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trans-Fluorine Effect in Cyclopropane: Diastereoselective Synthesis of Fluorocyclopropyl Cabozantinib Analogs
- Source :
- ACS Med Chem Lett
- Publication Year :
- 2020
- Publisher :
- American Chemical Society (ACS), 2020.
-
Abstract
- [Image: see text] Investigation of the trans-fluorine effect on the hydrolysis rate of diethyl 2-fluorocyclopropane-1,1-dicarboxylate provides synthetic access to both diastereomers of the fluorocyclopropyl analog of cabozantinib, a c-Met and VEGFR-2 inhibitor used as a first-line treatment for thyroid cancer and as a second-line treatment for renal cell carcinoma. Despite some known potent examples, there are only a few drug molecules that contain fluorocyclopropane moieties. Herein, we present a case study in which the monofluoro analog of a known cyclopropane-containing drug molecule displays an improved in vitro profile compared to the parent nonfluorinated structure. The fluorocyclopropane moiety may offer valuable fine-tuning options for lead optimization in drug discovery.
- Subjects :
- Drug
Cabozantinib
010405 organic chemistry
Drug discovery
media_common.quotation_subject
Organic Chemistry
Diastereomer
01 natural sciences
Biochemistry
Combinatorial chemistry
In vitro
0104 chemical sciences
Cyclopropane
010404 medicinal & biomolecular chemistry
chemistry.chemical_compound
chemistry
Drug Discovery
Moiety
Molecule
media_common
Subjects
Details
- ISSN :
- 19485875
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- ACS Medicinal Chemistry Letters
- Accession number :
- edsair.doi.dedup.....0ec5bebca5e875a0161fff327f79de71