Metabolism-guided discovery of a potent and orally bioavailable urea-based calcimimetic for the treatment of secondary hyperparathyroidism

Bioorganic and Medicinal Chemistry Letters

Volumn 23, Issue 24, 2013, Pages 6625-6628

  Wehn, Paul M ^a   Harrington, Paul E ^a   Carlson, Timothy J ^a   Davis, James ^a   Deprez, Pierre ^b   Fotsch, Christopher H ^a   Grillo, Mark P ^a   Lu, Jenny Ying Lin ^a   Morony, Sean ^a   Pattabiraman, Kanaka ^a   Poon, Steve F ^a   Reagan, Jeff D ^a   St Jean, David J ^a   Temal, Taoues ^b   Wang, Minghan ^a   Yang, Yuhua ^a   Henley III, Charles ^a   Lively, Sarah E ^a  

^a AMGEN INC   (United States)

^b Galapagos SASU   (France)

Author keywords

1,2,4 Thiadiazoles; Calcimimetics; Metabolite ID; Positive allosteric modulators; Time dependent inhibition

Indexed keywords

1,2,4 THIADIAZOLE DERIVATIVE; CALCIMIMETIC AGENT; CYTOCHROME P450 3A4; THIOUREA DERIVATIVE;

ARTICLE; CHEMICAL MODIFICATION; COVALENT BOND; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG METABOLISM; DRUG POTENCY; DRUG STABILITY; ENZYME INHIBITION; EPOXIDATION; FLUORINATION; HORNER WADSWORTH EMMONS REACTION; IN VIVO STUDY; LIVER MICROSOME; NEPHRECTOMY; NONHUMAN; SECONDARY HYPERPARATHYROIDISM;

RATTUS;

1,2,4-THIADIAZOLES; CALCIMIMETICS; METABOLITE ID; POSITIVE ALLOSTERIC MODULATORS; TIME DEPENDENT INHIBITION;

ADMINISTRATION, ORAL; ANIMALS; BIOLOGICAL AVAILABILITY; HALF-LIFE; HYPERPARATHYROIDISM, SECONDARY; MALE; PARATHYROID HORMONE; PROTEIN BINDING; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, CALCIUM-SENSING; THIAZOLES; UREA;

EID: 84888864571     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2013.10.050     Document Type: Article

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