2-[[1-(7-chloroquinolin-4-yl)-5-(2,6-dimethoxyphenyl)pyrazole-3-carbonyl]amino]adamantane-2-carboxylic acid
Meclinertant (SR-48692) is a drug which acts as a selective, non-peptide antagonist at the neurotensin receptor NTS1, and was the first non-peptide antagonist developed for this receptor.[1][2] It is used in scientific research to explore the interaction between neurotensin and other neurotransmitters in the brain,[3][4][5][6][7][8] and produces anxiolytic, anti-addictive and memory-impairing effects in animal studies.[9][10][11][12]
PatentSubmittedGranted1-(7-chloroquinolin-4-yl)pyrazole-3-carboxamide N-oxide derivatives, method of preparing them, and their pharmaceutical compositions [US5561234]1996-10-01
Substituted 1-naphthyl-3-pyrazolecarboxamides which are active on neurotensin [US5585497]1996-12-17
3-amidopyrazole derivatives, process for preparing these and pharmaceutical composites containing them [US5420141]1995-05-30
Substituted 1-naphthyl-3-pyrazolecarboxamides which are active on neurotensin, their preparation and pharmaceutical compositions containing them [US5523455]1996-06-04
3-amidopyrazole derivatives, process for preparing these and pharmaceutical compositions containing them [US5607958]1997-03-04
3-amidopyrazole derivatives, process for preparing these and pharmaceutical compositions containing them [US5616592]1997-04-01
3-amidopyrazole derivatives, process for preparing these and pharmaceutical compositions containing them [US5635526]1997-06-03
Substituted 1-phenyl-3-pyrazolecarboxamides active on neurotensin receptors, their preparation and pharmaceutical compositions containing them [US5965579]1999-10-12
| Systematic (IUPAC) name | |
|---|---|
| 2-([1-(7-Chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)-1H-pyrazole-3-carbonyl]amino)admantane-2-carboxylic acid | |
| Clinical data | |
| Legal status |
?
|
| Identifiers | |
| CAS number | 146362-70-1  |
| ATC code | ? |
| PubChem | CID 119192 |
| IUPHAR ligand | 1582 |
| UNII | 5JBP4SI96H |
| Chemical data | |
| Formula | C32H31ClN4O5 |
| Mol. mass | 587.064 |
A Machine-Assisted Flow Synthesis of SR48692: A Probe for the Investigation of Neurotensin Receptor-1 (pages 7917–7930)
Dr. Claudio Battilocchio, Benjamin J. Deadman, Dr. Nikzad Nikbin, Dr. Matthew O. Kitching, Prof. Ian R. Baxendale and Prof. Steven V. Ley
Article first published online: 16 APR 2013 | DOI: 10.1002/chem.201300696
Flow and pharmaceuticals? An investigation into whether machine-assisted technologies can be of true help in the multistep synthesis of a potent neurotensin receptor-1 probe, Meclinertant (SR48692; see structure), is reported.
Meclinertant (SR 48692)
We developed an improved synthesis of the neurotensin antagonist biological probe SR 48692. The preparation includes an number of chemical conversions and strategies involving the use of flow chemistry platforms which helped overcome some of the limiting synthetic transformations in the original chemical route .
Meclinertant (SR 48692): The synthesis of neurotensin antagonist SR 48692 for prostate cancer research I.R. Baxendale, S. Cheung, M.O. Kitching, S.V. Ley, J.W. Shearman Bio. Org. Med. Chem. 2013, 21, 4378-4387.
A synthesis of the neurotensin 1 receptor probe Merclinertant (SR48692) has been reported using a range of continuous flow through synthesis, in-line reaction monioring and purification techniques. This strategy has been contrasted with a more conventional batch synthesis approach.
Notably the safe use of phosgene gas (generated in situ), the superheating of solvents to accelerate reaction rates, the processing of a reagent suspension under continuous flow-through conditions and the application of semi-permeable membrane technology to facilitate work-up and purification were all techniques that could be beneficially applied in the synthetic scheme.
Abstract:
Meclinertant, Reminertant, SR-48692
The condensation of 2′,6′-dimethoxyacetophenone (I) with diethyl oxalate (II) by means of sodium methoxide in refluxing methanol gives the dioxobutyrate (III), which is cyclized with 7-chloroquinoline-4-hydrazine (IV) in refluxing acetic acid yielding the pyrazole derivative (V). The hydrolysis of the ester group of (V) with KOH in refluxing methanol/water affords the corresponding carboxylic acid (VI), which is finally treated with SOCl2 in refluxing toluene and condensed with 2-aminoadamantane-2-carboxylic acid.
EP 0477049; FR 2665898; JP 1992244065; US 5420141; US 5607958; US 5616592; US 5635526; US 5744491; US 5744493
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