Piperidinyl-3-phosphinic acids as novel uptake inhibitors of the neurotransmitter gamma-aminobutyric acid (GABA).
Piperidinyl-3-phosphinic acid 2, piperidinyl-3-methylphosphinic acid 3 and N-(4,4-diphenyl-3-butenyl)piperidinyl-3-phosphinic acid 4 have been synthesized as bioisosteres of the corresponding amino carboxylic acids, which are potent and specific GABA-uptake inhibitors. The novel amino phosphinic acids were tested for their GABA-uptake inhibitory activity and 2 and 4 were identified as the first phosphinic acid based GABA-uptake inhibitors. The methylphosphinic acid 3 was found to be inactive.
Kehler
J
J
Department of Medicinal Chemistry, The Royal Danish School of Pharmacy.
Stensbøl
T B
TB
Krogsgaard-Larsen
P
P
D000818:Animals; D001921:Brain / Q000378:metabolism; D018756:GABA Antagonists / Q000138:chemical synthesis*; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D014179:Neurotransmitter Uptake Inhibitors / Q000138:chemical synthesis*; D010721:Phosphinic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D010880:Piperidines / Q000138:chemical synthesis*; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism
D018756:GABA Antagonists; C119450:N-(4,4-diphenyl-3-butenyl)piperidinyl-3-phosphinic acid; D014179:Neurotransmitter Uptake Inhibitors; D010721:Phosphinic Acids; D010880:Piperidines; C119448:piperidinyl-3-phosphinic acid