title: Pyrazole-related nucleosides. 4. Synthesis and antitumor activity of some 1-tetrahydropyranyl-4-substituted pyrazoles.
abstract: Continuing our studies on the structure-activity relationships of some pyrazole nucleosides (1a-h) structurally related to ribavirin, tiazofurin and selenazofurin, we describe here the synthesis and antitumor/antiviral/antimicrobial activity of a new series of 1-tetrahydropyranyl-4-substituted pyrazoles. In this study, the tetrahydropyranyl moiety (THP), designed as a mimic of the glycosidic portion of the parent compounds 1a-h, has led to a few derivatives with moderate cytotoxic activity against leukemia/lymphoma and solid tumor-derived cell lines (IC50 14-100 microM). The compounds obtained through substitution of the ribofuranosyl moiety by the THP moiety were still active, the free heterocyclic bases were devoid of any activity.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Manfredini
authors.forename: R
authors.initials: R
authors.lastname: Bazzanini
authors.forename: P G
authors.initials: PG
authors.lastname: Baraldi
authors.forename: M
authors.initials: M
authors.lastname: Bonora
authors.forename: M
authors.initials: M
authors.lastname: Marangoni
authors.forename: D
authors.initials: D
authors.lastname: Simoni
authors.forename: A
authors.initials: A
authors.lastname: Pani
authors.forename: F
authors.initials: F
authors.lastname: Scintu
authors.forename: E
authors.initials: E
authors.lastname: Pinna
authors.forename: L
authors.initials: L
authors.lastname: Pisano
authors.forename: P
authors.initials: P
authors.lastname: La Colla
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects; D002175:Candida / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D007938:Leukemia / Q000188:drug therapy; D008223:Lymphoma / Q000188:drug therapy; D011714:Pyrans / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: C099880:1-tetrahydropyranyl-4-(2-bromovinyl)-3-(ethoxycarbonyl)pyrazole; C099879:1-tetrahydropyranyl-4-(2-nitrovinyl)-3-(ethoxycarbonyl)pyrazole; C099878:1-tetrahydropyranyl-4-formyl-3-(ethoxycarbonyl)pyrazole; D000970:Antineoplastic Agents; D011714:Pyrans; D011720:Pyrazoles