JNJ-63533054   Click here for help

GtoPdb Ligand ID: 8766

Synonyms: compound 7c [PMID: 26396690] | JNJ63533054
Compound class: Synthetic organic
Comment: JNJ-63533054 is a small molecule agonist of GPR139 [1,3]. It is orally bioavailable and can cross the blood-brain barrier [4]. It is a surrogate ligand that can be used to examine GPR139 function in the absence of a validated endogenous ligand.
Both PubChem (CID 4879329) and ChEMBL (CHEMBL1509813) record this compound with no specified stereochemistry.
Patent WO2014152917 A2 describes the search for physiological ligands for GPR139 [2].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 58.2
Molecular weight 316.1
XLogP 3.46
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES O=C(NC(c1ccccc1)C)CNC(=O)c1cccc(c1)Cl
Isomeric SMILES O=C(N[C@H](c1ccccc1)C)CNC(=O)c1cccc(c1)Cl
InChI InChI=1S/C17H17ClN2O2/c1-12(13-6-3-2-4-7-13)20-16(21)11-19-17(22)14-8-5-9-15(18)10-14/h2-10,12H,11H2,1H3,(H,19,22)(H,20,21)/t12-/m0/s1
InChI Key MWDVCHRYCKXEBY-LBPRGKRZSA-N
References
1. Dvorak CA, Coate H, Nepomuceno D, Wennerholm M, Kuei C, Lord B, Woody D, Bonaventure P, Liu C, Lovenberg T et al.. (2015)
Identification and SAR of Glycine Benzamides as Potent Agonists for the GPR139 Receptor.
ACS Med Chem Lett, 6 (9): 1015-8. [PMID:26396690]
2. Dvorak CA, Liu C, Kuei C. (2014)
Physiological ligands for gpr139.
Patent number: WO2014152917 A2. Assignee: Janssen Pharmaceutica Nv. Priority date: 14/03/2013. Publication date: 25/09/2014.
3. Liu C, Bonaventure P, Lee G, Nepomuceno D, Kuei C, Wu J, Li Q, Joseph V, Sutton SW, Eckert W et al.. (2015)
GPR139, an Orphan Receptor Highly Enriched in the Habenula and Septum, Is Activated by the Essential Amino Acids L-Tryptophan and L-Phenylalanine.
Mol Pharmacol, 88 (5): 911-25. [PMID:26349500]
4. Shoblock JR, Welty N, Fraser I, Wyatt R, Lord B, Lovenberg T, Liu C, Bonaventure P. (2019)
In vivo Characterization of a Selective, Orally Available, and Brain Penetrant Small Molecule GPR139 Agonist.
Front Pharmacol, 10: 273. DOI: 10.3389/fphar.2019.00273 [PMID:30949055]