Synthesis and antitumor activity of a new class of pyrazolo[4,3-e]pyrrolo[1,2-a][1,4]diazepinone analogues of pyrrolo[1,4][2,1-c]benzodiazepines.
A new class of pyrrolo[1,4]benzodiazepine (PBD) analogues featuring a pyrazolo[4,3-e]pyrrolo[1,2-a][1,4]diazepinone ring system has been designed and synthesized. These compounds, 2a-o, are characterized by the substitution of the aromatic A ring, characteristic of the PBDs, with a disubstituted pyrazole ring bearing alkyl and benzyl substituents at N6 or N7 and alkyl or carbomethoxy substituents at C8. Biological evaluation revealed an appreciable in vitro cytotoxic activity for compounds 2a,b,f-i.
Baraldi
P G
PG
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy.
Leoni
A
A
Cacciari
B
B
Manfredini
S
S
Simoni
D
D
Bergomi
M
M
Menta
E
E
Spinelli
S
S
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents; D001570:Benzodiazepinones / Q000138:chemical synthesis* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology; D006801:Humans; D007939:Leukemia L1210 / Q000473:pathology; D051379:Mice; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D001570:Benzodiazepinones; D011720:Pyrazoles