Category: 60025-09-4

Design and Synthesis of Soluble and Cell-Permeable PI3K鏈?Inhibitors for Long-Acting Inhaled Administration was written by Perry, Matthew W. D.;Bjoerhall, Karin;Bonn, Britta;Carlsson, Johan;Chen, Yunhua;Eriksson, Anders;Fredlund, Linda;Hao, Hai’e;Holden, Neil S.;Karabelas, Kostas;Lindmark, Helena;Liu, Feifei;Pemberton, Nils;Petersen, Jens;Rodrigo Blomqvist, Sandra;Smith, Reed W.;Svensson, Tor;Terstiege, Ina;Tyrchan, Christian;Yang, Wenzhen;Zhao, Shuchun;Oester, Linda. And the article was included in Journal of Medicinal Chemistry in 2017.Electric Literature of C5H3ClN4 This article mentions the following:

PI3K鏈?is a lipid kinase that is believed to be important in the migration and activation of cells of the immune system. Inhibition is hypothesized to provide a powerful yet selective immunomodulatory effect that may be beneficial for the treatment of conditions such as asthma or rheumatoid arthritis. In this work, identification of inhibitors based on a thiazolopyridone core structure and their subsequent optimization for inhalation is described. The initially identified compound I had good potency and isoform selectivity but was not suitable for inhalation. Addition of basic substituents to a region of the mol. pointing to solvent was tolerated (enzyme inhibition pIC₅₀ > 9), and by careful manipulation of the pK_a and lipophilicity, the authors were able to discover compounds II (R = Me or i-Bu) with good lung retention and cell potency that could be taken forward to in vivo studies where significant target engagement could be demonstrated. In the experiment, the researchers used many compounds, for example, 4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4Electric Literature of C5H3ClN4).

4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4) belongs to nitriles. Nitrile carbon shifts are in the range of 115閳?25 ppm whereas in isonitriles the shifts are around 155閳?65 ppm. 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.Electric Literature of C5H3ClN4

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Design and Synthesis of Soluble and Cell-Permeable PI3Kδ Inhibitors for Long-Acting Inhaled Administration was written by Perry, Matthew W. D.;Bjoerhall, Karin;Bonn, Britta;Carlsson, Johan;Chen, Yunhua;Eriksson, Anders;Fredlund, Linda;Hao, Hai’e;Holden, Neil S.;Karabelas, Kostas;Lindmark, Helena;Liu, Feifei;Pemberton, Nils;Petersen, Jens;Rodrigo Blomqvist, Sandra;Smith, Reed W.;Svensson, Tor;Terstiege, Ina;Tyrchan, Christian;Yang, Wenzhen;Zhao, Shuchun;Oester, Linda. And the article was included in Journal of Medicinal Chemistry in 2017.Electric Literature of C5H3ClN4 This article mentions the following:

PI3Kδ is a lipid kinase that is believed to be important in the migration and activation of cells of the immune system. Inhibition is hypothesized to provide a powerful yet selective immunomodulatory effect that may be beneficial for the treatment of conditions such as asthma or rheumatoid arthritis. In this work, identification of inhibitors based on a thiazolopyridone core structure and their subsequent optimization for inhalation is described. The initially identified compound I had good potency and isoform selectivity but was not suitable for inhalation. Addition of basic substituents to a region of the mol. pointing to solvent was tolerated (enzyme inhibition pIC₅₀ > 9), and by careful manipulation of the pK_a and lipophilicity, the authors were able to discover compounds II (R = Me or i-Bu) with good lung retention and cell potency that could be taken forward to in vivo studies where significant target engagement could be demonstrated. In the experiment, the researchers used many compounds, for example, 4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4Electric Literature of C5H3ClN4).

4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4) belongs to nitriles. Nitrile carbon shifts are in the range of 115–125 ppm whereas in isonitriles the shifts are around 155–165 ppm. 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.Electric Literature of C5H3ClN4

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Synthesis, Characterization, Antimicrobial Activity Screening, and Molecular Docking Study of Pyrimidine Carbonitrile Derivatives was written by Bhat, Radhika;Begum, Noor Shahina. And the article was included in Russian Journal of Organic Chemistry in 2021.Computed Properties of C5H3ClN4 This article mentions the following:

The synthesis of pyrimidine carbonitrile derivatives I [R = 1-piperidyl, 2-phenylethylamino, 2-(1H-indol-3-ylmethylene)hydrazino, etc.] was described. The compounds I were characterized by FT-IR and ¹H and ¹³C- NMR spectroscopy and mass spectrometry. All the compounds I were evaluated for in-vitro antimicrobial activity against different bacterial and fungal strains. The min. inhibitory concentrations (MICs) of all the compounds I were validated. Compounds I [R = 2-[(3,4-dimethoxyphenyl)methylene]hydrazino, 1-piperidyl], which had the lowest MIC values were selected for cell leakage anal. and bacterial growth curve study. It was found that both the compounds I [R = 2-[(3,4-dimethoxyphenyl)methylene]hydrazino, 1-piperidyl] have potential to induce bacterial cell membrane rupture and disintegration. Field emission scanning electron microscopic anal. confirmed the effect of the selected compounds on the morphol. of both Gram-pos. (S. aureus) and Gram-neg. (E. coli) bacteria. The mechanism of interaction between the drug and the target protein of S. aureus and E. coli was studied by mol. docking. In the experiment, the researchers used many compounds, for example, 4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4Computed Properties 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. Asymmetric bioreduction of nitriles is an attractive route to produce optically active nitriles as current metal-catalyzed hydrogenations tend to have low reactivity.Computed Properties of C5H3ClN4

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Discovery and in Vivo Evaluation of the Potent and Selective PI3Kδ Inhibitors 2-((1S)-1-((6-Amino-5-cyano-4-pyrimidinyl)amino)ethyl)-6-fluoro-N-methyl-3-(2-pyridinyl)-4-quinolinecarboxamide (AM-0687) and 2-((1S)-1-((6-Amino-5-cyano-4-pyrimidinyl)amino)ethyl)-5-fluoro-N-methyl-3-(2-pyridinyl)-4-quinolinecarboxamide (AM-1430) was written by Gonzalez-Lopez de Turiso, Felix;Hao, Xiaolin;Shin, Youngsook;Bui, Minna;Campuzano, Iain D. G.;Cardozo, Mario;Dunn, Michelle C.;Duquette, Jason;Fisher, Benjamin;Foti, Robert S.;Henne, Kirk;He, Xiao;Hu, Yi-Ling;Kelly, Ron C.;Johnson, Michael G.;Lucas, Brian S.;McCarter, John;McGee, Lawrence R.;Medina, Julio C.;Metz, Daniela;San Miguel, Tisha;Mohn, Deanna;Tran, Thuy;Vissinga, Christine;Wannberg, Sharon;Whittington, Douglas A.;Whoriskey, John;Yu, Gang;Zalameda, Leeanne;Zhang, Xuxia;Cushing, Timothy D.. And the article was included in Journal of Medicinal Chemistry in 2016.Product Details of 60025-09-4 This article mentions the following:

Optimization of the potency and pharmacokinetic profile of the lead 2,3,4-trisubstituted quinoline led to the discovery of two potent, selective, and orally bioavailable PI3Kδ inhibitors, I (AM-0687) and II (AM-1430). On the basis of their improved profile, these analogs were selected for in vivo pharmacodynamic (PD) and efficacy experiments in animal models of inflammation. The in vivo PD studies, which were carried out in a mouse pAKT inhibition animal model, confirmed the observed potency of I and II in biochem. and cellular assays. Efficacy experiments in a keyhole limpet hemocyanin model in rats demonstrated that administration of either I or II resulted in a strong dose-dependent reduction of IgG and IgM specific antibodies. The excellent in vitro and in vivo profiles of these analogs make them suitable for further development. In the experiment, the researchers used many compounds, for example, 4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4Product Details of 60025-09-4).

4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4) 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. 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.Product Details of 60025-09-4

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Discovery, Optimization, and in Vivo Evaluation of Benzimidazole Derivatives AM-8508 and AM-9635 as Potent and Selective PI3Kδ Inhibitors was written by Shin, Youngsook;Suchomel, Julia;Cardozo, Mario;Duquette, Jason;He, Xiao;Henne, Kirk;Hu, Yi-Ling;Kelly, Ron C.;McCarter, John;McGee, Lawrence R.;Medina, Julio C.;Metz, Daniela;San Miguel, Tisha;Mohn, Deanna;Tran, Thuy;Vissinga, Christine;Wong, Simon;Wannberg, Sharon;Whittington, Douglas A.;Whoriskey, John;Yu, Gang;Zalameda, Leeanne;Zhang, Xuxia;Cushing, Timothy D.. And the article was included in Journal of Medicinal Chemistry in 2016.COA of Formula: C5H3ClN4 This article mentions the following:

Lead optimization efforts resulted in the discovery of two potent, selective, and orally bioavailable PI3Kδ inhibitors, 1 (AM-8508) and 2 (AM-9635), with good pharmacokinetic properties. The compounds inhibit B cell receptor (BCR)-mediated AKT phosphorylation (pAKT) in PI3Kδ-dependent in vitro cell based assays. These compounds which share a benzimidazole bicycle are effective when administered in vivo at unbound concentrations consistent with their in vitro cell potency as a consequence of improved unbound drug concentration with lower unbound clearance. Furthermore, the compounds demonstrated efficacy in a Keyhole Limpet Hemocyanin (KLH) study in rats, where the blockade of PI3Kδ activity by inhibitors 1 and 2 led to effective inhibition of antigen-specific IgG and IgM formation after immunization with KLH. In the experiment, the researchers used many compounds, for example, 4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4COA of Formula: C5H3ClN4).

4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4) 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. Asymmetric bioreduction of nitriles is an attractive route to produce optically active nitriles as current metal-catalyzed hydrogenations tend to have low reactivity.COA of Formula: C5H3ClN4

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts