124663-30-5Relevant articles and documents
SP1-independent inhibition of FOXM1 by modified thiazolidinediones
Tabatabaei Dakhili, Seyed Amirhossein,Pérez, David J.,Gopal, Keshav,Haque, Moinul,Ussher, John R.,Kashfi, Khosrow,Velázquez-Martínez, Carlos A.
, (2020/10/21)
This research article describes an approach to modify the thiazolidinedione scaffold to produce test drugs capable of binding to, and inhibit, the in vitro transcriptional activity of the oncogenic protein FOXM1. This approach allowed us to obtain FOXM1 i
Gram-scale synthesis of a novel core building block for the new GPR40 agonist design
Lukin, Alexey,Bagnyukova, Daria,Zhurilo, Nikolay,Krasavin, Mikhail
, p. 491 - 495 (2016/11/19)
Background: 3-[4-(Benzyloxy)phenyl]propanoic acid moiety is central to many advanced agonists of free fatty acid receptor 1 (FFA1 or GPR40) which are a new, promising class of antidiabetic drugs. An aldehydo carboxylic acid tert-butyl ester building block is required for speedy SAR exploration of analogs of Eli Lilly's GPR40 agonist LY2881835 which was in phase I clinical trials. Methods: The aldehyde functionality of the target building block was masked as methyl carboxylate. The phenylpropionic acid tert-butyl ester portion was constructed using Horner-Wadsworth-Emmons chemistry followed by olefin hydrogenation. The aldehyde function was unmasked via methyl ester hydrolysis, mixed anhydride reduction to alcohol and back-oxidation with manganese (IV) dioxide. Results: The synthesis of the target building block was realized in 7 chemical steps (the final three of which were conducted in succession not requiring interim purifications) involving isolation and characterization of four hitherto undescribed intermediates. Conclusion: The method described is suitable for production of the target alehydo carboxylic acid tertbutyl ester building block on a multigram scale, which will facilitate the parallel synthesis of LY2881835 analogs and expedite the respective SAR exploration.
NOVEL COMPOUNDS
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Page/Page column, (2014/06/23)
Compounds of formula (I) described herein are inhibitors of the phosphodiesterase 4 (PDE4) enzyme and muscarinic M3 receptor antagonists and are useful for the prevention and/or treatment of diseases of the respiratory tract characterized by airway obstru
