BMS-564,929

BMS-564,929
Legal status

Legal status	Investigational new drug
Identifiers
IUPAC name 4-[(7R,7aS)-7-hydroxy-1,3-dioxo-hexahydro-1H-pyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile
CAS Number	627530-84-1^N
PubChem (CID)	9882972
DrugBank	DB07286^N
ChemSpider	8058647^N
UNII	9BLW27W4X7^N
ChEMBL	CHEMBL229264^N
Chemical and physical data
Formula	C₁₄H₁₂ClN₃O₃
Molar mass	305.716 g/mol
3D model (Jmol)	Interactive image
SMILES CC1=C(C=CC(=C1Cl)C#N)N2C(=O)[C@@H]3[C@@H](CCN3C2=O)O
InChI InChI=1S/C14H12ClN3O3/c1-7-9(3-2-8(6-16)11(7)15)18-13(20)12-10(19)4-5-17(12)14(18)21/h2-3,10,12,19H,4-5H2,1H3/t10-,12+/m1/s1^N Key:KEJORAMIZFOODM-PWSUYJOCSA-N^N
^NY (what is this?) (verify)

BMS-564,929 is an investigational selective androgen receptor modulator, which is being developed by Bristol-Myers Squibb for treatment of the symptoms of age-related decline in androgen levels in men ("andropause"). These symptoms may include depression, loss of muscle mass and strength, reduction in libido and osteoporosis. Treatment with exogenous testosterone is effective in counteracting these symptoms but is associated with a range of side effects, the most serious of which is enlargement of the prostate gland, which can lead to benign prostatic hypertrophy and even prostate cancer. This means there is a clinical need for selective androgen receptor modulators, which produce anabolic effects in some tissues such as muscle and bone, but without stimulating androgen receptors in the prostate.^[1]

BMS-564,929 is one such compound currently in early human clinical trials, which is an orally active, potent and selective agonist for androgen receptors (Ki 2.1nM, 20x functional selectivity for muscle tissue over prostate) and in studies on castrated rats it was shown to counteract decrease in muscle mass over time, and at higher doses even increased muscle mass, without significantly affecting prostate tissue.^[2] It does however vastly reduce luteinizing hormone levels, it being an astonishing 33x more suppressive compound than testosterone, which may be a problem in human clinical use.^[3]

Selective androgen receptor modulators may also be used by athletes to assist in training and increase physical stamina and fitness, potentially producing effects similar to anabolic steroids but with significantly fewer side effects. For this reason, SARMs have already been banned by the World Anti-Doping Agency since January 2008 despite no drugs from this class yet being in clinical use, and blood tests for all known SARMs are currently being developed.^[4]^[5]

References

↑ Gao, W; Dalton, JT (2007). "Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs)". Drug Discovery Today. 12 (5–6): 241–8. doi:10.1016/j.drudis.2007.01.003. PMC 2072879. PMID 17331889.
↑ Ostrowski, J; Kuhns, JE; Lupisella, JA; Manfredi, MC; Beehler, BC; Krystek Jr, SR; Bi, Y; Sun, C; et al. (2007). "Pharmacological and x-ray structural characterization of a novel selective androgen receptor modulator: potent hyperanabolic stimulation of skeletal muscle with hypostimulation of prostate in rats". Endocrinology. 148 (1): 4–12. doi:10.1210/en.2006-0843. PMID 17008401.
↑ Gao, W; Dalton, JT (2007). "Ockham's Razor and Selective Androgen Receptor Modulators (SARMs): Are We Overlooking the Role of 5α-Reductase?". Molecular interventions. 7 (1): 10–3. doi:10.1124/mi.7.1.3. PMC 2040232. PMID 17339601.
↑ Thevis, M; Kohler, M; Schlörer, N; Kamber, M; Kühn, A; Linscheid, MW; Schänzer, W (2008). "Mass spectrometry of hydantoin-derived selective androgen receptor modulators". Journal of mass spectrometry : JMS. 43 (5): 639–50. doi:10.1002/jms.1364. PMID 18095383.
↑ Thevis, M; Kohler, M; Thomas, A; Maurer, J; Schlörer, N; Kamber, M; Schänzer, W (2008). "Determination of benzimidazole- and bicyclic hydantoin-derived selective androgen receptor antagonists and agonists in human urine using LC-MS/MS". Analytical and Bioanalytical Chemistry. 391 (1): 251–61. doi:10.1007/s00216-008-1882-6. PMID 18270691.

External links

Crystal Structure Of The Rat Androgen Receptor Ligand Binding Domain Complex With Bms-564929 at Protein Data Bank

Androgen receptor modulators

Agonists	Testosterone derivatives: 4-Androstenediol 4-Androstenedione 4-Dehydroepiandrosterone (4-DHEA) 4-Hydroxytestosterone 5-Androstenediol 5-Androstenedione 11-Ketotestosterone 11β-Hydroxyandrostenedione Adrenosterone (11-ketoandrostenedione, 11-oxoandrostenedione) Atamestane Boldenone Boldenone undecylenate Boldione (1,4-androstadienedione) Clostebol Clostebol acetate Clostebol caproate Clostebol propionate Cloxotestosterone Cloxotestosterone acetate DHEA (androstenolone, prasterone; 5-DHEA) DHEA enanthate (prasterone enanthate) DHEA sulfate Exemestane Formestane Plomestane Quinbolone Silandrone Testosterone^# Testosterone acetate Testosterone acetate butyrate Testosterone acetate propionate Testosterone benzoate Testosterone butyrate Testosterone buciclate Testosterone capropate Testosterone cyclohexylpropionate Testosterone cypionate Testosterone decanoate Testosterone diacetate Testosterone dipropionate Testosterone enanthate Testosterone formate Testosterone furoate Testosterone hexahydrobenzoate Testosterone hexahydrobenzylcarbonate Testosterone hexyloxyphenylpropionate Testosterone isobutyrate Testosterone isocaproate Testosterone isovalerate Testosterone ketolaurate Testosterone nicotinate Testosterone palmitate Testosterone phenylacetate Testosterone phenylbutyrate Testosterone phenylpropionate Testosterone phosphate Testosterone propionate Testosterone stearate Testosterone sulfate Testosterone undecanoate Testosterone valerate Dihydrotestosterone derivatives: 1-Androstenediol 1-Androstenedione 1-Androsterone (1-andro, 1-DHEA) 1-Testosterone 3α-Androstanediol 7β-Hydroxyepiandrosterone 11-Ketodihydrotestosterone Androsterone Bolazine Bolazine capronate Dihydrotestosterone (androstanolone, stanolone) Dihydrotestosterone acetate Dihydrotestosterone benzoate Dihydrotestosterone butyrate Dihydrotestosterone enanthate Dihydrotestosterone formate Dihydrotestosterone propionate Dihydrotestosterone valerate Drostanolone Drostanolone propionate Epiandrosterone Epitiostanol Mepitiostane Mesabolone Mesterolone Nisterime Nisterime acetate Prostanozol Stenbolone Stenbolone acetate 19-Nortestosterone derivatives: 7α-Methyl-19-norandrostenedione (MENT dione, trestione) 11β-Methyl-19-nortestosterone 11β-Methyl-19-nortestosterone dodecylcarbonate 19-Nor-5-androstenediol 19-Nor-5-androstenedione Bolandiol Bolandiol dipropionate Bolandione (19-nor-4-androstenedione) Bolmantalate (nandrolone adamantoate) Dienedione Dienolone Dimethandrolone Dimethandrolone buciclate Dimethandrolone dodecylcarbonate Dimethandrolone undecanoate LS-1727 (nandrolone 17β-N-(2-chloroethyl)-N-nitrosocarbamate) Methoxydienone (methoxygonadiene) Nandrolone Nandrolone acetate Nandrolone caproate Nandrolone cypionate Nandrolone cyclohexanecarboxylate Nandrolone cyclohexylpropionate Nandrolone cyclotate Nandrolone decanoate Nandrolone formate Nandrolone furylpropionate Nandrolone hexyloxyphenylpropionate Nandrolone hydrogen succinate Nandrolone laurate Nandrolone phenylpropionate Nandrolone propionate Nandrolone sulfate Nandrolone sulfate sodium Nandrolone undecanoate Norclostebol Norclostebol acetate Normethandrone (methylestrenolone, normethisterone) Oxabolone Oxabolone cipionate (oxabolone cypionate) Trenbolone Trenbolone acetate Trenbolone enanthate Trenbolone hexahydrobenzylcarbonate Trestolone (MENT) Trestolone acetate Dihydrotestosterone and 19-nortestosterone derivatives: 5α-Dihydronandrolone 19-Norandrosterone 17α-Alkylated testosterone derivatives: Bolasterone Calusterone Chlorodehydromethylandrostenediol (CDMA) Chlorodehydromethyltestosterone (CDMT) Chloromethylandrostenediol (CMA) Enestebol Ethyltestosterone Fluoxymesterone Formebolone Hydroxystenozole Metandienone (methandrostenolone) Methandriol (methylandrostenediol) Methandriol bisenanthoyl acetate Methandriol diacetate Methandriol dipropionate Methandriol propionate Methylclostebol (chloromethyltestosterone) Methyltestosterone Oxymesterone Penmesterol Tiomesterone 17α-Alkylated dihydrotestosterone derivatives: Androisoxazole Desoxymethyltestosterone Furazabol Mebolazine (dimethazine) Mestanolone Metenolone Metenolone acetate Metenolone enanthate Methasterone Methyl-1-testosterone Methylepitiostanol Methylstenbolone Oxandrolone Oxymetholone Stanozolol 17α-Alkylated 19-nortestosterone derivatives: Bolenol Dimethyltrienolone (7α-methylmetribolone, 7α,17α-dimethyltrenbolone) Ethyldienolone Ethylestrenol Methyldienolone Methylhydroxynandrolone (MOHN, MHN) Metribolone Mibolerone Norboletone Norethandrolone Propetandrol Tetrahydrogestrinone 17α-Vinyltestosterone derivatives: Norvinisterone (vinylnortestosterone) Vinyltestosterone 17α-Ethynyltestosterone derivatives: Δ^4-Tibolone Chloroethynyl norgestrel Danazol Desogestrel Ethisterone (ethynyltestosterone) Etonogestrel Gestodene Gestrinone Levonorgestrel Levonorgestrel butanoate Norethisterone Norethisterone acetate Norethisterone acetate oxime Norethisterone enanthate Norgestrel Norgestrienone Quingestanol acetate Tibolone Progesterone derivatives: Medroxyprogesterone acetate Others/unsorted: Cl-4AS-1

Mixed (SARMs)	Non-steroidal: 198RL26 ACP-105 AC-262,356 Acetothiolutamide Andarine (acetamidoxolutamide, androxolutamide, GTx-007, S-4) BMS-564,929 Enobosarm (ostarine, MK-2866, GTx-024, S-22) FTBU-1 GSK-4336A GSK-8698 LG-121071 (LGD-121071) LGD-2226 LGD-2941 (LGD-122941) LGD-3303 LGD-4033 JNJ-26146900 JNJ-28330835 JNJ-37654032 ORM-11984 RAD140 R-1 R-2 R-3 S-1 S-23 S-40503 S-101479 Steroidal: MK-0773 TFM-4AS-1 YK-11

Antagonists	Steroidal: 3α-Hydroxytibolone 3β-Hydroxytibolone 11α-Hydroxyprogesterone 15β-Hydroxycyproterone acetate Abiraterone acetate Allyltestosterone Benorterone BOMT Canrenoic acid Canrenone Chlormadinone acetate Clometerone Cortexolone 17α-propionate (CB-03-01) Cyproterone Cyproterone acetate Delanterone Dienogest Drospirenone Edogestrone Epitestosterone Galeterone Guggulsterone Medrogestone Megestrol acetate Mespirenone Metogest Mexrenone Mifepristone Nomegestrol acetate Nordinone Osaterone Osaterone acetate Oxendolone Potassium canrenoate Prorenone Rosterolone SC-5233 (spirolactone) Spironolactone Spirorenone Topterone Trimethyltrienolone (R-2956) Zanoterone Non-steroidal: AA560 Apalutamide Atraric acid AZD-3514 BAY-1024767 Bicalutamide Bisphenols (e.g., BADGE, BFDGE, bisphenol A, bisphenol F, bisphenol S) BMS-641,988 Cimetidine Cioteronel Darolutamide DDT (via metabolite p,p’-DDE) Dieldrin DIMP Endosulfan Enzalutamide EPI-001 EPI-506 Fenarimol Flutamide Hydroxyflutamide Inocoterone Inocoterone acetate Ketoconazole Lavender oil LG-105 LG-120907 Linuron Methiocarb N-Butylbenzenesulfonamide N-Desmethylenzalutamide Nilutamide ONC1-13B ORM-15341 Pentomone PF-998425 Phenothrin Prochloraz Procymidone RU-22930 RU-58642 RU-58841 Seviteronel Thalidomide Topilutamide (fluridil) Valproic acid Vinclozolin

GPRC6A

Agonists	Cations (incl. aluminum, calcium, gadolinium, magnesium, strontium) Dehydroandrosterone Dihydrotestosterone Estradiol L-α-Amino acids (incl. L-arginine, L-lysine, L-ornithine) Osteocalcin Testosterone

See also: Estrogenics • Glucocorticoidics • Mineralocorticoidics • Progestogenics • Steroid hormone metabolism modulators • List of androgens/anabolic steroids

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