- SELECTIVE INHIBITORS OF CLINICALLY IMPORTANT MUTANTS OF THE EGFR TYROSINE KINASE
-
The present invention provides compounds of Formula (I) or a subgeneric structure or species thereof, or a pharmaceutically acceptable salt, ester, solvate, and/or prodrug thereof, and methods and compositions for treating or ameliorating abnormal cell proliferative disorders, such as cancer, wherein A, R2, R3, R10, E1, E2, E3, Y, and Z are as defined herein.
- -
-
Page/Page column 277
(2017/08/01)
-
- Indazole derivatives selectively inhibiting the activity of Janus kinase 1
-
The present invention relates to indazole derivatives having activity selectively inhibiting Janus kinase 1 (Janananananus Kinase 1) and their use as a therapeutic agent for rheumatoid arthritis.
- -
-
Paragraph 0057-0058
(2021/06/15)
-
- Linear propargylic alcohol functionality attached to the indazole-7-carboxamide as a JAK1-specific linear probe group
-
Selective inhibition of JAK1 has recently been proposed as an appropriate therapeutic rationale for the treatment of inflammatory diseases such as rheumatoid arthritis (RA) In this study, through pairwise comparison and 3D alignment of the JAK isozyme structures bound to the same inhibitor molecule, we reasoned that an alkynol functionality would serve as an isozyme-specific probe group, which would enable the resulting inhibitor to differentiate the ATP-binding site of JAK1 from those of other isozymes The 3-alkynolyl-5- (4′-indazolyl)indazole-7-carboxamide derivatives were thus prepared, and in vitro evaluation of their inhibitory activity against the JAK isozymes revealed that the propargyl alcohol functionality endowed the 5-(4′-indazolyl)indazole-7-carboxamide scaffold with JAK1 selectivity over other JAK isozymes, particularly JAK2
- Kim, Mi Kyoung,Shin, Heerim,Cho, Seo Young,Chong, Youhoon
-
p. 1156 - 1162
(2014/02/14)
-
- Fluorogenic azidofluoresceins for biological imaging
-
Fluorogenic probes activated by bioorthogonal chemical reactions can enable biomolecule imaging in situations where it is not possible to wash away unbound probe. One challenge for the development of such probes is the a priori identification of structure
- Shieh, Peyton,Hangauer, Matthew J.,Bertozzi, Carolyn R.
-
supporting information
p. 17428 - 17431
(2013/01/15)
-
- IMIDAZOLE DERIVATIVES AS FUNCTIONALLY SELECTIVE ALPHA2C ADRENORECEPTOR AGONISTS
-
In its many embodiments, the present invention provides imidazole derivatives which are inhibitors of alPha2C adrenergic receptor agonists, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition or amelioration of one or more conditions associated with the alpha2C adrenergic receptors using such compounds or pharmaceutical compositions. Formula (I).
- -
-
Page/Page column 86
(2008/06/13)
-
- BROMINATION OF DEACTIVATED AROMATIC COMPOUNDS
-
Unreactive aromatic compounds can be brominated with high yields by the action of bromine and nitric acid or another oxidizing agent (iodic acid, hydrogen peroxide, etc.) in concentrated sulfuric acid or oleum.Bromination in the presence of nitric acid has lower substrate selectivity than the concurrent nitration.Moderately deactivated aromatic substrates are nitrated initially, whereas inactive substrates are brominated.It is suggested that the electrophilic brominating agent is sulfohypobromite in the form of a complex with sulfuric acid.
- Andrievskii, A.M.,Gorelik, M.V.,Avidon, S.V.,Al'tman, E.Sh.
-
p. 1519 - 1524
(2007/10/02)
-
- Electrophilic Aromatic Substitution. Part 35. Chlorination of 1,3-Dinitrobenzene, 1-Chloro-2,4-dinitrobenzene, and 2,4-Dinitrotoluene with Nitric Acid and Hydrogen Chloride or Chlorine in Sulphuric Acid or Oleum
-
Solutions of sulphuric acid or oleum containing HCl or Cl2 and nitric acid have been found both to chlorinate and nitrate deactivated aromatic compounds.The kinetics and products of the chlorination of 1,3-dinitrobenzene and 1-chloro-2,4-dinitrobenzene in sulphuric acid or oleum containing HCl and nitric acid at 130 deg C, and the kinetics and products of the chlorination of 2,4-dinitrotoluene at 90 deg C in sulphuric acid or oleum containing Cl2 and nitric acid, are reported. 1,3-Dinitrobenzene and 1-chloro-2,4-dinitrobenzene were predominantly chlorinated. 2,4-Dinitrotoluene gave approximately equal amounts of 6-chloro-2,4-dinitrotoluene and 2,4,6-trinitrotoluene.The results show that under these conditions, chlorination and nitration are competing electrophilic reactions, and that chlorination is less selective than nitration.Possible mechanisms for chlorination are discussed.
- Melhuish, Martin W.,Moodie, Roy B.
-
p. 667 - 674
(2007/10/02)
-