Short-acting 5-(trifluoromethyl)pyrido[4,3-d]pyrimidin-4(3H)-one derivatives as orally-active calcium-sensing receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 16, 2009, Pages 4555-4559

  Didiuk, Mary T ^a   Griffith, David A ^a   Benbow, John W ^a   Liu, Kevin K C ^a   Walker, Daniel P ^a   Christopher Bi, F ^a   Morris, Joel ^a   Guzman Perez, Angel ^a   Gao, Hua ^a   Bechle, Bruce M ^a   Kelley, Ryan M ^a   Yang, Xiaojing ^a   Dirico, Kenneth ^a   Ahmed, Syed ^a   Hungerford, William ^a   DiBrinno, Joseph ^a   Zawistoski, Michael P ^a   Bagley, Scott W ^a   Li, Jianke ^a   Zeng, Yuan ^a   Santucci, Stephanie ^a   Oliver, Robert ^a   Corbett, Matthew ^a   Olson, Thanh ^a   Chen, Chiliu ^a   Li, Mei ^a   Paralkar, Vishwas M ^a   Riccardi, Keith A ^a   Healy, David R ^a   Kalgutkar, Amit S ^a   Maurer, Tristan S ^a   Nguyen, Hang T ^a   Frederick, Kosea S ^a   more..

^a PFIZER INC   (United States)

Author keywords

Calcium receptor antagonists; Human parathyroid hormone; Osteoporosis; Pharmacokinetics; SAR exploration

Indexed keywords

2 CHLORO 6 [3 [1,1 DIMETHYL 2 (2 NAPHTHYL)ETHYLAMINO] 2 HYDROXYPROPOXY]BENZONITRILE; 5 (TRIFLUOROMETHYL)PYRIDO[4,3 D]PYRIMIDIN 4(3H) ONE DERIVATIVE; CALCIUM ANTAGONIST; CALCIUM SENSING RECEPTOR; PARATHYROID HORMONE; PARATHYROID HORMONE[1-34]; RECOMBINANT PARATHYROID HORMONE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG SYNTHESIS; IC 50; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADMINISTRATION, ORAL; ANABOLIC AGENTS; ANIMALS; MALE; PARATHYROID HORMONE; PYRIMIDINONES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, CALCIUM-SENSING; STRUCTURE-ACTIVITY RELATIONSHIP;

ANIMALIA;

EID: 67651115761     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.07.004     Document Type: Article

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30. Title compounds were prepared using the appropriate arylaldehyde derivatives according to the general protocol outlined in Scheme 1.
31. A plausible explanation for lack of significant glucuronidation of the phenolic OH group may be due to the formation of a stable internal H-bond as shown.{A figure is presented}
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