[Studies on as-triazine derivatives. XIX. Synthesis of 2,3-diarylpyrazine 2,3-diarylpyridine derivatives as blood platelet aggregation inhibitors].
4,5-Diphenyl-2-ethoxypyrimidine (1), 3,4-diphenyl-6-ethoxypyridazine (2) and 2,3-diphenyl-5-ethoxypyrazine (3) were evaluated for inhibitory activity towards arachidonic acid-induced aggregation of rabbit blood platelet in vitro. 2,3-Diphenyl-5-ethoxypyrazine (3) exhibited significant inhibitory activity. Thus, various 5-substituted 2,3-bis(4-methoxyphenyl)pyrazines were synthesized by the nucleophilic substitution reaction of 5-chloro-2,3-bis(4-methoxyphenyl)pyrazine (9). In a similar manner, substituted 2,3-bis(4-methoxyphenyl)pyridines were prepared from 2,3-bis(4-methoxyphenyl)-6-methylsulfonylpyridine (17), which was synthesized by the cycloaddition retro Diels-Alder reaction of 5,6-bis(4-methoxyphenyl)-3-methylsulfonyl-1,2,4-triazine (16) with norbornadiene. Among the compounds prepared, 6-isopropoxy-2,3-bis(4-methoxyphenyl)-pyrazine (10f) showed the most potent inhibitory activity, which was more than the activity of anitrazafen[5,6-bis(4-methoxyphenyl)-3-methyl-1,2,4-triazine.
Konno
S
S
Pharmaceutical Institute, Tohoku University, Aobayama Aoba-ku, Sendai, Japan.
Matsuya
Y
Y
Kumazawa
M
M
Amano
M
M
Kokubo
T
T
Sagi
M
M
Yamanaka
H
H
D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011719:Pyrazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship
D010975:Platelet Aggregation Inhibitors; D011719:Pyrazines; D011725:Pyridines