1986-47-6 Usage
Description
TRANS-2-PHENYLCYCLOPROPYLAMINE HYDROCHLORIDE, also known as TCP, is a cell-permeable phenylcyclopropylamine that acts as an inhibitor for monoamine oxidase and histone demethylase activities. It is a white to light beige powder or chunks and is known for its ability to form covalent adducts with the enzyme-bound FAD, affecting the function of four members of the flavin-dependent amine oxidase family enzymes.
Uses
Used in Pharmaceutical Industry:
TRANS-2-PHENYLCYCLOPROPYLAMINE HYDROCHLORIDE is used as an antidepressant for treating depressions that do not respond to other drugs. It is particularly effective due to its action as a non-selective MAO-A/B inhibitor, which helps in modulating the levels of monoamines in the brain, thereby alleviating depressive symptoms.
Used in Enzyme Inhibition:
TRANS-2-PHENYLCYCLOPROPYLAMINE HYDROCHLORIDE is used as an enzyme inhibitor for inhibiting the activities of MAO A/B and LSD1/2. It forms a covalent adduct with the enzyme-bound FAD, thereby preventing the demethylation activities of LSD1-CoREST and LSD1-HCF-1 complexes. This inhibition is essential for controlling the replication and latent infection of α-herpesviruses such as HSV and VZV.
Used in Stem Cell Research:
TRANS-2-PHENYLCYCLOPROPYLAMINE HYDROCHLORIDE is used as a reprogramming agent in the field of stem cell research. When combined with other compounds like CHIR99061, it enables the reprogramming of primary HNEKs (Human Neonatal Epidermal Keratinocytes) into iPS (induced Pluripotent Stem) cells, although with a lower efficiency compared to the use of 4-TFs (Oct4, Klf4, Sox2, and c-Myc).
Biological Activity
Irreversible inhibitor of lysine-specific demethylase 1 (LSD1/BHC110) and monoamine oxidase (MAO) (K i values are 242, 102 and 16 μ M for LSD1, MAO-A and MAO-B respectively). Inhibits histone demethylation.
Clinical Use
MAOI antidepressant
Synthesis
Tranylcypromine, (±)-trans-2-phenylcyclopropylamine (7.2.10),
differs from the drugs described above in that it is not a derivative of hydrazine. It is
synthesized from the ethyl ester of 2-phenylcyclopropan carboxylic acid (7.2.7), which is synthesized by the reaction of styrene with ethyl diazoacetate. 2-phenylcyclopropancarboxylic acid ethyl ester (7.2.7) is hydrolyzed by alkali to 2-phenylcyclopropancarboxylic acid (7.2.8) and the trans-isomer is separated for further reactions. The reaction
of the trans-isomer with thionyl chloride gives trans-2-phenylcyclopropancarboxylic
acid chloride (7.2.9), which upon reaction with sodium azide gives the respective acid
azide, which undergoes Curtius rearrangement to the transcyclopropylamine (7.2.10)
[48,49].
Drug interactions
Potentially hazardous interactions with other drugs
Alcohol: some alcoholic and dealcoholised drinks
contain tyramine which can cause hypertensive crisis.
Alpha-blockers: enhanced hypotensive effect; avoid
with indoramin.
Analgesics: CNS excitation or depression with
pethidine, other opioids and nefopam - avoid;
increased risk of serotonergic effects and convulsions
with tramadol - avoid.
Antibacterials: increased risk of hypertension and
CNS excitation with linezolid and tedizolid - avoid
for at least 2 weeks after stopping MAOIs.
Antidepressants: enhancement of CNS effects and
toxicity. Care with all antidepressants including drug
free periods when changing therapies.
Antidiabetics: possibly enhanced hypoglycaemic
effect.
Antiepileptics: antagonism of anticonvulsant effect;
avoid carbamazepine with or within 2 weeks of
MAOIs.
Antihypertensives: enhanced hypotensive effect.
Antimalarials: avoid with artemether/lumefantrine
and piperaquine with artenimol.
Antipsychotics: effects enhanced by clozapine.
Anxiolytics: avoid buspirone with or within 2 weeks
of MAOIs.
Atomoxetine: avoid concomitant use and for 2 weeks
after use; increased risk of convulsions.
Bupropion: avoid with or for 2 weeks after MAOIs.
Dapoxetine: risk of hypertensive crisis - avoid.
Diuretics: enhanced hypotensive effect; avoid with
indoramin.
Dopaminergics: avoid with entacapone, safinamide
and tolcapone; hypertensive crisis with levodopa and
rasagiline - avoid for at least 2 weeks after stopping
MAOI; hypotension with selegiline.
5HT1
agonist: risk of CNS toxicity with
sumatriptan, rizatriptan and zolmitriptan - avoid
sumatriptan and rizatriptan for 2 weeks after MAOI.
Metaraminol: risk of hypertensive crisis - avoid for
at least 2 weeks after stopping MAOIs.
Methyldopa: avoid concomitant use.
Opicapone: avoid concomitant use.
Sympathomimetics: hypertensive crisis with
sympathomimetics - avoid.
Tetrabenazine: risk of CNS excitation and
hypertension avoid.
Metabolism
Tranylcypromine undergoes considerable hepatic metabolism, including breakdown of the side chain and probably conjugation. Excretion is renal mainly as metabolites.
Check Digit Verification of cas no
The CAS Registry Mumber 1986-47-6 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 1,9,8 and 6 respectively; the second part has 2 digits, 4 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 1986-47:
(6*1)+(5*9)+(4*8)+(3*6)+(2*4)+(1*7)=116
116 % 10 = 6
So 1986-47-6 is a valid CAS Registry Number.
InChI:InChI=1/C9H11N/c10-9-6-8(9)7-4-2-1-3-5-7/h1-5,8-9H,6,10H2/p+1/t8-,9+/m0/s1
1986-47-6Relevant articles and documents
Diastereoselective Photoredox-Catalyzed [3 + 2] Cycloadditions of N-Sulfonyl Cyclopropylamines with Electron-Deficient Olefins
White, Dawn H.,Noble, Adam,Booker-Milburn, Kevin I.,Aggarwal, Varinder K.
supporting information, p. 3038 - 3042 (2021/05/04)
A highly diastereoselective, visible-light-induced [3 + 2] cycloaddition between N-sulfonyl cyclopropylamines and electron-deficient olefins is reported. The reactions proceed via the oxidation of a sulfonamide aza-anion by an organic photocatalyst to generate a nitrogen-centered radical. Strain-induced ring opening and intermolecular addition to the olefin generate an intermediate carbon-centered radical that is reduced to an anion prior to 5-exo cyclization. This enables a highly diastereoselective construction of trans-cyclopentanes possessing synthetically useful functional groups.
C-H activation enables a rapid structure-activity relationship study of arylcyclopropyl amines for potent and selective LSD1 inhibitors
Miyamura, Shin,Araki, Misaho,Ota, Yosuke,Itoh, Yukihiro,Yasuda, Shusuke,Masuda, Mitsuharu,Taniguchi, Tomoyuki,Sowa, Yoshihiro,Sakai, Toshiyuki,Suzuki, Takayoshi,Itami, Kenichiro,Yamaguchi, Junichiro
supporting information, p. 8576 - 8585 (2016/09/28)
We describe the structure-activity relationship of various arylcyclopropylamines (ACPAs), which are potent LSD1 inhibitors. More than 45 ACPAs were synthesized rapidly by an unconventional method that we have recently developed, consisting of a C-H borylation and cross-coupling sequence starting from cyclopropylamine. We also generated NCD38 derivatives, which are known as LSD1 selective inhibitors, and discovered a more effective inhibitor compared to the original NCD38.
(HETERO)ARYL CYCLOPROPYLAMINE COMPOUNDS AS LSD1 INHIBITORS
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Page/Page column 141; 152; 153, (2013/05/09)
The invention relates to (hetero)aryl cyclopropylamine compounds, including particularly the compounds of formula (I) as described and defined herein, and their use in therapy, including, e.g., in the treatment or prevention of cancer, a neurological disease or condition, or a viral infection.