Indoline derivatives I: synthesis and factor Xa (FXa) inhibitory activities
Tetsuji Noguchi1, Naoki Tanaka, Toyoki Nishimata
1Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd, Tokyo, Japan.
Abstract:
A series of bisamidine derivatives each having a ring structure in the center of the molecule was synthesized and their Factor Xa (FXa) inhibitory activities were evaluated. Among them, some indoline derivatives showed potent inhibitory activities in vitro. In particular, (R)-18a having an (R)-configuration at the 2-position of the indoline ring exhibited the most potent FXa inhibitory activity in vitro, more potent than DX-9065a. Furthermore, (R)-18a exhibited more potent anticoagulant activity than DX-9065a. We also succeeded in obtaining an X-ray crystal structure of FXa bound with (R)-18a.
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