6425-46-3

Usage

Chemical Properties

yellow-orange to orange crystalline powder

InChI:InChI=1/C11H14N2O3/c14-13(15)11-3-1-10(2-4-11)9-12-5-7-16-8-6-12/h1-4H,5-9H2

Upstream product

• 110-91-8 morpholine 
• 100-14-1 4-nitrobenzyl chloride 
• 4394-85-8 4-morpholinecarboxaldehyde 
• 109-02-4 4-methyl-morpholine 
• 586-78-7 para-nitrophenyl bromide 
• 100-00-5 4-chlorobenzonitrile 
• 555-16-8 4-nitrobenzaldehdye 
• 670-80-4 4-cyclohexen-1-ylmorpholine 
• 100-11-8 1-bromomethyl-4-nitro-benzene 
• 3145-86-6 4-nitrobenzyl iodide 
• 619-73-8 4-nitrobenzyl chloride 
• 99-99-0 1-methyl-4-nitrobenzene 
• 500-11-8 4-nitrobenzyl fluoride 
• 1233656-34-2 C₁₆H₁₈NO₆P 

Downstream Products

• 51013-67-3 4-morpholinomethyl aniline 
• 95539-61-0 1-amino-2-(N-morpholinomethyl)benzene 
• 100061-08-3 4-(p-nitrobenzyl)morpholin-3-one 

Relevant academic research and scientific papers

Discovery of novel 2,4‐dianilinopyrimidine derivatives containing 4‐(Morpholinomethyl)phenyl and n‐substituted benzamides as potential fak inhibitors and anticancer agents

Focal adhesion kinase (FAK) is responsible for the development and progression of various malignancies. With the aim to explore novel FAK inhibitors as anticancer agents, a series of 2,4‐ dianilinopyrimidine derivatives 8a–8i and 9a–9g containing 4‐(morpholinomethyl)phenyl and N‐ substituted benzamides have been designed and synthesized. Among them, compound 8a dis-played potent anti‐FAK activity (IC50 = 0.047 ± 0.006 μM) and selective antiproliferative effects against H1975 (IC50 = 0.044 ± 0.011 μM) and A431 cells (IC50 = 0.119 ± 0.036 μM). Furthermore, compound 8a also induced apoptosis in a dose‐dependent manner, arresting the cells in S/G2 phase and inhibiting the migration of H1975 cells, all of which were superior to those of TAE226. The docking analysis of compound 8a was performed to elucidate its possible binding modes with FAK. These results established 8a as our lead compound to be further investigated as a potential FAK inhibitor and anticancer agent.

PYRIMIDINE COMPOUND, PREPARATION METHOD THEREOF AND MEDICAL USE THEREOF

The present invention discloses a pyrimidine compound, a preparation method thereof and a medical use thereof. Specifically, the present invention discloses a pyrimidine compound represented by formula (I), pharmaceutically acceptable salts thereof, a preparation method thereof, and a use thereof as a cyclin-dependent kinase 9 (CDK9) inhibitor, particularly for the treatment of cancer. The definition of each group in formula (I) is the same as that in the specification.

Thiourea-Catalyzed C?F Bond Activation: Amination of Benzylic Fluorides

We describe the first thiourea-catalyzed C?F bond activation. The use of a thiourea catalyst and Ti(OiPr)4 as a fluoride scavenger allows the amination of benzylic fluorides to proceed in moderate to excellent yields. Preliminary results with S- and O-based nucleophiles are also presented. DFT calculations reveal the importance of hydrogen bonds between the catalyst and the fluorine atom of the substrate to lower the activation energy during the transition state.

Synthesis and biological activity of thieno[3,2-d]pyrimidines as potent JAK3 inhibitors for the treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a serious and fatal lung disease, with a median survival of only 3–5 years from diagnosis. Janus kinase 3 (JAK3) has a well-established role in the pathogenesis of various autoimmune diseases, including rheumatoid arthritis (RA) and autoimmune-related pulmonary fibrosis. In this study, through the use of a conformationally-constrained design strategy, a series of thieno[3,2-d]pyrimidines were synthesized as potent JAK3 inhibitors for the treatment of IPF. Among them, the most potent JAK3 inhibitor, namely 8e (IC50 = 1.38 nM), significantly reduced the degree of airsacculitis and fibrosis according to hematoxylin-eosin (HE) staining assay for the lung tissue in the bleomycin (BLM)-induced pulmonary fibrosis mouse model. The clear reduction of the lung collagen deposition by the determination of Masson and hydroxyproline (HYP) content also demonstrated its efficacy in the treatment of fibrosis. In addition, 8e also reduced the expression of the inflammatory markers IL-6, IL-17A, TNF-α and malondialdehyde (MDA) in lung tissue, which indicated its higher anti-inflammatory activity compared with that of the reference agents (nintedanib and gefitinib). Furthermore, it possessed low cytotoxicity against normal human bronchial epithelia (HBE) cells (IC50 > 39.0 μM) and C57BL mice. All these evaluated biological properties suggest that 8e may be a potential JAK3 inhibitor for the treatment of IPF.

Exploiting the Tolerant Region i of the Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Binding Pocket: Discovery of Potent Diarylpyrimidine-Typed HIV-1 NNRTIs against Wild-Type and E138K Mutant Virus with Significantly Improved Water Solubility an

Diarylpyrimidine derivatives (DAPYs) exhibit robust anti-HIV-1 potency, although they have been compromised by E138K variant and severe side-effects and been suffering from poor water solubility. In the present work, hydrophilic morpholine or methylsulfon

4-(saturated aliphatic ring-pyrimidine/pyridine substituted)amino-1H-3-pyrazol carboxamide FMS-like tyrosine kinase 3 (FLT3) inhibitor and application thereof

The invention relates to 4-(saturated aliphatic ring-pyrimidine/pyridine substituted)amino-1H-3-pyrazol carboxamide FMS-like tyrosine kinase 3 (FLT3) inhibitor, an application thereof, or pharmaceutically acceptable salt, solvate, isomer, ester, acid, met

HISTONE METHYLTRANSFERASE EZH2 INHIBITOR, PREPARATION METHOD AND PHARMACEUTICAL USE THEREOF

The invention relates to a histone methyltransferase EZH2 inhibitor, a preparation method and pharmaceutical use thereof. In particular, the invention relates to a compound represented by the general formula (I), a preparation method thereof, a pharmaceut

Discovery of 4-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazole-3-carboxamide (FN-1501), an FLT3- and CDK-Kinase Inhibitor with Potentially High Efficiency against Acute Myelocytic Leukemia

A series of 1-H-pyrazole-3-carboxamide derivatives have been designed and synthesized that exhibit excellent FLT3 and CDK inhibition and antiproliferative activities. A structure-activity-relationship study illustrates that the incorporation of a pyrimidine-fused heterocycle at position 4 of the pyrazole is critical for FLT3 and CDK inhibition. Compound 50 (FN-1501), which possesses potent inhibitory activities against FLT3, CDK2, CDK4, and CDK6 with IC50 values in the nanomolar range, shows antiproliferative activities against MV4-11 cells (IC50: 0.008 μM), which correlates with the suppression of retinoblastoma phosphorylation, FLT3, ERK, AKT, and STAT5 and the onset of apoptosis. Acute-toxicity studies in mice show that compound 50 (LD50: 186 mg/kg) is safer than AT7519 (32 mg/kg). In MV4-11 xenografts in a nude-mouse model, compound 50 can induce tumor regression at the dose of 15 mg/kg, which is more efficient than cytarabine (50 mg/kg). Taken together, these results demonstrate the potential of this unique compound for further development into a drug applied in acute-myeloid-leukemia (AML) therapeutics.

Discovery of the selective and efficacious inhibitors of FLT3 mutations

Fms-like tyrosine kinase 3 (FLT3) is among the most frequently mutated protein in acute myeloid leukemia (AML), which has been confirmed as an important drug target for AML chemotherapy. Starting from the lead compound LT-106-175, a series of 1-H-pyrazole-3-carboxamide derivatives were synthesized to improve the FLT3 inhibitory potency and selectivity. Among them, compound 50 was identified as a highly potent and selective FLT3 inhibitor (IC50 = 0.213 nM), which showed equal activities against various mutants of FLT3 including FLT3 (ITD)-D835V and FLT3 (ITD)-F691L that is resistant to quizartinib. Compound 50 also exhibited efficacy against the human AML cell line MV4-11 (IC50 = 16.1 nM) harboring FLT3-ITD mutants. Inversely, compound 50 displayed no cytotoxicity to FLT3-independent cells, and the biochemical analyses showed that its effects were related to the inhibition of FLT3 signal pathways. Additionally, compound 50 induced apoptosis in MV4-11 cell as demonstrated by flow cytometry. Moreover, compound 50 showed enhanced metabolic stability. Altogether, it was concluded that compound 50 could be a promising FLT3 inhibitor for further developing therapeutic remedy of AML.

Synthesis, β-hematin inhibition studies and antimalarial evaluation of new dehydroxy isoquine derivatives against Plasmodium berghei: A promising antimalarial agent

Many people are affected by Malaria around the world, and the parasite is developing resistance against available drugs. Currently, isoquine and N-tert-butyl isoquine are some of the most promising antimalarial candidates that have already reached Phase I