trans-Fluorine Effect in Cyclopropane: Diastereoselective Synthesis of Fluorocyclopropyl Cabozantinib Analogs.
ACS Med Chem Lett
; 11(11): 2146-2150, 2020 Nov 12.
Article
em En
| MEDLINE
| ID: mdl-33214822
ABSTRACT
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.
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01-internacional
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MEDLINE
Idioma:
En
Revista:
ACS Med Chem Lett
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Letônia