Moxazocine
{{short description|Chemical compound}}
{{Drugbox
| IUPAC_name = (1S,9R,13S)-10-(cyclopropylmethyl)-13-methoxy-1-methyl-10-azatricyclo[7.3.1.02,7]trideca-2,4,6-trien-4-ol
| image = moxazocine structure.svg
| image_class = skin-invert-image
| CAS_number = 58239-89-7
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = BNB57S7DWT
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| ChemSpiderID = 16737008
| C = 18 | H = 25 | N = 1 | O = 2
| smiles = Oc1ccc2C[C@H]3N(CC[C@@](C)(c2c1)[C@@H]3OC)CC4CC4
| StdInChI = 1S/C18H25NO2/c1-18-7-8-19(11-12-3-4-12)16(17(18)21-2)9-13-5-6-14(20)10-15(13)18/h5-6,10,12,16-17,20H,3-4,7-9,11H2,1-2H3/t16-,17-,18+/m1/s1
| StdInChIKey = IOZWXJXXVLARQC-KURKYZTESA-N
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Moxazocine (BL-4566) is an opioid analgesic of the benzomorphan family which was never marketed.{{cite book | title = Dictionary of Pharmacological Agents Volume 2 | url = https://books.google.com/books?id=A0THacd46ZsC&pg=PA1382 | access-date = 22 April 2012 | publisher = CRC Press | isbn = 978-0-412-46630-4 | page = 1382|date = 1996-11-21}} It acts as a partial agonist or mixed agonist/antagonist of the opioid receptors and binds preferentially to the κ-opioid receptor.{{cite journal | vauthors = Hayes AG, Sheehan MJ, Tyers MB | title = Differential sensitivity of models of antinociception in the rat, mouse and guinea-pig to mu- and kappa-opioid receptor agonists | journal = British Journal of Pharmacology | volume = 91 | issue = 4 | pages = 823–832 | date = August 1987 | pmid = 2822190 | pmc = 1853585 | doi = 10.1111/j.1476-5381.1987.tb11281.x }} Despite its failure to reach the market, clinical studies demonstrated moxazocine to be approximately 10x as potent by weight as morphine as an analgesic.{{cite journal | title = Moxazocine and morphine in patients with severe postoperative pain | vauthors = Dobkin AB, Esposito BF, Noveck RJ, Caruso FS | journal = Current Therapeutic Research | volume = 22 | issue = 4 |date=October 1977 | pages = 469–478 | url = http://psycnet.apa.org/psycinfo/1978-23576-001}}
Synthesis
File:Moxazocine synthesis.svg|inventor1-last=Montzka|inventor = Montzka TA, Matiskella JD }}Montzka TA, Matiskella JD, Chem. Abstr. 84, 59832k (1976).]]
Reduction of the carbonyl group in oxygenated benzomorphan 1 affords the corresponding alcohol (2). This intermediate is then N-demethylated by means of BrCN. Acylation with cyclopropylcarbonyl chloride{{Cite journal|url=http://caod.oriprobe.com/articles/6521356/Synthesis_of_Cyclopropanecarbonyl_chloride.htm|title = Synthesis of Cyclopropanecarbonyl chloride|journal = Chemical Industry Times|year = 2003|volume = 17|issue = 7|pages = 36–38| vauthors = Zhang K, Lu M, Li Y }}{{US patent|5504245}} gives the amide (3). The alcohol is then converted to the ether by treatment with MeI and base (4). Treatment with LiAlH4 serves to reduce the amide function. Cleavage of the phenolic ether by one of the standard schemes affords moxazocine (6).
See also
References
{{Reflist}}
{{Analgesics}}
{{Antitussives}}
{{Opioidergics}}