1423-61-6Relevant articles and documents
Antagonizing STAT3 activation with benzo[b]thiophene 1, 1-dioxide based small molecules
Zhang, Wenda,Ma, Ting,Li, Shanshan,Yang, Yanwei,Guo, Jianpeng,Yu, Wenying,Kong, Lingyi
, p. 538 - 550 (2017)
STAT3 is an attractive therapeutic target for cancer therapy. However, due to low potency or poor druggability, none of its inhibitors are clinically available. Herein, a series of aminobenzo[b]thiophene 1, 1-dioxides with good drug-likeness properties were designed, synthesized and evaluated as STAT3 inhibitors. Most of them exhibited higher antitumor activity than the small-molecule STAT3 inhibitor, Stattic. Compound 15 was the most potent and had an IC50range in 0.33–0.75?μM in various cancer cell lines. The overexpressed and IL-6 induced phosphorylation levels of STAT3 were both inhibited by 15 without influencing the phosphorylation levels of the upstream kinases Src and Jak2. 15 also suppressed the expressions of STAT3 downstream gene, Bcl-2. 15 effectively increased the ROS levels of cancer cells, induced cancer cell apoptosis and abolished the colony formation ability of cancer cells without affecting bypass kinase p-Erk. Furthermore, 15 in?vivo induced significant antitumor responses, and exhibited less toxicity than Doxorubicin. Together, this study described a class of new STAT3 inhibitors as antitumor agents.
Synthesis and pharmacological evaluation of N-benzyl substituted 4-bromo-2,5-dimethoxyphenethylamines as 5-HT2A/2C partial agonists
Hansen, Martin,Jacobsen, Stine Engesgaard,Plunkett, Shane,Liebscher, Gudrun Eckhard,McCorvy, John D.,Br?uner-Osborne, Hans,Kristensen, Jesper Langgaard
supporting information, p. 3933 - 3937 (2015/01/30)
N-Benzyl substitution of phenethylamine 5-HT2A receptor agonists has dramatic effects on binding affinity, receptor selectivity and agonist activity. In this paper we examine how affinity for the 5-HT2A/2C receptors are influenced by N-benzyl substitution of 4-bromo-2,5-dimethoxyphenethylamine derivatives. Special attention is given to the 2′ and 3′-position of the N-benzyl as such compounds are known to be very potent. We found that substitutions in these positions are generally well tolerated. The 2′-position was further examined using a range of substituents to probe the hydrogen bonding requirements for optimal affinity and selectivity, and it was found that small changes in the ligands in this area had a profound effect on their affinities. Furthermore, two ligands that lack a 2′-benzyl substituent were also found to have high affinity contradicting previous held notions. Several high-affinity ligands were identified and assayed for functional activity at the 5-HT2A and 5-HT2C receptor, and they were generally found to be less efficacious agonists than previously reported N-benzyl phenethylamines.
OLIGOMERISATION OF ETHYLENE TO MIXTURES OF 1-HEXENE AND 1-OCTENE
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Page/Page column 26-27, (2014/12/09)
A process for the otigomerisation of ethylene to predominantly 1-hexene or 1-octene or mixtures of 1-hexene and 1-octene includes contacting ethylene with a catalyst under ethylene oligomerisation conditions. The catalyst comprises a source of chromium, a diphosphine ligating compound, and optionally an activator. The diphosphine ligating compound includes at least one optionally substituted fused cyclic structure including at least two rings, the optionally substituted fused cyclic structure including a 5- to 7- membered aromatic first ring bonded to a phosphorus atom, the aromatic first ring being fused to a 4- to 8-membered heterocyclic second ring, the heterocyclic second ring including a heteroatom which is separated by two ring atoms along the shortest connecting path from the phosphorous atom that is bonded to the first aromatic ring.
