Anthranilamide-based N,N-dialkylbenzamidines as potent and orally bioavailable factor Xa inhibitors: P4 SAR.
Anthranilamide-based benzamidine compound 4 and its N-substituted analogs were designed and examined as factor Xa inhibitors using substituted benzamidines as unconventional S4 binding element. A group of N,N-dialkylbenzamidines (11, 17 and 24) have been discovered as potent factor Xa inhibitors with strong anticoagulant activity and promising oral PK profiles.
Zhang
Penglie
P
Millennium Pharmaceuticals, Inc, South San Francisco, CA 94080, USA.
Bao
Liang
L
Fan
Jingmei
J
Jia
Zhaozhong J
ZJ
Sinha
Uma
U
Wong
Paul W
PW
Park
Gary
G
Hutchaleelaha
Athiwat
A
Scarborough
Robert M
RM
Zhu
Bing-Yan
BY
D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D001550:Benzamidines / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D001682:Biological Availability; D004285:Dogs; D015951:Factor Xa / Q000493:pharmacokinetics; D065427:Factor Xa Inhibitors; D006801:Humans; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D062367:ortho-Aminobenzoates / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000493:pharmacokinetics
D000925:Anticoagulants; D001550:Benzamidines; D065427:Factor Xa Inhibitors; D062367:ortho-Aminobenzoates; D015951:Factor Xa; C000219:anthranilamide