Ciramadol

Ciramadol
Clinical data
Other names	Ciramadol, WY-15705
Routes of; administration	Oral
ATC code	none;
Identifiers
	IUPAC name 3-{(R)-Dimethylamino-[(1R,2R)-2-hydroxycyclohexyl]}methyl]phenol;
CAS Number	63269-31-8 ;
PubChem CID	44463;
ChemSpider	40461 ;
UNII	9NQ109OW0G;
KEGG	D03523 ;
ChEMBL	ChEMBL2104132;
CompTox Dashboard (EPA)	DTXSID601018412 ;
Chemical and physical data
Formula	C15H23NO2
Molar mass	249.354 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES OC1=CC=CC([C@@H]([C@H]2CCCC[C@H]2O)N(C)C)=C1;
	InChI InChI=1S/C15H23NO2/c1-16(2)15(11-6-5-7-12(17)10-11)13-8-3-4-9-14(13)18/h5-7,10,13-15,17-18H,3-4,8-9H2,1-2H3/t13-,14+,15-/m0/s1 ; Key:UVTLONZTPXCUPU-ZNMIVQPWSA-N ;
	(verify)

Ciramadol (WY-15,705) is an opioid analgesic that was developed in the late 1970s^[1] and is related to phencyclidine, tramadol, tapentadol and venlafaxine.^[2] It is a mixed agonist-antagonist for the μ-opioid receptor with relatively low abuse potential^[3] and a ceiling on respiratory depression^[4] which makes it a relatively safe drug. It has a slightly higher potency and effectiveness as an analgesic than codeine,^[5] but is weaker than morphine.^[6] Other side effects include sedation and nausea but these are generally less severe than with other similar drugs.^[7]

Synthesis

The Claisen-Schmidt condensation between 3-(methoxymethoxy)benzaldehyde [13709-05-2] (1) and cyclohexanone (2) afforded CID:54364197 (3). Michael addition of dimethylamine leads the aminoketone, i.e. 2-[dimethylamino-[3-(methoxymethoxy)phenyl]methyl]cyclohexan-1-one, CID21518320. Reduction of the ketone proceeds stereospecifically to afford the cis aminoalcohol [51356-58-2] (4). Mild hydrolysis of the product gives the free phenol ciramadol (5).

References

^ US 3928626, "Benzylamine Analgesics"
^ Cochrane AD, Bell R, Sullivan JR, Shaw J (November 1979). "Ciramadol. A new analgesic". The Medical Journal of Australia. 2 (9): 501–2. doi:10.5694/j.1326-5377.1979.tb125803.x. PMID 522808.
^ Preston KL, Bigelow GE, Liebson IA (March 1987). "Comparative evaluation of morphine, pentazocine and ciramadol in postaddicts". The Journal of Pharmacology and Experimental Therapeutics. 240 (3): 900–10. PMID 3559982.
^ Romagnoli A, Keats AS (1986). "Low ceiling respiratory depression by ciramadol". International Journal of Clinical Pharmacology Research. 6 (6): 451–5. PMID 3100462.
^ Downing JW, Brock-Utne JG, Holloway AM (December 1983). "Ciramadol--a new synthetic analgesic. A double-blind comparison with oral codeine for postoperative pain relief". South African Medical Journal = Suid-Afrikaanse Tydskrif vir Geneeskunde. 64 (25): 978–82. PMID 6359486.
^ Powell WF (November 1985). "A double-blind comparison of multiple intramuscular doses of ciramadol, morphine, and placebo for the treatment of postoperative pain". Anesthesia and Analgesia. 64 (11): 1101–7. doi:10.1213/00000539-198511000-00012. PMID 3901821.
^ Stambaugh JE, McAdams J (February 1987). "Comparison of the analgesic efficacy and safety oral ciramadol, codeine, and placebo in patients with chronic cancer pain". Journal of Clinical Pharmacology. 27 (2): 162–6. doi:10.1002/j.1552-4604.1987.tb02178.x. PMID 3680568. S2CID 21229861.
^ Yardley, J. P.; Fletcher, H.; Russell, P. B. (1978). "A potent benzylamine analgesic:(−)cis-2(α-dimethylamino-m-hydroxybenzyl)cyclohexanol". Experientia 34(9): 1124–1125. doi:10.1007/BF01922905.
^ Paton, D.M.; Castaner, J.; Ciramadol. Drugs Fut 1980, 5, 6, 283.
^ Peter B Russell, John P Yardley, U.S. patent 3,928,626, U.S. patent 4,017,637 (1975 and 1977 to American Home Products Corporation).
^ John Patrick Yardley, Peter Byrom Russell, DE 2317183 (1986 to American Home Prod).
^ John P. Yardley & Peter B. Russell, U.S. patent 4,155,935 (1979 to Wyeth LLC).

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[1] US 3928626, "Benzylamine Analgesics"

[pmid522808-2] Cochrane AD, Bell R, Sullivan JR, Shaw J (November 1979). "Ciramadol. A new analgesic". The Medical Journal of Australia. 2 (9): 501–2. doi:10.5694/j.1326-5377.1979.tb125803.x. PMID 522808.

[pmid3559982-3] Preston KL, Bigelow GE, Liebson IA (March 1987). "Comparative evaluation of morphine, pentazocine and ciramadol in postaddicts". The Journal of Pharmacology and Experimental Therapeutics. 240 (3): 900–10. PMID 3559982.

[pmid3100462-4] Romagnoli A, Keats AS (1986). "Low ceiling respiratory depression by ciramadol". International Journal of Clinical Pharmacology Research. 6 (6): 451–5. PMID 3100462.

[pmid6359486-5] Downing JW, Brock-Utne JG, Holloway AM (December 1983). "Ciramadol--a new synthetic analgesic. A double-blind comparison with oral codeine for postoperative pain relief". South African Medical Journal = Suid-Afrikaanse Tydskrif vir Geneeskunde. 64 (25): 978–82. PMID 6359486.

[6] Powell WF (November 1985). "A double-blind comparison of multiple intramuscular doses of ciramadol, morphine, and placebo for the treatment of postoperative pain". Anesthesia and Analgesia. 64 (11): 1101–7. doi:10.1213/00000539-198511000-00012. PMID 3901821.

[pmid3680568-7] Stambaugh JE, McAdams J (February 1987). "Comparison of the analgesic efficacy and safety oral ciramadol, codeine, and placebo in patients with chronic cancer pain". Journal of Clinical Pharmacology. 27 (2): 162–6. doi:10.1002/j.1552-4604.1987.tb02178.x. PMID 3680568. S2CID 21229861.

[8] Yardley, J. P.; Fletcher, H.; Russell, P. B. (1978). "A potent benzylamine analgesic:(−)cis-2(α-dimethylamino-m-hydroxybenzyl)cyclohexanol". Experientia 34(9): 1124–1125. doi:10.1007/BF01922905.

[9] Paton, D.M.; Castaner, J.; Ciramadol. Drugs Fut 1980, 5, 6, 283.

[10] Peter B Russell, John P Yardley, U.S. patent 3,928,626, U.S. patent 4,017,637 (1975 and 1977 to American Home Products Corporation).

[11] John Patrick Yardley, Peter Byrom Russell, DE 2317183 (1986 to American Home Prod).

[12] John P. Yardley & Peter B. Russell, U.S. patent 4,155,935 (1979 to Wyeth LLC).

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Synthesis

See also

References