Design, synthesis, and biological activity of piperidine diamine derivatives as factor Xa inhibitor.
Previously, we identified cyclohexane diamine derivative 1 as orally bioavailable factor Xa inhibitor. We have investigated two racemic cis-piperidine diamine derivatives 2 and 3 based on 1. Compounds 2a-e showed higher fXa inhibitory activity, anticoagulant activity, and aqueous solubility than 3a-e having same substituent. Compounds 2a, 2c, 2e, and 2g-m having sp2 nitrogen, especially amide and urea derivatives, showed potent anticoagulant activity. Compounds 2h and 2k showed high oral activities in rats.
Mochizuki
Akiyoshi
A
Medicinal Chemistry Research Laboratory I, Daiichi Sankyo Co., Ltd, 1-2-58, Hiromachi, Tokyo 140-8710, Japan. mochizuki.akiyoshi.yk@daiichisankyo.co.jp
Nakamoto
Yumi
Y
Naito
Hiroyuki
H
Uoto
Kouichi
K
Ohta
Toshiharu
T
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D003959:Diamines / Q000737:chemistry; D015195:Drug Design; D065427:Factor Xa Inhibitors; D000882:Haplorhini; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D010880:Piperidines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D003959:Diamines; D065427:Factor Xa Inhibitors; D010880:Piperidines; D015842:Serine Proteinase Inhibitors