- N-HETEROARYL INDAZOLE DERIVATIVES AS LRRK2 INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF
-
The present invention is directed to substituted certain N-heteroaryl indazole derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, X, Y, and Z are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of diseases, such as Parkinson's disease, in which LRRK-2 kinase is involved.
- -
-
Page/Page column 99
(2020/05/28)
-
- Synthesis and Activity Evaluation of Nasopharyngeal Carcinoma Inhibitors Based on 6-(Pyrimidin-4-yl)-1H-indazole
-
Human nasopharyngeal carcinoma is a common head and neck malignancy with high incidence in Southeast Asia and Southern China. It is necessary to develop safe, effective and inexpensive anticancer agents to improve the therapeutics of patients with nasopharyngeal carcinoma. A series of small molecular compounds based on 6-(pyrimidin-4-yl)-1H-indazole were synthesized and evaluated for antiproliferative activities against human nasopharyngeal carcinoma cell lines SUNE1. Compounds 6b, 6c, 6e and 6l showed potent antiproliferative activities similar to positive control drug cisplatin in vitro with lower nephrotoxicity than it. N-[4-(1H-Indazol-6-yl)pyrimidin-2-yl]benzene-1,3-diamine (6l) was selected for further study. It was found that 6l induced mitochondria-mediated apoptosis and G2/M phase arrest in SUNE1 cells. Furthermore, compound 6l at 10 mg/kg can suppress the growth of an implanted SUNE1 xenograft with a TGI% (tumor growth inhibition) value of 50 % and did not cause serious side effects in BALB/c nude mice. This study suggests that 6-(pyrimidin-4-yl)-1H-indazole derivatives are a series of small molecule compounds with anti-nasopharyngeal carcinoma activities.
- Liao, Bohong,Peng, Lingrong,Zhou, Jin,Mo, Huiting,Zhao, Jialan,Yang, Zike,Guo, Xiaowen,Zhang, Peiquan,Zhang, Xin,Zhu, Zhibo
-
-
- COMPOUNDS
-
Provided are novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, compositions containing them and their use in the treatment of or prevention of diseases associated with or characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).
- -
-
-
- IRAK4 INHIBITING AGENTS
-
Provided are compounds of Formula (I), or pharmaceutically acceptable salts thereof, and methods for their use and production.
- -
-
Page/Page column 55; 218
(2016/03/13)
-
- FUSED PYRIMIDINE COMPOUND, AND PREPARATION METHOD, INTERMEDIATE, COMPOSITION AND USES THEREOF
-
Disclosed are a fused pyrimidine compound as represented by formula I, pharmaceutically acceptable salt, hydrate or solvate thereof, an optical isomer or a prodrug thereof, as well as a preparation method, an intermediate, a composition and uses thereof. The fused pyrimidine compound according to the present invention can inhibit activity of PI3 kinase, and can be used to treat diseases such as cancer caused by abnormal activity of the PI3 kinase, or can be used to prepare medicine for treating these diseases.
- -
-
Paragraph 0101; 0102
(2015/04/22)
-
- Protected indazole boronic acid pinacolyl esters: Facile syntheses and studies of reactivities in Suzuki-Miyaura cross-coupling and hydroxydeboronation reactions
-
The paper describes a rapid and efficient synthesis for the isolation of protected indazolylboronic esters. These compounds were synthesized by reaction between prepared protected haloindazoles and bis(pinacolato)diboron. The effects of solvent, temperature, reaction time, and the nature of halogen atom as well as protecting group were investigated. Additionaly, these compounds reacted either with aryl halides in a Suzuki-Miyaura cross-coupling reaction or with hydrogen peroxide in a hydroxydeboronation reaction showing the potential access to new aryl and hydroxyindazole libraries. Georg Thieme Verlag Stuttgart.
- Crestey, Fran?ois,Lohou, Elodie,Stiebing, Silvia,Collot, Valérie,Rault, Sylvain
-
experimental part
p. 615 - 619
(2009/07/09)
-