- 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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- Cnoline compound PI3K kinase inhibitor as well as preparation method and application thereof in pharmacy
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The invention provides a cinnoline compound PI3K kinase inhibitor as shown in a formula I. In the cinnoline compound PI3K kinase inhibitor, and R1, R2 and R3 are defined in the specification. The invention also provides a pharmaceutical composition of the
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- Thiazolidine derivatives or salts thereof as an active ingredient an inhibitor Pim
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PROBLEM TO BE SOLVED: To provide compounds which have excellent Pim inhibitory action and are useful as pharmaceuticals.SOLUTION: A compound is a thiazolidine derivative represented by the general formula (1) in the figure, or a salt thereof. (In the formula, X represents O or S; Rrepresents a hydrogen atom or a Calkyl group; Z, Z, Z, Z, Zand Zeach independently represent CH or N; Y represents an optionally substituted, divalent Caromatic hydrocarbon group or the like; Am represents a disubstituted amino group, or an optionally substituted, nitrogen-containing saturated heterocyclic group; and Rand Reach independently represent a hydrogen atom, a halogen atom, an alkyl group or the like.)
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- Protozoan Parasite Growth Inhibitors Discovered by Cross-Screening Yield Potent Scaffolds for Lead Discovery
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Tropical protozoal infections are a significant cause of morbidity and mortality worldwide; four in particular (human African trypanosomiasis (HAT), Chagas disease, cutaneous leishmaniasis, and malaria) have an estimated combined burden of over 87 million disability-adjusted life years. New drugs are needed for each of these diseases. Building on the previous identification of NEU-617 (1) as a potent and nontoxic inhibitor of proliferation for the HAT pathogen (Trypanosoma brucei), we have now tested this class of analogs against other protozoal species: T. cruzi (Chagas disease), Leishmania major (cutaneous leishmaniasis), and Plasmodium falciparum (malaria). Based on hits identified in this screening campaign, we describe the preparation of several replacements for the quinazoline scaffold and report these inhibitors' biological activities against these parasites. In doing this, we have identified several potent proliferation inhibitors for each pathogen, such as 4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-6-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)quinoline-3-carbonitrile (NEU-924, 83) for T. cruzi and N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-7-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)cinnolin-4-amine (NEU-1017, 68) for L. major and P. falciparum.
- Devine, William,Woodring, Jennifer L.,Swaminathan, Uma,Amata, Emanuele,Patel, Gautam,Erath, Jessey,Roncal, Norma E.,Lee, Patricia J.,Leed, Susan E.,Rodriguez, Ana,Mensa-Wilmot, Kojo,Sciotti, Richard J.,Pollastri, Michael P.
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p. 5522 - 5537
(2015/08/03)
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- Discovery of a novel series of thienopyrimidine as highly potent and selective PI3K inhibitors
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Inhibition of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway provides a promising new approach for cancer therapy. Through a rational design, a novel series of thienopyrimidine was discovered as highly pote
- Han, Fangbin,Lin, Songwen,Liu, Peng,Liu, Xiujie,Tao, Jing,Deng, Xiaobing,Yi, Chongqin,Xu, Heng
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p. 434 - 438
(2015/04/27)
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- PROTOZOAN PARASITE GROWTH INHIBITORS
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Compounds and methods for inhibiting growth of a protozoan parasite. Methods of treating a protozoan parasite infection in a subject by administering a therapeutically effective amount of a compound as disclosed herein. The compounds and methods can be us
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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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