128883-83-0Relevant academic research and scientific papers
Design and Synthesis of a Series of Novel Macrocycle Janus Kinase 2 Inhibitors
Wang, Yanling,Ge, Huan,Wang, Disha,He, Huan,Li, Lu,Diao, Yanyan,Shen, Zihao,Zhu, Lili,Li, Shiliang,Zhao, Zhenjiang,Li, Honglin
, p. 1259 - 1263 (2019)
Macrocycle has attracted the attention of many researchers in the field of medicinal chemistry due to its unique advantages and good prospects, but the difficulties in drug design and synthesis of macrocycle limit its applications. In this study, a series of macrocyclic derivatives designed from anaplastic lymphoma kinase (ALK) inhibitor lorlatinib were synthesized as Janus kinase 2 (JAK2) selective inhibitors. Among them, 17f had the best inhibitory activity (IC50 = 0.177 μmol·L–1) and selectivity for JAK2 over JAK1 and JAK3, which indicated that design of the macrocyclic derivatives might be a feasible strategy for the discovery of novel selective JAK2 inhibitors.
Alternative heterocycles for DNA recognition: An N-methylpyrazole/N-methylpyrrole pair specifies for A·T/T·A base pairs
Nguyen, Doan H.,Szewczyk, Jason W.,Baird, Eldon E.,Dervan, Peter B.
, p. 7 - 17 (2001)
Side-by-side pairs of three five-membered rings, N-methylpyrrole (Py), N-methylimidazole (Im), and N-methylhydroxypyrrole (Hp), have been demonstrated to distinguish each of the four Watson-Crick base pairs in the minor groove of DNA. However, not all DNA sequences targeted by these pairing rules achieve affinities and specificities comparable to DNA binding proteins. We have initiated a search for new heterocycles which can expand the sequence repetoire currently available. Two heterocyclic aromatic amino acids, N-methylpyrazole (Pz) and 4-methylthiazole (Th), were incorporated into a single position of an eight-ring polyamide of sequence ImImXPy-γ-ImPyPyPy-β-Dp to examine the modulation of affinity and specificity for DNA binding by a Pz/Py pair and/or a Th/Py pair. The X/Py pairings Pz/Py and Th/Py were evaluated by quantitative DNase I footprint titrations on a DNA fragment with the four sites 5′-TGGNCA-3′ (N=T, A, G, C). The Pz/Py pair binds T·A and A·T with similar affinity to a Py/Py pair but with improved specificity, disfavoring both G·C and C·G by about 100-fold. The Th/Py pair binds poorly to all four Watson-Crick base pairs. These results demonstrate that in some instances new heterocyclic aromatic amino acid pairs can be incorporated into imidazole-pyrrole polyamides to mimic the DNA specificity of Py/Py pairs which may be relevant as biological criteria in animal studies become important.
MACROCYCLIC COMPOUNDS FOR THE TREATMENT OF PROLIFERATIVE DISEASES
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Paragraph 00316; 00318, (2015/04/22)
The compounds and salts of the present invention inhibit kinases, especially the anaplastic lymphoma kinase (ALK) and the HGF receptor tyrosine kinase (RTK) c-Met, and are useful for treating or ameliorating abnormal cell proliferative disorders, such as
The Preparation of Partially Protected 3-Amino-1-methylpyrazole-5-carboxylic Acids to be Used as Intermediates in the Synthesis of Analogues of Distamycin A
Ding, Lu,Grehn, Leif,Ragnarsson, Ulf
, p. 75 - 81 (2007/10/02)
Partially protected 3-amino-1-methylpyrazole-5-carboxylic acid derivatives have been prepared by a convenient route from 3-amino-1-methylpyrazole.The structures of these compounds have been correlated with recent work in the field.Such derivatives, blocke
