2106-20-9Relevant academic research and scientific papers
Rational Design and Development of Low-Price, Scalable, Shelf-Stable and Broadly Applicable Electrophilic Sulfonium Ylide-Based Trifluoromethylating Reagents
Ge, Hangming,Ling, Yijing,Liu, Yafei,Lu, Long,Shen, Qilong
, p. 1667 - 1682 (2021/05/28)
The development of two highly reactive electrophilic trifluoromethylating reagents (trifluoromethyl)(4-nitrophenyl)bis(carbomethoxy)methylide (1g) and (trifluoromethyl)(3-chlorophenyl)bis(carbomethoxy)methylide (1j) through structure-activity study was described. Under mild conditions, reagent 1g reacted with β-ketoesters and silyl enol ethers to give α-trifluoromethylated-β-ketoesters or α-trifluoromethylated ketones in high yields. In addition, reagent 1g could serve as a trifluoromethyl radical for a variety of trifluoromethylative transformations under visible light irradiation, including radical trifluoromethylation of electron-rich indoles and pyrroles and sodium aryl sulfinates as well as trifluoromethylative difunctionalization with styrene derivatives. On the other hand, as a complimentary, under reductive coupling conditions, reagent 1j reacted with a variety of (hetero)aryl iodides for the formation of trifluoromethylated (hetero)arenes.
IMIDAZO [1,2-A] PYRIDINE COMPOUNDS
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Page/Page column 96-97, (2009/08/14)
This invention relates generally to imidazo [1,2-a] pyridine-based modulators of Liver X receptors (LXRs) and related methods.
Structure-based design of lipophilic quinazoline inhibitors of thymidylate synthase
Jones, Terence R.,Varney, Michael D.,Webber, Stephen E.,Lewis, Kathleen K.,Marzoni, Gifford P.,Palmer, Cindy L.,Kathardekar, Vinit,Welsh, Katharine M.,Webber, Stephanie,Matthews, David A.,Appelt, Krzysztof,Smith, Ward W.,Janson, Cheryl A.,Villafranca,Bacquet, Russell J.,Howland, Eleanor F.,Booth, Carol L. J.,Herrmann, Steven M.,Ward, Robert W.,White, Jennifer,Moomaw, Ellen W.,Bartlett, Charlotte A.,Morse, Cathy A.
, p. 904 - 917 (2007/10/03)
To develop novel lipophilic thymidylate synthase (TS) inhibitors, the X- ray structure of Escherichia coli TS in ternary complex with FdUMP and the inhibitor 10-propargyl-5,8-dideazafolic acid (CB3717) was used as a basis for structure-based design. A total of 31 novel lipophilic TS inhibitors, lacking a glutamate residue, were synthesized; 26 of them had in common a N-((3,4- dihydro-2-methyl-6-quinazolinyl)methyl)-N-prop-2-ynylaniline structure in which the aniline was appropriately substituted with simple lipophilic substituents either in position 3 or 4, or in both. Compounds were tested for their inhibition of E. coli TS and human TS and also for their inhibition of the growth in tissue culture of a murine leukemia, a human leukemia, and a thymidine kinase-deficient human adenocarcinoma. The crystal structures of five inhibitors complexed with E. coli TS were determined. Five main conclusions are drawn from this study. (i) A 3-substituent such as CF3, iodo, or ethynyl enhances binding by up to 1 order of magnitude and in the case of CF3 was proven to fill a nearby pocket in the enzyme. (ii) A simple strongly electron-withdrawing substituent such as NO2 or CF3SO2 in the 4- position enhances binding by 2 orders of magnitude; it is hypothesized that the transannular dipole so induced interacts favorably with the protein. (iii) Attempts to combine the enhancements of i and ii in the same molecule were generally unsuccessful. (iv) A 4-C6H5SO2 substituent provided both electron withdrawal and a van der Waal's interaction of the phenyl group with a hydrophobic surface at the mouth of the active site. The inhibition (K(is) = 12 nM) of human TS by this compound, 7n, showed that C6H5SO2 provided virtually as much binding affinity as the CO-glutamate which it had replaced. (v) The series of compounds were poorly water soluble, and also the potent TS inhibition shown by several of them did not translate into good cytotoxicity. Compounds with large cyclic groups linked to position 4 by an SO or SO; group did, however, have IC50's in the range 1-5 μM. Of these, 4-(N-((3,4- dihydro-2-methyl-6-quinazolinyl)methyl)-N-prop-2-ynylamino)phenyl phenyl sulfone, 7n, had IC50's of about 1 μM and was chosen for further elaboration.
Electronic nature of perfluoroalkylthio-, perfluoroalkylseleno-, and perfluoroalkyltelluro-containing substituents
Kondratenko, N. V.,Popov, V. I.,Kolomeitsev, A. A.,Saenko, E. P.,Prezhdo, V. V.,et al.
, p. 1049 - 1054 (2007/10/02)
The ? constants of perfluoroalkylthio, perfluoroalkylseleno, perfluoroalkyltelluro, and perfluoroalkylsulfonyl groups were determined by the 19F NMR method.It was shown that the perfluoro-tert-butylsulfonyl group is the most electron-withdrawing of all the known stable substituents.The dipole moments of aryl perfluoroalkyl sulfides and sulfones were determined.
