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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alanine / analogs & derivatives*
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Alanine / chemical synthesis*
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Alanine / chemistry
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Drug Stability
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Hydrogen-Ion Concentration
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Lysine / analogs & derivatives*
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Lysine / chemical synthesis*
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Lysine / chemistry
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Prodrugs / chemical synthesis*
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Prodrugs / chemistry
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Solubility
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Structure-Activity Relationship
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Thiazoles / chemical synthesis*
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Thiazoles / chemistry
Substances
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2,6-diaminohexanoic acid (4-(5-fluorobenzothiazol-2-yl)-2-methylphenyl)amide
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Antineoplastic Agents
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Prodrugs
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Thiazoles
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Lysine
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Alanine