- Synthesis and biological evaluation of novel pyrazolo[3,4-b]pyridines as cis-restricted combretastatin A-4 analogues
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Twenty-six novel pyrazolo[3,4-b]pyridine-bridged analogues of combretastatin A-4 possessing 3,4,5-trimethoxylphenyl groups, were synthesized and evaluated for their antiproliferative and tubulin polymerization inhibitory activities. Preliminary biological evaluation demonstrated that some of the target compounds displayed significant antiproliferative effect against four different cell lines including MCF-7, MDA-MB-231, HeLa and Kyse150. The most active analogue 6n was found to induce HeLa cells arrest in the G2/M phase in a dose-dependent manner. Molecular modeling studies indicated that derivative 6n most likely occupies the colchicine site of tubulin. The initial results suggest that the 3,4,5-trimethoxyphenyl substituted pyrazolo[3,4-b]pyridine could serve as a promising scaffold for development of potent tubulin inhibitors as anticancer agents.
- Jian, Xie-Er,Jiang, Cui-Shan,Yang, Fang,You, Wen-Wei,Zhao, Pei-Liang
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Read Online
- Selective C-H Iodination of (Hetero)arenes
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Iodoarenes are versatile intermediates and common synthetic targets in organic synthesis. Here, we present a strategy for selective C-H iodination of (hetero)arenes with a broad functional group tolerance. We demonstrate the utility and differentiation to other iodination methods of supposed sulfonyl hypoiodites for a set of carboarenes and heteroarenes.
- Tanwar, Lalita,B?rgel, Jonas,Lehmann, Johannes,Ritter, Tobias
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Read Online
- BIARYL DERIVATIVE AND MEDICINE CONTAINING SAME
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Provided is a compound showing excellent antifungal activity against Trichophyton fungus, which is a major causative microorganism of superficial mycosis, and high effectiveness on diseases caused by Trichophyton fungi. A biaryl derivative represented by the formula (I) or a salt thereof: wherein ring A is an optionally substituted phenyl, or an optionally substituted 5- or 6-membered ring heteroaryl (ring A may be further condensed to form an optionally substituted fused ring); Q is CH2, C=O, NH, O, S or the like; X1, X2 and X3 are CR1 or N; Y is CH or N; Z is CR2b or N; R2a and R2b are each a hydrogen atom, a halogen atom, an optionally substituted C1-C6 alkyl group, a C1-C6 haloalkyl group or the like; R2a and R2b may form, together with carbon atoms bonded thereto, an optionally substituted carbocycle, or an optionally substituted heterocycle.
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Paragraph 0201; 0202
(2018/08/07)
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- PHARMACEUTICALS COMPRISING BIARYL DERIVATIVES OR SALTS THEREOF
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PROBLEM TO BE SOLVED: To provide compounds with excellent antimycotic activity against Trichophyton. SOLUTION: The invention provides pharmaceuticals comprising biaryl derivatives represented by general formula (I) or salts thereof, where ring A is optionally substituted phenyl or the like; Q is CH2 or the like; X1, X2 and X3 are CR1 or the like; and Y is CH or N. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT
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Paragraph 0210; 0211; 0212
(2018/10/24)
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- PYRIMIDINE AND TRIAZINE DERIVATIVES AND THEIR USE AS AXL INHIBITORS
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Compounds of the general formula(I): (I) processes for the preparation of these compounds, compositions containing these compounds, and the uses of these compounds.
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Page/Page column 51-52
(2016/07/05)
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- Use of 3-(trifluoromethyl)-1H-pyrazolo-[3,4-b]pyridine as a versatile building block
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A one-pot multigram synthesis of 3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridine starting from 2-fluoropyridine using directed ortho metallation (DoM) technique is described. The compound contains an anionically activatable trifluoromethyl group and is a versatile building block for the microwave assisted synthesis of 3-substituted 1H-pyrazolo[3,4-b]pyridines.
- Schirok, Hartmut,Griebenow, Nils,Fürstner, Chantal,Dilmac, Alicia M.
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p. 5597 - 5601
(2015/08/03)
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- PYRROLIDINE DERIVATIVES AND THEIR USE AS COMPLEMENT PATHWAY MODULATORS
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The present invention provides a compound of formula I: (I) a method for manufacturing the compounds of the invention, and its therapeutic uses as complement alternative inhibitors for the treatment of ocular diseases. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
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Page/Page column 52
(2014/01/17)
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- Design, synthesis and evaluation of 7-azaindazolyl-indolyl-maleimides as glycogen synthase kinase-3β (GSK-3β) inhibitors
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A series of 7-azaindazolyl-indolyl-maleimides were designed, synthesized and evaluated for their GSK-3β inhibitory activity. Most compounds exhibited potent activity against GSK-3β. Among them, compounds 17a, 17b, 17g, 17i, 29a and 30 significantly reduced Aβ-induced Tau hyperphosphorylation, showin;g the inhibition of GSK-3β at the cell level. Preliminary structure-activity relationships were discussed based on the experimental data obtained.
- Ye, Qing,Shen, Yanhong,Zhou, Yubo,Lv, Dan,Gao, Jianrong,Li, Jia,Hu, Yongzhou
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p. 361 - 371
(2013/10/01)
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- INDAZOLEPROPIONIC ACID AMIDE COMPOUND
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Disclosed is a compound which is useful in preventing and treating cardiac arrhythmia such as atrial fibrillation. A compound represented by formula (1) or a pharmaceutically acceptable salt of the same. In formula (1), ring X represents benzene or pyridine; R1 represents an optionally substituted alkyl group; R2 represents an optionally substituted aryl group, an optionally substituted heterocyclic group, an optionally substituted arylalkyl group or an optionally substituted heterocyclic group-substituted alkyl group; R3, R4, R5, R6, R7, R8 and R9 represent each hydrogen or an alkyl group, provided that R3 and R5 may be bonded to each other to form, together with the carbon atom adjacent thereto, a cycloalkyl group; and m represents 0 or 1.
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Page/Page column 28
(2012/02/01)
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- SOLUBLE GUANYLATE CYCLASE ACTIVATORS
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A compound of Formula (I): or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate ("cGMP") and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I , or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the above mentioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical preparations which comprise compounds of Formula (I) or a pharmaceutically acceptable salt thereof
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Page/Page column 98
(2011/12/14)
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- Design, synthesis, and structure-activity relationships of 3-ethynyl-1 H-indazoles as inhibitors of the phosphatidylinositol 3-kinase signaling pathway
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A new series of 3-ethynyl-1H-indazoles has been synthesized and evaluated in both biochemical and cell-based assays as potential kinase inhibitors. Interestingly, a selected group of compounds identified from this series exhibited low micromolar inhibitio
- Barile, Elisa,De, Surya K.,Carlson, Coby B.,Chen, Vida,Knutzen, Christine,Riel-Mehan, Megan,Yang, Li,Dahl, Russell,Chiang, Gary,Pellecchia, Maurizio
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scheme or table
p. 8368 - 8375
(2011/02/23)
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- Synthesis and evaluation of novel 7-azaindazolyl-indolyl-maleimide derivatives as antitumor agents and protein kinase C inhibitors
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A series of novel 7-azaindazolyl-indolyl-maleimides were synthesized and evaluated for their antiproliferative activity in vitro against various human cancer cell lines and protein kinase C inhibitory activity. Compounds 8a-c, 8e and 14a were the most pro
- Ye, Qing,Cao, Ji,Zhou, Xinglu,Lv, Dan,He, Qiaojun,Yang, Bo,Hu, Yongzhou
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experimental part
p. 4763 - 4772
(2009/11/30)
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- Synthesis of 3-(1H-benzimidazol-2-yl)-5-isoquinolin-4-ylpyrazolo[1,2-b]pyridine, a potent cyclin dependent kinase 1 (CDK1) inhibitor
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The novel compound 3-(1H-benzimidazol-2-yl)-5-isoquinolin-4-ylpyrazolo[1,2-b]pyridine was discovered to be a potent CDK1 inhibitor. Described here is the chemistry for its synthesis, including Pd(II) catalyzed Stille coupling reaction and sulfur(0) induced benzimidazole formation. Its effects on VEGFR-2 kinase activity and tumour cell proliferation are also described.
- Huang, Shenlin,Lin, Ronghui,Yu, Yang,Lu, Yanhua,Connolly, Peter J.,Chiu, George,Li, Shengjian,Emanuel, Stuart L.,Middleton, Steven A.
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p. 1243 - 1245
(2007/10/03)
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- HIV reverse transcriptase inhibitors
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Compounds having the structure: are HIV reverse transcriptase inhibitors, wherein A, X, Y, Z, R1 and R2 are defined herein. The compounds and their pharmaceutically acceptable salts are useful in the inhibition of HIV reverse transcriptase, the prophylaxis and treatment of infection by HIV and in the prophylaxis, delay in the onset, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.
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Page/Page column 56
(2010/11/25)
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- 3-BENZOIMIDAZOLYL-PYRAZOLOPYRIDINES USEFUL IN TREATING KINASE DISORDERS
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The present invention is directed to novel 3-benzoimidazolyl-pyrazolopyridine compounds of formula (I): and pharmaceutically acceptable forms thereof and their synthesis and use as inhibitors of serine-threonine protein kinases and tyrosine protein kinases and interactions thereof.
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Page/Page column 86
(2008/06/13)
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- The Semmler-Wolff Aromatization and Schmidt Reaction Applied to Some Pyridopyrazolobenzotriazines
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Pyridopyrazolobenzotriazin-4(1H)ones were transformed via their oximes in a Semmler-Wolff aromatization process in the tetracyclic heteroaromatic amines 4 or by Schmidt reaction into a mixture of the same amine 4 and a ring enlarg
- Kocevar, Marijan,Stanovnik, Branko,Tisler, Miha
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p. 597 - 604
(2007/10/02)
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