Conorfone

Conorfone
Clinical data
ATC code	None;
Identifiers
	IUPAC name (5α,8β)-17-(Cyclopropylmethyl)-8-ethyl-3-methoxy-4,5-epoxymorphinan-6-one;
CAS Number	72060-05-0;
PubChem CID	172964;
ChemSpider	151049;
UNII	9H58696D23;
ChEMBL	ChEMBL2106064;
Chemical and physical data
Formula	C23H29NO3
Molar mass	367.489 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C4[C@@H]5Oc1c2c(ccc1OC)CC3N(CC[C@]25[C@H]3[C@@H](CC)C4)CC6CC6;
	InChI InChI=1S/C23H29NO3/c1-3-14-11-17(25)22-23-8-9-24(12-13-4-5-13)16(19(14)23)10-15-6-7-18(26-2)21(27-22)20(15)23/h6-7,13-14,16,19,22H,3-5,8-12H2,1-2H3/t14-,16?,19-,22-,23-/m0/s1 ; Key:JMPUQJQXECRLKY-MNABOLNXSA-N ;

Conorfone (INN; TR-5109), also known as conorphone and codorphone, as well as conorphone hydrochloride (USAN), is an opioid analgesic that was never marketed.^[1] It is an analogue of hydrocodone substituted with an 8-ethyl group and an N-cyclopropyl methyl group. It acts as a mixed agonist-antagonist at the μ-opioid receptor, and is slightly more potent than codeine in analgesic effects, but associated with somewhat greater side effects.^[2]

Synthesis

Exposure of thebaine (1) to mild acid leads to hydrolysis of the enol ether function, followed by migration of the double bond to yield the conjugated enone (2). Addition of lithium diethylcuprate proceeds by 1,4-addition from the less hindered side to give the intermediate (3). Treatment of that with cyanogen bromide under von Braun reaction conditions leads to the isolable aminocyanide. This is the converted to the secondary amine (4) by treatment with aqueous base. Alkylation of that intermediate with cyclopropylmethyl chloride yields the analgesic codorphone.^[3]

References

^ Macdonald F (1997). Dictionary of Pharmacological Agents. CRC Press. p. 514. ISBN 978-0-412-46630-4. Retrieved 12 May 2012.
^ Dionne RA, Wirdezk PR, Butler DP, Fox PC (1984). "Comparison of conorphone, a mixed agonist-antagonist analgesic, to codeine for postoperative dental pain". Anesthesia Progress. 31 (2): 77–81. PMC 2515536. PMID 6597688.
^ Kotick MP, Leland DL, Polazzi JO, Schut RN (February 1980). "Analgesic narcotic antagonists. 1. 8 beta-Alkyl-, 8 beta-acyl-, and 8 beta-(tertiary alcohol)dihydrocodeinones and -dihydromorphinones". Journal of Medicinal Chemistry. 23 (2): 166–174. doi:10.1021/jm00176a012. PMID 6153723.

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[Macdonald1997-1] Macdonald F (1997). Dictionary of Pharmacological Agents. CRC Press. p. 514. ISBN 978-0-412-46630-4. Retrieved 12 May 2012.

[pmid6597688-2] Dionne RA, Wirdezk PR, Butler DP, Fox PC (1984). "Comparison of conorphone, a mixed agonist-antagonist analgesic, to codeine for postoperative dental pain". Anesthesia Progress. 31 (2): 77–81. PMC 2515536. PMID 6597688.

[3] Kotick MP, Leland DL, Polazzi JO, Schut RN (February 1980). "Analgesic narcotic antagonists. 1. 8 beta-Alkyl-, 8 beta-acyl-, and 8 beta-(tertiary alcohol)dihydrocodeinones and -dihydromorphinones". Journal of Medicinal Chemistry. 23 (2): 166–174. doi:10.1021/jm00176a012. PMID 6153723.

[1]

[2]

[3]

Synthesis

See also

References