108351-35-5 Usage
Enzyme inhibitor
This (–)-(R)-phosphonic acid (FW = 249.63 g/mol; CAS 108351-35-5), systematically named as 3-amino-2-(4-chlorophenyl)propanephosphonic acid, is a GABABγ-aminobutyric acid receptor antagonist. Although synaptic action of GABA is mediated by bicuculline-sensitive GABAA receptors that selectively increase chloride conductance, GABA has a presynaptic inhibitory action that is bicuculline-insensitive and is mimicked by baclofen. This distinctive behavior defines the GABAB receptor, allowing one to distinguish them from classic bicuculline-sensitive GABAAreceptors. In hippocampal slices, phaclofen (baclofen’s phosphonate derivative) is a remarkably selective antagonist of both the postsynaptic action of baclofen and GABA’s bicuculline-resistant action. Phaclofen selectively abolishes the slow inhibitory postsynaptic potential in pyramidal cells. It is ineffective in antagonizing competitively the synapticallymediated Late Hyperpolarizing Response (LHP) recorded from the same or similar Dorsolateral Septal Nucleus (DLSN) neurons, from which baclofen responses were recorded. Such findings support the usefulness of phaclofen as a competitive antagonist of baclofen, and suggest that when larger stimulus intensities are applied, the LHP in the rat DLS may be mediated by a transmitter in addition to GABA. Moreover,-(R)- phaclofen inhibits the binding of [3H]-(R)-baclofen to GABAB receptor sites on rat cerebellar membranes (IC50 = 76 μM), whereas (+)-(S)-phaclofen is inactive (IC50 > 1000 μM).
Check Digit Verification of cas no
The CAS Registry Mumber 108351-35-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,0,8,3,5 and 1 respectively; the second part has 2 digits, 3 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 108351-35:
(8*1)+(7*0)+(6*8)+(5*3)+(4*5)+(3*1)+(2*3)+(1*5)=105
105 % 10 = 5
So 108351-35-5 is a valid CAS Registry Number.
InChI:InChI=1/C9H13ClNO3P/c10-9-3-1-7(2-4-9)8(5-11)6-15(12,13)14/h1-4,8H,5-6,11H2,(H2,12,13,14)
108351-35-5Relevant articles and documents
Enantioselective Rh-catalyzed hydrogenation of 3-aryl-4-phosphonobutenoates with a P-stereogenic BoPhoz-type ligand
Duan, Zheng-Chao,Hu, Xiang-Ping,Zhang, Cheng,Zheng, Zhuo
, p. 8319 - 8321 (2011/03/17)
A series of chiral 3-aryl-4-phosphonobutyric acid esters were synthesized in high enantioselectivities (93-98% ee) via the Rh-catalyzed asymmetric hydrogenation of the corresponding 3-aryl-4-phosphonobutenoates using a P-stereogenic BoPhoz-type phosphine-aminophosphine ligand. The methodology has been successfully applied to the asymmetric synthesis of a potential GABA B antagonist, (R)-phaclofen, in high enantioselectivity.
The Synthesis of Phosphonobaclofen, an Antagonist of Baclofen
Chiefari, John,Galanopoulos, Speros,Janowski, Wit K.,Kerr, David I. B.,Prager, Rolf H.
, p. 1511 - 1518 (2007/10/02)
Phosphonobaclofen 3-amino-2-(4-chlorophenyl)propylphosphonic acid, has been synthesized in five steps from ethyl 3-(4-chlorophenyl)but-2-enoate, and is a specific antagonist of baclofen.The alternative synthetic pathways, involving conjugate addition of phosphite to 2-(4-chlorophenyl)propenenitrile and of cyanide to 2-(4-chlorophenyl)ethylphosphonate ester, failed.Cyanide ion did add efficiently to ethyl 3-(4-chlorophenyl)-2-diethoxyphosphinylprop-2-enoate and hydrogenation followed by hydrolysis of the product gave (2 S, 3 S)- and (2R, 3 R)-4-amino-3-(4-chlorophenyl)-2-phosphonobutanoic acid, which is also undergoing pharmacological evaluation.
