JNJ-40411813 (formerly known as ADX71149) is a novel positive allosteric modulator of the mGlu2R receptor (metabotropic Glutamate 2 receptor) with EC50 of 147 nM. JNJ-40411813 demonstrated an ideal interaction between potency, selectivity, a favorable ADMET/PK and cardiovascular safety profile, and central EEG activity, according to complete in vitro and in vivo profiles. In the clinic, JNJ-40411813 has been studied for anxious depression disorders and schizophrenia. A distinct investigation from the lead compound resulted in the identification of a novel subseries of pyridones substituted with phenylpiperidine. The lead compound's phenyl ring and pyridone core were separated by various spacers as part of the optimization strategy.
Physicochemical Properties
| Molecular Formula | C20H25CLN2O | |
| Molecular Weight | 344.88 | |
| Exact Mass | 344.166 | |
| Elemental Analysis | C, 69.65; H, 7.31; Cl, 10.28; N, 8.12; O, 4.64 | |
| CAS # | 1127498-03-6 | |
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| PubChem CID | 25195461 | |
| Appearance | White to off-white solid powder | |
| LogP | 4.75 | |
| Hydrogen Bond Donor Count | 0 | |
| Hydrogen Bond Acceptor Count | 2 | |
| Rotatable Bond Count | 5 | |
| Heavy Atom Count | 24 | |
| Complexity | 500 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | O=C1C(Cl)=C(N2CCC(C3=CC=CC=C3)CC2)C=CN1CCCC |
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| InChi Key | HYOGJHCDLQSAHX-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C20H25ClN2O/c1-2-3-12-23-15-11-18(19(21)20(23)24)22-13-9-17(10-14-22)16-7-5-4-6-8-16/h4-8,11,15,17H,2-3,9-10,12-14H2,1H3 | |
| Chemical Name | 1-butyl-3-chloro-4-(4-phenylpiperidin-1-yl)pyridin-2-one | |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | mGlu2 Receptor ( EC50 = 147 nM ) | ||
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| Cell Assay | JNJ-40411813, formerly known as ADX71149, is a new positive allosteric modulator with an EC50 of 147 nM that targets the metabotropic glutamate 2 receptor, or mGlu2R. | ||
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| References |
[1]. Discovery of 1-Butyl-3-chloro-4-(4-phenyl-1-piperidinyl)-(1H)-pyridone (JNJ-40411813): A Novel Positive Allosteric Modulator of the Metabotropic Glutamate 2 Receptor. J Med Chem. 2014 Aug 14;57(15):6495-512. [2]. Pharmacological and pharmacokinetic properties of JNJ-40411813, a positive allosteric modulator of the mGlu2 receptor. Pharmacol Res Perspect 2015 Feb;3(1):e00096. [3]. Schizophrenia drug discovery and development in an evolving era: are new drug targets fulfilling expectations?. Journal of Psychopharmacology. 29 (2): 230–8. |
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| Additional Infomation | JNJ-40411813 has been used in trials studying the treatment and basic science of Confusion, Schizophrenia, Perceptual Disorders, and Major Depressive Disorder. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (7.25 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.25 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: 2.5 mg/mL (7.25 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8996 mL | 14.4978 mL | 28.9956 mL | |
| 5 mM | 0.5799 mL | 2.8996 mL | 5.7991 mL | |
| 10 mM | 0.2900 mL | 1.4498 mL | 2.8996 mL |