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.
ALKYNE COMPOUNDS AS S-NITROSOGLUTATHIONE REDUCTASE INHIBITORS
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Page/Page column 74; 80, (2016/05/02)
Provided are compounds of formula (Ia) and pharmaceutically acceptable salts thereof, wherein A, B, R 1, R 2, m and n are as defined herein, which are active as inhibitors of S-Nitrosoglutathione reductase (GSNOR). These compounds prevent, inhibit, or suppress the action of GSNOR and are therefore useful in the treatment of GSNOR mediated diseases, disorders, syndromes or conditions such as, e.g., pulmonary hypertension, acute respiratory distress syndrome (ARDS), asthma, bronchospasm, cough, pneumonia, pulmonary fibrosis, interstitial lung diseases, cystic fibrosis and chronic obstructive pulmonary disease (COPD).
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.
