Discovery of zoniporide: A potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility

Authors
Guzman-Perez, A Wester, RT Allen, MC Brown, JA Buchholz, AR Cook, ER Day, WW Hamanaka, ES Kennedy, SP Knight, DR Kowalczyk, PJ Marala, RB Mularski, CJ Novomisle, WA Ruggeri, RB Tracey, WR Hill, RJ
Citation
A. Guzman-perez et al., Discovery of zoniporide: A potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility, BIOORG MED, 11(6), 2001, pp. 803-807
Citations number
41
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
6
Year of publication
2001
Pages
803 - 807
Database
ISI
SICI code
0960-894X(20010326)11:6<803:DOZAPA>2.0.ZU;2-R
Abstract
Zoniporide (CP-597,396) is a potent and selective inhibitor of NHE-1, which exhibits high aqueous solubility and acceptable pharmacokinetics for intra venous administration. The discovery, synthesis, activities, and rat and do g pharmacokinetics of this compound are presented. The potency and selectiv ity of zoniporide may be due to the conformation that the molecule adopts d ue to the presence of a cyclopropyl and a 5-quinolinyl substituent on the c entral pyrazole ring of the molecule. (C) 2001 Elsevier Science Ltd. All ri ghts reserved.