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

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 15, 2010, Pages 4578-4581

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

^a Endocyte Inc   (United States)

^b BRISTOL MYERS SQUIBB   (United States)

Author keywords

Disulfide linkers; Folate; Folate receptor targeting; Folate epothilone conjugate

Indexed keywords

ANTINEOPLASTIC AGENT; BMS 753493; DISULFIDE; EPOFOLATE; EPOTHILONE DERIVATIVE; FOLATE RECEPTOR; FOLIC ACID DERIVATIVE; UNCLASSIFIED DRUG; WATER;

ARTICLE; CLINICAL TRIAL; CYTOTOXICITY; DISULFIDE BOND; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HYDROGEN BOND; SOLID TUMOR;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; DISULFIDES; EPOTHILONES; FOLATE RECEPTORS, GPI-ANCHORED; FOLIC ACID; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 77955424402     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.06.016     Document Type: Article

References (25)

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18. General procedure for preparing of drug carbonates: To a solution of epothilone derivative in anhydrous dichloromethane at 0 °C was added DMAP (1.2 equiv) and 5 (1.0 equiv). The reaction mixture was stirred at 0 °C under argon and monitored by TLC. Additional DMAP (1.2 equiv) and 5 (1.0 equiv) were added as necessary until all of epothilone derivative was consumed. The reaction was quenched with MeOH at 0 °C, the solvent was removed under vacuum, and the residue was purified by chromatography (silica gel, 2.5-5% MeOH in DCM) to afford the epothilone carbonate derivative.
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