Rational design of orally-active, pyrrolidine-based progesterone receptor partial agonists

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 16, 2009, Pages 4777-4780

  Thompson, Scott K ^a   Washburn, David G ^a   Frazee, James S ^a   Madauss, Kevin P ^a   Hoang, Tram H ^a   Lapinski, Leahann ^a   Grygielko, Eugene T ^a   Glace, Lindsay E ^a   Trizna, Walter ^a   Williams, Shawn P ^a   Duraiswami, Chaya ^a   Bray, Jeffrey D ^a   Laping, Nicholas J ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

Agonist; Endometriosis; Hormone receptors; Nuclear receptor; Partial agonist; Progesterone receptor

Indexed keywords

2 CHLORO 4 [(1 METHYL 3 PYRROLIDINYL)[[2 (TRIFLUOROMETHYL)PHENYL]METHYL]AMINO]BENZONITRILE; PARTIAL AGONIST; PROGESTERONE; PROGESTERONE RECEPTOR; PROGESTERONE RECEPTOR PARTIAL AGONIST; PYRROLIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; FEMALE; HUMAN; HUMAN CELL; LIGAND BINDING; NONHUMAN; PROTEIN DOMAIN; RAT; STRUCTURE ANALYSIS;

ADMINISTRATION, ORAL; ANIMALS; BINDING SITES; COMPUTER SIMULATION; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; MODELS, ANIMAL; PROTEIN STRUCTURE, TERTIARY; PYRROLIDINES; RATS; RECEPTORS, PROGESTERONE;

RATTUS;

EID: 67651123094     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.06.055     Document Type: Article

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7. Compound 1's PDB code is 3G8N.
8. Compound 22's PDB code is 3HQ5.
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15. 3)δ: 7.75 (d, J = 3.6 Hz, 1H), 7.55-7.35 (m, 3H), 7.2 (d, J = 3.6 Hz, 1H), 6.75 (d, J = 2.8 Hz, 1H), 6.52 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 5.07 (d, J = 18.8 Hz, 1H), 4.72 (d, J = 18.8 Hz, 1H), 4.64 (m, 1H), 2.90 (m, 1H), 2.7 (m, 2H), 2.6-2.4 (m, 5H), 1.87 (m, 1H).