4548-34-9

Usage

Uses

Used in Pharmaceutical Industry:
TranylcyproMine (2-PCPA) HCl is used as a monoamine oxidase inhibitor for its ability to selectively inhibit the enzyme CYP2A6. This makes it a potential candidate for the development of treatments targeting various neurological and psychiatric disorders, as well as other conditions where monoamine oxidase inhibition can be beneficial.
Used in Research Applications:
In the field of research, TranylcyproMine (2-PCPA) HCl is used as a tool compound to study the role of monoamine oxidase enzymes in various biological processes. Its selective inhibition of CYP2A6 allows researchers to investigate the specific functions and interactions of this enzyme in cellular and molecular studies.
Used in Drug Development:
TranylcyproMine (2-PCPA) HCl is utilized in drug development as a lead compound for the creation of new medications targeting monoamine oxidase enzymes. Its high specificity for CYP2A6 makes it a promising starting point for designing drugs with improved efficacy and reduced side effects compared to existing treatments.
Used in Toxicology Studies:
In toxicology, TranylcyproMine (2-PCPA) HCl is employed as a reference compound to evaluate the potential toxic effects of other substances on the monoamine oxidase enzyme system. Its well-defined inhibitory profile helps researchers understand the mechanisms of action and potential risks associated with exposure to various chemicals and compounds.

Upstream product

• 847644-86-4 ((1SR,2RS)-tert-butyl-2-phenylcyclopropyl)carbamate 
• 103-26-4 Methyl cinnamate 
• 3721-28-6 (1S,2R)-tranylcypromine 
• 100-42-5 styrene 
• 97-71-2 ethyl (S,S)-2-phenylcyclopropane-1-carboxylate 
• 185256-49-9 trans-tert-buthyl-2-phenylcyclopropyl carbamate 
• 847644-86-4 C₁₄H₁₉NO₂ 
• 5861-31-4 methyl trans-2-phenylcyclopropanecarboxylate 
• 939-90-2 trans-2-phenylcyclopropane-1-carboxylic acid 

Downstream Products

• 133941-07-8 (+/-)-N-trans-(2-phenylcyclopropyl)bromoacetamide 
• 133941-05-6 (+/-)-N-(trans-2-phenylcyclopropyl)nicotinamide 
• 21087-29-6 trans-3-phenylprop-2-enyl chloride 
• 4407-36-7 (2E)-3-phenyl-2-propen-1-ol 
• 133941-13-6 chloromethyl (+/-)-trans-(2-phenylcyclopropyl)carbamate 
• 133941-14-7 2-bromoethyl (+/-)-trans-(2-phenylcyclopropyl)carbomate 
• 21040-45-9 Cinnamyl acetate 
• 7217-71-2 1-phenyl-2-propenyl acetate 
• 750644-54-3 (2R,3S,4S,5R)-9-(3,4-dihydroxy-5-hydroxymethyl-tetrahydrofuran-2-yl)-6-(2-phenyl-cyclopropylamino)-9H-purine-2-carbonitrile 
• 658683-57-9 C₁₅H₁₆N₂O₂ 
• 14177-80-1 trans-N,N-dimethyl-2-phenylcyclopropan-1-amine 
• 1986-47-6 tranylcypromine hydrochloride 

Relevant academic research and scientific papers

Diastereoselective Photoredox-Catalyzed [3 + 2] Cycloadditions of N-Sulfonyl Cyclopropylamines with Electron-Deficient Olefins

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.

Cross-Coupling of Alkyl Redox-Active Esters with Benzophenone Imines: Tandem Photoredox and Copper Catalysis

Alkyl amines are an important class of organic compounds in medicinal and materials chemistry. Until now very have been very few methods for the synthesis of alkyl amines by metal-catalyzed cross-coupling of alkyl electrophiles with nitrogen nucleophiles. Described here is an approach to employ tandem photoredox and copper catalysis to enable the cross-coupling of alkyl N-hydroxyphthalimide esters, readily derived from alkyl carboxylic acids, with benzophenone-derived imines. Hydrolysis of the coupling products furnish alkylated primary amines. Primary, secondary, and tertiary alkyl groups can be transferred, and the coupling tolerates a diverse set of functional groups. The method allows rapid functionalization of natural products and drugs, and can be used to expedite syntheses of pharmaceuticals from readily available chemical feedstocks.

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.

C-H activation enables a rapid structure-activity relationship study of arylcyclopropyl amines for potent and selective LSD1 inhibitors

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.

Stereodivergent synthesis of arylcyclopropylamines by sequential C-H borylation and Suzuki-Miyaura coupling

A step-economical and stereodivergent synthesis of privileged 2-arylcyclopropylamines (ACPAs) through a C-(sp3)-H borylation and Suzuki-Miyaura coupling sequence has been developed. The iridium-catalyzed C-H borylation of N-cyclopropylpivalamide proceeds with cis selectivity. The subsequent B-cyclopropyl Suzuki-Miyaura coupling catalyzed by [PdCl2(dppf)]/Ag2O proceeds with retention of configuration at the carbon center bearing the Bpin group, while epimerization at the nitrogen-bound carbon atoms of both the starting materials and products is observed under the reaction conditions. This epimerization is, however, suppressed in the presence of O2. The present new ACPA synthesis results in not only a significant reduction in the steps required for making ACPA derivatives, but also the ability to access either isomer (cis or trans) by simply changing the atmosphere (N2 or O2) in the coupling stage.

(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.

Biochemical, structural, and biological evaluation of tranylcypromine derivatives as inhibitors of histone demethylases LSD1 and LSD2

LSD1 and LSD2 histone demethylases are implicated in a number of physiological and pathological processes, ranging from tumorigenesis to herpes virus infection. A comprehensive structural, biochemical, and cellular study is presented here to probe the potential of these enzymes for epigenetic therapies. This approach employs tranylcypromine as a chemical scaffold for the design of novel demethylase inhibitors. This drug is a clinically validated antidepressant known to target monoamine oxidases A and B. These two flavoenzymes are structurally related to LSD1 and LSD2. Mechanistic and crystallographic studies of tranylcypromine inhibition reveal a lack of selectivity and differing covalent modifications of the FAD cofactor depending on the enantiomeric form. These findings are pharmacologically relevant, since tranylcypromine is currently administered as a racemic mixture. A large set of tranylcypromine analogues were synthesized and screened for inhibitory activities. We found that the common evolutionary origin of LSD and MAO enzymes, despite their unrelated functions and substrate specificities, is reflected in related ligand-binding properties. A few compounds with partial enzyme selectivity were identified. The biological activity of one of these new inhibitors was evaluated with a cellular model of acute promyelocytic leukemia chosen since its pathogenesis includes aberrant activities of several chromatin modifiers. Marked effects on cell differentiation and an unprecedented synergistic activity with antileukemia drugs were observed. These data demonstrate that these LSD1/2 inhibitors are of potential relevance for the treatment of promyelocytic leukemia and, more generally, as tools to alter chromatin state with promise of a block of tumor progression.

Enantiomerically pure cyclopropylamines from cyclopropylboronic esters

Cyclopropylamines are versatile intermediates and products both in organic synthesis in general and for active substances in particular. Although the synthesis of the corresponding enantiomerically pure cyclopropylboronic esters had been established previously, the C-B to C-N transformation was elusive. A detailed, study directed towards the synthesis of several enantiomerically pure cyclopropylamines is disclosed; tranylcypromine [(1S, 2R)-36] and the known belactosin A intermediate 43 were both obtained by use of trifluoroborates as key intermediates.

Novel trans-2-aryl-cyclopropylamine analogues as potent and selective dipeptidyl peptidase IV inhibitors

A series of trans-2-aryl-cyclopropylamine derived compounds were synthesized and evaluated their biological activities against DPP-IV. The structure-activity relationships (SAR) led to the discovery of novel series of DPP-IV inhibitors, having IC50 values of 100 nM with excellent selectivity over the closely related enzymes, DPP8, DPP-II and FAP. The studies identified a potent and selective DPP-IV inhibitor 24b, which exhibited the ability to both significantly inhibit plasma DPP-IV activity in rats and improve glucose tolerance in lean mice and diet induced obese mice.

A novel approach to enantiopure cyclopropane compounds from biotransformation of nitriles

Rhodococcus sp. AJ270, a powerful and versatile nitrile hydratase/amidase containing microbial whole-cell system, catalyzed the enantioselective hydrolysis of both racemic trans- and cis-2-arylcyclopropanecarbonitriles to afford the corresponding amides and acids with enantiomeric excesses as high as >99%. The reaction rate and enantioselectivity observed for both nitrile hydratase and amidase were also strongly dependent upon the nature of the substituent and substitution pattern on the benzene ring of the substrates. The application of and the advantages of biotransformation of nitriles were demonstrated by preparing (1S,2R)-2-phenylcyclopropylamine and (1R,2R)-2-phenylcyclopropylmethylamine through facile and straightforward chemical manipulations of (1S,2S)-2-phenylcyclopropanecarboxylic acid and (1R,2R)-2-phenylcyclopropanecarboxamide, respectively.