- INDOLE AHR INHIBITORS AND USES THEREOF
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The present invention provides compounds useful as inhibitors of AHR, compositions thereof, and methods of using the same.
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Paragraph 00368; 00367
(2020/05/21)
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- Design and optimization of N-acylhydrazone pyrimidine derivatives as E. coli PDHc E1 inhibitors: Structure-activity relationship analysis, biological evaluation and molecular docking study
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By targeting the thiamin diphosphate (ThDP) binding site of Escherichia coli (E. coli) pyruvate dehydrogenase multienzyme complex E1 (PDHc E1), a series of novel ‘open-chain’ classes of ThDP analogs A, B, and C with N-acylhydrazone moieties was designed and synthesized to explore their activities against E. coli PHDc E1 in vitro and their inhibitory activity against microbial diseases were further evaluated in vivo. As a result, A1–23 exhibited moderate to potent inhibitory activities against E. coli PDHc E1 (IC50 = 0.15–23.55 μM). The potent inhibitors A13, A14, A15, C2, had strong inhibitory activities with IC50 values of 0.60, 0.15, 0.39 and 0.34 μM against E. coli PDHc E1 and with good enzyme-selective inhibition between microorganisms and mammals. Especially, the most powerful inhibitor A14 could 99.37% control Xanthimonas oryzae pv. Oryzae. Furthermore, the binding features of compound A14 within E. coli PDHc E1 were investigated to provide useful insights for the further construction of new inhibitor by molecular docking, site-directed mutagenesis, and enzymatic assays. The results indicated that A14 had most powerful inhibition against E. coli PDHc E1 due to the establishment of stronger interaction with Glu571, Met194, Glu522, Leu264 and Phe602 at active site of E.coli PDHc E1. It could be used as a lead compound for further optimization, and may have potential as a new microbicide.
- He, Haifeng,Xia, Hongying,Xia, Qin,Ren, Yanliang,He, Hongwu
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p. 5652 - 5661
(2017/10/09)
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- cGAS ANTAGONIST COMPOUNDS
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Disclosed are novel compounds of Formula (I) that are cGAS antagonists, methods of preparation of the compounds, pharmaceutical compositions comprising the compounds, and their use in medical therapy.
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Paragraph 0258
(2017/11/06)
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- PYRIDO PYRIMIDINES
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Compounds of formula and pharmaceutically acceptable salts thereof are described, as well as the pharmaceutical compositions containing said compounds and their pharmaceutically acceptable salts, and the use of said compounds and pharmaceutical compositions for the treatment, control or amelioration of proliferative diseases, including cancer, Down syndrome or early onset Alzheimer's disease.
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Page/Page column 79
(2012/07/28)
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- Bicarbonate receptor compounds
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The invention relates to a compound having the general formula I wherein A1 and A2 are selected from the group consisting of carbon (=CH-) and nitrogen (=N-); D1 and D2 are selected from the group consisting of-OH, -SH and -NHR1 groups, wherein R1 is hydrogen, hydrophilic substituent, hydrophobic substituent or linker; X1 and X2 are selected from the group consisting of oxygen (=O), sulphur (=S) and =NR2 group, wherein R2 is hydrogen, hydrophilic substituent, hydrophobic substituent or linker; X3 is selected from the group consisting of oxygen (=O), sulphur (=S), =NR2 group and two singly bonded moieties, wherein both moieties are hydrogen or one moiety is hydrogen and the other moiety is selected from the group of hydrophilic substituent, hydrophobic substituent and linker; and R1-R9 are selected from the group consisting of hydrogen, electron donating substituent, electron accepting substituent, hydrophilic substituent, hydrophobic substituent and linker, or R3 and R4 and/or R6 and R7 form together an aromatic or heteroaromatic, substituted or unsubstituted ring and the remaining moieties R1-R9 are as defined above.
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- Antihypertensive Activity of 6-Arylpyridopyrimidin-7-amine Derivatives
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A series of 51 6-arylpyridopyrimidin-7-amine derivatives was prepared and evaluated for antihypertensive activity in the conscious spontaneously hypertensive rat.A number of these compounds, notably 6-(2,6-dichlorophenyl)-2-methylpyridopyrimidin-7-amine (36), lowered blood pressure in these rats in a gradual and sustained manner to normotensive levels at oral doses of 10-50 mg/kg.Normalized blood pressure levels could then be maintained by single daily oral doses.The effect of structural variation in the 6-aryl group and in the 2 and 4 positions of the pyridopyrimidine ring on activity is reported and discussed.
- Bennett, Lawrence R.,Blankley, C. John,Fleming, Robert W.,Smith, Ronald D.,Tessman, Deirdre K.
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p. 382 - 389
(2007/10/02)
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