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

Iontcho R Vlahov; Hari Krishna R Santhapuram; Paul J Kleindl; Stephen J Howard; Katheryn M Stanford; Christopher P Leamon

doi:10.1016/j.bmcl.2006.07.030

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

Bioorg Med Chem Lett. 2006 Oct 1;16(19):5093-6. doi: 10.1016/j.bmcl.2006.07.030. Epub 2006 Jul 25.

Authors

Iontcho R Vlahov¹, Hari Krishna R Santhapuram, Paul J Kleindl, Stephen J Howard, Katheryn M Stanford, Christopher P Leamon

Affiliation

¹ Endocyte Inc., 3000 Kent Ave, Suite A1-100, West Lafayette, IN 47906, USA. [email protected]

PMID: 16870437
DOI: 10.1016/j.bmcl.2006.07.030

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacokinetics
Antineoplastic Agents / toxicity
Disulfides / chemistry
Drug Delivery Systems
Drug Design
Folic Acid / chemical synthesis*
Folic Acid / pharmacology
Solubility
Structure-Activity Relationship
Vinblastine / analogs & derivatives*
Vinblastine / chemical synthesis
Vinblastine / pharmacology

Substances

Antineoplastic Agents
Disulfides
4-desacetylvinblastine hydrazide
Vinblastine
Folic Acid