70456-63-2Relevant academic research and scientific papers
Electrophile-Directed Diastereoselective Oxonitrile Alkylations
Chepyshev, Sergiy V.,Pitta, Bhaskar Reddy,Vangala, Saidi Reddy,Lujan-Montelongo, J. Armando,Steward, Omar W.,Fleming, Fraser F.
, p. 2850 - 2853 (2018)
Diastereoselective alkylation of prochiral oxonitrile dianions with secondary alkyl halides efficiently installs two contiguous stereogenic centers. The confluence of nucleophilic trajectory and the electrophile chirality causes distinct steric differences that allow efficient discrimination for one of the six possible conformers. Numerous oxonitrile-derived dianions efficiently displace secondary alkyl halides propagating the electrophile chirality to efficiently install two contiguous tertiary centers. The prevalence of chiral, secondary electrophiles makes the interdigitated alkylation of chiral electrophiles a particularly attractive route because the resulting oxonitriles are readily transformed into bioactive heterocycles.
Identification, characterization and initial hit-to-lead optimization of a series of 4-arylamino-3-pyridinecarbonitrile as protein kinase C theta (PKCθ) inhibitors
Cole, Derek C.,Asselin, Magda,Brennan, Agnes,Czerwinski, Robert,Ellingboe, John W.,Fitz, Lori,Greco, Rita,Huang, Xinyi,Joseph-McCarthy, Diane,Kelly, Michael F.,Kirisits, Matthew,Lee, Julie,Li, Yuanhong,Morgan, Paul,Stock, Joseph R.,Tsao, Désirée H. H.,Wissner, Allan,Yang, Xiaoke,Chaudhary, Divya
experimental part, p. 5958 - 5963 (2009/10/09)
The protein kinase C (PKC) family of serine/threonine kinases is implicated in a wide variety of cellular processes. The PKC theta (PKCθ) isoform is involved in TCR signal transduction and T cell activation and regulates T cell mediated diseases, including lung inflammation and airway hyperresponsiveness. Thus inhibition of PKCθ enzyme activity by a small molecule represents an attractive strategy for the treatment of asthma. A PKCθ high-throughput screening (HTS) campaign led to the identification of 4-(3-bromophenylamino)-5- (3,4-dimethoxyphenyl)-3-pyridinecarbonitrile 4a, a low μM ATP competitive PKCθ inhibitor. Structure based hit-to-lead optimization led to the identification of 5-(3,4-dimethoxyphenyl)-4-(1H-indol-5-ylamino)-3- pyridinecarbonitrile 4p, a 70 nM PKCθ inhibitor. Compound 4p was selective for inhibition of novel PKC isoforms over a panel of 21 serine/threonine, tyrosine, and phosphoinositol kinases, in addition to the conventional and atypical PKCs, PKCβ, and PKCζ, respectively. Compound 4p also inhibited IL-2 production in antiCD3/anti-CD28 activated T cells enriched from splenocytes.
Substituted 3-cyanopyridines as protein kinase inhibitors
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Page/Page column 28, (2008/06/13)
The present teachings provide compounds of formula I and their pharmaceutically acceptable salts, hydrates, and esters, wherein R1, R2, and X are as defined herein. The present teachings also provide methods of making the compounds of formula I, and methods of treating autoimmune and inflammatory diseases by administering a therapeutically effective amount of a compound or compounds of formula I to a mammal including a human.
Substituted Cyanopyridines as protein kinase inhibitors
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Page/Page column 17, (2008/06/13)
The present teachings provide compounds of formula I and their pharmaceutically acceptable salts, hydrates, and esters, wherein R1, R2, and X are as defined herein. The present teachings also provide methods of making the compounds of formula I, and methods of treating autoimmune and inflammatory diseases by administering a therapeutically effective amount of a compound or compounds of formula I to a mammal including a human.
