491855-89-1

Usage

Uses

Used in Pharmaceutical Industry:
4-(6-Nitro-3-pyridyl)Morpholine is used as a key intermediate in the synthesis of anti-cancer drugs, contributing to the development of novel therapeutic agents that target various types of cancer. Its chemical structure allows for the formation of new compounds with potential anti-tumor activity, enhancing the arsenal of treatments available for cancer patients.
Used in Agrochemical Industry:
In the agrochemical sector, 4-(6-Nitro-3-pyridyl)Morpholine serves as a precursor in the production of pesticides, specifically those designed to combat pests and diseases affecting crops. Its role in the synthesis of these agrochemicals helps to improve agricultural productivity and protect crops from harmful organisms.
It is crucial to handle 4-(6-Nitro-3-pyridyl)Morpholine with care, adhering to safety guidelines to mitigate potential health and environmental hazards associated with its use. Proper management and disposal of this chemical are essential to ensure the safety of both individuals and the environment.

Upstream product

• 110-91-8 morpholine 
• 779345-37-8 5-fluoro-2-nitro-pyridine 
• 39856-50-3 5-bromo2-nitropyridine 
• 311-28-4 tetra-(n-butyl)ammonium iodide 

Downstream Products

• 571189-78-1 5-morpholinopyridin-2-amine 

Relevant academic research and scientific papers

Antimalarial Lead-Optimization Studies on a 2,6-Imidazopyridine Series within a Constrained Chemical Space to Circumvent Atypical Dose-Response Curves against Multidrug Resistant Parasite Strains

A lead-optimization program around a 2,6-imidazopyridine scaffold was initiated based on the two early lead compounds, 1 and 2, that were shown to be efficacious in an in vivo humanized Plasmodium falciparum NODscidIL2Rγnull mouse malaria infection model. The observation of atypical dose-response curves when some compounds were tested against multidrug resistant malaria parasite strains guided the optimization process to define a chemical space that led to typical sigmoidal dose-response and complete kill of multidrug resistant parasites. After a structure and property analysis identified such a chemical space, compounds were prepared that displayed suitable activity, ADME, and safety profiles with respect to cytotoxicity and hERG inhibition.

DERIVATIVES OF 4-(IMIDAZO[L,2-A]PYRIDIN-3-YL)-N-(PYRIDINYL)PYRIMIDIN- 2-AMINE AS THERAPEUTIC AGENTS

A novel class of heteroaryl compounds for use in the prevention and/or treatment of proliferative diseases and conditions including cancers. The compounds are considered to be capable of inhibiting cell proliferation by inhibiting the activity of FLT3 and its mutant forms and/or other protein kinases such as CDKs. The compounds have the general structure I:

ARYL AND HETEROARYL-CARBOXAMIDE SUBSTITUTED HETEROARYL COMPOUNDS AS TYK2 INHIBITORS

Novel carboxamide substituted compounds of Formula (I) are disclosed; as well as processes for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Tyrosine Kinase 2 (Tyk2).

Discovery and in Vivo Anti-inflammatory Activity Evaluation of a Novel Non-peptidyl Non-covalent Cathepsin C Inhibitor

Cathepsin C (Cat C) participates in inflammation and immune regulation by affecting the activation of neutrophil serine proteases (NSPs). Therefore, cathepsin C is an attractive target for treatment of NSP-related inflammatory diseases. Here, the complete discovery process of the first potent "non-peptidyl non-covalent cathepsin C inhibitor"was described with hit finding, structure optimization, and lead discovery. Starting with hit 14, structure-based optimization and structure-activity relationship study were comprehensively carried out, and lead compound 54 was discovered as a potent drug-like cathepsin C inhibitor both in vivo and in vitro. Also, compound 54 (with cathepsin C Enz IC50 = 57.4 nM) exhibited effective anti-inflammatory activity in an animal model of chronic obstructive pulmonary disease. These results confirmed that the non-peptidyl and non-covalent derivative could be used as an effective cathepsin C inhibitor and encouraged us to continue further drug discovery on the basis of this finding.

Discovery and SARs of 5-Chloro- N4-phenyl- N2-(pyridin-2-yl)pyrimidine-2,4-diamine Derivatives as Oral Available and Dual CDK 6 and 9 Inhibitors with Potent Antitumor Activity

Cyclin-dependent kinases (CDKs) are promising therapeutic targets for cancer therapy. Herein, we describe our efforts toward the discovery of a series of 5-chloro-N4-phenyl-N2-(pyridin-2-yl)pyrimidine-2,4-diamine derivatives as dual CDK6 and 9 inhibitors. Intensive structural modifications lead to the identification of compound 66 as the most active dual CDK6/9 inhibitor with balancing potency against these two targets and good selectivity over CDK2. Further biological studies revealed that compound 66 was directly bound to CDK6/9, resulting in suppression of their downstream signaling pathway and inhibition of cell proliferation by blocking cell cycle progression and inducing cellular apoptosis. More importantly, compound 66 significantly inhibited tumor growth in a xenograft mouse model with no obvious toxicity, indicating the promising therapeutic potential of CDK6/9 dual inhibitors for cancer treatment. Therefore, the above results are of great importance in the development of dual CDK6/9 inhibitors for cancer therapy.

Design, synthesis and biological evaluation of novel osthole-based derivatives as potential neuroprotective agents

A total of 26 compounds based on osthole skeleton were designed, synthesized. Their cytoprotective abilities of antioxidation, anti-inflammation and Aβ42(Amyloid β-protein 42)-induced neurotoxicity were evaluated by MTT assays. Mechanism of the action of selected compounds were investigated by molecular docking. AlogP, logS and blood–brain barrier (BBB) permeability of all these compounds were simulated by admetSAR. Most of the compounds showed better antioxidative and anti-inflammatory activities compared with osthole, especially OST7 and OST17. The compound OST7 showed relative high activity in neuroprotection against H2O2 (45.7 ± 5.5%), oxygen glucose deprivation (64.6 ± 4.8%) and Aβ42 (61.4 ± 5.2%) at a low concentration of 10 μM. EC50 of selected compounds were measured in both H2O2 and OGD induced cytotoxicity models. Moreover, NO inhibiting ability of OST17(50.4 ± 7.1%) already surpassed the positive drug indomethacin. The structure activity relationship study indicated that introduction of piperazine group, tetrahydropyrrole group and aromatic amine group might be beneficial for enhancement of osthole neuroprotective properties. Molecular docking explained that the reason OST7 exhibited relatively stronger neuroprotection against Aβ because of the greater area of interactions between molecule and target protein. OST7 and OST17 both provided novel methods to investigate osthole as anti-AD drugs.

UREA DERIVATIVES AS INHIBITORS OF ASK1

The present technology is directed to compounds, compositions, and methods related to inhibition of ASK1. In particular, the present compounds (e.g., compounds of Formula I as defined herein) and compositions may be used to treat ASK1-mediated disorders and conditions, including, e.g., fibrotic diseases and acute and chronic liver diseases, among others.

PYRIMIDINE-BASED COMPOUNDS FOR THE TREATMENT OF CANCER

This invention is in the area of pyrimidine-based compounds for the treatment of disorders involving abnormal cellular proliferation, including but not limited to tumors and cancers.

Synthesis and SAR of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as potent and selective CDK4/6 inhibitors

CDK4/6 pathway is an attractive target for development of anti-cancer drugs. Herein, we reported the design and synthesis of a series of 4,5-dihydro-1H-pyrazolo [4,3-h]quinazoline derivatives as selective CDK4/6 inhibitors. Applied with the optimizing strategy to the initial scaffold, it is found that compound 13n is able to selectively inhibit CDK4 and CDK6 with IC50 values 0.01 and 0.026 μM, respectively. The compound showed good anti-proliferative activity when tested in a panel of tumor cell lines with CDK4/6 related mechanism of action, the results clearly suggest that compound 13n works much better than Ly2385219 which is a selective CDK4/6 inhibitor. This compound was also found to have favorable pharmacokinetic parameters. Taken together, compound 13n could be selected for further preclinical evaluation.

Discovery and pharmacological characterization of a novel series of highly selective inhibitors of cyclin-dependent kinases 4 and 6 as anticancer agents

Background and Purpose: Cyclin D-dependent kinases 4 and 6 (CDK4/6) are crucial regulators of the G1 to S phase transition of the cell cycle and are actively pursued as therapeutic targets in cancer. We sought to discover a novel series of orally bioavailable and highly selective small molecule inhibitors of CDK4/6. Experimental Approach: The discovery of pharmacological inhibitors and optimization for potency, selectivity and drug properties were achieved by iterative chemical synthesis, biochemical screening against a panel of kinases, cell-based assays measuring cellular viability, cell cycle distribution, induction of apoptosis and the level of retinoblastoma tumour suppressor protein (Rb) phosphorylation and E2 factor (E2F)-regulated gene expression and in vitro biopharmaceutical and in vivo pharmacokinetic profiling. Key Results: We discovered several lead compounds that displayed >1000-fold selectivity for CDK4/6 over other members of the CDK family. The lead compounds, 82, 91 and 95, potently inhibited the growth of cancer cells by inducing G1 arrest with a concomitant reduction in the phosphorylation of Rb at S780 and in E2F-regulated gene expression. With a remarkable selectivity for CDK4 over 369 human protein kinases, 91 was identified as a highly potent and orally bioavailable drug candidate. Conclusions and Implications: We have identified unique and new inhibitors of CDK4/6 as potential drug candidates. Compound 91 represents an ideal candidate for further development as targeted cancer therapy.