Advances on the Bioactivities, Total Synthesis, Structural Modification, and Structure-Activity Relationships of Cytisine Derivatives

Author(s): Xiaobo Huang, Hui Xu*

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 20 , Issue 5 , 2020


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Graphical Abstract:


Abstract:

Cytisine is a quinolizidine alkaloid isolated from various Leguminosae plants. Cytisine and its derivatives exhibit a broad range of biological properties, such as smoking cessation aid, antidepressant, neuroprotective, nootropic, anticancer, antiviral, antiparasitic, antidiabetic, insecticidal, and nematicidal activities. In this review, the progress of cytisine and its derivatives in regard to bioactivities, total synthesis, structural modifications focusing on their N-12 position and lactam ring is reported. Additionally, the structure-activity relationships of cytisine and its derivatives are also discussed.

Keywords: Cytisine, bioactivities, total synthesis, structural modification, lactam ring, structure-activity relationship.

[1]
Husemann, A.; Husemann, T. Die Pflanzenstoffe in Chemischer Physiologischer; Pharmakologischer und Toxikologischer Hinsicht: Verlagvon Julius Springer, Berlin, 1871, pp. 64-68.
[2]
Partheil, A. Zur Frage der Identität von. Cytisin und Ulexin. Arch. Pharm. (Weinheim, Ger.), 1894, 232, 486.
[3]
Wang, H.; Tong, Y.; Li, W.; Zhang, X.; Gao, X.; Yong, J.; Zhao, J.; Koike, K. Enhanced ultrasound-assisted enzymatic hydrolysis extraction of quinolizidine alkaloids from Sophora alopecuroides L. seeds. J. Nat. Med., 2018, 72(2), 424-432.
[http://dx.doi.org/10.1007/s11418-017-1165-7] [PMID: 29236225]
[4]
Lee, S.T.; Cook, D.; Molyneux, R.J. Identification of the quinolizidine alkaloids in Sophora leachiana. Biochem. Syst. Ecol., 2014, 54, 1-4.
[http://dx.doi.org/10.1016/j.bse.2013.12.020]
[5]
Pan, Q.M.; Zhang, G.J.; Huang, R.Z.; Pan, Y.M.; Wang, H.S.; Liang, D. Cytisine-type alkaloids and flavonoids from the rhizomes of Sophora tonkinensis. J. Asian Nat. Prod. Res., 2016, 18(5), 429-435.
[http://dx.doi.org/10.1080/10286020.2015.1131680] [PMID: 26757778]
[6]
Zhang, S.Y.; Li, W.; Nie, H.; Liao, M.; Qiu, B.; Yang, Y.L.; Chen, Y.F. Five new alkaloids from the roots of Sophora flavescens. Chem. Biodivers., 2018, 15(3) e1700577
[http://dx.doi.org/10.1002/cbdv.201700577] [PMID: 29356325]
[7]
Hajek, P.; McRobbie, H.; Myers, K. Efficacy of cytisine in helping smokers quit: Systematic review and meta-analysis. Thorax, 2013, 68(11), 1037-1042.
[http://dx.doi.org/10.1136/thoraxjnl-2012-203035] [PMID: 23404838]
[8]
Han, J.; Wang, D.S.; Liu, S.B.; Zhao, M.G. Cytisine, a partial agonist of α4β2 nicotinic acetylcholine receptors, reduced unpredictable chronic mild stress-induced depression-like behaviors. Biomol. Ther. (Seoul), 2016, 24(3), 291-297.
[http://dx.doi.org/10.4062/biomolther.2015.113] [PMID: 27098858]
[9]
Li, Y.J.; Yang, Q.; Zhang, K.; Guo, Y.Y.; Li, X.B.; Yang, L.; Zhao, M.G.; Wu, Y.M. Cytisine confers neuronal protection against excitotoxic injury by down-regulating GluN2B-containing NMDA receptors. Neurotoxicology, 2013, 34, 219-225.
[http://dx.doi.org/10.1016/j.neuro.2012.09.009] [PMID: 23022271]
[10]
Zhao, P.; Yang, J.M.; Wang, Y.S.; Hao, Y.J.; Li, Y.X.; Li, N.; Wang, J.; Niu, Y.; Sun, T.; Yu, J.Q. Neuroprotection of cytisine against cerebral ischemia-reperfusion injury in mice by regulating NR2B-ERK/CREB signal pathway. Neurochem. Res., 2018, 43(8), 1575-1586.
[http://dx.doi.org/10.1007/s11064-018-2572-1] [PMID: 29948728]
[11]
Tsypysheva, I.P.; Koval’skaya, A.V.; Lobov, A.N.; Makara, N.S.; Petrova, P.R.; Farafontova, E.I.; Zainullina, L.F.; Vakhitova, Y.V.; Zarudii, F.S. Synthesis and nootropic activity of new 3-amino-12-N-methylcytisine derivatives. Chem. Nat. Compd., 2015, 51, 910-915.
[http://dx.doi.org/10.1007/s10600-015-1446-x]
[12]
Makara, N.S.; Gabdrakhmanova, S.F.; Sapozhnikova, T.A.; Khisamutdinova, R.Y.; Koval’skaya, A.V.; Tsypysheva, I.P.; Zarudii, F.S. New (−)−cytisine derivatives with nootropic activity. Pharm. Chem. J., 2015, 49, 301-303.
[http://dx.doi.org/10.1007/s11094-015-1283-z]
[13]
Gerchikov, A.Y.; Vasil’ev, M.N.; Khairullina, V.R.; Tsypysheva, I.P.; Zarudii, F.S. Search for nootropic substances based on molecular docking of methanepyrido[1,2-a][1,5]diazocin[(-)-cytisine] derivatives to the active center of the nicotinic acetylcholine receptor. Pharm. Chem. J., 2015, 49, 582-586.
[http://dx.doi.org/10.1007/s11094-015-1333-6]
[14]
Makara, N.S.; Sapozhnikova, T.A.; Khisamutdinova, R.Y.; Tsypysheva, I.P.; Borisevich, S.S.; Kovalskaya, A.V.; Petrova, P.R.; Khursan, C.L.; Zarudii, F.S. Nootropic activity of a novel (-)-cytisine derivative (3aR,4S,8S,12R, 12aS,12bR)-10-methyl-2-phenyloctahydro-1H-4,12a-etheno-8,12-methanopyrrolo[3′,4′:3,4]pyrido[1,2-a] [1,5]diazocine-1,3,5(4H)-trione. Bull. Exp. Biol. Med., 2018, 164(4), 434-438.
[http://dx.doi.org/10.1007/s10517-018-4006-0] [PMID: 29500804]
[15]
Yu, L.; Wang, X.; Chen, Z.F.; Jiang, B.; Shang, D.Y.; Sun, Y.X.; Yang, J.H.; Zhang, L.F.; Ji, Y.B. Cytisine induces apoptosis of HepG2 cells. Mol. Med. Rep., 2017, 16(3), 3363-3370.
[http://dx.doi.org/10.3892/mmr.2017.6991] [PMID: 28713951]
[16]
Yu, L.; Jiang, B.; Chen, Z.; Wang, X.; Shang, D.; Zhang, X.; Sun, Y.; Yang, J.; Ji, Y. Cytisine induces endoplasmic reticulum stress caused by calcium overload in HepG2 cells. Oncol. Rep., 2018, 39(3), 1475-1484.
[http://dx.doi.org/10.3892/or.2018.6200] [PMID: 29328482]
[17]
Tsypysheva, I.P.; Koval’skaya, A.V.; Lobov, A.N.; Zarubaev, V.V.; Karpinskaya, L.A.; Petrenko, I.A.; Nikolaeva, E.A.; Shtro, A.A.; Yunusov, M.S. Search for compounds with antiviral activity among synthetic (-)-cytisine derivatives. Chem. Nat. Compd., 2013, 48, 1042-1046.
[http://dx.doi.org/10.1007/s10600-013-0460-0]
[18]
Rakhimov, S.B.; Islamova, Z.I.; Vinogradova, V.I.; Khushbaktova, Z.A.; Osipova, S.O.; Syrov, V.N. Synthesis and antiparasitic activity of N-benzyl cytisine derivatives. Pharm. Chem. J., 2013, 47, 209-212.
[http://dx.doi.org/10.1007/s11094-013-0929-y]
[19]
Dai, Z.T.; Zhang, Y.; Tang, S.; Li, Y.H.; Kong, W.J.; Song, D.Q. Design, synthesis and evaluation of cytisinic derivatives for hypoglycemic activity. Yao Xue Xue Bao, 2018, 53, 416-424.
[20]
Ma, T.; Yan, H.; Shi, X.L.; Liu, B.T.; Ma, Z.Q.; Zhang, X. Comprehensive evaluation of effective constituents in total alkaloids from Sophora alopecuroides L. and their joint action against aphids by laboratory toxicity and field efficacy. Ind. Crops Prod., 2018, 111, 149-157.
[http://dx.doi.org/10.1016/j.indcrop.2017.10.021]
[21]
Matsuda, K.; Yamada, K.; Kimura, M.; Hamada, M. Nematicidal activity of matrine and its derivatives against pine wood nematodes. J. Agric. Food Chem., 1991, 39, 189-191.
[http://dx.doi.org/10.1021/jf00001a038]
[22]
Imming, P.; Klaperski, P.; Stubbs, M.T.; Seitz, G.; Gündisch, D. Syntheses and evaluation of halogenated cytisine derivatives and of bioisosteric thiocytisine as potent and selective nAChR ligands. Eur. J. Med. Chem., 2001, 36(4), 375-388.
[http://dx.doi.org/10.1016/S0223-5234(01)01222-3] [PMID: 11461763]
[23]
Rouden, J.; Lasne, M.C.; Blanchet, J.; Baudoux, J. (-)-Cytisine and derivatives: Synthesis, reactivity, and applications. Chem. Rev., 2014, 114(1), 712-778.
[http://dx.doi.org/10.1021/cr400307e] [PMID: 24117010]
[24]
Prochaska, J.J.; Das, S.; Benowitz, N.L. Cytisine, the world’s oldest smoking cessation aid. BMJ, 2013, 347, f5198.
[http://dx.doi.org/10.1136/bmj.f5198] [PMID: 23974638]
[25]
Igari, M.; Alexander, J.C.; Ji, Y.; Qi, X.; Papke, R.L.; Bruijnzeel, A.W. Varenicline and cytisine diminish the dysphoric-like state associated with spontaneous nicotine withdrawal in rats. Neuropsychopharmacology, 2014, 39(2), 455-465.
[http://dx.doi.org/10.1038/npp.2013.216] [PMID: 23966067]
[26]
Grebenstein, P.E.; Harp, J.L.; Rowland, N.E. The effects of noncontingent and self-administered cytisine on body weight and meal patterns in male Sprague-Dawley rats. Pharmacol. Biochem. Behav., 2013, 110, 192-200.
[http://dx.doi.org/10.1016/j.pbb.2013.07.012] [PMID: 23876236]
[27]
Sala, M.; Braida, D.; Pucci, L.; Manfredi, I.; Marks, M.J.; Wageman, C.R.; Grady, S.R.; Loi, B.; Fucile, S.; Fasoli, F.; Zoli, M.; Tasso, B.; Sparatore, F.; Clementi, F.; Gotti, C. CC4, a dimer of cytisine, is a selective partial agonist at α4β2/α6β2 nAChR with improved selectivity for tobacco smoking cessation. Br. J. Pharmacol., 2013, 168(4), 835-849.
[http://dx.doi.org/10.1111/j.1476-5381.2012.02204.x] [PMID: 22957729]
[28]
Yu, L.F.; Zhang, H.K.; Caldarone, B.J.; Eaton, J.B.; Lukas, R.J.; Kozikowski, A.P. Recent developments in novel antidepressants targeting α4β2-nicotinic acetylcholine receptors. J. Med. Chem., 2014, 57(20), 8204-8223.
[http://dx.doi.org/10.1021/jm401937a] [PMID: 24901260]
[29]
Mineur, Y.S.; Somenzi, O.; Picciotto, M.R. Cytisine, a partial agonist of high-affinity nicotinic acetylcholine receptors, has antidepressant-like properties in male C57BL/6J mice. Neuropharmacology, 2007, 52(5), 1256-1262.
[http://dx.doi.org/10.1016/j.neuropharm.2007.01.006] [PMID: 17320916]
[30]
Mineur, Y.S.; Eibl, C.; Young, G.; Kochevar, C.; Papke, R.L.; Gündisch, D.; Picciotto, M.R. Cytisine-based nicotinic partial agonists as novel antidepressant compounds. J. Pharmacol. Exp. Ther., 2009, 329(1), 377-386.
[http://dx.doi.org/10.1124/jpet.108.149609] [PMID: 19164465]
[31]
Mineur, Y.S.; Einstein, E.B.; Bentham, M.P.; Wigestrand, M.B.; Blakeman, S.; Newbold, S.A.; Picciotto, M.R. Expression of the 5-HT1A serotonin receptor in the hippocampus is required for social stress resilience and the antidepressant-like effects induced by the nicotinic partial agonist cytisine. Neuropsychopharmacology, 2015, 40(4), 938-946.
[http://dx.doi.org/10.1038/npp.2014.269] [PMID: 25288485]
[32]
Li, X.N.; Lu, Z.Q.; Qin, S.; Yan, H.X.; Yang, M.; Guan, S.H.; Liu, X.; Hua, H.M.; Wu, L.J.; Guo, D.A. Tonkinensines A and B, two novel alkaloids from Sophora tonkinensis. Tetrahedron Lett., 2008, 49, 3797-3801.
[http://dx.doi.org/10.1016/j.tetlet.2008.04.003]
[33]
Peng, T.T.; Sun, X.R.; Liu, R.H.; Hua, L.X.; Cheng, D.P.; Mao, B.; Li, X.N. Cytisine-pterocarpan-derived compounds: Biomimetic synthesis and apoptosis-inducing activity in human breast cancer cells. Molecules, 2018, 23(12), 3059.
[http://dx.doi.org/10.3390/molecules23123059] [PMID: 30467293]
[34]
Zhang, Y.B.; Zhan, L.Q.; Li, G.Q.; Wang, F.; Wang, Y.; Li, Y.L.; Ye, W.C.; Wang, G.C. Dimeric matrine-type alkaloids from the roots of Sophora flavescens and their anti-hepatitis B virus activities. J. Org. Chem., 2016, 81(15), 6273-6280.
[http://dx.doi.org/10.1021/acs.joc.6b00804] [PMID: 27352066]
[35]
Jin, L.; Tu, J.; Jia, J.; An, W.; Tan, H.; Cui, Q.; Li, Z. Drug-repurposing identified the combination of Trolox C and Cytisine for the treatment of type 2 diabetes. J. Transl. Med., 2014, 12, 153.
[http://dx.doi.org/10.1186/1479-5876-12-153] [PMID: 24885253]
[36]
Luo, W.C.; Li, Y.S.; Mu, L.Y.; Shin-Foon, C. Toxicity of cytisine against the mustard aphid Lipaphis erysimi Kaltenbach (Homoptera: Aphididae) and its effect on esterases. Pestic. Biochem. Physiol., 1999, 65, 1-5.
[http://dx.doi.org/10.1006/pest.1999.2400]
[37]
Liu, L.; Alam, M.S.; Hirata, K.; Matsuda, K.; Ozoe, Y. Actions of quinolizidine alkaloids on Periplaneta americana nicotinic acetylcholine receptors. Pest Manag. Sci., 2008, 64(12), 1222-1228.
[http://dx.doi.org/10.1002/ps.1622] [PMID: 18566954]
[38]
Zhao, B.G. Nematicidal activity of quinolizidine alkaloids and the functional group pairs in their molecular structure. J. Chem. Ecol., 1999, 25, 2205-2214.
[http://dx.doi.org/10.1023/A:1020809521068]
[39]
Tsypysheva, I.P. Koval’Skaya, A. V.; Khalilova, I. U.; Bakhtina, Y. Y.; Khisamutdinova, R. Y.; Gabdrakhmanova, S. F.; Lobov, A. N.; Zarudii, F.S.; Yunusov, M.S. New 12-N-β-hydroxyethyl-cytisine derivatives with potential antiarrhythmic activity. Chem. Nat. Compd., 2014, 50, 333-336.
[http://dx.doi.org/10.1007/s10600-014-0945-5]
[40]
Jiao, Y.F.; Lu, M.; Zhao, Y.P.; Liu, N.; Niu, Y.T.; Niu, Y.; Zhou, R.; Yu, J.Q. N-Methylcytisine ameliorates dextran-sulfate-sodium-induced colitis in mice by inhibiting the inflammatory response. Molecules, 2018, 23(3), 510.
[http://dx.doi.org/10.3390/molecules23030510] [PMID: 29495327]
[41]
Vakhitova, Y.V.; Farafontova, E.I.; Zainullina, L.F.; Vakhitov, V.A.; Tsypysheva, I.P.; Yunusov, M.S. Search for (-)-cytisine derivatives as potential inhibitors of NF-κB and STAT1. Russ. J. Bioorganic Chem., 2015, 41, 297-304.
[http://dx.doi.org/10.1134/S1068162015030103]
[42]
Stead, D.; O’Brien, P. Total synthesis of the lupin alkaloid cytisine: Comparison of synthetic strategies and routes. Tetrahedron, 2007, 63, 1885-1897.
[http://dx.doi.org/10.1016/j.tet.2006.10.017]
[43]
Struth, F.R.; Hirschhäuser, C. A modular approach to the asymmetric synthesis of cytisine. Eur. J. Org. Chem., 2016, 2016, 958-964.
[http://dx.doi.org/10.1002/ejoc.201501435]
[44]
Barát, V.; Csókás, D.; Bates, R.W. Synthesis of (-)-cytisine using a 6-endo aza-Michael addition. J. Org. Chem., 2018, 83(16), 9088-9095.
[http://dx.doi.org/10.1021/acs.joc.8b01156] [PMID: 29998734]
[45]
Rakhimov, S.B.; Vinogradova, V.I.; Levkovich, M.G. Synthesis of N-[2′-bromo-4′-methoxy-3′-(β-cytisinylethoxy)benzyl]cytisine. Chem. Nat. Compd., 2016, 52, 874-876.
[http://dx.doi.org/10.1007/s10600-016-1799-9]
[46]
Nurkenov, O.A.; Satpaeva, Z.B.; Fazylov, S.D.; Seilkhanov, T.M.; Turdybekov, K.M.; Turdybekov, D.M.; Akhmetova, S.B.; Makhmutova, A.S.; Gazaliev, A.M. Synthesis of thiourea derivatives of the alkaloids anabasine, cytisine, and d-pseudoephedrine. Crystal structure of N-ethyl-N-anabasinocarbothioamide. Chem. Nat. Compd., 2016, 52, 276-279.
[http://dx.doi.org/10.1007/s10600-016-1613-8]
[47]
Yazlovitskii, A.V.; Garazd, M.M.; Kartsev, V.G. Synthesis of N-acylamino-acid derivatives of cytisine. Chem. Nat. Compd., 2016, 52, 272-275.
[http://dx.doi.org/10.1007/s10600-016-1612-9]
[48]
Zhong, H.J.; Lee, B.R.; Boyle, J.W.; Wang, W.; Ma, D.L.; Hong Chan, P.W.; Leung, C.H. Structure-based screening and optimization of cytisine derivatives as inhibitors of the menin-MLL interaction. Chem. Commun. (Camb.), 2016, 52(34), 5788-5791.
[http://dx.doi.org/10.1039/C6CC01079B] [PMID: 27004852]
[49]
Gazaliev, A.M.; Ibraev, M.K.; Isabaeva, M.B.; Ibataev, Z.A. Synthesis and spatial structure of 1-(cytisin-1-ylmethyl)benzimidazole-2-thione. Russ. J. Gen. Chem., 2013, 83, 1098-1102.
[http://dx.doi.org/10.1134/S1070363213060169]
[50]
Brel, V.K. Click chemistry methodology in the synthesis of anabasine and cytisine conjugates with isoxazole derivatives. Russ. J. Org. Chem., 2016, 52, 54-60.
[http://dx.doi.org/10.1134/S1070428016010115]
[51]
Abdurakhmanova, E.R.; Pil’o, S.G.; Kondratyuk, K.M.; Golovchenko, A.V.; Brovarets, V.S. 1,3-Oxazole derived cytisines. Russ. J. Gen. Chem., 2017, 87, 244-251.
[http://dx.doi.org/10.1134/S1070363217020153]
[52]
Ismailova, D.S.; Ziyaev, A.A.; Levkovich, M.G.; Toshmurodov, T.T. Synthesis of 1,3,4-oxa(thia)diazole derivatives of amidomethylcytisine. Chem. Nat. Compd., 2018, 54, 826-827.
[http://dx.doi.org/10.1007/s10600-018-2489-6]
[53]
Sharova, E.V.; Genkina, G.K.; Matveeva, E.V.; Goryunova, I.B.; Goryunov, E.I.; Artyushin, O.I.; Brel, V.K. Phosphorylation of cytisine using azide—alkyne click chemistry. Russ. Chem. Bull., 2014, 63, 2546-2550.
[http://dx.doi.org/10.1007/s11172-014-0774-5]
[54]
Zarezin, D.P.; Kabylda, A.M.; Vinogradova, V.I.; Dorovatovskii, P.V.; Khrustalev, V.N.; Nenajdenko, V.G. Efficient synthesis of tetrazole derivatives of cytisine using the azido-Ugi reaction. Tetrahedron, 2018, 74, 4315-4322.
[http://dx.doi.org/10.1016/j.tet.2018.06.045]
[55]
Polienko, Y.F.; Vinogradova, V.I.; Sagdullaev, S.S.; Abdullaev, N.D.; Svyatchenko, V.A.; Kiselev, N.N.; Loktev, V.B.; Grigor’ev, I.A. First bis-phosphonic acid derivatives of the plant alkaloid cytisine. Chem. Nat. Compd., 2013, 49, 781-782.
[http://dx.doi.org/10.1007/s10600-013-0744-4]
[56]
Matveeva, E.V.; Kovaleva, E.Y.; Brel, V.K. Reaction of vinyl- and allenylphosphorylated compounds with cytisine in aqueous medium. Russ. J. Gen. Chem., 2015, 85, 2592-2595.
[http://dx.doi.org/10.1134/S1070363215110146]
[57]
Brel, V.K. Reaction of cytisine with alka-1,3- and -2,3-dien-2-ylphosphonates. Russ. J. Org. Chem., 2016, 52, 1804-1811.
[http://dx.doi.org/10.1134/S1070428016120162]
[58]
Brel’, V.K.; Kovaleva, E.Y.; Enchev, D.D. Reaction of diphenylphosphinoylallene derivatives of cytisine. Russ. J. Gen. Chem., 2017, 87, 1731-1736.
[http://dx.doi.org/10.1134/S1070363217080163]
[59]
Bondarenko, S.P.; Frasinyuk, M.S.; Vinogradova, V.I.; Khilya, V.P. Synthesis of flavonoid derivatives of cytisine. 3. Synthesis of 7-[2-(cytisin-12-yl)ethoxy]isoflavones. Chem. Nat. Compd., 2013, 48, 970-973.
[http://dx.doi.org/10.1007/s10600-013-0441-3]
[60]
Frasinyuk, M.S.; Zhang, W.; Wyrebek, P.; Yu, T.; Xu, X.; Sviripa, V.M.; Bondarenko, S.P.; Xie, Y.; Ngo, H.X.; Morris, A.J.; Mohler, J.L.; Fiandalo, M.V.; Watt, D.S.; Liu, C. Developing antineoplastic agents that target peroxisomal enzymes: Cytisine-linked isoflavonoids as inhibitors of hydroxysteroid 17-beta-dehydrogenase-4 (HSD17B4). Org. Biomol. Chem., 2017, 15(36), 7623-7629.
[http://dx.doi.org/10.1039/C7OB01584D] [PMID: 28868548]
[61]
Bondarenko, S.P.; Frasinyuk, M.S.; Vinogradova, V.I.; Khilya, V.P. Synthesis of 4-aryl-3-[2-hydroxy-4-(2-cytisin-12-ylethoxy)phenyl] pyrazoles. Chem. Nat. Compd., 2014, 50, 889-891.
[http://dx.doi.org/10.1007/s10600-014-1107-5]
[62]
Bondarenko, S.P.; Frasinyuk, M.S.; Vinogradova, V.I.; Khilya, V.P. Synthesis of 4-aryl-5-[2-hydroxy-4-(2-cytisin-12-ylethoxy) phenyl]isoxazoles. Chem. Nat. Compd., 2016, 52, 463-467.
[http://dx.doi.org/10.1007/s10600-016-1673-9]
[63]
Kosheleva, N.V.; Chernyak, E.I.; Morozov, S.V.; Vinogradova, V.I.; Sagdullaev, S.S.; Abdullaev, N.D.; Grigor’ev, I.A. Synthesis of the first dihydroquercetin–cytisine conjugates. Chem. Nat. Compd., 2014, 50, 443-445.
[http://dx.doi.org/10.1007/s10600-014-0982-0]
[64]
Popova, A.V.; Bondarenko, S.P.; Podobii, E.V.; Frasinyuk, M.S.; Vinogradova, V.I. Synthesis of flavonoid derivatives of cytisine. 5. Aminomethylation of 6-hydroxyaurones. Chem. Nat. Compd., 2017, 53, 708-713.
[http://dx.doi.org/10.1007/s10600-017-2096-y]
[65]
Muzychuk, O.I.; Garazd, M.M. Synthesis of the conjugate of cytisine and Kojic acid. Chem. Nat. Compd., 2017, 53, 517-518.
[http://dx.doi.org/10.1007/s10600-017-2035-y]
[66]
Eibl, C.; Munoz, L.; Tomassoli, I.; Stokes, C.; Papke, R.L.; Gündisch, D. The 3,7-diazabicyclo[3.3.1]nonane scaffold for subtype selective nicotinic acetylcholine receptor ligands. Part 2: Carboxamide derivatives with different spacer motifs. Bioorg. Med. Chem., 2013, 21(23), 7309-7329.
[http://dx.doi.org/10.1016/j.bmc.2013.09.060] [PMID: 24145137]
[67]
Rego Campello, H.; Del Villar, S.G.; Honraedt, A.; Minguez, T.; Oliveira, A.S.F.; Ranaghan, K.E.; Shoemark, D.K.; Bermudez, I.; Gotti, C.; Sessions, R.B.; Mulholland, A.J.; Wonnacott, S.; Gallagher, T. Unlocking nicotinic selectivity via direct C‒H functionalization of (−)-cytisine. Chem, 2018, 4, 1710-1725.
[http://dx.doi.org/10.1016/j.chempr.2018.05.007]
[68]
Tsypysheva, I.P. Koval′Skaya, A. V.; Lobov, A. N.; Nikolaeva, E. A.; Yunusov, M. S. Synthesis of 3- and 5-amino derivatives of methylcytisine. Chem. Nat. Compd., 2013, 49, 902-906.
[http://dx.doi.org/10.1007/s10600-013-0773-z]
[69]
Tsypysheva, I.P.; Lobov, A.N.; Kovalskaya, A.V.; Vinogradova, V.I.; Suponitsky, K.Y.; Khursan, S.L.; Yunusov, M.S. Synthesis of Diels-Alder adducts of the quinolizidine alkaloids N-methyl-cytisine, (−)-leontidine, and (−)-thermopsine with N-phenyl-maleimide. Tetrahedron Asymmetry, 2013, 24, 1318-1323.
[http://dx.doi.org/10.1016/j.tetasy.2013.09.002]
[70]
Petrova, P.R.; Koval’skaya, A.V.; Lobov, A.N.; Tsypysheva, I.P. Direct formylation of 2-pyridone core of 3-N-methylcytisine via Duff reaction; synthesis of 9-enyl, 9-ynyl and 9-imino derivatives. Nat. Prod. Res., 2018, 1-6.
[PMID: 29792344]
[71]
Kuranov, S.O.; Tsypysheva, I.P.; Khvostov, M.V.; Zainullina, L.F.; Borisevich, S.S.; Vakhitova, Y.V.; Luzina, O.A.; Salakhutdinov, N.F. Synthesis and evaluation of camphor and cytisine-based cyanopyrrolidines as DPP-IV inhibitors for the treatment of type 2 diabetes mellitus. Bioorg. Med. Chem., 2018, 26(15), 4402-4409.
[http://dx.doi.org/10.1016/j.bmc.2018.07.018] [PMID: 30056037]
[72]
Tsypysheva, I.P.; Koval’skaya, A.V.; Makara, N.S.; Lobov, A.N.; Petrenko, I.A.; Galkin, E.G.; Sapozhnikova, T.A.; Zarudii, F.S.; Yunusov, M.S. Synthesis and specific nootropic activity of (–)-cytisine derivatives with carbamide and thiocarbamide moieties in their structure. Chem. Nat. Compd., 2012, 48, 629-634.
[http://dx.doi.org/10.1007/s10600-012-0329-7]
[73]
Tsypysheva, I.P.; Lobov, A.N.; Kovalskaya, A.V.; Petrova, P.R.; Ivanov, S.P.; Rameev, S.A.; Borisevich, S.S.; Safiullin, R.L.; Yunusov, M.S. Aza-Michael reaction of 12-N-carboxamide of (-)-cytisine under high pressure conditions. Nat. Prod. Res., 2015, 29(2), 141-148.
[http://dx.doi.org/10.1080/14786419.2014.968150] [PMID: 25330752]
[74]
Tsypysheva, I.P.; Borisevich, S.S.; Lobov, A.N.; Kovalskaya, A.V.; Shamukaev, V.V.; Safiullin, R.L.; Khursan, S.L. Inversion of diastereoselectivity under high pressure conditions: Diels-Alder reactions of 12-N-substituted derivatives of (−)-cytisine with N-phenylmaleimide. Tetrahedron Asymmetry, 2015, 26, 732-737.
[http://dx.doi.org/10.1016/j.tetasy.2015.06.005]
[75]
Patrikei, S.Y.; Garazd, Y.L.; Garazd, M.M. Modified coumarins. 40. Synthesis of benzopyran-2-one carbonyl derivatives of 9-nitrocytisine. Chem. Nat. Compd., 2017, 53, 448-452.
[http://dx.doi.org/10.1007/s10600-017-2020-5]
[76]
Fitch, R.W.; Kaneko, Y.; Klaperski, P.; Daly, J.W.; Seitz, G.; Gündisch, D. Halogenated and isosteric cytisine derivatives with increased affinity and functional activity at nicotinic acetylcholine receptors. Bioorg. Med. Chem. Lett., 2005, 15(4), 1221-1224.
[http://dx.doi.org/10.1016/j.bmcl.2004.11.073] [PMID: 15686946]
[77]
Tasso, B.; Canu Boido, C.; Terranova, E.; Gotti, C.; Riganti, L.; Clementi, F.; Artali, R.; Bombieri, G.; Meneghetti, F.; Sparatore, F. Synthesis, binding, and modeling studies of new cytisine derivatives, as ligands for neuronal nicotinic acetylcholine receptor subtypes. J. Med. Chem., 2009, 52(14), 4345-4357.
[http://dx.doi.org/10.1021/jm900225j] [PMID: 19548687]


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VOLUME: 20
ISSUE: 5
Year: 2020
Published on: 24 April, 2020
Page: [369 - 395]
Pages: 27
DOI: 10.2174/1389557519666191104121821
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