Antitumor Benzothiazoles. 16. Synthesis and Pharmaceutical Properties of Antitumor 2-(4-Aminophenyl)benzothiazole Amino Acid Prodrugs
journal contributionposted on 20.12.2001 by Ian Hutchinson, Sharon A. Jennings, B. Rao Vishnuvajjala, Andrew D. Westwell, Malcolm F. G. Stevens
Any type of content formally published in an academic journal, usually following a peer-review process.
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.