2840-71-3Relevant articles and documents
Design, Synthesis, and Biological Evaluation of IRAK4-Targeting PROTACs
Chen, Yun,Ning, Yi,Bai, Gang,Tong, Linjiang,Zhang, Tao,Zhou, Jinpei,Zhang, Huibin,Xie, Hua,Ding, Jian,Duan, Wenhu
supporting information, p. 82 - 87 (2021/01/12)
Interleukin-1 receptor associated kinase 4 (IRAK4) is a promising therapeutic target for diffuse large B-cell lymphoma driven by MYD88 L265P mutant, acting both as a kinase and a scaffolding protein for downstream signaling molecules. While previous efforts to modulate IRAK4 activity with kinase inhibitors alone displayed moderate efficacy, protein degradation may offer a solution to blocking both IRAK4 kinase activity and scaffolding capabilities. To this end, the potent IRAK4 degrader 9 was discovered, and it effectively inhibited the activation of downstream NF-κB signaling and outperformed the parent compound 1. In addition, compound 9 displayed a substantial advantage in reduction of the viability of OCI-LY10 and TMD8 cells over the parent compound 1. These results underline the potential that eliminating both the kinase and scaffolding functions of IRAK4 may result in superior and broader efficacy than inhibiting the kinase activity alone.
Synthesis, characterization, and DGAT1 inhibition of new 5-piperazinethiazole and 5-piperidinethiazole analogs
Kadam, Kishorkumar S.,Gandhi, Thirumanavelan,Reddy, M. Maheshkumar,Gupte, Amol,Sharma, Rajiv
, p. 802 - 814 (2015/05/13)
In this study, a novel series of 5-piperazinethiazole 2,2-dimethylbutanoic acid and 5-piperidinethiazole 2,2-dimethylbutanoic acid derivatives have been synthesized. Structures of the newly synthesized compounds have been elucidated using 1H-NMR, 13C-NMR, high-resolution mass spectroscopy, and high-performance liquid chromatographic analysis. The synthesized derivatives have been evaluated in vitro for their ability to inhibit the enzyme diacylglycerol acyltransferase 1 responsible for triglyceride biosynthesis.
Novel CGRP receptor antagonists from central amide replacements causing a reversal of preferred chirality
Wood, Michael R.,Schirripa, Kathy M.,Kim, June J.,Bednar, Rodney A.,Fay, John F.,Bruno, Joseph G.,Moore, Eric L.,Mosser, Scott D.,Roller, Shane,Salvatore, Christopher A.,Vacca, Joseph P.,Selnick, Harold G.
scheme or table, p. 6827 - 6830 (2011/01/04)
A previously utilized quinoline-for-N-phenylamide replacement strategy was employed against a central amide in a novel class of CGRP receptor antagonists. A unique and unexpected substitution pattern was ultimately required to maintain reasonable affinity
