339370-40-0Relevant articles and documents
COMPOUNDS AND COMPOSITIONS FOR USE IN TREATING SKIN DISORDERS
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Paragraph 1006-1008, (2021/08/06)
Provided herein is a compound of formula (XXXII) or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer thereof or a physiologically functional derivative thereof, wherein R1, R2, R3, G, A, E, n, p, and q are defined herein. Also provided herein are compositions comprising a compound of formula (XXXII), and methods of using a compound of formula (XXXII), e.g., in the treatment or prevention of skin disorders.
Radiosynthesis and preliminary evaluation of 11C-labeled 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e] [1,2,4] thiadiazine 1,1-dioxide for PET imaging AMPA receptors
Chen, Jiahui,Chen, Zhen,Collier, Lee,Deng, Xiaoyun,Fu, Hualong,Gan, Jiefeng,Gong, Jian,Liang, Steven H.,Rong, Jian,Shang, Jingjie,Shao, Tuo,Sun, Jiyun,Wang, Lu,Xu, Hao
supporting information, (2020/01/31)
The α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) belong to the family of ionotropic transmembrane receptors for glutamate (iGluRs) that are implicated in the pathology of neurological disorders and neurodegenerative diseases. Inspired by a recently developed positive allosteric modulator of AMPARs, 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide (16; EC50 = 2.0 nM), we designed a new synthetic route for N-protected phenolic precursor 13 and efficiently radiolabeled a PET ligand [11C]AMPA-1905 ([11C]16) using a modified one-pot two-step strategy in high radiochemical yield and high molar activity. Preliminary in vivo evaluation was carried out to investigate the suitability of [11C]16 as a potential PET probe for AMPAR imaging.
Discovery of a novel series of potent and orally bioavailable phosphoinositide 3-kinase γ inhibitors
Leahy, James W.,Buhr, Chris A.,Johnson, Henry W. B.,Kim, Byung Gyu,Baik, Taegon,Cannoy, Jonah,Forsyth, Timothy P.,Jeong, Joon Won,Lee, Matthew S.,Ma, Sunghoon,Noson, Kevin,Wang, Longcheng,Williams, Matthew,Nuss, John M.,Brooks, Eric,Foster, Paul,Goon, Leanne,Heald, Nathan,Holst, Charles,Jaeger, Christopher,Lam, Scott,Lougheed, Julie,Nguyen, Lam,Plonowski, Arthur,Song, Joanne,Stout, Thomas,Wu, Xiang,Yakes, Michael F.,Yu, Peiwen,Zhang, Wentao,Lamb, Peter,Raeber, Olivia
experimental part, p. 5467 - 5482 (2012/09/25)
The phosphoinositide 3-kinases (PI3Ks) have been linked to an extraordinarily diversified group of cellular functions making these enzymes compelling targets for the treatment of disease. A large body of evidence has linked PI3Kγ to the modulation of autoimmune and inflammatory processes making it an intriguing target for drug discovery. Our high-throughput screening (HTS) campaign revealed two hits that were nominated for further optimization studies. The in vitro activity of the first HTS hit, designated as the sulfonylpiperazine scaffold, was optimized utilizing structure-based design. However, nonoptimal pharmacokinetic properties precluded this series from further studies. An overlay of the X-ray structures of the sulfonylpiperazine scaffold and the second HTS hit within their complexes with PI3Kγ revealed a high degree of overlap. This feature was utilized to design a series of hybrid analogues including advanced leads such as 31 with desirable potency, selectivity, and oral bioavailability.