J-113,397: Difference between revisions

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+{{Short description|Chemical compound}}
-{{drugbox |
+{{Drugbox
-| IUPAC_name        = 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1, 3-dihydro-2H-benzimidazol-2-one
+| Verifiedfields = changed
-| image             = J-113,397_structure.png
+| verifiedrevid = 411032647
-| width             = 200
+| IUPAC_name = 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1, 3-dihydro-2H-benzimidazol-2-one
-| CAS_number        =
-| synonyms          = J-113,397
+| image = J-113,397.svg
+| width = 200
-| ATC_prefix        =
-| ATC_suffix        =
+<!--Clinical data-->
-| PubChem           = 5311194
+| tradename =
+| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
+| pregnancy_US = <!-- A / B            / C / D / X -->
+| pregnancy_category =
+| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
+| legal_CA =
+| legal_UK =
+| legal_US =
+| legal_status =
+| routes_of_administration =
+<!--Pharmacokinetic data-->
+| bioavailability =
+| protein_bound =
+| metabolism =
+| elimination_half-life =
+| excretion =
+<!--Identifiers-->
+| CAS_number_Ref = {{cascite|changed|CAS}}
+| CAS_number = 256640-45-6
+| CAS_supplemental = <br />{{CAS|217461-40-0}} (racemic)
+| UNII_Ref = {{fdacite|changed|FDA}}
+| UNII =  00M5444DIY
+| ATC_prefix =
+| ATC_suffix =
+| PubChem = 5311194
 | IUPHAR_ligand = 1691
+| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
-| DrugBank          =
+| DrugBank =
-| C = 24 | H = 37 | N = 3 | O = 2
+| ChEMBL_Ref = {{ebicite|changed|EBI}}
-| molecular_weight  = 399.568 g/mol
+| ChEMBL = 357076
-| smiles            = C4CCCCCCC4CN(CC1CO)CCC1n3c2ccccc2n(CC)c3=O
+| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
-| bioavailability   =
-| protein_bound     =
+| ChemSpiderID      = 4470714
-| metabolism        =
+<!--Chemical data-->
-| elimination_half-life =
-| excretion         =
+| C=24 | H=37 | N=3 | O=2
+| smiles = C4CCCCCCC4CN(CC1CO)CCC1n3c2ccccc2n(CC)c3=O
-| pregnancy_AU      =  <!-- A / B1 / B2 / B3 / C / D / X -->
+| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
-| pregnancy_US      =  <!-- A / B            / C / D / X -->
+| StdInChI          = 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
-| pregnancy_category=
+| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
-| legal_AU          =  <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
-| legal_CA          =
+| StdInChIKey       = MBGVUMXBUGIIBQ-LEWJYISDSA-N
-| legal_UK          =
+| synonyms = J-113,397
-| legal_US          =
-| legal_status      =
-| routes_of_administration =
 }}
-'''J-113,397''' is an [[opioid]] [[analgesic]] drug which was the first compound found to be a highly selective antagonist for the [[nociceptin receptor]], also known as the ORL-1 receptor.<ref>Kawamoto H, Ozaki S, Itoh Y, Miyaji M, Arai S, Nakashima H, Kato T, Ohta H, Iwasawa Y. Discovery of the first potent and selective small molecule opioid receptor-like (ORL1) antagonist: 1-[(3R,4R)-1-cyclooctylmethyl-3- hydroxymethyl-4-piperidyl]-3-ethyl-1, 3-dihydro-2H-benzimidazol-2-one (J-113397). ''Journal of Medicinal Chemistry''. 1999 Dec 16;42(25):5061-3. PMID 10602690</ref><ref>De Risi C, Piero Pollini G, Trapella C, Peretto I, Ronzoni S, Giardina GA. A new synthetic approach to 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-benzimidazol-2-one(J-113397), the first non-peptide ORL-1 receptor antagonist. ''Bioorganic and Medicinal Chemistry''. 2001 Jul;9(7):1871-7. PMID 11425589</ref> It is several hundred times selective for the ORL-1 receptor over other opioid receptors,<ref>Ozaki S, Kawamoto H, Itoh Y, Miyaji M, Iwasawa Y, Ohta H. A potent and highly selective nonpeptidyl nociceptin/orphanin FQ receptor (ORL1) antagonist: J-113397. ''European Journal of Pharmacology''. 2000 Jan 17;387(3):R17-8. PMID 10650183</ref><ref>Smith ED, Ariane Vinson N, Zhong D, Berrang BD, Catanzaro JL, Thomas JB, Navarro HA, Gilmour BP, Deschamps J, Carroll FI. A new synthesis of the ORL-1 antagonist 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397) and activity in a calcium mobilization assay. ''Bioorganic and Medicinal Chemistry''. 2008 Jan 15;16(2):822-9. PMID 17976996</ref> and its effects in animals include preventing the development of [[tachyphylaxis|tolerance]] to [[morphine]]<ref>Chung S, Pohl S, Zeng J, Civelli O, Reinscheid RK. Endogenous orphanin FQ/nociceptin is involved in the development of morphine tolerance. ''Journal of Pharmacology and Experimental Therapeutics''. 2006 Jul;318(1):262-7. PMID 16595734</ref>, the prevention of [[hyperalgesia]] induced by intracerebroventricular administration of nociceptin (orphanin FQ),<ref>Ozaki S, Kawamoto H, Itoh Y, Miyaji M, Azuma T, Ichikawa D, Nambu H, Iguchi T, Iwasawa Y, Ohta H. In vitro and in vivo pharmacological characterization of J-113397, a potent and selective non-peptidyl ORL1 receptor antagonist. ''European Journal of Pharmacology''. 2000 Aug 18;402(1-2):45-53. PMID 10940356</ref> as well as the stimulation of [[dopamine]] release in the [[striatum]],<ref>Marti M, Mela F, Veronesi C, Guerrini R, Salvadori S, Federici M, Mercuri NB, Rizzi A, Franchi G, Beani L, Bianchi C, Morari M. Blockade of nociceptin/orphanin FQ receptor signaling in rat substantia nigra pars reticulata stimulates nigrostriatal dopaminergic transmission and motor behavior. ''Journal of Neuroscience''. 2004 Jul 28;24(30):6659-66. PMID 15282268</ref> which increases the rewarding effects of [[cocaine]],<ref>Marquez P, Nguyen AT, Hamid A, Lutfy K. The endogenous OFQ/N/ORL-1 receptor system regulates the rewarding effects of acute cocaine. ''Neuropharmacology''. 2008 Mar;54(3):564-8. PMID 18082848</ref> but may have clinical application in the treatment of [[Parkinson's disease]].<ref>Marti M, Trapella C, Viaro R, Morari M. The nociceptin/orphanin FQ receptor antagonist J-113397 and L-DOPA additively attenuate experimental parkinsonism through overinhibition of the nigrothalamic pathway. ''Journal of Neuroscience''. 2007 Feb 7;27(6):1297-307. PMID 17287504</ref><ref>Viaro R, Sanchez-Pernaute R, Marti M, Trapella C, Isacson O, Morari M. Nociceptin/orphanin FQ receptor blockade attenuates MPTP-induced parkinsonism. ''Neurobiology of Disease''. 2008 Jun;30(3):430-8. PMID 18413287</ref><ref>Visanji NP, de Bie RM, Johnston TH, McCreary AC, Brotchie JM, Fox SH. The nociceptin/orphanin FQ (NOP) receptor antagonist J-113397 enhances the effects of levodopa in the MPTP-lesioned nonhuman primate model of Parkinson's disease. ''Movement Disorders''. 2008 Oct 15;23(13):1922-5. PMID 18759357</ref>
+'''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.<ref>{{cite journal | vauthors = Kawamoto H, Ozaki S, Itoh Y, Miyaji M, Arai S, Nakashima H, Kato T, Ohta H, Iwasawa Y | display-authors = 6 | title = Discovery of the first potent and selective small molecule opioid receptor-like (ORL1) antagonist: 1-[(3R,4R)-1-cyclooctylmethyl-3- hydroxymethyl-4-piperidyl]-3-ethyl-1, 3-dihydro-2H-benzimidazol-2-one (J-113397) | journal = Journal of Medicinal Chemistry | volume = 42 | issue = 25 | pages = 5061–3 | date = December 1999 | pmid = 10602690 | doi = 10.1021/jm990517p }}</ref><ref>{{cite journal | vauthors = De Risi C, Piero Pollini G, Trapella C, Peretto I, Ronzoni S, Giardina GA | title = A new synthetic approach to 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-benzimidazol-2-one(J-113397), the first non-peptide ORL-1 receptor antagonist | journal = Bioorganic & Medicinal Chemistry | volume = 9 | issue = 7 | pages = 1871–7 | date = July 2001 | pmid = 11425589 | doi = 10.1016/s0968-0896(01)00085-2 }}</ref> It is several hundred times selective for the ORL-1 receptor over other opioid receptors,<ref>{{cite journal | vauthors = Ozaki S, Kawamoto H, Itoh Y, Miyaji M, Iwasawa Y, Ohta H | title = A potent and highly selective nonpeptidyl nociceptin/orphanin FQ receptor (ORL1) antagonist: J-113397 | journal = European Journal of Pharmacology | volume = 387 | issue = 3 | pages = R17-8 | date = January 2000 | pmid = 10650183 | doi = 10.1016/s0014-2999(99)00822-5 }}</ref><ref>{{cite journal | vauthors = Smith ED, Ariane Vinson N, Zhong D, Berrang BD, Catanzaro JL, Thomas JB, Navarro HA, Gilmour BP, Deschamps J, Carroll FI | display-authors = 6 | title = A new synthesis of the ORL-1 antagonist 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397) and activity in a calcium mobilization assay | journal = Bioorganic & Medicinal Chemistry | volume = 16 | issue = 2 | pages = 822–9 | date = January 2008 | pmid = 17976996 | doi = 10.1016/j.bmc.2007.10.023 | pmc = 2323199 }}</ref> and its effects in animals include preventing the development of [[tachyphylaxis|tolerance]] to [[morphine]],<ref>{{cite journal | vauthors = Chung S, Pohl S, Zeng J, Civelli O, Reinscheid RK | title = Endogenous orphanin FQ/nociceptin is involved in the development of morphine tolerance | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 318 | issue = 1 | pages = 262–7 | date = July 2006 | pmid = 16595734 | doi = 10.1124/jpet.106.103960 | s2cid = 15569763 }}</ref> the prevention of [[hyperalgesia]] induced by intracerebroventricular administration of [[nociceptin]] (orphanin FQ),<ref>{{cite journal | vauthors = Ozaki S, Kawamoto H, Itoh Y, Miyaji M, Azuma T, Ichikawa D, Nambu H, Iguchi T, Iwasawa Y, Ohta H | display-authors = 6 | title = In vitro and in vivo pharmacological characterization of J-113397, a potent and selective non-peptidyl ORL1 receptor antagonist | journal = European Journal of Pharmacology | volume = 402 | issue = 1–2 | pages = 45–53 | date = August 2000 | pmid = 10940356 | doi = 10.1016/s0014-2999(00)00520-3 }}</ref> as well as the stimulation of [[dopamine]] release in the [[striatum]],<ref>{{cite journal | vauthors = Marti M, Mela F, Veronesi C, Guerrini R, Salvadori S, Federici M, Mercuri NB, Rizzi A, Franchi G, Beani L, Bianchi C, Morari M | display-authors = 6 | title = Blockade of nociceptin/orphanin FQ receptor signaling in rat substantia nigra pars reticulata stimulates nigrostriatal dopaminergic transmission and motor behavior | journal = The Journal of Neuroscience | volume = 24 | issue = 30 | pages = 6659–66 | date = July 2004 | pmid = 15282268 | doi = 10.1523/JNEUROSCI.0987-04.2004 | pmc = 6729727 | doi-access = free }}</ref> which increases the rewarding effects of [[cocaine]],<ref>{{cite journal | vauthors = Marquez P, Nguyen AT, Hamid A, Lutfy K | title = The endogenous OFQ/N/ORL-1 receptor system regulates the rewarding effects of acute cocaine | journal = Neuropharmacology | volume = 54 | issue = 3 | pages = 564–8 | date = March 2008 | pmid = 18082848 | doi = 10.1016/j.neuropharm.2007.11.003 | pmc = 2276976 }}</ref> but may have clinical application in the treatment of [[Parkinson's disease]].<ref>{{cite journal | vauthors = Marti M, Trapella C, Viaro R, Morari M | title = The nociceptin/orphanin FQ receptor antagonist J-113397 and L-DOPA additively attenuate experimental parkinsonism through overinhibition of the nigrothalamic pathway | journal = The Journal of Neuroscience | volume = 27 | issue = 6 | pages = 1297–307 | date = February 2007 | pmid = 17287504 | doi = 10.1523/JNEUROSCI.4346-06.2007 | pmc = 6673573 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Viaro R, Sanchez-Pernaute R, Marti M, Trapella C, Isacson O, Morari M | title = Nociceptin/orphanin FQ receptor blockade attenuates MPTP-induced parkinsonism | journal = Neurobiology of Disease | volume = 30 | issue = 3 | pages = 430–8 | date = June 2008 | pmid = 18413287 | doi = 10.1016/j.nbd.2008.02.011 | pmc = 2605654 }}</ref><ref>{{cite journal | vauthors = Visanji NP, de Bie RM, Johnston TH, McCreary AC, Brotchie JM, Fox SH | title = The nociceptin/orphanin FQ (NOP) receptor antagonist J-113397 enhances the effects of levodopa in the MPTP-lesioned nonhuman primate model of Parkinson's disease | journal = Movement Disorders | volume = 23 | issue = 13 | pages = 1922–5 | date = October 2008 | pmid = 18759357 | doi = 10.1002/mds.22086 | s2cid = 46116472 }}</ref>
+==Synthesis==
+Patents for treating [[arrhythmia]]:<ref>Guo Zheng, et al. {{Cite patent|CN|111249279}} & {{Cite patent|CN|111265663}} (2020).</ref>
+[[File:J-113,397 synthesis (2007).svg|thumb|center|700px|Improved synthesis:<ref>{{cite journal | vauthors=((Sulima, A.)), ((Folk, J.)), ((Jacobson, A.)), ((Rice, K.)) | journal=Synthesis | title=A New Approach to the Synthesis of the Nonpeptide NOP Receptor Antagonist J-113397 | volume=2007 | issue=10 | pages=1547–1553 | date=2 May 2007 | doi=10.1055/s-2007-966037}}</ref> Additional patents:<ref>Satoshi Ozaki, et al. {{Cite patent|WO|1998054168}} (to MSD KK).</ref><ref>Hiroshi Kawamoto, et al. {{Cite patent|WO|2000031061}} (to MSD KK).</ref>]]
+Condensation between 1-Benzyl-3-methoxycarbonyl-4-piperidone [57611-47-9] ('''1''') and [[O-Phenylenediamine]] ('''2''') gives [https://pubchem.ncbi.nlm.nih.gov/compound/16726310 CID:16726310] ('''3'''). Reaction with [[boc anhydride]] followed by treatment with [[trifluoroacetic acid]] gives [https://pubchem.ncbi.nlm.nih.gov/compound/16726358 CID:16726358] ('''4'''). Reaction with [[iodoethane]] in the presence of base alkylates the urea nitrogen giving [https://pubchem.ncbi.nlm.nih.gov/compound/16726359 CID:16726359] ('''5'''). Reduction of the enamine by treatment with magnesium metal in methanol solvent occurs to give predominantly the trans isomer, [https://pubchem.ncbi.nlm.nih.gov/compound/16726360 CID:16726360] ('''6'''). Catalytic removal of the benzyl group gives [https://pubchem.ncbi.nlm.nih.gov/compound/16726362 CID:16726362] ('''7'''). Reductive amination with Cyclooctanecarbaldehyde [6688-11-5] ('''7''') gives [https://pubchem.ncbi.nlm.nih.gov/compound/16726364 CID:16726364] ('''9'''). Lastly, reduction of the ester with lithium aluminium hydride completed the synthesis of J-113397 ('''10''').
-==See also==
+== See also ==
 * [[JTC-801]]
+* [[LY-2940094]]
 * [[SB-612,111]]
+* [https://pubchem.ncbi.nlm.nih.gov/compound/11494970 Trap-101] (unsaturated olefin not reduced).
 == References ==
-{{reflist}}
+{{Reflist|2}}
+{{Opioidergics}}
 [[Category:Synthetic opioids]]
@@ Line 44: / Line 77: @@
 [[Category:Piperidines]]
 [[Category:Ureas]]
-[[Category:Alcohols]]
+[[Category:Primary alcohols]]
+[[Category:Nociceptin receptor antagonists]]