Moxazocine

Moxazocine (BL-4566) is an opioid analgesic of the benzomorphan family which was never marketed.^[1] It acts as a partial agonist or mixed agonist/antagonist of the opioid receptors and binds preferentially to the κ-opioid receptor.^[2] Despite its failure to reach the market, clinical studies demonstrated moxazocine to be approximately 10x as potent by weight as morphine as an analgesic.^[3]

Moxazocine

Identifiers
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
CAS Number	58239-89-7
ChemSpider	16737008
UNII	BNB57S7DWT
CompTox Dashboard (EPA)	DTXSID80866681
Chemical and physical data
Formula	C18H25NO2
Molar mass	287.403 g·mol−1
3D model (JSmol)	Interactive image
SMILES Oc1ccc2C[C@H]3N(CC[C@@](C)(c2c1)[C@@H]3OC)CC4CC4
InChI InChI=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 Key:IOZWXJXXVLARQC-KURKYZTESA-N

Synthesis

Moxazocine synthesis:^[4][5]

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^[6][7] 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

• Benzomorphan

References

1. Dictionary of Pharmacological Agents Volume 2. CRC Press. 1996-11-21. p. 1382. ISBN 978-0-412-46630-4. Retrieved 22 April 2012.
2. Hayes AG, Sheehan MJ, Tyers MB (August 1987). "Differential sensitivity of models of antinociception in the rat, mouse and guinea-pig to mu- and kappa-opioid receptor agonists". British Journal of Pharmacology. 91 (4): 823–832. doi:10.1111/j.1476-5381.1987.tb11281.x. PMC 1853585. PMID 2822190.
3. Dobkin AB, Esposito BF, Noveck RJ, Caruso FS (October 1977). "Moxazocine and morphine in patients with severe postoperative pain". Current Therapeutic Research. 22 (4): 469–478.
4. DE 2517220, Montzka TA, Matiskella JD, "9-Alkoxy-5-methyl-6,7-benzomophane, VerfahrenE zu ihrer Herstellung und sie enthaltende Mittel [9-Alkoxy-5-methyl-6,7-benzomophanes, processes for their preparation and compositions containing them]", published 1975-11-06, assigned to Bristol-Myers Co.
5. Montzka TA, Matiskella JD, Chem. Abstr. 84, 59832k (1976).
6. Zhang K, Lu M, Li Y (2003). "Synthesis of Cyclopropanecarbonyl chloride". Chemical Industry Times. 17 (7): 36–38.
7. U.S. patent 5,504,245