Non-nucleoside HIV-1 reverse-transcriptase inhibitors - Part 10 - Synthesis and anti-HIV activity of 5-Alkyl-6-(1-naphthylmethyl)pyrimidin-4(3H)-ones with a mono- or disubstituted 2-amino function as novel 'Dihydro-Alkoxy-Benzyl-Oxopyrimidine' (DABO) analogues

作者：Wang Yueping^*; Chen Fen Er; Balzarini Jan; De Clercq Erik; Pannecouque Christophe

来源：Chemistry and Biodiversity, 2008, 5(1): 168-176.

DOI：10.1002/cbdv.200890008

A series of structurally related 2,5-disubstituted 6-(1-naphthylmethyl)-pyrimidin-4(3H)-ones, compounds 6a-6r, were synthesized and evaluated for their in vitro anti-HIV activities in MT-4 cells. Most of the new compounds investigated showed moderate-to-good activities against wild-type HIV-1, with IC50 values in the range5.64-0.21 mu M. Compound 6d was the most potent congener (IC50=0.21 mu M, SI=724) in inhibiting HIV-1 replication, which is ca. 25 times more effective than the reference compound 2',3'-dideoxyinosine (DDI). Preliminary structure -activity relationship (SAR) studies revealed that both modulation of the amino function at C(2) and of the alkyl group at C(5) of the pyrimidine ring are crucial for high anti-HIV-1 activity.

• 出版日期2008
• 单位河北医科大学; 复旦大学