Quantitative structure-activity relationships of antitumor guanidinothiazolecarboxamides with survival enhancement for therapy in the 3LL Lewis lung carcinoma model.
Guanidinothiazolecarboxamides (GTCs) are a novel class of antitumor agents found to be systemically active against experimental pulmonary metastases of 3LL Lewis lung carcinoma. A series of substituted benzothiazole GTCs were found to produce enhancement of survival in this model by using 8 days of intraperitoneal dosing initiated 2 days after intravenous tumor challenge. Quantitative structure-activity relationships have been discovered in the GTC series with survival enhancement correlated to substituent parameters. Optimal correlations were found between the probit transform of the drug-induced increased lifespan (ILS) and field and pi parameters. Among the most effective analogues in this series was N-(5-fluorobenzothiazol-2-yl)-2-guanidinothiazole-4-carboxam ide.
Schnur
R C
RC
Central Research, Pfizer Inc., Groton, Connecticut 06840.
Gallaschun
R J
RJ
Singleton
D H
DH
Grissom
M
M
Sloan
D E
DE
Goodwin
P
P
McNiff
P A
PA
Fliri
A F
AF
Mangano
F M
FM
Olson
T H
TH
D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D006146:Guanidines / Q000138:chemical synthesis* / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality; D051379:Mice; D008954:Models, Biological; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000401:mortality; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D006146:Guanidines; D013844:Thiazoles; C067815:N-(5-fluorobenzothiazol-2-yl)-2-guanidinothiazole-4-carboxamide