Noraporphines are a class of chemical compounds related to the aporphine alkaloids like nuciferine and glaucine and synthetic aporphines like apomorphine.[1][2] They are N-desmethyl analogues of the aporphines.[1][2] Some noraporphines are alkaloids similarly to aporphines, for instance nornuciferine and asimilobine occurring naturally in Nelumbo nucifera and other plants.[1][3][4]
Some noraporphines, such as asimilobine, nornuciferine, MQ02-439 (1-methoxynoraporphine), and 11-chloroasimilobine, have been found to act as potent and selective serotonin 5-HT2C receptor agonists.[5][6][7][8] Others, such as racemic asimilobine, 1-propoxy-2-hydroxynoraporphine, 11-methoxyasimilobine, 2-hydroxy-11-propoxynoraporphine, and 2-hydroxy-11-(2-methylallyl)oxynoraporphine, have been found to act as potent mixed serotonin 5-HT2A and 5-HT2C receptor agonists.[8] Conversely, aporphines, like nuciferine, dicentrine, isolaureline, and crebanine, tend to be antagonists or very weak partial agonists of the serotonin 5-HT2A and/or 5-HT2C receptors,[9][10][11][12] although exceptions with higher efficacy such as glaucine are known.[10]
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Many other noraporphine alkaloids are also known, including norlaureline, puterine, norstephalagine, norisocorydine, nordicentrine, norboldine (laurolistine), norpurpureine, norpredicentrine, laetanine, oduocine, norannuradhapurine, nornantenine, and norushinsunine (michelalbine), among others.[2][13]
See also
[edit]References
[edit]- 1 2 3 Shamma, Maurice; Slusarchyk, William A. (1964-02-01). "The Aporphine Alkaloids". Chemical Reviews. 64 (1): 59–79. Bibcode:1964ChRv...64...59S. doi:10.1021/cr60227a004. ISSN 0009-2665. Retrieved 2026-04-06.
- 1 2 3 Guinaudeau, Hélène; Leboeuf, Michel; Cavé, André (1988). "Aporphinoid Alkaloids, IV". Journal of Natural Products. 51 (3): 389–474. Bibcode:1988JNAtP..51..389G. doi:10.1021/np50057a001. ISSN 0163-3864. Retrieved 6 April 2026.
- ↑ Kunitomo, J.; Yoshikawa, Y.; Tanaka, S.; Imori, Y.; Isoi, K.; Masada, Y.; Hashimoto, K.; Inoue, T. (1973). "Alkaloids of Nelumbo nucifera". Phytochemistry. 12 (3): 699–701. Bibcode:1973PChem..12..699K. doi:10.1016/S0031-9422(00)84467-2. Retrieved 6 April 2026.
- ↑ Shoji N, Umeyama A, Saito N, Iuchi A, Takemoto T, Kajiwara A, Ohizumi Y (1987). "Asimilobine and lirinidine, serotonergic receptor antagonists, from Nelumbo nucifera". J Nat Prod. 50 (4): 773–774. Bibcode:1987JNAtP..50..773S. doi:10.1021/np50052a044. PMID 3430176.
- ↑ Zhang B, Zhao S, Yang D, Wu Y, Xin Y, Cao H, Huang XP, Cai X, Sun W, Ye N, Xu Y, Peng Y, Zhao S, Liu ZJ, Zhong G, Wang MW, Shui W (February 2020). "A Novel G Protein-Biased and Subtype-Selective Agonist for a G Protein-Coupled Receptor Discovered from Screening Herbal Extracts". ACS Cent Sci. 6 (2): 213–225. doi:10.1021/acscentsci.9b01125. PMC 7047268. PMID 32123739.
- ↑ Mao Q, Zhang B, Li W, Tian S, Shui W, Ye N (February 2020). "Identification of Novel 1-O-Substituted Aporphine Analogues as Potent 5-HT2C Receptor Agonists". ACS Chem Neurosci. 11 (4): 549–559. doi:10.1021/acschemneuro.9b00563. PMID 31968160.
- ↑ Mao Q, Zhang B, Tian S, Qin W, Chen J, Huang XP, Xin Y, Yang H, Zhen XC, Shui W, Ye N (June 2022). "Structural optimizations and bioevaluation of N-H aporphine analogues as Gq-biased and selective serotonin 5-HT2C receptor agonists". Bioorg Chem. 123 105795. doi:10.1016/j.bioorg.2022.105795. PMID 35430417.
- 1 2 Qin W, Zhang B, Wang Q, Jiang G, Cui J, Chen F, Wang L, Chen J, Tian S, Zhen XC, Shui W, Ye N (November 2025). "Discovery of New N-H Aporphine Derivatives As Brain-Penetrant Gq-Biased 5-HT2C Receptor Agonists and Dual 5-HT2C/5-HT2A Receptor Agonists". J Med Chem. 68 (21): 23300–23323. doi:10.1021/acs.jmedchem.5c02115. PMID 41108743.
- ↑ Farrell MS, McCorvy JD, Huang XP, Urban DJ, White KL, Giguere PM, Doak AK, Bernstein AI, Stout KA, Park SM, Rodriguiz RM, Gray BW, Hyatt WS, Norwood AP, Webster KA, Gannon BM, Miller GW, Porter JH, Shoichet BK, Fantegrossi WE, Wetsel WC, Roth BL (2016). "In Vitro and In Vivo Characterization of the Alkaloid Nuciferine". PLOS ONE. 11 (3) e0150602. Bibcode:2016PLoSO..1150602F. doi:10.1371/journal.pone.0150602. PMC 4786259. PMID 26963248.
- 1 2 Heng HL, Chee CF, Thy CK, Tee JT, Chin SP, Herr DR, Buckle MJ, Paterson IC, Doughty SW, Abd Rahman N, Chung LY (February 2019). "In vitro functional evaluation of isolaureline, dicentrine and glaucine enantiomers at 5-HT2 and α1 receptors". Chem Biol Drug Des. 93 (2): 132–138. doi:10.1111/cbdd.13390. PMID 30216681.
- ↑ Peng Y, Zhao S, Wu Y, Cao H, Xu Y, Liu X, Shui W, Cheng J, Zhao S, Shen L, Ma J, Quinn RJ, Stevens RC, Zhong G, Liu ZJ (2018). "Identification of natural products as novel ligands for the human 5-HT2C receptor". Biophys Rep. 4 (1): 50–61. doi:10.1007/s41048-018-0047-1. PMC 5860131. PMID 29577069.
- ↑ Chaudhary S, Ponnala S, Legendre O, Gonzales JA, Navarro HA, Harding WW (October 2011). "New aporphinoid 5-HT2A and α1A antagonists via structural manipulations of nantenine". Bioorg Med Chem. 19 (19): 5861–5868. doi:10.1016/j.bmc.2011.08.019. PMC 3196372. PMID 21900013.
However, homologation did not improve the antagonist activity. In fact in the case of 6c, this compound had weak agonist activity (19% of 5-HT Emax). Next we decided to investigate other cycloalkyloxy analogs. The cyclohexylmethyloxy analog (6g) showed moderate activity, albeit 25-fold lower than the cyclopropyloxy analog. Other cycloalkyloxy derivatives tested showed weak agonist activity (25% and 35% of 5-HT Emax for 6e and 6f, respectively).
- ↑ Bentley KW (June 1988). "beta-Phenylethylamines and the isoquinoline alkaloids". Nat Prod Rep. 5 (3): 265–292. doi:10.1039/np9880500265. PMID.