title: Antitumor benzothiazoles. 16. Synthesis and pharmaceutical properties of antitumor 2-(4-aminophenyl)benzothiazole amino acid prodrugs.
abstract: A series of water-soluble L-lysyl- and L-alanyl-amide prodrugs of the lipophilic antitumor 2-(4-aminophenyl)benzothiazoles has been synthesized to address formulation and bioavailability issues related to the desired parenteral administration of the chosen clinical candidate. The prodrugs exhibit the required pharmaceutical properties of good water solubility (in weak acid) and stability at ambient temperature and degradation to free base in vivo. The lysyl-amide of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (NSC 710305, 6d) has been selected for phase 1 clinical evaluation.
authors.affiliation: Cancer Research Laboratories, School of Pharmaceutical Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Hutchinson
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Jennings
authors.forename: B Rao
authors.initials: BR
authors.lastname: Vishnuvajjala
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Westwell
authors.forename: Malcolm F G
authors.initials: MF
authors.lastname: Stevens
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D008239:Lysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry; D012995:Solubility; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C446999:2,6-diaminohexanoic acid (4-(5-fluorobenzothiazol-2-yl)-2-methylphenyl)amide; D000970:Antineoplastic Agents; D011355:Prodrugs; D013844:Thiazoles; D008239:Lysine; D000409:Alanine