121458-01-3Relevant academic research and scientific papers
Propenyl Carboxamide Derivatives as Antagonists of Platelet Activating Factor
Guthrie, Robert W.,Kaplan, Gerald L.,Mennona, Francis A.,Tilley, Jefferson W.,Kierstead, Richard W.,et al.
, p. 2856 - 2864 (2007/10/02)
A series of N- 3-substituted propenyl carboxamide derivatives bearing an unsaturated bicyclic moiety in the 3-position was prepared and evaluated for PAF (platelet activating factor) antagonist activity.These compounds represent conformationally constrained direct analogues of the corresponding potent 5-arylpentadienecarboxamides (5).Most of the new compounds were active in a PAF-binding assay employing whole, washed dog platelets as the receptor source and inhibited PAF-induced bronchoconstriction in guinea pigs after intravenous administration.However, oral activity in the PAF-induced bronchoconstriction model was highly sensitive to the nature and substitution of the bicyclic ring system.The most interesting compounds included -(1-butyl-6-methoxy-2-naphthyl)-N--2-propenamide (4b), -(3-butyl-6-methoxy-2-benzothiophene-yl)-N--2-propenamide (4k), and -(3-butyl-6-methoxy-1-methyl-2-indolyl)-N--2-propenamide (4l) which inhibited PAF-induced bronchoconstriction in guinea pigs with IC50s of 3.0-5.4 mg/kg, when the animals were challenged 2 h after drug treatment.They were also highly effective 6 h after a 50 mg/kg oral dose.This study supports the notion that the key remote aromatic ring present in the 5-arylpentadienecarboxamides (5) is preferentially coplanar with the diene system for good PAF antagonist activity.
Pyridine compounds which are useful in treating a disease state characterized by an excess of platelet activating factors
-
, (2008/06/13)
The invention relates to compounds of the formula STR1 wherein Y and Y' are hydrogen or taken together are O or S, *A is paraphenylene or *----(CH2)n --(X)s --(CH2)r ----, X is O, S or --CH=CH--, n or r, independently, are integers from 0 to 3, m is an integer from 0 to 1, s is an integer from 0 to 1, provided that when s is 1, n+m must be at least 2, t is an integer from 0 to 10, R1 and R2, independently, are lower alkyl, lower alkenyl or aryl, or one of R1 or R2 is hydrogen and the other is STR2 wherein W is STR3 --CH2 --CH2 --, --CH2 --, O, S, or STR4 and X1 is lower alkyl, phenyl unsubstituted or mono-, di- or trisubstituted by lower alkoxy, lower alkyl or halogen, and X2, X3 and X4, independently, are hydrogen, lower alkyl, lower alkoxy or halogen, R3 is hydrogen, lower alkyl or aryl, R4 is hydrogen, lower alkyl, aryl, aryl-lower alkyl or acyl, R5 is hydrogen or lower alkyl, R6 is hydrogen, lower alkyl, cycloalkyl, Het-lower alkyl or aryl, Het is a monocyclic 6-membered heteroaromatic radical containing one or two nitrogen atoms, which radical may be substituted by lower alkyl, halogen or aryl, and the asterisk denotes the point of attachment, and when R5 and R6 are different, their enantiomers and racemic mixtures thereof, when R1 and R2 are different, their geometric isomers, and pharmaceutically acceptable acid addition salts thereof.
