U-47700: Difference between revisions
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{{Drugbox |
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| Verifiedfields = changed |
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| verifiedrevid = 477235538 |
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| IUPAC_name = ''trans''-3,4-dichloro-''N''-(2-(dimethylamino)cyclohexyl)-N-methylbenzamide |
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| image = U-47700_molecule.svg |
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| width = 200 |
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<!--Clinical data--> |
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| tradename = |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| pregnancy_category = |
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| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> |
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| legal_CA = |
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| legal_UK = |
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| legal_US = |
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| routes_of_administration = oral, parenteral |
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<!--Pharmacokinetic data--> |
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| bioavailability = |
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| metabolism = |
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| elimination_half-life = |
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<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|changed|??}} |
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| CAS_number = |
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| ATC_prefix = none |
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| ATC_suffix = |
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| PubChem = 13544015 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 163208 |
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<!--Chemical data--> |
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| Formula C16H22Cl2N2O |
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| molecular_weight = 329.265 g/mol |
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| smiles = CN([C@@H]1CCCC[C@H]1N(C)C(C2=CC=C(Cl)C(Cl)=C2)=O)C |
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| InChI = 1S/C17H24Cl2N2O/c1-20(2)15-6-4-5-7-16(15)21(3)17(22)11-12-8-9-13(18)14(19)10-12/h8-10,15-16H,4-7,11H2,1-3H3/t15-,16-/m0/s1 [ChEMBL] |
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| InChIKey = ISJUYFBACBKWBV-HOTGVXAUSA-N [ChEMBL] |
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| StdInChI_Ref = |
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| StdInChI = 1S/C16H22Cl2N2O/c1-19(2)14-6-4-5-7-15(14)20(3)16(21)11-8-9-12(17)13(18)10-11/h8-10,14-15H,4-7H2,1-3H3/t14-,15-/m1/s1 |
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| StdInChIKey_Ref = |
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| StdInChIKey = ISJUYFBACBKWBV-HOTGVXAUSA-N |
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}} |
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'''U-47700'''<ref>{{citation|url=http://www.distilbio.com/show/compound/U-47700 |title=U-47700 at DistilBio}}</ref> is an [[opioid]] [[analgesic]] drug developed by a team at [[Upjohn]] in the 1970s.<ref>US Patent 4098904 - Analgesic N-(2-aminocycloaliphatic)benzamides</ref> U-47700 was derived from an earlier opioid [[AH-7921]]. U-47700 is selective for the [[µ-opioid receptor]], having around 7.5 x the potency of [[morphine]] in animal models.<ref>'Factors Affecting Binding of trans-N-[2-(Methylamino)cyclohexyl]benzamides at the Primary Morphine receptor' B. Vernon Cheney, Jacob Smuszkovicz, Robert A. Lahtr & Dominic A. Zichi - J Med Chem. 1985 Dec;28(12):1853-64.</ref> |
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U-47700 is the result of a great deal of work elucidating the [[quantitative structure–activity relationship]] of the scaffold. The team looked for the key [[moiety (chemistry)|moieties]] which gave the greatest activity.<ref>Medicinal agents incorporating the 1,2-diamine functionality - Erik T. Michalson, Jacob Szmuszkovicz, Progress in Drug Research Volume 33, 1989, pp 135-149</ref> Upjohn posted over a dozen patents on related compounds, each optimizing one moiety <ref>US Patent 3258489 N-1(aminocyclohexyl)anilines and N-(1-nitrocyclhexylmethyl)Anilines</ref><ref>US Patent 3975443 (3,4-dichlorobenzamidomethyl)-Cyclohexyldimethylamine, US Patent 3499033 Ethers of alpha-phenyl-2-aminocycloalkanemethanols</ref><ref>US Patent 3510492 2-anilino and 2-anilinomethyl cycloalkylamines</ref><ref>US Patent 3647804 Cycloalkanecarboxamides</ref><ref>US Patent 3825595 N-cyclopentyl-n-2-hydroxyalkyl-ring-substituted benzamides</ref><ref>US Patent 4049663 Ethylene Diamine Derivatives</ref> until they discovered that U-47700 was the most active.<ref>'Opioid Analgesics, Chemistry and Receptors' Page395 Alan F. Casy & Robert T Parfitt ISBN 0-306-42130-5</ref> |
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U-47700 became the lead-compound of selective kappa ligands such as [[U-50488]] and [[U-69,593]], which share a very similar structure (a single methylene spacer difference).<ref>'Structure Activity Studies of Two Classes of Beta-Amino-Amides: The Search for Kappa-Selective' Opioids G.Loew, J.Lawson, L.Toll, G.Frenking, I.Berzetei-Gurske and W. Polgar Pages 144-151 NIDA Research Monograph Series 90 PMID 2855852</ref> Its structure lead to other chemists experimenting with it to see if rigid analogues would retain activity.<ref>'Phenanthridone Analogs of the Opiate Agonist U-47,700 in the trans-1,2-Diaminocyclohexane Benzamide Series' Shikai Zhao, Michael J. Totleben, Stephen A. Mizsak, Jeremiah P. Freeman, and Jacob Szmuszkovicz - Heterocycles Special issue | Vol 52, No. 1, 2000, pp.325-332 Published online, 1st January, 1970</ref> Although not used medically, the selective kappa ligands are used in research.<ref>'U-50,488 and the к receptor: A personalized account covering the period 1973 to 1990' by Jacob Szmuszkovic, Progress in Drug Research Volume 52, 1999, pp 167-195</ref> |
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U-47700 has never been studied in humans, but would be expected to produce effects similar to those of other potent opioid agonists, including strong analgesia, sedation, euphoria, constipation, itching and respiratory depression which could be harmful or fatal. Tolerance and dependence would be expected to develop. Since affinity to kappa receptors has not been measured, it may also induce dysphoria and other unwanted side-effects but it's 3DQSAR, make it this unlikely<ref>'Differentiation of ς, μ and ϰ opioid receptor agonists based on pharmocore development and computed physicochemical properties' Journal of Computer-Aided Molecular design, 15: 297-307, 2001</ref>. Its structure is similar to [[U-50488]], a pure kappa agonist. |
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== References == |
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{{Reflist|2}} |
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{{Opioidergics}} |
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[[Category:Synthetic opioids]] |
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[[Category:Benzamides]] |
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[[Category:Mu-opioid agonists]] |
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[[Category:Amines]] |
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[[Category:Organobromides]] |
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{{analgesic-stub}} |
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