Novel agents combining platelet activating factor (PAF) receptor antagonist with thromboxane synthase inhibitor (TxSI).
Compounds 1 or 2 which possess dual-acting PAF antagonist/TxSI in a previous paper were modified and evaluated for the dual-acting activity. It was found that several compounds were potent dual-acting PAF antagonist/TxSI in and ex vivo. 6-(2-Chlorophenyl)-3-[4-[(E/Z)-6-ethoxycarbonyl-1-(3-pyridyl)-1-hexenyl]phenylmethyl]-8,11-dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3': 4,5]thieno[3,2-f]triazolo[4,3-a]diazepine (12) is excellent orally dual-acting PAF antagonist/TxSI.
Fujita
Masakazu
M
Omiya Research Laboratory, Nikken Chemicals Co., Ltd., 1-346, Kitabukuro-cho, Saitama-shi, 330-0835, Saitama, Japan. souyaku@jade.dti.ne.jp
Seki
Taketsugu
T
Inada
Haruaki
H
Shimizu
Kazuhiro
K
Takahama
Akane
A
Sano
Tetsuro
T
D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D051381:Rats; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors* / Q000737:chemistry
C461194:6-(2-chlorophenyl)-3-(4-(6-ethoxycarbonyl-1-(3-pyridyl)-1-hexenyl)phenyllmethyl)-8,11-dimethyl-2,3,4,5-tetrahydro-8H-pyrido(4',3'-4,5)thieno(3,2-f)(1,2,4)triazolo(4,3-a)diazepine; D001381:Azepines; D004791:Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013876:Thiophenes; C039351:platelet activating factor receptor; D013930:Thromboxane-A Synthase