Premium
Synthesis and Anti‐HIV‐1 Activity of New MKC‐442 Analogues with an Alkynyl‐Substituted 6‐Benzyl Group*
Author(s) -
Aly Youssef L.,
Pedersen Erik B.,
La Colla Paolo,
Loddo Roberta
Publication year - 2007
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200600163
Subject(s) - substituent , chemistry , alkyl , stereochemistry , human immunodeficiency virus (hiv) , structure–activity relationship , group (periodic table) , in vitro , virology , organic chemistry , biochemistry , biology
Synthesis and antiviral activities are reported of a series of 6‐(3‐alkynyl benzyl)‐substituted analogues of MKC‐442 (6‐benzyl‐1‐(ethoxymethyl)‐5‐isopropyluracil), a highly potent agent against HIV. The 3‐alkynyl group is assumed to give a better stacking of the substituted benzyl group to reverse transcriptase (RT) and this was believed to improve antiviral activity against HIV‐1. The bromo derivatives, 5‐alkyl‐6‐(3‐bromo‐benzyl)‐1‐ethoxymethyl derivatives 7a, b and 5‐alkyl‐6‐(3‐bromobenzyl)‐1‐allyloxymethyl derivatives 9a, b, showed activity against HIV on the same level as their corresponding analogues 10a–d with a 3‐trimethylsilylalkynylbenzyl substituent and their desilylated analogues 11a–d. However, they all showed activity against HIV‐1 wild type in the range of more than 10fold lower than the one of MKC‐442. Moderate activity against Y181C and Y181C + K103N mutated strains was also observed and, in some cases, they were marginally better than those found for MKC‐442. A few amino‐DABO and S ‐DABO analogues were also synthesized but they were found to be inactive against HIV.