4,5-Disubstituted cis-pyrrolidinones as inhibitors of type II 17β-hydroxysteroid dehydrogenase. Part 3. Identification of lead candidate

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 18, 2006, Pages 4965-4968

  Wood, Jill ^a   Bagi, Cedo M ^a   Akuche, Christiana ^a   Bacchiocchi, Antonietta ^a   Baryza, Jeremy ^a   Blue, Marie Luise ^a   Brennan, Catherine ^a   Campbell, Ann Marie ^a   Choi, Soongyu ^a   Cook, James H ^a   Conrad, Patricia ^a   Dixon, Brian R ^a   Ehrlich, Paul P ^a   Gane, Todd ^a   Gunn, David ^a   Joe, Ted ^a   Johnson, Jeffrey S ^a   Jordan, Jerold ^a   Kramss, Richard ^a   Liu, Peiying ^a   Levy, Joan ^a   Lowe, Derek B ^a   McAlexander, Ian ^a   Natero, Reina ^a   Redman, Anikó M ^a   Scott, William J ^a   Town, Christopher ^a   Wang, Ming ^a   Wang, Yamin ^a   Zhang, Zhonghua ^a   more..

^a BAYER CORPORATION   (United States)

Author keywords

Hydroxysteroid dehydrogenase; Inhibitor; Osteoporosis; Pyrrolidinone

Indexed keywords

2 PYRROLIDONE DERIVATIVE; TESTOSTERONE 17BETA DEHYDROGENASE;

ANIMAL EXPERIMENT; ARTICLE; DRUG STRUCTURE; ENZYME INHIBITION; NONHUMAN; RAT; STEREOCHEMISTRY;

17-HYDROXYSTEROID DEHYDROGENASES; ANIMALS; CELL LINE; ENZYME INHIBITORS; HUMANS; INHIBITORY CONCENTRATION 50; MACACA FASCICULARIS; PYRROLIDINONES; RATS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; THIOPHENES;

EID: 33746843579     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.06.041     Document Type: Article

References (10)

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4. In Tables 1-3 biochemical data are given, compounds are racemic unless otherwise noted.
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6. Wood, J. E.; Baryza, J. L.; Brennan, C. R.; Choi, S.; Cook, J. H.; Dixon, B. R.; Ehrlich, P. P.; Gunn, D. E.; McAlexander, I.; Liu, P.; Lowe, D. B.; Redman, A. M.; Scott, W. J.; Wang, Y. US Patent 6,784,167 B2, 2004.
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8. The human and the rat 17β-HDS II (Accession # NM_ 002153 and BC088134, respectively) are 60% homologous at the protein level using Omiga software.
9. Alcohol 29 could also be resolved by HPLC and used as a late stage intermediate.
10. Absolute stereochemistry as shown was determined by NMR studies on the methoxy-phenylacetic esters of both enantiomers of one analog in the cis-pyrrolidinone series.