title: Quantitative structure-activity relationships of antitumor guanidinothiazolecarboxamides with survival enhancement for therapy in the 3LL Lewis lung carcinoma model.
abstract: 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.
authors.affiliation: Central Research, Pfizer Inc., Groton, Connecticut 06840.
authors.forename: R C
authors.initials: RC
authors.lastname: Schnur
authors.forename: R J
authors.initials: RJ
authors.lastname: Gallaschun
authors.forename: D H
authors.initials: DH
authors.lastname: Singleton
authors.forename: M
authors.initials: M
authors.lastname: Grissom
authors.forename: D E
authors.initials: DE
authors.lastname: Sloan
authors.forename: P
authors.initials: P
authors.lastname: Goodwin
authors.forename: P A
authors.initials: PA
authors.lastname: McNiff
authors.forename: A F
authors.initials: AF
authors.lastname: Fliri
authors.forename: F M
authors.initials: FM
authors.lastname: Mangano
authors.forename: T H
authors.initials: TH
authors.lastname: Olson
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D006146:Guanidines; D013844:Thiazoles; C067815:N-(5-fluorobenzothiazol-2-yl)-2-guanidinothiazole-4-carboxamide