27958-77-6

Usage

Uses

Used in Pharmaceutical Industry:
3-AMINO-N,N-DIMETHYLBENZYLAMINE is used as a reagent for the preparation of amino-triazole-carboxamide derivatives. These derivatives are specifically utilized in the treatment of Trypanosoma cruzi, a parasitic disease also known as Chagas disease. The compound plays a crucial role in the synthesis of these pharmaceuticals, targeting the parasite and aiding in the development of potential therapeutic agents.

InChI:InChI=1/C9H14N2/c1-11(2)7-8-4-3-5-9(10)6-8/h3-6H,7,10H2,1-2H3

Upstream product

• 15184-95-9 N-(3-nitrophenylmethyl)dimethylamine 
• 121-90-4 m-nitrobenzoic acid chloride 
• 99-61-6 3-nitro-benzaldehyde 
• 619-23-8 3-Nitrobenzyl chloride 
• 3958-57-4 1-bromomethyl-3-nitrobenzene 

Downstream Products

• 4280-12-0 N-(3-Dimethylaminomethyl-phenyl)-2-[(E)-hydroxyimino]-acetamide 
• 872511-33-6 N-(3-dimethylaminomethyl-phenyl)-N'-methyl-pyrimidine-4,6-diamine 
• 75447-25-5 Trimethyl-(3-aminobenzyl)-ammonium methosulphate 
• 928789-40-6 2-(3-Dimethylaminomethyl-phenylamino)-8-indan-5-yl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester 
• 1038550-44-5 N-[3-(3-dimethylaminomethyl-phenylcarbamoyl)-benzyl]-3,4-dimethoxy-benzamide 
• 109508-33-0 trimethyl-(3-trimethylammonio-benzyl)-ammonium; diiodide 
• 1403819-30-6 N-(3-((dimethylamino)methyl)phenyl)-5-(2-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine 
• 1403819-10-2 N-(3-((dimethylamino)methyl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine 
• 941318-47-4 4-[2-(3-aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-{3-[(dimethylamino)methyl]phenyl}-2-pyrimidinamine 
• 850450-20-3 N-{3-[7-(3-dimethylaminomethyl-phenylamino)-1-methyl-2-oxo-1,2-dihydro-[1,6]naphthyridin-3-yl]-4-methyl-phenyl}-3-trifluoromethyl-benzamide 

Relevant academic research and scientific papers

WEE1 KINASE INHIBITORS AND METHODS OF TREATING CANCER USING THE SAME

A compound, or a pharmaceutically acceptable salts or prodrugs thereof, having the chemical structure (I) and methods of using these compounds to inhibit WEE1 kinase and treat cancer in a subject.

Development of Potent Pyrazolopyrimidinone-Based WEE1 Inhibitors with Limited Single-Agent Cytotoxicity for Cancer Therapy

WEE1 kinase regulates the G2/M cell-cycle checkpoint, a critical mechanism for DNA repair in cancer cells that can confer resistance to DNA-damaging agents. We previously reported a series of pyrazolopyrimidinones based on AZD1775, a known WEE1 inhibitor, as an initial investigation into the structural requirements for WEE1 inhibition. Our lead inhibitor demonstrated WEE1 inhibition in the same nanomolar range as AZD1775, and potentiated the effects of cisplatin in medulloblastoma cells, but had reduced single-agent cytotoxicity. These results prompted the development of a more comprehensive series of WEE1 inhibitors. Herein we report a series of pyrazolopyrimidinones and identify a more potent WEE1 inhibitor than AZD1775 and additional compounds that demonstrate that WEE1 inhibition can be achieved with reduced single-agent cytotoxicity. These studies support that WEE1 inhibition can be uncoupled from the potent cytotoxic effects observed with AZD1775, and this may have important ramifications in the clinical setting where WEE1 inhibitors are used as chemosensitizers for DNA-targeted chemotherapy.

Thieno[3,2-b]pyrrole-5-carboxamides as New Reversible Inhibitors of Histone Lysine Demethylase KDM1A/LSD1. Part 1: High-Throughput Screening and Preliminary Exploration

Lysine specific demethylase 1 KDM1A (LSD1) regulates histone methylation and it is increasingly recognized as a potential therapeutic target in oncology. We report on a high-throughput screening campaign performed on KDM1A/CoREST, using a time-resolved fluorescence resonance energy transfer (TR-FRET) technology, to identify reversible inhibitors. The screening led to 115 hits for which we determined biochemical IC50, thus identifying four chemical series. After data analysis, we have prioritized the chemical series of N-phenyl-4H-thieno[3, 2-b]pyrrole-5-carboxamide for which we obtained X-ray structures of the most potent hit (compound 19, IC50 = 2.9 μM) in complex with the enzyme. Initial expansion of this chemical class, both modifying core structure and decorating benzamide moiety, was directed toward the definition of the moieties responsible for the interaction with the enzyme. Preliminary optimization led to compound 90, which inhibited the enzyme with a submicromolar IC50 (0.162 μM), capable of inhibiting the target in cells.

Discovery of Potent, Selective Stem Cell Factor Receptor/Platelet Derived Growth Factor Receptor Alpha (c-KIT/PDGFRα) Dual Inhibitor for the Treatment of Imatinib-Resistant Gastrointestinal Stromal Tumors (GISTs)

Stem cell factor receptor (c-KIT) and platelet derived growth factor receptor alpha (PDGFRα) kinases play an important role in gastrointestinal stromal tumors (GISTs). Here, we have discovered an c-KIT/PDGFRα dual inhibitor, compound 31, with single-digit nanomolar potency against c-KIT and PDGFRα. Compared to Imatinib (1), 31 showed better antiproliferative efficacy against various TEL-c-KIT/PDGFRα-BaF3 isogenic cells, including three 1-resistant BaF3 cell lines, as well as against GIST-T1 and GIST-882 cell lines. Furthermore, compound 31 showed a good KinomeScan selectivity (468 kinases) (S score (1) = 0.01 at 1 μM concentration), good metabolic stability in liver microsomes, and no hERG inhibitory activity. It was worth noting that 31 inhibited GIST-T1 tumor growth (TGI = 81.5%) and even the BaF3-TEL-cKIT-T670I tumor progression (TGI = 41.9%, 1-resistant GISTs) at a dosage of 100 mg/kg/day without exhibiting apparent toxicity.

Hydrogenation of (N,N-disubstituted aminomethyl)nitrobenzenes to (N,N-disubstituted aminomethyl)anilines catalyzed by palladium-nickel bimetallic nanoparticles

Since palladium-catalysts have strong abilities for both hydrogenation of nitro-group and hydrogenolysis of benzylamine, they have a much lower chemoselectivity for the hydrogenation of (N,N-disubstituted aminomethyl)nitrobenzenes. In this article, component stable Pd-Ni bimetallic nanoparticles were prepared by simply heating RANEY-Ni and Na2PdCl4 together in water. They demonstrated novel synergistic effects when they were used as a bimetallic catalyst, by which a highly efficient and chemoselective hydrogenation of (N,N-disubstituted aminomethyl)nitrobenzenes to (N,N-disubstituted aminomethyl)anilines was achieved.

Phenyl ether- and aniline-containing 2-aminoquinolines as potent and selective inhibitors of neuronal nitric oxide synthase

Excess nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is implicated in neurodegenerative disorders. As a result, inhibition of nNOS and reduction of NO levels is desirable therapeutically, but many nNOS inhibitors are poorly bioavailable. Promising members of our previously reported 2-aminoquinoline class of nNOS inhibitors, although orally bioavailable and brain-penetrant, suffer from unfavorable off-target binding to other CNS receptors, and they resemble known promiscuous binders. Rearranged phenyl ether- and aniline-linked 2-aminoquinoline derivatives were therefore designed to (a) disrupt the promiscuous binding pharmacophore and diminish off-target interactions and (b) preserve potency, isoform selectivity, and cell permeability. A series of these compounds was synthesized and tested against purified nNOS, endothelial NOS (eNOS), and inducible NOS (iNOS) enzymes. One compound, 20, displayed high potency, selectivity, and good human nNOS inhibition, and retained some permeability in a Caco-2 assay. Most promisingly, CNS receptor counterscreening revealed that this rearranged scaffold significantly reduces off-target binding.

IMIDAZOPYRIDINES AS A NOVEL SCAFFOLD FOR MULTI-TARGETED KINASE INHIBITION

Compounds that inhibit protein kinases, compositions containing the compounds and methods of treating diseases using the compounds are disclosed. Formula (I).

QUINOLINE DERIVATIVES

The invention concerns quinoline derivatives of Formula (I): or a pharmaceutically-acceptable salt thereof, wherein each of X1, p, R1, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders.

QUINAZOLINE DERIVATIVES

The invention concerns quinazoline derivatives of Formula (I) or a pharmaceutically-acceptable salt, solvate or pro-drug thereof, wherein each of X1, p, R1, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders or in the treatment of disease states associated with angiogenesis and/or vascular permeability.

QUINOLINE DERIVATIVES

The invention concerns quinoline derivatives of Formula (I) or a pharmaceutically-acceptable salt, solvate or pro-drug thereof, wherein each of p, R1, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders or in the treatment of disease states associated with angiogenesis and/or vascular permeability.