161111-23-5

Upstream product

• 161111-21-3 (1S,5S)-1--3-(methoxycarbonyl)bicyclo<3.1.0>-2-hexene 
• 4518-10-9 Methyl 3-aminobenzoate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 161111-19-9 (1S,2S)-1--1-(methoxycarbonyl)-2-(2-(methoxycarbonyl)ethyl)cyclopropane 
• 93-58-3 benzoic acid methyl ester 
• 4248-19-5 tert-butyl carbazate 
• 99-05-8 meta-aminobenzoic acid 
• 691-64-5 di-tert-butyl oxalate 
• 618-95-1 methyl 3-nitrobenzoate 
• 121-92-6 3-nitrobenzoic acid 
• 161111-18-8 (1S,2S)-1--1-(methoxycarbonyl)-2-(2-(methoxycarbonyl)ethyl)cyclopropane 
• 1026476-80-1 (1S,5S)-1-tert-Butoxycarbonylamino-2-oxo-bicyclo[3.1.0]hexane-3-carboxylic acid methyl ester 

Downstream Products

• 168162-31-0 methyl 3-((tert-butoxycarbonyl)(methyl)amino)benzoate 
• 1422535-71-4 methyl 3-[benzyl(tert-butoxycarbonyl)amino]benzoate 
• 1422535-72-5 3-[benzyl(tert-butoxycarbonyl)amino]benzoic acid 
• 168162-32-1 3-[N-(tert-butoxycarbonyl)-N-methyl-amino]phenyl isocyanate 
• 168162-30-9 3-(N-tert-butoxycarbonyl-N-methyl-amino)-benzoic acid 
• 111331-82-9 3-[(tert-butoxycarbonyl)amino]benzoic acid 
• 942631-63-2 methyl 5-((tert-butoxycarbonyl)amino)-2-chlorobenzoate 

Relevant academic research and scientific papers

DIACYLGLYCEROL KINASE MODULATING COMPOUNDS

The present disclosure provides diacylglycerol kinase modulating compounds, and pharmaceutical compositions thereof, for treating cancer, including solid tumors, and viral infections, such as HIV or hepatitis B virus infection. The compounds can be used alone or in combination with other agents.

Tert-Butyl(3-cyano-4,6-dimethylpyridin-2-yl)carbonate as a green and chemoselective N-tert-butoxycarbonylation reagent

The use of tert-butyl(3-cyano-4,6-dimethylpyridin-2-yl)carbonate as a chemoselective tert-butoxycarbonylation reagent for aromatic and aliphatic amines has been demonstrated. To gain insight into this reaction, in situ React IR technology was used to confirm the effectivity and chemoselectivity of this novel Boc reagent. The reaction was carried out chemoselectively in high yield under mild, environment-friendly conditions and was completed quickly within 1 hour. Simultaneously, the Boc carrier was easily recyclable, and has great application prospects for industrial production.

Palladium-Catalyzed Suzuki–Miyaura Cross-Coupling of Secondary α-(Trifluoromethyl)benzyl Tosylates

A palladium-catalyzed C(sp3)?C(sp2) Suzuki–Miyaura cross-coupling of aryl boronic acids and α-(trifluoromethyl)benzyl tosylates is reported. A readily available, air-stable palladium catalyst was employed to access a wide range of functionalized 1,1-diaryl-2,2,2-trifluoroethanes. Enantioenriched α-(trifluoromethyl)benzyl tosylates were found to undergo cross-coupling to give the corresponding enantioenriched cross-coupled products with an overall inversion in configuration. The crucial role of the CF3 group in promoting this transformation is demonstrated by comparison with non-fluorinated derivatives.

Identification and preliminary structure–activity relationships of 1-Indanone derivatives as novel indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors

Indoleamine 2,3-dioxygenase 1 (IDO1) plays a vital role in the catabolism of tryptophan along with the kynurenine pathway which is involved in many human diseases including cancer, Alzheimer's disease, etc. In this study, compound 1 bearing a 1-Indanone scaffold was identified as a novel IDO1 inhibitor by structure-based virtual screening, with moderate to good enzymatic and cellular inhibitory activities. Also, surface plasmon resonance analysis validated the direct interaction between compound 1 and IDO1 protein. The preliminary SAR was further explored and the binding mode with IDO1 protein was predicted by experiment along with molecular docking. Subsequent ADME properties of these active compounds were analyzed in silico, and the results showed good pharmacokinetic efficiencies. We believe this study contributes a lot to the structural diversity for the future development of highly potent IDO1 inhibitors.

Photocatalytic Hydrogen-Evolution Cross-Couplings: Benzene C-H Amination and Hydroxylation

We present a blueprint for aromatic C-H functionalization via a combination of photocatalysis and cobalt catalysis and describe the utility of this strategy for benzene amination and hydroxylation. Without any sacrificial oxidant, we could use the dual catalyst system to produce aniline directly from benzene and ammonia, and phenol from benzene and water, both with evolution of hydrogen gas under unusually mild conditions in excellent yields and selectivities.

Structural Optimization of 4-Chlorobenzoylpiperidine Derivatives for the Development of Potent, Reversible, and Selective Monoacylglycerol Lipase (MAGL) Inhibitors

Monoacylglycerol lipase (MAGL) inhibitors are considered potential therapeutic agents for a variety of pathological conditions, including several types of cancer. Many MAGL inhibitors are reported in literature; however, most of them showed an irreversible mechanism of action, which caused important side effects. The use of reversible MAGL inhibitors has been only partially investigated so far, mainly because of the lack of compounds with good MAGL reversible inhibition properties. In this study, starting from the (4-(4-chlorobenzoyl)piperidin-1-yl)(4-methoxyphenyl)methanone (CL6a) lead compound that showed a reversible mechanism of MAGL inhibition (Ki = 8.6 μM), we started its structural optimization and we developed a new potent and selective MAGL inhibitor (17b, Ki = 0.65 μM). Furthermore, modeling studies suggested that the binding interactions of this compound replace a structural water molecule reproducing its H-bonds in the MAGL binding site, thus identifying a new key anchoring point for the development of new MAGL inhibitors.

BENZODIAZEPINE DERIVATIVES AS CCK2/GASTRIN RECEPTOR ANTAGONISTS

The invention relates to benzodiazepine derivatives of formula (A) useful as CCK2/gastrin receptor antagonists, their preparation and their use in the treatment or prevention of disorders associated with CCK2/gastrin receptors, disorders caused by or associated with hypergastrinaemia, and gastric acid-related disorders.

Ligand-Promoted Meta-C-H Arylation of Anilines, Phenols, and Heterocycles

Here we report the development of a versatile 3-acetylamino-2-hydroxypyridine class of ligands that promote meta-C-H arylation of anilines, heterocyclic aromatic amines, phenols, and 2-benzyl heterocycles using norbornene as a transient mediator. More than 120 examples are presented, demonstrating this ligand scaffold enables a wide substrate and coupling partner scope. Meta-C-H arylation with heterocyclic aryl iodides as coupling partners is also realized for the first time using this ligand. The utility for this transformation for drug discovery is showcased by allowing the meta-C-H arylation of a lenalidomide derivative. The first steps toward a silver-free protocol for this reaction are also demonstrated.

Design and Synthesis of Janus Kinase 2 (JAK2) and Histone Deacetlyase (HDAC) Bispecific Inhibitors Based on Pacritinib and Evidence of Dual Pathway Inhibition in Hematological Cell Lines

Blockage of more than one oncoprotein or pathway is now a standard approach in modern cancer therapy. Multiple inhibition is typically achieved with two or more drugs. Herein, we describe a pharmacophore merging strategy combining the JAK2/FLT3 inhibitor pacritnib with the pan-HDAC inhibitor, vorinostat, to create bispecific single molecules with both JAK and HDAC targeted inhibition. A preferred ether hydroxamate, 51, inhibits JAK2 and HDAC6 with low nanomolar potency, is 50-fold selective for JAK2 in a panel of 97 kinases. Broad cellular antiproliferative potency is supported by demonstration of JAK-STAT and HDAC pathway blockade in several hematological cell lines, inhibition of colony formation in HEL cells, and analysis of apoptosis. This study provides new tool compounds for further exploration of dual JAK-HDAC pathway inhibiton achieved with a single molecule.

Highly ortho-Selective Chlorination of Anilines Using a Secondary Ammonium Salt Organocatalyst

An organocatalytic, highly facile, efficient, and regioselective ortho-chlorination of anilines is described. A secondary ammonium chloride salt has been employed as the catalyst and the reaction can be conducted at room temperature without protection from air and moisture. In addition, the reaction is readily scalable and the catalyst can be recycled and reused. This catalytic protocol has been applied to the efficient synthesis of a highly potent c-Met kinase inhibitor. Mechanistic studies revealed that unique structural features of the secondary ammonium chloride salt are important for both the catalysis and regioselectivity of the electrophilic ortho-chlorination.