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.