title: Synthesis and antiviral activity of N9-[3-fluoro-2-(phosphonomethoxy)propyl] analogues derived from N6-substituted adenines and 2,6-diaminopurines.
abstract: An efficient method for the synthesis of N(9)-[3-fluoro-2-(phosphonomethoxy)propyl] (FPMP) derivatives of purine bases has been developed. Both (R)- and (S)-enantiomers of the N(6)-substituted FPMP derivatives of adenine and 2,6-diaminopurine were prepared and their anti-human immunodeficiency virus (HIV) and anti-Moloney murine sarcoma virus (MSV) activity was evaluated. Whereas none of the 6-substituted FPMPA derivatives showed any antiviral activity, several FPMPDAP derivatives had a moderate antiretroviral activity. Moreover, the data obtained from the study of the substrate activity of the active derivatives towards N(6)-methyl-AMP aminohydrolase support the notion that the studied N(6)-substituted FPMPDAP derivatives act as prodrugs of the antiretroviral FPMPG analogues.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i. Flemingovo nám. 2, 16610 Prague 6, Czech Republic.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Baszczyňski
authors.forename: Petr
authors.initials: P
authors.lastname: Jansa
authors.forename: Martin
authors.initials: M
authors.lastname: Dračínský
authors.forename: Blanka
authors.initials: B
authors.lastname: Klepetářová
authors.forename: Antonín
authors.initials: A
authors.lastname: Holý
authors.forename: Ivan
authors.initials: I
authors.lastname: Votruba
authors.forename: Erik
authors.initials: E
authors.lastname: de Clercq
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Janeba
mesh_terms: D015075:2-Aminopurine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016475:3T3 Cells; D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008980:Moloney murine sarcoma virus / Q000187:drug effects; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D011687:Purines; D015075:2-Aminopurine; C007300:2,6-diaminopurine; D000225:Adenine