26455-36-7Relevant academic research and scientific papers
Crystallography-guided discovery of carbazole-based retinoic acid-related orphan receptor gamma-t (RORγt) modulators: insights into different protein behaviors with “short” and “long” inverse agonists
Yu, Ming-cheng,Yang, Feng,Ding, Xiao-yu,Sun, Nan-nan,Jiang, Zheng-yuan,Huang, Ya-fei,Yan, Yu-rong,Zhu, Chen,Xie, Qiong,Chen, Zhi-feng,Guo, Si-qi,Jiang, Hua-liang,Chen, Kai-xian,Luo, Cheng,Luo, Xiao-min,Chen, Shi-jie,Wang, Yong-hui
, p. 1524 - 1534 (2020/12/01)
A series of 6-substituted carbazole-based retinoic acid-related orphan receptor gamma-t (RORγt) modulators were discovered through 6-position modification guided by insights from the crystallographic profiles of the “short” inverse agonist 6. With the increase in the size of the 6-position substituents, the “short” inverse agonist 6 first reversed its function to agonists and then to “long” inverse agonists. The cocrystal structures of RORγt complexed with the representative “short” inverse agonist 6 (PDB: 6LOB), the agonist 7d (PDB: 6LOA) and the “long” inverse agonist 7h (PDB: 6LO9) were revealed by X-ray analysis. However, minor differences were found in the binding modes of “short” inverse agonist 6 and “long” inverse agonist 7h. To further reveal the molecular mechanisms of different RORγt inverse agonists, we performed molecular dynamics simulations and found that “short” or “long” inverse agonists led to different behaviors of helixes H11, H11’, and H12 of RORγt. The “short” inverse agonist 6 destabilizes H11’ and dislocates H12, while the “long” inverse agonist 7h separates H11 and unwinds H12. The results indicate that the two types of inverse agonists may behave differently in downstream signaling, which may help identify novel inverse agonists with different regulatory mechanisms.
AGRICULTURAL CHEMICALS
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Page/Page column 59; 111, (2019/08/08)
The present invention relates to picolinic acid derivatives that are useful in treating fungal diseases ofplants.
5-SULFAMOYL-2-HYDROXYBENZAMIDE DERIVATIVES
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Page/Page column 143, (2017/09/27)
The invention is directed to substituted salicylamide derivatives. Specifically, the invention is directed to compounds according to Formula (I): wherein R, R1 and R2 are as defined herein, or a pharmaceutically acceptable salt thereof. The compounds of the invention are inhibitors of CD73 and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with CD73 inhibition, such as AIDS, the treatment of HIV, autoimmune diseases, infections, atherosclerosis, and ischemia–reperfusion injury. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting CD73 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
CERAMIDE GALACTOSYLTRANSFERASE INHIBITORS FOR THE TREATMENT OF DISEASE
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Paragraph 000838; 000840, (2018/01/17)
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme ceramide galactosyltransferase (CGT), such as, for example, lysosomal storage diseases. Examples of lysosomal storage diseases include, for example, Krabbe disease and Metachromatic Leukodystrophy.
INHIBITORS OF BRUTON'S TYROSINE KINASE
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Page/Page column 48; 51; 75, (2015/06/25)
This application discloses compounds according to generic Formula (I): wherein all variables are defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are useful for the treatment of oncological, auto-immune, and inflammatory diseases caused by aberrant B-cell activation. Also disclosed are compositions containing compounds of Formula I and at least one carrier, diluent or excipient.
Functionalized alkoxy arene diazonium salts from paracetamol
Schmidt, Bernd,Berger, Rene,Hoelter, Frank
supporting information; experimental part, p. 1406 - 1414 (2010/06/19)
Arene diazonium tetrafluoroborates can be synthesized from aromatic acetamides via a sequence of deacetylation, diazotation and precipitation, induced by anion exchange. The reaction is conducted as a convenient one-flask transformation with consecutive addition of the appropriate reagents. Exchange of solvents or removal of byproducts prior to isolation of the product is not required. The arene diazonium salts are isolated from the reaction mixture by simple filtration. Two complementary protocols are presented, and the utility of the reaction is exemplified for a synthesis of the diarylheptanoid natural product de-O-methyl centrolobine.
COMPOUNDS AND METHODS FOR PKC THETA INHIBITION
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Page/Page column 20 - 21; sheet 1, (2010/04/25)
The present invention provides a method of selectively inhibiting PKC in the presence of PKC, by administering to a subject in need thereof, a therapeutically effective amount of a compound of Formula I. The present invention also provides a method of inhibiting cytokine synthesis in a T cell, a method of inhibiting T cell proliferation, and a method of inhibiting the replication of and cytokine production by T lymphocytes, while not stimulating or inhibiting the replication of B lymphocytes.
Cycloalkyl-substituted aryl chloroethylureas inhibiting cell cycle progression in G0/G1 phase and thioredoxin-1 nuclear translocation
Fortin, Jessica S.,Cote, Marie-France,Lacroix, Jacques,Patenaude, Alexandre,Petitclerc, Eric,C.-Gaudreault, Rene
supporting information; experimental part, p. 3526 - 3531 (2009/04/11)
1-(2-Chloroethyl)-3-(4-cyclohexylphenyl)urea (cHCEU) has been shown to abrogate the presence of thioredoxin-1 into the nucleus through its selective covalent alkylation. In the present letter we have evaluated the structure-activity relationships of the s
ARYL-SUBSTITUTED POLYCYCLIC AMINES, METHOD FOR THE PRODUCTION THEREOF, AND USE THEREOF AS A MEDICAMENT
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, (2008/06/13)
The invention relates to aryl-substituted polycyclic amines of the formula I, especially bicyclic amines, and to the physiologically tolerated salts and physiologically functional derivatives thereof; where the symbols and radicals are explained in the de
ARYL-SUBSTITUTED POLYCYCLIC AMINES, METHOD FOR THE PRODUCTION THEREOF, AND USE THEREOF AS A MEDICAMENT
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Page/Page column 67, (2008/06/13)
The invention relates to aryl-substituted polycyclic amines of formula I, particularly bicyclic amines, and the physiologically acceptable salts and physiologically functional derivatives thereof, the symbols and radicals being defined as indicated in the description.
