Synthesis and SAR studies of novel 2-(6-aminomethylaryl-2-aryl-4-oxo- quinazolin-3(4H)-yl)acetamide Vasopressin V 1b receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 12, 2011, Pages 3813-3817

  Napier, Susan E ^a   Letourneau, Jeffrey J ^b   Ansari, Nasrin ^b   Auld, Douglas S ^b   Baker, James ^a   Best, Stuart ^a   Campbell Wan, Leigh ^a   Chan, Ray ^b   Craighead, Mark ^a   Desai, Hema ^b   Ho, Koc Kan ^b   MacSweeney, Cliona ^a   Milne, Rachel ^a   Richard Morphy, J ^a   Neagu, Irina ^b   Ohlmeyer, Michael H J ^b   Pick, Jack ^a   Presland, Jeremy ^a   Riviello, Chris ^b   Zanetakos, Heather A ^b   Zhao, Jiuqiao ^b   Webb, Maria L ^b   more..

^a MSD   (United Kingdom)

^b Ligand Pharmaceuticals Inc   (United States)

Author keywords

Antagonist; HPA; V1b

Indexed keywords

ACETAMIDE DERIVATIVE; VASOPRESSIN RECEPTOR ANTAGONIST; VASOPRESSIN V1B RECEPTOR; VASOPRESSIN V2 RECEPTOR;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; DRUG CLEARANCE; DRUG ELIMINATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; MALE; NONHUMAN; RAT; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION;

ACETAMIDES; ANIMALS; CACO-2 CELLS; HUMANS; HYPOTHALAMO-HYPOPHYSEAL SYSTEM; INHIBITORY CONCENTRATION 50; MALE; MOLECULAR STRUCTURE; QUINAZOLINONES; RATS; RATS, WISTAR; RECEPTORS, VASOPRESSIN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 79957797698     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.04.022     Document Type: Article

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16. Rats were orally administered either vehicle (5% mulgofen in saline) or compound at the appropriate dose at T = 0. At T + 100 min CRH (0.3 μg/kg) or 0.9% phoshpate buffered saline (PBS) was administered through a jugular vein catheter. Desmopressin (dDAVP; 0.5 mg/kg) or PBS was administered iv via the catheter at T + 120 min. At T + 130 min a 0.5 ml blood sample was collected. Samples were stored on ice immediately after collection and then centrifuged (2500 rpm, 4 °C, 15 min). Plasma was extracted and stored at -40 °C. Samples were then analysed for drug and ACTH concentrations by mass spectroscopy and enzyme-linked immunosorbent assay (ELISA: IDS U.K.), respectively.