913067-90-0Relevant academic research and scientific papers
1H-1,8- NAPHTHYRIDIN-2ONES AS ANTI PROLIFERATIVE COMPOUNDS
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Page/Page column 38, (2015/12/30)
The present invention relates to novel antiproliferative1H-1, 8-naphthyridin-2-ones of the general formula (I) or pharmaceutically acceptable salts thereof: In which the variable groups are as defined herein, and their preparation and use in therapeutic treatment of disorders related to inhibition of tyrosine kinases in warm blooded animals. The compounds can overcome imatinib induced drug resistance.
EPHA4 RTK INHIBITORS FOR TREATMENT OF NEUROLOGICAL AND NEURODEGENERATIVE DISORDERS AND CANCER
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Page/Page column 17, (2010/08/08)
The present invention is directed to compounds of generic formula (I) which are inhibitors of ephrin A4. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases regulated by the EphA4 RTK signaling, such as neurological and neurodegenerative disorders and cancer.
9-(Arenethenyl)purines as dual Src/Abl kinase inhibitors targeting the inactive conformation: Design, synthesis, and biological evaluation
Huang, Wei-Sheng,Zhu, Xiaotian,Wang, Yihan,Azam, Mohammad,Wen, David,Sundaramoorthi, Raji,Thomas, R. Mathew,Liu, Shuangying,Banda, Geetha,Lentini, Scott P.,Das, Sasmita,Xu, Qihong,Keats, Jeff,Wang, Frank,Wardwell, Scott,Ning, Yaoyu,Snodgrass, Joseph T.,Broudy, Marc I.,Russian, Karin,Daley, George Q.,Iuliucci, John,Dalgarno, David C.,Clackson, Tim,Sawyer, Tomi K.,Shakespeare, William C.
experimental part, p. 4743 - 4756 (2010/03/03)
A novel series of potent dual Src/Abl kinase inhibitors based on a 9-(arenethenyl)purine core has been identified. Unlike traditional dual Src/Abl inhibitors targeting the active enzyme conformation, these inhibitors bind to the inactive, DFG-out conformation of both kinases. Extensive SAR studies led to the discovery of potent and orally bioavailable inhibitors, some of which demonstrated in vivo efficacy. Once-daily oral administration of inhibitor 9i (AP24226) significantly prolonged the survival of mice injected intravenously with wild type Bcr-Abl expressing Ba/F3 cells at a dose of 10 mg/kg. In a separate model, oral administration of 9i to mice bearing subcutaneous xenografts of Src Y527F expressing NIH 3T3 cells elicited dose-dependent tumor shrinkage with complete tumor regression observed at the highest dose. Notably, several inhibitors (e.g., 14a, AP24163) exhibited modest cellular potency (IC50 = 300-400 nM) against the Bcr-Abl mutant T315I, a variant resistant to all currently marketed therapies for chronic myeloid leukemia. 2009 American Chemical Society.
SUBSTITUTED HETEROCYCLES AS JANUS KINASE INHIBITORS
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Page/Page column 57, (2008/12/07)
The present invention provides substituted tricyclic heteroaryl compounds, including, for example, pyridoindoles, pyrimidinoindoles and triazinoindoles that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases such as immune-related diseases, skin disorders, myeloid proliferative disorders, cancer, and other diseases.
UNSATURATED HETEROCYCLIC DERIVATIVES
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Page/Page column 36, (2008/06/13)
This invention relates to compounds of the general formula: in which the variable groups are as defined herein, and to their preparation and use.
Discovery of aminoquinazolines as potent, orally bioavailable inhibitors of Lck: Synthesis, SAR, and in vivo anti-inflammatory activity
DiMauro, Erin F.,Newcomb, John,Nunes, Joseph J.,Bemis, Jean E.,Boucher, Christina,Buchanan, John L.,Buckner, William H.,Cee, Victor J.,Chai, Lilly,Deak, Holly L.,Epstein, Linda F.,Faust, Ted,Gallant, Paul,Geuns-Meyer, Stephanie D.,Gore, Anu,Gu, Yan,Henkle, Brad,Hodous, Brian L.,Hsieh, Faye,Huang, Xin,Kim, Joseph L.,Lee, Josie H.,Martin, Matthew W.,Masse, Craig E.,McGowan, David C.,Metz, Daniela,Mohn, Deanna,Morgenstern, Kurt A.,Oliveira-Dos-Santos, Antonio,Patel, Vinod F.,Powers, David,Rose, Paul E.,Schneider, Stephen,Tomlinson, Susan A.,Tudor, Yan-Yan,Turci, Susan M.,Welcher, Andrew A.,White, Ryan D.,Zhao, Huilin,Zhu, Li,Zhu, Xiaotian
, p. 5671 - 5686 (2007/10/03)
The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and natural killer (NK) cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activation. Selective inhibition of Lck is expected to offer a new therapy for the treatment of T-cell-mediated autoimmune and inflammatory disease. Screening of our kinase-preferred collection identified aminoquinazoline 1 as a potent, nonselective inhibitor of Lck and T cell proliferation. In this report, we describe the synthesis and structure-activity relationships of a series of novel aminoquinazolines possessing in vitro mechanism-based potency. Optimized, orally bioavailable compounds 32 and 47 exhibit anti-inflammatory activity (ED50 of 22 and 11 mg/kg, respectively) in the anti-CD3-induced production of interleukin-2 (IL-2) in mice.
