alkylcarbonyl, cycloalkylcarbonyl, heterocyclylcarbonyl, arylcarbonyl, --NR.sup.5SO.sub.2R.sup.5, --C(O)N(R.sup.5).sub.2, --CO.sub.2R.sup.5, optionally substituted phenylalkylenyl, optionally substituted heterocyclylalkylenyl, --NR.sup.5C(O)N(R.sup.5).sub.2, --NR.sup.5C(O)R.sup.5 and --NR.sup.5CO.sub.2R.sup.5; [0061] preferably 5-6 membered heterocyclyl; [0062] more preferably 5-membered heteroaryl; [0063] even more preferably thienyl, thiazolyl, oxazolyl, imidazolyl, pyrrolyl, furyl, pyrazolyl, isoxazolyl, thiadiazolyl, triazolyl and isothiazolyl; [0064] particularly thienyl, thiazolyl, oxazolyl, furyl, isoxazolyl and isothiazolyl; [0065] more particularly thiazolyl, oxazolyl, and thienyl; [0066] wherein Z is selected from H, --N(R.sup.5).sub.2, --SR.sup.5, --OR.sup.5, --C(R.sup.5).sub.3 and aryl; [0067] preferably H, --N(R.sup.5).sub.2, --OR.sup.5, (C.sub.1-C.sub.3)alkyl, and phenyl; [0068] more preferably H, --N(R.sup.5).sub.2, and phenyl; [0069] even more preferably H, amino and phenyl; [0070] wherein n is 0, 1 or 2; [0071] preferably 2; [0072] wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently selected from H, --OR.sup.5, halo, aryl, alkenyl, alkynyl, --NR.sup.5.sub.2, --(C.sub.1-C.sub.8)alkyl-N(R.sup.5).sub.2, --S(O).sub.n--NR.sup.5R.sup.5, (C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.10)cycloalkyl, nitro, cyano, optionally substituted 4-10 membered heterocyclyl, --C(O)R.sup.5; --NR.sup.5SO.sub.2R.sup.5, --SO.sub.2R.sup.5, --C(O)N(R.sup.5).sub.2, --CO.sub.2R.sup.5; optionally substituted arylalkyl, optionally substituted 4-10 membered heterocyclylalkyl, --NR.sup.5C(O)N(R.sup.5).sub.2, --NR.sup.5C(O)R.sup.5 and --NR.sup.5CO.sub.2R.sup.5; wherein R.sup.1 and R.sup.2 may be joined to form a 5-10 membered saturated or unsaturated carbocyclic or heterocyclic ring; wherein R.sup.2 and R.sup.3 may be joined to form a 5-10-membered saturated or unsaturated carbocyclic or heterocyclic ring; or wherein R.sup.3 and R.sup.4 may be joined to form a 5-10 membered saturated or unsaturated carbocyclic or heterocyclic ring; [0073] wherein R.sup.5 is independently selected from H, lower alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted C.sub.3-C.sub.6 cycloalkyl, optionally substituted C.sub.3-C.sub.6cycloalkylalkyl, and lower-haloalkyl; [0074] preferably H, (C.sub.1-C.sub.6)alkyl, optionally substituted phenyl, optionally substituted phenyl-(C.sub.1-C.sub.4)alkyl, optionally substituted 4-10 membered heterocyclyl, optionally substituted 4-10 membered heterocyclyl-(C.sub.1-C.sub.4)alkyl, optionally substituted C.sub.3-C.sub.6 cycloalkyl, optionally substituted C.sub.3-C.sub.6 cycloalkyl-(C.sub.1-C.sub.4) alkyl, and (C.sub.1-C.sub.4) haloalkyl; [0075] more preferably H, (C.sub.1-C.sub.6)alkyl, optionally substituted C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 cycloalkyl-(C.sub.1-C.sub.4)alkyl, optionally substituted phenyl, optionally substituted phenyl-(C.sub.1-C.sub.3)alkyl, optionally-substituted 4-6 membered heterocyclyl-(C.sub.1-C.sub.4) alkyl, (C.sub.1-C.sub.2) haloalkyl, and optionally substituted 4-6 membered heterocyclyl; [0076] even more preferably H, methyl, ethyl, propyl, tert-butyl, 2-methylbutyl, cyclopropyl, cyclopentyl, cyclobutyl, cyclohexyl, phenyl, benzyl, phenylethyl, 2-amino-3-phenylpropyl, cyclopropylmethyl, 4-piperidylmethyl, -(1-methylpyrrolidin-2-yl)methyl, (pyrrolidin-2-yl)methyl, piperidinylethyl, (pyrrolidin-1-yl)ethyl, (morpholin-4-yl)ethyl, piperidinylpropyl, (pyrrolidin-1-yl)propyl, (morpholin-4-yl)propyl, trifluoromethyl, 2-furylmethyl, pyridyl, 2-thienyl, piperazinyl, 3,5-dimethylpiperazin-1-yl, 3-aminopyrrolidin-1-yl and 4-methylpiperazin-1-yl; [0077] wherein R.sup.6 is selected from H, (C.sub.1-C.sub.2)alkyl, and a lone pair of electrons; [0078] wherein a solid line with a dashed line represents either a single or a double bond; [0079] wherein each alkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, alkynyl, alkynyl, and alkoxy moiety of any R.sup.1, R.sup.2, R.sup.3, R.sup.4, or R.sup.5 can optionally join with another R.sup.1, R.sup.2, R.sup.3, R.sup.4, or R.sup.5 to form a 3-7 membered ring; and [0080] wherein each alkyl, aryl, heteroaryl, cycloalkyl, alkynyl, alkynyl, heterocyclyl, and alkoxy moiety of any R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, Q and W is optionally substituted with one or more groups selected from halo, --NH.sub.2, --OH, --CO.sub.2H, (C.sub.1-C.sub.6)alkylamino, (C.sub.1-C.sub.6)alkyl, C.sub.1-C.sub.6)alkoxy, C.sub.1-C.sub.6)haloalkyl, di(C.sub.1-C.sub.6)alkylamino, (C.sub.1-C.sub.6)alkylamino-(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)hydroxyalkylamino, (C.sub.1-C.sub.6)alkylamino-(C.sub.1-C.sub.6)alkylamino, phenyl, and heterocyclyl; [0081] preferably halo, --NH.sub.2, --OH, CO.sub.2H, (C.sub.1-C.sub.4) alkylamino, (C.sub.1-C.sub.4)alkyl, di(C.sub.1-C.sub.4)alkylamino, pyrrolidinyl, piperazinyl, piperidinyl, morpholinyl, and azetidinyl; [0082] more preferably chloro, fluoro, --NH.sub.2, --OH, methoxy, --CO.sub.2H, (C.sub.1-C.sub.2)alkylamino, (C.sub.1-C.sub.2)alkyl, di(C.sub.1-C.sub.2)alkylamino; pyrrolidinyl; piperazinyl, piperidinyl, morpholinyl, and azetidinyl; [0083] provided W is not pyridinium; further provided W is not dihydropyrazolyl or oxadiazolyl when Ar is aryl; further provided Z is not OH when Ar is aryl; further provided Z is not H when W is or pyrazol-3-yl, when Ar is phenyl and when Q is phenyl; further provided Q is not unsubstituted phenyl when W is thiazol-4-yl, when Z is H and when F is C--OCH.sub.3; further provided Q is not 3,4-dimethoxyphenyl when W is thiazol-4-yl, when Z is H and when R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are H; further provided Q is not 3,4-dihydroxyphenyl when W is thiazol-2-yl, when Z is H and when R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are H; further provided Z is not phenyl when Q is phenyl, when W is tetrahydropyrazinyl and when Ar is phenyl; and further provided Z is not phenyl when Q is phenyl, when W is pyrazol-3-yl or dihydro-isoxazol-3-yl and when Ar is phenyl; [0084] and pharmaceutically acceptable derivatives thereof. [0085] The invention also relates to compounds of Formula I wherein W is thiazolyl, such as thiazol-4-yl or thiazol-2-yl. [0086] The invention also relates to compounds of Formula I wherein Q is R.sup.5SO.sub.2--(C.sub.1-C.sub.6)alkyl-, such as phenylsulfonylmethyl. [0087] The invention also relates to compounds of Formula I wherein Q is --N(C.sub.1-C.sub.6-alkyl)-S(O).sub.nR.sup.5, such as N-methyl-N-(phenylsulfonyl)amino. [0088] The invention also relates to compounds of Formula I wherein Z is H. [0089] The invention also relates to compounds of Formula I wherein Q is pyridyl, such as 4-pyridyl. [0090] The invention also relates to compounds of Formula I wherein E is CR.sup.2 and D, F and G are independently CH; and wherein R.sup.2 is selected from H, cyclopropylmethylamino; 3-hydroxypropylamino, 2-(piperidin-1-yl)ethylamino, 2-(pyrrolidin-1-yl)-ethylamino, 2-(morpholin-4-yl)ethylamino, 3-(piperidin-1-yl)propylamino, 3-(pyrrolidin-1-yl)propylamino, 3-(morpholin-4-yl)propylamino, N-methyl-N-(2-piperid-1-ylethyl)amino, N-methyl-N-(2-pyrrolidin-1-ylethyl)amino, N-methyl-N-(2-morpholin-4-ylethyl)amino, ((2S)-2-amino-3-phenylpropyl)amino, 4-methylpiperazin-1-ylamino, N-methyl-N-((tetrahydrofur-2-yl)methyl)amino, (4-piperidylmethyl)amino, amino, methylamino, (2-methylbutyl)amino, diethylamino, (diethylamino)ethylamino, aminomethyl, dimethylaminoethyl, isopropylaminomethyl, diethylaminomethyl, N-methyl-N-(isopropyl)aminomethyl, N-methyl-N-(diethylaminoethyl)aminomethyl, N-ethyl-N-(dimethylaminoethyl)aminomethyl, (1-hydroxymethyl-2-methylpropyl)amino, cyclopentylaminomethyl, 2-(dimethylamino)ethoxy, 3-(dimethylamino)propoxy, 2-(methylamino)ethoxy, ((2R)pyrrolidin-2-yl)methoxy, ((2R)-1-methylpyrrolidin-2-yl)methoxy, 2-(piperid-1-yl)ethoxy, 2-(piperazin-1-yl)ethoxy, 2-(morpholin-4-yl)ethoxy, hydroxy, benzyloxy, methoxy, chloro, fluoro, phenyl, aminosulfonyl, piperazinylsulfonyl, methylthio, methylsulfonyl, methyl, cyclopropyl, pyrrolidinyl, piperazinyl, piperidin-1-yl, morpholinyl, 4-methylpiperazin-1-yl, 3-aminopyrrolidin-1-yl, 3,5-dimethylpiperazin-1-yl, methylcarbonyl, phenylcarbonyl, piperidin-1-ylcarbonyl, 4-methylpiperazin-1-ylcarbonyl, --morpholin-4-ylcarbonyl, trifluoromethyl, hydroxymethyl, hydroxyethyl, diethylaminocarbonyl, ethylaminocarbonyl, methoxycarbonyl, carboxy, optionally substituted benzyl, piperazinylmethyl, azetidin-1-ylmethyl, pyrrolidin-1-ylmethyl, 3-hydroxypyrrolidin-1-ylmethyl, 4-methylpiperazin-1-ylmethyl, 3-methylpiperazin-1-ylmethyl, 3,5-dimethylpiperazin-1-ylmethyl, 3-isopropylpiperazin-1-ylmethyl, 3,6-dihydropyridin-1-ylmethyl, 3-methylpiperidin-1-ylmethyl, 3,5-dimethylpiperidin-1-ylmethyl, 3-hydroxypiperidin-1-ylmethyl, 4-hydroxypiperidin-1-ylmethyl, piperidin-1-ylmethyl, 2,6-dimethylmorpholin-4-ylmethyl and morpholin-4-ylmethyl. [0091] The invention also relates to compounds wherein W is --C(O)NR.sup.5R.sup.5a; wherein R.sup.1, R.sup.2R.sup.3, and R.sup.4 are independently --OR.sup.5a; and wherein R.sup.5a is alkylaminoalkyl, such as (C.sub.1-C.sub.3)alkylamino-(C.sub.1-C.sub.6)alkyl, specifically dimethylaminomethyl, dimethylaminopropyl, dimethylaminoethyl, and diethylaminoethyl. [0092] The invention also relates to compounds of Formula II [0093] wherein X.sup.1 is C, CR.sup.10 or N; wherein X.sup.2 is selected from NH, N(CH.sub.3), S and O; wherein X.sup.3 is C, CR.sup.10 or N; wherein X.sup.4 is C, CR.sup.10 or N; provided at least one of X.sup.1, X.sup.2, X.sup.3 and X.sup.4 is not N, NH or N(CH.sub.3); [0094] preferably X.sup.2 is S; [0095] wherein Z is selected from H, --N(R.sup.11).sub.2, --OR.sup.11, (C.sub.1-C.sub.4)alkyl, and phenyl; [0096] preferably H, amino, and phenyl; [0097] wherein R.sup.8 is selected from --N(--R.sup.11).sub.2, R.sup.11S(O).sub.n--(C.sub.1-C.sub.8)alkyl, N--(C.sub.1-C.sub.8-alkyl)-N--[R.sup.11S(O).sub.n]amino, optionally substituted phenyl, benzodioxolyl, optionally substituted pyridyl, optionally substituted pyrazinyl, optionally substituted pyrimidinyl and optionally substituted-pyridazinyl; wherein R.sup.8 is unsubstituted or substituted with one or more substituents selected from chloro, fluoro, --NH.sub.2, --OH, --CO.sub.2H, (C.sub.1-C.sub.2)alkylamino, (C.sub.1-C.sub.2)alkyl, di(C.sub.1-C.sub.2)alkylamino, pyrrolidinyl, piperazinyl, piperidinyl, morpholinyl and azetidinyl; [0098] preferably amino, 2-pyridylamino, 3-pyridylamino, 4-pyridylamino, phenylsulfonylamino, N-methyl-N-(3-fluorobenzylsulfonyl)amino, N-methyl-N-(2-pyridylsulfonyl)amino, N-methyl-N-(3-pyridylsulfonyl)amino, N-methyl-N-(4-pyridylsulfonyl)amino, N-methyl-N-(2-thienylsulfonyl)amino, N-methyl-N-(phenylsulfonyl)amino, N-methyl-N-(1-methylimidazol-4-ylsulfonyl)amino, 2-pyridylsulfonylmethyl, 3-pyridylsulfonylmethyl, 4-pyridylsulfonylmethyl, 2-thienylsulfonylmethyl, phenylsulfonylmethyl, 1-phenylsulfonyl-1-methylethyl, 2-furylmethylsulfonylmethyl, 3-trifluloromethylphenylmethyl-sulfonylmethyl, methylsulfonylmethyl, tert-butylsulfonylmethyl, 4-fluorophenyl-methylsulfonylmethyl, 4-chlorophenyl-methylsulfonylmethyl, [0099] phenyl substituted with one or more substituents selected from H, hydroxyl, chloro, fluoro, methoxy, amino, aminomethyl, methylsulfonyl, methyl, cyano, trifluoromethyl, and pyrrolyl, [0100] unsubstituted pyridyl, and [0101] pyridyl substituted with one or more substituents selected from chloro, fluoro, --NH.sub.2, --OH, --CO.sub.2H, methylamino, methyl, ethyl, diethyl-amino, pyrrolidinyl, piperazinyl, piperidinyl, morpholinyl and azetidinyl; [0102] wherein R.sup.9 is one or more substituents selected from H, --OR.sup.11, chloro, fluoro, phenyl, --N(R.sup.11).sub.2, --(C.sub.1-C.sub.2)alkyl-N(R.sup.11).sub.2, --S(O).sub.n--N(R.sup.11).sub.2, --S(O).sub.nR.sup.11, (C.sub.1-C.sub.4)alkyl, (C.sub.3-C.sub.6)cycloalkyl, hydroxy-(C.sub.1-C.sub.4)-alkylamino, (C.sub.1-C.sub.2) alkylamino-(C.sub.1-C.sub.2)-alkylamino, (C.sub.1-C.sub.2)-alkylamino-(C.sub.1-C.sub.2)-alkoxy, optionally substituted heterocyclyl selected from pyrrolidinyl, piperazinyl, piperidinyl, and morpholinyl, --C(O)R.sup.11, --NR.sup.11SO.sub.2R.sup.11, --C(O)N(R.sup.11).sub.2, --CO.sub.2R.sup.11, optionally substituted benzyl, optionally substituted 4-6 membered heterocyclyl-C.sub.1-C.sub.2-alkyl, --NR.sup.11C(O)R.sup.11 and --NR.sup.11CO.sub.2R.sup.11; [0103] preferably H, cyclopropylmethylamino, 3-hydroxypropylamino, 2-(piperidin-1-yl)ethylamino, 2-(pyrrolidin-1-yl)ethylamino, 2-(morpholin-4-yl)ethylamino, 3-(piperidin-1-yl)propylamino, 3-(pyrrolidin-1-yl)propylamino, 3-(morpholin-4-yl)propylamino, N-methyl-N-(2-piperid-1-ylethyl)amino, N-methyl-N-(2-pyrrolidin-1-ylethyl)amino, N-methyl-N-(2-morpholin-4-ylethyl)amino, ((2S)-2-amino-3-phenylpropyl)amino, 4-methylpiperazin-1-ylamino, N-methyl-N-((tetrahydrofur-2-yl)methyl)amino, (4-piperidylmethyl)amino, amino, methylamino, (2-methylbutyl)amino, diethylamino, (diethylamino ethylamino, aminomethyl, dimethylaminoethyl, isopropylaminomethyl, diethylaminomethyl, N-methyl-N-(isopropyl)aminomethyl, N-methyl-N-(diethylaminoethyl)aminomethyl, N-ethyl-N-(dimethylaminoethyl)aminomethyl, (1-hydroxymethyl-2-methylpropyl)amino, cyclopentylaminomethyl, 2-(dimethylamino)ethoxy, 3-(dimethylamino)propoxy, 2-(methylamino)ethoxy, ((2R)pyrrolidin-2-yl)methoxy, ((2R)-1-methylpyrrolidin-2-yl)methoxy, 2-(piperid-1-yl)ethoxy, 2-(piperazin-1-yl)ethoxy, 2-(morpholin-4-yl)ethoxy, hydroxy, benzyloxy, methoxy, chloro, fluoro, phenyl, aminosulfonyl, piperazinylsulfonyl, methylthio, methylsulfonyl, methyl, cyclopropyl, pyrrolidinyl, piperazinyl, piperidin-1-yl, morpholinyl, 4-methylpiperazin-1-yl, 3-aminopyrrolidin-1-yl, 3,5-dimethylpiperazin-1-yl, methylcarbonyl, phenylcarbonyl, piperidin-1-ylcarbonyl, 4-methylpiperazin-1-ylcarbonyl, morpholin-4-ylcarbonyl, trifluoromethyl, hydroxymethyl, hydroxyethyl, diethylaminocarbonyl, ethylaminocarbonyl, methoxycarbonyl, carboxy, optionally substituted benzyl, piperazinylmethyl, azetidin-1-ylmethyl, pyrrolidin-1-ylmethyl, 3-hydroxypyrrolidin-1-ylmethyl, 4-methylpiperazin-1-ylmethyl, 3-methylpiperazin-1-ylmethyl, 3,5-dimethylpiperazin-1-ylmethyl, 3-isopropylpiperazin-1-ylmethyl, 3,6-dihydropyridin-1-ylmethyl, 3-methylpiperidin-1-ylmethyl, 3,5-dimethylpiperidin-1-ylmethyl, 3-hydroxypiperidin-1-ylmethyl, 4-hydroxypiperidin-1-ylmethyl, piperidin-1-ylmethyl, 2,6-dimethylmorpholin-4-ylmethyl and morpholin-4-ylmethyl; [0104] wherein R.sup.10 is selected from H, halo, aryl, cycloalkyl, --OR.sup.11, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, --N(R.sup.11).sub.2, --(C.sub.1-C.sub.8)alkyl-N(R.sup.11).sub.2, --SO.sub.2NR.sup.11R.sup.11, (C.sub.1-C.sub.8)alkyl, cycloalkylalkyl, nitro, cyano, heteroaryl, optionally substituted 5-6 membered heterocyclyl, formyl, alkylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, heterocyclylcarbonyl, --NR.sup.11SO.sub.2R.sup.11, --C(O)N(R.sup.11).sub.2, --CO.sub.2R.sup.11, optionally substituted phenylalkyl, optionally substituted hetetoarylalkyl, --NR.sup.11C(O)N(R.sup.11).sub.2, --NR.sup.11C(O)R.sup.11 and --NR.sup.11CO.sub.2R.sup.11; [0105] preferably H; [0106] wherein n is 0, 1 or 2; [0107] preferably 2; and [0108] wherein R.sup.11 is selected from H, (C.sub.1-C.sub.6)alkyl, optionally substituted phenyl, optionally substituted phenyl-(C.sub.1-C.sub.4)alkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyl-(C.sub.1-C.sub.4)alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 cycloalkyl-(C.sub.1-C.sub.4)alkyl and (C.sub.1-C.sub.2) haloalkyl; [0109] preferably H, methyl, ethyl, propyl, tert-butyl, 2-methylbutyl, cyclopropyl, cyclopentyl, cyclobutyl, cyclohexyl, phenyl, benzyl, phenylethyl, 2-amino-3-phenylpropyl, cyclopropylmethyl, 4-piperidylmethyl, -(1-methylpyrrolidin-2-yl)methyl, (pyrrolidin-2-yl)methyl, piperidinylethyl, (pyrrolidin-1-yl)ethyl, (morpholin-4-yl)ethyl, piperidinylpropyl, (pyrrolidin-1-yl)propyl, (morpholin-4-yl)propyl, trifluoromethyl, 2-furylmethyl, pyridyl, 2-thienyl, piperazinyl, 3,5-dimethylpiperazin-1-yl, 3-aminopyrrolidin-1-yl and 4-methylpiperazin-1-yl; [0110] wherein each alkyl, phenyl, cycloalkyl, and heterocyclyly moiety is optionally substituted with one or more groups selected from halo, --NH.sub.2, --OH, --CO.sub.2H, (C.sub.1-C.sub.4)alkylamino, (C.sub.1-C.sub.4)alkyl, di(C.sub.1-C.sub.4)alkylamino, (C.sub.1-C.sub.4)haloalkyl, pyrrolidinyl, piperazinyl, piperidinyl, morpholinyl, and azetidinyl; and [0111] pharmaceutically acceptable derivatives thereof; [0112] provided Z is not OH; further provided ring W' is not oxadiazolyl or pyrazolyl; further provided R.sup.8 is not unsubstituted 2-phenyl when Z is H, when ring W' is thiazol-4-yl and when R.sup.9 is 6-methoxy; further provided R.sup.8 is not 2-phenyl or 2-[3,4-dimethoxyphenyl] when Z is H, ring W' is thiazol-4-yl and when R.sup.9 is H; and further provided R.sup.8 is not 4-[3,4-dihydroxyphenyl] when Z is H, ring W' is, thiazol-2-yl and when R.sup.9 is H. [0113] The invention also relates to compounds of Formula III [0114] wherein Z is selected from H, hydroxy, amino and phenyl; preferably H, amino and phenyl; [0115] wherein R.sup.8 is selected from pyridyl, pyrazinyl, pyrimidinyl and pyridazinyl; wherein R.sup.8 is unsubstituted or substituted with one or more substituents selected from chloro, fluoro, --NH.sub.2, --OH, --CO.sub.2H, (C.sub.1-C.sub.2)alkylamino(C.sub.1-C.sub.2)alkyl, di(C.sub.1-C.sub.2)alkylamino, (C.sub.1-C.sub.2)alkylamino(C.sub.1-C.sub.2)alkyl, hydroxy-(C.sub.1-C.sub.2)alkylamino, 5-6-membered heterocyclyloxy, 5-6-membered heterocyclyl-(C.sub.1-C.sub.2) alkoxy, [(C.sub.1-C.sub.2)alkoxy].sub.1-3, phenyl, pyrrolidinyl, piperazinyl, piperidinyl, morpholinyl and azetidinyl; [0116] preferably unsubstituted pyridyl or pyridyl substituted with one or more substituents selected from chloro, fluoro, --NH.sub.2, --OH, --CO.sub.2H, methylamino, methyl, ethyl, diethyl-amino, pyrrolidinyl, piperazinyl, piperidinyl, morpholinyl and azetidinyl; [0117] wherein R.sup.9 is one or more radicals selected from H, --OR.sup.11, chloro, fluoro, phenyl, --N(R.sup.11).sub.2, --(C.sub.1-C.sub.2)alkyl-N(R.sup.11).sub.2, --S(O).sub.n--N(R.sup.11).sub.2, --S(O).sub.nR.sup.11, (C.sub.1-C.sub.4)alkyl, (C.sub.3-C.sub.6)cycloalkyl, hydroxy-(C.sub.1-C.sub.4)-alkylamino, (C.sub.1-C.sub.2)-alkylamino-(C.sub.1-C.sub.2)-alkylamino, (C.sub.1-C.sub.2)-alkylamino-(C.sub.1-C.sub.2)-alkoxy, optionally substituted heterocyclyl selected from pyrrolidinyl, piperazinyl, piperidinyl, and morpholinyl, --C(O)R.sup.11, --NR.sup.11SO.sub.2R.sup.11, --C(O)N(R.sup.11).sub.2, --CO.sub.2R.sup.11, optionally substituted benzyl, optionally substituted 4-6 membered heterocyclyl-C.sub.1-C.sub.2-alkyl, --NR.sup.11C(O)R.sup.11 and --NR.sup.11CO.sub.2R.sup.11; [0118] preferably H, cyclopropylmethylamino, 3-hydroxypropylamino, 2-(piperidin-1-yl)ethylamino, 2-(pyrrolidin-1-yl)ethylamino, 2-(morpholin-4-yl)ethylamino, 3-(piperidin-1-yl)propylamino, 3-(pyrrolidin-1-yl)propylamino, 3-(morpholin-4-yl)propylamino, N-methyl-N-(2-piperidin-1-ylethyl)amino, N-methyl-N-(2-pyrrolidin-1-ylethyl)amino, N-methyl-N-(2-morpholin-4-ylethyl)amino, ((2S)-2-amino-3-phenylpropyl)amino, 4-methylpiperazin-1-ylamino, N-methyl-N-((tettahydrofur-2-yl)methyl)amino, (4-piperidylmethyl)amino, amino, methylamino, (2-methylbutyl)amino, diethylamino, (diethylamino)ethylamino, aminomethyl, dimethylaminoethyl, isopropylaminomethyl, diethylaminomethyl, N-methyl-N-(isopropyl)aminomethyl, N-methyl-N-(diethylaminoethyl)aminomethyl, N-ethyl-N-(dimethylaminoethyl)aminomethyl, (1-hydroxymethyl-2-methylpropyl)amino, cyclopentylaminomethyl, 2-(dimethylamino)ethoxy, 3-(dimethylamino)propoxy, 2-(methylamino)ethoxy, ((2R)pyrrolidin-2-yl)methoxy, ((2R)-1-methylpyrrolidin-2-yl)methoxy, 2-(piperid-1-yl)ethoxy, 2-(piperazin-1-yl)ethoxy, 2-(morpholin-4-yl)ethoxy, hydroxy, benzyloxy, methoxy, chloro, fluoro, phenyl, aminosulfonyl, piperazinylsulfonyl, methylthio, methylsulfonyl, methyl, cyclopropyl, pyrrolidinyl, piperazinyl, piperidin-1-yl, morpholinyl, 4-methylpiperazin-1-yl, 3-aminopyrrolidin-1-yl, 3,5-dimethylpiperazin-1-yl, methylcarbonyl, phenylcarbonyl, piperidin-1-ylcarbonyl, 4-methylpiperazin-1-ylcarbonyl, morpholin-4-ylcarbonyl, trifluoromethyl, hydroxymethyl, hydroxyethyl, diethylaminocarbonyl, ethylaminocarbonyl, methoxycarbonyl, carboxy, optionally substituted benzyl, piperazinylmethyl, azetidin-1-ylmethyl, pyrrolidin-1-ylmethyl, 3-hydroxpyrrolidin-1-ylmethyl, 4-methylpiperazin-1-ylmethyl, 3-methylpiperazin-1-ylmethyl, 3,5-dimethylpiperazin-1-ylmethyl, 3-isopropylpiperazin-1-ylmethyl, 3,6-dihydropyridin-1-ylmethyl, 3-methylpiperidin-1-ylmethyl, 3,5-dimethylpiperidin-1-ylmethyl, 3-hydroxypiperidin-1-ylmethyl, 4-hydroxypiperidin-1-ylmethyl, piperidin-1-ylmethyl, 2,6-dimethylmorpholin-4-ylmethyl and morpholin-4-ylmethyl, [0119] wherein n is 0, 1 or 2; [0120] preferably 2; and [0121] wherein R.sup.11 is selected from H, (C.sub.1-C.sub.6)alkyl, optionally substituted phenyl, optionally substituted phenyl-(C.sub.1-C.sub.4) alkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyl-(C.sub.1-C.sub.4)alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6-cycloalkyl-(C.sub.1-C.sub.4) alkyl and, (C.sub.1-C.sub.2) haloalkyl; [0122] preferably H, methyl, ethyl, propyl, tert-butyl, 2-methylbutyl, cyclopropyl, cyclopentyl, cyclobutyl, cyclohexyl, phenyl, benzyl, phenylethyl, 2-amino-3-phenylpropyl, cyclopropylmethyl, 4-piperidylmethyl, -(1-methylpyrrolidin-2-yl)methyl, (pyrrolidin-2-yl)methyl piperidinylethyl, (pyrrolidin-1-yl)ethyl, (morpholin-4-yl)ethyl, piperidinylpropyl, (pyrrolidin-1-yl)propyl, (morpholin-4-yl)propyl, trifluoromethyl, 2-furylmethyl, pyridyl, 2-thienyl, piperazinyl, 3,5-dimethylpiperazin-1-yl, 3-aminopyrrolidin-1-yl and 4-methylpiperazin-1-yl; [0123] wherein each alkyl, phenyl, cycloalkyl, and heterocyclyl moiety is optionally substituted with one or more groups selected from halo, --NH.sub.2, --OH, --CO.sub.2H, (C.sub.1-C.sub.4) alkylamino, (C.sub.1-C.sub.4) alkyl, di(C.sub.1-C.sub.4) alkylamino, (C.sub.1-C.sub.4)haloalkyl, pyrrolidinyl, piperazinyl, piperidinyl, morpholinyl, and azetidinyl; [0124] and pharmaceutically acceptable derivatives thereof. 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