title: Novel N-3 substituted TSAO-T derivatives: synthesis and anti-HIV-evaluation.
abstract: Novel derivatives of the anti-HIV-1 agent, TSAO-T, bearing at the N-3 position alkylating groups or photoaffinity labels were prepared and evaluated for their anti-HIV activity. All of these compounds demonstrated pronounced anti-HIV-1 activity and inhibited HIV-1 RT; however, we were unable to detect stable covalent linkages between inhibitor and enzyme. In addition, compounds with an alcohol functional group connected to the N-3 position through a cis or trans double bond have been prepared. These compounds have been useful to study how the conformational restriction of the linker affects in the interaction between the N-3 substituent and the HIV-1 RT enzyme.
authors.affiliation: Instituto de Química Médica (C.S.I.C.), Madrid, Spain.
authors.forename: María-Cruz
authors.initials: MC
authors.lastname: Bonache
authors.forename: Ernesto
authors.initials: E
authors.lastname: Quesada
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Sheen
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sluis-Cremer
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Pérez-Pérez
authors.forename: María-José
authors.initials: MJ
authors.lastname: Camarasa
authors.forename: Ana
authors.initials: A
authors.lastname: San-Félix
mesh_terms: D001386:Azides / Q000737:chemistry / Q000378:metabolism; D001577:Benzophenones / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D015195:Drug Design; D006678:HIV / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015498:HIV-2 / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D011485:Protein Binding / Q000528:radiation effects; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013379:Substrate Specificity; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D014466:Ultraviolet Rays; D014529:Uridine / Q000031:analogs & derivatives; D014779:Virus Replication / Q000187:drug effects
chemical_list: D001386:Azides; D001577:Benzophenones; D018894:Reverse Transcriptase Inhibitors; D013141:Spiro Compounds; C047723:benzophenone; D054303:HIV Reverse Transcriptase; D013936:Thymidine; C075132:TSAO-T; D014529:Uridine