title: Identification and optimization of novel 2-(4-oxo-2-aryl-quinazolin-3(4H)-yl)acetamide vasopressin V3 (V1b) receptor antagonists.
abstract: The discovery, synthesis, and preliminary structure-activity relationship (SAR) of a novel class of vasopressin V3 (V1b) receptor antagonists is described. Compound 1, identified by high throughput screening of a diverse, three million-member compound collection, prepared using ECLiPS technology, had good activity in a V3 binding assay (IC50=0.20 microM), but less than desirable physicochemical properties. Optimization of compound 1 yielded potent analogs 19 (IC50=0.31 microM) and 24 (IC50=0.12 microM) with improved drug-like characteristics.
authors: Ligand Pharmaceuticals, Inc., 3000 Eastpark Boulevard, Cranbury, NJ 08512, USA. jletourneau@ligand.com
authors: Jeffrey J
authors: JJ
authors: Letourneau
authors: Christopher M
authors: CM
authors: Riviello
authors: Hong
authors: H
authors: Li
authors: Andrew G
authors: AG
authors: Cole
authors: Koc-Kan
authors: KK
authors: Ho
authors: Heather A
authors: HA
authors: Zanetakos
authors: Hema
authors: H
authors: Desai
authors: Jiuqiao
authors: J
authors: Zhao
authors: Douglas S
authors: DS
authors: Auld
authors: Susan E
authors: SE
authors: Napier
authors: Fiona J
authors: FJ
authors: Thomson
authors: Katharine A
authors: KA
authors: Goan
authors: J Richard
authors: JR
authors: Morphy
authors: Michael H J
authors: MH
authors: Ohlmeyer
authors: Maria L
authors: ML
authors: Webb
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D003866:Depressive Disorder / Q000188:drug therapy; D006801:Humans; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017483:Receptors, Vasopressin / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D065092:Antidiuretic Hormone Receptor Antagonists; D011799:Quinazolines; D017483:Receptors, Vasopressin; C030686:acetamide