Pyrazole-related nucleosides. 4. Synthesis and antitumor activity of some 1-tetrahydropyranyl-4-substituted pyrazoles.
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.
Manfredini
S
S
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy.
Bazzanini
R
R
Baraldi
P G
PG
Bonora
M
M
Marangoni
M
M
Simoni
D
D
Pani
A
A
Scintu
F
F
Pinna
E
E
Pisano
L
L
La Colla
P
P
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
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