Moxazocine

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;

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]

Synthesis

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).

References

^ Dictionary of Pharmacological Agents Volume 2. CRC Press. 1996-11-21. p. 1382. ISBN 978-0-412-46630-4. Retrieved 22 April 2012.
^ 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.
^ 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.
^ 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.
^ Montzka TA, Matiskella JD, Chem. Abstr. 84, 59832k (1976).
^ Zhang K, Lu M, Li Y (2003). "Synthesis of Cyclopropanecarbonyl chloride". Chemical Industry Times. 17 (7): 36–38.
^ U.S. patent 5,504,245

[Triggle1997-1] Dictionary of Pharmacological Agents Volume 2. CRC Press. 1996-11-21. p. 1382. ISBN 978-0-412-46630-4. Retrieved 22 April 2012.

[pmid2822190-2] 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.

[Dobkin1977-3] 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

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[2]

[3]

[4]

[5]

[6]

[7]

Synthesis

See also

References