NOVEL UREA DERIVATIVES AS TEC KINASE INHIBITORS AND USES THEREOF
Provided are urea compounds of formula (I) as Tec kinase inhibitors, in particular ITK (interleukin-2 inducible tyrosine kinase) inhibitors. Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders mediated by ITK.
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Page/Page column 39; 46
(2013/03/26)
Discovery of potent inhibitors of interleukin-2 inducible T-cell kinase (ITK) through structure-based drug design
Interleukin-2 inducible T-cell kinase (ITK) is a member of the Tec kinase family and is involved with T-cell activation and proliferation. Due to its critical role in acting as a modulator of T-cells, ITK inhibitors could provide a novel route to anti-inf
Cook, Brian N.,Bentzien, J?rg,White, Andre,Nemoto, Peter A.,Wang, Ji,Man, Chuk C.,Soleymanzadeh, Fariba,Khine, Hnin Hnin,Kashem, Mohammed A.,Kugler Jr., Stanley Z.,Wolak, John P.,Roth, Gregory P.,De Lombaert, Stéphane,Pullen, Steven S.,Takahashi, Hidenori
scheme or table
p. 773 - 777
(2009/08/15)
2-Aminobenzimidazoles as potent ITK antagonists: trans-stilbene-like moieties targeting the kinase specificity pocket
Based on the information from molecular modeling and X-ray crystal structures, the kinase specificity pocket of ITK could be occupied upon extension of the right-hand-side of the 2-benzimidazole core of the inhibitors. 2-Aminobenzimidazoles with a trans-stilbene-like extension were designed and synthesized as novel ITK antagonists. Significant improvement on binding affinity and cellular activity were obtained through the trans-stilbene-like antagonists. Several compounds showed inhibitory activity in an IL-2 functional assay.
Lo, Ho Yin,Bentzien, Joerg,Fleck, Roman W.,Pullen, Steven S.,Khine, Hnin Hnin,Woska Jr., Joseph R.,Kugler, Stanley Z.,Kashem, Mohammed A.,Takahashi, Hidenori
scheme or table
p. 6218 - 6221
(2009/07/18)
Itk kinase inhibitors: Initial efforts to improve the metabolical stability and the cell activity of the benzimidazole lead
Previously, we reported a series of novel benzimidazole based Itk inhibitors that exhibited excellent enzymatic potency and selectivity but low microsomal stability. Employing a structure based approach a new series of inhibitors with comparable potency a
Moriarty, Kevin J.,Winters, Michael,Qiao, Lei,Ryan, Declan,DesJarlis, Renee,Robinson, Darius,Cook, Brian N.,Kashem, Mohammed A.,Kaplita, Paul V.,Liu, Lisa H.,Farrell, Thomas M.,Khine, Hnin Hnin,King, Josephine,Pullen, Steven S.,Roth, Gregory P.,Magolda, Ronald,Takahashi, Hidenori
scheme or table
p. 5537 - 5540
(2009/06/30)
Discovery, SAR and X-ray structure of 1H-benzimidazole-5-carboxylic acid cyclohexyl-methyl-amides as inhibitors of inducible T-cell kinase (Itk)
A series of novel potent benzimidazole based inhibitors of interleukin-2 T-cell kinase (Itk) were prepared. In this report, we discuss the structure-activity relationship (SAR), selectivity, and cell-based activity for the series. We also discuss the SAR associated with an X-ray structure of one of the small-molecule inhibitors bound to ITK.
Moriarty, Kevin J.,Takahashi, Hidenori,Pullen, Steven S.,Khine, Hnin Hnin,Sallati, Rosemarie H.,Raymond, Ernest L.,Woska Jr., Joseph R.,Jeanfavre, Deborah D.,Roth, Gregory P.,Winters, Michael P.,Qiao, Lei,Ryan, Declan,DesJarlais, Renee,Robinson, Darius,Wilson, Matthew,Bobko, Mark,Cook, Brian N.,Lo, Ho Yin,Nemoto, Peter A.,Kashem, Mohammed A.,Wolak, John P.,White, André,Magolda, Ronald L.,Tomczuk, Bruce
scheme or table
p. 5545 - 5549
(2009/06/18)
THIOPHENE -2- CARBOXYLIC ACID - (1H - BENZIMIDAZOL - 2 YL) - AMIDE DERIVATIVES AND RELATED COMPOUNDS AS INHIBITORS OF THE TEC KINASE ITK (INTERLEUKIN -2- INDUCIBLE T CELL KINASE) FOR THE TREATMENT OF INFLAMMATION, IMMUNOLOGICAL AND ALLERGIC DISORDERS
Disclosed are compounds of formula (I): wherein Ar1, Ar2, R1, R2, R3, R4 and Xa are defined herein. The compounds of the invention inhibit Itk kinase and are therefore useful for
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Page/Page column 129-131
(2010/02/13)
SUBSTITUTED BENZIMIDAZOLE COMPOUNDS
Disclosed are substituted benzimidazole compounds of formula (I) wherein R1, R2, R3, R4 and Xa are defined herein. The compounds of the invention inhibit Itk kinase and are therefore useful for treating diseases and pathological conditions involving inflammation, immunological disorders and allergic disorders. Also disclosed are processes for preparing these compounds and the pharmaceutical compositions comprising these compounds.
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Page 156
(2008/06/13)
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