63876-46-0Relevant articles and documents
Bypassing Biocatalytic Substrate Limitations in Oxidative Dearomatization Reactions by Transient Substrate Mimicking
Milzarek, Tobias M.,Einsiedler, Manuel,Aldemir, Hülya,D'Agostino, Paul M.,Evers, Julia K.,Hertrampf, Gesa,Lamm, Katharina,Malay, Mert,Matura, Anke,Müller, Jonas I.,Gulder, Tobias A. M.
supporting information, p. 4520 - 4524 (2019/06/27)
Enzymatic oxidative dearomatization is an efficient way to generate chiral molecules from simple arenes. One example is the flavin-dependent monooxygenase SorbC involved in sorbicillinoid biosynthesis. However, SorbC requires a long-chain keto substituent at its phenolic substrate, thus preventing its application beyond the synthesis of natural sorbicillinoids or close structural analogues. This work describes an approach to broaden the accessible product spectrum of SorbC by employing an ester functionality mimicking the natural substrate structure during enzymatic oxidation.
Design and synthesis of systemically active metabotropic glutamate subtype-2 and -3 (mGlu2/3) receptor positive allosteric modulators (PAMs): Pharmacological characterization and assessment in a rat model of cocaine dependence
Dhanya, Raveendra-Panickar,Sheffler, Douglas J.,Dahl, Russell,Davis, Melinda,Lee, Pooi San,Yang, Li,Nickols, Hilary Highfield,Cho, Hyekyung P.,Smith, Layton H.,D'Souza, Manoranjan S.,Conn, P. Jeffrey,Der-Avakian, Andre,Markou, Athina,Cosford, Nicholas D.P.
, p. 4154 - 4172 (2014/06/09)
As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure-activity relationship (SAR) studies around a series of group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu2 receptor PAMs and no activity at mGlu3. Compound optimization led to the identification of potent mGlu2/3 selective PAMs with no in vitro activity at mGlu1,4-8 or 45 other CNS receptors. In vitro pharmacological characterization of representative compound 44 indicated agonist-PAM activity toward mGlu2 and PAM activity at mGlu 3. The most potent mGlu2/3 PAMs were characterized in assays predictive of ADME/T and pharmacokinetic (PK) properties, allowing the discovery of systemically active mGlu2/3 PAMs. On the basis of its overall profile, compound 74 was selected for behavioral studies and was shown to dose-dependently decrease cocaine self-administration in rats after intraperitoneal administration. These mGlu2/3 receptor PAMs have significant potential as small molecule tools for investigating group II mGlu pharmacology.
Allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2). Part 1: Identification and synthesis of phenyl-tetrazolyl acetophenones
Pinkerton, Anthony B.,Cube, Rowena V.,Hutchinson, John H.,Rowe, Blake A.,Schaffhauser, Hervé,Zhao, Xiumin,Daggett, Lorrie P.,Vernier, Jean-Michel
, p. 5329 - 5332 (2007/10/03)
We have identified and synthesized a series of aryl-tetrazoyl acetophenones as positive allosteric potentiators of the metabotropic glutamate receptor 2. Structure activity relationship studies directed toward improving the potency and level of potentiation led to the discovery of 22 (EC50 = 93 nM, 128% potentiation). We have identified and synthesized a series of aryl-tetrazoyl acetophenones as positive allosteric potentiators of the metabotropic glutamate receptor 2. Structure activity relationship studies directed toward improving the potency and level of potentiation led to the discovery of 22 (EC50 = 93 nM, 128% potentiation).
