123690-79-9

Usage

Uses

Used in Neuroscience Research:
CGP 35348 is used as a GABAB receptor inhibitor for studying its effects on intrinsic optical signals (IOS) in the rat hippocampus. This application helps researchers understand the role of GABAB receptors in neural communication and signal processing.
Used in Auditory Research:
In the field of auditory research, CGP 35348 is used alone or in combination with sodium salicylate to study its effects on auditory responses in the rat's dorsal cortex. This application aids in comprehending the underlying mechanisms of sound processing and the potential therapeutic uses of GABAB receptor inhibition in auditory disorders.
Used in Oncology Research:
CGP 35348 is also used in oncology research to study its effects on hepatocellular carcinoma cells (HCC). This application is crucial for understanding the potential of GABAB receptor inhibition in cancer treatment and the development of novel therapeutic strategies for liver cancer.

Biological Activity

Selective, brain penetrant GABA B receptor antagonist (IC 50 = 34 μ M as measured in rat cortical membranes). Has higher affinity for postsynaptic versus presynaptic receptors.

Biochem/physiol Actions

CGP 35348 is a γ-aminobutyric acid-B (GABAB) receptor antagonist. It has a higher affinity towards post-versus presynaptic receptors that can penetrate the blood-brain barrier.

references

[1]. olpe hr, karlsson g, pozza mf, et al. cgp 35348: a centrally active blocker of gabab receptors. eur j pharmacol, 1990, 187(1): 27-38.[2]. hammond dl, washington jd. antagonism of l-baclofen-induced antinociception by cgp 35348 in the spinal cord of the rat. eur j pharmacol, 1993, 234(2-3): 255-262.[3]. hao jx, xu xj, wiesenfeld-hallin z. intrathecal gamma-aminobutyric acidb (gabab) receptor antagonist cgp 35348 induces hypersensitivity to mechanical stimuli in the rat. neurosci lett, 1994, 182(2): 299-302.[4]. patel sm, ebenezer is. the effects of intraperitoneal and intracerebroventricular administration of the gabab receptor antagonist cgp 35348 on food intake in rats. eur j pharmacol, 2004, 503(1-3): 89-93.

InChI:InChI=1/C8H20NO4P/c1-3-12-8(13-4-2)14(10,11)7-5-6-9/h8H,3-7,9H2,1-2H3,(H,10,11)

Upstream product

• 7440-44-0 pyrographite 
• 103680-62-2 3-aminopropyl(diethoxymethyl)-phosphinic acid ethyl ester 
• 57-41-0 phenythoin 
• 123912-25-4 ethyl 2-cyanoethyl(diethoxymethyl)phosphinate 

Relevant academic research and scientific papers

Methods for restoring cognitive function following systemic stress

The invention provides methods for treating cognitive decline that is associated with systemic stress.

Phosphinic acid analogues of GABA. 2. Selective, orally active GABA(B) antagonists

In 1987, 25 years after the synthesis of the potent and selective GABA(B) agonist baclofen (1), Kerr et al. described the first GABA(B) antagonist phaclofen 2. However, phaclofen and structurally similar derivatives 3-5 did not cross the blood-brain barrier and hence were inactive in vivo as central nervous system agents. As a consequence, the therapeutic potential of GABA(B) antagonists remained unclear. In exploring GABA and baclofen derivatives by replacing the carboxylic acid residue with various phosphinic acid groups, we discovered more potent and water soluble GABA(B) antagonists. Electrophysiological experiments in vivo demonstrated that some of the new compounds were capable of penetrating the blood-brain barrier after oral administration. Neurotransmitter release experiments showed that they interacted with several presynaptic GABA(B) receptor subtypes, enhancing the release of GABA, glutamate, aspartate, and somatostatin. The new GABA(B) antagonists interacted also with postsynaptic GABA(B) receptors, as they blocked late inhibitory postsynaptic potentials. They facilitated the induction of long-term potentiation in vitro and in vivo, suggesting potential cognition enhancing effects. Fifteen compounds were investigated in various memory and learning paradigms in rodents. Although several compounds were found to be active, only 10 reversed the age-related deficits of old rats in a multiple-trial one-way active avoidance test after chronic treatment. The cognition facilitating effects of 10 were confirmed in learning experiments in Rhesus monkeys. The novel GABA(B) antagonists showed also protective effects in various animal models of absence epilepsy.

Certain N-substituted-amino-alkane phosphinic acid derivatives having anti-epileptic properties

Compounds having GABAB -antagonistic properties, for example those of formula I STR1 wherein one of the radicals R1, R2 and R3 is hydrogen or an aliphatic, cycloaliphatic, araliphatic or aromatic radical, another is hydrogen or, in the case of R1 or R2, hydroxy or, in the case of R1, halogen or, in the case of R2 together with R2 ', oxo, and the remaining radical is hydrogen, R1 ' is hydrogen or halogen, R2 ' is hydrogen, hydroxy or, together with R2, is oxo, R4 and R5 are hydrogen or R4 is an araliphatic or heteroarylaliphatic radical and R5 is hydrogen or an aliphatic radical, and R is an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic, araliphatic, heteroarylaliphatic or aromatic radical having at least 2 carbon atoms or, when R1 is hydrogen or hydroxy, R2 is an aromatic radical and R1 ', R2 ' and R3 are hydrogen, R is methyl, and their pharmaceutically acceptable salts, can be used as active ingredients in medicaments for the treatment of epilepsies of the "petit mal" type. The invention relates also to novel compounds of formula I and processes for the preparation thereof.

Substituted propane-phosphinic acid compounds

Compounds of the formula I STR1 wherein R denotes an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic radical having 2 or more carbon atoms, and wherein one of the groups R1, R2 and R3 represents hydrogen or an aliphatic, cycloaliphatic, araliphatic or aromatic radical, another one of R1, R2 and R3 is hydrogen or, in the case of R1 and R2, is hydroxy, and the remaining one of R1, R2 and R3 is hydrogen, or wherein R denotes methyl, R1 denotes hydrogen or hydroxy, R2 denotes an aromatic radical and R3 represents hydrogen, and their salts have GABAB -antagonistic properties and can be used as GABAB -antagonists. They are obtained when in a compound of formula II STR2 in which R, R1, R2 and R3 have their previous significances, Z represents --NH2 and R4 denotes a hydroxy-protective group R5 or, when R1 and R3 denote hydrogen and R2 denotes hydrogen or alkyl, denotes an alkali metal or ammonium ion R6, or Z represents a protected or latent amino group Z° and R4 denotes hydrogen or a hydroxy-protective group R5, any group R5 or R6 is replaced by hydrogen, and/or any group Z° is converted into --NH2.