113919-36-1

Basic information

• Product Name: 2-(PHOSPHONOMETHYL)-PENTANEDIOIC ACID
• Synonyms: 4-(PHOSPHONOMETHYL)-2-PIPERAZINECARBOXYLIC ACID;2-(PHOSPHONOMETHYL)-PENTANEDIOIC ACID;2-PHOSPHONOMETHYL-PENTANEDOIC ACID;PMPA;PMPA(NMDAantagonist);2-Piperazinecarboxylicacid, 4-(phosphonomethyl)-
• CAS NO: 113919-36-1
• Molecular Formula: C₆H₁₃N₂O₅P
• Molecular Weight: 226.12
• Product Categories: chemical
• Mol File: 113919-36-1.mol
• Article Data: 1

Chemical Properties

• Appearance: /
• Storage Temp.: Store at +4°C
• CAS DataBase Reference: 2-(PHOSPHONOMETHYL)-PENTANEDIOIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: 2-(PHOSPHONOMETHYL)-PENTANEDIOIC ACID(113919-36-1)
• EPA Substance Registry System: 2-(PHOSPHONOMETHYL)-PENTANEDIOIC ACID(113919-36-1)

Safety Data

• Hazardous Substances Data: 113919-36-1(Hazardous Substances Data)

Usage

Uses

PMPA (NMDA antagonist) is a selective competitive antagonist at the NMDA receptor.

Biological Activity

Competitive NMDA receptor antagonist. Displays K i values of 0.84, 2.74, 3.53 and 4.16 μ M at NR2A, NR2B, NR2C and NR2D subunit-containing receptors respectively. Selective over AMPA receptors.

Synthetic route

4-(Diethoxy-phosphorylmethyl)-piperazine-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester → 4-Phosphonomethyl-piperazine-2-carboxylic acid (113919-36-1)

Conditions	Yield
With hydrogenchloride 1.) reflux, 24 h, 2.) 25 deg C, 3.5 d;	86%

2-methyl 1-phenylmethyl 1,2-piperazinedicarboxilate, trifluoroacetate (126937-44-8) → 4-Phosphonomethyl-piperazine-2-carboxylic acid (113919-36-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 41 percent / K2CO3 / acetonitrile / 1.) reflux, 4 h, 2.) 25 deg C, 2.5 d 2: 86 percent / 6 M aq. HCl / 1.) reflux, 24 h, 2.) 25 deg C, 3.5 d View Scheme

Upstream product

• 126937-44-8 2-methyl 1-phenylmethyl 1,2-piperazinedicarboxilate, trifluoroacetate 

Relevant articles and documents

New and versatile approaches to the synthesis of CPP-related competitive NMDA antagonists. Preliminary structure-activity relationships and pharmacological evaluation

Fourteen new CPP analogues have been prepared with methyl 1-(phenylmethyl) (±)-1,2-piperazinedicarboxylate 3 as a versatile synthetic intermediate. Derivatives were evaluated as NMDA ligands by their ability to displace [3H]CPP from rat cortical membranes. The binding affinity of various chain lengths and the N4-position of the CPP analogues, 5a, 5b, and 9a mimics the binding affinity observed for the acyclic derivatives AP6, AP8, and AP5. Analogue 9a, with a single methylene group in its phosphonate side chain, exhibited diminished affinity for the NMDA receptor when compared to the structurally similar piperidine compound CGS 19755. Replacement of the phosphonic acid moiety with monoionizable acidic groups such as a carboxylase or a phosphinate resulted in a reduction of binding affinity. An aryl spacer between the N4-nitrogen and the distal acidic group was detrimental to binding as was alkylation at the N1-position. Steric bulk, however, was better tolerated when a phenyl group was positioned α to the phosphonate, as seen with analogues 21 and 22.