3-(2-(3-Pyridinyl)thiazolidin-4-oyl)indoles, a novel series of platelet activating factor antagonists.
(2RS,4R)-3-(2-(3-Pyridinyl)thiazolidin-4-oyl)indoles represent a new class of potent, orally active antagonists of platelet activating factor (PAF). The compounds were prepared by acylation of the magnesium or zinc salts of substituted indoles with (2RS,4R)-2-(3-pyridinyl)-3-(tert-butoxycarbonyl)thiazolidin-4-oyl chloride. The 3-acylindole moiety functions as a hydrolytically stabilized and conformationally restricted anilide replacement, which imparts a considerable boost in potency to the series. Structure-activity relationships observed for substitution on the indole ring system are discussed. Members of the series compare favorably with other reported PAF antagonists.
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064.
G S
GS
Sheppard
D
D
Pireh
G M
GM
Carrera
M G
MG
Bures
H R
HR
Heyman
D H
DH
Steinman
S K
SK
Davidsen
J G
JG
Phillips
D E
DE
Guinn
P D
PD
May
D000284:Administration, Oral; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000097:blood; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
D007211:Indoles; D010972:Platelet Activating Factor; D013844:Thiazoles; D012701:Serotonin