182485-36-5

Usage

Uses

Used in Neurochemical Research:
(1,2,5,6-TETRAHYDROPYRIDIN-4-YL)METHYLPHOSPHINIC ACID is used as a neurochemical tool for studying the role and function of GABAC receptors in the central nervous system. Its selectivity allows researchers to investigate the specific mechanisms and pathways associated with GABAC receptor activity, leading to a better understanding of their involvement in various neurological processes.
Used in Pharmaceutical Development:
TPMPA is used as a selective, competitive GABAC antagonist in the development of pharmaceuticals targeting the GABAC receptor subtype. Its minimal effects on GABAA and GABAB receptors make it an ideal candidate for the development of drugs that can specifically modulate GABAC receptor activity, potentially leading to more targeted and effective treatments for neurological disorders.
Used in Retinal Ganglion Cell Research:
(1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid hydrate has been used as a γ-aminobutyric acid C (GABAc) blocker in retinal ganglion cells. This application allows researchers to study the role of GABAc receptors in the retina and their potential involvement in retinal diseases and disorders. Understanding the function of GABAc receptors in the retina can lead to the development of new therapeutic strategies for retinal conditions.

Biological Activity

A selective, competitive GABA C antagonist with only minimal effects on GABA A and GABA B receptors (K b values are 2.1 μ M (antagonist), 320 μ M (antagonist) and EC 50 ~ 500 μ M (weak agonist) respectively). Displays 8-fold selectivity for human recombinant ρ 1 receptors over ρ 2 receptors.

Biochem/physiol Actions

TPMPA is a hybrid of isoguvacine and 3-APMPA designed to retain affinity for GABAC receptors but not to interact with GABAA or GABAB receptors. Electrical assays show that TPMPA is a competitive antagonist of cloned human mu 1 GABAC receptors expressed in Xenopus laevis oocytes (Kb approx. 2 μM). TPMPA is >100-fold weaker as an inhibitor of rat brain GABAA receptors expressed in oocytes (Kb approx. 320 μM) and has only weak agonist activity on GABAB receptors assayed in rat hippocampal slices (EC50 approx. 500 μM). TPMPA may be used to investigate GABAC receptor function in the outer retina and in any other areas of the nervous system in which these types of receptor are present.

Upstream product

• 215930-30-6 isopropyl [1-(2,2,2-trichloroethoxycarbonyl)-1,2,5,6-tetrahydropyridin-4-yl]methylphosphinate 
• 404380-38-7 isopropyl (pyridin-4-yl)methylphosphinate 
• 190127-10-7 (1-Benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-methyl-phosphinic acid methyl ester 
• 143427-63-8 1-Benzyl-4-iodo-1,2,5,6-tetrahydropyridine 
• 15854-87-2 4-iodopyridine 
• 138647-49-1 4-Trifluoromethanesulfonyloxy-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
• 190127-12-9 4-(Methoxy-methyl-phosphinoyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid 2-trimethylsilanyl-ethyl ester 
• 404380-42-3 isopropyl (1-methyl-1,2,5,6-tetrahydropyridin-4-yl)methylphosphinate 
• 464194-36-3 4-hydroxyphosphinoyl-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
• 74-88-4 methyl iodide 

Relevant academic research and scientific papers

An improved, versatile synthesis of the GABAC antagonists (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) and (piperidin-4-yl)methylphosphinic acid (P4MPA)

Synthesis of the highly selective GABAc antagonist (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid (TPMPA) and the saturated analogue P4MPA was discussed. γ-Aminobutyric acid, GABA is the major inhibitory neurotransmitter in the mammalian central nervous system (CNS). Results showed that reaction temperatures above 70°C result in conversion of starting material into pyridine.

Palladium-catalyzed cross-coupling reaction of anilinium hypophosphite with alkenyl bromides and triflates: Application to the synthesis of GABA analogs

Alkenyl bromides and triflates undergo palladium-catalyzed cross-coupling with anilinium hypophosphite to afford mono-substituted phosphinates (salts of alkenylphosphonous acids). The reaction is an extension of our previously reported methodology for the synthesis of aryl- and benzyl-phosphonous acids. Our preliminary results show that the best reaction conditions are observed with Pd(OAc)2/dppp as a catalyst, in refluxing benzene or tetrahydrofuran. This novel P-C bond forming reaction conditions are observed synthesis of (1,2,3,6-tetrahydropyridin-4-y1)-methylphosphinic acid (TPMPA), a selective competitive antagonist for GABAc receptors. The divergent synthesis proceeds through protected (1,2,3,6-tetrahydropyridin-4-y1)-phosphinic acid, a previously unknown isoguvacine-like GABA analog. This synthetic intermediate is also an ideal precursor to other biologically interesting GABA analogs.

The first selective antagonist for a GABAC receptor

(1,2,5,6-Tetrahydropyridine-4-yl)methylphosphinic acid (TPMPA, 1), which is synthesized in six steps from 3-butyn-1-ol, is the first γ-aminobutyric acid (GABA) receptor antagonist that shows strong selectivity for mammalian GABAc receptors. Copyright