1049022-58-3Relevant academic research and scientific papers
Indazole derivative, preparation method and application thereof
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Paragraph 0104; 0107-0110, (2021/04/26)
The invention relates to an indazole derivative, a preparation method and application thereof, and belongs to the field of chemical medicines. The invention provides a compound shown as a formula I or a pharmaceutically acceptable salt thereof. The invention also provides a preparation method and application of the compound. Biological experiments show that the compounds show an obvious inhibition effect on FGFR1, and part of the compounds can effectively inhibit breast cancer cells, colorectal cancer cells, lung cancer cells and other cancer cells under the condition of single use, so that the compounds have a broad-spectrum anti-cancer effect; besides, the compound also has an obvious inhibiting effect on proliferation of fibroblasts and human hepatic stellate cells, the effect of resisting bleomycin-induced pulmonary fibrosis in an animal body is equivalent to that of a current clinical drug nintedanib for treating pulmonary fibrosis, and the anti-fibrosis curative effect is remarkable. The invention provides a new choice for development and application of anti-cancer and anti-fibrosis drugs.
Medicinal chemistry optimization of antiplasmodial imidazopyridazine hits from high throughput screening of a softfocus kinase library: Part 2
Le Manach, Claire,Paquet, Tanya,Gonzàlez Cabrera, Diego,Younis, Yassir,Taylor, Dale,Wiesner, Lubbe,Lawrence, Nina,Schwager, Sylva,Waterson, David,Witty, Michael J.,Wittlin, Sergio,Street, Leslie J.,Chibale, Kelly
supporting information, p. 8839 - 8848 (2015/03/14)
On the basis of our recent results on a novel series of imidazopyridazine-based antimalarials, we focused on identifying compounds with improved aqueous solubility and hERG profile while maintaining metabolic stability and in vitro potency. Toward this objective, 41 compounds were synthesized and evaluated for antiplasmodial activity against NF54 (sensitive) and K1 (multidrug resistant) strains of the malaria parasite Plasmodium falciparum and evaluated for both aqueous solubility and metabolic stability. Selected compounds were tested for in vitro hERG activity and in vivo efficacy in the P. berghei mouse model. Several compounds were identified with significantly improved aqueous solubility, good metabolic stability, and a clean hERG profile relative to a previous frontrunner lead compound. A sulfoxide-based imidazopyridazine analog 45, arising from a prodrug-like strategy, was completely curative in the Plasmodium berghei mouse model at 4 × 50 mg/kg po.
On DABAL-Me3 promoted formation of amides
Dubois, Nathalie,Glynn, Daniel,McInally, Thomas,Rhodes, Barrie,Woodward, Simon,Irvine, Derek J.,Dodds, Chris
, p. 9890 - 9897 (2013/10/22)
The range and utility of DABAL-Me3 couplings of methyl esters and free carboxylic acids with primary and secondary amines under a variety of conditions (reflux, sealed tube, microwave) has been compared for a significant range of coupling partners of relevance to the preparation of amides of interest in pharmaceutical chemistry. Commercial microwave reactors promote the fastest couplings and allow the use of significantly sterically hindered amines (primary and secondary) and carboxylic acids derivatives. The influence of microwave energy on the reaction system was shown to be typically related to thermal effects (over-pressuring and superheating).
Aminolysis of 3-Phenyl propylthiol esters leading to diverse sets of amides
Tomaszewski, Mirosoaw J.,Subramanian, Pandiaraju,Santhakumar, Vijayaratnam
experimental part, p. 2614 - 2624 (2009/12/04)
3-Phenyl propylthiol esters were investigated as "activatable" solution phase linkers. These linkers can be activated with silver salts and upon treatment with amines can be converted to the corresponding amides. Under unactivated conditions, the linker i
