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Agonists of the ?-aminobutyric acid type B (GABAB) receptor derived from ?-hydroxy and ?-amino difluoromethyl ketones.

ABSTRACT: ?-Hydroxy difluoromethyl ketones represent the newest class of agonists of the GABA-B receptor, and they are structurally distinct from all other known agonists at this receptor because they do not display the carboxylic acid or amino group of ?-aminobutyric acid (GABA). In this report, the design, synthesis, and biological evaluation of additional analogues of ?-hydroxy difluoromethyl ketones characterized the critical nature of the substituted aromatic group on the lead compound. The importance of these new data is interpreted by docking studies using the X-ray structure of the GABA-B receptor. Moreover, we also report that the synthesis and biological evaluation of ?-amino difluoromethyl ketones provided the most potent compound across these two series.

SUBMITTER: Sowaileh MF

PROVIDER: S-EPMC6152937 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Agonists of the γ-aminobutyric acid type B (GABA<sub>B</sub>) receptor derived from β-hydroxy and β-amino difluoromethyl ketones.

Sowaileh Munia F MF Salyer Amy E AE Roy Kuldeep K KK John Jinu P JP Woods James R JR Doerksen Robert J RJ Hockerman Gregory H GH Colby David A DA

Bioorganic & medicinal chemistry letters 20180407 16

β-Hydroxy difluoromethyl ketones represent the newest class of agonists of the GABA-B receptor, and they are structurally distinct from all other known agonists at this receptor because they do not display the carboxylic acid or amino group of γ-aminobutyric acid (GABA). In this report, the design, synthesis, and biological evaluation of additional analogues of β-hydroxy difluoromethyl ketones characterized the critical nature of the substituted aromatic group on the lead compound. The importanc ...[more]

PMID: 29657102

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