16292-95-8Relevant academic research and scientific papers
Synthesis and Antileishmanial Evaluation of Arylimidamide-Azole Hybrids Containing a Phenoxyalkyl Linker
Abdelhameed, Ahmed,Feng, Mei,Joice, April C.,Zywot, Emilia M.,Jin, Yiru,La Rosa, Chris,Liao, Xiaoping,Meeds, Heidi L.,Kim, Yena,Li, Junan,McElroy, Craig A.,Wang, Michael Zhuo,Werbovetz, Karl A.
, p. 1901 - 1922 (2021/02/22)
Due to the limitations of existing medications, there is a critical need for new drugs to treat visceral leishmaniasis. Since arylimidamides and antifungal azoles both show oral activity in murine visceral leishmaniasis models, a molecular hybridization approach was employed where arylimidamide and azole groups were separated by phenoxyalkyl linkers in an attempt to capitalize on the favorable antileishmanial properties of both series. Among the target compounds synthesized, a greater antileishmanial potency against intracellular Leishmania donovani was observed as the linker length increased from two to eight carbons and when an imidazole ring was employed as the terminal group compared to a 1,2,4-triazole group. Compound 24c (N-(4-((8-(1H-imidazol-1-yl)octyl)oxy)-2-isopropoxyphenyl) picolinimidamide) displayed activity against L. donovani intracellular amastigotes with an IC50 value of 0.53 μM. When tested in a murine visceral leishmaniasis model, compound 24c at a dose of 75 mg/kg/day p.o. for five consecutive days resulted in a modest 33% decrease in liver parasitemia compared to the control group, indicating that further optimization of these molecules is needed. While potent hybrid compounds bearing an imidazole terminal group were also strong inhibitors of recombinant CYP51 from L. donovani, as assessed by a fluorescence-based assay, additional targets are likely to play an important role in the antileishmanial action of these compounds.
COMPOUNDS FOR INHIBITING TNIK AND MEDICAL USES THEREOF
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Paragraph 459-461, (2019/08/29)
The present disclosure provides the compound having inhibitory property against TNIK having a specific chemical structure or its pharmaceutically acceptable salt. The present disclosure also provides a composition comprising the compound or its pharmaceutically acceptable salt. The present disclosure also provides a medical use of the compound, its salt or the composition comprising the compound or its pharmaceutically acceptable salt for treating or preventing cancer. The present disclosure also provides a method of treatment or prevention of cancer comprising administering the compound, its salt or the composition comprising the compound or its salt to a subject in need of such treatment or prevention.
TYROSINE KINASE INHIBITOR AND PHARMACEUTICAL COMPOSITION COMPRISING SAME
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Paragraph 0211; 0212, (2018/03/25)
The present invention relates to a tyrosine kinase inhibitor and a pharmaceutical composition comprising same. The tyrosine kinase inhibitor of the present invention has the structures as shown in the following formula (I) or (II):
ANTI-PARASITIC COMPOUNDS
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Paragraph 00125, (2018/03/25)
Provided are compounds, methods, and pharmaceutical compositions useful for treatment of parasites, e.g., Leishmania. For example, the compound may he represented by Ar—C(=NR1)NR2—A—X—Y—Het2, and pharmaceutically acceptable salts thereof. Ar may be an optionally substituted, aryl or nitrogen-containing heteroaryl. R1 and R2 may independently represent H, optionally substituted C1-C6 alkyl, or optionally substituted C3-C6 cycloalkyl. A may be a bond or an optionally substituted linking moiety comprising 1, 2, or 3 rings. Each ring in the optionally substituted linking moiety may independently be one of: aryl, cycloalkyl, heterocycloalkyl, and heteroaryl. X may be O, S, amide, or a bond. Y may be optionally substituted C1-C14 alkyl or optionally substituted C2-C14 alkenyl. Het2 may be an optionally substituted five-membered nitrogen-containing heteroaromatic ring comprising 1, 2, or 3 ring heteroatoms.
ANTI-FUNGAL TREATMENT
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Paragraph 00100, (2018/03/25)
Provided are compounds, methods, and pharmaceutical compositions useful for treatment of fungal infections, e.g., aspergillosis, candidiasis, cryptococcosis, histoplasmosis, and the like. For example, the pharmaceutical composition may include a pharmaceutically acceptable carrier or excipient, and a compound represented by Ar— C(=NR1)NR2— A---X— Y— Het2 and pharmaceutically acceptable salts thereof. Ar may be an optionally substituted aryl or nitrogen- containing heteroaryl. R1 and R2 may independently be H, optionally substituted C1-C6 aikyi, or optionally substituted C3-C6 cyeloalkyi. A may be a bond or an optionally substituted linking moiety comprising 1, 2, or 3 rings. Each ring in the optionally substituted linking moiety may independently be one of: aryl, cyeloalkyi, heterocycloalkyl, and heteroaryl. X may be O, S, amide, or a bond. Y may be optionally substituted C1-C10 alkyi or optionally substituted C2-C10 alkenyl. Het2 may be an optionally substituted five-membered nitrogen-containing heteroaromatic ring comprising 1, 2, or 3 ring heteroatoms.
Dual Inhibition of Mnk2 and FLT3 for potential treatment of acute myeloid leukaemia
Diab, Sarah,Abdelaziz, Ahmad M.,Li, Peng,Teo, Theodosia,Basnet, Sunita K.C.,Noll, Ben,Rahaman, Muhammed H.,Lu, Jingfeng,Hou, Jinqiang,Yu, Mingfeng,Le, Bich T.,Albrecht, Hugo,Milne, Robert W.,Wang, Shudong
supporting information, p. 762 - 772 (2017/09/02)
The discovery of novel anti-AML therapeutic agents is urgently needed, but the complex heterogeneity of the disease has so far hampered the development of a curative treatment. FLT3 inhibitors have shown therapeutic potential in clinical trials; but a monotherapy regimen has been associated with resistance mediated by the activation of parallel signalling circuitry, including MAPK and mTOR. Therefore, inhibiting a nexus of the two signalling pathways along with inhibition of FLT3 might be advantageous. Herein, we propose that a dual inhibition of FLT3 and Mnk would provide a better clinical option for AML patients compared to targeting FLT3 alone. Thus, a series of N-phenyl-4-(thiazol-5-yl)pyrimidin-2-amines and 4-(indol-3-yl)-N-phenylpyrimidin-2-amines were prepared. Potent Mnk2 inhibitors, FLT3 inhibitors, and dual inhibitors of Mnk2 and FLT3 were identified and their anti-proliferative activities assessed against MV4-11 AML cell lines. Dual inhibition of FLT3 and Mnk2 caused the increased apoptotic cell death of MV4-11 cells compared to inhibition of FLT3 or Mnk2 alone.
Tyrosine Kinase Inhibitor And Uses Thereof
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Paragraph 0914-0915, (2017/05/15)
Disclosed is a compound of Formula (I) or a pharmaceutically acceptable salt, ester, or solvate thereof, or their stereoisomers, which can be used as tyrosine kinase inhibitor. Also disclosed is a method for preparing the compound, a pharmaceutical composition and a kit comprising the compound, and uses of the compound. The compound can be used as tyrosine kinase inhibitor, or can be used to reduce or inhibit activity of EGFR or mutant thereof, such as EGFR mutant comprising T790M mutation, in a cell, or to treat and/or prevent a disease associated with overactivity of EGFR, such as cancer.
ALKYNE COMPOUNDS AS S-NITROSOGLUTATHIONE REDUCTASE INHIBITORS
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Page/Page column 66, (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).
Heterocyclic derivate tyrosine kinase inhibitor
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Paragraph 0266; 0267; 0268, (2017/01/02)
The invention belongs to the technical field of medicine and particularly relates to a heterocyclic derivate tyrosine kinase inhibitor shown in the formula (I), a pharmaceutically acceptable salt and ester thereof and stereoisomers thereof, wherein Y, W, Q m, L, R1, R2, R3, R4, R5, R6, R7, R7', R8 and R8' are defined in the specification. The invention further relates to a preparation method of the compounds and a pharmaceutical preparation and pharmaceutical compositions containing the compounds, and application of the compounds as the tyrosine kinase inhibitor for preparing medicine for preventing and/or treating cancer diseases caused by EGFR mutation and drug resistance diseases caused by EGFR T790M mutation.
Improved Protocol for Mononitration of Phenols with Bismuth(III) and Iron(III) Nitrates
W?sińska, Ma?gorzata,Korczewska, Anna,Giurg, Miros?aw,Skarzewski, Jacek
supporting information, p. 143 - 150 (2015/10/20)
A simple and efficient multigram procedure was developed for the selective mononitration of various activated phenols. The reaction proceeded smoothly with 0.5 equivalents of Bi(NO3)3 · 5H2O or Fe(NO3)3 · 9H2O in acetone at ambient temperature or at reflux. The desired products were isolated in 62-93% total yield and essentially no overnitrated compounds were detected.
