Design and regioselective synthesis of a new generation of targeted chemotherapeutics. Part 1: EC145, a folic acid conjugate of desacetylvinblastine monohydrazide

• Published in: Bioorganic & medicinal chemistry letters Vol. 16; no. 19; pp. 5093 - 5096
• Main Authors: Vlahov, Iontcho R., Santhapuram, Hari Krishna R., Kleindl, Paul J., Howard, Stephen J., Stanford, Katheryn M., Leamon, Christopher P.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.10.2006; Elsevier
• Subjects: Anti-cancer; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - toxicity; Biological and medical sciences; Chemistry; Desacetylvinblastine; Disulfide; Disulfides - chemistry; Drug Delivery Systems; Drug Design; Exact sciences and technology; Folate; Folic Acid - chemical synthesis; Folic Acid - pharmacology; General aspects; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Medical sciences; Organic chemistry; Pharmacology. Drug treatments; Preparations and properties; Solubility; Structure-Activity Relationship; Targeted therapeutics; Vinblastine - analogs & derivatives; Vinblastine - chemical synthesis; Vinblastine - pharmacology; Targeted therapeutics; Anti-cancer; Folate; Desacetylvinblastine; Disulfide; Antineoplastic agent; Organic hydrazide; Spacer arm; Targeting; Peptides; Regioselectivity; Vitamin; Folic acid; Water soluble compound; Alkaloid; Organic disulfide; Chemical modification; Conjugated compound; Chemical synthesis; Biological receptor
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2006.07.030

An efficient synthesis of the folate receptor (FR) targeting conjugate EC145 is described. EC145 is a water soluble derivative of the vitamin folic acid and the potent cytotoxic agent, desacetylvinblastine monohydrazide. Both molecules are connected in regioselective manner via a hydrophilic peptide spacer and a reductively labile disulfide linker.