Tetrahydroisoquinoline

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This article is about the simple heterocyclic amine. For the selective MC4 agonist, see THIQ.
Tetrahydroisoquinoline
Tetrahydroisoquinoline-structure.svg
Identifiers
CAS number 91-21-4 YesY
PubChem 7046
ChemSpider 6779 YesY
ChEMBL CHEMBL14346 YesY
RTECS number NX4900000
Jmol-3D images Image 1
Properties
Molecular formula C9H11N
Molar mass 133.19 g/mol
Appearance Deep yellow liquid
Density 1.05 g/mL
Melting point −30 °C (−22 °F; 243 K)
Boiling point 235 to 239 °C (455 to 462 °F; 508 to 512 K)
Hazards
EU classification Irritant (Xi)
R-phrases R36/37/38
S-phrases S26 S36
Flash point 99 °C (210 °F; 372 K) (closed cup)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
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Infobox references

Tetrahydroisoquinoline is a secondary amine with the chemical formula C9H11N.

Reactions[edit]

Like other secondary amines, tetrahydroisoquinoline can be oxidized to the corresponding nitrone using hydrogen peroxide, catalyzed by selenium dioxide.[1]

Tetrahydroisoquinolines[edit]

The tetrahydroisoquinoline skeleton is commonly encountered in pharmaceutical drugs, notably quaternary ammonium muscle relaxants such as tubocurarine.

Toxicology[edit]

Tetrahydroisoquinoline derivatives may be formed in the body as metabolites of some drugs, and this was once thought to be involved in the development of alcoholism.[2][3][4] This theory has now been discredited and is no longer generally accepted by the scientific community,[5][6][7][8] but endogenous production of neurotoxic tetrahydroisoquinoline derivatives such as norsalsolinol continue to be investigated as possible causes for some conditions such as Parkinson's disease.[9][10][11][12][13][14][15]

4'-Ar-tetrahydroisoquinolines[edit]

These useful drugs like nomifensine[16] and diclofensine are made as follows: BG 49761  4-phenyl-THIQ.png

Natural sources of these alkaloids: cherylline and latifine.

References[edit]

  1. ^ Murahashi, S. (1987). "Selenium dioxide catalyzed oxidation of secondary amines with hydrogen peroxide. Simple synthesis of nitrones from secondary amines". Tetrahedron Letters 28 (21): 2383–2386. doi:10.1016/S0040-4039(00)96130-6.  edit
  2. ^ Blum, K.; Hamilton, M. G.; Hirst, M.; Wallace, J. E. (1978). "Putative role of isoquinoline alkaloids in alcoholism: a link to opiates". Alcoholism, clinical and experimental research 2 (2): 113–120. doi:10.1111/j.1530-0277.1978.tb04710.x. PMID 350073.  edit
  3. ^ Altshuler, H. L.; Shippenberg (1982). "Tetrahydroisoquinoline and opioid substrates of alcohol actions". Progress in clinical and biological research 90: 329–344. PMID 7202207.  edit
  4. ^ Myers, R. D. (1989). "Isoquinolines, beta-carbolines and alcohol drinking: involvement of opioid and dopaminergic mechanisms". Experientia 45 (5): 436–443. doi:10.1007/BF01952025. PMID 2656285.  edit
  5. ^ Myers, R. D. (1996). "Tetrahydroisoquinolines and alcoholism: where are we today?". Alcoholism, clinical and experimental research 20 (3): 498–500. doi:10.1111/j.1530-0277.1996.tb01081.x. PMID 8727243.  edit
  6. ^ Musshoff, F.; Daldrup, T.; Bonte, W.; Leitner, A.; Lesch, O. M. (1996). "Formaldehyde-derived tetrahydroisoquinolines and tetrahydro-beta-carbolines in human urine". Journal of Chromatography B 683 (2): 163–176. doi:10.1016/0378-4347(96)00106-5. PMID 8891913.  edit
  7. ^ Sällström Baum, S.; Hill, R.; Kiianmaa, K.; Rommelspacher, H. (1999). "Effect of ethanol on (R)- and (S)-salsolinol, salsoline, and THP in the nucleus accumbens of AA and ANA rats". Alcohol (Fayetteville, N.Y.) 18 (2–3): 165–169. doi:10.1016/S0741-8329(98)00080-9. PMID 10456568.  edit
  8. ^ Musshoff, F.; Lachenmeier, D. W.; Schmidt, P.; Dettmeyer, R.; Madea, B. (2005). "Systematic regional study of dopamine, norsalsolinol, and (R/S)-salsolinol levels in human brain areas of alcoholics". Alcoholism, clinical and experimental research 29 (1): 46–52. doi:10.1097/01.ALC.0000150011.81102.C2. PMID 15654290.  edit
  9. ^ Makino, Y; Ohta; Tasaki; Tachikawa; Kashiwasake; Hirobe (1990). "A novel and neurotoxic tetrahydroisoquinoline derivative in vivo: formation of 1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline, a condensation product of amphetamines, in brains of rats under chronic ethanol treatment". Journal of Neurochemistry 55 (3): 963–9. doi:10.1111/j.1471-4159.1990.tb04585.x. PMID 2384762.  edit
  10. ^ Kotake Y, Tasaki Y, Makino Y, Ohta S, Hirobe M (December 1995). "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 65 (6): 2633–8. doi:10.1046/j.1471-4159.1995.65062633.x. PMID 7595560. 
  11. ^ McNaught KS, Carrupt PA, Altomare C, Cellamare S, Carotti A, Testa B, Jenner P, Marsden CD (October 1998). "Isoquinoline derivatives as endogenous neurotoxins in the aetiology of Parkinson's disease". Biochemical Pharmacology 56 (8): 921–33. doi:10.1016/S0006-2952(98)00142-7. PMID 9776302. 
  12. ^ Lorenc-Koci E, Smiałowska M, Antkiewicz-Michaluk L, Gołembiowska K, Bajkowska M, Wolfarth S (2000). "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 95 (4): 1049–59. doi:10.1016/S0306-4522(99)00511-4. PMID 10682712. 
  13. ^ Storch A, Ott S, Hwang YI, Ortmann R, Hein A, Frenzel S, Matsubara K, Ohta S, Wolf HU, Schwarz J (March 2002). "Selective dopaminergic neurotoxicity of isoquinoline derivatives related to Parkinson's disease: studies using heterologous expression systems of the dopamine transporter". Biochemical Pharmacology 63 (5): 909–20. doi:10.1016/S0006-2952(01)00922-4. PMID 11911843. 
  14. ^ Lorenc-Koci E, Antkiewicz-Michaluk L, Kamińska A, Lenda T, Zieba B, Wierońska J, Smiałowska M, Schulze G, Rommelspacher H (October 2008). "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 156 (4): 973–86. doi:10.1016/j.neuroscience.2008.08.050. PMID 18809471. 
  15. ^ Kobayashi H, Fukuhara K, Tada-Oikawa S, Yada Y, Hiraku Y, Murata M, Oikawa S (January 2009). "The mechanisms of oxidative DNA damage and apoptosis induced by norsalsolinol, an endogenous tetrahydroisoquinoline derivative associated with Parkinson's disease". Journal of Neurochemistry 108 (2): 397–407. doi:10.1111/j.1471-4159.2008.05774.x. PMID 19012744. 
  16. ^ Schneider, C. S.; Weber, K. H.; Daniel, H.; Bechtel, W. D.; Boeke-Kuhn, K. (1984). "Synthesis and antidepressant activity of 4-aryltetrahydrothieno[2,3-c]pyridine derivatives". Journal of Medicinal Chemistry 27 (9): 1150. doi:10.1021/jm00375a011.  edit