Dihydroxy-pyrimidine and N

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• 作者：Emanuela Nizi ; Maria Vittoria Orsale ; Benedetta Crescenzi ; Giovanna Pescatore ; Ester Muraglia ; Anna Alfieri ; Cristina Gardelli ; Sté ; phane A.H. Spieser ; Vincenzo Summa
• 关键词：HIV-1 integrase ; Pyrimidines ; N-Methylpyrimidones ; PAMPA
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2009
• 出版时间：15 August 2009
• 年：2009
• 卷：19
• 期：16
• 页码：4617-4621
• 全文大小：580 K

文摘

In the context of HIV-integrase, dihydroxypyrimidine and N-methyl pyrimidone inhibitors the cellular activity of this class of compounds has been optimized by the introduction of a simple methyl substituent in the α-position of the C-2 side chains. Enhanced passive membrane permeability has been identified as the key factor driving the observed cell-based activity improvement. The rat PK profile of the α-methyl derivative 26a was also improved over its des-methyl exact analog.