- BICYCLIC DIAMINES AS JANUS KINASE INHIBITORS
-
The instant invention provides compounds of formula I which are Jak inhibitors, and as such are useful for the treatment of Jak-mediated diseases such as rheumatoid arthritis, asthma, COPD and cancer.
- -
-
Paragraph 0092
(2019/01/04)
-
- Novel 3-azaindolyl-4-arylmaleimides exhibiting potent antiangiogenic efficacy, protein kinase inhibition, and antiproliferative activity
-
Tumor growth and metastasis are highly associated with the overexpression of protein kinases (PKs) regulating cell growth, apoptosis resistance, and prolonged cell survival. This study describes novel azaindolyl-maleimides with significant inhibition of PKs, such as VEGFR, FLT-3, and GSK-3β which are related to carcinogenesis. Furthermore, these compounds exhibit high kinase selectivity and potent inhibition of angiogenesis and cell proliferation, offering versatile options in cancer treatment strategies.
- Ganser, Christopher,Lauermann, Eva,Maderer, Annett,Stauder, Torsten,Kramb, Jan-Peter,Plutizki, Stanislav,Kindler, Thomas,Moehler, Markus,Dannhardt, Gerd
-
p. 9531 - 9540
(2013/01/16)
-
- 3-(indolyl)- or 3-(azaindolyl)-4-arylmaleimide derivatives for use in the treatment of colon and gastric adenocarcinoma
-
The present invention relates to the use of a compound of formula (I) wherein R1, and R3 are as defined in the description and R2 is a phenyl group which is substituted with 2 or 3 C1-G6 alkoxy groups, or a physiologically acceptable salt thereof, or a solvate of the compound of formula (I) or of the salt thereof, for treatment of colorectal or gastric adenocarcinoma.
- -
-
-
- 3-(INDOLYL)- OR 3-(AZAINDOLYL)-4-ARYLMALEIMIDE COMPOUNDS AND THEIR USE IN TUMOR TREATMENT
-
The present invention relates to a compound of formula (I) wherein R, R and R are as defined in the description and the physiologically acceptable salts thereof as well as the physiologically acceptable solvates of the compounds of formula I and of the salts thereof. The compounds of formula I are suitable for treating tumors
- -
-
Page/Page column 34
(2011/07/07)
-
- 3' SUBSTITUTED COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
-
The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein Q, R1, R4, m and Ar are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
- -
-
Page/Page column 136-137
(2009/04/25)
-
- Site-selective azaindole arylation at the azine and azole rings via N-oxide activation
-
Subjection of N-methyl 6-and 7-azaindole N-oxides to a Pd(OAc) 2/DavePhos catalyst system enables regioselective direct arylation of the azine ring. Following deoxygenation, 7-azaindole substrates undergo an additional regioselective azole direct arylation event in good yield.
- Huestis, Malcolm P.,Fagnou, Keith
-
supporting information; scheme or table
p. 1357 - 1360
(2009/09/05)
-
- Discovery of cyclopentane- and cyclohexane-trans-1,3-diamines as potent melanin-concentrating hormone receptor 1 antagonists
-
We herein report the optimization of cyclopentane- and cyclohexane-1,3-diamine derivatives as novel and potent MCH-R1 antagonists. Structural modifications of the 2-amino-quinoline and thiophene moieties found in the initial lead compound served to improve its metabolic stability profile and MCH-R1 affinity, and revealed unprecedented SAR when compared to other 2-amino-quinoline-containing MCH-R1 antagonists.
- Giordanetto, Fabrizio,Karlsson, Olle,Lindberg, Jan,Larsson, Lars-Olof,Linusson, Anna,Evertsson, Emma,Morgan, David G.A.,Inghardt, Tord
-
p. 4232 - 4241
(2008/12/21)
-
- An effective procedure for the preparation of 3-substituted-4- or 6-azaindoles from ortho-methyl nitro pyridines
-
3-Substituted-4- and 6-azaindoles were prepared from ortho-methyl-nitropyridines in a practically convenient, one-pot process based on the Leimgruber-Batcho reaction. The procedure comprises a sequence of (a) condensation of an ortho-methyl-nitropyridine with N,N-dimethylformamide dimethyl acetal; (b) alkylation or acylation of the enamine intermediate; (c) reduction of the nitro group to an aniline with in situ cyclization and elimination of dimethylamine to generate the 3-substituted azaindole heterocycle.
- Zhu, Juliang,Wong, Henry,Zhang, Zhongxing,Yin, Zhiwei,Meanwell, Nicholas A.,Kadow, John F.,Wang, Tao
-
p. 5653 - 5656
(2007/10/03)
-
- Excited state tautomerization of azaindole
-
Fluorescent tryptophan analogs, like azatryptophan, offer an advantage for exploring protein and peptide structure and dynamics. The chromophoric moieties, azaindole, of the azatryptophan analogs are investigated for their potential as fluorescent probes. The photophysical properties of 4-azaindole (4AI) and 5-azaindole (5AI) and their tautomers are characterized through computational and experimental methods. Both 4AI and 5AI undergo excited state tautomerization in the presence of 1 M NaOH. The protonated forms of 4AI and 5AI have a fluorescence emission of 415 and 410 nm, respectively, while the tautomers of 4AI and 5AI have a fluorescent emission of 480 and 450 nm, respectively. Gas phase computations (B3LYP/6-31+G**) show that the N1H azaindole tautomer is lower in energy in the ground state by as much as 12.5 kcal mol-1, while the N″H azaindole tautomer is lower in energy in the excited state by as much as 18.1 kcal mol-1. Solvent effects on the tautomer energy differences were computed using the isodensity polarized continuum model (IPCM). The polarity of the solvent helps to reduce the energy difference between the tautomers in the ground state by as much as 5.8 kcal mol-1, but not enough to reverse the ground state tautomer preference. The Royal Society of Chemistry 2005.
- Cash, Michael T.,Schreiner, Peter R.,Phillips, Robert S.
-
p. 3701 - 3706
(2007/10/03)
-
- Synthesis of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP)
-
Palladium-catalyzed cross-coupling of methylboronic acid with 2-chloro- 3-nitropyridine produced 2-methyl-3-nitropyridine 4 in one step in high yield. Oxidation of 4 with selenium dioxide gave aldehyde 5. Alternatively, condensation of 4 with DMFDMA followed by oxidation gave 5 in a two step higher yielding conversion. Subsequent direct coupling of 5 with thiosemicarbazide followed by reduction of the nitro group using stannous chloride or sodium sulfide provided 3-AP (3). Reduction with sodium hydrosulfite gave 3-HAP (8). Finally a route which avoids the reduction of a nitro function was devised. Thus direct coupling of styrene with 2-chloro-3- aminopyridine 9 under Heck reaction conditions gave 16 which was converted to 17, oxidized to the aldehyde 18 and converted to 3-AP (3) with in situ deblocking of the t-Boc functionality.
- Niu, Chuansheng,Li, Jun,Doyle, Terrence W.,Chen, Shu-Hui
-
p. 6311 - 6318
(2007/10/03)
-
- Synthesis of Pyrrolopyridines (Azaindoles)
-
Improved, convenient, and reliable routes for synthesis of 4-,5-,6-, and 7-azaindole, 7-methyl-4-azaindole, 7-methyl-6-azaindole, and the hithero unreported 7-amino-4-azaindole are described.The syntheses have been accomplished either by significant modifications to established procedures or by new methods with afford the compounds in improved yields.
- Mahadevan,Indumathy,Rasmussen, Malcolm
-
p. 359 - 367
(2007/10/02)
-