125775-23-7

Upstream product

• 18370-81-5 (3-bromopropyl)amine 
• 122-01-0 4-chloro-benzoyl chloride 
• 74-11-3 para-chlorobenzoic acid 
• 5003-71-4 3-bromopropylamine hydrochloride 

Downstream Products

• 80254-31-5 2-(4-chlorophenyl)-5,6-dihydro-4H-1,3-oxazine 
• 134221-77-5 4-Chloro-N-(3-methylamino-propyl)-N-phenyl-benzamide 
• 134221-68-4 2-(4-Chloro-phenyl)-1-methyl-3-phenyl-3,4,5,6-tetrahydro-pyrimidin-1-ium; iodide 
• 52289-27-7 2-(p-chlorophenyl)-1-phenyl-1,4,5,6-tetrahydropyrimidine 
• 134221-85-5 4-Chloro-N-methyl-N-(3-phenylamino-propyl)-benzamide 
• 134221-62-8 N-(p-chlorobenzoyl)-N'-phenyltrimethylenediamine 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of lazabemide derivatives as inhibitors of monoamine oxidase

In the studied a series novel of lazabemide derivatives were designed, synthesized and evaluated as inhibitors of monoamine oxidase (MAO-A or MAO-B). These compounds used lazabemide as the lead compound, and the chemistry structures were modified by used the bioisostere and modification of compound with alkyl principle. The two types of inhibitors (inhibition of MAO-A and inhibition of MAO-B) were screened by inhibition activity of MAO. In vitro experiments showed that compounds 3a, 3d and 3f had intensity inhibition the biological activity of MAO-A, while compounds 3i and 3m had intensity inhibition the biological activity of MAO-B. It could be seen from the data of inhibition activity experiments in vitro, that the compound 3d was IC50 = 3.12 ± 0.05 μmol/mL of MAO-A and compound 3m was IC50 = 5.04 ± 0.06 μmol/mL. In vivo inhibition activity experiments were conducted to evaluate the inhibitory activity of compounds 3a, 3d, 3f, 3i and 3m by detecting the contents of 5-HT, NE, DA and activity of MAO-A and MAO-B in plasma and brain tissue. In vivo inhibition activity evaluation results showed that the compounds 3a, 3d, 3f, 3i and 3m had increased the contents of 5-HT, NE and DA in plasma and brain tissues. Meanwhile, the determination results activity of MAO in plasma and brain tissue showed that the compounds 3a, 3d, and 3f had a significant inhibitory effect on the activity of MAO-A, while the compounds 3i and 3m showed inhibitory effect on the activity of MAO-B. This study provided a new inhibitors for inhibiting of MAO activity.

In silico identification, design and synthesis of novel piperazine-based antiviral agents targeting the hepatitis C virus helicase

A structure-based virtual screening of commercial compounds was carried out on the HCV NS3 helicase structure, with the aim to identify novel inhibitors of HCV replication. Among a selection of 13 commercial structures, one compound was found to inhibit the subgenomic HCV replicon in the low micromolar range. Different series of new piperazine-based analogues were designed and synthesised, and among them, several novel structures exhibited antiviral activity in the HCV replicon assay. Some of the new compounds were also found to inhibit HCV NS3 helicase function in?vitro, and one directly bound NS3 with a dissociation constant of 570?±?270?nM.

Synthesis and pharmacological evaluation of benzamide derivatives as potent and selective sigma-1 protein ligands

A series of novel benzamide-derived compounds was designed, synthesized and pharmacologically evaluated. Among all 37 synthesized compounds, two series were developed with the modulation of the nature, the position of atoms or groups on the benzamide scaffold, but also the nature of the amine group separated from the benzamide with 2, 3 or 4 methylene groups. In vitro competition binding assays against sigma proteins (sigma-1 S1R and sigma-2 S2R) revealed that most of them conferred S2R/S1R selectivity toward without cytotoxic effects on SY5Y cells, especially with the first series with compounds 7a-z. Some selected compounds were also evaluated for their agonist and antagonist activities on a panel of 40 receptors. Results showed the importance of the nature and the position with halogeno atom on the benzamide scaffold, the length chain but also the contribution of the hydrophobic part on the amine group. Among them, compounds 7i, w, y with Cl, CN or NO2 groups at the 4-position of the benzamide scaffold showed excellent affinity for S1R (Ki = 1.2–3.6 nM), selectivity for S2R (Ki up to 1400 nM) and high selectivity index (IC50(SY5Y)/Ki (S1R) ratio from 28 000 to 83 000). Futhermore, these compounds presented an excellent safety profile over 40 other receptors. These derivatives will be selected for further biological investigations.

COMPOUNDS, PHARMACEUTICAL COMPOSITION AND THEIR USE IN TREATING NEURODEGENERATIVE DISEASES

The present invention is directed to novel compounds of Formula (I), pharmaceutically acceptable salts or solvates thereof, and their use.

Synthesis and Hydrolysis of Substituted Tetrahydropyrimidinium Salts. Behaviour of the Degradation Products on Varying pH.

Reaction of 1,2-diaryl-3-methyl-1,4,5,6-tetrahydropyrimidinium iodides 1a-i with alkaline solutions afforded N-aroyl-N-aryl-N'-methyltrimethylenediamines 2a-i.Compounds 2 are stable under acid conditions but in neutral or alkaline media spontaneously rearrange giving N-aroyl-N'-aryl-N-methyltrimethylenediamines 3a-i.Treating compound 3 with concentrated acids reverse reaction takes place. Kinetic studies were performed on this intramolecular N->N' aroyl transfer over the H0-pH range -0.9 to 2.30.Compounds 3 undergo acyl transfer to give 2 by a mechanism which involves a change in the rate determining step from formation to acid-c atalysed decomposition of a six-membered heterocyclic intermediate on going from H0 to pH values.The existence of maxima in the pH rate profile allow to determine apparent pKa values of the hexahydropyrimidine intermediates which gave good correlation with the Swain F substituent constants.Stability of these heterocycles was also predicted by determination of thermodynamic parameters.Comparisons are made with the behaviour of five-membered heterocyclic intermediates (imidazolidine derivatives) which were studied in an earlier paper.