156094-64-3Relevant academic research and scientific papers
Discovery of a tricyclic farnesoid X receptor agonist HEC96719, a clinical candidate for treatment of non-alcoholic steatohepatitis
Cao, Shengtian,Yang, Xinye,Zhang, Zheng,Wu, Junwen,Chi, Bo,Chen, Hong,Yu, Jianghong,Feng, Shanshan,Xu, Yulin,Li, Jing,Zhang, Yingjun,Wang, Xiaojun,Wang, Yan
supporting information, (2022/01/24)
Non-alcoholic fatty liver disease (NAFLD) is becoming the most predominant burden of chronic liver disease worldwide. Non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD, can develop into cirrhosis and hepatocellular cancer. Unfortunately, current options for therapeutic treatment of NASH are very limited. Among multiple pathways in NASH, farnesoid X receptor (FXR), a nuclear bile acid receptor, is well-recognized as an important effective target. Here we report the synthesis and characterization of compound HEC96719 a novel tricyclic FXR agonist based on a prior high-affinity nonsteroidal molecule GW4064. HEC96719 exhibits excellent potency superior to GW4064 and obeticholic acid in in vitro and in vivo assays of FXR activation. It also shows higher FXR selectivity and more favorable tissue distribution dominantly in liver and intestine. Preclinical data on pharmacokinetic properties, efficacy, and safety profiles overall indicate that HEC96719 is a promising drug candidate for NASH treatment.
SHP2 PHOSPHATASE INHIBITORS AND METHODS OF USE THEREOF
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Paragraph 0233, (2019/10/15)
The present disclosure relates to novel compounds including formula (X) and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure.
Preparation of 1,5-Dihydropyrazolo[3′,4′:5,6]pyrano[3,4- b]pyridines via a Microwave-Assisted, Palladium-Catalyzed Regioselective C-H Heteroarylation of Electron-Rich Pyrazoles
Garrison, Aaron T.,Childress, Elizabeth S.,Davis, Dexter C.,Lindsley, Craig W.
, p. 5855 - 5862 (2019/03/19)
Here we report the first synthesis of a family of novel heterocyclic compounds based on a 5-dihydropyrazolo[3′,4′:5,6]pyrano[3,4-b]pyridine core. In the course of our drug discovery programs, we had need to access the previously unknown 5-dihydropyrazolo[3′,4′:5,6]pyrano[3,4-b]pyridine core. Initial attempts required long reaction times, which led to degradation and side products. Reaction optimization identified a Pd-catalyzed, microwave-assisted C-H heteroarylation protocol for the rapid, general, and high yielding synthesis of this tricyclic core (as well as related analogs) suitable to drive optimization efforts.
NITROGEN-CONTAINING TRICYCLIC COMPOUNDS AND USES THEREOF IN MEDICINE
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Page/Page column 59, (2018/03/01)
A nitrogen-containing tricyclic compound which acts as modulator of FXR, or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and the use of the compoun
A process for the synthesis of intermediates in the preparation method of the huperzine-a
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Paragraph 0027; 0029; 0031; 0032; 0033, (2018/11/03)
The invention discloses a preparation method of an intermediate for synthesizing huperzine A. The preparation method comprises the following steps: substituting 3-bromine-6-methoxy-2-methyl pyridine taken as a raw material with N-bromosuccinimide so as to obtain a substitution product; carrying out a reaction on the substitution product and methyl acetoacetate and then carrying out ring closing reaction under the action of cuprous iodide so as to obtain 2-methoxy-6-hydroxy-7,8-dihydro-5-quinoline carboxylic methyl ester. According to the method provided by the invention, the synthesis reaction cost is low, so that the production cost is effectively lowered; the reaction conditions are moderate, so that the safety of operating personnel is ensured; a refining process is convenient and simple to operate; the intermediate obtained via the reaction is good in quality, high in yield and good in environmental friendliness.
A new approach to the bicyclo[3.3.1]nonane framework of huperzine A-like molecules via palladium-catalyzed intramolecular γ-arylation
Ding, Rui,Lu, Yunyu,Yao, Hequan,Sun, Bingfeng,Lin, Guoqiang
, p. 1097 - 1100 (2012/08/28)
In our synthetic studies toward huperzine A, a diastereoselective α′-alkylation of the α-amido-γ-methyl hexenone 4 was realized through a dianion intermediate which significantly enhanced the reactivity. Under the attempted Heck reaction conditions, an unexpected and unprecedented palladium-catalyzed intramolecular γ-arylation of 3 was observed, which generated 18 with bicyclo[3.3.1]nonane framework in satisfactory yield.
Methoxypyridines in the synthesis of lycopodium alkaloids: Total synthesis of (±)-lycoposerramine R
Bisai, Vishnumaya,Sarpong, Richmond
supporting information; experimental part, p. 2551 - 2553 (2010/08/06)
A methoxypyridine serves as a masked pyridone in a concise synthesis of the Lycopodium alkaloid lycoposerramine R, which has been prepared for the first time. The key step of the synthesis is the use of an Eschenmoser Claisen rearrangement to forge a key quaternary carbon center.
A convergent approach to huperzine A and analogues
Kelly, Sean A.,Foricher, Yann,Mann, John,Bentley, Jonathan M.
, p. 2865 - 2876 (2007/10/03)
We describe a concise and convergent synthesis of (rac)-5-methoxy-6-azatricyclco[7.3.1.02,7]trideca-2(7),3,5,11-tetraen -13-ol, which has the basic ring system of huperzine A, a potent inhibitor of acetylcholinesterase. We also describe the syn
Functionalisation of 2-methoxy-6-methylpyridine
Gray,Konopski,Langlois
, p. 1367 - 1379 (2007/10/02)
Selective bromination of 2-methoxy-6-methylpyridine 2 afforded 5-bromo-2- methoxy-6-methylpyridine 8. Deprotonation of this pyridine derivative in benzylic position or lithium-bromine exchange allowed the regio-selective introduction of various electrophiles.
