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ONO-2952 is a potent, selective and orally active translocator protein 18 kDa (TSPO) antagonist with K i of 0.33-9.30 nM for rat and human TSPO . ONO-2952 is more selective for TSPO than other receptors, transporters, ion channels and enzymes. ONO-2952 exerts its anti-stress effects through inhibition of excessive activation of noradrenergic system in the brain without the amnesic effect. ONO-2952 has the potential for irritable bowel syndrome treatment
In Vitro
As for its selectivity for TSPO, ONO-2952 at a concentration of 10 μM showed good selectivity for TSPO against 98 off-targets (<50% inhibition). Determination of ONO-2952 K i or IC 50 values for the remaining 35 targets (50% inhibition at 10 μM) reveal K i values of less than 1 μM only for 3 receptors, i.e. melatonin 2, progesterone B, and adrenergic α2C. The affinity of ONO-2952 for these receptors is at least 59 times lower than that for TSPO. ONO-2952 K i value for the GABA A receptor is more than 600 times higher than that for TSPO. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
ONO-2952 (0.03-3 mg/kg; oral administration; male Sprague Dawley rats) treatment dose-dependently suppresses restraint stress-induced defecation in rats with brain TSPO occupancy of more than 50%. ONO-2952 also suppresses conditioned fear stress-induced freezing behavior in rats . ONO-2952 inhibits both neurosteroid accumulation and noradrenaline release in the brain of rats exposed to acute stress . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male Sprague Dawley rats (8 weeks old) under conditioned fear stress test Dosage: 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg Administration: Oral administration Result: Dose-dependently suppressed restraint stress-induced defecation in rats. And suppressed conditioned fear stress-induced freezing behavior in rats.
Form:Solid
IC50& Target:Ki: 0.33-9.30 nM (Rat and human TSPO)
| ALogP | 4.1 |
|---|
| Canonical Smiles | CC(=O)N1CC2(CC2)C3=C([C@@H]1C4=C(C=C(C=C4)Cl)OC)NC5=C3C(=CC=C5)F |
|---|---|
| IUPAC Name | 1-[(1S)-1-(4-chloro-2-methoxyphenyl)-5-fluorospiro[3,9-dihydro-1H-pyrido[3,4-b]indole-4,1'-cyclopropane]-2-yl]ethanone |
| InChIKey | ZBQMTQGDBFZUBG-NRFANRHFSA-N |
| INCHI | 1S/C22H20ClFN2O2/c1-12(27)26-11-22(8-9-22)19-18-15(24)4-3-5-16(18)25-20(19)21(26)14-7-6-13(23)10-17(14)28-2/h3-7,10,21,25H,8-9,11H2,1-2H3/t21-/m0/s1 |
| Isomeric SMILES | CC(=O)N1CC2(CC2)C3=C([C@@H]1C4=C(C=C(C=C4)Cl)OC)NC5=C3C(=CC=C5)F |
| PubChem CID | 11524127 |
| Molecular Weight | 398.86 |
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View spec sheet →Taxonomy Tree
| Kingdom | Organic compounds |
|---|---|
| Superclass | Alkaloids and derivatives |
| Class | Harmala alkaloids |
| Subclass | Not available |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Harmala alkaloids |
| Alternative Parents | Beta carbolines 3-alkylindoles Phenoxy compounds Anisoles Methoxybenzenes Alkyl aryl ethers Chlorobenzenes Aryl chlorides Aryl fluorides Tertiary carboxylic acid amides Acetamides Pyrroles Heteroaromatic compounds Azacyclic compounds Organochlorides Organofluorides Organic oxides Carbonyl compounds Hydrocarbon derivatives Organonitrogen compounds |
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | Harman - Beta-carboline - Pyridoindole - 3-alkylindole - Indole - Indole or derivatives - Phenoxy compound - Anisole - Methoxybenzene - Phenol ether - Alkyl aryl ether - Halobenzene - Chlorobenzene - Aryl chloride - Aryl fluoride - Aryl halide - Monocyclic benzene moiety - Benzenoid - Heteroaromatic compound - Acetamide - Tertiary carboxylic acid amide - Pyrrole - Carboxamide group - Azacycle - Organoheterocyclic compound - Carboxylic acid derivative - Ether - Organonitrogen compound - Carbonyl group - Organooxygen compound - Organic oxygen compound - Organic nitrogen compound - Hydrocarbon derivative - Organofluoride - Organic oxide - Organochloride - Organohalogen compound - Aromatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as harmala alkaloids. These are compounds with a structure based on harmaline, harmine, harmalol, harman or a derivative of those parents. These parents are beta-carbolines, consisting of a pyrimidine fused to the pyrrole moiety of an indole to form a pyrido[3,4-b]indole. |
| External Descriptors | Not available |
| Solubility | DMSO : 180 mg/mL (451.29 mM; Need ultrasonic) |
|---|---|
| Molecular Weight | 398.900 g/mol |
| XLogP3 | 4.100 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 2 |
| Exact Mass | 398.12 Da |
| Monoisotopic Mass | 398.12 Da |
| Topological Polar Surface Area | 45.300 Ų |
| Heavy Atom Count | 28 |
| Formal Charge | 0 |
| Complexity | 630.000 |
| Isotope Atom Count | 0 |
| Defined Atom Stereocenter Count | 1 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| The total count of all stereochemical bonds | 0 |
| Covalently-Bonded Unit Count | 1 |