51207-86-4

Usage

Uses

Used in Pharmaceutical Industry:
(4-AMINO-PHENYL)-MORPHOLIN-4-YL-METHANONE is used as a key intermediate compound for the synthesis of tyrosine kinase inhibitors. These inhibitors play a crucial role in the development of targeted therapies for various types of cancer, as they can specifically block the activity of tyrosine kinase enzymes, which are often overactive in cancer cells, leading to uncontrolled cell growth and tumor formation.
Additionally, (4-AMINO-PHENYL)-MORPHOLIN-4-YL-METHANONE is used as a building block for the development of other biologically active agents. These agents may have potential applications in treating various diseases and conditions, including neurological disorders, inflammatory diseases, and cardiovascular diseases, by modulating specific biological targets and pathways involved in these conditions.

InChI:InChI=1/C11H14N2O2/c12-10-3-1-9(2-4-10)11(14)13-5-7-15-8-6-13/h1-4H,5-8,12H2

Upstream product

• 1090724-68-7 tert-butyl (4-(morpholine-4-carbonyl)phenyl)carbamate 
• 110-91-8 morpholine 
• 201230-82-2 carbon monoxide 
• 106-40-1 4-bromo-aniline 
• 15159-40-7 4-morpholinocarbonyl chloride 
• 540-37-4 p-aminoiodobenzene 
• 636-98-6 p-nitrobenzene iodide 
• 619-45-4 4-methoxycarbonyl aniline 
• 556-18-3 4-aminobenzaldehyde 
• 62-23-7 4-nitro-benzoic acid 
• 150-13-0 4-amino-benzoic acid 
• 122-04-3 4-nitro-benzoyl chloride 
• 5397-76-2 1-morpholin-4-yl-1-(4-nitro-phenyl)-methanone 

Downstream Products

• 72752-78-4 4-{4-[(4-oxo-4H-quinazolin-3-ylmethyl)-amino]-benzoyl}-morpholine 
• 72752-59-1 4-{4-[(2-oxo-benzooxazol-3-ylmethyl)-amino]-benzoyl}-morpholine 
• 72752-64-8 4-{4-[(2-thioxo-benzooxazol-3-ylmethyl)-amino]-benzoyl}-morpholine 
• 104183-62-2 5-(p-Fluorobenzylidene)-3--4-oxo-thiazolidine-2-thione 
• 104183-51-9 5-(p-Methoxybenzylidene)-3--4-oxo-thiazolidine-2-thione 
• 104183-55-3 5-(p-Dimethylaminobenzylidene)-3--4-oxo-thiazolidine-2-thione 
• 81820-29-3 3-[4-(Morpholine-4-carbonyl)-phenyl]-2-phenyl-5-[1-phenyl-meth-(Z)-ylidene]-3,5-dihydro-imidazol-4-one 
• 104183-66-6 5-(p-Nitrobenzylidene)-3--4-oxo-thiazolidine-2-thione 
• 81820-38-4 5-[1-(2-Methoxy-phenyl)-meth-(Z)-ylidene]-3-[4-(morpholine-4-carbonyl)-phenyl]-2-phenyl-3,5-dihydro-imidazol-4-one 
• 372095-27-7 N-[4-(Morpholin-4-ylcarbonyl)phenyl]-(2-chloro-5-nitrophenyl)carboxamide 
• 1206706-48-0 (4-(6-amino-3-(2-methyl-3-nitrophenyl)-1,2,4-triazin-5-ylamino)phenyl)(morpholino)methanone 
• 1232399-45-9 {4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-morpholin-4-yl-methanone 
• 1243268-20-3 cyclobutanecarboxylic acid (3-{2-[4-(morpholine-4-carbonyl)-phenylamino]-pyrrolo[2,3-d]pyrimidin-7-yl}-propyl)-amide 
• 1372892-89-1 C₂₁H₁₇ClN₂O₄ 

Relevant academic research and scientific papers

Structure-Based Optimization of Quinazolines as Cruzain and TbrCATL Inhibitors

The cysteine proteases, cruzain and TbrCATL (rhodesain), are therapeutic targets for Chagas disease and Human African Trypanosomiasis, respectively. Among the known inhibitors for these proteases, we have described N4-benzyl-N2-phenylquinazoline-2,4-diamine (compound 7 in the original publication, 1a in this study), as a competitive cruzain inhibitor (Ki = 1.4 μM). Here, we describe the synthesis and biological evaluation of 22 analogs of 1a, containing modifications in the quinazoline core, and in the substituents in positions 2 and 4 of this ring. The analogs demonstrate low micromolar inhibition of the target proteases and cidal activity against Trypanosoma cruzi with up to two log selectivity indices in counterscreens with myoblasts. Fourteen compounds were active against Trypanosoma brucei at low to mid micromolar concentrations. During the optimization of 1a, structure-based design and prediction of physicochemical properties were employed to maintain potency against the enzymes while removing colloidal aggregator characteristics observed for some molecules in this series.

Applicability of aluminum amalgam to the reduction of arylnitro groups

An array of arylnitro compounds with various functionality were treated with freshly-prepared aluminum amalgam in THF/water solution and resulted in the corresponding arylamines. The Al(Hg)-mediated reductions are relatively rapid with consumption of the amalgam and disappearance of starting material occurring over 20–30 min. The workup of the reductions involves only removal of the insoluble by-products by filtration followed by concentration. Only in some cases is chromatography required to secure the pure product. The desired arylamines are furnished in quantities of 25–100 mg, which in some cases, could be taken on to the next reaction without further purification. Reductions of 4-nitrobenzyl derivatives of carbohydrates or nucleosides were selective in affording the corresponding 4-aminobenzyl products. To show applicability in click chemistry, selected aminobenzyl products are directly azidated to yield products that were then used in click reactions to afford the corresponding 1,2,3-triazoles.

JAK3 inhibitors based on thieno[3,2-d]pyrimidine scaffold: design, synthesis and bioactivity evaluation for the treatment of B-cell lymphoma

JAK3 is predominantly expressed in hematopoietic cells and has been a promising therapeutic target for the treatment of B-cell lymphoma. In this study, a new class of thieno[3,2-d]pyrimidines harboring acrylamide pharmacophore were synthesized as potent covalent JAK3 inhibitors (IC50 50 values of 1.9 nM and 1.8 nM, respectively. Furthermore, compared with the reference agents, Spebrutinib and Ibrutinib, 9a not only demonstrated enhanced antiproliferative activity against B lymphoma cells, but also showed very weak proliferative inhibition against normal peripheral blood mononuclear cells (PBMCs) at a concentration of 20 μM. Analysis of the mechanism revealed that 9a could induce the obvious apoptosis in B lymphoma cells and prevent JAK3-STAT3 cascade as well as BTK pathway. Taken together, 9a may be served as a potential new JAK3 inhibitor for the treatment of B-cell lymphoma.

S-triazine compounds as well as preparation method and application thereof

The invention discloses s-triazine compounds and pharmaceutically acceptable salts thereof; experiments prove that the compounds can be used for treating or preventing diseases related to protein kinase activity, such as leukemia and lymphoma, by inhibiti

Palladium nanoparticles on a pyridinium supported ionic liquid phase: a recyclable and low-leaching palladium catalyst for aminocarbonylation reactions

A new SILP (Supported Ionic Liquid Phase) palladium catalyst was prepared and characterized by 13C and 29Si CP MAS NMR, DTG, FTIR and TEM. The presence of the grafted pyridinium cations on the surface of the support was found to result in the formation of highly dispersed Pd nanoparticles with their diameter in the range of 1-2 nm. The catalyst was proved to be active not only in the aminocarbonylation of some model compounds but also in the synthesis of active pharmaceutical ingredients. Catalyst recycling and palladium leaching studies were carried out for the first time in aminocarbonylations leading to CX-546(1-(1,4-benzodioxan-6-ylcarbonyl)piperidine), Moclobemide, Nikethamide and a precursor of Finasteride. The latter reaction proves that not only aryl iodides but also an iodoalkene can be converted into the products with the help of the heterogeneous catalyst. The results show that the conditions should be always fine-tuned in the reactions of different substrates to achieve optimal results. Palladium loss was also observed to depend considerably on the nature of the reaction partners. This journal is

Double carbonylation of iodoarenes in the presence of a pyridinium SILP-Pd catalyst

The efficiency of a palladium catalyst, immobilised on a supported ionic liquid phase (SILP) with adsorbed 1-butyl-4-methylpyridinium chloride, was investigated in aminocarbonylation reactions. Double carbonylation was found to be the main reaction using different iodoarenes and aliphatic amines as substrates. Application of aniline derivatives as nucleophiles led to the exclusive formation of substituted benzamides. The stabilisation effect of the adsorbed pyridinium ionic liquid was compared to that of imidazolium and phosphonium derivatives. It was proved that the pyridinium SILP-palladium catalyst could be reused in at least 10 cycles. Recyclability was tested in five successive runs for all of the substrates.

FUSED HETEROCYCLIC DERIVATIVES, THEIR PREPARATION METHODS THEREOF AND MEDICAL USES THEREOF

The present invention relates to fused heterocyclic derivatives, processes for their preparation and their use in medicine. Specifically, the present invention relates to a novel derivative represented by the formula (I′), or its pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the derivative or its pharmaceutically acceptable salt thereof, and the method for preparing the derivative and its pharmaceutically acceptable salt thereof. The present invention also relates to the use of the derivative and its pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing the derivative and its pharmaceutically acceptable salt thereof in the preparation of medicines, in particularly as IDO inhibitor medicines, for treating and/or preventing cancers. Wherein each substituent of the formula (I′) is the same as defined in the specification.

Coolade. A Low-Foaming Surfactant for Organic Synthesis in Water

Several types of reduction reactions in organic synthesis are performed under aqueous micellar-catalysis conditions (in water at ambient temperature), which produce a significant volume of foam owing to the combination of the surfactant and the presence of gas evolution. The newly engineered surfactant “Coolade” minimizes this important technical issue owing to its low-foaming properties. Coolade is the latest in a series of designer surfactants specifically tailored to enable organic synthesis in water. This study reports the synthesis of this new surfactant along with its applications to gas-involving reactions.

Design, synthesis and biological evaluation of novel 2-phenyl pyrimidine derivatives as potent Bruton's tyrosine kinase (BTK) inhibitors

BTK is an effective target for the treatment of B-cell malignant tumors and autoimmune diseases. In this work, a series of 2-phenyl pyrimidine derivatives were prepared and their preliminary in vitro activities on B-cell leukemia cells as well as the BTK enzyme were determined. The results showed that compound 11g displayed the best inhibitory activity on BTK with an inhibition rate of 82.76% at 100 nM and excellent anti-proliferation activity on three B-cell leukemia lines (IC50 = 3.66 μM, 6.98 μM, and 5.39 μM against HL60, Raji and Ramos, respectively). Besides, the flow cytometry analysis results indicated that 11g inhibited the proliferation of the Raji cells in a dose- and time-dependent manner, and blocked the Ramos cells at the G0/G1 phase, which is in accordance with the positive control ibrutinib. The mechanism investigation demonstrated that 11g could inhibit the phosphorylation of BTK and its downstream substrate phospholipase γ2 (PLCγ2). All these results showed that 11g was a promising lead compound that merited further optimization as a novel class of BTK inhibitor for the treatment of B-cell lymphoblastic leukemia.

Amide-tethered quinoline-resorcinol conjugates as a new class of HSP90 inhibitors suppressing the growth of prostate cancer cells

The study is focused on the design and synthesis of amide tethered quinoline-resorcinol hybrid constructs as a new class of HSP90 inhibitor. In-vitro studies of the synthetic compounds led to the identification of compound 11, which possesses potent cell growth inhibitory effects against HCT116, Hep3B and PC-3 cell lines, exerted through HSP90 inhibition. Compound 11 triggers degradation of HSP90 client proteins along with concomitant induction of HSP70, demonstrates apoptosis inducing ability and causes G2M phase cell cycle arrest in PC-3 cells. Molecular modeling was used to dock compound 11 into the HSP90 active site and key interactions with the amino acid residues of the HSP90 chaperone protein were determined.