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.
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).
Takeuchi
K
K
Lilly Research Laboratories, Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
Kohn
T J
TJ
Mais
D E
DE
True
T A
TA
Wyss
V L
VL
Jakubowski
J A
JA
D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D017482:Receptors, Thromboxane; D013930:Thromboxane-A Synthase