- Synthesis of functionalized cyclohexenone core of welwitindolinones via rhodium-catalyzed [5 + 1] cycloaddition
-
The cyclohexenone core of welwitindolinones was synthesized by a Rh(I)-catalyzed [5 + 1]-cycloaddition of an allenylcyclopropane with CO. A pentasubstituted cyclopropane was prepared successfully by a Rh(II)-catalyzed intramolecular cyclopropanation of alkenes with chlorodiazoacetates.
- Zhang, Min,Tang, Weiping
-
-
Read Online
- 4-Indolyl-N-hydroxyphenylacrylamides as potent HDAC class I and IIB inhibitors in?vitro and in?vivo
-
A series of 4,5-indolyl-N-hydroxyphenylacrylamides, as HDAC inhibitors, has been synthesized and evaluated in?vitro and in?vivo. 4-Indolyl compounds 13 and 17 functions as potent inhibitors of HDAC1 (IC50 1.28?nM and 1.34?nM) and HDAC 2 (ICsub
- Mehndiratta, Samir,Wang, Ruei-Shian,Huang, Han-Li,Su, Chih-Jou,Hsu, Chia-Ming,Wu, Yi-Wen,Pan, Shiow-Lin,Liou, Jing-Ping
-
-
Read Online
- Identification of a novel series of azabenzimidazole-derived inhibitors of spleen tyrosine kinase
-
Spleen Tyrosine Kinase (SYK) is a well-studied enzyme with therapeutic applications in oncology and autoimmune diseases. We identified an azabenzimidazole (ABI) series of SYK inhibitors by mining activity data of 86,000 compounds from legacy biochemical assays with SYK and other homologous kinases as target enzymes. A structure-based design and hybridization approach was then used to improve the potency and kinase selectivity of the hits. Lead compound 23 from this novel ABI series has a SYK IC50 = 0.21 nM in a biochemical assay and inhibits growth of SUDHL-4 cells at a GI50 = 210 nM.
- Barlaam, Bernard,Boiko, Scott,Dowling, James E.,Dry, Hannah,Edmondson, Scott D.,Ikeda, Timothy,Kawatkar, Sameer P.,Kemmitt, Paul,Lamont, Scott,Patel, Joe,Pike, Andy,Pollard, Hannah,Read, Jon,Sarkar, Ujjal,Simpson, Iain,Su, Qibin,Wang, Haiyun,Wang, Peng,Watson, David,Wen, Quanshan,Yan, Zhiyuan
-
-
Read Online
- TRPML MODULATORS
-
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
- -
-
Paragraph 0290
(2021/06/26)
-
- Synthesis and evaluation of selenium-containing indole chalcone and diarylketone derivatives as tubulin polymerization inhibition agents
-
Sixteen new selenium-containing indole chalcone and diarylketone derivatives were synthesized and evaluated as tubulin polymerization inhibitors. Among them, compound 25b exhibited the most potent antiproliferative activities against six human cancer cell lines with IC50 values of 0.004-0.022 μM. A microtubule dynamics assay and an immunofluorescence assay confirmed that 25b could effectively inhibit tubulin polymerization (IC50 = 2.1 ± 0.27 μM). Further cellular mechanism studies revealed that 25b induced G2/M phase arrest, which was further evidenced by the decrease in the mitochondrial membrane potential (MMP).
- Zhang, Shun,An, Baijiao,Li, Jiayan,Hu, Jinhui,Huang, Ling,Li, Xingshu,Chan, Albert S. C.
-
p. 7404 - 7410
(2017/09/25)
-
- Design, synthesis and biological evaluation of a series of pyrano chalcone derivatives containing indole moiety as novel anti-tubulin agents
-
A new series of pyrano chalcone derivatives containing indole moiety (3-42, 49a-49r) were synthesized and evaluated for their antiproliferative activities. Among all the compounds, compound 49b with a propionyloxy group at the 4-position of the left phenyl ring and N-methyl-5-indoly on the right ring displayed the most potent cytotoxic activity against all tested cancer cell lines including multidrug resistant phenotype, which inhibits cancer cell growth with IC50 values ranging from 0.22 to 1.80 μM. Furthermore, 49b significantly induced cell cycle arrest in G2/M phase and inhibited the polymerization of tubulin. Molecular docking analysis demonstrated the interaction of 49b at the colchicine binding site of tubulin. In experiments in vivo, 49b exerted potent anticancer activity in HepG2 human liver carcinoma in BALB/c nude mice. These results indicated these compounds are promising inhibitors of tubulin polymerization for the potential treatment of cancer.
- Wang, Guangcheng,Li, Chunyan,He, Lin,Lei, Kai,Wang, Fang,Pu, Yuzi,Yang, Zhuang,Cao, Dong,Ma, Liang,Chen, Jinying,Sang, Yun,Liang, Xiaolin,Xiang, Mingli,Peng, Aihua,Wei, Yuquan,Chen, Lijuan
-
p. 2060 - 2079
(2014/04/17)
-
- DIHYDROBENZOQUINAZOLINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
-
The present invention is directed to dihydrobenzoquinazilinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease
- -
-
Page/Page column 32
(2012/04/23)
-
- Novel achiral indole-substituted titanocenes: Synthesis and preliminary cytotoxicity studies
-
A series of eight new titanocene dichloride derivatives has been synthesised and characterized. Four compounds from the series are lypophilic indole-functionalised titanocenes and four are hydrochloride salts of their dimethylaminomethyl-functionalised counterparts, which are water soluble. The compounds were tested for their in vitro cytotoxicities against the human kidney cancer cell line CAKI-1 and their results are compared with previously synthesised structural analogues. Surprisingly, two of the compounds showed no activity against the CAKI-1 cell line; however six compounds exhibited medium to high potency with IC50 values as low as 7.0 μM. These six complexes were tested further on this cell line using the co-solvent Soluphor P, which has been shown to improve both solubility and cytotoxicity of similar complexes. One of the compounds carrying a N-methylindole-substituent was obtained in the form of single crystals and allowed for the characterisation by X-ray crystallography; the compound crystallised in the space group P21/n (#14) with four molecules present in the monoclinic unit cell.
- Deally, Anthony,Gleeson, Brendan,Müller-Bunz, Helge,Patil, Siddappa,O'Shea, Donal F.,Tacke, Matthias
-
body text
p. 1072 - 1083
(2011/04/25)
-
- THERAPEUTIC AGENTS, AND METHODS OF MAKING AND USING THE SAME
-
In part, the present invention is directed to antibacterial compounds
- -
-
Page/Page column 178
(2010/11/27)
-
- PURINE DERIVATIVES AS KINASE INHIBITORS
-
The present invention provides kinase inhibitors of Formula I.
- -
-
Page/Page column 45
(2008/06/13)
-
- KINASE INHIBITORS
-
The present invention provides kinase inhibitors of Formula (I)
- -
-
Page/Page column 30
(2010/02/07)
-
- CALCIUM RECEPTOR MODULATING ARYLALKYLAMINES
-
The compounds of the invention are represented by the following general structure (I) or a pharmaceutically acceptable salt thereof, and compositions containing them, wherein the variables are defined herein, and their use to reduce or inhibit PTH secretion, including methods for reducing or inhibiting PTH secretion and methods for treatment or prophylaxis of diseases associated with bone disorders, such as osteoporosis, or associated with excessive secretion of PTH, such as hyperparathyroidism. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
- -
-
Page 102-103
(2008/06/13)
-
- Thiazolidinedione derivatives, method for preparing the derivatives and pharmaceutical compositions containing same
-
A thiazolidinedione derivative represented by the following general formula (I): STR1 ?wherein the dotted line represents a single bond or a double bond, the thiazolidinedione ring residue is linked to either of 2-, 3-, 4-, 5- and 6-positions on the indole ring and R represents a group selected from the group consisting of hydrogen atom and alkyl, alkenyl, alkynyl, phenyl, aralkyl, heterocycloalkyl, arylsulfonyl and arylaminocarbonyl groups! or a pharmaceutically acceptable salt thereof exhibits excellent effects of reducing the blood sugar level and of reducing the lipid concentration in blood and is accordingly useful as a therapeutic agent for treating diabates mellitus. These derivatives and pharmaceutically acceptable salt thereof are almost free of any side effect.
- -
-
-
- 4-benzyl-1H-indoles and anti-arrthymic use thereof
-
Novel 4-benzyl-1H-indoles of the formula STR1 in all diastereoisomeric forms and mixtures thereof having antiarhythmic activity.
- -
-
-
