四氢异喹啉

四氢异喹啉
	IUPAC名; 1,2,3,4-Tetrahydroisoquinoline
识别
缩写	TIQ, THIQ
CAS号	91-21-4
PubChem	7046
ChemSpider	6779
SMILES	c1ccc2c(c1)CCNC2;
InChI	1/C9H11N/c1-2-4-9-7-10-6-5-8(9)3-1/h1-4,10H,5-7H2;
InChIKey	UWYZHKAOTLEWKK-UHFFFAOYAB
RTECS	NX4900000
性质
化学式	C9H11N
摩尔质量	133.19 g·mol⁻¹
外观	深黄色液体
密度	1.05 g/mL
熔点	-30 °C（243 K）
沸点	235—239 °C（455—462 °F；508—512 K）
危险性
	GHS危险性符号;
GHS提示词	Danger
H-术语	H301, H310, H314, H332, H371, H412
P-术语	P260, P261, P262, P264, P270, P271, P273, P280, P301+310, P301+330+331, P302+350, P302+352, P303+361+353, P304+312
	若非注明，所有数据均出自标准状态（25 ℃，100 kPa）下。

四氢异喹啉（英文：Tetrahydroisoquinoline，缩写：TIQ或THIQ）是一种有机化合物，化学式为C₉H₁₁N。它属于仲胺类，由异喹啉经氢化而得。它是一种无色粘稠液体，可与大多数有机溶剂混溶。在许多生物活性化合物和药物中都会遇到四氢异喹啉结构。^[1]^[2]

反应

作为仲胺，四氢异喹啉具有弱碱性，与强酸形成盐。四氢异喹啉脱氢可生成异喹啉，加氢可生成十氢异喹啉。与其他仲胺一样，四氢异喹啉可以在二氧化硒的催化下使用过氧化氢氧化成相应的硝酮。^[3]

毒理学

四氢异喹啉的衍生物可能作为某些药物的代谢产物在体内形成，这曾被认为与酒精中毒的发展有关。^[4]这一理论现在已被质疑，不再被科学界普遍接受，^[5]但神经毒性四氢异喹啉的衍生物（如norsalsolinol）的内源性生产仍然被研究为帕金森氏病等某些疾病的可能原因。^[6]^[7]^[8]^[9]^[10]^[11]

四氢异喹啉

四氢异喹啉结构存在于许多药物中，^[12]例如筒箭毒碱（种神经肌肉阻滞药）。基于4-取代四氢异喹啉的药物包括诺米芬辛^[13]和双氯芬辛。它们可以通过苄胺与卤化苯乙酮的N-烷基化来制备。^[14]天然存在的四氢异喹啉包括車瑞靈^[15]和宽叶啉。

Esproquin^[16]由四氢异喹啉制成，凭借其α-肾上腺素能阻滞特性显示出降压活性。

参考文献

^ Mitchenson, Andrew. Saturated nitrogen heterocycles. Journal of the Chemical Society, Perkin Transactions 1. 2000, (17): 2862–2892. doi:10.1039/A908537H.
^ Scott, Jack D.; Williams, Robert M. Chemistry and Biology of the Tetrahydroisoquinoline Antitumor Antibiotics. Chemical Reviews. 2002, 102 (5): 1669–1730. PMID 11996547. doi:10.1021/cr010212u.
^ Murahashi, S. Selenium dioxide catalyzed oxidation of secondary amines with hydrogen peroxide. Simple synthesis of nitrones from secondary amines. Tetrahedron Letters. 1987, 28 (21): 2383–2386. doi:10.1016/S0040-4039(00)96130-6.
^ Blum, K.; Hamilton, M. G.; Hirst, M.; Wallace, J. E. Putative role of isoquinoline alkaloids in alcoholism: a link to opiates. Alcoholism: Clinical and Experimental Research. 1978, 2 (2): 113–120. PMID 350073. doi:10.1111/j.1530-0277.1978.tb04710.x. ,Altshuler, H. L.; Shippenberg. Tetrahydroisoquinoline and opioid substrates of alcohol actions. Progress in Clinical and Biological Research. 1982, 90: 329–344. PMID 7202207. , Myers, R. D. Isoquinolines, beta-carbolines and alcohol drinking: involvement of opioid and dopaminergic mechanisms. Experientia. 1989, 45 (5): 436–443. PMID 2656285. S2CID 1513683. doi:10.1007/BF01952025.
^ Myers, R. D. Tetrahydroisoquinolines and alcoholism: where are we today?. Alcoholism: Clinical and Experimental Research. 1996, 20 (3): 498–500. PMID 8727243. doi:10.1111/j.1530-0277.1996.tb01081.x. , Musshoff, F.; Daldrup, T.; Bonte, W.; Leitner, A.; Lesch, O. M. Formaldehyde-derived tetrahydroisoquinolines and tetrahydro-beta-carbolines in human urine. Journal of Chromatography B. 1996, 683 (2): 163–176. PMID 8891913. doi:10.1016/0378-4347(96)00106-5. , Sällström Baum, S.; Hill, R.; Kiianmaa, K.; Rommelspacher, H. Effect of ethanol on (R)- and (S)-salsolinol, salsoline, and THP in the nucleus accumbens of AA and ANA rats. Alcohol (Fayetteville, N.Y.). 1999, 18 (2–3): 165–169. PMID 10456568. doi:10.1016/S0741-8329(98)00080-9. , Musshoff, F.; Lachenmeier, D. W.; Schmidt, P.; Dettmeyer, R.; Madea, B. Systematic regional study of dopamine, norsalsolinol, and (R/S)-salsolinol levels in human brain areas of alcoholics. Alcoholism: Clinical and Experimental Research. 2005, 29 (1): 46–52. PMID 15654290. doi:10.1097/01.ALC.0000150011.81102.C2.
^ Kotake Y, Tasaki Y, Makino Y, Ohta S, Hirobe M. 1-Benzyl-1,2,3,4-tetrahydroisoquinoline as a parkinsonism-inducing agent: a novel endogenous amine in mouse brain and parkinsonian CSF. Journal of Neurochemistry. December 1995, 65 (6): 2633–8. PMID 7595560. S2CID 39449026. doi:10.1046/j.1471-4159.1995.65062633.x.
^ McNaught KS, Carrupt PA, Altomare C, Cellamare S, Carotti A, Testa B, Jenner P, Marsden CD. Isoquinoline derivatives as endogenous neurotoxins in the aetiology of Parkinson's disease. Biochemical Pharmacology. October 1998, 56 (8): 921–33. PMID 9776302. doi:10.1016/S0006-2952(98)00142-7.
^ Lorenc-Koci E, Smiałowska M, Antkiewicz-Michaluk L, Gołembiowska K, Bajkowska M, Wolfarth S. Effect of acute and chronic administration of 1,2,3,4-tetrahydroisoquinoline on muscle tone, metabolism of dopamine in the striatum and tyrosine hydroxylase immunocytochemistry in the substantia nigra, in rats. Neuroscience. 2000, 95 (4): 1049–59. PMID 10682712. S2CID 13549697. doi:10.1016/S0306-4522(99)00511-4.
^ Storch A, Ott S, Hwang YI, Ortmann R, Hein A, Frenzel S, Matsubara K, Ohta S, Wolf HU, Schwarz J. Selective dopaminergic neurotoxicity of isoquinoline derivatives related to Parkinson's disease: studies using heterologous expression systems of the dopamine transporter. Biochemical Pharmacology. March 2002, 63 (5): 909–20. PMID 11911843. doi:10.1016/S0006-2952(01)00922-4.
^ Lorenc-Koci E, Antkiewicz-Michaluk L, Kamińska A, Lenda T, Zieba B, Wierońska J, Smiałowska M, Schulze G, Rommelspacher H. The influence of acute and chronic administration of 1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline on the function of the nigrostriatal dopaminergic system in rats. Neuroscience. October 2008, 156 (4): 973–86. PMID 18809471. S2CID 44658852. doi:10.1016/j.neuroscience.2008.08.050.
^ Kobayashi H, Fukuhara K, Tada-Oikawa S, Yada Y, Hiraku Y, Murata M, Oikawa S. The mechanisms of oxidative DNA damage and apoptosis induced by norsalsolinol, an endogenous tetrahydroisoquinoline derivative associated with Parkinson's disease. Journal of Neurochemistry. January 2009, 108 (2): 397–407. PMID 19012744. doi:10.1111/j.1471-4159.2008.05774.x .
^ Scott, Jack D.; Williams, Robert M. Chemistry and Biology of the Tetrahydroisoquinoline Antitumor Antibiotics. Chemical Reviews. 2002, 102 (5): 1669–1730. PMID 11996547. doi:10.1021/cr010212u.
^ Schneider, C. S.; Weber, K. H.; Daniel, H.; Bechtel, W. D.; Boeke-Kuhn, K. Synthesis and antidepressant activity of 4-aryltetrahydrothieno[2,3-c]pyridine derivatives. Journal of Medicinal Chemistry. 1984, 27 (9): 1150–1155. PMID 6471069. doi:10.1021/jm00375a011.
^ BG 49761
^ cherylline. [2022-12-10]. （原始内容存档于2022-12-10）.
^ Gray, Allan P.; Shiley, Richard H. Preparation and cardiovascular actions of a group of tetrahydroisoquinoline derivatives. Journal of Medicinal Chemistry. 1973, 16 (7): 859–861. ISSN 0022-2623. PMID 4146907. doi:10.1021/jm00265a028.

[1] Mitchenson, Andrew. Saturated nitrogen heterocycles. Journal of the Chemical Society, Perkin Transactions 1. 2000, (17): 2862–2892. doi:10.1039/A908537H.

[Scott-2] Scott, Jack D.; Williams, Robert M. Chemistry and Biology of the Tetrahydroisoquinoline Antitumor Antibiotics. Chemical Reviews. 2002, 102 (5): 1669–1730. PMID 11996547. doi:10.1021/cr010212u.

[3] Murahashi, S. Selenium dioxide catalyzed oxidation of secondary amines with hydrogen peroxide. Simple synthesis of nitrones from secondary amines. Tetrahedron Letters. 1987, 28 (21): 2383–2386. doi:10.1016/S0040-4039(00)96130-6.

[4] Blum, K.; Hamilton, M. G.; Hirst, M.; Wallace, J. E. Putative role of isoquinoline alkaloids in alcoholism: a link to opiates. Alcoholism: Clinical and Experimental Research. 1978, 2 (2): 113–120. PMID 350073. doi:10.1111/j.1530-0277.1978.tb04710.x. ,Altshuler, H. L.; Shippenberg. Tetrahydroisoquinoline and opioid substrates of alcohol actions. Progress in Clinical and Biological Research. 1982, 90: 329–344. PMID 7202207. , Myers, R. D. Isoquinolines, beta-carbolines and alcohol drinking: involvement of opioid and dopaminergic mechanisms. Experientia. 1989, 45 (5): 436–443. PMID 2656285. S2CID 1513683. doi:10.1007/BF01952025.

[5] Myers, R. D. Tetrahydroisoquinolines and alcoholism: where are we today?. Alcoholism: Clinical and Experimental Research. 1996, 20 (3): 498–500. PMID 8727243. doi:10.1111/j.1530-0277.1996.tb01081.x. , Musshoff, F.; Daldrup, T.; Bonte, W.; Leitner, A.; Lesch, O. M. Formaldehyde-derived tetrahydroisoquinolines and tetrahydro-beta-carbolines in human urine. Journal of Chromatography B. 1996, 683 (2): 163–176. PMID 8891913. doi:10.1016/0378-4347(96)00106-5. , Sällström Baum, S.; Hill, R.; Kiianmaa, K.; Rommelspacher, H. Effect of ethanol on (R)- and (S)-salsolinol, salsoline, and THP in the nucleus accumbens of AA and ANA rats. Alcohol (Fayetteville, N.Y.). 1999, 18 (2–3): 165–169. PMID 10456568. doi:10.1016/S0741-8329(98)00080-9. , Musshoff, F.; Lachenmeier, D. W.; Schmidt, P.; Dettmeyer, R.; Madea, B. Systematic regional study of dopamine, norsalsolinol, and (R/S)-salsolinol levels in human brain areas of alcoholics. Alcoholism: Clinical and Experimental Research. 2005, 29 (1): 46–52. PMID 15654290. doi:10.1097/01.ALC.0000150011.81102.C2.

[pmid7595560-6] Kotake Y, Tasaki Y, Makino Y, Ohta S, Hirobe M. 1-Benzyl-1,2,3,4-tetrahydroisoquinoline as a parkinsonism-inducing agent: a novel endogenous amine in mouse brain and parkinsonian CSF. Journal of Neurochemistry. December 1995, 65 (6): 2633–8. PMID 7595560. S2CID 39449026. doi:10.1046/j.1471-4159.1995.65062633.x.

[pmid9776302-7] McNaught KS, Carrupt PA, Altomare C, Cellamare S, Carotti A, Testa B, Jenner P, Marsden CD. Isoquinoline derivatives as endogenous neurotoxins in the aetiology of Parkinson's disease. Biochemical Pharmacology. October 1998, 56 (8): 921–33. PMID 9776302. doi:10.1016/S0006-2952(98)00142-7.

[pmid10682712-8] Lorenc-Koci E, Smiałowska M, Antkiewicz-Michaluk L, Gołembiowska K, Bajkowska M, Wolfarth S. Effect of acute and chronic administration of 1,2,3,4-tetrahydroisoquinoline on muscle tone, metabolism of dopamine in the striatum and tyrosine hydroxylase immunocytochemistry in the substantia nigra, in rats. Neuroscience. 2000, 95 (4): 1049–59. PMID 10682712. S2CID 13549697. doi:10.1016/S0306-4522(99)00511-4.

[pmid11911843-9] Storch A, Ott S, Hwang YI, Ortmann R, Hein A, Frenzel S, Matsubara K, Ohta S, Wolf HU, Schwarz J. Selective dopaminergic neurotoxicity of isoquinoline derivatives related to Parkinson's disease: studies using heterologous expression systems of the dopamine transporter. Biochemical Pharmacology. March 2002, 63 (5): 909–20. PMID 11911843. doi:10.1016/S0006-2952(01)00922-4.

[pmid18809471-10] Lorenc-Koci E, Antkiewicz-Michaluk L, Kamińska A, Lenda T, Zieba B, Wierońska J, Smiałowska M, Schulze G, Rommelspacher H. The influence of acute and chronic administration of 1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline on the function of the nigrostriatal dopaminergic system in rats. Neuroscience. October 2008, 156 (4): 973–86. PMID 18809471. S2CID 44658852. doi:10.1016/j.neuroscience.2008.08.050.

[pmid19012744-11] Kobayashi H, Fukuhara K, Tada-Oikawa S, Yada Y, Hiraku Y, Murata M, Oikawa S. The mechanisms of oxidative DNA damage and apoptosis induced by norsalsolinol, an endogenous tetrahydroisoquinoline derivative associated with Parkinson's disease. Journal of Neurochemistry. January 2009, 108 (2): 397–407. PMID 19012744. doi:10.1111/j.1471-4159.2008.05774.x .

[Scott2-12] Scott, Jack D.; Williams, Robert M. Chemistry and Biology of the Tetrahydroisoquinoline Antitumor Antibiotics. Chemical Reviews. 2002, 102 (5): 1669–1730. PMID 11996547. doi:10.1021/cr010212u.

[13] Schneider, C. S.; Weber, K. H.; Daniel, H.; Bechtel, W. D.; Boeke-Kuhn, K. Synthesis and antidepressant activity of 4-aryltetrahydrothieno[2,3-c]pyridine derivatives. Journal of Medicinal Chemistry. 1984, 27 (9): 1150–1155. PMID 6471069. doi:10.1021/jm00375a011.

[14] BG 49761

[15] rylline. [2022-12-10]. （原始内容存档于2022-12-10）.

[GrayShiley1973-16] Gray, Allan P.; Shiley, Richard H. Preparation and cardiovascular actions of a group of tetrahydroisoquinoline derivatives. Journal of Medicinal Chemistry. 1973, 16 (7): 859–861. ISSN 0022-2623. PMID 4146907. doi:10.1021/jm00265a028.

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