24192-96-9

Usage

Uses

Used in Pharmaceutical Industry:
4-(4-chloropyrimidin-2-yl)morpholine is used as a potential therapeutic agent for neurodegenerative diseases such as Parkinson's and Alzheimer's. It is employed for its ability to inhibit the formation of toxic protein aggregates associated with these diseases, which is a key factor in their progression.
Used in Scientific Research:
In the field of scientific research, 4-(4-chloropyrimidin-2-yl)morpholine serves as a valuable compound for studying the mechanisms underlying neurodegenerative diseases. Its unique chemical structure and mechanism of action provide insights into potential therapeutic targets and strategies for the development of novel treatments.
Used in Drug Development:
4-(4-chloropyrimidin-2-yl)morpholine is utilized in drug development as a promising candidate for the creation of new medications aimed at treating neurodegenerative disorders. Its demonstrated neuroprotective effects and potential to slow down disease progression make it an attractive option for further research and clinical trials.

InChI:InChI=1/C8H10ClN3O/c9-7-1-2-10-8(11-7)12-3-5-13-6-4-12/h1-2H,3-6H2

Upstream product

• 110-91-8 morpholine 
• 3934-20-1 2,6-Dichloropyrimidine 

Downstream Products

• 1333108-41-0 1-cyclopropyl-3-(4-(2-morpholinopyrimidin-4-yl)phenyl)urea 
• 1446007-91-5 (S)-N-(1-{4-[3-(2-morpholin-4-yl-pyrimidine-4-yloxy)-azetidin-1-yl]-phenyl}-ethyl)-acetamide 

Relevant academic research and scientific papers

Triazine-pyrimidine based molecular hybrids: Synthesis, docking studies and evaluation of antimalarial activity

A series of novel triazine-pyrimidine hybrids have been synthesized and evaluated for their in vitro antimalarial activity. Some of the compounds showed promising antimalarial activity against both CQ-sensitive and CQ-resistant strains at micromolar level with a high selectivity index. All the compounds displayed better activity (IC50 = 1.32-10.70 μM) than the standard drug pyrimethamine (>19 μM) against the chloroquine-resistant strain W2. All the tested compounds were nontoxic against mammalian cell lines. Further, docking studies of the most active compounds were performed on both wild type and quadruple mutant (N51I, C59R, S108N, I164L) PfDHFR-TS using Glide to analyse the interaction of the compounds with the binding site of the protein. The binding poses of compounds 14 and 19, having a high Glide XP score and the lowest Glide energies, show an efficient binding pattern similar to that of the DHFR substrate (dihydrofolate) in the wild type and mutant DHFR active site. The analysis of the pharmacokinetic properties of the most active compounds using ADMET prediction attests to the possibility of developing compound 14 as a potent antimalarial lead. This journal is

An automated continuous-flow platform for the estimation of multistep reaction kinetics

Automated continuous flow systems coupled with online analysis and feedback have been previously demonstrated to model and optimize chemical syntheses with little a priori reaction information. However, these methods have yet to address the challenge of modeling and optimizing for product yield or selectivity in a multistep reaction network, where low selectivity toward desired product formation can be encountered. Here we demonstrate an automated system capable of rapidly estimating accurate kinetic parameters for a given reaction network using maximum likelihood estimation and a D-optimal design of experiments. The network studied is the series-parallel nucleophilic aromatic substitution of morpholine onto 2,4-dichloropyrimidine. To improve the precision of the estimated parameters, we demonstrate the use of the automated platform first in optimization of the yield of the less kinetically favorable 2-substituted product. Then, upon isolation of the intermediates, we use the automated system with maximum a posteriori estimation to minimize uncertainties in the network parameters. From considering the steps of the reaction network in isolation, the kinetic parameter uncertainties are reduced by 50%, with less than 5 g of the dichloropyrimidine substrate consumed over all experiments. We conclude that isolating pathways in the multistep reaction network is important to minimizing uncertainty for low sensitivity rate parameters.

Quinoline-pyrimidine hybrids: Synthesis, antiplasmodial activity, SAR, and mode of action studies

For the treatment of malaria which affects nearly 200 million people each year and the continued exacerbation by the emergence of drug resistance to most of the available antimalarials, the "covalent bitherapy" suggests hybrid molecules to be the next-generation antimalarial drugs. In this investigation, new hybrids of 4-aminoquinoline and pyrimidine moieties that show antiplasmodial activity in the nM range against chloroquine-resistant as well as chloroquine-sensitive strains of Plasmodium falciparum have been prepared. Cytotoxicity evaluation and mode of action of most potent hybrid molecule have been conducted.

Optimization of physicochemical properties for 4-anilinoquinazoline inhibitors of trypanosome proliferation

Human African trypanosomiasis (HAT) is a deadly disease in need of new chemotherapeutics that can cross into the central nervous system. We previously reported the discovery of 2 (NEU-617), a small molecule with activity against T. brucei bloodstream prol

Discovery of 1-(3-aryl-4-chlorophenyl)-3-(p-aryl)urea derivatives against breast cancer by inhibiting PI3K/Akt/mTOR and Hedgehog signalings

PI3K/Akt/mTOR and hedgehog (Hh) signalings are two important pathways in breast cancer, which are usually connected with the drug resistance and cancer migration. Many studies indicated that PI3K/Akt/mTOR inhibitors and Hh inhibitors displayed synergistic effects, and the combination of the two signaling drugs could delay drug resistance and inhibit cancer migration in breast cancer. Therefore, the development of molecules simultaneously inhibiting these two pathways is urgent needed. Based on the structures of PI3K inhibitor buparlisib and Hh inhibitor vismodegib, a series of hybrid structures were designed and synthesized utilizing rational drug design and computer-based drug design. Several compounds displayed excellent antiproliferative activities against several breast cancer cell lines, including triple-negative breast cancer (TNBC) MDA-MB-231 cell. Further mechanistic studies demonstrated that the representative compound 9i could inhibit both PI3K/Akt/mTOR and hedgehog (Hh) signalings by inhibiting the phosphorylation of S6K and Akt as well as decreasing the SAG elevated expression of Gli1. Compound 9i could also induce apoptosis remarkably in T47D and MDA-MB-231 cells. In the transwell assay, 9i showed significant inhibition on the migration of MDA-MB-231.

Identification and optimisation of novel and selective small molecular weight kinase inhibitors of mTOR

A pharmacophore mapping approach, derived from previous experience of PIKK family enzymes, was used to identify a hit series of selective inhibitors of the mammalian target of rapamycin (mTOR). Subsequent refinement of the SAR around this hit series based