Design, synthesis, and SAR of cis-1,2-diaminocyclohexane derivatives as potent factor Xa inhibitors. Part II: exploration of 6-6 fused rings as alternative S1 moieties.
A series of cis-1,2-diaminocyclohexane derivatives possessing a 6-6 fused ring for the S1 moiety were synthesized as novel factor Xa (fXa) inhibitors. The synthesis, structure-activity relationship (SAR), and physicochemical properties are reported herein, together with the discovery of compound 45c, which has potent anti-fXa activity, good physicochemical properties and pharmacokinetic (PK) profiles, including a reduced negative food effect.
Yoshikawa
Kenji
K
R&D Division, Daiichi Sankyo Co, Ltd, 1-16-13, Kita-Kasai, Tokyo 134-8630, Japan. yoshikawa.kenji.t6@daiichisankyo.co.jp
Kobayashi
Shozo
S
Nakamoto
Yumi
Y
Haginoya
Noriyasu
N
Komoriya
Satoshi
S
Yoshino
Toshiharu
T
Nagata
Tsutomu
T
Mochizuki
Akiyoshi
A
Watanabe
Kengo
K
Suzuki
Makoto
M
Kanno
Hideyuki
H
Ohta
Toshiharu
T
D000925:Anticoagulants / Q000737:chemistry* / Q000494:pharmacology; D000990:Antithrombin III / Q000627:therapeutic use; D001665:Binding Sites; D003514:Cyclohexylamines / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D015394:Molecular Structure; D011485:Protein Binding; D013329:Structure-Activity Relationship
D000925:Anticoagulants; D003514:Cyclohexylamines; D000990:Antithrombin III; C030435:1,2-cyclohexanediamine