Regioselective synthesis of folate receptor-targeted agents derived from epothilone analogs and folic acid.
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.
Vlahov
Iontcho R
IR
Endocyte Inc., West Lafayette, IN 47906, USA. ivlahov@endocyte.com
Vite
Gregory D
GD
Kleindl
Paul J
PJ
Wang
Yu
Y
Santhapuram
Hari Krishna R
HK
You
Fei
F
Howard
Stephen J
SJ
Kim
Soong-Hoon
SH
Lee
Francis F Y
FF
Leamon
Christopher P
CP
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004220:Disulfides / Q000737:chemistry; D034261:Epothilones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D058973:Folate Receptors, GPI-Anchored / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005492:Folic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004220:Disulfides; D034261:Epothilones; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid