22002-68-2

Upstream product

• 860767-75-5 ethyl-phenethyl-carbamonitrile 
• 140-29-4 phenylacetonitrile 
• 3240-95-7 N-benzylidene-2-phenylethanamine 
• 75-03-6 ethyl iodide 
• 75-04-7 ethylamine 
• 103-63-9 1-phenyl-2-bromoethane 
• 645-54-5 2-phenylthioacetamide 
• 74-96-4 ethyl bromide 
• 67-66-3 chloroform 
• 64-04-0 phenethylamine 
• 64-17-5 ethanol 
• 368-39-8 triethyloxonium fluoroborate 
• 102-96-5 (2-nitroethenyl)benzene 
• 22560-16-3 lithium triethylborohydride 

Downstream Products

• 73676-26-3 ethyl-methyl-phenethyl-amine 
• 6707-93-3 ethyl-diphenethyl-amine 
• 91553-32-1 N-Aethyl-N-<2-hydroxy-aethyl>-phenaethylamin 
• 6121-12-6 1-Aethyl-1-phenaethyl-biuret 
• 67293-50-9 3,4,5-Trimethoxy-benzoesaeure-[3-(N-aethyl-N-phenaethyl)-amino-propylester] 
• 1053244-32-8 (4S,5R,6R)-5-Acetylamino-4-tert-butoxycarbonylamino-6-(ethyl-phenethyl-carbamoyl)-5,6-dihydro-4H-pyran-2-carboxylic acid benzhydryl ester 
• 73676-21-8 N-ethyl-N-propyl-2-phenylethylamine 
• 1094173-20-2 C₁₇H₁₈INO 
• 66887-16-9 N-Ethyl-N-(2-phenylethyl)acetamide 

Relevant academic research and scientific papers

Profiling substrate specificity of two series of phenethylamine analogs at monoamine oxidase A and B

The membrane bound enzyme monoamine oxidase exist in two splice variants designated A and B (MAO-A and MAO-B) and are key players in the oxidative metabolism of monoamines in mammalians. Despite their importance and being a prevalent target for the development of inhibitors as drugs, no systematic study of substrate specificity has been reported. In this study we present a systematic study of the MAO-A and MAO-B substrate specificity profile by probing two series of phenethylamine analogs. Kmand kcatvalues were determined for four N-alkyl analogs 2 -5 and four aryl halide analogs 6-9 at MAO-A and MAO-B. A following in silico study disclosed a new adjacent compartment to the MAO-B substrate pocket defined by amino acids Tyr188, Tyr435, Tyr398, Thr399, Cys172 and Gly434. This new insight is important for the understanding of the substrate specificity of the MAO-B enzyme and will be relevant for future drug design within the field of monoamines.

Structure-Activity Relationship Studies of Pyrimidine-4-Carboxamides as Inhibitors of N-Acylphosphatidylethanolamine Phospholipase D

N-Acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is regarded as the main enzyme responsible for the biosynthesis of N-acylethanolamines (NAEs), a family of bioactive lipid mediators. Previously, we reported N-(cyclopropylmethyl)-6-((S)-3-hydroxypyrrolidin-1-yl)-2-((S)-3-phenylpiperidin-1-yl)pyrimidine-4-carboxamide (1, LEI-401) as the first potent and selective NAPE-PLD inhibitor that decreased NAEs in the brains of freely moving mice and modulated emotional behavior [ Mock et al. Nat Chem. Biol., 2020, 16, 667-675 ]. Here, we describe the structure-activity relationship (SAR) of a library of pyrimidine-4-carboxamides as inhibitors of NAPE-PLD that led to the identification of LEI-401. A high-throughput screening hit was modified at three different substituents to optimize its potency and lipophilicity. Conformational restriction of an N-methylphenethylamine group by replacement with an (S)-3-phenylpiperidine increased the inhibitory potency 3-fold. Exchange of a morpholine substituent for an (S)-3-hydroxypyrrolidine reduced the lipophilicity and further increased activity by 10-fold, affording LEI-401 as a nanomolar potent inhibitor with drug-like properties. LEI-401 is a suitable pharmacological tool compound to investigate NAPE-PLD function in vitro and in vivo.

INHIBITORS OF N-ACYLPHOSPHATIDYLETHANOLAMINE PHOSPHOLIPASE D (NAPE-PLD)

The invention relates to a compound of the formula (I) as novel inhibitor of N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD), and to use thereof for the prophylaxis or treatment of diseases associated with NAPE-PLD. wherein in a ring A, X1 is N, or CR4; X2 is N or CR5; X3 is N or CH; with the proviso that at least one of X1 and X3 is N.

Mechanistic Insight into the Catalytic Promiscuity of Amine Dehydrogenases: Asymmetric Synthesis of Secondary and Primary Amines

Biocatalytic asymmetric amination of ketones, by using amine dehydrogenases (AmDHs) or transaminases, is an efficient method for the synthesis of α-chiral primary amines. A major challenge is to extend amination to the synthesis of secondary and tertiary amines. Herein, for the first time, it is shown that AmDHs are capable of accepting other amine donors, thus giving access to enantioenriched secondary amines with conversions up to 43 %. Surprisingly, in several cases, the promiscuous formation of enantiopure primary amines, along with the expected secondary amines, was observed. By conducting practical laboratory experiments and computational experiments, it is proposed that the promiscuous formation of primary amines along with secondary amines is due to an unprecedented nicotinamide (NAD)-dependent formal transamination catalysed by AmDHs. In nature, this type of mechanism is commonly performed by pyridoxal 5′-phosphate aminotransferase and not by dehydrogenases. Finally, a catalytic pathway that rationalises the promiscuous NAD-dependent formal transamination activity and explains the formation of the observed mixture of products is proposed. This work increases the understanding of the catalytic mechanism of NAD-dependent aminating enzymes, such as AmDHs, and will aid further research into the rational engineering of oxidoreductases for the synthesis of α-chiral secondary and tertiary amines.

Catalyst-Free Reductive Coupling of Aromatic and Aliphatic Nitro Compounds with Organohalides

A rare reductive coupling of nitro compounds with organohalides has been realized. The reaction is initiated by a partial reduction of the nitro group to a nitrenoid intermediate. Therefore, not only aromatic but also aliphatic nitro compounds are efficiently transformed into monoalkylated amines, with organohalides as the alkylating agent. Given the innate reactivity of the nitrenoid, a catalyst is not required, resulting in a high tolerance for aryl halide substituents in both starting materials.

Direct Reductive N-Functionalization of Aliphatic Nitro Compounds

The first general protocol for the direct reductive N-functionalization of aliphatic nitro compounds is presented. The nitro group is partially reduced to a nitrenoid, with a mild and readily available combination of B2pin2 and zinc organyls. Thereby, the formation of an unstable nitroso intermediate is avoided, which has so far severely limited reductive transformations of aliphatic nitro compounds. The reaction is concluded by an electrophilic amination of zinc organyls.

O2-Mediated Oxidation of Aminoboranes through 1,2-N Migration

In analogy to the classical reaction of C?B bonds with peroxides, the first oxidative functionalization of aminoboranes through a 1,2-N migration was realized. Readily available aliphatic nitro compounds are thereby transformed into N- and O-functionalized hydroxylamines in a single synthetic operation. Addition of hazardous peroxides is avoided. Instead, the insertion of O2, as the terminal oxidant, into Zn?C bonds provides the necessary peroxides. The required zinc organyls, in turn, are formed through a boron-to-zinc exchange, from an organoboronic ester byproduct of the nitro-to-aminoborane transformation.

Ruthenium-catalyzed N-alkylation of amines with alcohols under mild conditions using the borrowing hydrogen methodology

Using a simple amino amide ligand, ruthenium-catalyzed one-pot alkylation of primary and secondary amines with simple alcohols was carried out under a wide range of conditions. Using the alcohol as solvent, alkylation was achieved under mild conditions, even as low as room temperature. Reactions occurred with high conversion and selectivity in many cases. Reactions can also be carried out at high temperatures in organic solvent with high selectivity using stoichiometric amounts of the alcohol.

Selective N-alkylation of amines using nitriles under hydrogenation conditions: Facile synthesis of secondary and tertiary amines

Nitriles were found to be highly effective alkylating reagents for the selective N-alkylation of amines under catalytic hydrogenation conditions. For the aromatic primary amines, the corresponding secondary amines were selectively obtained under Pd/C-catalyzed hydrogenation conditions. Although the use of electron poor aromatic amines or bulky nitriles showed a lower reactivity toward the reductive alkylation, the addition of NH4OAc enhanced the reactivity to give secondary aromatic amines in good to excellent yields. Under the same reaction conditions, aromatic nitro compounds instead of the aromatic primary amines could be directly transformed into secondary amines via a domino reaction involving the one-pot hydrogenation of the nitro group and the reductive alkylation of the amines. While aliphatic amines were effectively converted to the corresponding tertiary amines under Pd/C-catalyzed conditions, Rh/C was a highly effective catalyst for the N-monoalkylation of aliphatic primary amines without over-alkylation to the tertiary amines. Furthermore, the combination of the Rh/C-catalyzed N-monoalkylation of the aliphatic primary amines and additional Pd/C-catalyzed alkylation of the resulting secondary aliphatic amines could selectively prepare aliphatic tertiary amines possessing three different alkyl groups. According to the mechanistic studies, it seems reasonable to conclude that nitriles were reduced to aldimines before the nucleophilic attack of the amine during the first step of the reaction.

Monoalkylation of primary amines and N-sulfinylamides

An efficient monoalkylation of primary amines with primary or secondary alcohols catalyzed by Ra-Ni under mild conditions is described. The Royal Society of Chemistry.