title: Investigation on the role of the tetrazole in the binding of thiotetrazolylacetanilides with HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases.
abstract: The role of the tetrazole moiety in the binding of aryl thiotetrazolylacetanilides with HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases was explored. Different acyclic, cyclic and heterocyclic replacements were investigated in order to evaluate the conformational and electronic contribution of the tetrazole ring to the binding of the inhibitors in the NNRTI pocket. The replacement of the tetrazole by a pyrazolyl group led to reversal of selectivity, providing inhibitors with excellent potency against the double mutant reverse transcriptase.
authors.affiliation: Boehringer Ingelheim (Canada) Ltd., Research and Development, 2100 Cunard Street, Laval, Que., Canada H7S 2G5. alexandre.gagnon@boehringer-ingelheim.com
authors.forename: Alexandre
authors.initials: A
authors.lastname: Gagnon
authors.forename: Serge
authors.initials: S
authors.lastname: Landry
authors.forename: René
authors.initials: R
authors.lastname: Coulombe
authors.forename: Araz
authors.initials: A
authors.lastname: Jakalian
authors.forename: Ingrid
authors.initials: I
authors.lastname: Guse
authors.forename: Bounkham
authors.initials: B
authors.lastname: Thavonekham
authors.forename: Pierre R
authors.initials: PR
authors.lastname: Bonneau
authors.forename: Christiane
authors.initials: C
authors.lastname: Yoakim
authors.forename: Bruno
authors.initials: B
authors.lastname: Simoneau
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D013777:Tetrazoles; D054303:HIV Reverse Transcriptase