کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1395467 1501126 2015 29 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Aspartic protease inhibitors containing tertiary alcohol transition-state mimics
ترجمه فارسی عنوان
مهار کننده های پروتئاز آسپارتیسی که حاوی حالت انتقال دولتی ترتیبی دارند، تقلید می کنند
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
چکیده انگلیسی


• Tertiary alcohol aspartic protease inhibitors were designed and evaluated.
• HIV-1 protease inhibitors with tert-alcohol transition-state mimics were prepared.
• HIV-1 protease inhibitors with excellent pharmaceutical profiles were identified.

Aspartic proteases (APs) are a class of enzymes engaged in the proteolytic digestion of peptide substrates. APs play important roles in physiological and infectious pathways, making them plausible drug targets. For instance in the treatment of HIV infections, access to an efficient combination of protease and reverse transcriptase inhibitors have changed a terminal illness to a chronic but manageable disease. However, the benefits have been limited due to the emergence of drug resistant viral strains, poor pharmacokinetic properties of peptidomimetic inhibitors and adverse effects associated with the treatment. In the 1980s, D. Rich and co-workers proposed a novel strategy for the development of AP inhibitors by replacing the secondary hydroxyl group with a tertiary alcohol as part of the transition state (TS) mimicking moiety. This strategy has been extensively explored over the last decade with a common belief that masking of the polar group, e.g. by intramolecular hydrogen bonding, has the potential to enhance transcellular transport. This is the first review presenting the advances of AP inhibitors comprising a tertiary hydroxyl group. The inhibitors have been classified into different tert-hydroxy TS mimics and their design strategies, synthesis, biological activities, structure–activity-relationships and X-ray structures are discussed.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 90, 27 January 2015, Pages 462–490
نویسندگان
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