کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1376598 981962 2008 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Identification of halosalicylamide derivatives as a novel class of allosteric inhibitors of HCV NS5B polymerase
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Identification of halosalicylamide derivatives as a novel class of allosteric inhibitors of HCV NS5B polymerase
چکیده انگلیسی

Halosalicylamide derivatives were identified from high-throughput screening as potent inhibitors of HCV NS5B polymerase. The subsequent structure and activity relationship revealed the absolute requirement of the salicylamide moiety for optimum activity. Methylation of either the hydroxyl group or the amide group of the salicylamide moiety abolished the activity while the substitutions on both phenyl rings are acceptable. The halosalicylamide derivatives were shown to be non-competitive with respect to elongation nucleotide and demonstrated broad genotype activity against genotype 1–3 HCV NS5B polymerases. Inhibitor competition studies indicated an additive binding mode to the initiation pocket that is occupied by the thiadiazine class of compounds and an additive binding mode to the elongation pocket that is occupied by diketoacids, but a mutually exclusive binding mode with respect to the allosteric thumb pocket that is occupied by the benzimidazole class of inhibitors. Therefore, halosalicylamides represent a novel class of allosteric inhibitors of HCV NS5B polymerase.

Halosalicylamide derivatives were evaluated as broad genotype inhibitors of HCV polymerase.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 18, Issue 11, 1 June 2008, Pages 3173–3177
نویسندگان
, , , , , , , , , , , , , ,