212309-47-2Relevant academic research and scientific papers
Development of dual-acting agents for thromboxane receptor antagonism and thromboxane synthase inhibition. 3. Synthesis and biological activities of oxazolecarboxamide-substituted ω-phenyl-ω-(3-pyridyl)alkenoic acid derivatives and related compounds
Takeuchi, Kumiko,Kohn, Todd J.,True, Timothy A.,Mais, Dale E.,Wikel, James H.,Utterback, Barbara G.,Wyss, Virginia L.,Jakubowski, Joseph A.
, p. 5362 - 5374 (2007/10/03)
A novel series of oxazolecarboxamide-substituted ω-phenyl-ω-(3- pyridyl)alkenoic acid derivatives was discovered as potent dual-acting agents to block the TXA2 receptor and to inhibit the thromboxane synthase (TRA/TSI). Synthesis, structure-activity relationship (SAR), and in vitro and in vivo pharmacology of this series of compounds are described. Modification of the series revolved around the oxazole moiety to increase the hydrophilicity of the compounds and to correlate the biological activity with lipophilicity of the compounds. The most potent in the series was (E)-7-[4- [4-[[(4-cyclohexylbutyl)amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept- 6-enoic acid (14) with K(d) = 9.9 ± 0.4 nM for the thromboxane receptor antagonism and IC50 = 55.0 ± 17.9 nM for thromboxane synthase inhibition. The compound 14 was a selective TRA/TSI which exhibited desirable characteristics for oral activity, 'shunt' effect to elevate PGI2 level, and absence of agonist activity.
Stereoselectivity in the Wittig reaction of phenyl 3-pyridyl ketones: Amide substituent effect on the preferential (E)-olefin formation
Takeuchi, Kumiko,Kohn, Todd J.
, p. 5689 - 5692 (2007/10/03)
A Wittig reaction of amide substituted phenyl 3-pyridyl ketones with 'nonstabilized' phosphorus ylides which contain a carboxyl terminus preferentially forms (E)-olefin. The preference for this stereoselectivity stems from either hydrogen bonding or salt-bridge formation between the amide group and the carboxyl terminus during the oxaphosphetane intermediate formation.
