- Short-acting 5-(trifluoromethyl)pyrido[4,3-d]pyrimidin-4(3H)-one derivatives as orally-active calcium-sensing receptor antagonists
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Synthesis and structure-activity relationship (SAR) studies on 5-trifluoromethylpyrido[4,3-d]pyrimidin-4(3H)-ones, a novel class of calcium receptor antagonists is described with particular emphasis on optimization of the pharmacokinetic/pharmacodynamic parameters required for a short duration of action compound. Orally-active compounds were identified which displayed the desired animal pharmacology (rapid and transient stimulation of parathyroid hormone) essential for bone anabolic effects.
- Didiuk, Mary T.,Griffith, David A.,Benbow, John W.,Liu, Kevin K.C.,Walker, Daniel P.,Christopher Bi,Morris, Joel,Guzman-Perez, Angel,Gao, Hua,Bechle, Bruce M.,Kelley, Ryan M.,Yang, Xiaojing,Dirico, Kenneth,Ahmed, Syed,Hungerford, William,DiBrinno, Joseph,Zawistoski, Michael P.,Bagley, Scott W.,Li, Jianke,Zeng, Yuan,Santucci, Stephanie,Oliver, Robert,Corbett, Matthew,Olson, Thanh,Chen, Chiliu,Li, Mei,Paralkar, Vishwas M.,Riccardi, Keith A.,Healy, David R.,Kalgutkar, Amit S.,Maurer, Tristan S.,Nguyen, Hang T.,Frederick, Kosea S.
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- Synthesis of quinazolin-4(3 H)-ones via amidine N-arylation
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Pyrido[4,3-d]pyrimidin-4(3H)-one (1) was prepared by reacting 2-trifluoromethyl-4-iodo-nicotinic acid (2) with amidine 9a catalyzed by Pd 2(dba)3 and Xantphos, followed by cyclization effected with HBTU and subsequent demethylation u
- Li, Bryan,Samp, Lacey,Sagal, John,Hayward, Cheryl M.,Yang, Christine,Zhang, Zhijun
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p. 1273 - 1277
(2013/04/10)
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- PYRIDO [4,3-d] PYRIMIDIN-4 (3H) -ONE DERIVATIVES AS CALCIUM RECEPTOR ANTAGONISTS
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The present invention is directed to novel pyrido[4,3-d]pyrimidin-4(3H)-one derivatives and pharmaceutically acceptable salts thereof of structural formula I wherein the variables R1, R2, R3, R4 and R5 are as described herein. Also provided are pharmaceutical compositions comprising the compounds of formula I as well as methods of treatment employing compounds of formula I to treat a disease or disorder characterized by abnormal bone or mineral homeostasis such as hypoparathyroidism, osteoporosis, osteopenia, periodontal disease, Paget's disease, bone fracture, osteoarthritis, rheumatoid arthritis, and humoral hypercalcemia of malignancy.
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Page/Page column 24
(2008/06/13)
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