J-113,397

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J-113,397
Clinical data
Other namesJ-113,397
Identifiers
  • 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1, 3-dihydro-2H-benzimidazol-2-one
JSmol)
  • C4CCCCCCC4CN(CC1CO)CCC1n3c2ccccc2n(CC)c3=O
  • 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
 ☒NcheckY (what is this?)  (verify)

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]

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

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

References

  1. PMID 10602690
    .
  2. PMID 11425589
    .
  3. PMID 10650183
    .
  4. PMID 17976996
    .
  5. S2CID 15569763
    .
  6. PMID 10940356
    .
  7. PMID 15282268
    .
  8. PMID 18082848
    .
  9. PMID 17287504
    .
  10. PMID 18413287
    .
  11. S2CID 46116472
    .
  12. ^ Guo Zheng, et al. CN 111249279  & CN 111265663  (2020).
  13. doi:10.1055/s-2007-966037
    .
  14. ^ Satoshi Ozaki, et al. WO 1998054168  (to MSD KK).
  15. ^ Hiroshi Kawamoto, et al. WO 2000031061  (to MSD KK).
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