Discovery of novel aminobenzisoxazole derivatives as orally available factor IXa inhibitors

Autor: Harold B. Wood, Shunsuke Shimada, Hiroshi Nagasue, Takashi Mizuno, Tomokazu Hirabayashi, Toshiya Endo, Shigeki Matsumoto, Yutaka Kato, Shoji Furusako, Katsuyoshi Hikita, Ting Zhang, Keiko Taguchi, Yoshitaka Maeda, Kazunari Nakao, Alan Hruza, Paul Reichert, Isao Sakurada, Teruyuki Nishimura, Tooru Yokoyama, Yoshitaka Hosaka, Mikihiko Shinozaki, Katsutoshi Takeuchi
Rok vydání: 2016
Předmět:
Drug
medicine.drug_class
media_common.quotation_subject
Clinical Biochemistry
Drug Evaluation
Preclinical
Pharmaceutical Science
030204 cardiovascular system & hematology
Pharmacology
Molecular Dynamics Simulation
Crystallography
X-Ray
01 natural sciences
Biochemistry
Factor IXa
03 medical and health sciences
Inhibitory Concentration 50
Structure-Activity Relationship
0302 clinical medicine
Dogs
Pharmacokinetics
Drug Discovery
medicine
Animals
Humans
Molecular Biology
Blood Coagulation
media_common
Binding Sites
010405 organic chemistry
Chemistry
Organic Chemistry
Anticoagulant
Isoxazoles
Highly selective
In vitro
0104 chemical sciences
Protein Structure
Tertiary
Rats
Drug Design
Prothrombin Time
Molecular Medicine
Structure based
Partial Thromboplastin Time
Coagulation factor IXa
Half-Life
Zdroj: Bioorganicmedicinal chemistry letters. 27(11)
ISSN: 1464-3405
Popis: Using structure based drug design, novel aminobenzisoxazoles as coagulation factor IXa inhibitors were designed and synthesized. Highly selective inhibition of FIXa over FXa was demonstrated. Anticoagulation profile of selected compounds was evaluated by aPTT and PT tests. In vitro ADMET and pharmacokinetic (PK) profiles were also evaluated.
Databáze: OpenAIRE
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