Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-07-13
2003-03-18
Solola, Taofiq (Department: 1626)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S311000, C514S341000, C514S365000, C514S372000, C530S306000, C544S114000, C546S272400, C546S176000, C548S304400, C548S304700
Reexamination Certificate
active
06534503
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to melanocortin receptors and more specifically to the treatment of sexual dysfunction using melanocortin receptor 3 ligands.
2. Background Information
Sexual dysfunction can be due to several physiological, as well as psychological, factors. In males, erectile dysfunction can be associated with diseases such as diabetes mellitus, syphilis, alcoholism, drug dependency, hypopituitarism and hypothyroidism. Erectile dysfunction can also be caused by vascular and neurogenic disorders, or be a side effect of drugs such as hypertensives, sedatives, tranquilizers and amphetamines. In all, erectile dysfunction is estimated to affect up to 10 million men in the United States, with its incidence increasing with age up to 25% of men at age 65.
While various pharmaceutical treatments are commercially available or being developed, the underlying physiological bases for sexual dysfunction are not well understood. Attention has recently been drawn to melanocortin (MC) receptors, which are a group of cell surface proteins that mediate a variety of physiological effects. The MC receptors have been implicated in the regulation of adrenal gland function such as production of the glucocorticoid cortisol and aldosterone, control of melanocyte growth and pigment production, control of feeding, thermoregulation, immunomodulation, inflammation and analgesia. Five distinct MC receptors have been cloned, although the specific role of each MC receptor is still unclear.
Certain compounds, termed “melanocortins” have been found to bind MC receptors, causing the activity of the receptors to increase or decrease. These melanocortins include melanocyte-stimulating hormones (MSH) such as &agr;-MSH, &bgr;-MSH and &ggr;-MSH, as well as adrenocorticotropic hormone (ACTH). Other compounds may bind as ligands to MC receptors, increasing or decreasing the activity of the receptors.
Thus, there is a need for compounds that can affect the activity of specific MC receptors that are involved with sexual dysfunction. The present invention satisfies this need and provides related advantages as well.
SUMMARY OF THE INVENTION
The present invention provides a method for treating sexual dysfunction, such as erectile dysfunction or sexual arousal disorder, with a compound having the generic formula X
1
—X
2
-(D)Phe-Arg-(D)Trp-X
3
. A particularly useful compound is HP-228, which has the formula Ac-Nle-Gln-His-(D)Phe-Arg-(D)Trp-Gly-NH
2
.
The invention also provides methods for selecting melanocortin receptor-3 ligands by determining whether a compound modulates the activity of MC-3 as an agonist or antagonist. These methods can be used to screen compound libraries for ligands to treat MC-3-associated conditions. Such conditions include sexual dysfunction, including erectile dysfunction and sexual arousal disorder.
REFERENCES:
patent: 5010175 (1991-04-01), Rutter et al.
patent: 5182366 (1993-01-01), Huebner et al.
patent: 5288514 (1994-02-01), Ellman
patent: 5324483 (1994-06-01), Cody et al.
patent: 5420109 (1995-05-01), Suto et al.
patent: 5439938 (1995-08-01), Snyder et al.
patent: 5618791 (1997-04-01), Yu-Cang Du
patent: 5726156 (1998-03-01), Girten et al.
patent: 5728156 (1998-03-01), Girten et al.
patent: 5837521 (1998-11-01), Cone et al.
patent: 5874443 (1999-02-01), Kiely et al.
patent: 5889056 (1999-03-01), Hodson et al.
patent: 5916899 (1999-06-01), Kiely et al.
patent: 6054556 (2000-04-01), Huby et al.
patent: 6100048 (2000-04-01), Cone et al.
patent: 0 590 455 (1993-09-01), None
patent: WO 91/19735 (1991-12-01), None
patent: WO 94/01102 (1994-01-01), None
patent: WO 95/02566 (1995-01-01), None
patent: WO 95/04277 (1995-02-01), None
patent: WO 95/13086 (1995-05-01), None
patent: WO 96/27386 (1996-09-01), None
patent: WO 97/22356 (1997-06-01), None
Abou-Mohamed et al., “HP-228, a novel synthetic peptide, inhibits the induction of nitric oxide synthase in vivo but not in vitro,”J. Pharmacology Experimental Therapeutics,275:584-591 (1995).
Berge et al., “Pharmaceutical salts,”J. Pharm. Sci.,66:1-19 (1977).
Castagnoli, “The condensation of succinic anhydride with benzylidinemethylamine. A stereoselective synthesis of trans- and cis-1-Methyl-4-carboxy-5-phenyl-2-pyrrolidinone.”J. of Org. Chem.,34(10):3187-3189 (1969).
Catania and Lipton, “&agr;-Melanocyte-Stimulating Hormone Peptides in Host Response, From Basic Evidence to Human Research,”Annals N.Y. Acad.Sci.,680:412-423 (1993).
Catania et al., “The Neuropeptide &agr;-MSH Has Specific Receptors on Neutrophils and Reduces Chemotaxis In Vitro,”Peptides,17(4):675-679 (1996).
Chowdhary et al., “Localization of the human melanocortin-5 receptor gene (MC5R) to chromosome band 18p11.2 by fluorescence in situ hybridization,”Cytogenet. Cell Genet.68:79-81 (1995).
Coppola, Gary, “Novel heterocycles. 8. Fused isoquinolines derived from the reaction of homophthalic anhydride with cyclic imino ethers.”J. Heterocyclic Chem.,18:767-770 (1981).
Cushman and Castagnoli, “The synthesis of trans-3-methylnicotine.”J. Org. Chem.,37(8):1268-1271 (1972).
Cushman and Castagnoli, “Synthesis of pharmacologically active nitrogen analogs of the tetrahydrocannabinols.”J. Org. Chem.,39(11):1546-1550 (1974).
Cushman and Castagnoli, “The condensation of succinic anhydrides with schiff bases. Scope and mechanism.”J. Org. Chem.,36(22):3404-3406 (1971).
Cushman and Castagnoli, “A novel approach to the synthesis of nitrogen analogs of the tetrahydrocannabinols.”J. Org. Chem.,38(3):440-448 (1973).
Cushman and Madaj, “A study and mechanistic interpretation of the electronic and steric effects that determine the stereochemical outcome of the reaction of schiff bases with homophthalic anhydride and a 3-phenylsuccinic anhydride.”J. Org. Chem.,52(5):907-915 (1987).
Dooley et al., “Melanocortin receptor binding assay in rat brain homogenate: identification of tetrapeptide ligands from a combinatorial library,”Society for Neuroscience23:964 Abstract 383.18 (Aug. 21, 1997).
Dorr et al., “Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study,”Life Sci.,58(20):1777-1784 (1996).
Fan et al., “Role of melanocortinergic neurons in feeding and the agouti obesity syndrome,”Nature,385:165-168 (1997).
Frandberg et al., “Glutamine235and arginine272in human melanocortin 5 receptor determines its low affinity to MSH,”Biochem. Biophys. Res. Commun.236:489-492 (1997).
Friedman, “The alphabet of weight control,”Nature,385:119-120 (1997).
Gallop et al., “Applications of Combinatorial Technologies to Drug Discovery. 1. Background and Peptide Combinatorial Libraries,”J. Med. Chem.,37:1233-1251 (1994).
Gantz et al., “Molecular cloning, expression, and gene localization of a fourth melancortin receptor,”J. Biol. Chem.268:15174-15179 (1993).
Gantz et al., “Molecular cloning of a novel melanocortin receptor,”J. Biol. Chem.268:8246-8250 (1993).
Gantz et al., “Molecular cloning, expression, and characterization of a fifth melanocortin receptor,”Biochem. Biophys. Res. Commun.200:1214-1220 (1994).
Goff and Zuckermann, “Solid-phase synthesis of highly substituted peptide 1(2H)-Isoquinolinones.”J. Org. Chem.,60:5748-5749 (1995).
Gordon et al., “Application of combinatorial technologies to drug discovery. 2. Combinatorial organic synthesis, library screening strategies, and future directions.”J. of Med. Chem.,37(10):1385-1401 (1994).
Gura, “Obesity Sheds Its Secrets,”Science,275:751-753 (1997).
Haimova et al., “A highly stereoselective synthesis of 3,4-dihydro-1(2H)-isoquinolinones and 8-oxoberbines from homophthalic anhydrides and azomethines.”Tetrahedron,33:331-336 (1977).
Haskell-Luevano et al., “Binding and cAMP studies of melanotropin peptides with the cloned human peripheral melanocortin receptor, hMC1R,”Biochem. Biophys. Res. Commun.204:1137-1142 (1994).
Haskell-Luevano et al., “Discovery of prototype peptidomimetic agonists at the human melanocortin receptors MC1R and MC4R,”J. Med. Chem.40:2133-2139 (1997).
Hotamisligil and Spiegelman, “Tumor necrosis factor &agr;: A key component of the obesity-diabet
Dines Kevin C.
Gahman Timothy C.
Girten Beverly E.
Hitchin Douglas L.
Holme Kevin R.
Campbell & Flores LLP
Lion Bioscience AG
Solola Taofiq
LandOfFree
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