Synthesis and SAR studies of novel 2-(4-oxo-2-aryl-quinazolin-3(4H)-yl) acetamide vasopressin V1b receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 6, 2011, Pages 1871-1875

  Napier, Susan E ^b   Letourneau, Jeffrey J ^a   Ansari, Nasrin ^a   Auld, Douglas S ^a   Baker, James ^b   Best, Stuart ^b   Campbell Wan, Leigh ^b   Chan, Jui Hsiang ^a   Craighead, Mark ^b   Desai, Hema ^a   Goan, Katharine A ^b   Ho, Koc Kan ^a   Hulskotte, Ellen G J ^c   MacSweeney, Cliona P ^b   Milne, Rachel ^b   Morphy, J Richard ^b   Neagu, Irina ^a   Ohlmeyer, Michael H J ^a   Peeters, Ard W M M ^c   Presland, Jeremy ^b   Riviello, Chris ^a   Ruigt, Ge S F ^c   Thomson, Fiona J ^b   Zanetakos, Heather A ^a   Zhao, Jiuqiao ^a   Webb, Maria L ^a   more..

^a Ligand Pharmaceuticals Inc   (United States)

^b MSD   (United Kingdom)

^c MSD   (Netherlands)

Author keywords

HPA axis; Vasopressin

Indexed keywords

2 [4 OXO 2 ARYL QUINAZOLIN 3[4H] YL]ACETAMIDE; ACETAMIDE DERIVATIVE; HORMONE RECEPTOR BLOCKING AGENT; NELIVAPTAN; OXYTOCIN RECEPTOR; UNCLASSIFIED DRUG; VASOPRESSIN V1A RECEPTOR; VASOPRESSIN V1B RECEPTOR; VASOPRESSIN V1B RECEPTOR ANTAGONIST; VASOPRESSIN V2 RECEPTOR;

ARTICLE; DRUG ACTIVITY; DRUG IDENTIFICATION; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; NONHUMAN; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION;

ANIMALS; HUMANS; QUINAZOLINES; RATS; RECEPTORS, VASOPRESSIN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 79952363767     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.12.081     Document Type: Article

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18. 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% phosphate 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 UK), respectively.