Tag: 100-200

Structurally novel PI3Kδ/γ dual inhibitors characterized by a seven-membered spirocyclic spacer: The SARs investigation and PK evaluation was written by Tao, Qiangqiang;Chen, Yuqing;Liang, Xiao;Hu, Yongzhou;Li, Jiaming;Fang, Fang;Wang, Huchuan;Meng, Chang;Liang, Jingtai;Ma, Xiaodong;Gui, Shuangying. And the article was included in European Journal of Medicinal Chemistry in 2020.HPLC of Formula: 60025-09-4 This article mentions the following:

Herein, we communicate our recent medicinal chem. efforts which have culminated in a series of PI3Kδ/γ dual inhibitors structurally featuring a seven-membered spirocyclic spacer. Compound 26, the most potent one among them, exhibited superior PI3Kδ inhibitory activity (IC₅₀ = 1.0 nM) to that of the approved PI3Kδ inhibitor Idelalisib. Besides, it exerted remarkable anti-proliferative efficacy against human malignant B-cell line SU-DHL-6 with GI₅₀ value of 33 nM. The biochem. assay against the other three class I PI3K isoforms identified compound 26 as a potent PI3Kδ/γ dual inhibitor with considerable selectivity over PI3Kα and PI3Kβ. In SU-DHL-6 cells, a dramatic down-regulation of PI3K signaling was observed following compound 26-treatment at the concentration as low as 10 nM. Inspiringly, the pharmacokinetic (PK) study in Sprague-Dawley (SD) rats revealed it was orally available with a favorable bioavailability (F = 87.5%). Overall, compound 26, a promising PI3Kδ/γ dual inhibitor, has the potential to emerge as a clin. candidate for the treatment of leukocyte-mediated malignancies after extensive functional investigation. In the experiment, the researchers used many compounds, for example, 4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4HPLC of Formula: 60025-09-4).

4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4) 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.HPLC of Formula: 60025-09-4

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Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Novel pyrazolo[1,5-a]pyridines as p110α-selective PI3 kinase inhibitors: Exploring the benzenesulfonohydrazide SAR was written by Kendall, Jackie D.;Giddens, Anna C.;Tsang, Kit Yee;Frederick, Raphael;Marshall, Elaine S.;Singh, Ripudaman;Lill, Claire L.;Lee, Woo-Jeong;Kolekar, Sharada;Chao, Mindy;Malik, Alisha;Yu, Shuqiao;Chaussade, Claire;Buchanan, Christina;Rewcastle, Gordon W.;Baguley, Bruce C.;Flanagan, Jack U.;Jamieson, Stephen M. F.;Denny, William A.;Shepherd, Peter R.. And the article was included in Bioorganic & Medicinal Chemistry in 2012.SDS of cas: 60710-80-7 This article mentions the following:

Structure-activity relationship studies of the pyrazolo[1,5-a]pyridine class of PI3 kinase inhibitors show that substitution off the hydrazone nitrogen and replacement of the sulfonyl both gave a loss of p110α selectivity, with the exception of an N-hydroxyethyl analog. Limited substitutions were tolerated around the Ph ring; in particular the 2,5-substitution pattern was important for PI3 kinase activity. The N-hydroxyethyl compound also showed good inhibition of cell proliferation and inhibition of phosphorylation of Akt/PKB, a downstream marker of PI3 kinase activity. It had suitable pharmacokinetics for evaluation in vivo, and showed tumor growth inhibition in two human tumor cell lines in xenograft studies. This work has provided suggestions for the design of more soluble analogs. In the experiment, the researchers used many compounds, for example, 3-Amino-4-methylbenzonitrile (cas: 60710-80-7SDS of cas: 60710-80-7).

3-Amino-4-methylbenzonitrile (cas: 60710-80-7) 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. Some nitriles are manufactured by heating carboxylic acids with ammonia in the presence of catalysts. This process is used to make nitriles from natural fats and oils, the products being used as softening agents in synthetic rubbers, plastics, and textiles and for making amines.SDS of cas: 60710-80-7

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Discovery of 4-aminopyrimidine analogs as highly potent dual P70S6K/Akt inhibitors was written by Xiao, Yufang;Huck, Bayard R.;Lan, Ruoxi;DeSelm, Lizbeth;Chen, Xiaoling;Qiu, Hui;Neagu, Constantin;Johnson, Theresa;Mochalkin, Igor;Gardberg, Anna;Jiang, Xuliang;Tian, Hui;Dutt, Vikram;Santos, Dusica;Head, Jared;Jackson, Jennifer;Syed, Sakeena;Lin, Jing;Wilker, Erik;Ma, Jianguo;Clark, Anderson;Machl, Andreas;Bankston, Donald;Jones, Christopher C. V.;Goutopoulos, Andreas;Sherer, Brian. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2021.Safety of 4-Amino-6-chloropyrimidine-5-carbonitrile This article mentions the following:

Activation of the PI3K/Akt/mTOR kinase pathway is associated with human cancers. A dual p70S6K/Akt inhibitor is sufficient to inhibit strong tumor growth and to block neg. impact of the compensatory Akt feedback loop activation. A scaffold docking strategy based on an existing quinazoline carboxamide series identified 6-[4-(2-Amino-1-phenyl-ethyl)-piperazin-1-yl]-5-(4-fluoro-phenyl)-pyrimidin-4-ylamine, which showed a single-digit nanomolar and a micromolar potencies in p70S6K and Akt enzymic assays. SAR optimization improved Akt enzymic and p70S6K cellular potencies, reduced hERG liability, and ultimately discovered the promising candidate 4-Amino-6-{4-[1-(2-azetidin-1-yl-ethyl)-4-(4-fluoro-3-trifluoromethyl-phenyl)-1H-imidazol-2-yl]-piperidin-1-yl}pyrimidine-5-carboxylic acid amide, which exhibited with a single digit nanomolar value in both p70S6K and Akt biochem. assays, and hERG activities (IC50 = 17.4 μM). This agent demonstrated dose-dependent efficacy in inhibiting mice breast cancer tumor growth and covered more than 90% pS6 inhibition up to 24 h at a dose of 200 mg/kg po. In the experiment, the researchers used many compounds, for example, 4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4Safety of 4-Amino-6-chloropyrimidine-5-carbonitrile).

4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4) belongs to nitriles. Nitriles are polar, as indicated by high dipole moments. As liquids, they have high relative permittivities, often in the 30s. 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.Safety of 4-Amino-6-chloropyrimidine-5-carbonitrile

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Nitrile – Wikipedia,
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Some amine derivatives of acrylonitrile was written by Wiedemann, O. F.;Montgomery, W. H.. And the article was included in Journal of the American Chemical Society in 1945.Recommanded Product: 3,3′,3”-Nitrilotripropanenitrile This article mentions the following:

Correction. In C.A. 40, 832.2 the m.p. of IV is 59°, not 99°. n_D²⁵ of VI is 1.4802, not 1.4910. (CH₂)₂O in line 38 should read HOCH₂CH₂CN. In the experiment, the researchers used many compounds, for example, 3,3′,3”-Nitrilotripropanenitrile (cas: 7528-78-1Recommanded Product: 3,3′,3”-Nitrilotripropanenitrile).

3,3′,3”-Nitrilotripropanenitrile (cas: 7528-78-1) 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.Recommanded Product: 3,3′,3”-Nitrilotripropanenitrile

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

The [2+2] cycloaddition vs. substitution in photochemical reactions of methoxybenzene-acrylonitrile systems was written by Ohashi, Mamoru;Tanaka, Yoshio;Yamada, Shuzo. And the article was included in Tetrahedron Letters in 1977.SDS of cas: 5351-07-5 This article mentions the following:

Irradiation of PhOMe and RCH:CR¹CN (I; R, R¹ = H, Me) in MeCN gave the corresponding [2+2]cycloadducts II, whereas irradiation of PhOMe and I (R, R¹ = H, Me) in MeOH gave substitution products in addition to II. Thus the photochem. reactions of I (R, R¹ = H, Me) with PhOMe in MeCN are similar to those of I (R = R¹ = H) with PhOMe in MeCN (O. et al., 1976) whereas the reactions in MeOH differ, since I (R = R¹ = H) gave only substitution products, the amount decreasing in the order I (R = R¹ = H) > I (R = H, R¹ = Me) > I (R = Me, R¹ = H). A similar tendency is also observed for (MeO)₂C₆H₄-RCH:CR¹CN systems. The higher the reduction potential (or electron affinity) of the olefin or the lower the oxidation potential of the aromatic, the larger the amount of substitution products. Although participation of the proton-transfer step is revealed by the use of MeOD in place of MeOH, the rate-determining step of the substitution is electron transfer. A reaction scheme consistent with these results is given. In the experiment, the researchers used many compounds, for example, 2-(4-Methoxyphenyl)-2-methylpropanenitrile (cas: 5351-07-5SDS of cas: 5351-07-5).

2-(4-Methoxyphenyl)-2-methylpropanenitrile (cas: 5351-07-5) 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.SDS of cas: 5351-07-5

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Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Utilization of tetraethylammonium cyanide for preparation of cyclopentadienyl iron cyanocyclohexadienyl complexes. Study of their electrochemical and chemical oxidation. was written by Guennec, N.;Moinet, C.. And the article was included in Journal of Organometallic Chemistry in 1995.Product Details of 64113-86-6 This article mentions the following:

Addition of Et₄NCN to a solution of (η⁵-cyclopentadienyl)(η⁶-arene)iron(1+), in MeCN was studied by voltammetry. With electron-withdrawing groups such as nitro, keto, sulfone, azo and azoxy bonded to the arene, the reaction occurs immediately and a wave resulting from oxidation of hexadienyl species is observed in the range 0-1V vs. SCE. Preparation of various hexadienyl compounds, e.g. I (X = NO₂, COPh, SO₂Ph) was achieved with good yields. To obtain ortho-substituted benzonitriles, electrochem. and chem. oxidations of hexadienyl complexes were compared. The best results were obtained with N-bromosuccinimide (NBS) and a demetalation generally occurs. A 1-pot synthesis of benzonitrile compounds can be achieved after addition of cyanide ion and then NBS to a solution of (η⁵-cyclopentadienyl)(η⁶-arene)iron(1+) in MeCN. [CpFe{η⁶-C₆H₅N(O):NC₆H₄CN-2}]⁺ is directly obtained from the azoxy dicationic compound [(CpFe)₂(PhN(O)NPh)]²⁺. In the experiment, the researchers used many compounds, for example, 5-Methyl-2-nitrobenzonitrile (cas: 64113-86-6Product Details of 64113-86-6).

5-Methyl-2-nitrobenzonitrile (cas: 64113-86-6) belongs to nitriles. The electronic structure of nitriles is very similar to that of an alkyne with the main difference being the presence of a set of lone pair electrons on the nitrogen. 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 64113-86-6

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One-Pot Synthesis of Quinazolines via Elemental Sulfur-Mediated Oxidative Condensation of Nitriles and 2-(Aminomethyl)anilines was written by Tan, Yuxing;Jiang, Wujiu;Ni, Penghui;Fu, Yang;Ding, Qiuping. And the article was included in Advanced Synthesis & Catalysis in 2022.Recommanded Product: 2-Amino-3-chlorobenzonitrile This article mentions the following:

A strategy for the synthesis of quinazolines I [R = H, 6-Me, 8-Br, etc.; Ar = Ph, 4-MeC₆H₄, 2-ClC₆H₄, etc.] via elemental sulfur-mediated oxidative condensation of nitriles and 2-(aminomethyl)anilines was developed. The reaction was carried out under metal-/solvent-free conditions, tolerated a wide range of functional groups to provide the corresponding products in 56%-91% yield, and was performed on a gram-scale. The UV/Vis absorption and fluorescence spectra of several product derivatives were measured to study their photophys. properties. In the experiment, the researchers used many compounds, for example, 2-Amino-3-chlorobenzonitrile (cas: 53312-77-9Recommanded Product: 2-Amino-3-chlorobenzonitrile).

2-Amino-3-chlorobenzonitrile (cas: 53312-77-9) belongs to nitriles. Nitriles are polar, as indicated by high dipole moments. As liquids, they have high relative permittivities, often in the 30s. 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.Recommanded Product: 2-Amino-3-chlorobenzonitrile

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Organophosphorus compounds with β-cyanoethyl-type structural components. I. Synthesis of β-cyanoethylated amidophosphites and phosphoramides was written by Petrov, Pavel;Vlad, Florin-Iosif;Muresan, Sorel;Valceanu, Radu. And the article was included in Revista de Chimie (Bucharest) in 1995.Electric Literature of C9H12N4 This article mentions the following:

This paper presents three types of phosphorylation reactions for mixtures of NH(CH₂CH₂CN)₂ with N(CH₂CH₂CN)₃, obtained by nucleophilic addition reaction of NH₃ to acrylonitrile. Thus, reaction of 10 equiv (MeO)₂P(O)H with a 10:1 mixture of the above amines in PhMe containing CCl₄ and Et₃N gave (MeO)₂P(O)N(CH₂CH₂CN)₂. Reaction of 4 equiv PCl₃ or P(O)Cl₃ with a 21:3 mixture of the amines in dichloroethane gave P[N(CH₂CH₂CN)₂]₃ or P(O)[N(CH₂CH₂CN)₂]₃, resp. In the experiment, the researchers used many compounds, for example, 3,3′,3”-Nitrilotripropanenitrile (cas: 7528-78-1Electric Literature of C9H12N4).

3,3′,3”-Nitrilotripropanenitrile (cas: 7528-78-1) 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. Asymmetric bioreduction of nitriles is an attractive route to produce optically active nitriles as current metal-catalyzed hydrogenations tend to have low reactivity.Electric Literature of C9H12N4

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Observation of hyperpositive non-linear effect in catalytic asymmetric organozinc additions to aldehydes was written by Geiger, Yannick;Achard, Thierry;Maisse-Francois, Aline;Bellemin-Laponnaz, Stephane. And the article was included in Chirality in 2020.SDS of cas: 101219-69-6 This article mentions the following:

Asym. amplification is a phenomenon that is believed to play a key role in the emergence of homochirality in life. In asym. catalysis, theor. and exptl. models have been investigated to provide an understanding of how chiral amplification is possible, in particular based on non-linear effects. Interestingly, it has been proposed a quarter century ago that chiral catalysts, when not enantiopure might even be more enantioselective than their enantiopure counterparts. We show here that such hyperpos. non-linear effect in asym. catalysis is indeed possible. An in-depth study into the underlying mechanism was carried out, and the scheme we derive differs from the previous proposed models. In the experiment, the researchers used many compounds, for example, (R)-4-(1-Hydroxyethyl)benzonitrile (cas: 101219-69-6SDS of cas: 101219-69-6).

(R)-4-(1-Hydroxyethyl)benzonitrile (cas: 101219-69-6) belongs to nitriles. The R-C-N bond angle in and nitrile is 180° which give a nitrile functional group a linear shape. Both the carbon and the nitrogen are sp hydridized which leaves them both with two p orbitals which overlap to form the two π bond in the triple bond. 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. SDS of cas: 101219-69-6

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Nitrile – Wikipedia,
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Synthesis of Aromatic Nitriles via the Temporary Complexation of Nitroarenes to the Cationic Cyclopentadienyliron Moiety was written by Abd-El-Aziz, Alaa S.;Boraie, Waleed;Gavel, Nicole T.. And the article was included in Organometallics in 1999.Name: 5-Methyl-2-nitrobenzonitrile This article mentions the following:

Cyanide addition to cationic cyclopentadienyliron complexes of substituted nitroarenes (I; R = 4-Me, -Et, -CHMe₂, -n-Bu, -tert-Bu, -sec-Bu, -(CH)₄CH₃; 2-CHMe₂; 2,3-, 2,4-, 3,4-, 3,5-Me₂) produced nitrile adducts (II, R = same as above) where the cyano group added regioselectively in the ortho position with respect to the nitro group. Cleavage of the cyclopentadienyliron moiety via oxidative demetalation with DDQ gave functionalized benzonitriles (III, R = same as above) in good yields. Thus, I (R = 4-Me) reacted with a 7-fold excess of NaCN in DMF under mild exptl. conditions to give 72% II (R = 4-Me) which subsequently underwent oxidative demetalation with DDQ to give 83% III (R = 4-Me). In the experiment, the researchers used many compounds, for example, 5-Methyl-2-nitrobenzonitrile (cas: 64113-86-6Name: 5-Methyl-2-nitrobenzonitrile).

5-Methyl-2-nitrobenzonitrile (cas: 64113-86-6) belongs to nitriles. Nitrile carbon shifts are in the range of 115�25 ppm whereas in isonitriles the shifts are around 155�65 ppm. Asymmetric bioreduction of nitriles is an attractive route to produce optically active nitriles as current metal-catalyzed hydrogenations tend to have low reactivity.Name: 5-Methyl-2-nitrobenzonitrile

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts