120608-03-9Relevant academic research and scientific papers
Using Peptide Mimics to Study the Biosynthesis of the Side-Ring System of Nosiheptide
Wang, Bo,LaMattina, Joseph W.,Badding, Edward D.,Gadsby, Lauren K.,Grove, Tyler L.,Booker, Squire J.
, p. 241 - 268 (2018)
Thiopeptide natural products have gained interest recently for their diverse pharmacological properties, including antibacterial, antifungal, anticancer, and antimalarial activities. Due to their inherent poor solubility and uptake, there is interest in d
Structure-based discovery of 1H-indole-2-carboxamide derivatives as potent ASK1 inhibitors for potential treatment of ulcerative colitis
Hou, Shaohua,Yang, Xiping,Tong, Yu,Yang, Yuejing,Chen, Quanwei,Wan, Boheng,Wei, Ran,Wang, Yuchen,Zhang, Yanmin,Kong, Bo,Huang, Jianhang,Chen, Yadong,Lu, Tao,Hu, Qinghua,Du, Ding
, (2020/12/29)
Apoptosis signal-regulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase (MAPK) family, is implicated in many human diseases. Here, we describe the structural optimization of hit compound 7 and conduct further structure-activity relationship (SAR) studies that result in the development of compound 19 with a novel indole-2-carboxamide hinge scaffold. Compound 19 displays potent anti-ASK1 kinase activity and stronger inhibitory effect on ASK1 in AP1-HEK293 cells than previously described ASK1 inhibitor GS-4997. Besides improved in vitro activity, compound 19 also exhibits an appropriate in vivo PK profile. In a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis (UC), compound 19 shows significant anti-UC efficacy and markedly attenuates DSS-induced body weight loss, colonic shortening, elevation in disease activity index (DAI) and inflammatory cell infiltration in colon tissues. Mechanistically, compound 19 represses the phosphorylation of ASK1-p38/JNK signaling pathways and suppresses the overexpression of inflammatory cytokines. Together, these findings suggest that ASK1 inhibitors can potentially be used as a therapeutic strategy for UC.
NosN, a Radical S-Adenosylmethionine Methylase, Catalyzes Both C1 Transfer and Formation of the Ester Linkage of the Side-Ring System during the Biosynthesis of Nosiheptide
LaMattina, Joseph W.,Wang, Bo,Badding, Edward D.,Gadsby, Lauren K.,Grove, Tyler L.,Booker, Squire J.
supporting information, p. 17438 - 17445 (2017/12/15)
Nosiheptide, a member of the e series of macrocyclic thiopeptide natural products, contains a side-ring system composed of a 3,4-dimethylindolic acid (DMIA) moiety connected to Glu6 and Cys8 of the thiopeptide backbone via ester and thioester linkages, re
SUBSTITUTED PYRIDINE DERIVATIVES AS FABI INHIBITORS
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Page/Page column 38-39, (2013/06/27)
The present invention provides substituted pyridine derivatives of formula (I), which may be therapeutically useful as as anti-bacterial agents, more particulalrly FabI inhibitors. Formula(I) in which R1 to R5 and L have the meanings given in the specification, and pharmaceutically acceptable salts thereof that are useful in the treatment and prevention in diseases or disorder, in particular their use in diseases or disorder where there is an advantage anti-bacterial agents, more particularly FabI inhibitors. The present invention also provides methods for synthesizing and administering the FabI inhibitor compounds. The present invention also provides pharmaceutical formulations comprising at least one of the FabI inhibitor compounds together with a pharmaceutically acceptable carrier, diluent or excipient therefor.
Synthesis of Substituted 5,6-Dihydro-6,13-dioxo-13H-indolodiazepines
Hiremath, Shivayogi P.,Bajji, Ashok C.,Biradar, Jaiprakash S.
, p. 756 - 757 (2007/10/02)
The activity of the title diazepindiones (4), synthesized from the appropriate indole-2-carboxylic acids (1), against S. aureus and E. coli has been assessed.
