1159607-48-3Relevant academic research and scientific papers
Structural Development of Salicylanilide-Based SPAK Inhibitors as Candidate Antihypertensive Agents
Fujii, Shinya,Kikuchi, Eriko,Suzuyama, Honoka,Watanabe, Yuko,Ishigami-Yuasa, Mari,Masuno, Hiroyuki,Mori, Takayasu,Isobe, Kiyoshi,Uchida, Shinichi,Kagechika, Hiroyuki
, p. 2817 - 2822 (2021/07/12)
Hypertension is an important target for drug discovery. We have focused on the with-no-lysine kinase (WNK)-oxidative stress-responsive 1 (OSR1) and STE20/SPS1-related proline-alanine-rich protein kinase (SPAK)-NaCl cotransporter (NCC) signal cascade as a potential target, and we previously developed a screening system for inhibitors of WNK-OSR1/SPAK-NCC signaling. Herein we used this system to examine the structure-activity relationship (SAR) of salicylanilide derivatives as SPAK kinase inhibitors. Structural design and development based on our previous hit compound, aryloxybenzanilide derivative 2, and the veterinary anthelmintic closantel (3) led to the discovery of compound 10 a as a potent SPAK inhibitor with reduced toxicity. Compound 10 a decreased the phosphorylation level of NCC in mouse kidney in vivo, and appears to be a promising lead compound for a new class of antihypertensive drugs.
Discovery of 8-Methyl-pyrrolo[1,2-a]pyrazin-1(2 H)-one Derivatives as Highly Potent and Selective Bromodomain and Extra-Terminal (BET) Bromodomain Inhibitors
Li, Zizhou,Xiao, Senhao,Yang, Yaxi,Chen, Chao,Lu, Tian,Chen, Zhifeng,Jiang, Hualiang,Chen, Shijie,Luo, Cheng,Zhou, Bing
, p. 3956 - 3975 (2020/05/27)
The bromodomain and extra-terminal (BET) family proteins have recently emerged as promising drug targets for cancer therapy. In this study, identification of an 8-methyl-pyrrolo[1,2-a]pyrazin-1(2H)-one fragment (47) as a new binder to the BET bromodomains
Structural development of N-(4-phenoxyphenyl)benzamide derivatives as novel SPAK inhibitors blocking WNK kinase signaling
Fujii, Shinya,Ishigami-Yuasa, Mari,Isobe, Kiyoshi,Kagechika, Hiroyuki,Kikuchi, Eriko,Mori, Takayasu,Suzuyama, Honoka,Uchida, Shinichi,Watanabe, Yuko
, (2020/07/21)
We report here structural development of N-(4-phenoxyphenyl)benzamide derivatives as novel SPAK (STE20/SPS1-related proline/alanine-rich kinase) inhibitors. Abnormal activation of the signal cascade of with-no-lysine kinase (WNK) with OSR1 (oxidative stress-responsive kinase 1)/SPAK and NCC (NaCl cotransporter) results in characteristic salt-sensitive hypertension, and therefore inhibitors of the WNK-OSR1/SPAK-NCC cascade are candidates for antihypertensive drugs. Based on the structure of lead compound 2, we examined the SAR of N-(4-phenoxyphenyl)benzamide derivatives, and developed compound 20l as a potent SPAK inhibitor. Compounds 20l is a promising candidate for a new class of antihypertensive drugs.
Bromine structural domain inhibitor compound and application thereof
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, (2019/08/02)
The invention relates to a bromine structural domain inhibitor and provides a compound shown in a general formula I, pharmaceutical salt, an enantiomer, a diastereoisomer, an atropisomer, racemate, apolymorphic substance and solvate of the compound or an isotope labelled compound (including a deuterium substituted compound), a preparation method of the compound, pharmaceutical composition containing the compound and an application of the above components in pharmaceuticals.
PYRROLO[2,3-C]PYRIDINE DERIVATIVE, PREPARATION METHOD THEREFOR, AND USE THEREOF IN MEDICINE
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, (2018/08/03)
Disclosed are a pyrrolo[2,3-c]pyridine derivative, a preparation method therefor, and use thereof in medicine. Specifically, disclosed are a pyrrolo[2,3-c]pyridine derivative as represented by general formula (1), a preparation method therefor, a pharmaceutical composition comprising the derivative, as well as use thereof as a BRD4 inhibitor in the treatment of related diseases such as cancers, inflammations, chronic liver diseases, diabetes, cardiovascular diseases and AIDS, each substituent in general formula (I) being same as defined in the description.
Fragment-Based, Structure-Enabled Discovery of Novel Pyridones and Pyridone Macrocycles as Potent Bromodomain and Extra-Terminal Domain (BET) Family Bromodomain Inhibitors
Wang, Le,Pratt, John K.,Soltwedel, Todd,Sheppard, George S.,Fidanze, Steven D.,Liu, Dachun,Hasvold, Lisa A.,Mantei, Robert A.,Holms, James H.,McClellan, William J.,Wendt, Michael D.,Wada, Carol,Frey, Robin,Hansen, T. Matthew,Hubbard, Robert,Park, Chang H.,Li, Leiming,Magoc, Terrance J.,Albert, Daniel H.,Lin, Xiaoyu,Warder, Scott E.,Kovar, Peter,Huang, Xiaoli,Wilcox, Denise,Wang, Rongqi,Rajaraman, Ganesh,Petros, Andrew M.,Hutchins, Charles W.,Panchal, Sanjay C.,Sun, Chaohong,Elmore, Steven W.,Shen, Yu,Kati, Warren M.,McDaniel, Keith F.
, p. 3828 - 3850 (2017/05/19)
Members of the BET family of bromodomain containing proteins have been identified as potential targets for blocking proliferation in a variety of cancer cell lines. A two-dimensional NMR fragment screen for binders to the bromodomains of BRD4 identified a
Discovery of N-(4-(2,4-Difluorophenoxy)-3-(6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenyl)ethanesulfonamide (ABBV-075/Mivebresib), a Potent and Orally Available Bromodomain and Extraterminal Domain (BET) Family Bromodomain Inhibitor
McDaniel, Keith F.,Wang, Le,Soltwedel, Todd,Fidanze, Steven D.,Hasvold, Lisa A.,Liu, Dachun,Mantei, Robert A.,Pratt, John K.,Sheppard, George S.,Bui, Mai H.,Faivre, Emily J.,Huang, Xiaoli,Li, Leiming,Lin, Xiaoyu,Wang, Rongqi,Warder, Scott E.,Wilcox, Denise,Albert, Daniel H.,Magoc, Terrance J.,Rajaraman, Ganesh,Park, Chang H.,Hutchins, Charles W.,Shen, Jianwei J.,Edalji, Rohinton P.,Sun, Chaohong C.,Martin, Ruth,Gao, Wenqing,Wong, Shekman,Fang, Guowei,Elmore, Steven W.,Shen, Yu,Kati, Warren M.
, p. 8369 - 8384 (2017/11/03)
The development of bromodomain and extraterminal domain (BET) bromodomain inhibitors and their examination in clinical studies, particularly in oncology settings, has garnered substantial recent interest. An effort to generate novel BET bromodomain inhibi
BROMODOMAIN INHIBITORS
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, (2014/06/24)
The present invention provides for compounds of formula (I) wherein A1, A2, A3, A4, X1, X2, Y1, L1, G1, Rx, and Ry have any of the values defined thereof in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula (I).
BROMODOMAIN INHIBITORS
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, (2014/09/29)
The present invention provides for compounds of formula (I) wherein R1, R2, A1, A2, A3, A4, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable sal
PYRIDINONE AND PYRIDAZINONE DERIVATIVES
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, (2014/01/08)
Compounds of formula (I) wherein A1, A2, A3, A4, J, L, G, and R1 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, diabetes, obesity, cancer, and AIDS are disclosed. Pharmaceutical compositions comprising one or more compounds of formula (I) also are disclosed.
