4,5-Dihydroxypyrimidine Carboxamides and N-Alkyl-5-hydroxypyrimidinone Carboxamides Are Potent, Selective HIV Integrase Inhibitors with Good Pharmacokinetic Profiles in Preclinical Species
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- 作者：Vincenzo Summa ; Alessia Petrocchi ; Victor G. Matassa ; Cristina Gardelli ; Ester Muraglia ; Michael Rowley ; Odalys Gonzalez Paz ; Ralph Laufer ; Edith Monteagudo ; Paola Pace
- 刊名：Journal of Medicinal Chemistry
- 出版年：2006
- 出版时间：November 16, 2006
- 年：2006
- 卷：49
- 期：23
- 页码：6646 - 6649
- 全文大小：69K
- 年卷期：v.49,no.23(November 16, 2006)
- ISSN：1520-4804
文摘
The dihydroxypyrimidine carboxamide 4a was discoveredas a potent and selective HIV integrase strand transfer inhibitor. Theoptimization of physicochemical properties, pharmacokinetic profiles,and potency led to the identification of 13 in the dihydroxypyrimidineseries and 18 in the N-methylpyrimidinone series having low nanomolaractivity in the cellular HIV spread assay in the presence of 50% normalhuman serum and very good pharmacokinetics in preclinical species.