934601-20-4Relevant articles and documents
Novel Indazole-based MKK7–TIPRL Interaction Inhibitors as TRAIL Sensitizers
Gu, Sujin,Jung, Myoung Eun,Yoon, Ji-Yong,Yoon, Sang-Eun,Lee, Jeong-Ju,Lee, Kwangho,Choi, Gildon,Kim, Nam-Soon,Jeon, Moon-Kook
, p. 1125 - 1138 (2018/09/12)
This work describes the process by which a metabolically unstable TRT-0002 compound exhibiting Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-sensitizing activity for Huh7 cells at a high working concentration (40 μM) is converted to more potent and metabolically improved analogues by modifying the 5-amino group and the 1-aryl moiety in the 1H-indazole skeleton. The efforts enabled us to identify 5-sulfonamido derivatives, TRT-0029 and TRT-0173 compounds, working at lower concentrations (10 and 20 μM, respectively) and with improved metabolic stabilities. As reported previously by us, co-treating cultured Huh7 cells with either TRT-0029 or TRT-0173 and TRAIL resulted in TRAIL-induced apoptosis due to the inhibition of the MKK7–TOR signaling pathway regulator-like (TIPRL) interaction and subsequent phosphorylation of MKK7 and JNK. In addition, the injection of TRT-0029 or TRT-0173 compound suppressed tumor growth in combination with TRAIL in an in vivo hepatocellular carcinoma (HCC) mouse xenograft model. TRT-0029 and TRT-0173 compounds and the relevant structure–activity relationship can provide an insight into further study on optimization of potency and metabolic stability.
4-(PIPERRAZIN-1-YL)-PYRROLIDIN-2-ONE COMPOUNDS AS MONOACYLGLYCEROL LIPASE (MAGL) INHIBITORS
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Paragraph 1595; 1596, (2016/11/17)
The present invention aims to provide a compound having an MAGL inhibitory action, and useful as a prophylactic or therapeutic agent for neurodegenerative diseases (e.g., Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, glaucoma, multiple sclerosis and the like), anxiety disorder, pain (e.g., inflammatory pain, carcinomatous pain, nervous pain and the like), epilepsy and the like. The present invention relates to a compound represented by the formula (I): wherein each symbol is as described in the DESCRIPTION, or a salt thereof.
MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-κB ACTIVITY AND USE THEREOF
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Page/Page column 127, (2008/12/05)
Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity including inflammatory and immune diseases, obesity and diabetes having the structure of formula (I), its enantiomers, diastereomers, or a pharmaceutically acceptable salt, or hydrate, thereof, wherein X is (Ia); or X is (Ib); or X is (Ic); (Id) is heterocycle or heteroaryl; E is -N-, -NR1-, -O-, -S-, -SO2- or -CR2-; F is -N-, -NR1a-, -O-, -S-, SO2- or -CR2a-; G is N, -NR1b-, -O-, -S-, SO2- or -CR2b-, provided that the E-F-G containing heterocyclic ring formed does not contain a S-S or S-O bond, and at least one of E, F and G is a heteroatom; J, Ja, M, Ma, Q, Rx, Ry, R1, R1a, R1b, R2, R2a, R2b, and R3 to R21, Z, Za, Zb, and Zc are as defined above.