Tetrahydroisoquinoline

Last updated
Tetrahydroisoquinoline
Tetrahydroisoquinoline-structure.svg
Names
Preferred IUPAC name
1,2,3,4-Tetrahydroisoquinoline
Identifiers
3D model (JSmol)
AbbreviationsTIQ, THIQ
ChEMBL
ChemSpider
ECHA InfoCard 100.001.864 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 202-050-0
PubChem CID
RTECS number
  • NX4900000
UNII
  • InChI=1S/C9H11N/c1-2-4-9-7-10-6-5-8(9)3-1/h1-4,10H,5-7H2 Yes check.svgY
    Key: UWYZHKAOTLEWKK-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C9H11N/c1-2-4-9-7-10-6-5-8(9)3-1/h1-4,10H,5-7H2
    Key: UWYZHKAOTLEWKK-UHFFFAOYAB
  • c1ccc2c(c1)CCNC2
Properties
C9H11N
Molar mass 133.19 g/mol
AppearanceDeep 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
GHS classification and labelling: [1]
GHS-pictogram-acid.svg GHS-pictogram-skull.svg GHS-pictogram-silhouette.svg
Danger
H301, H310, H314, H332, H371, H412
P260, P261, P262, P264, P270, P271, P273, P280, P301+P310, P301+P330+P331, P302+P350, P302+P352, P303+P361+P353, P304+P312, P304+P340, P305+P351+P338, P309+P311, P310, P312, P322, P330, P332+P313, P337+P313, P361, P362, P363, P403+P233, P405, P501
Flash point 99 °C (210 °F; 372 K)(closed cup)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)
Infobox references

Tetrahydroisoquinoline (TIQ or THIQ) is an organic compound with the chemical formula C9H11N. Classified as a secondary amine, it is derived from isoquinoline by hydrogenation. It is a colorless viscous liquid that is miscible with most organic solvents. The tetrahydroisoquinoline skeleton is encountered in a number of bioactive compounds and drugs. [2] [3]

Contents

Reactions

As a secondary amine, tetrahydroisoquinoline has weakly basic properties and forms salts with strong acids. It can be dehydrogenated to give isoquinoline and hydrogenated to decahydroisoquinoline. Like other secondary amines, tetrahydroisoquinoline can be oxidized to the corresponding nitrone using hydrogen peroxide, catalyzed by selenium dioxide. [4]

Toxicology

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. [5] This theory has now been discredited and is no longer generally accepted by the scientific community, [6] 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. [7] [8] [9] [10] [11] [12]

Tetrahydroisoquinolines

The tetrahydroisoquinoline skeleton is present in a number of drugs, [3] such as tubocurarine, one of the quaternary ammonium muscle relaxants. Drugs based on 4-substituted tetrahydroisoquinolines include nomifensine [13] and diclofensine. They can be prepared by N-alkylation of benzyl amines with haloacetophenones. [14] Naturally occurring tetrahydroisoquinolines include cherylline [15] and latifine.

Esproquin, [16] which shows hypotensive activity by virtue of its α-adrenergic blocking properties, is made from THIQ.

Related Research Articles

Substantia nigra Structure in the basal ganglia of the brain

The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. Substantia nigra is Latin for "black substance", reflecting the fact that parts of the substantia nigra appear darker than neighboring areas due to high levels of neuromelanin in dopaminergic neurons. Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta.

Dopamine Organic chemical that functions both as a hormone and a neurotransmitter

Dopamine is a neuromodulatory molecule, often mistaken as a neurotransmitter, that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% of the catecholamine content in the brain. It is an amine synthesized by removing a carboxyl group from a molecule of its precursor chemical, L-DOPA, which is synthesized in the brain and kidneys. Dopamine is also synthesized in plants and most animals. In the brain, dopamine functions as a neurotransmitter—a chemical released by neurons to send signals to other nerve cells. Neurotransmitters are synthesized in specific regions of the brain, but affect many regions systemically. The brain includes several distinct dopamine pathways, one of which plays a major role in the motivational component of reward-motivated behavior. The anticipation of most types of rewards increases the level of dopamine in the brain, and many addictive drugs increase dopamine release or block its reuptake into neurons following release. Other brain dopamine pathways are involved in motor control and in controlling the release of various hormones. These pathways and cell groups form a dopamine system which is neuromodulatory.

Monoamine neurotransmitter

Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin.

Phenethylamine

Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace amine-associated receptor 1 (TAAR1) and inhibiting vesicular monoamine transporter 2 (VMAT2) in monoamine neurons. To a lesser extent, it also acts as a neurotransmitter in the human central nervous system. In mammals, phenethylamine is produced from the amino acid L-phenylalanine by the enzyme aromatic L-amino acid decarboxylase via enzymatic decarboxylation. In addition to its presence in mammals, phenethylamine is found in many other organisms and foods, such as chocolate, especially after microbial fermentation.

<i>beta</i>-Carboline Chemical compound also known as norharmane

β-Carboline (9H-pyrido[3,4-b]indole) represents the basic chemical structure for more than hundred alkaloids and synthetic compounds. The effects of these substances depend on their respective substituent. Natural β-carbolines primarily influence brain functions but can also exhibit antioxidant effects. Synthetically designed β-carboline derivatives have recently been shown to have neuroprotective, cognitive enhancing and anti-cancer properties.

Aromatic <small>L</small>-amino acid decarboxylase

Aromatic L-amino acid decarboxylase, also known as DOPA decarboxylase (DDC), tryptophan decarboxylase, and 5-hydroxytryptophan decarboxylase, is a lyase enzyme.

Isoquinoline Chemical compound

Isoquinoline is a heterocyclic aromatic organic compound. It is a structural isomer of quinoline. Isoquinoline and quinoline are benzopyridines, which are composed of a benzene ring fused to a pyridine ring. In a broader sense, the term isoquinoline is used to make reference to isoquinoline derivatives. 1-Benzylisoquinoline is the structural backbone in naturally occurring alkaloids including papaverine. The isoquinoline ring in these natural compound derives from the aromatic amino acid tyrosine.

Apomorphine

Apomorphine, sold under the brand name Apokyn among others, is a type of aporphine having activity as a non-selective dopamine agonist which activates both D2-like and, to a much lesser extent, D1-like receptors. It also acts as an antagonist of 5-HT2 and α-adrenergic receptors with high affinity. The compound is historically a morphine decomposition product made by boiling morphine with concentrated acid, hence the -morphine suffix. Contrary to its name, apomorphine does not actually contain morphine or its skeleton, nor does it bind to opioid receptors. The apo- prefix relates to it being a morphine derivative ("[comes] from morphine").

Dopamine agonist

A dopamine agonist(DA) is a compound that activates dopamine receptors. There are two families of dopamine receptors, D2-like and D1-like, and they are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the D2-like family includes D2, D3 and D4 receptors. Dopamine agonists are used in Parkinson’s disease and, to a lesser extent, to treat depression, hyperprolactinemia and restless legs syndrome.

The pars compacta is a portion of the substantia nigra, located in the midbrain. It is formed by dopaminergic neurons and located medial to pars reticulata. Parkinson's disease is characterized by the death of dopaminergic neurons in this region.

Dihydroergocryptine

Dihydroergocryptine (DHEC), sold under the brand names Almirid and Cripar among others, is a dopamine agonist of the ergoline group that is used as an antiparkinson agent in the treatment of Parkinson's disease. It is taken by mouth.

Nuclear receptor 4A2

The nuclear receptor 4A2 (NR4A2) also known as nuclear receptor related 1 protein (NURR1) is a protein that in humans is encoded by the NR4A2 gene. NR4A2 is a member of the nuclear receptor family of intracellular transcription factors.

<i>N</i>-Methylphenethylamine Chemical compound

N-Methylphenethylamine (NMPEA) is a naturally occurring trace amine neuromodulator in humans that is derived from the trace amine, phenethylamine (PEA). It has been detected in human urine and is produced by phenylethanolamine N-methyltransferase with phenethylamine as a substrate. PEA and NMPEA are both alkaloids that are found in a number of different plant species as well. Some Acacia species, such as A. rigidula, contain remarkably high levels of NMPEA. NMPEA is also present at low concentrations in a wide range of foodstuffs.

Dopamine receptor D<sub>1</sub>

Dopamine receptor D1, also known as DRD1. It is one of the two types of D1-like receptor family - receptors D1 and D5. It is a protein that in humans is encoded by the DRD1 gene.

Diclofensine Chemical compound

Diclofensine was developed by Hoffmann-La Roche in the 1970s in the search for a new antidepressant. It was found that the (S)-isomer was responsible for activity. Is a stimulant drug which acts as a triple monoamine reuptake inhibitor, primarily inhibiting the reuptake of dopamine and norepinephrine, with affinities (Ki) of 16.8 nM, 15.7 nM, and 51 nM for DAT, NET, and SERT, respectively. It was found to be an effective antidepressant in human trials, with relatively few side effects, but was ultimately dropped from clinical development, possibly due to concerns about its abuse potential.

EMD-386088

EMD-386088 is an indole derivative which is used in scientific research. It acts as a potent 5-HT6 receptor partial agonist, with a Ki of 1 nM, a significantly higher affinity than older 5-HT6 agonists such as EMDT, although it possesses moderate affinity for the 5-HT3 receptor as well. Subsequent research has determined that EMD-386088 is also a dopamine reuptake inhibitor and that this action is involved in the antidepressant-like effects of the drug in rodents.

Norsalsolinol Chemical compound

Norsalsolinol is a chemical compound that is produced naturally in the body through metabolism of dopamine. It has been shown to be a selective dopaminergic neurotoxin, and has been suggested as a possible cause of neurodegenerative conditions such as Parkinson's disease and the brain damage associated with alcoholism, although evidence for a causal relationship is unclear.

Salsoline Chemical compound

Salsoline is a tetrahydroisoquinoline alkaloid found in some plants of the genus Salsola. Salsoline is the monomethylated metabolite of salsolinol which has been thought to contribute to Parkinson's disease. Also, this has been tied to the neuropathology of chronic alcoholism.

BNN-20

BNN-20, also known as 17β-spiro-(androst-5-en-17,2'-oxiran)-3β-ol, is a synthetic neurosteroid, "microneurotrophin", and analogue of the endogenous neurosteroid dehydroepiandrosterone (DHEA). It acts as a selective, high-affinity, centrally active agonist of the TrkA, TrkB, and p75NTR, receptors for the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), as well as for DHEA and DHEA sulfate (DHEA-S). The drug has been suggested as a potential novel treatment for Parkinson's disease and other conditions.

9-Methyl-β-carboline Chemical compound

9-Methyl-β-carboline (9-Me-BC) is a heterocyclic amine of the β-carboline family, and a research chemical.

References

  1. ↑ "1,2,3,4-Tetrahydroisoquinoline". pubchem.ncbi.nlm.nih.gov. Retrieved 12 December 2021.
  2. ↑ Mitchenson, Andrew (2000). "Saturated nitrogen heterocycles". Journal of the Chemical Society, Perkin Transactions 1 (17): 2862–2892. doi:10.1039/A908537H.
  3. 1 2 Scott, Jack D.; Williams, Robert M. (2002). "Chemistry and Biology of the Tetrahydroisoquinoline Antitumor Antibiotics". Chemical Reviews. 102 (5): 1669–1730. doi:10.1021/cr010212u. PMID   11996547.
  4. ↑ 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.
  5. ↑ 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.,Altshuler, H. L.; Shippenberg (1982). "Tetrahydroisoquinoline and opioid substrates of alcohol actions". Progress in Clinical and Biological Research. 90: 329–344. PMID   7202207., 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. S2CID   1513683.
  6. ↑ 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., 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., 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., 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.
  7. ↑ 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. S2CID   39449026.
  8. ↑ 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.
  9. ↑ 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. S2CID   13549697.
  10. ↑ 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.
  11. ↑ 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. S2CID   44658852.
  12. ↑ 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.
  13. ↑ 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): 1150–1155. doi:10.1021/jm00375a011. PMID   6471069.
  14. ↑ BG 49761
  15. ↑ cherylline
  16. ↑ Gray, Allan P.; Shiley, Richard H. (1973). "Preparation and cardiovascular actions of a group of tetrahydroisoquinoline derivatives". Journal of Medicinal Chemistry. 16 (7): 859–861. doi:10.1021/jm00265a028. ISSN   0022-2623. PMID   4146907.
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