21675-02-5Relevant articles and documents
Novel Aryl-Substituted Pyrimidones as Inhibitors of 3-Mercaptopyruvate Sulfurtransferase with Antiproliferative Efficacy in Colon Cancer
Bantzi, Marina,Augsburger, Fiona,Loup, Jérémie,Berset, Yan,Vasilakaki, Sofia,Myrianthopoulos, Vassilios,Mikros, Emmanuel,Szabo, Csaba,Bochet, Christian G.
, p. 6221 - 6240 (2021/05/06)
The enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) is one of the more recently identified mammalian sources of H2S. A recent study identified several novel 3-MST inhibitors with micromolar potency. Among those, (2-[(4-hydroxy-6-methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one) or HMPSNE was found to be the most potent and selective. We now took the central core of this compound and modified the pyrimidone and the arylketone sides independently. A 63-compound library was synthesized; compounds were tested for H2S generation from recombinant 3-MST in vitro. Active compounds were subsequently tested to elucidate their potency and selectivity. Computer modeling studies have delineated some of the key structural features necessary for binding to the 3-MST's active site. Six novel 3-MST inhibitors were tested in cell-based assays: they exerted inhibitory effects in murine MC38 and CT26 colon cancer cell proliferation; the antiproliferative effect of the compound with the highest potency and best cell-based activity (1b) was also confirmed on the growth of MC38 tumors in mice.
Alkoxy pyridone compound as well as preparation method and application thereof
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Paragraph 0164-0166, (2020/12/15)
The invention belongs to the field of medicinal chemistry, specifically, the invention relates to a series of inhibitors of factor XIa (FXIa for short) with a novel structure as well as a preparationmethod and an application thereof. The structure is shown as the following general formula (I). These compounds or stereoisomers, racemates, geometric isomers, tautomers, prodrugs, hydrates, solvatesor pharmaceutically acceptable salts and pharmaceutical compositions thereof can be used to treat or/and prevent related diseases mediated by factor XIa (FXIa for short).
Synthesis of Some New Thiazole Derivatives and Their Biological Activity Evaluation
Yurtta?, Leyla,?zkay, Yusuf,Karaca Gen?er, Hülya,Acar, Ulviye
, (2015/07/15)
New 2-(4-arylpiperazine-1-yl)-N-[4-(2-(4-substituted phenyl)thiazol-4-yl)phenyl]acetamide derivatives were synthesized and evaluated for their antimicrobial and anticholinesterase activities. Acetylcholinesterase inhibitory activities of the compounds were found weak contrary to expectations. It is unlikely that antifungal activity of the compounds was found significant, especially against Candida parapsilosis.
INHIBITORS OF HISTONE DEACETYLASE
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Paragraph 0259, (2016/04/26)
This invention provides compounds that are inhibitors of HDAC2. The compounds (e.g., compounds according to Formula (I), (II), (IIa), (III), (IV), (V), or (VI)) accordingly are useful for treating, alleviating, or preventing a condition in a subject such as a neurological disorder, memory or cognitive function disorder or impairment, extinction learning disorder, fungal disease or infection, inflammatory disease, hematological disease, or neoplastic disease, or for improving memory or treating, alleviating, or preventing memory loss or impairment.
Synthesis and anticancer activity evaluation of N-[4-(2-methylthiazol-4-yl) phenyl]acetamide derivatives containing (benz)azole moiety
Yurtta?, Leyla,?zkay, Yusuf,Akalin-?ift?i, Gül?en,Ulusoylar-Yildirim, ?afak
, p. 175 - 184 (2014/04/03)
A new class of novel thiazole-(benz)azole derivatives was synthesized to investigate their anticancer activity. The structure of the compounds was confirmed by IR, 1H-NMR, and MS spectral data and elemental analyses. Anticancer effect of the compounds was evaluated against A549 and C6 tumor cell lines. MTT, analysis of DNA synthesis, acridine orange/ethidium bromide staining method and analysis of caspase-3 activation assays were performed for anticancer activity investigations. Compounds 6f and 6g, which carry 5-chloro and 5-methylbenzimidazole groups showed significant anticancer activity. Potential of these compounds to direct tumor cells to apoptotic pathway, which is a precondition of anticancer action, was also observed.
Synthesis, anticandidal activity, and cytotoxicity of some thiazole derivatives with dithiocarbamate side chains
Yurtta, Leyla,?zkay, Yusuf,?ztürk, ?mer,Kaplancikli, Zafer Asim,Demirci, Fatih,G?ger, Gamze,Ulusoylar Yildirim, afak,Abu Mohsen, Usama
, p. 815 - 824 (2014/12/10)
Some thiazole derivatives bearing dithiocarbamic acid esters were synthesized in order to investigate their anticandidal activity and cytotoxicity. The structures of the obtained final compounds (6a-j) were confirmed by spectral data (IR, 1H NMR, 13C NMR, and MS) and elemental analysis. The anticandidal activity of the compounds was determined (6a-j) using the microbroth dilution method and their cytotoxicity was evaluated according to the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay against normal cells. Contrary to expectations, weak antifungal activity was observed with IC50values ranging between 30 and 403 μg/mL.
Design, synthesis and evaluation of new thiazole-piperazines as acetylcholinesterase inhibitors
Yurttas, Leyla,Kaplancikli, Zafer Asim,Oezkay, Yusuf
, p. 1040 - 1047 (2013/10/01)
In this study, some new 2-(4-substituted piperazine-1-yl)-N-[4-(2- methylthiazol-4-yl)phenyl]acetamide derivatives were synthesized. The synthesized compounds were screened for their anticholinesterase activity on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes by in vitro Ellman's method. The structural elucidation of the compounds was performed by using IR, 1H-NMR, 13C-NMR and FAB+-MS spectral data and elemental analyses results. Biological assays revealed that at 0.1 μM concentration, the most active compounds against AChE were 5n, 5o and 5p that indicated 96.44, 99.83 and 89.70% inhibition rates, respectively. Besides, IC50 value of the compound 5o was determined as 0.011 μM, whereas IC50 value of standard drug donepezil was 0.054 μM. The synthesized compounds did not show any notable inhibitory activity against BChE.
COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDERS
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Page/Page column 185, (2010/08/04)
The present disclosure is directed to corn- pounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders. The methods generally comprise administering to a mammal in need thereof a pharmaceutically effective amount of a compound, or a pharmaceutical composition comprising such a compound, that is designed to be substantially active in the gastrointestinal (GI) tract to inhibit NHE-mediated antiport of sodium ions and hydrogen ions therein. More particularly, the method comprises administering to a mammal in need thereof a pharmaceutically effective amount of a compound, or a pharmaceutical composition comprising such a compound, that inhibits NHE-3, -2 and/ or -8 mediated antiport of sodium and/or hydrogen ions in the GI tract and is designed to be substantially impermeable to the layer of epithelial cells, or more specifically the epithelium of the GI tract. As a result of the compound being substantially impermeable, it is not absorbed and is thus essentially systemically non-bioavailable, so as to limit the exposure of other internal organs (e.g., liver, heart, brain, etc.) thereto. The present disclosure is still further directed to a method wherein a mammal is administered such a compound with a fluid-absorbing polymer, such that the combination acts as described above and further provides the ability to sequester fluid and/or salt present in the GI tract
Rational design of 4-amino-5,6-diaryl-furo[2,3-d]pyrimidines as potent glycogen synthase kinase-3 inhibitors
Miyazaki, Yasushi,Maeda, Yutaka,Sato, Hideyuki,Nakano, Masato,Mellor, Geoffrey W.
, p. 1967 - 1971 (2008/12/22)
4-Amino-5,6-diaryl-furo[2,3-d]pyrimidines have been identified as inhibitors of glycogen synthase kinase-3β (GSK-3β). One representative derivative, 4-amino-3-(4-(benzenesulfonylamino)-phenyl)-2-(3-pyridyl)-furo[2,3-d]pyr imidine (12) exhibited potent GSK-3β inhibitory activity in low nanomolar level of IC50. The binding mode was proposed from a docking study.
Orally active 4-amino-5-diarylurea-furo[2,3-d]pyrimidine derivatives as anti-angiogenic agent inhibiting VEGFR2 and Tie-2
Miyazaki, Yasushi,Tang, Jun,Maeda, Yutaka,Nakano, Masato,Wang, Liping,Nolte, Robert T.,Sato, Hideyuki,Sugai, Masaki,Okamoto, Yuji,Truesdale, Anne T.,Hassler, Daniel F.,Nartey, Eldridge N.,Patrick, Denis R.,Ho, Maureen L.,Ozawa, Kazunori
, p. 1773 - 1778 (2007/10/03)
During our effort to develop dual VEGFR2 and Tie-2 inhibitors as anti-angiogenic agents for cancer therapy, we discovered 4-amino-5-(4-((2-fluoro-5-(trifluoromethyl)phenyl)- aminocarbonylamino)phenyl)furo[2,3-d]pyrimidine (8a) possessing strong inhibitory activity at both the enzyme and cellular level against VEGFR2 and Tie-2. Compound 8a demonstrated high pharmacokinetic exposure through oral administration, and showed marked tumor growth inhibition and anti-angiogenic activity in mouse HT-29 xenograft model via once-daily oral administration.
