112279-61-5Relevant articles and documents
Design, Synthesis, and Biological Evaluation of a Novel Series of Teriflunomide Derivatives as Potent Human Dihydroorotate Dehydrogenase Inhibitors for Malignancy Treatment
Chen, Qiang,Gou, Kun,Li, Chungen,Liu, Huan,Liu, Xiaocong,Luo, Youfu,Luo, Yuan,Tao, Lei,Yang, Xiaowei,Yang, Xinyu,Zeng, Ting,Zhao, Yinglan,Zhong, Xi,Zhou, Xia,Zhou, Yue
, p. 18175 - 18192 (2021/12/27)
Human dihydroorotate dehydrogenase (hDHODH), as the fourth and rate-limiting enzyme of the de novo pyrimidine synthesis pathway, is regarded as an attractive target for malignancy therapy. In the present study, a novel series of teriflunomide derivatives were designed, synthesized, and evaluated as hDHODH inhibitors. 13t was the optimal compound with promising enzymatic activity (IC50 = 16.0 nM), potent antiproliferative activity against human lymphoma Raji cells (IC50 = 7.7 nM), and excellent aqueous solubility (20.1 mg/mL). Mechanistically, 13t directly inhibited hDHODH and induced cell cycle S-phase arrest in Raji cells. The acute toxicity assay indicated a favorable safety profile of 13t. Notably, 13t displayed significant tumor growth inhibition activity with a tumor growth inhibition (TGI) rate of 81.4% at 30 mg/kg in a Raji xenograft model. Together, 13t is a promising inhibitor of hDHODH and a preclinical candidate for antitumor therapy, especially for lymphoma.
INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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Page/Page column 45, (2016/11/07)
The present invention provides compounds of Formula (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
PYRAZOLE DERIVATIVES AS 5-LO INHIBITORS
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Page/Page column 90, (2009/07/03)
The invention relates to compounds of formula (I) processes for their preparation, their use as 5-lipoxygenase inhibitors and pharmaceutical compositions containing the same.
