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Latest revision as of 04:32, 16 January 2024 edit undoClueBot NG (talk | contribs)Bots, Pending changes reviewers, Rollbackers6,439,772 editsm Reverting possible vandalism by 173.64.94.7 to version by Entranced98. Report False Positive? Thanks, ClueBot NG. (4295242) (Bot)Tag: Rollback |
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{{short description|Chemical compound}} |
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{{Drugbox |
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{{Drugbox |
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| verifiedrevid = 407229371 |
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| IUPAC_name = (5R)-5-(3,4-dichlorophenyl)bicyclohexane |
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| verifiedrevid = 407870872 |
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| image = DOV-102,677 structure.png |
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| IUPAC_name = (1S,5R)-1-(3,4-dichlorophenyl)-3-azabicyclohexane |
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| CAS_number = |
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| image = DOV-102677.svg |
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| ATC_prefix = |
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| width = 170 |
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| ATC_suffix = |
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<!--Clinical data--> |
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| legal_US = Investigational New Drug |
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<!--Pharmacokinetic data--> |
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<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct|CAS}} |
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| CAS_number = 410074-75-8 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = NS8NWQ6NF4 |
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| ATC_prefix = |
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| PubChem = 11637190 |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = 9811932 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 488638 |
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<!--Chemical data--> |
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| C=11 | H=11 | Cl=2 | N=1 |
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| smiles = C121(CNC2)C3=CC(=C(C=C3)Cl)Cl |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI = 1S/C11H11Cl2N/c12-9-2-1-7(3-10(9)13)11-4-8(11)5-14-6-11/h1-3,8,14H,4-6H2/t8-,11+/m0/s1 |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey = BSMNRYCSBFHEMQ-GZMMTYOYSA-N |
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'''DOV 102,677''' is a ] being ] by ] as an ] and is currently in ].<ref name="Popik">{{Cite pmid|16636898}}</ref> It is a so-called ] (TUI), or ] (SNDRI).<ref name="Popik"/> |
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'''DOV-102,677''' is a ] being ] by ] and is currently in ].<ref name="Popik">{{cite journal | vauthors = Popik P, Krawczyk M, Golembiowska K, Nowak G, Janowsky A, Skolnick P, Lippa A, Basile AS | display-authors = 6 | title = Pharmacological profile of the "triple" monoamine neurotransmitter uptake inhibitor, DOV 102,677 | journal = Cellular and Molecular Neurobiology | volume = 26 | issue = 4–6 | pages = 857–73 | year = 2006 | pmid = 16636898 | doi = 10.1007/s10571-006-9012-5 | s2cid = 34989472 }}</ref> It is a ] (TRI), or ] (SNDRI).<ref name="Popik"/> It is the (−)-enantiomer of ], and its (+)-enantiomer is DOV-21,947 (]). |
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Instead of being developed for ], DOV-102,677 is being developed for the treatment of ].<ref>{{cite journal | vauthors = McMillen BA, Shank JE, Jordan KB, Williams HL, Basile AS | title = Effect of DOV 102,677 on the volitional consumption of ethanol by Myers' high ethanol-preferring rat | journal = Alcoholism: Clinical and Experimental Research | volume = 31 | issue = 11 | pages = 1866–71 | date = November 2007 | pmid = 17908267 | doi = 10.1111/j.1530-0277.2007.00513.x }}</ref> |
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] values for the ], ] and ] are 129 nM, 103 nM, and 133 nM.<ref name="Popik"/> |
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Instead of being developed for ], DOV-102,677 is being developed for the treatment of ].<ref>{{Cite pmid|17908267}}</ref> |
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] values for the ], ] and ] are 129 nM, 103 nM, and 133 nM.<ref name="Popik"/> |
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{| class="wikitable" border="1" |
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{| class="wikitable" border="1" |
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! rowspan=2 | Com |
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! rowspan=2 | Compound |
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! colspan=3 | Uptake |
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! colspan=3 | Uptake |
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! colspan=3 | Binding |
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! colspan=3 | Binding |
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|DOV-216,303 |
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"DOV 102,677 (20 mg/kg IP) increased extracellular levels of DA and 5-HT in the prefrontal cortex to 320 and 280% above baseline 100 min after administration. DA levels were stably increased for the duration (240 min) of the study, but serotonin levels declined to baseline by 200 min after administration. NE levels increased linearly to a maximum of 348% at 240 min post-dosing."<ref name="Popik"/> |
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DOV-102,677 (20 mg/kg IP) increased extracellular levels of dopamine and serotonin in the prefrontal cortex to 320 and 280% above baseline 100 min after administration. Dopamine levels were stably increased for the duration (240 min) of the study, but serotonin levels declined to baseline by 200 min after administration. Norepinephrine levels increased linearly to a maximum of 348% at 240 min post-dosing.<ref name="Popik"/> |
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==Chemistry== |
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DOV scientists and their collaborators have developed an efficient, asymmetric synthesis of 102,677.<ref>Skolnick P, Basile A, Chen Z (2006) {{Cite patent|WO|2006096810}}</ref> |
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This economical and robust new route uses phenylacetonitrile and (R)-] as starting materials to synthesize 102,677 in 3 steps: |
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#Phenylacetonitrile is reacted with (R)-epichlorohydrin in the presence of base to give the cyclopropyl compounds. |
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#The nitrile group is then hydrogenated into the amino alcohol compounds. |
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#Cyclization is achieved with SOCl<sub>2</sub> under acidic conditions. |
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#The product is neutralized with base. |
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== References == |
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== References == |
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{{Reflist|2}} |
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{{Reflist}} |
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{{Drugs used in addictive disorders}} |
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{{Antidepressants}} |
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{{Monoamine reuptake inhibitors}} |
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{{Anxiolytics}} |
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{{Stimulants}} |
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{{Psychostimulants}} |
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{{Adrenergics}} |
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{{Dopaminergics}} |
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{{Serotonergics}} |
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] |
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] |
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{{nervous-system-drug-stub}} |
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{{psychoactive-stub}} |