Identification and synthesis of major metabolites of Vasopressin V2-receptor agonist WAY-151932, and antagonist, Lixivaptan

Albert J Molinari; Eugene J Trybulski; Jehan Bagli; Susan Croce; John Considine; Jian Qi; Kadum Ali; William Demaio; Lynne Lihotz; David Cochran

doi:10.1016/j.bmcl.2007.08.053

Identification and synthesis of major metabolites of Vasopressin V2-receptor agonist WAY-151932, and antagonist, Lixivaptan

Bioorg Med Chem Lett. 2007 Nov 1;17(21):5796-800. doi: 10.1016/j.bmcl.2007.08.053. Epub 2007 Aug 28.

Authors

Albert J Molinari¹, Eugene J Trybulski, Jehan Bagli, Susan Croce, John Considine, Jian Qi, Kadum Ali, William Demaio, Lynne Lihotz, David Cochran

Affiliation

¹ Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA. Molinaa@wyeth.com

PMID: 17855087
DOI: 10.1016/j.bmcl.2007.08.053

Abstract

Small molecule agonists and antagonists of the V(2)-vasopressin receptor have been discovered and have undergone clinical trials. In conjunction with these discovery programs, the synthesis and biological testing of various metabolites associated with these clinical targets were actively pursued. We now report the results of our synthetic efforts and the corresponding biological data generated for several of the metabolites of WAY-151932 and CL-347985 (Lixivaptan).

MeSH terms

Antidiuretic Hormone Receptor Antagonists*
Azepines / chemical synthesis
Azepines / chemistry*
Azepines / pharmacology
Benzamides / chemical synthesis
Benzamides / chemistry*
Benzamides / pharmacology
Benzazepines / chemical synthesis
Benzazepines / chemistry*
Benzazepines / pharmacology
Humans
In Vitro Techniques
Pyrroles
Receptors, Vasopressin / agonists*

Substances

Antidiuretic Hormone Receptor Antagonists
Azepines
Benzamides
Benzazepines
Pyrroles
Receptors, Vasopressin
WAY-151932
lixivaptan