201023-69-0Relevant academic research and scientific papers
Protein Degradation via CRL4CRBN Ubiquitin Ligase: Discovery and Structure-Activity Relationships of Novel Glutarimide Analogs That Promote Degradation of Aiolos and/or GSPT1
Hansen, Joshua D.,Condroski, Kevin,Correa, Matthew,Muller, George,Man, Hon-Wah,Ruchelman, Alexander,Zhang, Weihong,Vocanson, Fan,Crea, Tim,Liu, Wei,Lu, Gang,Baculi, Frans,Lebrun, Laurie,Mahmoudi, Afshin,Carmel, Gilles,Hickman, Matt,Lu, Chin-Chun
, p. 492 - 503 (2018)
We previously disclosed the identification of cereblon modulator 3 (CC-885), with potent antitumor activity mediated through the degradation of GSPT1. We describe herein the structure-activity relationships for analogs of 3 with exploration of the structurally related dioxoisoindoline class. The observed activity of protein degradation could in part be rationalized through docking into the previously disclosed 3-CRBN-GSPT1 cocrystal ternary complex. For SAR that could not be rationalized through the cocrystal complex, we sought to predict SAR through a QSAR model developed in house. Through these analyses, selective protein degradation could be achieved between the two proteins of interest, GSPT1 and Aiolos.
Sulfur-containing compound based on glutaryl imide skeleton and application of compound
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Paragraph 0167; 0629-0630, (2020/09/12)
The present disclosure relates to compound shown in a formula (I) or salts, solvates, isotope-enriched analogs, tautomers, polymorphs, stereoisomers, or mixtures of stereoisomers of the compound, andthe application thereof in the treatment of tumours. The present disclosure also provides tumor treatment application of the compound showed in a formula (I') or pharmaceutically acceptable salts, solvates, isotope-enriched analogs, tautomers, polymorphic substances, stereoisomers, or mixtures of stereoisomers of the compound.
THERAPEUTICALLY ACTIVE PYRAZOLO-PYRIMIDINE DERIVATIVES
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Page/Page column 64; 65, (2014/07/08)
A series of pyrazolo[3,4-d]pyrimidine derivatives that are substituted at the 4- position by a diaza monocyclic, bridged bicyclic or spirocyclic moiety, are beneficial in the treatment and/or prevention of various human ailments, including inflammatory, autoimmune and oncological disorders; viral diseasesand malaria; and organ and cell transplant rejection.
Design and synthesis of novel triazole antifungal derivatives by structure-based bioisosterism
Sheng, Chunquan,Che, Xiaoying,Wang, Wenya,Wang, Shengzheng,Cao, Yongbing,Miao, Zhenyuan,Yao, Jianzhong,Zhang, Wannian
experimental part, p. 5276 - 5282 (2011/12/03)
The incidence of life-threatening fungal infections is increasing dramatically. In an attempt to develop novel antifungal agents, our previously synthesized phenoxyalkylpiperazine triazole derivatives were used as lead structures for further optimization. By means of structure-based bioisosterism, triazolone was used as a new bioisostere of oxygen atom. This type of bioisosteric replacement can improve the water solubility without loss of hydrogen-bonding interaction with the target enzyme. A series of triazolone-containing triazoles were rationally designed and synthesized. As compared with fluconazole, several compounds showed higher antifungal activity with broader spectrum, suggesting their potential for further evaluations.
