209960-91-8

Usage

Uses

Used in Pharmaceutical Industry:
Memantine is used as a therapeutic agent for the treatment of Alzheimer's disease and dementia. It functions by blocking the activity of N-methyl-D-aspartate (NMDA) receptors in the brain, which are involved in learning and memory processes. This action helps to mitigate the effects of excessive glutamate activity, a factor believed to contribute to the progression of Alzheimer's disease.
As an Alzheimer's Treatment:
Memantine is utilized as a neuroprotective agent to improve cognitive function and slow the progression of Alzheimer's disease in patients. It is available in various pharmaceutical forms, such as oral tablets, oral solutions, and extended-release capsules, and is administered under the guidance of healthcare professionals.
In managing side effects:
While Memantine can cause side effects like dizziness, headache, confusion, and constipation, its use is carefully directed by doctors to ensure patient safety and efficacy. The medication's dosing and administration are tailored to minimize these potential side effects while maximizing therapeutic benefits for patients with Alzheimer's disease and dementia.

Upstream product

• 448-19-1 4-fluoro-2-methoxy-1-nitrobenzene 
• 6627-53-8 1-chloro-3-methoxy-4-nitrobenzene 
• 175135-19-0 AMA₅₆ 
• 6950-88-5 4-(3-methoxy-4-nitro-phenyl)morpholine 

Downstream Products

• 442548-62-1 6-Methoxy-8-(4-methyl-piperazin-1-yl)-4-oxo-4H-chromene-2-carboxylic acid (2-methoxy-4-morpholin-4-yl-phenyl)-amide 
• 1061353-83-0 2-(2-(2-methoxy-4-morpholinophenylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N,N-dimethylbenzamide trifluoroacetate 
• 1061355-73-4 2-(5-cyano-2-(2-methoxy-4-morpholinophenylamino)pyridin-4-ylamino)-N-methylbenzamide trifluoroacetate 
• 1089279-86-6 Methyl 3-[3-(2-{[2-(methyloxy)-4-(4-morpholinyl)phenyl]amino}-4-pyrimidinyl)-imidazo[1,2-a]pyridin-2-yl]benzoate 
• 1042672-97-8 C₂₀H₂₀N₄O₃S 
• 1184931-49-4 4-iodo-5-methyl-N-[2-(methyloxy)-4-(4-morpholinyl)phenyl]-2-pyridinamine 
• 1184931-51-8 5-chloro-4-iodo-N-[2-(methyloxy)-4-(4-morpholinyl)phenyl]-2-pyridinamine 
• 1061353-68-1 2-(2-(2-methoxy-4-morpholinophenylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N-methylbenzamide 
• 1061355-87-0 2-[(5-bromo-2-{[2-(methyloxy)-4-(4-morpholinyl)phenyl]amino}-4-pyridinyl)amino]-N-methylbenzamide 
• 1184931-55-2 2-[(5-chloro-2-{[2-(methyloxy)-4-(4-morpholinyl)phenyl]amino}-4-pyridinyl)amino]benzoic acid 
• 1184931-44-9 2-[5-cyclopropyl-2-(2-methoxy-4-morpholin-4-yl-phenylamino)-pyridin-4-ylamino]-N-methoxy-benzamide 
• 1184931-46-1 2-[5-cyclopropyl-2-(2-methoxy-4-morpholin-4-yl-phenylamino)-pyridin-4-ylamino]-N-methyl-benzamide 
• 1184931-47-2 2-[2-(2-methoxy-4-morpholin-4-yl-phenylamino)-5-vinyl-pyridin-4-ylamino]-N-methyl-benzamide 
• 1097916-78-3 2-(4-(2-methoxy-4-morpholinophenylamino)-1,3,5-triazin-2-ylamino)-N-methylbenzamide 

Relevant academic research and scientific papers

Optimization of WZ4003 as NUAK inhibitors against human colorectal cancer

NUAK, the member of AMPK (AMP-activated protein kinase) family of protein kinases, is phosphorylated and activated by the LKB1 (liver kinase B1) tumor suppressor protein kinase. Recent work has indicated that NUAK1 is a key component of the antioxidant stress response pathway, and the inhibition of NUAK1 will suppress the growth and survival of colorectal tumors. As a promising target for anticancer drugs, few inhibitors of NUAK were developed. With this goal in mind, based on NUAK inhibitor WZ4003, a series of derivatives has been synthesized and evaluated for anticancer activity. Compound 9q, a derivative of WZ4003 by removing a methoxy group, was found to be the most potential one with stronger inhibitory against NUAK1/2 enzyme activity, tumor cell proliferation and inducing apoptosis of tumor cells. By in vivo efficacy evaluations of colorectal SW480 xenografts, 9q suppresses tumor growth more effectively with an excellent safety profile in vivo and is therefore seen as a suitable candidate for further investigation.

Discovery and structure ? activity relationship exploration of pyrazolo[1,5-a]pyrimidine derivatives as potent FLT3-ITD inhibitors

Internal tandem duplications of FLT3 (FLT3-ITD) occur in approximately 25% of all acute myeloid leukemia (AML) cases and confer a poor prognosis. Optimization of the screening hit 1 from our in-house compound library led to the discovery of a series of pyrazolo[1,5-a]pyrimidine derivatives as potent and selective FLT3-ITD inhibitors. Compounds 17 and 19 displayed potent FLT3-ITD activities both with IC50 values of 0.4 nM and excellent antiproliferative activities against AML cell lines. Especially, compounds 17 and 19 inhibited the quizartinib resistance- conferring mutations, FLT3D835Y, both with IC50 values of 0.3 nM. Moreover, western blot analysis indicated that compounds 17 and 19 potently inhibited the phosphorylation of FLT3 and attenuated downstream signaling in AML cells. These results indicated that pyrazolo[1,5-a]pyrimidine derivatives could be promising FLT3-ITD inhibitors for the treatment AML.

COMPOUNDS AND THEIR USES AS MIF INHIBITORS

The present invention provides compounds of Formula I which can be used as macrophage migration inhibitory factor (MIF) inhibitors; methods for the production of the compounds of the invention; pharmaceutical compositions comprising the compounds of the i

Design, synthesis and biological evaluation of novel pteridinone derivatives as potent dual inhibitors of PLK1 and BRD4

To develop novel simultaneous inhibition of PLK1 and BRD4 bromodomain by a single molecule, three series of novel pteridinone derivatives were designed, synthesized and evaluated for their biological activity. Most compounds exhibited moderate to excellent cytotoxic activity against A549, HCT116, PC-3 and MCF-7 cell lines. The most promising compound III4 showed high antiproliferative effects on four cell lines with IC50 values of 1.27 μM, 1.36 μM, 3.85 μM and 4.06 μM, respectively. The enzymatic assay identified III4 as a potent PLK1 and BRD4 dual inhibitor with % inhibition values of 96.6 and 59.1, respectively. Furthermore, to clarify the anticancer mechanism of the target compounds, explorations in the bioactivity were conducted. The results showed that compound III4 obviously inhibited the proliferation of HCT-116 cell lines, induced a great decrease in the mitochondrial membrane potential leading to apoptosis of cancer cells, suppressed the migration of tumor cells, and arrested the S phase of HCT116 cells.

A class of FLT3 kinase inhibitors, preparation and application thereof

The invention relates to a class of FLT3 kinase inhibitors, preparation and application thereof, wherein specifically the compound has a structure represented by a formula (I), and all groups and substituents are defined in the specification. The invention also discloses a preparation method of the compound, and application of the compound in inhibition of FLT3.

Aminopyrimidine compound and application thereof in anti-cancer drugs

The invention provides an aminopyrimidine compound and application thereof in anti-cancer drugs. The compound is of the structure shown in the general formula (I), wherein m is 0-4, and n is 0-4; R1 is selected from amino, an alkyl amino group, an amino alkyl group and an alkyl amino carbonyl group; R2 is selected from hydrogen, hydroxyl, nitro, halogen, amino, a cyano group, an alkyl group, an alkenyl group, a halogen alkyl group, a hetero alkyl group, an alkyl amino group, an amino alkyl group, an alkyl carbonyl group, an alkyl amino carbonyl group and a aryl carbonyl group; X is selected from an oxygen atom, an amino group or a methylamino group. The compound can be used for improving the inhibition rate of EGFRT790M and has higher anticancer activity.

NOVEL FUSED PYRIDINE DERIVATIVES USEFUL AS FAK/AURORA KINASE INHIBITORS

This invention relates to certain novel pyrimidine derivatives of the Formula (I). The invention also relates to process for the preparation of the compound of the formula (I), pharmaceutical agents or compositions containing the compound or a method of using the compound for the treatment of proliferative diseases, such as cancer.

PYRIMIDINE DERIVATIVE AND USE THEREOF

The present invention provides a pyrimidine derivative and a use thereof. The pyrimidine derivative is the compound shown in formula I or a pharmaceutically acceptable salt, hydrate, solvate, metabolite or prodrug thereof, wherein, R1, R2, R3, R4 and R5 are, for example, as defined in the specification. The compound can act as an ALK inhibitor, and is for preparing an anti-tumor medicament for suppressing an anaplastic lymphoma kinase.

2,4-dibasic miazines compound

The invention belongs to the field of medical chemistry, relates to a 2,4-dibasic miazines compound and specifically relates to a compound shown as formula (I) or a pharmaceutically acceptable salt thereof, a drug compound thereof and an application thereof in treating EGFR or/and ALK mediated diseases.

Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase

In the treatment of echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase positive (ALK+) non-small-cell lung cancer (NSCLC), secondary mutations within the ALK kinase domain have emerged as a major resistance mechanism to both first- and second-generation ALK inhibitors. This report describes the design and synthesis of a series of 2,4-diarylaminopyrimidine-based potent and selective ALK inhibitors culminating in identification of the investigational clinical candidate brigatinib. A unique structural feature of brigatinib is a phosphine oxide, an overlooked but novel hydrogen-bond acceptor that drives potency and selectivity in addition to favorable ADME properties. Brigatinib displayed low nanomolar IC50s against native ALK and all tested clinically relevant ALK mutants in both enzyme-based biochemical and cell-based viability assays and demonstrated efficacy in multiple ALK+ xenografts in mice, including Karpas-299 (anaplastic large-cell lymphomas [ALCL]) and H3122 (NSCLC). Brigatinib represents the most clinically advanced phosphine oxide-containing drug candidate to date and is currently being evaluated in a global phase 2 registration trial.