Cycloproylpropenamides useful as platelet activing factor (PAF)

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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514269, 514274, 514275, 544296, 544298, 544316, 544319, 544322, 544327, 544329, 544332, 544334, 544335, C07D23942, C07D40312, A61K 31505

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049278266

ABSTRACT:
The invention relates to compounds of the formula ##STR1## Y is O or S, *A is paraphenylene or *--(CH.sub.2).sub.n --(X).sub.m --(CH.sub.2).sub.r --, X is O, S or --CH.dbd.CH--, n or r, independently, are integers from 0 to 3, s is an integer from 0 to 1, m is an integer from 0 to 1, provided that when m is 1, n+s must be at least 2, R.sub.1 and R.sub.2, independently, are hydrogen, lower alkyl, cycloalkyl, lower alkenyl. Het or aryl, *E is ##STR2## or --(CH.sub.2).sub.k -- wherein k is an integer fro 0 to 4. R.sub.3, R.sub.4 and R.sub.8 are independently hydrogen or lower alkyl, R.sub.5 and R.sub.6, independently are hydrogen or lower alkyl, R.sub.7 is hydrogen, lower alkyl, cycloalkyl, Het-lower alkyl or aryl, Het is a monocyclic 5- or 6-membered hetero aromatic or a bicyclic heteroaromatic radical containing one or two hetero atoms selected from nitrogen, oxygen and sulfur, which radical may be substituted by lower alkyl, halogen or aryl, and the asterisk denotes the point of attachment,
and their enantiomers, diastereomers and racemic mixtures thereof, as well as when *E is ##STR3## their geometric isomers and pharmaceutically acceptable acid addition salts thereof.
The compounds of formula 1 exhibit activity as paltelet activiating factor (PAF) antagonists and are, therefore, useful in disease states characterized by excess platelet activating factor or for the prevention and treatment of cardiovascular diseases, pulmonary diseases, immunological disorders, inflammatory diseases, dermatological disorders, shock or transplant rejection.

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