title: Synthesis and anti-HIV-1 activity evaluation of 5-alkyl-2-alkylthio-6-(arylcarbonyl or alpha-cyanoarylmethyl)-3,4-dihydropyrimidin-4(3H)-ones as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.
abstract: A series of novel S-DABO analogues (S-DABOs, 1) were synthesized and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Key structural modifications included replacement of the 6-arylmethyl group by a 6-arylcarbonyl or 6-(alpha-cyanoarylmethyl) group. Most of the compounds showed only micromolar potency against HIV-1 in MT-4 cells in vitro, though two of them (3e and 3g) were unusually potent (IC50=0.09 and 0.23 [corrected] microM, respectively) and selective (SI=1500 and 1033 [corrected] respectively). Structure-activity relationships among the newly synthesized S-DABOs are discussed.
authors: Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China.
authors: Lei
authors: L
authors: Ji
authors: Fen-Er
authors: FE
authors: Chen
authors: Erik
authors: E
authors: De Clercq
authors: Jan
authors: J
authors: Balzarini
authors: Christophe
authors: C
authors: Pannecouque
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D054303:HIV Reverse Transcriptase / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: C520341:2-benzoylmethylthio-6-(alpha-cyano-(1-naphthylmethyl))-3,4-dihydro-5-methylpyrimidin-4(3H)-one; C520342:6-(alpha-cyanobenzyl)-3,4-dihydro-2-isopropylthio-5-methylpyrimidin-4(3H)-one; D019380:Anti-HIV Agents; D009570:Nitriles; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase