α-Fluorination of tropane compounds and its impact on physicochemical and ADME properties
[Display omitted] Using an electrochemical C(sp3)-H fluorination reaction, a series of α-fluorinated tropane compounds were synthesized and their druglikeness parameters were assessed to compare with the parent compounds. Improvements were observed in membrane permeability, P-gp liability, and inhib...
Saved in:
Published in | Bioorganic & medicinal chemistry letters Vol. 108; p. 129798 |
---|---|
Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
OXFORD
Elsevier Ltd
01.08.2024
Elsevier |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | [Display omitted]
Using an electrochemical C(sp3)-H fluorination reaction, a series of α-fluorinated tropane compounds were synthesized and their druglikeness parameters were assessed to compare with the parent compounds. Improvements were observed in membrane permeability, P-gp liability, and inhibitory effects on hERG and Nav1.5 channels, accompanied with a trend of decreased aqueous solubility and microsomal stability. It was also revealed that α-fluorination reduced the basicity of tropane nitrogen atom for about 1000-fold. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0960-894X 1464-3405 |
DOI: | 10.1016/j.bmcl.2024.129798 |