Synthesis and antitumor activities of a series of novel quinoxalinhydrazides.
Recently, we discovered a novel class of anticancer compounds with remarkable potency in a panel of cancer cell lines. A prototype compound, SC144, showed significant in vivo efficacy in mice xenograft models of human breast cancer cells. Herein, we report on a new synthetic route to SC144 and the synthesis of several of its analogues in order to understand required features for activity. A one-step coupling of 7-fluoro-4-chloropyrrolo[1,2-a]quinoxaline with pyrazin-2-carbohydrazide improved the yield significantly. Although several of the analogues showed significant activities, modification of the heteroacyl moiety had a dramatic effect on potency.
Grande
Fedora
F
Dipartimento di Scienze Farmaceutiche, Università della Calabria, 87036 Arcavacata di Rende (Cs), Italy.
Aiello
Francesca
F
Grazia
Osvaldo De
OD
Brizzi
Antonella
A
Garofalo
Antonio
A
Neamati
Nouri
N
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D006834:Hydrazines; D011810:Quinoxalines