Design, synthesis and SAR of novel ethylenediamine and phenylenediamine derivatives as factor Xa inhibitors
- Resource Type
- Authors
- Kenji Yoshikawa; Toshiharu Yoshino; Makoto Takemura; Akiyoshi Mochizuki; Toshiharu Ohta; Tsutomu Nagata; Kouichi Uoto; Yoshihiro Yokomizo; Hiroyuki Naito; Katsuhiro Kawakami; Hideyuki Kanno; Makoto Suzuki
- Source
- Bioorganic & Medicinal Chemistry Letters. 21:2133-2140
- Subject
- Models, Molecular
Serine Proteinase Inhibitors
Molecular model
medicine.drug_mechanism_of_action
Stereochemistry
Carboxylic acid
Clinical Biochemistry
Factor Xa Inhibitor
Substituent
Pharmaceutical Science
Ethylenediamine
Crystallography, X-Ray
Biochemistry
Chemical synthesis
Structure-Activity Relationship
chemistry.chemical_compound
Drug Discovery
medicine
Structure–activity relationship
Moiety
Molecular Biology
chemistry.chemical_classification
Organic Chemistry
chemistry
Drug Design
Molecular Medicine
Factor Xa Inhibitors
- Language
- ISSN
- 0960-894X
We previously reported on a series of cyclohexanediamine derivatives as highly potent factor Xa inhibitors. Herein, we describe the modification of the spacer moiety to discover an alternative scaffold. Ethylenediamine derivatives possessing a substituent at the C1 position in S configuration and phenylenediamine derivatives possessing a substituent at the C5 position demonstrated moderate to strong anti-fXa activity. Further SAR studies led to the identification of compound 30 h which showed both good in vitro activity (fXa IC(50) = 2.2 nM, PTCT2 = 3.9 μM) and in vivo antithrombotic efficacy.