Regioselective synthesis of folate receptor-targeted agents derived from epothilone analogs and folic acid

Iontcho R Vlahov; Gregory D Vite; Paul J Kleindl; Yu Wang; Hari Krishna R Santhapuram; Fei You; Stephen J Howard; Soong-Hoon Kim; Francis F Y Lee; Christopher P Leamon

doi:10.1016/j.bmcl.2010.06.016

Regioselective synthesis of folate receptor-targeted agents derived from epothilone analogs and folic acid

Bioorg Med Chem Lett. 2010 Aug 1;20(15):4578-81. doi: 10.1016/j.bmcl.2010.06.016. Epub 2010 Jun 8.

Authors

Iontcho R Vlahov¹, Gregory D Vite, Paul J Kleindl, Yu Wang, Hari Krishna R Santhapuram, Fei You, Stephen J Howard, Soong-Hoon Kim, Francis F Y Lee, Christopher P Leamon

Affiliation

¹ Endocyte Inc., West Lafayette, IN 47906, USA. ivlahov@endocyte.com

PMID: 20594844
DOI: 10.1016/j.bmcl.2010.06.016

Abstract

Efficient regioselective syntheses of conjugates of folic acid and cytotoxic agents derived from natural epothilones are described. These folate receptor (FR) targeting compounds are water soluble and incorporate a hydrophilic peptide-based spacer unit and a reducible self-immolative disulfide-based linker system between the FR-targeting ligand and the parent drug.

Publication types

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

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Cell Line, Tumor
Disulfides / chemistry
Epothilones / chemical synthesis
Epothilones / chemistry*
Epothilones / pharmacology
Folate Receptors, GPI-Anchored / antagonists & inhibitors*
Folate Receptors, GPI-Anchored / metabolism
Folic Acid / chemical synthesis
Folic Acid / chemistry*
Folic Acid / pharmacology
Stereoisomerism
Structure-Activity Relationship

Substances

Antineoplastic Agents
Disulfides
Epothilones
Folate Receptors, GPI-Anchored
Folic Acid