155-09-9

Usage

Uses

Used in Pharmaceutical Industry:
Tranylcypromine is used as an antidepressant for the treatment of major depressive disorder and atypical depression. It works by inhibiting the activity of monoamine oxidase enzymes, leading to an increase in the levels of neurotransmitters such as serotonin, norepinephrine, and dopamine in the brain. This results in an improvement in mood and a reduction in depressive symptoms.
Used in Research Applications:
Tranylcypromine is used as a research tool in neuroscience and pharmacology to study the role of monoamine oxidase enzymes in the regulation of neurotransmitter levels and their involvement in various psychiatric and neurological disorders. It is also used to investigate the mechanisms of action of other drugs that target these enzymes.
Used in Combination Therapy:
Tranylcypromine is used in combination with other medications, such as selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs), to enhance their therapeutic effects in patients with treatment-resistant depression or anxiety disorders. The combination of tranylcypromine with these medications can help to achieve better control of symptoms and improve the overall response to treatment.
Used in Veterinary Medicine:
Tranylcypromine is also used in veterinary medicine for the treatment of behavioral disorders and anxiety in animals, such as dogs and cats. It can help to alleviate symptoms of separation anxiety, noise phobia, and other anxiety-related conditions in pets.

Originator

Parnate,SKF,UK,1960

Manufacturing Process

A solution containing 167 grams of stabilized styrene and 183 grams of ethyl diazoacetate is cooled to 0°C and dropped into 83.5 grams of styrene with stirring, in a dry nitrogen atmosphere, at 125° to 135°C. This produced the ester ethyl 2-phenylcyclopropanecarboxylate. A solution of the above ester (207.8 grams) and 64.5 grams of sodium hydroxide in 80 cc of water and 600 cc of ethanol is refluxed for 9 hours. The carboxylic acid of 2-phenylcyclopropane is liberated with 200 cc of concentrated hydrochloric acid. The 2-phenylcyclopropanecarboxylic acid contains 3 to 4 parts of the trans isomer to 1 part of the cis isomer. The acid is recrystallized from hot water. The pure trans isomer comes out as crystalline material (solid) while the cis isomer stays in solution. A solution of 4.62 grams of 2-phenylcyclopropanecarboxylic acid in 15 cc of dry benzene is refluxed with 4 cc of thionyl chloride for 5 hours, the volatile liquids are removed and the residue once more distilled with benzene. Fractionation of the residue yields the carbonyl chloride of 2- phenylcyclopropane. A mixture of 15 grams of technical sodium azide and 50 cc of dry toluene is stirred and warmed and a solution of 10 grams of 2- phenylcyclopropanecarbonyl chloride in 50 cc of dry toluene is added slowly. Inorganic salts are filtered and washed well with dry benzene and the solvents are removed under reduced pressure. The RCON3 compound produced undergoes the Curtius rearrangement to RNCO + N2. The residual isocyanate is a clear red oil of characteristic odor. It is cooled to 10°C and treated cautiously with 100 cc of 35% hydrochloric acid whereupon RNCO + H2O gives RNH2 + CO2.After most of the evolution of carbon dioxide has subsided the mixture is refluxed for 13 hours, the cooled solution is diluted with 75 cc of water and extracted with three 50 cc portions of ether. The acid solution is evaporated under reduced pressure with occasional additions of toluene to reduce foaming. The almost dry residue is cooled to 0°C and made strongly alkaline with a 50% potassium hydroxide solution. The amine is extracted into several portions of ether, dried over potassium hydroxide, the solvent removed, and the base fractioned. Reaction of the base with a half-molar quantity of sulfuric acid gives the sulfate.

Therapeutic Function

Psychostimulant

World Health Organization (WHO)

Tranylcypromine, a monoamine oxidase inhibitor (MAOI), was introduced in 1961 for the treatment of depressive illness. By 1964 its use had been associated with transient hypertensive crises and other adverse effects when taken together with certain cheeses and other foods containing tyramine. This led to the withdrawal of the drug in several countries and the suspension of marketing on a worldwide basis by the major manufacturer pending review of these adverse reactions. Subsequently, in response to requests from the medical profession, tranylcypromine was resubmitted for registration with appropriate warnings in the product information and it is now marketed in more than 30 countries.

InChI:InChI=1/C9H11N/c10-9-6-8(9)7-4-2-1-3-5-7/h1-5,8-9H,6,10H2/t8?,9-/m1/s1

Upstream product

• 1444-65-1 (RS)-2-phenylcyclohexanone 
• 93-92-5 1-phenylethyl acetate 
• 141-78-6 ethyl acetate 
• 874341-82-9 [(1S,2R)-2-nitrocyclopropyl]benzene 
• 3471-10-1 (1R,2R)-trans-2-phenyl-1-cyclopropanecarboxylic acid 
• 185256-47-7 (-)-(1R,2S)-trans (2-phenyl-cyclopropyl)carbaminic acid tert-butyl ester 
• 4407-36-7 (2E)-3-phenyl-2-propen-1-ol 
• 110659-58-0 (1R,2R)-1-hydroxymethyl-2-phenylcyclopropane 
• 939-90-2 trans-2-phenylcyclopropane-1-carboxylic acid 
• 939-89-9 (1S*,2R*)-2-phenylcyclopropane-1-carboxylic acid 
• 97-71-2 (1R,2R)-2-phenyl-cyclopropanecarboxylic acid ethyl ester 
• 97-71-2 ethyl (S,S)-2-phenylcyclopropane-1-carboxylate 
• 23020-15-7 (1S,2S)-2-phenylcyclopropane-1-carboxylic acid 
• 100-42-5 styrene 

Downstream Products

• 103477-53-8 (-)-ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-<<(1'R,2'S)-2'-phenylcyclopropyl>amino>acrylate 
• 97905-55-0 N⁶-[(1R,2S)-2-phenyl-1-cyclopropyl]adenosine 
• 83586-90-7 C₂₄H₂₆N₄O₅ 
• 872576-64-2 2-((1R,2S)-2-phenyl-cyclopropylamino)-thiazol-4-one 
• 103531-44-8 (-)-7-chloro-6-fluoro-1-<(1'R,2'S)-2'-phenylcyclopropyl>-1,4-dihydro-4-oxoquinoline-3-carboxylic acid 
• 103531-42-6 (-)-7-chloro-6-fluoro-1-<(1'R,2'S)-2'-phenylcyclopropyl>-1,4-dihydro-3-ethoxycarbonyl-4-oxoquinoline 
• 103531-48-2 (+)-6-fluoro-1-<(1'R,2'S)-2'-phenylcyclopropyl>-7-piperazino-1,4-dihydro-4-oxoquinoline-3-carboxylic acid 
• 103531-46-0 (+)-7-<4-(ethoxycarbonyl)piperazino>-6-fluoro-1-<(1'R,2'S)-2'-phenylcyclopropyl>-1,4-dihydro-4-oxoquinoline-3-carboxylic acid ethyl piperazinecarboxylate salt 
• 1022945-05-6 C₂₅H₂₉N₇O₂S 
• 1351165-22-4 C₂₁H₂₂Cl₂N₄O₂ 
• 1351165-63-3 C₂₁H₂₂Cl₂N₄O₂ 
• 1211400-41-7 (8aS)-N-(2,3-dichlorophenyl)-1,3-dioxo-2-[(1R,2S)-2-phenylcyclopropyl]hexahydroimidazo[1,5-a]pyrazine-7(1H)-carboxamide 
• 1351165-31-5 C₂₂H₂₅N₃O₃ 

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Relevant academic research and scientific papers

CYCLOPROPYLAMINE COMPOUND AS LSD1 INHIBITOR AND USE THEREOF

Provided is a cyclopropylamine compound as lysine-specific demethylase 1 (LSD1) inhibitor, and a use thereof in preparation of drug for treating diseases associated with LSD1. The cyclopropylamine compound is a compound represented by formula (I), an isomer thereof, and a pharmaceutically acceptable salt thereof.

SALT OF LSD1 INHIBITOR AND A POLYMORPH THEREOF

Provided are a compound III serving as an LSD1 inhibitor and a crystal form thereof, as well as use of the compound and the crystal form thereof in preparation of a medicament for treating an LSD1 related disease.

The synergistic effect of copper chromite spinel nanoparticles (CuCr2O4) and basic ionic liquid on the synthesis of cyclopropanecarboxylic acids

Abstract: An efficient synthesis of cyclopropanecarboxylic acids using copper chromite spinel nanoparticles and basic ionic liquid is described. In this study, a relatively simple method starting with trans-cinnamic acid for the synthesis of (±)-trans-2-phenylcyclopropanecarboxylic acid, a key intermediate in the synthesis of tranylcypromine sulfate as an active pharmaceutical ingredient, was employed. Using a combination of basic ionic liquid [Bmim]OH and copper chromite spinel nanoparticles as a catalytic system, the best results were obtained in THF as a polar solvent. This method is a useful alternative to other approaches described in the literature. The use of commercially available chemicals, decreased environmental hazards, with no need for the separation of stereoisomers, and consequently a reduced number of overall steps, are the advantages of this approach that make it an appropriate choice at an increased scale. Graphical Abstract: [Figure not available: see fulltext.]

Gram-Scale Synthesis of Chiral Cyclopropane-Containing Drugs and Drug Precursors with Engineered Myoglobin Catalysts Featuring Complementary Stereoselectivity

Engineered hemoproteins have recently emerged as promising systems for promoting asymmetric cyclopropanations, but variants featuring predictable, complementary stereoselectivity in these reactions have remained elusive. In this study, a rationally driven strategy was implemented and applied to engineer myoglobin variants capable of providing access to 1-carboxy-2-aryl-cyclopropanes with high trans-(1R,2R) selectivity and catalytic activity. The stereoselectivity of these cyclopropanation biocatalysts complements that of trans-(1S,2S)-selective variants developed here and previously. In combination with whole-cell biotransformations, these stereocomplementary biocatalysts enabled the multigram synthesis of the chiral cyclopropane core of four drugs (Tranylcypromine, Tasimelteon, Ticagrelor, and a TRPV1 inhibitor) in high yield and with excellent diastereo- and enantioselectivity (98–99.9% de; 96–99.9% ee). These biocatalytic strategies outperform currently available methods to produce these drugs.

Reversible C-C bond activation enables stereocontrol in Rh-catalyzed carbonylative cycloadditions of aminocyclopropanes

Upon exposure to neutral or cationic Rh(I)-catalyst systems, amino-substituted cyclopropanes undergo carbonylative cycloaddition with tethered alkenes to provide stereochemically complex N-heterocyclic scaffolds. These processes rely upon the generation and trapping of rhodacyclopentanone intermediates, which arise by regioselective, Cbz-directed insertion of Rh and CO into one of the two proximal aminocyclopropane C-C bonds. For cyclizations using cationic Rh(I)-systems, synthetic and mechanistic studies indicate that rhodacyclopentanone formation is reversible and that the alkene insertion step determines product diastereoselectivity. This regime facilitates high levels of stereocontrol with respect to substituents on the alkene tether. The option of generating rhodacyclopentanones dynamically provides a new facet to a growing area of catalysis and may find use as a (stereo)control strategy in other processes.

KDM1A INHIBITORS FOR THE TREATMENT OF DISEASE

Disclosed herein are new compounds and compositions and their application as pharmaceuticals for the treatment of diseases. Methods of inhibition of KDMIA, and methods of increasing gamma globin gene expression in a human or animal subject are also provided for the treatment diseases such as sickle cell disease.

COMPLEMENT PATHWAY MODULATORS AND USES THEREOF

The present invention provides a compound of formula I: (I) a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

(HETERO)ARYL CYCLOPROPYLAMINE COMPOUNDS AS LSD1 INHIBITORS

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.

(HETERO)ARYL CYCLOPROPYLAMINE COMPOUNDS AS LSD1 INHIBITORS

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.

Asymmetric syntheses of pharmaceuticals containing a cyclopropane moiety using catalytic asymmetric Simmons-Smith reactions of allylalcohols: Syntheses of optically active tranylcypromine and milnacipran

Asymmetric synthesis of tranylcypromine was achieved using an enantioselective Simmons-Smith cyclopropanation catalyzed by a simple disulfonamide derived from an -amino acid. The optically active milnacipran was also synthesized by porcine pancreas lipase-catalyzed selective monoacylation of the C4-hydroxy group in (Z)-2-phenylbut-2-ene-1,4-diol and the enantioselective Simmons-Smith cyclopropanation as the key steps.