| Delta opioid receptor agonist compounds -> Monitor Keywords |
|
|
 
Delta opioid receptor agonist compoundsRelated 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 Two Nitrogens And Four Carbon Atoms (e.g., Pyridazines, Etc.), 1,4-diazine As One Of The Cyclos, Piperazines (i.e., Fully Hydrogenated 1,4-diazines), Plural Carbocyclic Rings Bonded Directly To The Same Acyclic Carbon Atom Which Is Attached Directly Or Indirectly To The Piperazine Ring By Nonionic BondingDelta opioid receptor agonist compounds description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070173515, Delta opioid receptor agonist compounds. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS-REFERENCE TO RELATED APPLICATION [0001] This application is a continuation of and claims priority from copending U.S. patent application Ser. No. 10/335,764, which in turn claims priority from U.S. Provisional Patent Application No. 60/345,216 filed on Jan. 2, 2002. BACKGROUND OF THE INVENTION [0002] 1. Field of the Invention [0003] The present invention relates to compositions and methods of treatment for sexual dysfunctions, and more particularly, to the treatment of premature ejaculation in male subjects by administration of delta receptor agonist compound(s), optionally in combination with other agents. [0004] 2. Description of the Related Art [0005] Premature ejaculation is one of the most common male sexual dysfunctions, estimated to affect up to 40% of men, irrespective of age. Premature ejaculation is defined as a persistent or recurrent ejaculation with minimal sexual stimulation before, on or shortly after penetration. Although premature ejaculation is common, there is some disagreement on its precise cause and treatment. [0006] The reasons for premature ejaculation are generally thought to include a malfunction of the repressor center due to the fatigue of nervous transmission, hypersensitivity of a specific site due to genital disorders, hormonal disorders, physical problems and the like. It is believed that the premature ejaculation is generally caused by a complex interaction of the above-mentioned reasons or by a loss of cooperation among the related sexual nerve centers. [0007] Premature ejaculation has been treated with psychotherapy and drug therapy. Psychotherapy requires sexual training for a long period of time, which involves discussions and cooperation with a physician and the patient and his partner. However, since psychotherapy necessitates a long period of time for the doctor, patient and partner to work together in order to be effective, its success rate is low. That is, changes in living style, external stress, etc., undermine its success such that the problem is never solved or it reoccurs. Therefore, drug therapy is now more widely used since time restrictions are not as great. [0008] Methods for treating premature ejaculation by systemic administration of several different antidepressant compounds have been described in U.S. Pat. Nos. 5,151,448 and 5,276,042. However, these drugs may not be effective for all patients, and the side effects of these drugs can halt treatment or impair patient compliance. Disease states or adverse interactions with other drugs may contraindicate the use of these compounds or require lower dosages that may not be effective to delay the onset of ejaculation. Additionally, the stigma of mental illness associated with antidepressant therapy can discourage patients from beginning or continuing such treatments. [0009] Administration of the antidepressant fluoxetine has been claimed to treat premature ejaculation (U.S. Pat. No. 5,151,448). However, the administration of fluoxetine has many undesired aspects. Patients with hepatic or renal impairments may not be able to use fluoxetine due to its metabolism in the liver and excretion via the kidney. Systemic events during fluoxetine treatment involving the lungs, kidneys or liver have occurred, and death has occurred from overdoses. In addition, side effects of oral fluoxetine administration include hair loss, nausea, vomiting, dyspepsia, diarrhea, anorexia, anxiety, nervousness, insomnia, drowsiness, fatigue, headache, tremors, dizziness, convulsions, sweating and skin rashes. Fluoxetine interacts with a range of drugs, often by impairing their metabolism by the liver. [0010] U.S. Pat. No. 5,276,042 describes the administration of paroxetine for the treatment of premature ejaculation. Paroxetine is predominantly excreted in the urine, and decreased doses are recommended in patients with hepatic and renal impairments. Paroxetine cannot be given to patients undergoing treatment with a monoamine oxidase inhibitor. Side effects from oral administration of paroxetine include hyponatremia, asthenia, sweating, nausea, decreased appetite, oropharynx disorder, somnolence, dizziness, insomnia, tremors, anxiety, impaired micturition, weakness and paresthesia. [0011] Other therapies include the application of local anesthetics for blunting the sensitivity of the sexual peripheral nerve. However, local anesthetics, such as lidocaine ointment or spray, may induce vasoconstriction, which may lead to transient erectile failure, and can be transferred to sexual partners thereby decreasing their sensitivity and pleasure as well. [0012] Thus, present day drug therapy cannot successfully solve the problems associated with premature ejaculation. Accordingly there is a need for a method of treating premature ejaculation that requires no specialized psychological therapy, can be used conveniently and without embarrassment, and does not involve the problems associated with prior therapeutic methods. SUMMARY OF THE INVENTION [0013] The present invention relates in one aspect to a method of treating premature ejaculation by administering to a subject a pharmaceutical composition comprising a delta opioid receptor agonist in an amount effective to delay the onset of ejaculation during sexual stimulation. The delta opioid receptor agonist is either peptidic or non-peptidic. The pharmaceutical formulation may further comprise an additional active agent, e.g., Viagra.RTM. (sildenafil citrate), Prozac.RTM. (fluoxetine), vasoactive agents and combination of two or more thereof. [0014] One aspect of the present invention provides a method for delaying the onset of ejaculation in a subject during sexual stimulation comprising administering to the subject an effective amount of at least one compound of the formulae: wherein: [0015] Ar.sup.1 is a 5- or 6-member carbocyclic or heterocyclic aromatic ring with atoms selected from the group consisting of carbon, nitrogen, oxygen and sulfur and may include thiophenyl, thiazolyl, furanyl, pyrrolyl, phenyl, or pyridyl, and having on a first carbon atom thereof a substituent Y and on a second ring carbon thereof a substituent R.sup.1, [0016] Y is selected from the group consisting of: [0017] hydrogen; [0018] halogen; [0019] C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl; [0020] C.sub.1-C.sub.6 haloalkyl; [0021] C.sub.1-C.sub.6 alkoxy; [0022] C.sub.3-C.sub.6 cycloalkoxy; [0023] sulfides of the formula SR.sup.8 where R.sup.8 is C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.3-C.sub.6 cycloalkyl, arylalkyl having a C.sub.5-C.sub.10 aryl moiety and an C.sub.1-C.sub.6 alkyl moiety, or C.sub.5-C.sub.10 aryl; [0024] sulfoxides of the formula SOR.sup.8 where R.sup.8 is the same as above; [0025] sulfones of the formula SO.sub.2R.sup.8 where R.sup.8 is the same as above; nitrile; [0026] C.sub.1-C.sub.6 acyl; [0027] alkoxycarbonylamino (carbamoyl) of the formula NHCO.sub.2R.sup.8 where R.sup.8 is the same as above; [0028] carboxylic acid, or an ester, amide, or salt thereof; [0029] aminomethyl of the formula CH.sub.2NR.sup.9R.sup.10 where R.sup.9 and R.sup.10 may be the same or different, and may be hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.2-C.sub.6 hydroxyalkyl, C.sub.2-C.sub.6 methoxyalkyl, C.sub.3-C.sub.6 cycloalkyl, or C.sub.5-C.sub.10 aryl, or R.sup.9 and R.sup.10 together may form a ring of 5 or 6 atoms, the ring atoms selected from the group consisting of N and C; [0030] carboxamides of the formula CONR.sup.9R.sup.10 where R.sup.9 and R.sup.10 are the same as above, or C.sub.2-C.sub.30 peptide conjugates thereof; and [0031] sulfonamides of the formula SO.sub.2NR.sup.9R.sup.10 where R.sup.9 and R.sup.10 are the same as above; [0032] Z is selected from the group consisting of: [0033] hydrogen, hydroxy and carboxy and esters thereof; [0034] alkoxy-carboxylic acid, --OCH.sub.3COOH, --ORCOOH; [0035] alkoxy, carboxyalkoxy, hydroxymethyl, and esters thereof; and [0036] amino, carboxamides and sulfonamides thereof; [0037] G is carbon or nitrogen; [0038] R.sup.1 is hydrogen, halogen, or C.sub.1-C.sub.4 alkyl, C.sub.2-C.sub.4 alkenyl, C.sub.2-C.sub.4 alkynyl; [0039] R.sup.2 is hydrogen, halogen, or C.sub.1-C.sub.4 alkyl, C.sub.2-C.sub.4 alkenyl, C.sub.2-C.sub.4 alkynyl; [0040] R.sup.3, R.sup.4 and R.sup.5 may be the same or different, and are independently selected from hydrogen and methyl, and wherein at least one of R.sup.3, R.sup.4 or R.sup.5 is not hydrogen, subject to the proviso that the total number of methyl groups does not exceed two, or any two of R.sup.3, R.sup.4 and R.sup.5 together may form a bridge of 1 to 3 carbon atoms; [0041] R.sup.6 is selected from the group consisting of: [0042] hydrogen; [0043] C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl; [0044] C.sub.3-C.sub.6 cycloalkyl; [0045] arylalkyl having C.sub.5-C.sub.10 aryl and C.sub.1-C.sub.6 alkyl moieties; [0046] alkoxyalkyl having C.sub.1-C.sub.4 alkoxy and C.sub.1-C.sub.4 alkyl moieties; [0047] C.sub.2-C.sub.4 cyanoalkyl; [0048] C.sub.2-C.sub.4 hydroxyalkyl; [0049] aminocarbonylalkyl having a C.sub.1-C.sub.4 alkyl moiety; and [0050] R.sup.12COR.sup.13, where R.sup.12 is C.sub.1-C.sub.4 alkylene, and R.sup.13 is C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 alkoxy or hydroxy, [0051] or R.sup.6 is [0052] and Ar.sup.2 is a 5 or 6-member carbocyclic or heterocyclic aromatic ring with atoms selected from the group consisting of carbon, nitrogen, oxygen and sulfur, and having on a carbon atom thereof a substituent X, [0053] wherein X is selected from the group consisting of a halogen (fluorine, bromine, chlorine, iodine), hydrogen, hydroxy and esters thereof, carboxy and esters thereof; C1-C4 carbosy alkyl and esters thereof; alkyl carboxylic acid, carboxylic acid, alkoxy, hydroxymethyl, and esters thereof; and [0054] amino, and carboxamides and sulfonamides thereof; and [0055] R.sup.7 is hydrogen or fluorine; wherein [0056] R.sub.1 and R.sub.2, which can be the same or different, are each hydrogen, linear or branched C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkenyl, C.sub.4-6 cycloalkylalkyl, C.sub.3-6 alkenyl, C.sub.3-5 alkynyl, aryl, aralkyl or furan-2 or 3-yl alkyl or may form together a C.sub.3-7 alkyl ring which may be interrupted by oxygen. [0057] R.sub.3 and R.sub.4, which can be the same or different, are each hydrogen, linear or branched C.sub.1-6 alkyl, or R.sub.4 is oxygen forming with the carbon atom to which is attached a C.dbd.O group; [0058] R.sub.5 is hydrogen, hydroxy, C.sub.1-3 alkoxy, thiol or alkylthio; [0059] R.sub.6 is phenyl, halogen, NH.sub.2 or a para or meta --C(Z)-R.sub.8 group, in which Z is oxygen or sulphur; [0060] R.sub.8 is C.sub.1-8-alkyl, C.sub.1-8-alkoxy or NR.sub.9R.sub.10, wherein R.sub.9 and R.sub.10, which may be the same or different, are hydrogen, straight or branched C.sub.1-6 allyl, C.sub.3-7 cycloalkyl, C.sub.4-6 cycloalkylalkyl, C.sub.3-6 alkenyl, aryl or aralkyl, [0061] or R.sub.6 is a para or meta group [0062] in which R.sub.11 and R.sub.12 which may the same or different are hydrogen, straight or branched C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.4-6 cycloalkylalkyl, C.sub.3-6 alkenyl, aryl, aralkyl or an optionally substituted heterocyclic ring, and Z is as defined above; and, [0063] R.sub.7 is hydrogen, straight or branched C.sub.1-8 alkyl or halogen; [0064] wherein, [0065] R.sub.1 and R.sub.2, can be the same or different, are each hydrogen, linear or branched C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkenyl, C.sub.4-6 cycloalkylalkyl, C.sub.3-6 alkenyl, C.sub.3-5 alkynyl, aryl, aralkyl or furan-2 or 3-yl alkyl or may form together a C.sub.3-7 alkyl ring which may be interrupted by oxygen. [0066] R.sub.3 and R.sub.4, can be the same or different, are each hydrogen, linear or branched C.sub.1-6 alkyl; [0067] R.sub.5 is hydroxy, C.sub.1-6 alkoxy, thiol or alkylthio; [0068] R.sub.6 is a --C(Z)-R.sub.8 group, wherein Z is oxygen or sulphur, R.sub.8 is C.sub.1-8-alkyl, C.sub.1-8-alkoxy or NR.sub.9R.sub.10, wherein R.sub.9 and R.sub.10, which may be the same or different, are hydrogen, straight or branched C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.4-6 cycloalkylalkyl, C.sub.3-6 alkenyl, aryl or aralkyl, [0069] or R.sub.6 is group [0070] wherein R.sub.11 and R.sub.12 have the same meaning as R.sub.9 and R.sub.10 or together form an optionally substituted heterocyclic ring and Z is as defined above, and R.sub.7 is hydrogen, straight or branched C.sub.1-8 alkyl or halogen; wherein [0071] A is N or C--X wherein [0072] X is H or C.sub.1-4 alkyl; [0073] G is C--Y wherein [0074] Y is H or C.sub.1-4 alkyl; B is an optional C.sub.1-6 hydrocarbyl group, optionally substituted; L is an optional C.sub.1-6 hydrocarbyl group, optionally substituted; and wherein A, B, and L in combination with the N constitute a first ring structure which has from 5-7 atoms in the ring; further wherein: either D is H or a C.sub.1-10 hydrocarbyl group, or D is a C.sub.1-10 hydrocarbyl group linked to B or L to form a second ring structure which includes the N of the first ring structure, which second ring structure is fused to the first ring structure and which second ring structure has from 5-7 atoms in the ring; E is a phenyl group substituted by at least one or more of hydroxy, C.sub.1-4 alkoxy, or NH.sub.2SO.sub.2--C.sub.1-4 alkylene; F represents a combination of a phenyl group and a heterocyclic group, wherein [0075] the phenyl group is positioned intermediate (in between) G and the heterocyclic group; [0076] the phenyl group is fused to the heterocyclic group or is linked directly to the heterocyclic group or is attached via a spacer group to the heterocyclic group, wherein the spacer group is any one of C.sub.1-4 alkylene, carbonyl or SO.sub.2; and [0077] the heterocyclic group is substituted by at least one or more of: a --COOH group, a bio-isostere of a --COOH group, a biolabile ester derivative of a --COOH group, a C.sub.1-10 hydrocarbyl group comprising one or more --COOH groups, a C.sub.1-10 hydrocarbyl group comprising one or more bio-isosteres of a --COOH group, or a C.sub.1-10 hydrocarbyl group comprising one or more biolabile ester derivatives of a --COOH group; and pharmaceutically acceptable esters and salts of compounds (I)-(IV). [0078] The pharmaceutical composition of the present invention may comprises an amount effective to treat sexual dysfunction with at least one a delta opioid receptor agonist described in the following references, the contents of which are incorporated by reference herein in their entireity for all purposes: [0079] Chang et al. U.S. Pat. No. 5,658,908 issued Aug. 19, 1997; [0080] Chang et al. U.S. Pat. No. 5,681,830 issued Oct. 28, 1997; [0081] Chang et al. U.S. Pat. No. 5,552,404 issued Sep. 3, 1996; [0082] Chang et al. U.S. Pat. No. 5,574,159 issued Nov. 12, 1996; [0083] Chang et al. U.S. Pat. No. 5,854,249 issued Dec. 29, 1998; [0084] Chang et al. U.S. Pat. No. 5,807,858 issued Sep. 15, 1998; [0085] Chang et al. U.S. Pat. No. 5,985,880 issued Nov. 16, 1999; [0086] Chang et al. U.S. Pat. No. 6,300,332 issued Oct. 9, 2001; [0087] WO 0146263; [0088] U.S. Pat. No. 6,130,222; [0089] U.S. Pat. No. 6,187,792; [0090] WO 0174804; [0091] WO 9852929; [0092] WO 0174805; and [0093] WO 0174806. [0094] In another aspect of the invention, a pharmaceutical composition is provided for carrying out the methods of the invention. The pharmaceutical composition comprises an effective amount of a delta opioid receptor agonist as provided herein, a pharmacologically acceptable carrier, and optionally another active agent. Other types of components may be incorporated into the composition as well, e.g., excipients, surfactants, preservatives, stabilizers, chelating agents and the like, as will be appreciated by those skilled in the art of pharmaceutical composition preparation and drug delivery. [0095] Administration of the pharmaceutical composition is carried out within the context of a predetermined dosing regime such that the delta opioid receptor agonist is effective in the treatment of premature ejaculation. [0096] Delivery of the pharmaceutical compositions may be accomplished through any route effective to provide relief from premature ejaculation, including, oral, rectal, topical, sub-lingual, mucosal, nasal, ophthalmic, subcutaneous, intramuscular, intravenous, transdermal, spinal, intrathecal, intra-articular, intra-arterial, sub-arachnoid, bronchial, lymphatic, transurethral, intracavernosal injection and urethral suppository administration. [0097] Yet another aspect of the present invention relates to damping male sexual response or diminishing sexual libido in a subject by administering to the subject in need thereof, an effective amount of a delta opioid receptor agonist. [0098] Various other aspects, features and embodiments of the invention will be more fully apparent from the ensuing disclosure and appended claims. BRIEF DESCRIPTION OF THE DRAWINGS Continue reading about Delta opioid receptor agonist compounds... Full patent description for Delta opioid receptor agonist compounds Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Delta opioid receptor agonist compounds patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. Start now! - Receive info on patent apps like Delta opioid receptor agonist compounds or other areas of interest. ### Previous Patent Application: Methods for suppressing an immune response or treating a proliferative disorder Next Patent Application: Pyrazine kinase inhibitors Industry Class: Drug, bio-affecting and body treating compositions ### FreshPatents.com Support Thank you for viewing the Delta opioid receptor agonist compounds patent info. IP-related news and info Results in 0.17606 seconds Other interesting Feshpatents.com categories: Novartis , Pfizer , Philips , Polaroid , Procter & Gamble , 174 |
 * Protect your Inventions * US Patent Office filing 
PATENT INFO |
|
