- TRPML MODULATORS
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The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
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Paragraph 0305
(2021/06/26)
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- Water-soluble 4-hydroxystyryl and 4-hydroxyphenyl-butadienyls dyes with switchable fluorescence
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Fluorescent 4-hydroxystyryl dyes are useful for many biomedical and pharmaceutical assays, and other analyte sensing applications. However, these dyes often suffer from limited applicability in analytical and bioanalytical utilization due to insufficient water-solubility, high acid-ionization constants (pKa) and short-wavelength absorption and emission. To solve these issues, a series of new, water-soluble 4-hydroxystyryl and longer-wavelength 4-hydroxyphenyl-butadienyl dyes were synthesized and the spectral and protolytic properties were studied. These new dyes contain electron-withdrawing substituents ortho to the triggering 4-hydroxyl group. The introduction of the cyano and formyl groups was found to decrease the pKa and extend the pH-sensing region of these fluorophores. In respect of the molecular structure, these dyes exhibit either a “turn-on” activatable fluorescence, or a dual-fluorescence that enables ratiometric measurements. The 4-hydroxyphenyl-butadienyl dye was evaluated for fluorescence monitoring of drug delivery. These new dyes are promising fluorophores for acidity measurements and other sensing applications.
- Bondar, Kateryna,Bokan, Maksym,Gellerman, Gary,Patsenker, Leonid D.
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- HURAT1 (human urate anion transporter 1) inhibitors and application thereof
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The invention belongs to the field of medicinal chemistry and particularly relates to hURAT1 (human urate anion transporter 1) inhibitors and an application thereof. Specifically, the hURAT1 inhibitors are compounds with structure shown as formula (I) or (II) in the description or pharmaceutically acceptable salts of the compounds. Experiments prove that the compounds have good inhibition effect on uric acid transport of the hURAT1 in an HEK293 transfection cell, which shows that the compounds have good application prospect in treatment of hyperuricemia or gout.
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Paragraph 0093; 0094; 0095
(2018/11/22)
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- Design, synthesis and biological evaluation of 1-hydroxy-2-phenyl-4-pyridyl-1H-imidazole derivatives as xanthine oxidase inhibitors
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In our previous study, we reported a series of 1-hydroxy-2-phenyl-1H-imidazole-5-carboxylic acid derivatives that presented excellent in vitro xanthine oxidase inhibitory potency. As a continuation study, a series of 1-hydroxy-2-phenyl-1H-imidazole derivatives containing a pyridine moiety (4a-g and 5a-g) at the 4-position was designed and synthesized. Evaluation of in vitro xanthine oxidase inhibition demonstrated that the 4a-g series was more potent than the 5a-g series. Compound 4f was the most promising derivative in the series with an IC50 value of 0.64 μM. A Lineweaver-Burk plot revealed that compound 4f acted as a mixed-type xanthine oxidase inhibitor. An iso-pentyloxy group at the 4′-position improved the inhibitory potency. More interestingly, structure-activity relationship analysis indicated that the pyridine para-N atom played a crucial role in the inhibition. Molecular modeling provided a reasonable explanation for the structure-activity relationships observed in this study. In addition, a three dimensional quantitative structure-activity relationships model which possessed reasonable statistics (q2 = 0.885 and r2 = 0.993) was conducted to further understand the structural basis of these compounds as xanthine oxidase inhibitors. These compounds, especially compound 4f, have good potential for further investigations.
- Zhang, Tingjian,Lv, Yunying,Lei, Yu,Liu, Dan,Feng, Yao,Zhao, Jiaxing,Chen, Shaolei,Meng, Fanhao,Wang, Shaojie
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p. 668 - 677
(2018/02/09)
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- IMMUNE CHECKPOINT INHIBITORS, COMPOSITIONS AND METHODS THEREOF
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The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula (I), or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof. For Formula (I) compounds R1, R2, X1, Y1 and n are as defined in the specification. The inventive Formula (I) compounds are inhibitors of the PD-1/PD-L1 protein/protein binding or functional interaction and find utility in any number of therapeutic applications, including but not limited to treatment of proliferative disorders such as cancer and infectious diseases.
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Paragraph 0369
(2018/03/25)
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- A highly efficient approach to vanillin starting from 4-cresol
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A highly efficient approach to the famous flavor and fragrance compound vanillin has been developed starting from 4-cresol with the attention focused on improving the sustainability of all the reactions. The approach involves a three-step sequence of the quasi-quantitative selective clean oxybromination of 4-cresol, the high-yield selective aerobic oxidation of 2-bromo-4-cresol, and the quantitative methoxylation of 3-bromo-4-hydroxybenzaldehyde with the recovery of pure methanol. Herein, the pivotal oxidation and methoxylation reactions are logically investigated and developed into two concise methodologies. As a green alternative, the approach holds significant value for the sustainable manufacturing of vanillin. the Partner Organisations 2014.
- Jiang, Jian-An,Chen, Cheng,Guo, Ying,Liao, Dao-Hua,Pan, Xian-Dao,Ji, Ya-Fei
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supporting information
p. 2807 - 2814
(2014/05/06)
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- NOVEL DIHYDROPYRIMIDIN-2(1H)-ONE COMPOUNDS AS S-NITROSOGLUTATHIONE REDUCTASE INHIBITORS
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The present invention is directed to novel dihydropyrimidin-2(1H)-one compounds useful as S-nitrosoglutathione reductase (GSNOR) inhibitors, pharmaceutical compositions comprising such compounds, and methods of making and using the same.
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Page/Page column 154-155
(2011/04/24)
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