- Discovery of cinnoline derivatives as potent PI3K inhibitors with antiproliferative activity
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Cinnoline is a potential pharmacophore which has rarely been reported for uses as PI3K inhibitors. In this study, a series of cinnoline derivatives were developed as PI3K inhibitors and evaluated for enzymatic and cellular activities. Most compounds displ
- Chen, Yi,Deng, Mingli,Jia, Yu,Ling, Yun,Liu, Xiaofeng,Lu, Mingzhu,Tian, Chengze,Wu, Tianze,Yang, Chengbin,Yang, Yongtai,Zhou, Yaming
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supporting information
(2021/07/28)
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- Copper-catalyzed tandem C-N bond formation: An efficient annulative synthesis of functionalized cinnolines
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Cinn-tillating synthesis: The combination of a readily available copper catalyst, a simple hydrazide nucleophile, and established difunctionalized building blocks provides a new, flexible route to an under-developed class of aromatic heterocycles, cinnolines (see scheme). Copyright
- Ball, Catherine J.,Gilmore, Jeremy,Willis, Michael C.
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supporting information; experimental part
p. 5718 - 5722
(2012/08/14)
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- Synthesis and SAR of indazole-pyridine based protein kinase B/Akt inhibitors
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A series of heteroaryl-pyridine containing inhibitors of Akt are reported. The synthesis and structure-activity relationships are discussed, leading to the discovery of a indazole-pyridine analogue (Ki = 0.16 nM). These compounds bind in the ATP binding site, are potent, ATP competitive, and reversible inhibitors of Akt activity. No selectivity amongst the Akt isoforms is observed for this analogue, but there is good selectivity against an panel of other kinases. It is least selective for other members of the AGC family of kinases but is nonetheless 40-fold selective for Akt over PKA. The compound shows cellular activity and significantly slows tumor growth in vivo.
- Woods, Keith W.,Fischer, John P.,Claiborne, Akiyo,Li, Tongmei,Thomas, Sheela A.,Zhu, Gui-Dong,Diebold, Robert B.,Liu, Xuesong,Shi, Yan,Klinghofer, Vered,Han, Edward K.,Guan, Ran,Magnone, Shayna R.,Johnson, Eric F.,Bouska, Jennifer J.,Olson, Amanda M.,Jong, Ron de,Oltersdorf, Tilman,Luo, Yan,Rosenberg, Saul H.,Giranda, Vincent L.,Li, Qun
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p. 6832 - 6846
(2007/10/03)
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- Kinase inhibitors
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Compounds having the formula are useful for inhibiting protein kinases. Also disclosed are compositions which inhibit protein kinases and methods of inhibiting protein kinases in a patient.
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- Kinase inhibitors
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Compounds having the formula are useful for inhibiting protein kinases. Also disclosed are compositions which inhibit protein kinases and methods of inhibiting protein kinases in a patient.
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Page/Page column 27
(2010/01/31)
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- Cyclization of 1-(2-alkynylphenyl)-3,3-dialkyltriazenes: A convenient, high-yield synthesis of substituted cinnolines and isoindazoles
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A new route to isoindazoles and cinnolines through the cyclization of (2-alkynylphenyl)triazenes under neutral conditions is presented. The products that result from heating the starting triazenes depend on both the type of alkyne ortho to the triazene functionality and the temperature used. Butadiyne moieties ortho to dialkyltriazenes yield bis-isoindazole dimers when heated to 150 °C in MeI. A requirement for cyclization in MeI is that the (2-alkynylphenyl)triazene must contain a suitably electron-withdrawing substituent on the phenyl ring to deactivate the triazene toward methylation-induced decomposition to an iodoarene. Ethynyl moieties ortho to dialkyltriazenes yield both isoindazole dimers as well as 3-formylisoindazoles when subjected to the same conditions. Replacing MeI with 1,2-dichlorobenzene as solvent allows for the general cyclization of (2-ethynylphenyl)dialkyltriazenes. Heating to 170 °C results in a mixture of isoindazole and cinnoline products, whereas the cinnolines are produced exclusively in high yield at 200 °C. Alternatively, the isoindazoles can be obtained in good to excellent yield by stirring a 1,2-dichloroethane solution of the starting triazene with CuCl overnight at 50 °C.
- Kimball, David B.,Weakley, Timothy J. R.,Haley, Michael M.
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p. 6395 - 6405
(2007/10/03)
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- Deciphering the mechanistic dichotomy in the cyclization of 1-(2-ethynylphenyl)-3,3-dialkyltriazenes: Competition between pericyclic and pseudocoarctate pathways
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The mechanistic aspects of the cyclization of (2-ethynylphenyl)triazenes under both thermal and copper-mediated conditions are reported. For cyclization to an isoindazole, a carbene mechanistic pathway is proposed. The carbene intermediate can react with oxygen, dimerize to give an alkene, or be trapped either intermolecularly (using 2,3-dimethyl-2-butene to generate a cyclopropane) or intramolecularly (using a biphenyl moiety at the terminus of the acetylene to form a fluorene). Density-functional theory (DFT) calculations support a pseudocoarctate pathway for this type of cyclization. Thermal cyclization to give a cinnoline from (2-ethynylphenyl)triazenes is proposed to occur through a pericyclic pathway. DFT calculations predict a zwitterionic dehydrocinnolinium intermediate that is supported by deuterium trapping studies as well as cyclizations performed using a 2,2,6,6-tetramethylpiperidine moiety at the 3-position of the triazene.
- Kimball, David B.,Weakley, Timothy J. R.,Herges, Rainer,Haley, Michael M.
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p. 13463 - 13473
(2007/10/03)
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- Thermal Cyclization of (2-Ethynylphenyl)triazenes: Facile Synthesis of Substituted Cinnolines and Isoindazoles
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formula presented High-temperature intramolecular cyclization of N,N-dialkyl-N′-substituted-2-ethynylphenyl)triazenes provides under neutral conditions both 6-substituted cinnolines and 5-substituted isoindazoles in moderate to excellent yields.
- Kimball, David B.,Hayes, Austin G.,Haley, Michael M.
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p. 3825 - 3827
(2007/10/03)
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