- AMINOPYRIMIDINE COMPOUND USED FOR INHIBITING ACTIVITY OF PROTEIN KINASE
-
The present invention relates to an aminopyrimidine compound having an inhibitory effect on the activity of protein kinase as well as the preparation and use thereof. Specifically, disclosed by the present invention is an aminopyrimidine compound represented by formula (I), or a pharmaceutically acceptable salt, stereoisomer, solvate or hydrate thereof, as well as a pharmaceutical composition comprising said compound and a use method therefor. The method comprises a method for treating cell proliferative diseases and conditions such as cancer and immune diseases.
- -
-
Paragraph 0142; 0145
(2021/10/02)
-
- Direct Synthesis of Nitriles from Aldehydes Using an O-Benzoyl Hydroxylamine (BHA) as the Nitrogen Source
-
The direct synthesis of nitriles from commercially available or easily prepared aldehydes has been achieved. O-(4-CF3-benzoyl)-hydroxylamine (CF3-BHA) was utilized as the nitrogen source to generate O-acyl oximes in situ with aldehydes, which can be converted to a nitrile with the assistance of a Bronsted acid. Several aliphatic, aromatic, and α,β-unsaturated nitriles that contain different functional groups were prepared in high yields (up to 94% yield). This method has notable advantages, such as simple and mild conditions, high yields, and good functional group tolerance.
- An, Xiao-De,Yu, Shouyun
-
supporting information
p. 5064 - 5067
(2015/11/03)
-
- Mechanism of Inactivation of Neuronal Nitric Oxide Synthase by (S)-2-Amino-5-(2-(methylthio)acetimidamido)pentanoic Acid
-
Nitric oxide synthase (NOS) catalyzes the conversion of L-arginine to L-citrulline and the second messenger nitric oxide. Three mechanistic pathways are proposed for the inactivation of neuronal NOS (nNOS) by (S)-2-amino-5-(2-(methylthio)acetimidamido)pentanoic acid (1): sulfide oxidation, oxidative dethiolation, and oxidative demethylation. Four possible intermediates were synthesized. All compounds were assayed with nNOS, their IC50, KI, and kinact values were obtained, and their crystal structures were determined. The identification and characterization of the products formed during inactivation provide evidence for the details of the inactivation mechanism. On the basis of these studies, the most probable mechanism for the inactivation of nNOS involves oxidative demethylation with the resulting thiol coordinating to the cofactor heme iron. Although nNOS is a heme-containing enzyme, this is the first example of a NOS that catalyzes an S-demethylation reaction; the novel mechanism of inactivation described here could be applied to the design of inactivators of other heme-dependent enzymes.
- Tang, Wei,Li, Huiying,Doud, Emma H.,Chen, Yunqiu,Choing, Stephanie,Plaza, Carla,Kelleher, Neil L.,Poulos, Thomas L.,Silverman, Richard B.
-
supporting information
p. 5980 - 5989
(2015/05/27)
-
- SUBSTITUTED PYRIMIDINES
-
Disclosed are substituted pyrimidines useful as HIF prolyl hydroxylase inhibitors to treat anemia and like conditions.
- -
-
Page/Page column 32
(2013/04/10)
-
- SUBSTITUTED PYRIMIDINES
-
The present invention relates to substituted pyrimidines useful as HIF prolyl hydroxylase inhibitors to treat anemia and like conditions.
- -
-
Page/Page column 32-33
(2013/04/10)
-
- RSK INHIBITORS AND THERAPEUTIC USES THEREOF
-
The present invention is directed to novel compounds and compositions that have Rsk specific inhibitory activity. In addition, inhibition of Rsk by the present compounds has been discovered to halt the proliferation of cancer cell lines while having little effect on the proliferation rate of normal cells. Therefore, the present invention identifies Rsk as a target for therapeutic intervention in diseased states in which the disease or the symptoms can be ameliorated by inhibition of Rsk catalytic activity.
- -
-
-