Discovery of N-{(1R,2S,5S)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide hydrochloride (DT-831j): A novel, potent and orally active direct inhibitor of factor Xa

MEDI 76

Tsutomu Nagata, nagatso1@daiichipharm.co.jp1, Toshiharu Yoshino1, Noriyasu Haginoya1, Kenji Yoshikawa1, Masatoshi Nagamochi1, Shozo Kobayashi1, Satoshi Komoriya1, Aki Yokomizo1, Ryo Muto1, Mitsuhiro Yamaguchi1, Ken Osanai1, Makoto Suzuki2, and Hideyuki Kanno1. (1) Medicinal Chemistry Research Laboratory, Daiichi Pharmaceutical Co., Ltd, 1-16-13, Kita-Kasai, Edogawa-ku, Tokyo, 134-8630, Japan, (2) Drug Discovery Research Laboratory, Daiichi Pharmaceutical Co., Ltd, 1-16-13, Kita-Kasai, Edogawa-ku, Tokyo, 134-8630, Japan
The extrinsic and intrinsic coagulation systems converge at the activation of factor X to Xa. Activated factor X (fXa) has an important role in conversion of prothrombin to thrombin, which produces blood clots. Thus, fXa is a key enzyme in the coagulation cascade and also an attractive target enzyme for the therapy of thrombosis and related diseases. We investigated fXa inhibitors and found cycloalkanediamine derivatives having a potent fXa inhibition. In this presentation, we would like to report on the SAR of cycloalkanediamine derivatives, and the discovery of DT-831j, a hightly potent and orally active, direct fXa inhibitor.
 

Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007