title: Synthesis and biological activity of 4-substituted 1-[1-(2-hydroxyethoxy)-methyl-1,2,3-triazol-(4 & 5)-ylmethyl]-1H-pyrazolo[3,4-d]pyrimidines.
abstract: The chemical synthesis of some 4-substituted 1-[1-(2-hydroxyethoxy)-methyl-1,2.3-triazol-(4 and 5)-ylmethyl]-1-H-pyrazolo[3,4-d]pyrimidines 12a,b, 13a,b and 14-23 as acyclic nucleosides is described. Treatment of (2-acetoxyethoxy)methylbromide with sodium azide afforded (2-acetoxyethoxy)methylazide 9. The heterocycles 6a,b were alkylated, separately, with propargyl bromide to obtain. regioselectively, 4-(methyl and benzyl)thio-1-(prop-2-ynyl)-1H-pyrazolo[3,4-d]pyrimidines 7a,b. These N-alkylated products were condensed with compound 9 via a 1,3-dipolar cycloaddition reaction to obtain, after separation and deprotection, 1,4- and 1,5-regioisomers 12a,b and 13a,b. The deprotected acyclic nucleosides 12a and 13a served as precursors for the preparation of 4-amino (14 and 15), 4-methylamino (16 and 17). 4-benzylamino (18 and 19), 4-methoxy (20 and 21) and 4-hydroxy (22 and 23) analogues. Compounds 7a,b and all deprotected acyclic nucleosides were evaluated for their inhibitory effects against the replication of HIV-(IIIB) and HIV-2(ROD) in MT-4 cells and for their anti-tumor activity. No marked activity was found. However, initial evaluation of 6a,b, 7a,b. 12a,b, 13a,b and 14-23 showed that compound 7b has marked activity against M. tuberculosis.
authors.affiliation: Laboratoire de Chimie Bio-Organique, Faculté des Sciences, Agadir, Morocco.
authors.forename: O
authors.initials: O
authors.lastname: Moukha-Chafiq
authors.forename: M L
authors.initials: ML
authors.lastname: Taha
authors.forename: H B
authors.initials: HB
authors.lastname: Lazrek
authors.forename: C
authors.initials: C
authors.lastname: Pannecouque
authors.forename: M
authors.initials: M
authors.lastname: Witvrouw
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: J L
authors.initials: JL
authors.lastname: Barascut
authors.forename: J L
authors.initials: JL
authors.lastname: Imbach
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002460:Cell Line; D006678:HIV / Q000378:metabolism; D006801:Humans; D008956:Models, Chemical; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D013696:Temperature
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D009705:Nucleosides; D011743:Pyrimidines