Discovery of MK-8718, an HIV Protease Inhibitor Containing a Novel Morpholine Aspartate Binding Group [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 547.2 Organic chemical reactions formerly 547.139
• Thông tin xuất bản: Argonne, Ill. : Oak Ridge, Tenn. : Argonne National Laboratory ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2016
• Mô tả vật lý: Size: p. 702-707 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 260927
• Chủ đề: 1. 37 inorganic, organic, physical, and analytical chemistry; 2. 60 applied life sciences; 3. Inhibitors; 4. Peptides and proteins; 5. Rodent models; 6. Substituents; 7. Viruses

Tóm tắt

A novel HIV protease inhibitor was designed using a morpholine core as the aspartate binding group. Analysis of the crystal structure of the initial lead bound to HIV protease enabled optimization of enzyme potency and antiviral activity. This afforded a series of potent orally bioavailable inhibitors of which MK-8718 was identified as a compound with a favorable overall profile.