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.
Medicinal Chemistry Research Laboratory I, Daiichi Sankyo Co., Ltd, 1-2-58, Hiromachi, Tokyo 140-8710, Japan. mochizuki.akiyoshi.yk@daiichisankyo.co.jp
Akiyoshi
A
Mochizuki
Yumi
Y
Nakamoto
Hiroyuki
H
Naito
Kouichi
K
Uoto
Toshiharu
T
Ohta
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