J-113,397

J-113,397 is an opioid drug which was the first compound found to be a highly selective antagonist for the nociceptin receptor, also known as the ORL-1 receptor.^[1][2] It is several hundred times selective for the ORL-1 receptor over other opioid receptors,^[3][4] and its effects in animals include preventing the development of tolerance to morphine,^[5] the prevention of hyperalgesia induced by intracerebroventricular administration of nociceptin (orphanin FQ),^[6] as well as the stimulation of dopamine release in the striatum,^[7] which increases the rewarding effects of cocaine,^[8] but may have clinical application in the treatment of Parkinson's disease.^[9][10][11]

J-113,397

Clinical data
Other names	J-113,397
Identifiers
IUPAC name 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1, 3-dihydro-2H-benzimidazol-2-one
CAS Number	256640-45-6 N 217461-40-0 (racemic)
PubChem CID	5311194
IUPHAR/BPS	1691
ChemSpider	4470714 N
UNII	00M5444DIY
ChEMBL	ChEMBL357076 N
CompTox Dashboard (EPA)	DTXSID801018432
Chemical and physical data
Formula	C24H37N3O2
Molar mass	399.579 g·mol−1
3D model (JSmol)	Interactive image
SMILES C4CCCCCCC4CN(CC1CO)CCC1n3c2ccccc2n(CC)c3=O
InChI InChI=1S/C24H37N3O2/c1-2-26-22-12-8-9-13-23(22)27(24(26)29)21-14-15-25(17-20(21)18-28)16-19-10-6-4-3-5-7-11-19/h8-9,12-13,19-21,28H,2-7,10-11,14-18H2,1H3/t20-,21+/m0/s1 N Key:MBGVUMXBUGIIBQ-LEWJYISDSA-N N
NY (what is this?)  (verify)

Synthesis

Patents for treating arrhythmia:^[12]

Improved synthesis:^[13] Additional patents:^[14][15]

Condensation between 1-Benzyl-3-methoxycarbonyl-4-piperidone [57611-47-9] (1) and O-Phenylenediamine (2) gives CID:16726310 (3). Reaction with boc anhydride followed by treatment with trifluoroacetic acid gives CID:16726358 (4). Reaction with iodoethane in the presence of base alkylates the urea nitrogen giving CID:16726359 (5). Reduction of the enamine by treatment with magnesium metal in methanol solvent occurs to give predominantly the trans isomer, CID:16726360 (6). Catalytic removal of the benzyl group gives CID:16726362 (7). Reductive amination with Cyclooctanecarbaldehyde [6688-11-5] (7) gives CID:16726364 (9). Lastly, reduction of the ester with lithium aluminium hydride completed the synthesis of J-113397 (10).

See also

• JTC-801
• LY-2940094
• SB-612,111
• Trap-101 (unsaturated olefin not reduced).