74609-49-7Relevant academic research and scientific papers
CONJUGATES COMPRISING RIPK2 INHIBITORS
-
Page/Page column 91; 92, (2017/11/15)
The present invention relates to compounds, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of RIP2 kinase, including degrading RIP2 kinase, the treatment of diseases and conditions mediated by the RIP2 kinase, in particular for the treatment of inflammatory diseases or conditions.
IMIDAZOPYRIDINE COMPOUNDS AND USES THEREOF
-
Paragraph 222, (2014/08/19)
This invention generally relates to substituted imidazopyridine compounds, particularly substituted 4-(imidazo[1,2-a]pyridin-2-yl)benzamide compounds and salts thereof. This invention also relates to pharmaceutical compositions and kits comprising such a compound, uses of such a compound (including, for example, treatment methods and medicament preparations), processes for making such a compound, and intermediates used in such processes.
Design, synthesis and crystal structure determination of dinuclear copper-based potential chemotherapeutic drug entities; In vitro DNA binding, cleavage studies and an evaluation of genotoxicity by micronucleus test and comet assay
Arjmand, Farukh,Muddassir, Mohd,Zaidi, Yusra,Ray, Debashis
, p. 394 - 405 (2013/06/26)
Copper-based potential chemotherapeutic complexes 1 and 2 were designed, synthesized and evaluated for in vitro DNA binding, cleaving capability and in vivo genotoxicity. The structural elucidation of complexes was done using elemental and spectroscopic data while the (R)-enantiomer of Cu(ii) complex 1 was studied by single crystal diffraction. In vitro DNA binding profiling of both (R)- and (S)-enantiomers of complexes 1 and 2 was carried out to evaluate their enantioselectivity, exhibiting a remarkable degree of enantioselectivity in their interaction with DNA, with the (R)-enantiomer exhibiting greater DNA binding propensity. Interaction between complexes and pBR322 DNA was evaluated by agarose gel electrophoresis assay; both the (R)-enantiomeric complexes exhibit effective DNA cleavage and proceed via an oxidative pathway. Furthermore, the in vivo genotoxicity of the (R)-enantiomer of complex 1 was evaluated by micronucleus testing on bone marrow cells and comet assay in peripheral blood lymphocytes. These results support our contention that the (R)-enantiomer of complex 1 is a suitable chemotherapeutic drug candidate showing reduced toxic effects on normal cells as compared to cisplatin and an antioxidant (EVOO). The Royal Society of Chemistry.
Structure-based design of potent and selective 3-phosphoinositide-dependent kinase-1 (PDK1) inhibitors
Medina, Jesús R.,Becker, Christopher J.,Blackledge, Charles W.,Duquenne, Celine,Feng, Yanhong,Grant, Seth W.,Heerding, Dirk,Li, William H.,Miller, William H.,Romeril, Stuart P.,Scherzer, Daryl,Shu, Arthur,Bobko, Mark A.,Chadderton, Antony R.,Dumble, Melissa,Gardiner, Christine M.,Gilbert, Seth,Liu, Qi,Rabindran, Sridhar K.,Sudakin, Valery,Xiang, Hong,Brady, Pat G.,Campobasso, Nino,Ward, Paris,Axten, Jeffrey M.
, p. 1871 - 1895 (2011/05/30)
Phosphoinositide-dependent protein kinase-1(PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDK1 might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDK1 inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OCl-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDK1 and the potential pharmacological uses of a PDK1 inhibitor.
CHEMICAL COMPOUNDS
-
Page/Page column 181, (2010/07/10)
The invention is directed to 6-(4-pyι?midinyl)-1 H-indazole derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein R1 - R4 are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of immune and metabolic diseases and disorders characterized by constitutively activated ACG kinases such as cancer and more specifically cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
CHEMICAL COMPOUNDS
-
Page/Page column 101, (2010/11/04)
The invention is directed to to substituted indazole derivatives. Specifically, the invention is directed to compounds according to Formula I: wherein R1 - R6 and X are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of disorders characterized by constitutively activated ACG kinases such as cancer and more specifically leukemia and cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
SUBSTITUTED PIPERAZINES AS CB1 ANTAGONISTS
-
Page/Page column 203-204, (2009/03/07)
Compounds of Formula (I) or pharmaceutically acceptable salts, solvates, or esters thereof, are useful in treating diseases or conditions mediated by CB1receptors, such as metabolic syndrome and obesity, neuroinflammatory disorders, cognitive disorders and psychosis, addiction (e.g., smoking cessation), gastrointestinal disorders, and cardiovascular conditions.
2-AMINOBENZOXAZOLE CARBOXAMIDES AS 5HT3 MODULATORS
-
Page/Page column 21, (2008/12/04)
Compounds of formulae I, II and III: are disclosed as 5-HT3 inhibitors. The compounds are useful in treating CINV, IBS-D and other diseases and conditions.
Phthalazine, aza- and diaza-phthalazine compounds and methods of use
-
Page/Page column 45, (2008/06/13)
The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have a general Formula I wherein A1, A2, B, R1, R2, R3 and R4 are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of kinase mediated diseases including rheumatoid arthritis, psoriasis and other inflammation disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.
Combination therapy with CHK1 inhibitors
-
, (2008/06/13)
Compounds of Structure I, and salts, tautomers, stereoisomers, and mixtures thereof may be used in methods of inhibiting checkpoint kinase 1 in subjects, in methods for inducing cell cycle progression, and in methods for increasing apoptosis in cells. Such compounds may be used to prepare pharmaceutical compositions and may be used in conjunction with DNA damaging agents.
