- HDAC inhibitor and preparation method and application thereof
-
The present invention discloses a compound represented by a formula I, a stereoisomer thereof, and a pharmaceutically acceptable salt thereof. The invention further relates to a pharmaceutical composition containing the compound shown in the formula I and application of the compound in preparation of HDAC inhibitor drugs. The compound or the pharmaceutical composition thereof can be used for treating cell proliferation diseases, autoimmune diseases, inflammation, neurodegenerative diseases or viral diseases.
- -
-
Paragraph 0272-0273; 0276-0277
(2020/11/12)
-
- NOVEL CARBAZOLE EHOP-016 DERIVATIVES AS ANTI-CANCER AND ANTI-MIGRATORY AGENTS
-
A series of novel of EHop-016 derivatives is presented herein via designing and synthesizing compounds that mimics its more favorable “U-shaped” conformation that appears to be critical for inhibitory activity against Rac. Based on modeling studies on EHop-016, compounds with a more rigid structural conformation can mimic this “U-shaped” conformation would improve the anti-migration activity against metastatic cells. Compounds are disclosed that inhibit RhoGTPases that are useful for inhibiting hyperprofilerative and neoplastic diseases. Specifically, the compounds inhibit the GTPases Rac and Cdc42 that are overactive or overexpressed in signaling pathways in cancer and metastasis. Methods for treatment of cancer and hyperproliferative diseases are disclosed.
- -
-
Paragraph 0182; 0183; 0184; 0185; 0186
(2019/05/15)
-
- Process for preparing 4-(5-bromine-3-fluoropyridine-2-yl) morpholine
-
The invention discloses a process for preparing 4-(5-bromine-3-fluoropyridine-2-yl) morpholine. The process comprises the following steps: (1) by taking 2-chlorine-3-nitropyridine as a raw material, performing a substitution reaction so as to generate 4-(3-nitropyridine-2-yl) morpholine; (2) performing a reduction reaction on 4-(3-nitropyridine-2-yl) morpholine to generate 2-morpholino pyridine-3-amine; (3) performing diazotization and substation reactions on 2-morpholino pyridine-3-amine to generate 4-(3-fluorine pyridine-2-yl) morpholine; and (4) performing a substitution reaction on 4-(3-fluorine pyridine-2-yl) morpholine, thereby obtaining a target compound, namely 4-(5-bromine-3-fluoropyridine-2-yl) morpholine. By adopting the process, raw materials are cheap and easy to obtain, operation conditions are gentle and easy to control, products are relatively easy to purify, and practical application can be facilitated.
- -
-
Paragraph 0018; 0028; 0038; 0048; 0058; 0065; 0067; 0068
(2018/05/03)
-
- Design, synthesis and biological evaluation of new carbazole derivatives as anti-cancer and anti-migratory agents
-
Based on the efficacy of EHop-016 as an inhibitor of migration and Rac1 activation, a new series of carbazole derivatives has been synthesized. Cytotoxic and anti-migratory effects of these compounds were evaluated in MCF-7 and MDA-MB-231 breast cancer cell lines. Preliminary investigations of their anticancer activity demonstrated that several compounds have moderate antiproliferative effects on cancer cell lines with GI50 values in the range of 13–50 μM. Furthermore, compounds 3b and 11b inhibit migration activity of metastatic cell line MDA-MB-231 by 32% and 34%, respectively. Compound 11b was shown to inhibit activation of the Rho GTPase Rac1 by 55% at 250 nM in both MDA-MB-231 and MDA-MB-435 cell lines. Compared with the IC50 of Rac1 inhibition by lead compound EHop-016 of 1.1 μM, compound 11b demonstrates 4X improved in vitro efficacy.
- Vlaar, Cornelis P.,Castillo-Pichardo, Linette,Medina, Julia I.,Marrero-Serra, Cathyria M.,Vélez, Ericka,Ramos, Zulma,Hernández, Eliud
-
supporting information
p. 884 - 890
(2018/01/27)
-