67305-24-2Relevant academic research and scientific papers
Synthesis of N-heteroaroyl aminosaccharide derivatives as fibroblast growth factor 2 signaling modulators
Dong, Jin,Yao, Shuowei,Zhou, Xiaodong,Zhang, Lijuan,Xu, Yungen
, p. 1210 - 1215 (2010)
Fibroblast growth factor 2 (FGF2) signaling plays an important role in angiogenesis. Heparin/heparan sulfate (HS) is required for FGF2 signaling but heparin mimics either promotes or inhibits FGF2 signaling. To take advantage such properties of heparin mimics, a series of N-heteroaroyl aminosaccharide derivatives were designed and synthesized as FGF2 signaling modulators. The bioactivity was determined in a FGF2 and heparin-dependent cell proliferation assay using FGFR1c expressing BaF3 cells. We found that most of the compounds inhibited heparin- and FGF2-dependent BaF3 cell proliferation while three compounds promoted the cell proliferation. These results suggest that the small molecular heparin mimics approach might be useful in developing novel anti-angiogenic agents.
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.
Novel imidazole derivatives having FLT3-inhibitory activity and use thereof
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Paragraph 0388-0391, (2020/04/22)
The present invention relates to a novel benzoimidazole derivative having fms-like tyrosine kinase 3 (FLT3) inhibitory activity, and a use thereof. The novel benzoimidazole derivative or a pharmaceutically acceptable salt thereof according to the present invention exhibits excellent inhibitory activity on FLT3, thereby being expected for target treatment through further fundamental approach in preventing or treating acute myeloid leukemia (AML).COPYRIGHT KIPO 2020
Synthesis and in vivo antifibrotic activity of novel leflunomide analogues
Hamdi, Abdelrahman,Said, Eman,Farahat, Abdelbasset A.,El-Bialy, Serry A.A.,Massoud, Mohammed A.M.
, p. 912 - 920 (2016/10/31)
Novel Leflunomide analogues were synthesized and evaluated in vivo against thioacetamide (TAA) induced liver fibrosis in rats. All the animals which were treated with the new analogues showed improved or comparable survival rates to those treated with Leflunomide. Animals which were treated with compounds 8d, 8e, 9 and 11 have shown improved liver parameters than Leflunomide treated animals. Histopathology of the liver has shown that compound 8a is the most active compound, which decreases fibrosis to a minimal level and compounds 8c, 8e and 11 are active compounds with fibrosis score 2-3 which is better than that of Leflunomide.
SPIROCYCLIC HAT INHIBITORS AND METHODS FOR THEIR USE
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Page/Page column 677, (2016/04/10)
Compounds having a structure of Formula (IX) or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, wherein R1, R2a, R2b, R3a, R3b, R4a, R4b, Q1----Q2, R6, R7, A, B, W, x, and y are as defined herein and are provided. Pharmaceutical compositions comprising such compounds and methods for treating various HAT-related conditions or diseases, including cancer, by administration of such compounds are also provided.
N-(5-arylamido-2-methylphenyl)-5-methylisooxazole-4-carboxamide deravative, pharmaceutical acceptable salt thereof, method for preparation thereof and FMS kinase inhibitor comprising the same
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Paragraph 0091-0094, (2017/01/05)
The present invention relates to a compound represented by chemical formula 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the same. The compound according to the present invention exhibits FMS kinase inhibitory activity, and thus can be used as a pharmaceutical composition for preventing or treating diseases related FMS kinase activity. In the chemical formula 1, the definition of R1 and R2 is the same as defined in the specification.COPYRIGHT KIPO 2016
A NOVEL PROCESS FOR THE PREPARATION OF TERIFLUNOMIDE
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Page/Page column 14; 19, (2017/01/02)
The present invention provides a process for the preparation of Teriflunomide (Formula-I). The present invention describes the synthesis of Teriflunomide without isolating the intermediate Leflunomide. Teriflunomide is prepared from 5-Methyl isoxazole-4-carboxylic acid by converting to its acid chloride and coupling with 4-trifluoromethyl aniline to obtain Leflunomide (which is not isolated) followed by ring opening reaction using aq. Sodium Hydroxide to form Teriflunomide. In other words, the process is telescoped from 5- methylisoxazole-4-carbonyl chloride.
Discovery of 4-arylamido 3-methyl isoxazole derivatives as novel FMS kinase inhibitors
Im, Daseul,Jung, Kyungjin,Yang, Songyi,Aman, Waqar,Hah, Jung-Mi
, p. 600 - 610 (2015/09/08)
A series of 4-arylamido 3-methyl isoxazoles were synthesized and evaluated for their antiproliferative activities against the A375P melanoma and U937 hematopoietic cell lines. Most compounds showed selective antiproliferative activity toward the U937 cell line and the activities were better than that of sorafenib, the reference standard. Derivatives were made as amide 5a-b, 6a-o and urea 7a-n, 8a-g with hydrophobic moieties, and one of the most potent inhibitor 6a, 5-methyl-N-(2-methyl-5-(3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)benzamido)phenyl)isoxazole-4-carboxamide was found to be very potent inhibitor of FMS kinase (GI50 Combining double low line 0.016 μM, IC50 Combining double low line 9.95 nM) with excellent selectivity profiles and is a promising candidate for further development in therapeutics for cancer.
CuCF3: A [18F]trifluoromethylating agent for arylboronic acids and aryl iodides
Ivashkin, Pavel,Lemonnier, Gerald,Cousin, Jonathan,Gregoire, Vincent,Labar, Daniel,Jubault, Philippe,Pannecoucke, Xavier
supporting information, p. 9514 - 9518 (2014/08/18)
Positron emission tomography has emerged as the leading method for medical imaging with fluorine-18 as the most widely used radioactive isotope. Here we report a semi-automated method for the preparation of valuable [ 18F]trifluoromethylcopper, as well as its use for the radiosynthesis of [18F]trifluoromethylarenes and heteroarenes. Mild conditions of [18F]trifluoromethylation make this method particularly useful for the radiosynthesis of pharmacologically relevant [18F] trifluoromethylarenes and heteroarenes. 18F Radiochemistry: A semi-automated method for the fast preparation of radiolabelled (trifluoromethyl)copper is reported (see scheme), thus making [ 18F]CuCF3 almost as accessible as [18F]fluoride itself for the preparation of radiolabelled trifluoromethylated probes. It can be used for the preparation of radiolabelled trifluoromethylarenes from arylboronic acids and aryliodides. This methodology is clean, efficient and consistent with the specific requirements of radiochemistry.
Copper-promoted sandmeyer trifluoromethylation reaction
Dai, Jian-Jun,Fang, Chi,Xiao, Bin,Yi, Jun,Xu, Jun,Liu, Zhao-Jing,Lu, Xi,Liu, Lei,Fu, Yao
supporting information, p. 8436 - 8439 (2013/07/19)
A copper-promoted trifluoromethylation reaction of aromatic amines is described. This transformation proceeds smoothly under mild conditions and exhibits good tolerance of many synthetically relevant functional groups. It provides an alternative approach for the synthesis of trifluoromethylated arenes and heteroarenes. It also constitutes a new example of the Sandmeyer reaction.
