- TRPML MODULATORS
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The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
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- A Practical Method for Continuous Production of sp3-Rich Compounds from (Hetero)Aryl Halides and Redox-Active Esters
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A practically useful coupling reaction between aromatic halides and redox-active esters was realized by nickel catalysis through the use of a packed zinc bed column in continuous flow. Multiple reuse of the column showed a negligible decrease in efficiency, affording high space/time yields. A wide range of substrates, including a number of heteroaryl halides and polyfunctional materials were coupled in generally good yields. Longer-time and larger-scale experiments further demonstrates the robustness of the system.
- Watanabe, Eiichi,Chen, Yiding,May, Oliver,Ley, Steven V.
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supporting information
p. 186 - 191
(2019/12/24)
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- Design, synthesis and evaluation of substituted piperidine based KCNQ openers as novel antiepileptic agents
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Epilepsy is a kind of disease with complicated pathogenesis. KCNQ (Kv7) is a voltage dependent potassium channel that is mostly associated with epilepsy and thus becomes an important target in the treatment of epilepsy. In this paper, a series of substituted piperidine derivatives targeting KCNQ were designed and synthesized by using scaffold hopping and active substructure hybridization. Compounds were evaluated by fluorescence-based thallium influx assay, Rb+ flow assay and electrophysiological patch-clamp assay. Results showed that some compounds possessed more potent potassium channel opening activity than Retigabine. More significantly, compound 11 was found to have good pharmacokinetic profiles in vivo.
- Yang, Shaoning,Lu, Dingqiang,Ouyang, Pingkai
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p. 1731 - 1735
(2018/05/04)
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- A Versatile Route to Unstable Diazo Compounds via Oxadiazolines and their Use in Aryl–Alkyl Cross-Coupling Reactions
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Coupling of readily available boronic acids and diazo compounds has emerged recently as a powerful metal-free carbon–carbon bond forming method. However, the difficulty in forming the unstable diazo compound partner in a mild fashion has hitherto limited their general use and the scope of the transformation. Here, we report the application of oxadiazolines as precursors for the generation of an unstable family of diazo compounds using flow UV photolysis and their first use in divergent protodeboronative and oxidative C(sp2)?C(sp3) cross-coupling processes, with excellent functional-group tolerance.
- Greb, Andreas,Poh, Jian-Siang,Greed, Stephanie,Battilocchio, Claudio,Pasau, Patrick,Blakemore, David C.,Ley, Steven V.
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p. 16602 - 16605
(2017/12/13)
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- Nickel-Catalyzed Cross-Coupling of Redox-Active Esters with Boronic Acids
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A transformation analogous in simplicity and functional group tolerance to the venerable Suzuki cross-coupling between alkyl-carboxylic acids and boronic acids is described. This Ni-catalyzed reaction relies upon the activation of alkyl carboxylic acids as their redox-active ester derivatives, specifically N-hydroxy-tetrachlorophthalimide (TCNHPI), and proceeds in a practical and scalable fashion. The inexpensive nature of the reaction components (NiCl2?6 H2O—$9.5 mol?1, Et3N) coupled to the virtually unlimited commercial catalog of available starting materials bodes well for its rapid adoption.
- Wang, Jie,Qin, Tian,Chen, Tie-Gen,Wimmer, Laurin,Edwards, Jacob T.,Cornella, Josep,Vokits, Benjamin,Shaw, Scott A.,Baran, Phil S.
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p. 9676 - 9679
(2016/08/10)
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- HETEROCYCLIC MODULATORS OF LIPID SYNTHESIS AND COMBINATIONS THEREOF
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Heterocyclic modulators of lipid synthesis are provided as well as pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising such compounds; and methods of treating conditions characterized by disregulation of a fatty acid synthase pathway by the administration of such compounds and combinations of such compounds and other therapeutic agents.
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Page/Page column 127
(2015/07/07)
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- Metal-free coupling of saturated heterocyclic sulfonylhydrazones with boronic acids
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The coupling of aromatic moieties with saturated heterocyclic partners is currently an area of significant interest for the pharmaceutical industry. Herein, we present a procedure for the metal-free coupling of 4-, 5-, and 6-membered saturated heterocyclic p-methoxyphenyl (PMP) sulfonylhydrazones with aryl and heteroaromatic boronic acids. This procedure enables a simple, two-step synthesis of a range of functionalized sp2-sp3 linked bicyclic building blocks, including oxetanes, piperidines, and azetidines, from their parent ketones.
- Allwood, Daniel M.,Blakemore, David C.,Brown, Alan D.,Ley, Steven V.
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p. 328 - 338
(2014/01/17)
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- HETEROCYCLIC MODULATORS OF LIPID SYNTHESIS
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Heterocyclic modulators of lipid synthesis are provided as well as pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising such compounds; and methods of treating conditions characterized by disregulation of a fatty acid synthase pathway by the administration of such compounds.
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Page/Page column 112
(2014/01/18)
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