161940-20-1Relevant articles and documents
HALOGENATED-HETEROARYL AND OTHER HETEROCYCLIC KINASE INHIBITORS, AND USES THEREOF
-
, (2021/11/04)
The invention relates to kinase inhibitors, in particular inhibitors of protein kinases including the SIK-family CSF1R, ABL/BCR-ABL, SRC, HCK, PDGFR, KIT and/or their mutants. Although structurally similar to dasatinib, the kinase inhibitors of the invention are distinctive; possessing a particular class of halogenated heteroaryls. Such kinase inhibitors can display one or more certain properties distinct to dasatinib and other structurally similar kinase inhibitors. The kinase inhibitors of the invention or pharmaceutical compositions comprising them may be used in the treatment of a disorder or condition, such as a proliferative disorder, for example, a leukaemia or solid tumour. In particular, these and other structurally similar kinase inhibitors may be used in the treatment of a proliferative disorder - such as a mixed phenotype acute leukaemia (MPAL) - characterised by (inter-alia) the presence of MEF2C protein, a human chromosomal translocation at 11q23, and/or a KMT2A fusion oncoprotein. The kinase inhibitors or pharmaceutical compositions disclosed herein may be used topically to modulate skin pigmentation in a subject, for example to impart UV protection and reduce skin cancer risk.
Scaffold Diversity Inspired by the Natural Product Evodiamine: Discovery of Highly Potent and Multitargeting Antitumor Agents
Wang, Shengzheng,Fang, Kun,Dong, Guoqiang,Chen, Shuqiang,Liu, Na,Miao, Zhenyuan,Yao, Jianzhong,Li, Jian,Zhang, Wannian,Sheng, Chunquan
, p. 6678 - 6696 (2015/09/07)
A critical question in natural product-based drug discovery is how to translate the product into drug-like molecules with optimal pharmacological properties. The generation of natural product-inspired scaffold diversity is an effective but challenging strategy to investigate the broader chemical space and identify promising drug leads. Extending our efforts to the natural product evodiamine, a diverse library containing 11 evodiamine-inspired novel scaffolds and their derivatives were designed and synthesized. Most of them showed good to excellent antitumor activity against various human cancer cell lines. In particular, 3-chloro-10-hydroxyl thio-evodiamine (66c) showed excellent in vitro and in vivo antitumor efficacy with good tolerability and low toxicity. Antitumor mechanism and target profiling studies indicate that compound 66c is the first-in-class triple topoisomerase I/topoisomerase II/tubulin inhibitor. Overall, this study provided an effective strategy for natural product-based drug discovery. (Figure Presented).
THIAZOLE DERIVATIVES AS PROTEIN KINASE INHIBITORS
-
Page/Page column 76-77, (2009/06/27)
The present invention relates to novel Thiazole Derivatives, compositions comprising the Thiazole Derivatives, and methods for using the Thiazole Derivatives for treating or preventing a proliferative disorder, an anti-proliferative disorder, inflammation, arthritis, a central nervous system disorder, a cardiovascular disease, alopecia, a neuronal disease, an ischemic injury, a viral infection, a fungal infection, or a disorder related to the activity of a protein kinase.
Competitive ortho metalation effects: The kinetic and thermodynamic lithiation of 3-(tert-butoxycarbonyl)amino-4-carbomethoxythiophene
Carroll, William A.,Zhang, Xiaolin
, p. 2637 - 2640 (2007/10/03)
Deprotanation of the thiophene 1 under kinetically controlled conditions with LDA takes place next to the NHBoc group and under thermodynamic conditions next to the methyl eater. N-Methylation leads to exclusive lithiation next to the ester. The methylester was found to be superior to the diethylamide in facilitating lithiation.
Synthesis and evaluation of heterocyclic carboxamides as potential antipsychotic agents
Norman, Mark H.,Navas III, Frank,Thompson, James B.,Rigdon, Greg C.
, p. 4692 - 4703 (2007/10/03)
Heterocyclic analogues of 1192U90, 2-amino-N-(4-(4-(1,2-benzisothiazol- 3-yl)-1-piperazinyl)-butyl)benzamide hydrochloride (1), were prepared and evaluated as potential antipsychotic agents. These analogues were evaluated in vitro for their binding to the dopamine D2, serotonin 5-HT2, and serotonin 5-HT(1a) receptors and in vivo for their ability to antagonize the apomorphine-induced climbing response in mice. Nine different types of heterocyclic carboxamides were studied in this investigation (i.e., pyridine- , thiophene-, benzothiophene-, quinoline-, 1,2,3,4-tetrahydroquinoline-, 2,3- dihydroindole-, indole-, benzimidazole-, and indazolecarbox-amides). Two derivatives exhibited potent in vivo activities comparable to 1: 3-amino-N- (4(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl)-2-pyridinecarboxamide (16) and 3-amino-N-(4(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl)-2- thiophenecarboxamide (29). Furthermore, these derivatives were found to be much less active in behavioral models predictive of extrapyramidal side effects than in the mouse climbing assay, which predicts antipsychotic activity. Carboxamides 16 and 29 were selected for further evaluation as potential backup compounds to 1.
