2109-72-0Relevant articles and documents
A simple and efficient method for the preparation of hindered alkyl- aryl ethers
Woiwode, Thomas F.,Rose, Christoph,Wandless, Thomas J.
, p. 9594 - 9596 (1998)
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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.
PHENAZINES AS INHIBITORS OF DISCOIDIN DOMAIN RECEPTORS 2 (DDR2)
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Page/Page column 22-23, (2020/10/21)
The invention concerns a compound of Formula (I) or a pharmaceutically acceptable salt or derivative thereof, wherein R1 and R2 are independently H or a group -O(CHR5)nR6, where n is an integer value from 1 to 3, R5 is independently H or CH3 for each integer value of n, R6 is H, an optionally substituted saturated heterocyclic ring or NR7R8, where R7 and R8 are independently H or (C1-C3)alkyl, R4 is H or CH3, R3 is a group selected from the group consisting of an optionally substituted aryl, (C3-C6)alkyl, benzyl, an optionally substituted saturated (C3-C6)cycloalkyl and an optionally substituted unsaturated heterocyclic ring for use as a medicament. The compounds as medicament are used in the treatment (DDR2)-mediated diseases and disorders such as a cancer, acute and chronic pain, osteoarthritis, inflammation-associated disorder as arthritis, rheumatoid arthritis, atherosclerosis, various fibrotic disorders, fibrosis or kidney injury.
Boron-Promoted Ether Interchange Reaction: Synthesis of Alkyl Nitroaromatic Ethers from Methoxynitroarenes
Liu, Zhenwei,Luan, Nannan,Lu, Hongtao,Liang, Apeng,Li, Jingya,Zou, Dapeng,Wu, Yangjie,Wu, Yusheng
, p. 702 - 707 (2020/02/11)
The first protocol for boron-promoted ether interchange reaction of methoxynitroarenes was described. A series of methoxynitroarenes and alcohols, including primary, secondary, as well as tertiary alcohols were reacted smoothly in moderate to good yields under the optimized reaction conditions. This protocol constitutes an operationally simple and scalable strategy for the synthesis of alkyl nitroaromatic ethers. Moreover, the new reactivity of boron reagents was discovered.
