Tetrahydroisoquinoline (TIQ or THIQ) is an
organic compound
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. T ...
with the chemical formula C
9H
11N. Classified as a
secondary amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such ...
, it is derived from
isoquinoline
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 isoqu ...
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.
[
]
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
Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3%â ...
, catalyzed by selenium dioxide
Selenium dioxide is the chemical compound with the formula SeO2. This colorless solid is one of the most frequently encountered compounds of selenium.
Properties
Solid SeO2 is a one-dimensional polymer, the chain consisting of alternating seleniu ...
.
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
Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomi ...
. This theory has now been discredited and is no longer generally accepted by the scientific community, but endogenous production of neurotoxic tetrahydroisoquinoline derivatives such as norsalsolinol
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 suc ...
continue to be investigated as possible causes for some conditions such as Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
.
Tetrahydroisoquinolines
The tetrahydroisoquinoline skeleton is present in a number of drugs, such as tubocurarine
Tubocurarine (also known as ''d''-tubocurarine or DTC) is a toxic alkaloid historically known for its use as an arrow poison. In the mid-1900s, it was used in conjunction with an anesthetic to provide skeletal muscle relaxation during surgery or ...
, one of the quaternary ammonium muscle relaxants
Neuromuscular-blocking drugs block neuromuscular transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished via their action on the post-synaptic acetylcholine (Nm) receptors.
In clin ...
. Drugs based on 4-substituted tetrahydroisoquinolines include nomifensine
Nomifensine (Merital, Alival) is a norepinephrine-dopamine reuptake inhibitor, i.e. a drug that increases the amount of synaptic norepinephrine and dopamine available to receptors by blocking the dopamine and norepinephrine reuptake transporters ...
and diclofensine
Diclofensine (Ro 8-4650) 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 Serotonin-noradrenaline-dopami ...
. They can be prepared by ''N''-alkylation of benzyl amines with haloacetophenone
Acetophenone is the organic compound with the chemical formula, formula C6H5C(O)CH3. It is the simplest aromatic ketone. This colorless, viscous liquid is a precursor to useful resins and fragrances.
Production
Acetophenone is formed as a byprodu ...
s. Naturally occurring tetrahydroisoquinolines include cheryllinecherylline
/ref> and latifine.
Esproquin, which shows hypotensive activity by virtue of its α-adrenergic blocking properties, is made from THIQ.
References
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