345617-18-7Relevant academic research and scientific papers
Discovery of 3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives as a novel selective inhibitor scaffold of JNK3
Cho, Hyunwook,Hah, Jung-Mi,Im, Daseul,Jang, Miyoung,Moon, Hyungwoo,Oh, Youri,Yang, Songyi
, p. 372 - 376 (2020)
3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives were designed and synthesised as selective inhibitors of JNK3, a target for the treatment of neurodegenerative diseases. Following previous studies, we have designed JNK3 inhibitors to reduce the molecular weight and successfully identified a lead compound that exhibits equipotent activity towards JNK3. Kinase profiling results also showed high selectivity for JNK3 among 38 kinases. Among the derivatives, the IC50 value of 8a, (R)-2-(1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-5-(3,4-dichlorophenyl)-1H-pyrazol-3-yl)acetonitrile exhibited 227 nM, showing the highest inhibitory activity against JNK3.
Computer-aided design and synthesis of 3-carbonyl-5-phenyl-1H-pyrazole as highly selective and potent BRAFV600E and CRAF inhibitor
Kim, Jinwoong,Choi, Byeongha,Im, Daseul,Jung, Hoyong,Moon, Hyungwoo,Aman, Waqar,Hah, Jung-Mi
, p. 1314 - 1320 (2019)
BRAF belongs to the upstream portion of the MAPK pathway, which is involved in cell proliferation and survival. When mutations occur in BRAF, downstream MEK and ERK are phosphorylated irrespective of RAS, resulting in melanoma-like cancer. Over the years, small molecules targeting BRAFV600E have been discovered to be very effective melanoma drugs, but they are known to cause the BRAF paradox. Recently, it was shown that this paradox is caused by the heterodimer phenomenon of BRAF/CRAF. Here, we suggest one method by which paradoxical activation can be avoided by selectively inhibiting BRAFV600E and CRAF but not wild-type BRAF. From previous report of N-(3-(3-alkyl-1H-pyrazol-5-yl) phenyl) aryl amide as a selective inhibitor of BRAFV600E and CRAF, we present compounds that offer enhanced selectivity and efficacy with the aid of molecular modelling.
Novel pyrazole derivatives having protein kinase activity and use thereof
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Paragraph 0194-0197; 0201; 0292, (2021/06/22)
The present invention relates to a novel pyrazole derivative compound. The present invention relates to an isomer or a pharmaceutically acceptable salt thereof and a pharmaceutical composition comprising the same. A pyrazole derivative compound is provided to selectively inhibit JNK, in particular JNK3, to be used as a pharmaceutical composition for preventing and treating neurological diseases.
Synthesis and structure-activity relationship of new chalcone linked 5-phenyl-3-isoxazolecarboxylic acid methyl esters potentially active against drug resistant Mycobacterium tuberculosis
Sahoo, Santosh Kumar,Rani, Bandela,Gaikwad, Nikhil Baliram,Ahmad, Mohammad Naiyaz,Kaul, Grace,Shukla, Manjulika,Nanduri, Srinivas,Dasgupta, Arunava,Chopra, Sidharth,Yaddanapudi, Venkata Madhavi
, (2021/06/14)
In search of novel therapeutic agents active against emerging drug-resistant Mycobacterium tuberculosis and to counter the long treatment protocol of existing drugs, herein we present synthesis and biological evaluation of a new series of 5-phenyl-3-isoxazolecarboxylic acid methyl ester-chalcone hybrids. Among 35 synthesized compounds, 32 analogues displayed potent in-vitro activity against Mycobacterium tuberculosis H37Rv with MIC 0.12–16 μg/mL. Cell viability test against Vero cells indicated 29 compounds to be non-cytotoxic (CC50 > 20 μg/mL & SI > 10). Most potent compounds with MIC 0.12 μg/mL (7 b, 7j, 7 ab) exhibited selectivity index (SI) in excess of 320. Further studies on activity against drug-resistant Mycobacterium tuberculosis revealed 7j as the most potent compound with MIC 0.03–0.5 μg/mL. Time-kill kinetic study suggested compound 7j displaying concentration-dependent bactericidal killing activity with relatively comparable potency to that of current first-line anti-TB drugs. Taken together, 7j presents a novel hit with potential to be translated into a potent antimycobacterial.
HETEROCYCLIC INHIBITORS OF MCT4
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Paragraph 0543, (2018/06/30)
Disclosed herein are compounds and compositions useful in the treatment of MCT4 mediated diseases, such as proliferative and inflammatory diseases, having the structure of Formula I: Methods of inhibition MCT4 activity in a human or animal subject are also provided.
MCT4 INHIBITORS FOR TREATING DISEASE
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Paragraph 0261, (2016/12/26)
Disclosed herein are compounds and compositions useful in the treatment of MCT4 mediated diseases, such as proliferative and inflammatory diseases, having the structure of Formula I: Methods of inhibition MCT4 activity in a human or animal subject are als
