title: The novel primaquine derivatives of N-alkyl, cycloalkyl or aryl urea: synthesis, cytostatic and antiviral activity evaluations.
abstract: The novel urea primaquine derivatives 3a-i were prepared by aminolysis of benzotriazolide 2 with the corresponding amine in the presence or absence of triethylamine. Compound 2 was prepared by acylation of primaquine with 1-benzotriazole carboxylic acid chloride. Among all compounds evaluated, the pyridine derivative 3h exhibited the best cytostatic activities against colon carcinoma, human T-lymphocyte and murine leukemia. However, this compound showed also rather marked cytotoxicity towards human normal fibroblasts. The highest selectivity in the inhibitory effects on human malignant tumor cell lines vs. normal fibroblasts was found for ureas 3c, 3d and 3g. Results of broad antiviral evaluation showed that pyridine and phenethyl derivatives of urea 3h and 3g exhibited some selective inhibition against cytomegalovirus.
authors.affiliation: Faculty of Pharmacy and Biochemistry, A. Kovacića 1, HR-10000 Zagreb, Croatia.
authors.forename: G
authors.initials: G
authors.lastname: Dzimbeg
authors.forename: B
authors.initials: B
authors.lastname: Zorc
authors.forename: M
authors.initials: M
authors.lastname: Kralj
authors.forename: K
authors.initials: K
authors.lastname: Ester
authors.forename: K
authors.initials: K
authors.lastname: Pavelić
authors.forename: G
authors.initials: G
authors.lastname: Andrei
authors.forename: R
authors.initials: R
authors.lastname: Snoeck
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: M
authors.initials: M
authors.lastname: Mintas
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D011319:Primaquine / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D053719:Tandem Mass Spectrometry; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D014508:Urea; D011319:Primaquine