190001-40-2

Usage

InChI:InChI=1/C11H19ClN2O3/c1-11(2,3)17-10(16)14-6-4-13(5-7-14)9(15)8-12/h4-8H2,1-3H3

Upstream product

• 79-04-9 chloroacetyl chloride 
• 57260-71-6 1-t-Butoxycarbonylpiperazine 
• 861359-74-2 diisopropylethyl amine 
• 24424-99-5 di-tert-butyl dicarbonate 

Downstream Products

• 930774-56-4 4-{[2-(3-ethoxycarbonylmethoxy-4-methoxy-phenyl)-5-hydroxy-4-oxo-4H-chromen-7-yloxy]-acetyl}-piperazine-1-carboxylic acid tert-butyl ester 
• 1010925-33-3 tert-butyl 4-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-acetyl]-piperazine-1-carboxylate 
• 1380297-11-9 benzyl 4-(2-(3-oxobenzo[d]isothiazol-2(3H)-yl)acetyl)piperazine-1-carboxylate 
• 1380297-12-0 4-nitrophenyl 4-(2-(3-oxobenzo[d]isothiazol-2(3H)-yl)acetyl)piperazine-1-carboxylate 
• 1190643-95-8 2-{1-[1-(4-chloro-phenyl)-cyclobutyl]-3,4-dihydro-isoquinolin-7-yloxy}-1-piperazin-1-yl-ethanone 

Relevant academic research and scientific papers

Parallel synthesis of isatin-based serine protease inhibitors

The synthesis of N-functionalised isatins using parallel, solution synthesis is described. Functionalised polymers were employed as stoichiometric and catalytic reagents as well as purification media in the exercise, and the derivatives were screened against a panel of serine proteases; high percentage inhibition was observed in several cases. (C) 2000 Elsevier Science Ltd.

Synthesis and antitumor activities of piperazine- and cyclen-conjugated dehydroabietylamine derivatives

A series of piperazine- and cyclen-conjugated dehydroabietylamine derivatives were synthesized and characterized by 1H NMR, 13C NMR, and HRMS. The in vitro antitumor activities of conjugates 10-13 against MCF-7 and HepG-2 tumor cell

Indoles and 1-(3-(benzyloxy)benzyl)piperazines: Reversible and selective monoamine oxidase B inhibitors identified by screening an in-house compound library

The therapeutic indications for monoamine oxidases A and B (MAO-A and MAO-B) inhibitors that have emerged from biological studies on animal and cellular models of neurological and oncological diseases have focused drug discovery projects upon identifying

Discovery of GPR183 Agonists Based on an Antagonist Scaffold

The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR

Design, synthesis, and in vivo and in silico evaluation of coumarin derivatives with potential antidepressant effects

In this study, a series of coumarin derivatives were designed and synthesized, their structures were characterized using nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) testing methods. In the pharmacological experiment, two behavior-monitoring methods, the forced swim test (FST) and the tail suspension test (TST), were used to determine the antidepressant activity of coumarin derivatives. Compounds that showed potential activity were analyzed for their effects on 5-hydroxytryptamine (5-HT) levels in the brains of mice. Molecular docking experiments to simulate the possible interaction of these compounds with the 5-HT1A receptor was also be predicted. The results of the pharmacological experiments showed that most coumarin derivatives exhibited significant antidepressant activity. Among these compounds, 7-(2-(4-(4-fluorobenzyl)piperazin-1-yl)-2-oxoethoxy)-2H-chromen-2-one (6i) showed the highest antidepressant activity. The results of the measurement of 5-HT levels in the brains of mice indicate that the antidepressant activity of coumarin derivatives may be mediated by elevated 5-HT levels. The results of molecular docking demonstrated that compound 6i had a significant interaction with amino acids around the active site of the 5-HT1A receptor in the homology model. The physicochemical and pharmacokinetic properties of the target compounds were also predicted using Discovery Studio (DS) 2020 and Chemdraw 14.0.

NEW COMPOUNDS FOR TREATMENT OF DISEASES RELATED TO DUX4 EXPRESSION

The present invention relates to compounds for the treatment of diseases related to DUX4 expression, such as muscular dystrophies. It also relates to use of such compounds, or to methods of use of such compounds.

Imaging Autotaxin in Vivo with 18F-Labeled Positron Emission Tomography Ligands

Autotaxin (ATX) is a secreted phosphodiesterase that has been implicated in a remarkably wide array of pathologies, especially in fibrosis and cancer. While ATX inhibitors have entered the clinical arena, a validated probe for positron emission tomography (PET) is currently lacking. With the aim to develop a suitable ATX-targeted PET radioligand, we have synthesized a focused library of fluorinated imidazo[1,2-a]pyridine derivatives, determined their inhibition constants, and confirmed their binding mode by crystallographic analysis. Based on their promising in vitro properties, compounds 9c, 9f, 9h, and 9j were radiofluorinated. Also, a deuterated analog of [18F]9j, designated as [18F]ATX-1905 ([18F]20), was designed and proved to be highly stable against in vivo radiodefluorination compared with [18F]9c, [18F]9f, [18F]9h, and [18F]9j. These results along with in vitro and in vivo studies toward ATX in a mouse model of LPS-induced liver injury suggest that [18F]ATX-1905 is a suitable PET probe for the non-invasive quantification of ATX.

TREATMENT OF HEMATOLOGICAL MALIGNANCIES WITH INHIBITORS OF MENIN

The present disclosure provides methods for treating hematological malignancies using menin inhibitors. Compositions for use in these methods are also provided.

Design and synthesis of tetrahydropyridopyrimidine derivatives as dual GPR119 and DPP-4 modulators

Based on the approach of merged pharmacophores of GPR119 agonists and DPP-4 inhibitors, a series of tetrahydropyridopyrimidine compounds were designed as dual GPR119 and DPP-4 modulators with hypoglycemic activity. Seven fragments extracted from DPP-4 inhibitors were hybridized with the scaffold of tetrahydropyridopyrimidine. Among them, compound 51 displayed most potent GPR119 agonistic activity (EC50 = 8.7 nM) and good inhibition rate of 74.5% against DPP-4 at 10 μM. Furthermore, the blood glucose AUC0-2h of 51 was reduced to 19.5% in the oral glucose tolerance test (oGTT) at the dose of 30 mg/kg in C57BL/6N mice, which was more potent than that of vildagliptin (16.4%) at the same dose. The docking study of compound 51 with DPP-4 indicated GPR119 agonists could inhibit DPP-4 to serve as dual GPR119 and DPP-4 modulators.

Usnic Acid Enaminone-Coupled 1,2,3-Triazoles as Antibacterial and Antitubercular Agents

(+)-Usnic acid, a product of secondary metabolism in lichens, has displayed a broad range of biological properties such as antitumor, antimicrobial, antiviral, anti-inflammatory, and insecticidal activities. Interested by these pharmacological activities and to tap into its potential, we herein present the synthesis and biological evaluation of new usnic acid enaminone-conjugated 1,2,3-triazoles 10-44 as antimycobacterial agents. (+)-Usnic acid was condensed with propargyl amine to give usnic acid enaminone 8 with a terminal ethynyl moiety. It was further reacted with various azides A1-A35 under copper catalysis to give triazoles 10-44 in good yields. Among the synthesized compounds, saccharin derivative 36 proved to be the most active analogue, inhibiting Mycobacterium tuberculosis (Mtb) at an MIC value of 2.5 μM. Analogues 16 and 27, with 3,4-difluorophenacyl and 2-acylnaphthalene units, respectively, inhibited Mtb at MIC values of 5.4 and 5.3 μM, respectively. Among the tested Gram-positive and Gram-negative bacteria, the new derivatives were active on Bacillus subtilis, with compounds 18 [3-(trifluoromethyl)phenacyl] and 29 (N-acylmorpholinyl) showing inhibitory concentrations of 41 and 90.7 μM, respectively, while they were inactive on the other tested bacterial strains. Overall, the study presented here is useful for converting natural (+)-usnic acid into antitubercular and antibacterial agents via incorporation of enaminone and 1,2,3-triazole functionalities.