Thienorphine

Thienorphine

Clinical data
ATC code	None
Identifiers
IUPAC name (1R,2R,6S,15R)-3-(cyclopropylmethyl)-16-[(2R)-2-hydroxy-4-(thiophen-2-yl)butan-2-yl]-15-methoxy-13-oxa-3-azahexacyclo[13.2.2.1²,⁸.0¹,⁶.0⁶,¹⁴.0⁷,¹²]icosa-7,9,11-trien-11-ol
PubChem (CID)	102212421
Chemical and physical data
Formula	C31H39NO4S
Molar mass	521.71066 g/mol
3D model (Jmol)	Interactive image
SMILES CC(CCC1=CC=CS1)(C2CC34CCC2(C5C36CCN(C4CC7=C6C(=C(C=C7)O)O5)CC8CC8)OC)O
InChI InChI=1S/C31H39NO4S/c1-28(34,10-9-21-4-3-15-37-21)23-17-29-11-12-31(23,35-2)27-30(29)13-14-32(18-19-5-6-19)24(29)16-20-7-8-22(33)26(36-27)25(20)30/h3-4,7-8,15,19,23-24,27,33-34H,5-6,9-14,16-18H2,1-2H3/t23?,24-,27?,28-,29+,30+,31-/m1/s1 Key:WTGSHWLSWVFVAH-HRHGHGIZSA-N

Thienorphine is a very potent, extremely long-acting, orally-active opioid analgesic with mixed agonist–antagonist properties which was developed by the Beijing Institute of Pharmacology and Toxicology as a potential treatment for opioid dependence.^[1][2][3] It is a high-affinity, balanced ligand of the μ- (K_i = 0.22 nM), δ- (K_i = 0.69 nM), and κ-opioid receptors (K_i = 0.14 nM), behaving as a partial agonist of the μ- (E_max = 19%–28%) and κ-opioid receptors (E_max = 65–75%) and as an antagonist of the δ-opioid receptor.^[4][5][6] It also possesses relatively low affinity for the nociceptin receptor (K_i = 36.5 nM), where it acts as an antagonist.^[6]

See also

• Buprenorphine
• Etorphine
• Dihydroetorphine
• Diprenorphine

References

1. HE Liu, Zhong Bo-Hua, Liu Chun-He, Bo Wu, Gong Ze-Hui (2005). "Synthesis, Crystal Structural and Pharmacological Study of N-Cyclopropylmehtyl-7α-[(R)-1-hydroxyl-1-methyl-3-(thien-2-yl)propyl]-6,14-endoethanotetrahydronooripavine" (PDF). Acta Chimica Slovenica. Slovenian Chemical Society. 52 (1): 80–85. ISSN 1318-0207.
2. Yu G, Liu YS, Yan LD, Wen Q, Gong ZH (2009). "[Structure-activity relationships analysis of thienorphine and its derivatives]". Yao Xue Xue Bao (in Chinese). 44 (7): 726–30. PMID 19806910.
3. Yu, Gang; Li, Shu-Hui; Cui, Meng-Xun; Yan, Ling-Di; Yong, Zheng; Zhou, Pei-Lan; Su, Rui-Bin; Gong, Ze-Hui (2014). "Multiple Mechanisms Underlying the Long Duration of Action of Thienorphine, A Novel Partial Opioid Agonist for the Treatment of Addiction". CNS Neuroscience & Therapeutics. 20 (3): 282–288. doi:10.1111/cns.12210. ISSN 1755-5930. PMID 24330593.
4. Yu, G. (2006). "Thienorphine Is a Potent Long-Acting Partial Opioid Agonist: A Comparative Study with Buprenorphine". Journal of Pharmacology and Experimental Therapeutics. 318 (1): 282–287. doi:10.1124/jpet.105.099937. ISSN 0022-3565. PMID 16569757.
5. Li, J.-X.; Becker, G. L.; Traynor, J. R.; Gong, Z.-H.; France, C. P. (2007). "Thienorphine: Receptor Binding and Behavioral Effects in Rhesus Monkeys". Journal of Pharmacology and Experimental Therapeutics. 321 (1): 227–236. doi:10.1124/jpet.106.113290. ISSN 0022-3565. PMID 17220427.
6. Wen, Quan; Yu, Gang; Li, Yu-lei; Yan, Ling-di; Gong, Ze-hui (2011). "Pharmacological mechanisms underlying the antinociceptive and tolerance effects of the 6,14-bridged oripavine compound 030418". Acta Pharmacologica Sinica. 32 (10): 1215–1224. doi:10.1038/aps.2011.83. ISSN 1671-4083. PMC 4010084. PMID 21863064.