Orally active factor Xa inhibitors: 4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine derivatives.
In our investigation of factor Xa inhibitors, a series of 1-(6-chloronaphthalen-2-yl)sulfonyl-4-(4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carbonyl)piperazines 3a-i were synthesized. In vitro inhibitory activities of the compounds against factor Xa and coagulation are summarized. Among the compounds, 3c and 3d, possessing a carbamoyl or N-methylcarbamoyl moiety, showed potent inhibitory activities when administered orally to rats.
Haginoya
Noriyasu
N
Medicinal Chemistry Research Laboratory, Daiichi Pharmaceutical Co. Ltd, 1-16-13, Kita-Kasai, Edogawa-ku, Tokyo 134-8630, Japan. hagin9kg@daiichipharm.co.jp
Kobayashi
Syozo
S
Komoriya
Satoshi
S
Hirokawa
Yumiko
Y
Furugori
Taketoshi
T
Nagahara
Takayasu
T
D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D001780:Blood Coagulation Tests; D065427:Factor Xa Inhibitors; D006801:Humans; D020128:Inhibitory Concentration 50; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011480:Protease Inhibitors; D011725:Pyridines; D013844:Thiazoles