93497-08-6Relevant articles and documents
Design, synthesis and structure-activity relationship study of novel urea compounds as FGFR1 inhibitors to treat metastatic triple-negative breast cancer
Akwii, Racheal,Alvina, Karina,Ashraf-Uz-Zaman, Md,Farshbaf, Mohammad Jodeiri,German, Nadezhda A.,Kallem, Raja Reddy,Mikelis, Constantinos M.,Putnam, William,Sajib, Md Sanaullah,Shahi, Sadisna,Trippier, Paul C.,Wang, Wei,Zhang, Ruiwen
supporting information, (2020/10/12)
Triple-negative breast cancer (TNBC) is an aggressive type of cancer characterized by higher metastatic and reoccurrence rates, where approximately one-third of TNBC patients suffer from the metastasis in the brain. At the same time, TNBC shows good responses to chemotherapy, a feature that fuels the search for novel compounds with therapeutic potential in this area. Recently, we have identified novel urea-based compounds with cytotoxicity against selected cell lines and with the ability to cross the blood-brain barrier in vivo. We have synthesized and analyzed a library of more than 40 compounds to elucidate the key features responsible for the observed activity. We have also identified FGFR1 as a molecular target that is affected by the presence of these compounds, confirming our data using in silico model. Overall, we envision that these compounds can be further developed for the potential treatment of metastatic breast cancer.
Design, synthesis, and evaluation of compounds capable of reducing Pseudomonas aeruginosa virulence
Hossain, Mohammad Anwar,Sattenapally, Narsimha,Parikh, Hardik I.,Li, Wei,Rumbaugh, Kendra P.,German, Nadezhda A.
supporting information, (2019/11/26)
Anti-virulence approaches in the treatment of Pseudomonas aeruginosa (PA)-induced infections have shown clinical potential in multiple in vitro and in vivo studies. However, development of these compounds is limited by several factors, including the lack of molecules capable of penetrating the membrane of gram-negative organisms. Here, we report the identification of novel structurally diverse compounds that inhibit PqsR and LasR-based signaling and diminish virulence factor production and biofilm growth in two clinically relevant strains of P. aeruginosa. It is the first report where potential anti-virulent agents were evaluated for inhibition of several virulence factors of PA. Finally, co-treatment with these inhibitors significantly reduced the production of virulence factors induced by the presence of sub-inhibitory levels of ciprofloxacin. Further, we have analyzed the drug-likeness profile of designed compounds using quantitative estimates of drug-likeness (QED) and confirmed their potential as hit molecules for further development.
Derivatives of 1H-imidazole-4,5-dicarboxamide and Use Thereof in Preparation of Anticoccidial Drugs
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Paragraph 0141; 0145; 0146, (2019/01/10)
Disclosed are derivatives of 1H-imidazole-4,5-dicarboxamide and use thereof in preparation of anticoccidial drugs. The derivatives have structural formulae as shown in formulae (I) to (VI). The derivatives of 1H-imidazole-4,5-dicarboxamide as disclosed in the present invention have significant anticoccidial effect, especially against coccidia that show a resistance to other anticoccidial drugs, and thus they can be used in preparation of anticoccidial drug.
THIAZOLE COMPOUNDS AS ACTIVATORS OF SOLUBLE GUANYLATE CYCLASE
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Page/Page column 54, (2010/04/03)
Disclosed are compounds of formula (I) wherein R1 and R2 are independently selected from hydrogen, halo, C1-4alkyl, C1-4alkoxy, CF3 and OCF3; -Y- represents formula (IA) R3 represents hydrogen, fluoro, chloro or C1-4alkyl; R4a and R4b each independently represent hydrogen, C1-4alkyl, C1-4alkoxy, CF3 or halo; and R5 represents a group Z-X; wherein Z is absent or represents (CH2)2 or O; and X represents formula (IB) wherein: J and L both represent CH, or one of J and L represents CH and the other represents N; when both J and L represent CH, R6 represents hydrogen, halo, CF3, C1-4alkyl or C1-4alkoxy in a meta or ortho position relative to the R7 substituent and R7 represents hydrogen, halo, CF3, OCF3, C1-4alkyl, C1-4alkoxy, CH2OH, CN, CONR8R9 or CO2H; or when one of J or L represents N, R6 represents hydrogen or halo in a meta or ortho position relative to the R7 substituent and R7 represents hydrogen, halo, CF3, C1-4alkyl, C1-4alkoxy, CH2OH, CN, CONR8R9 or CO2H; and R8 and R9 are independently selected from hydrogen and C1-4alkyl; or salts thereof which activate soluble guanylate cyclase (sGC), pharmaceutical compositions containing them, their use in medicine, and processes for their preparation.
Thio-substituted tricyclic and bicyclic aromatic methanesulfinyl derivatives
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Page/Page column 29, (2008/06/13)
The present invention is related to chemical compositions, processes for the preparation thereof and uses of the composition. Particularly, the present invention relates to compositions of compounds of Formula (A): wherein Ar, Y, R1 and q are as defined herein; and their use in the treatment of diseases, including treatment of sleepiness, promotion of wakefulness, treatment of Parkinson's disease, cerebral ischemia, stroke, sleep apneas, eating disorders, stimulation of appetite and weight gain, treatment of attention deficit hyperactivity disorder ("ADHD"), enhancing function in disorders associated with hypofunctionality of the cerebral cortex, including, but not limited to, depression, schizophrenia, fatigue, in particular, fatigue associated with neurologic disease, such as multiple sclerosis, chronic fatigue syndrome, and improvement of cognitive dysfunction.
Thio-substituted arylmethanesulfinyl derivatives
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Page/Page column 31, (2008/06/13)
The present invention is related to chemical compositions, processes for the preparation thereof and uses of the composition. Particularly, the present invention relates to compositions of compounds of Formula (A): wherein Ar, X, Y, R1, R2
Copper promoted synthesis of diaryl ethers
Ghosh, Rajshekhar,Samuelson, Ashoka G.
, p. 1390 - 1393 (2007/10/03)
An efficient protocol using copper based reagents for the coupling of aryl halides with phenols to generate diaryl ethers is described. A copper(I) complex, [Cu(CH3CN)4]ClO4, or the readily available copper(II) source, CuCO3·Cu(OH)2· H2O (in combination with potassium phosphate), can be used. Aryl halides and phenols with different steric and electronic demands have been used to assess the efficiency of the procedure. The latter source of copper gives better yields under all conditions.
Analogues of clofibrate and clobuzarit containing fluorine in the side chains
Haydock,Mulholland,Telford,et al.
, p. 205 - 214 (2007/10/02)
A series of analogues of clofibrate and 2-[4-(4-chlorophenyl)phenylmethoxy]-2-methylpropionic acid (clobuzarit) has been prepared by replacing the methyl groups by trifluoromethyl groups and changing the aromatic moiety. The activity of these compounds has been assayed on the plasma levels of cholesterol, Total Esterified Fatty Acids (T.E.F.A.) and fibrinogen in rats. It appears that derivatives of the first series which contain only one trifluoromethyl group are hypocholesterolaemic and that many mono- of bis- trifluoromethyl derivatives of the second series lower the levels of both cholesterol and T.E.F.A. in contrast to clobuzarit.
