Design and Synthesis of Novel Meta-Linked Phenylglycine Macrocyclic FVIIa Inhibitors [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 570 Life sciences Biology
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2016
• Mô tả vật lý: Size: p. 67-72 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 260716
• Chủ đề: 1. 60 applied life sciences; 2. Anticoagulant; 3. Antithrombotic; 4. Factor viia; 5. Fviia; 6. Macrocycle; 7. Thrombosis

Tóm tắt

Two novel series of meta-linked phenylglycine-based macrocyclic FVIIa inhibitors have been designed to improve the rodent metabolic stability and PK observed with the precursor para-linked phenylglycine macrocycles. Through iterative structure-based design and optimization, the TF/FVIIa Ki was improved to subnanomolar levels with good clotting activity, metabolic stability, and permeability.