Synthesis and antagonistic activities of enantiomers of cyclic platelet-activating factor analogues.

Abstract

Enantiomers of platelet-activating factor (PAF) antagonists, 3-(6-[O-(trans-3-heptadecylcarbamoyloxytetrahydropyran-2-yl)methyl ] phosphonoxy)hexylthiazolium (inner salt) (3), 3-[5-(trans-3-heptadecylcarbamoyloxytetrahydropyran-2-yl) methoxycarbonylamino]pentylthiazolium bromide (4) and 3-(5-[O-(cis-3-heptadecylcarbamoylthiotetrahydropyran-2-yl) methyl]phosphonoxy)pentylthiazolium (inner salt) (5), were synthesized, starting from (2R,2R)- and (2S,2S)-tartaric acid. Antagonistic activities of these compounds against C16-PAF were measured in vitro (rabbit platelet aggregation, IC50) and in vivo (hypotension in rats, ID50). In these three enantiomeric pairs, the (3S)-(tetrahydropyran numbering) enantiomers were one order more potent than the (3R)-isomers: (2R,3S)-3a (R-74,654), IC50 0.59 microM and ID50 0.054 mg/kg, i.v.; (2S,3R)-3b, IC50 4.7 microM and ID50 0.30 mg/kg, i.v.; (2R,3S)-4a, IC50 0.20 microM and ID50 0.032 mg/kg, i.v.; (2S,3R)-4b, IC50 2.2 microM and IC40 0.21 mg/kg, i.v.; (2R,3R)-5a, IC50 1.1 microM and ID50 0.92 mg/kg, i.v.; (2S,3S)-5b (R-74,717), IC50 0.27 microM and ID50 0.064 mg/kg, i.v.

• Authors: H Miyazaki, N Nakamura, T Ito, T Sada, T Oshima, H Koike
• Journal: Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 37 Issue 9 Pg. 2391-7 (Sep 1989) ISSN: 0009-2363 [Print] Japan
• PMID: 2605682 (Publication Type: Journal Article)

Chemical References

• Platelet Activating Factor

Topics

• Chemical Phenomena
• Chemistry
• Humans
• Platelet Activating Factor (antagonists & inhibitors)
• Stereoisomerism