Month: October 2022

Green, Neal; Hu, Yonghan; Janz, Kristin; Li, Huan-Qiu; Kaila, Neelu; Guler, Satenig; Thomason, Jennifer; Joseph-McCarthy, Diane; Tam, Steve Y.; Hotchandani, Rajeev; Wu, Junjun; Huang, Adrian; Wang, Qin; Leung, Louis; Pelker, Jefferey; Marusic, Suzana; Hsu, Sang; Telliez, Jean-Baptiste; Hall, J. Perry; Cuozzo, John W.; Lin, Lih-Ling published the artcile< Inhibitors of Tumor Progression Loci-2 (Tpl2) Kinase and Tumor Necrosis Factor α (TNF-α) Production: Selectivity and in Vivo Antiinflammatory Activity of Novel 8-Substituted-4-anilino-6-aminoquinoline-3-carbonitriles>, COA of Formula: C6H11NO2, the main research area is anilinoaminoquinoline carbonitrile derivative preparation structure Tpl2 kinase inhibitor antiinflammatory.

Tumor progression loci-2 (Tpl2) (Cot/MAP3K8) is a serine/threonine kinase in the MAP3K family directly upstream of MEK. Recent studies using Tpl2 knockout mice have indicated an important role for Tpl2 in the lipopolysaccharide (LPS) induced production of tumor necrosis factor α (TNF-α) and other proinflammatory cytokines involved in diseases such as rheumatoid arthritis. Initial 4-anilino-6-aminoquinoline-3-carbonitrile leads showed poor selectivity for Tpl2 over epidermal growth factor receptor (EGFR) kinase. Using mol. modeling and crystallog. data of the EGFR kinase domain with and without an EGFR kinase-specific 4-anilinoquinazoline inhibitor (erlotinib, Tarceva), the authors hypothesized that the authors could diminish the inhibition of EGFR kinase by substitution at the C-8 position of the 4-anilino-6-aminoquinoline-3-carbonitrile leads. The 8-substituted-4-anilino-6-aminoquinoline-3-carbonitriles were prepared from the appropriate 2-substituted 4-nitroanilines. Modifications to the C-6 and C-8 positions led to the identification of compounds with increased inhibition of TNF-α release from LPS-stimulated rat and human blood, and these analogs were also highly selective for Tpl2 kinase over EGFR kinase. Further structure-activity based modifications led to the identification of 8-bromo-4-(3-chloro-4-fluorophenylamino)-6-[(1-methyl-1H-imidazol-4-yl)methylamino]quinoline-3-carbonitrile, which demonstrated in vitro as well as in vivo efficacy in inhibition of LPS-induced TNF-α production

Journal of Medicinal Chemistry published new progress about Anti-inflammatory agents. 6136-93-2 belongs to class nitriles-buliding-blocks, and the molecular formula is C6H11NO2, COA of Formula: C6H11NO2.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Hattori, Yohei; Nishikawa, Michihiro; Kusamoto, Tetsuro; Kume, Shoko; Nishihara, Hiroshi published the artcile< Steric interference on the redox-conjugated pyrimidine ring rotation of mono- and dinuclear copper complexes with (4-methyl-2-pyrimidinyl)imine ligands>, Application of C6H11NO2, the main research area is copper phenanthroline methylpyrimidinylmethylene benzeneamine complex preparation; electrochem copper phenanthroline methylpyrimidinylmethylene benzeneamine complex; crystal structure copper phenanthroline methylpyrimidinylmethylene benzeneamine complex.

A mononuclear copper(I) complex with N-[(4-methyl-2-pyrimidinyl)methylene]-p-toluidine (1·BF4; [(Phen-anth2)Cu(L1)]·BF4) and a dinuclear copper(I) complex with N,N’-bis[(4-methyl-2-pyrimidinyl)-methylene]-p-phenylenediamine (2·(BF4)2; [(Phen-anth2)2Cu2(μ-L2)]·(BF4)2) (where Phen-anth2 = dianthracenylphenathroline, L1 = N-[(4-methyl-2-pyrimidinyl)methylene]-p-toluide and L2 = N,N’-bis[(4-methyl-2-pyrimidinyl)methylene]-p-phenylenediamine) were synthesized as BF4- salts to evaluate the influence of the imine moiety on the pyrimidine ring rotation isomerism. 1·BF4 existed in solution as a mixture of two isomers; 2·(BF4)2 was present as a mixture of three isomers. The redox potentials of the copper centers were changed by pyrimidine ring rotation. Comparison of 1+ and 22+ indicated that increasing the steric congestion around the copper center increased the o/i isomer ratio; the redox potentials of both the o- and i-isomers shifted in the pos. direction, and the CuII/I redox reaction became slower.

Chemistry Letters published new progress about Conformational transition, ring inversion (kinetics). 6136-93-2 belongs to class nitriles-buliding-blocks, and the molecular formula is C6H11NO2, Application of C6H11NO2.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Utimoto, Kiitiro; Wakabayashi, Yukio; Shishiyama, Yuho; Inoue, Masaharu; Nozaki, Hitosi published the artcile< 2-Alkoxy- and 2,2-dialkoxynitriles from acetals and ortho esters: exchange of alkoxy into cyano group by means of cyanotrimethylsilane>, Name: 2,2-Diethoxyacetonitrile, the main research area is acetal aromatic aliphatic cyanation; ortho ester cyanation catalyst; tin fluoroborane cyanation catalyst; borane fluoro catalyst cyanation; alkoxynitrile; nitrile alkoxy; methoxyacetonitrile lithiation octylation oxidation; acetonitrile methoxy lithiation octylation oxidation; nonanoate.

Thirteen RCR1(OR2)CN (R = H, alkyl, Ph, PhCH2; R1 = H, OMe, OEt; R2 = Me, Et) were prepared in 64-97% yield by cyanation of the corresponding RCR1(OR2)2 with Me3SiCN in the presence of SnCl2 or BF3.OEt2 catalysts. E.g., 80% (MeO)2CHCN (I) was obtained on treatment of (MeO)3CH with 1 equiv Me3SiCN and a catalytic amount of BF3.OEt2 at room temperature I was converted to Me(CH2)7CO2Me by sequential treatment with LiN(CHMe2)2, Me(CH2)7Br, and p-MeC6H4SO3H in Me2CO-H2O.

Tetrahedron Letters published new progress about Acetals Role: RCT (Reactant), RACT (Reactant or Reagent). 6136-93-2 belongs to class nitriles-buliding-blocks, and the molecular formula is C6H11NO2, Name: 2,2-Diethoxyacetonitrile.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Abe, Takumi; Noda, Kenta; Sawada, Daisuke published the artcile< Synthesis of α-substituted indolylacetamide using acetonitriles as acetamide enolate equivalents through O-transfer reactions>, Application In Synthesis of 21667-62-9, the main research area is indolylacetamide preparation; ammonium hemiaminal acetonitrile alkylation oxygen transfer reaction.

Authors introduce readily available ammonium hemiaminals as O-transfer reagents and com. available acetonitriles as a primary amide enolate precursor. The combination serves as an amide enolate equivalent, thereby providing one-pot access to α-substituted indolylacetamides I (EWG = COOMe, SO2Me, C(O)Ph, etc.; R1 = H, Ph). A broad substrate scope and good functional group tolerance as well as gram-scale synthesis make this protocol highly attractive. Mechanistic experiments suggest that the cyano group is trapped by a hydroxy group of hemiaminals en route to the desired primary amides under metal-free conditions.

Chemical Communications (Cambridge, United Kingdom) published new progress about Acetamides Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 21667-62-9 belongs to class nitriles-buliding-blocks, and the molecular formula is C9H6ClNO, Application In Synthesis of 21667-62-9.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Li, Quanzhe; Liu, Jiaxin; Wei, Yin; Shi, Min published the artcile< One-Pot Synthesis of Spirocyclopenta[a]indene Derivatives via a Cascade Ring Expansion and Intramolecular Friedel-Crafts-Type Cyclization>, Application In Synthesis of 38487-85-3, the main research area is spirocyclopentaindene derivative preparation; propargyl alc tethered alkylidenecyclobutane preparation cascade ring expansion cyclization.

A one-pot efficient synthetic approach for the rapid construction of spirocyclopenta[a]indene derivatives has been developed via an iodine-initiated cascade ring expansion and intramol. Friedel-Crafts-type cyclization from propargyl alc.-tethered alkylidenecyclobutanes under mild conditions with broad substrate scope. This cascade process can be elegantly conducted on a gram scale. A plausible reaction mechanism has been proposed on the basis of a series of deuterium labeling and control experiments

Journal of Organic Chemistry published new progress about Alcohols, propargyl Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 38487-85-3 belongs to class nitriles-buliding-blocks, and the molecular formula is C8H8N2O, Application In Synthesis of 38487-85-3.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Abou Elmaaty, Tarek; Elsisi, Hanan; Negm, Ilham published the artcile< Dyeing Characteristics of Polypropylene Fabric Dyed with Special Disperse Dyes Using Supercritical Carbon Dioxide>, Formula: C9H6ClNO, the main research area is polypropylene fabric dyeing disperse dye supercritical carbon dioxide.

Using disperse dyes of different colors and hues to produce a variety of shades is necessary for the industrialization of supercritical fluid dyeing of polypropylene. Eight derivatives of 3-(3-chlorophenyl)-1-phenyl-4-(diazenyl derivatives)-1H-pyrazol-5-amine dye were synthesized explicitly for use in supercritical carbon dioxide medium. Polypropylene dyeing was studied in supercritical carbon dioxide under varying conditions: Dyeing temperatures ranged from 100°C to 120°C, dying times ranged from 1 h to 2 h, concentrations ranged from 2% owf (on the weight of fabric) to 4%, and pressures ranged from 15 to 25 MPa. Significant improvement of the colorfastness to washing and rubbing was observed Raman spectroscopy was performed and showed conclusively that the dye was absorbed within all layers of polypropylene. This study achieved the elimination of water and its costly processing in the dyeing of synthetic fabrics.

Fibers and Polymers published new progress about Colorfastness. 21667-62-9 belongs to class nitriles-buliding-blocks, and the molecular formula is C9H6ClNO, Formula: C9H6ClNO.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Chen, Ying-Chu; Faver, John C.; Ku, Angela F.; Miklossy, Gabriella; Riehle, Kevin; Bohren, Kurt M.; Ucisik, Melek N.; Matzuk, Martin M.; Yu, Zhifeng; Simmons, Nicholas published the artcile< C-N Coupling of DNA-Conjugated (Hetero)aryl Bromides and Chlorides for DNA-Encoded Chemical Library Synthesis>, Category: nitriles-buliding-blocks, the main research area is DNA encoded heteroaryl amide library synthesis.

DNA-encoded chem. library (DECL) screens are a rapid and economical tool to identify chem. starting points for drug discovery. As a robust transformation for drug discovery, palladium-catalyzed C-N coupling is a valuable synthetic method for the construction of DECL chem. matter; however, currently disclosed methods have only been demonstrated on DNA-attached (hetero)aromatic iodide and bromide electrophiles. We developed conditions utilizing an N-heterocyclic carbene-palladium catalyst that extends this reaction to the coupling of DNA-conjugated (hetero)aromatic chlorides with (hetero)aromatic and select aliphatic amine nucleophiles. In addition, we evaluated steric and electronic effects within this catalyst series, carried out a large substrate scope study on two representative (hetero)aryl bromides, and applied this newly developed method within the construction of a 63 million-membered DECL.

Bioconjugate Chemistry published new progress about Anilines Role: CMB (Combinatorial Study), RCT (Reactant), RACT (Reactant or Reagent). 38487-85-3 belongs to class nitriles-buliding-blocks, and the molecular formula is C8H8N2O, Category: nitriles-buliding-blocks.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Kieft, Kristopher; Zhou, Zhichao; Anantharaman, Karthik published the artcile< VIBRANT: automated recovery, annotation and curation of microbial viruses, and evaluation of viral community function from genomic sequences>, Safety of 2-Amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile, the main research area is Crohn disease Enterobacteriale VIBRANT genomic microbiome environment dysbiosis ecosystem; Auxiliary metabolism; Bacteriophage; Machine learning; Metagenome; Software; Virome; Virus.

Viruses are central to microbial community structure in all environments. The ability to generate large metagenomic assemblies of mixed microbial and viral sequences provides the opportunity to tease apart complex microbiome dynamics, but these analyses are currently limited by the tools available for analyses of viral genomes and assessing their metabolic impacts on microbiomes. Here we present VIBRANT, the first method to utilize a hybrid machine learning and protein similarity approach that is not reliant on sequence features for automated recovery and annotation of viruses, determination of genome quality and completeness, and characterization of viral community function from metagenomic assemblies. VIBRANT uses neural networks of protein signatures and a newly developed v-score metric that circumvents traditional boundaries to maximize identification of lytic viral genomes and integrated proviruses, including highly diverse viruses. VIBRANT highlights viral auxiliary metabolic genes and metabolic pathways, thereby serving as a user-friendly platform for evaluating viral community function. VIBRANT was trained and validated on reference virus datasets as well as microbiome and virome data. VIBRANT showed superior performance in recovering higher quality viruses and concurrently reduced the false identification of non-viral genome fragments in comparison to other virus identification programs, specifically VirSorter, VirFinder, and MARVEL. When applied to 120,834 metagenome-derived viral sequences representing several human and natural environments, VIBRANT recovered an average of 94% of the viruses, whereas VirFinder, VirSorter, and MARVEL achieved less powerful performance, averaging 48%, 87%, and 71%, resp. Similarly, VIBRANT identified more total viral sequence and proteins when applied to real metagenomes. When compared to PHASTER, Prophage Hunter, and VirSorter for the ability to extract integrated provirus regions from host scaffolds, VIBRANT performed comparably and even identified proviruses that the other programs did not. To demonstrate applications of VIBRANT, we studied viromes associated with Crohn’s disease to show that specific viral groups, namely Enterobacteriales-like viruses, as well as putative dysbiosis associated viral proteins are more abundant compared to healthy individuals, providing a possible viral link to maintenance of diseased states. The ability to accurately recover viruses and explore viral impacts on microbial community metabolism will greatly advance our understanding of microbiomes, host-microbe interactions, and ecosystem dynamics. [media not available: see fulltext].

Microbiome published new progress about Algorithm. 69205-79-4 belongs to class nitriles-buliding-blocks, and the molecular formula is C7H5N5O, Safety of 2-Amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Ma, Xiao-Dong; Yang, Shi-Qiong; Gu, Shuang-Xi; He, Qiu-Qin; Chen, Fen-Er; De Clercq, Erik; Balzarini, Jan; Pannecouque, Christophe published the artcile< Synthesis and Anti-HIV Activity of Aryl-2-[(4-cyanophenyl)amino]-4-pyrimidinone hydrazones as Potent Non-nucleoside Reverse Transcriptase Inhibitors>, Reference of 658-99-1, the main research area is preparation antiviral HIV cyanophenyl amino pyrimidinone hydrazone RT inhibitor.

A series of novel diarylpyrimidines (DAPYs) with a ketone hydrazone substituent on the methylene linker between the pyrimidine nucleus and the aryl moiety at the C-4 position were synthesized, and their antiviral activity against human immunodeficiency virus (HIV)-1 in MT-4 cells was evaluated. Most compounds of this class exhibited excellent activity against wild-type HIV-1, with EC50 values in the range of 1.7-13.2 nM. Of these compounds, 2-bromophenyl-2-[(4-cyanophenyl)amino]-4-pyrimidinone hydrazone (9 k) displayed the most potent anti-HIV-1 activity (EC50=1.7±0.6 nM), with excellent selectivity for infected over uninfected cells (SI=5762). In addition, the 4-Me Ph analog 9 d (EC50=2.4±0.2 nM, SI=18461) showed broad spectrum HIV inhibitory activity, with EC50 values of 2.4±0.2 nM against wild-type HIV-1, 5.3±0.4 μM against HIV-1 double-mutated strain RES056 (K103N+Y181C), and 5.5 μM against HIV-2 ROD strain. Furthermore, structure-activity relationship (SAR) data and mol. modeling results for these compounds are also discussed.

ChemMedChem published new progress about Antiviral agents. 658-99-1 belongs to class nitriles-buliding-blocks, and the molecular formula is C8H5F2N, Reference of 658-99-1.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts