Category: nitriles-buliding-blocks

Structure-Based Design, Synthesis, and Biological Evaluation of Imidazo[4,5-b]Pyridin-2-one-Based p38 MAP Kinase Inhibitors: Part 2 was written by Kaieda, Akira;Takahashi, Masashi;Fukuda, Hiromi;Okamoto, Rei;Morimoto, Shinji;Gotoh, Masayuki;Miyazaki, Takahiro;Hori, Yuri;Unno, Satoko;Kawamoto, Tomohiro;Tanaka, Toshimasa;Itono, Sachiko;Takagi, Terufumi;Sugimoto, Hiroshi;Okada, Kengo;Lane, Weston;Sang, Bi-Ching;Saikatendu, Kumar;Matsunaga, Shinichiro;Miwatashi, Seiji. And the article was included in ChemMedChem in 2019.Application In Synthesis of 3-Amino-4-methylbenzonitrile This article mentions the following:

We identified novel potent inhibitors of p38 mitogen-activated protein (MAP) kinase using a structure-based design strategy, beginning with lead compound, 3-(butan-2-yl)-6-(2,4-difluoroanilino)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (1). To enhance the inhibitory activity of 1 against production of tumor necrosis factor-α (TNF-α) in human whole blood (hWB) cell assays, we designed and synthesized hybrid compounds in which the imidazo[4,5-b]pyridin-2-one core was successfully linked with the p-methylbenzamide fragment. Among the compounds evaluated, 3-(3-tert-butyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-6-yl)-4-methyl-N-(1-methyl-1H-pyrazol-3-yl)benzamide (25) exhibited potent p38 inhibition, superior suppression of TNF-α production in hWB cells, and also significant in vivo efficacy in a rat model of collagen-induced arthritis (CIA). In this paper, we report the discovery of potent, selective, and orally bioavailable imidazo[4,5-b]pyridin-2-one-based p38 MAP kinase inhibitors. In the experiment, the researchers used many compounds, for example, 3-Amino-4-methylbenzonitrile (cas: 60710-80-7Application In Synthesis of 3-Amino-4-methylbenzonitrile).

3-Amino-4-methylbenzonitrile (cas: 60710-80-7) belongs to nitriles. Nitriles are polar, as indicated by high dipole moments. As liquids, they have high relative permittivities, often in the 30s. Asymmetric bioreduction of nitriles is an attractive route to produce optically active nitriles as current metal-catalyzed hydrogenations tend to have low reactivity.Application In Synthesis of 3-Amino-4-methylbenzonitrile

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Targeting the K_v11.1 (hERG) channel with allosteric modulators. Synthesis and biological evaluation of three novel series of LUF7346 derivatives was written by van Veldhoven, Jacobus P. D.;Campostrini, Giulia;van Gessel, Constantijn J. E.;Ward-van Oostwaard, Dorien;Liu, Rongfang;Mummery, Christine L.;Bellin, Milena;IJzerman, Adriaan P.. And the article was included in European Journal of Medicinal Chemistry in 2021.COA of Formula: C8H8N2O This article mentions the following:

Three novel series of substituted benzophenones for their allosteric modulation of the human Kv11.1 (hERG) channel were synthesized and evaluated. Effects of this is compared with reference compound LUF7346 previously shown to shorten the action potential of cardiomyocytes derived from human stem cells. Most compounds behaved as neg. allosteric modulators (NAMs) of [3H]dofetilide binding to the channel. Compound III [R = 2-Cl; R¹ = CH₂cPr; X= Y = C] was the most potent amongst all ligands, remarkably reducing the affinity of dofetilide in competitive displacement assays. One of the other II [R = H; X = N] tested in a second radioligand binding set-up, displayed unusual displacement characteristics with a pseudo-Hill coefficient significantly distinct from unity, further indicative of its allosteric effects on the channel. Some compounds were evaluated in a more physiol. relevant context in beating cardiomyocytes derived from human induced pluripotent stem cells. Surprisingly, the compounds tested showed effects quite different from the reference NAM LUF7346. For instance, compound I [R = 3-Me] prolonged, rather than shortened, the field potential duration, while it did not influence this parameter when the field potential was already prolonged by dofetilide. In subsequent patch clamp studies on HEK293 cells expressing the hERG channel the compounds behaved as channel blockers. In conclusion, new allosteric modulators of the hERG channel were successfully synthesized and identified . Unexpectedly, their effects differed from the reference compound in functional assays on hERG-HEK293 cells and human cardiomyocytes, to the extent that the compounds behaved as stand-alone channel blockers. In the experiment, the researchers used many compounds, for example, 3-Amino-4-methoxybenzonitrile (cas: 60979-25-1COA of Formula: C8H8N2O).

3-Amino-4-methoxybenzonitrile (cas: 60979-25-1) belongs to nitriles. Trimerization of aromatic nitriles requires harsh reaction conditions, high temperatures, long reaction times, and pressure. Alkyl nitriles are sufficiently acidic to undergo deprotonation of the C-H bond adjacent to the CN group.Strong bases are required, such as lithium diisopropylamide and butyl lithium. The product is referred to as a nitrile anion. COA of Formula: C8H8N2O

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Nitrile – Wikipedia,
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A biomimetic catalytic aerobic functionalization of phenols was written by Esguerra, Kenneth Virgel N.;Fall, Yacoub;Lumb, Jean-Philip. And the article was included in Angewandte Chemie, International Edition in 2014.HPLC of Formula: 5351-07-5 This article mentions the following:

A biomimetic approach that converts phenolic C-H bonds into C-O, C-N, and C-S bonds at the sole expense of reducing O₂ to water (H₂O) was reported. This method hinges on a regio- and chemoselective Cu-catalyzed aerobic oxygenation to provide orthoquinones. Orthoquinones are versatile intermediates, whose direct catalytic aerobic synthesis from phenols enables a mild and efficient means of synthesizing polyfunctional aromatic rings. In the experiment, the researchers used many compounds, for example, 2-(4-Methoxyphenyl)-2-methylpropanenitrile (cas: 5351-07-5HPLC of Formula: 5351-07-5).

2-(4-Methoxyphenyl)-2-methylpropanenitrile (cas: 5351-07-5) belongs to nitriles. Nitrile compounds can be prepared by the incorporation of a cyanide source through C–C bond formation or by dehydration of primary carboxamides. In conventional organic reductions, nitrile is reduced by treatment with lithium aluminium hydride to the amine. Reduction to the imine followed by hydrolysis to the aldehyde takes place in the Stephen aldehyde synthesis, which uses stannous chloride in acid.HPLC of Formula: 5351-07-5

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Nitrile – Wikipedia,
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4-Amino-6-(piperidin-1-yl)pyrimidine-5-carbonitrile was written by Bhat, Radhika;Shraddha, K. N.;Begum, Noor Shahina. And the article was included in IUCrData in 2020.Recommanded Product: 60025-09-4 This article mentions the following:

In the title compound, C₁₀H₁₃N₅, the piperidine ring adopts a chair conformation with the exocyclic N-C bond in an axial orientation, and the dihedral angle between the mean planes of piperidine and pyrimidine rings is 49.57 (11)°. A short intramol. C-H···N contact generates an S(7) ring. In the crystal, N-H···N hydrogen bonds link the mols. into (100) sheets and a weak aromatic π-π stacking interaction is observed [centroid-centroid separation = 3.5559 (11) Å] between inversion-related pyrimidine rings. In the experiment, the researchers used many compounds, for example, 4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4Recommanded Product: 60025-09-4).

4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4) belongs to nitriles. Nitrile function is a very important functional group because it can be manipulated to other functional groups such as carboxylic acid by hydrolysis or amine by reduction, respectively. In addition, Nitriles can react with alkynes, which leads to an increase in carbon chain length (carbocyanation).Recommanded Product: 60025-09-4

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Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Design and discovery of 3-aryl-5-substituted-isoquinolin-1-ones as potent tankyrase inhibitors was written by Elliott, Richard J. R.;Jarvis, Ashley;Rajasekaran, Mohan B.;Menon, Malini;Bowers, Leandra;Boffey, Ray;Bayford, Melanie;Firth-Clark, Stuart;Key, Rebekah;Aqil, Rehan;Kirton, Stewart B.;Niculescu-Duvaz, Dan;Fish, Laura;Lopes, Filipa;McLeary, Robert;Trindade, Ines;Vendrell, Elisenda;Munkonge, Felix;Porter, Rod;Perrior, Trevor;Springer, Caroline;Oliver, Antony W.;Pearl, Laurence H.;Ashworth, Alan;Lord, Christopher J.. And the article was included in MedChemComm in 2015.Product Details of 37812-51-4 This article mentions the following:

The tankyrase proteins (TNKS, TNKS2), members of the PARP superfamily of enzymes, are attractive anti-cancer drug targets, particularly as inhibition of their catalytic activity has been shown to antagonize oncogenic WNT signalling. To identify chem. inhibitors of tankyrase we carried out an in silico small mol. screen using a set of ‘PARP-binding’ pharmacophores together with a generated (liganded) tankyrase homol. model. This approach identified a structurally diverse set of ∼1000 compounds for further study. Subsequent in vitro screening of recombinant tankyrase protein identified a subset of 59 confirmed inhibitors. Early optimization followed by cell-based studies in WNT-dependent tumor cells, as well as co-crystallization studies, identified a novel class of 3-aryl-5-substituted isoquinolin-1-ones, such as 21, that exhibit potent inhibition of tankyrase activity as well as growth inhibition of colorectal cancer cells. In the experiment, the researchers used many compounds, for example, 4-(Morpholinomethyl)benzonitrile (cas: 37812-51-4Product Details of 37812-51-4).

4-(Morpholinomethyl)benzonitrile (cas: 37812-51-4) belongs to nitriles. Nitrile compounds can be prepared by the incorporation of a cyanide source through C–C bond formation or by dehydration of primary carboxamides. Industrially, the main methods for producing nitriles are ammoxidation and hydrocyanation. Both routes are green in the sense that they do not generate stoichiometric amounts of salts.Product Details of 37812-51-4

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Nitrile – Wikipedia,
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Water-Soluble Hypervalent Iodine(III) Having an I-N Bond. A Reagent for the Synthesis of Indoles was written by Xia, Hai-Dong;Zhang, Yan-Dong;Wang, Yan-Hui;Zhang, Chi. And the article was included in Organic Letters in 2018.Name: 2-Amino-3-chlorobenzonitrile This article mentions the following:

A readily accessible and bench-stable water-soluble hypervalent iodine(III) reagent (phenyliodonio)sulfamate (PISA, PhI⁺NHSO₃^–) with an I-N bond was synthesized, and its structure was characterized by X-ray crystallog. anal. of its monoaqua complex. N-(Alkenylphenyl)amides such as I (R = Me, Et, BuCH₂, cyclopropyl, cyclohexyl, Ph, H, Et; R¹ = H, Me, n-Pr, PhCH₂) underwent regioselective rearrangement and oxidative cyclization mediated by PISA and H₂O in MeCN to yield acylindoles such as II (R = Me, Et, BuCH₂, cyclopropyl, cyclohexyl, Ph, H, Et; R¹ = H, Me, n-Pr, PhCH₂). Using this new method, the antiinflammatory agents indomethacin and zidometacin and 2-methylindole (an intermediate in the preparation of pravadoline) were prepared In the experiment, the researchers used many compounds, for example, 2-Amino-3-chlorobenzonitrile (cas: 53312-77-9Name: 2-Amino-3-chlorobenzonitrile).

2-Amino-3-chlorobenzonitrile (cas: 53312-77-9) belongs to nitriles. Nitrile function is a very important functional group because it can be manipulated to other functional groups such as carboxylic acid by hydrolysis or amine by reduction, respectively. In addition, Nitriles can react with alkynes, which leads to an increase in carbon chain length (carbocyanation).Name: 2-Amino-3-chlorobenzonitrile

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Nitrile – Wikipedia,
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C-N Bond Formation Catalysed by CuI Bonded to Polyaniline Nanofiber was written by Arundhathi, Racha;Kumar, Desitti Chaitanya;Sreedhar, Bojja. And the article was included in European Journal of Organic Chemistry in 2010.Recommanded Product: 10282-32-3 This article mentions the following:

Polyaniline nanofiber as a macroligand for the supported cuprous iodide catalyst (CuI-PANInf) has been developed for the coupling of aryl halides (including aryl chlorides) with aliphatic, aromatic, and N(H)-heterocyclic amines under ambient conditions (80 °C for aryl chlorides) has been developed. This simple and efficient method for coupling reactions is highly versatile, convenient, and also the catalyst can be used for several cycles with good-to-excellent yields. In the experiment, the researchers used many compounds, for example, 4-(Benzylamino)benzonitrile (cas: 10282-32-3Recommanded Product: 10282-32-3).

4-(Benzylamino)benzonitrile (cas: 10282-32-3) belongs to nitriles. Nitriles are polar, as indicated by high dipole moments. As liquids, they have high relative permittivities, often in the 30s. Nitriles are susceptible to hydrogenation over diverse metal catalysts. The reaction can afford either the primary amine (RCH2NH2) or the tertiary amine ((RCH2)3N), depending on conditions.Recommanded Product: 10282-32-3

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Nitrile – Wikipedia,
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Discovery of a Potent, Selective, and Orally Available PI3Kδ Inhibitor for the Treatment of Inflammatory Diseases was written by Erra, Montse;Taltavull, Joan;Greco, Angelique;Bernal, Francisco Javier;Caturla, Juan Francisco;Gracia, Jordi;Dominguez, Maria;Sabate, Mar;Paris, Stephane;Soria, Salome;Hernandez, Begona;Armengol, Clara;Cabedo, Judit;Bravo, Monica;Calama, Elena;Miralpeix, Montserrat;Lehner, Martin D.. And the article was included in ACS Medicinal Chemistry Letters in 2017.Synthetic Route of C5H3ClN4 This article mentions the following:

The delta isoform of the phosphatidylinositol 3-kinase (PI3Kδ) has been shown to have an essential role in specific immune cell functions and thus represents a potential therapeutic target for autoimmune and inflammatory diseases. Herein, the optimization of a series of pyrrolotriazinones as potent and selective PI3Kδ inhibitors is described. The main challenge of the optimization process was to identify an orally available compound with a good pharmacokinetic profile in preclin. species that predicted a suitable dosing regimen in humans. Structure-activity relationships and structure-property relationships are discussed. This medicinal chem. exercise led to the identification of LAS191954 as a candidate for clin. development. In the experiment, the researchers used many compounds, for example, 4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4Synthetic Route of C5H3ClN4).

4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4) belongs to nitriles. Nitrile compounds can be prepared by the incorporation of a cyanide source through C–C bond formation or by dehydration of primary carboxamides. Nitrile groups in organic compounds can undergo a variety of reactions depending on the reactants or conditions. A nitrile group can be hydrolyzed, reduced, or ejected from a molecule as a cyanide ion.Synthetic Route of C5H3ClN4

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts