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Novel Cyclic Phosphinic Acids as GABAC ? Receptor Antagonists: Design, Synthesis, and Pharmacology.

ABSTRACT: Understanding the role of GABAC receptors in the central nervous system is limited due to a lack of specific ligands. Novel ?-aminobutyric acid (GABA) analogues based on 3-(aminomethyl)-1-oxo-1-hydroxy-phospholane 17 and 3-(guanido)-1-oxo-1-hydroxy-phospholane 19 were investigated to obtain selective GABAC receptor antagonists. A compound of high potency (19, K B = 10 ?M) and selectivity (greater than 100 times at ?1 GABAC receptors as compared to ?1?2?2L GABAA and GABAB(1b,2) receptors) was obtained. The cyclic phosphinic acids (17 and 19) are novel lead agents for developing into more potent and selective GABAC receptor antagonists with increased lipophilicity for future in vivo studies.

SUBMITTER: Gavande N

PROVIDER: S-EPMC4018128 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Novel Cyclic Phosphinic Acids as GABAC ρ Receptor Antagonists: Design, Synthesis, and Pharmacology.

Gavande Navnath N Yamamoto Izumi I Salam Noeris K NK Ai Tu-Hoa TH Burden Peter M PM Johnston Graham A R GA Hanrahan Jane R JR Chebib Mary M

ACS medicinal chemistry letters 20101019 1

Understanding the role of GABAC receptors in the central nervous system is limited due to a lack of specific ligands. Novel γ-aminobutyric acid (GABA) analogues based on 3-(aminomethyl)-1-oxo-1-hydroxy-phospholane 17 and 3-(guanido)-1-oxo-1-hydroxy-phospholane 19 were investigated to obtain selective GABAC receptor antagonists. A compound of high potency (19, K B = 10 μM) and selectivity (greater than 100 times at ρ1 GABAC receptors as compared to α1β2γ2L GABAA and GABAB(1b,2) receptors) was obt ...[more]

PMID: 24900248

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