1, 2-Diamino-ethane-substituted-6, 7, 8, 9-tetrahydro-5H-pyrimido [4, 5-d] azepines as TRPV1 antagonists with improved properties

…, R Rynberg, J Buma, M Rizzolio, N Swanson…

Index: Lebsack, Alec D.; Rech, Jason C.; Branstetter, Bryan J.; Hawryluk, Natalie A.; Merit, Jeffrey E.; Allison, Brett; Rynberg, Raymond; Buma, Johnathan; Rizzolio, Michele; Swanson, Nadia; Ao, Hong; Maher, Michael P.; Herrmann, Michelle; Freedman, Jamie; Scott, Brian P.; Luo, Lin; Bhattacharya, Anindya; Wang, Qi; Chaplan, Sandra R.; Wickenden, Alan D.; Breitenbucher, J. Guy Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 23 p. 7142 - 7146

Full Text: HTML

Citation Number: 4

Abstract

Based upon a previously reported lead compound 1, a series of 1, 2-diamino-ethane- substituted-6, 7, 8, 9-tetrahydro-5H-pyrimido [4, 5-d] azepines were synthesized and evaluated for improved physiochemical and pharmacokinetic properties while maintaining TRPV1 antagonist activity. Structure–activity relationship studies directed toward improving the aqueous solubility (pH 2 and fasted-state simulated intestinal fluid (SIF)) and rat ...