کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2487258 | 1114410 | 2008 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Kinetics and Mechanism of the Hydrolytic Degradation of Indinavir: Intramolecular Catalysis
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The pH-rate profile of first-order rate constants for the lactonization of Indinavir in aqueous solutions with ionic strength Iâ=â1 (KCl) at 40°C is reported. The lactonization reaction is a subject of strong buffer catalysis with a nonlinear dependence of the first-order rate constants on the concentration of the buffer. The pH-rate profile is more complex than the pH-rate profiles for the hydrolysis of simple peptides and for the intramolecular OH-catalyzed hydrolysis of γ-hydroxyamides. This complexity appears unique to Indinavir and is a result of the cis-aminoindanol leaving group. The mechanistic pathways for the lactonization are discussed. The buffer catalysis data are consistent with kinetic general acid catalysis. The second-order rate constant for the specific-acid catalyzed hydrolysis of Indinavir at 40°C (kHâ=â2.2âÃâ10â4 Mâ1âminâ1) is similar to that for a simple peptide indicating similar interactions in the rate limiting transition state for both reactions.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 97, Issue 9, September 2008, Pages 3810-3819
Journal: Journal of Pharmaceutical Sciences - Volume 97, Issue 9, September 2008, Pages 3810-3819
نویسندگان
Maria M. Toteva, Roger Zanon, Drazen Ostovic,