Platelet aggregation is inhibited by aminoalkylpyrazoles

249

Phermaco~gicalResearchCommunications. Vol. 20, Supplement~ 1988 PLATELET AGGREGATION

L.Milani~ aDipartimento

Key word:

IS

XNHXBXTED BY AHXNOALKYLPYRAZOLES

M.Zaccarini,b

Scienze

Platelet

D.Simoni~

Farmaceutiche bIstituto Universit& di Ferrara

aggregation

therefor

platelet

Chimica

Biologica

inhibitors.

TWA 2 causes adverse c a r d i o v a s c u l a r friction,

R.Ferronia

aggregation,

effects

such as vasocos-

atherosclerosis,

ischemia

TXA 2 appears to be an i n t e r e s t i n g target

and

for selective

inhibition. Aminoalkylpyrazoles

were prepared to investigate

tial as t h r o m b o x a n e

synthetase

tested for a n t i a g g r e g a t i n g plasma

and were preliminary

a c b i v i t y on human plateiet

rich

in vitro.

The compounds were were stimulated more,

inhibitors

their poten-

found to be weakly

with ADP,

but the inhibitory

ADP to collagen

displaying

active when platelets ICso values of 3.10-3M or

activity was g e n e r a l l y

and from collagen to a r a c h i d o n i c

This suggest that they could interfere methabolism a nitrogen

and,

probabl@,

cycle by an alkyl chain, bitors of t h r o m b o x a n e

carboxilate are present

synthetase:

or pyridine

or amide,

acid

and

linked to hereto-

in most of the known inhi-

synthetase.

Of this new class of inhibitors, relationships

with arachidonic

imidazole

from

acid.

at level of t h r o m b o x a n e

c o n t a i n i n g heterocycle,

another polar function~

increasing

and s e l e c t i v i t y

mechanism~

structure

will be reported.

activity