Development of dual-acting agents for thromboxane receptor antagonism and thromboxane synthase inhibition. 2. Design, synthesis, and evaluation of a novel series of phenyl oxazole derivatives

K Takeuchi; T J Kohn; D E Mais; T A True; V L Wyss; J A Jakubowski

doi:10.1016/s0960-894x(98)00353-9

Development of dual-acting agents for thromboxane receptor antagonism and thromboxane synthase inhibition. 2. Design, synthesis, and evaluation of a novel series of phenyl oxazole derivatives

Bioorg Med Chem Lett. 1998 Aug 4;8(15):1943-8. doi: 10.1016/s0960-894x(98)00353-9.

Authors

K Takeuchi¹, T J Kohn, D E Mais, T A True, V L Wyss, J A Jakubowski

Affiliation

¹ Lilly Research Laboratories, Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.

PMID: 9873463
DOI: 10.1016/s0960-894x(98)00353-9

Abstract

Synthesis and initial in vitro evaluation of a novel series of phenyl oxazole derivatives are described. An SAR study of the novel dual-acting TRA/TSI agent has revealed that the lipophilicity of the oxazole amide substituents greatly influences the TRA activity but not the TSI. The chain length of the alkenoic acid side chain affects both TRA and TSI. The optimal chain length for the combined activities was found to be n = 4 (heptenoic acid).

MeSH terms

Drug Design*
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Receptors, Thromboxane / antagonists & inhibitors*
Structure-Activity Relationship
Thromboxane-A Synthase / antagonists & inhibitors*

Substances

Enzyme Inhibitors
Receptors, Thromboxane
Thromboxane-A Synthase