View source for Chemistry:BMS-564,929

{{short description|Chemical compound}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 424678818
| IUPAC_name = 4-[(7''R'',7a''S'')-7-hydroxy-1,3-dioxo-hexahydro-1''H''-pyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile
| image = BMS-564,929.svg
| width = 250px

<!--Clinical data-->
| tradename = 
| pregnancy_AU = <!-- A, B1, B2, B3, C, D, X -->
| pregnancy_US = <!-- A, B, C, D, X -->
| pregnancy_category = 
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
| legal_US = Investigational New Drug
| legal_status = 
| routes_of_administration =

<!--Pharmacokinetic data-->
| bioavailability = 
| protein_bound = 
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| elimination_half-life = 
| excretion =

<!--Identifiers-->
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 627530-84-1
| ATC_prefix = 
| ATC_suffix = 
| ATC_supplemental = 
| PubChem = 9882972
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB07286
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 8058647
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = KEJORAMIZFOODM-PWSUYJOCSA-N
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = 9BLW27W4X7
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 229264
| synonyms =

<!--Chemical data-->
| C=14 | H=12 | Cl=1 | N=3 | O=3 
| SMILES = CC1=C(C=CC(=C1Cl)C#N)N2C(=O)[C@@H]3[C@@H](CCN3C2=O)O
}}

'''BMS-564,929''' is an investigational [[Chemistry:Selective androgen receptor modulator|selective androgen receptor modulator]] (SARM) which is being developed by [[Company:Bristol-Myers Squibb|Bristol-Myers Squibb]] for treatment of the symptoms of age-related decline in androgen levels in men ("andropause"). These symptoms may include [[Medicine:Depression (mood)|depression]], loss of [[Biology:Muscle|muscle]] mass and strength, reduction in [[Philosophy:Libido|libido]] and [[Medicine:Osteoporosis|osteoporosis]]. Treatment with exogenous [[Chemistry:Testosterone (medication)|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 [[Medicine:Prostate cancer|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.<ref>{{cite journal | vauthors = Gao W, Dalton JT | title = Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs) | journal = Drug Discovery Today | volume = 12 | issue = 5–6 | pages = 241–8 | date = March 2007 | pmid = 17331889 | pmc = 2072879 | doi = 10.1016/j.drudis.2007.01.003 }}</ref>

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 ([[Chemistry:Dissociation constant|Ki]] 2.1nM, 20x [[Biology:Functional selectivity|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.<ref>{{cite journal | vauthors = Ostrowski J, Kuhns JE, Lupisella JA, Manfredi MC, Beehler BC, Krystek SR, Bi Y, Sun C, Seethala R, Golla R, Sleph PG, Fura A, An Y, Kish KF, Sack JS, Mookhtiar KA, Grover GJ, Hamann LG | display-authors = 6 | title = 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 | journal = Endocrinology | volume = 148 | issue = 1 | pages = 4–12 | date = January 2007 | pmid = 17008401 | doi = 10.1210/en.2006-0843 | doi-access = free }}</ref> It does however vastly reduce [[Biology:Luteinizing hormone|luteinizing hormone]] levels, it being an astonishing 33× more suppressive compound than testosterone, which may be a problem in human clinical use.<ref>{{cite journal | vauthors = Gao W, Dalton JT | title = Ockham's razor and selective androgen receptor modulators (SARMs): are we overlooking the role of 5alpha-reductase? | journal = Molecular Interventions | volume = 7 | issue = 1 | pages = 10–3 | date = February 2007 | pmid = 17339601 | pmc = 2040232 | doi = 10.1124/mi.7.1.3 }}</ref>

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 [[Chemistry:Anabolic steroid|anabolic steroid]]s but with significantly fewer side effects. For this reason, SARMs have already been banned by the [[Organization:World Anti-Doping Agency|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.<ref>{{cite journal | vauthors = Thevis M, Kohler M, Schlörer N, Kamber M, Kühn A, Linscheid MW, Schänzer W | title = Mass spectrometry of hydantoin-derived selective androgen receptor modulators | journal = Journal of Mass Spectrometry | volume = 43 | issue = 5 | pages = 639–50 | date = May 2008 | pmid = 18095383 | doi = 10.1002/jms.1364 | bibcode = 2008JMSp...43..639T }}</ref><ref>{{cite journal | vauthors = Thevis M, Kohler M, Thomas A, Maurer J, Schlörer N, Kamber M, Schänzer W | s2cid = 206899531 | title = Determination of benzimidazole- and bicyclic hydantoin-derived selective androgen receptor antagonists and agonists in human urine using LC-MS/MS | journal = Analytical and Bioanalytical Chemistry | volume = 391 | issue = 1 | pages = 251–61 | date = May 2008 | pmid = 18270691 | doi = 10.1007/s00216-008-1882-6 }}</ref>

== References ==
{{Reflist}}

== External links ==
* [http://www.rcsb.org/pdb/explore/explore.do?pdbId=2NW4 Crystal Structure Of The Rat Androgen Receptor Ligand Binding Domain Complex With Bms-564929] at [[Biology:Protein Data Bank|Protein Data Bank]]

{{Androgen receptor modulators}}

[[Category:Secondary alcohols]]
[[Category:Imides]]
[[Category:Lactams]]
[[Category:Nitriles]]
[[Category:Pyrroloimidazoles]]
[[Category:Selective androgen receptor modulators]]
[[Category:Ureas]]

{{Sourceattribution|BMS-564,929}}