Lactone and cyclic ether analogues of platelet-activating factor. Synthesis and biological activities.

Abstract

Six-membered lactone and tetrahydropyran analogues of platelet-activating factor (PAF), 4-11, and related antagonistic derivatives 41-46 were synthesized. None of the delta-lactones 4-7 showed PAF-like activities, while the corresponding cyclic ethers 8, 9 and 11 were slightly active. Some of the cyclic antagonists showed more potent inhibitory activities than the open chain antagonist CV-3988 against platelet aggregation (rabbit platelet-rich plasma, IC50) and hypotension (rat, ID50) induced by C16-PAF: e.g. dl-3-[6-[O-(trans-3-heptadecylcarbamoyloxytetrahydropyran-2- yl)methyl]phosphonoxy]hexylthiazolium (inner salt) (41d) (IC50 5.5 x 10(-7) M, ID50 0.046 mg/kg, i.v.); dl-3-[5-[O-(cis-3-heptadecylcarbamoylthiotetrahydropyran-2- yl)methyl]phosphonoxy]pentylthiazolium (inner salt) (43c) (IC50 5.7 x 10(-7) M, ID50 0.076 mg/kg, i.v.).

• Authors: H Miyazaki, N Ohkawa, N Nakamura, T Ito, T Sada, T Oshima, H Koike
• Journal: Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 37 Issue 9 Pg. 2379-90 (Sep 1989) ISSN: 0009-2363 [Print] Japan
• PMID: 2605681 (Publication Type: Journal Article)

Chemical References

• Lactones
• Platelet Activating Factor

Topics

• Animals
• Chemical Phenomena
• Chemistry
• In Vitro Techniques
• Lactones (chemical synthesis, pharmacology)
• Platelet Activating Factor (pharmacology)
• Platelet Aggregation (drug effects)
• Rabbits
• Rats
• Rats, Inbred Strains