View source for Cilobamine

{{Short description|Chemical compound}}
{{Infobox drug
| IUPAC_name = (2''R'',3''R'')-2-(3,4-Dichlorophenyl)-3-[(1-methylethyl)amino]bicyclo[2.2.2]octan-2-ol
| image = Cilobamine clear.svg
| image_class = skin-invert-image
| width = 200

<!--Clinical data-->
| tradename =  
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B            / C / D / X -->
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA = <!--             / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL         / P       / POM / CD / Class A, B, C -->
| legal_US = <!-- OTC                   / Rx-only  / Schedule I, II, III, IV, V -->

<!--Identifiers-->
| CAS_number = 69429-84-1
| ATC_prefix = none
| PubChem = 299379
| ChemSpiderID = 8557262
| ChEMBL = 2106470
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 067U1T4S30

<!--Chemical data-->
| C=17 | H=23 | Cl=2 | N=1 | O=1 
| smiles = Clc1ccc(cc1Cl)[C@@]3(O)[C@H](NC(C)C)C2CCC3CC2
}}

'''Cilobamine''' is a drug which acts as a [[norepinephrine-dopamine reuptake inhibitor]] (NDRI) and has [[stimulant]] and [[antidepressant]] effects.<ref>{{cite journal | vauthors = Leeson GA, Shaath ZA, Biedenbach SA, Yarrington JT, Okerholm RA | title = Dose related induction of the drug metabolizing enzymes of rat liver by cilobamine | journal = Fundamental and Applied Toxicology | volume = 4 | issue = 2 Pt 1 | pages = 261–9 | date = April 1984 | pmid = 6724198 | doi = 10.1016/0272-0590(84)90127-1 }}</ref><ref>{{Cite journal | vauthors = Wager S, Quitkin F, Stewart J, McGrath P, Harrison W, Markowitz J, Tricamo E | title = Cilobamine in the treatment of atypical depression | journal = Human Psychopharmacology: Clinical and Experimental | year = 1988 | pages = 201–205| volume = 3 | issue = 3 | doi = 10.1002/hup.470030308 | s2cid = 145253439 }}</ref>

It can clearly be seen that the structure is based on [[dichloroisoprenaline]] that has been fused onto the bicycloalkane scaffold.

==Synthesis==
[[File:Cilobamine synthesis.svg|class=skin-invert-image|500px|thumb|center|Patent:<ref>DE2003744 idem Jules Freedman, {{US patent|3651142}} (1970 to Colgate Palmolive Co).</ref>]]

An intramolecular [[Dieckmann cyclization]] on methyl 4-(2-methoxy-2-oxoethyl)cyclohexanecarboxylate [1401222-79-4] ('''3''') with sodium hydride base gives reaction Methyl 3-oxobicyclo[2.2.2]octane-2-carboxylate [30144-30-0] ('''4'''). Treatment with [[sodium nitrite]] introduces an isonitroso group adjacent to the ketone, giving 3-Hydroxyiminobicyclo[2.2.2]octan-2-one, [https://pubchem.ncbi.nlm.nih.gov/compound/131066320 CID:131066320] ('''5'''). Addition of the aryl Grignard reagent, and reduction of the oxime gives [https://pubchem.ncbi.nlm.nih.gov/compound/154108204 CID:154108204] ('''6'''). A reductive amination of the primary amino group with acetone then completed the synthesis of cilobamine ('''7''').

== See also ==
* [[Fencamfamine]]
* [[Manifaxine]]

== References ==
{{Reflist}}

{{Stimulants}}
{{Antidepressants}}
{{Adrenergics}}
{{Dopaminergics}}

[[Category:Antidepressants]]
[[Category:Beta-Hydroxyamphetamines]]
[[Category:Chloroarenes]]
[[Category:Stimulants]]
[[Category:Norepinephrine–dopamine reuptake inhibitors]]


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