176853-40-0Relevant articles and documents
Marbostat-100 Defines a New Class of Potent and Selective Antiinflammatory and Antirheumatic Histone Deacetylase 6 Inhibitors
Sellmer, Andreas,Stangl, Hubert,Beyer, Mandy,Grünstein, Elisabeth,Leonhardt, Michel,Pongratz, Herwig,Eichhorn, Emerich,Elz, Sigurd,Striegl, Birgit,Jenei-Lanzl, Zsuzsa,Dove, Stefan,Straub, Rainer H.,Kr?mer, Oliver H.,Mahboobi, Siavosh
, p. 3454 - 3477 (2018)
Epigenetic modifiers of the histone deacetylase (HDAC) family contribute to autoimmunity, cancer, HIV infection, inflammation, and neurodegeneration. Hence, histone deacetylase inhibitors (HDACi), which alter protein acetylation, gene expression patterns, and cell fate decisions, represent promising new drugs for the therapy of these diseases. Whereas pan-HDACi inhibit all 11 Zn2+-dependent histone deacetylases (HDACs) and cause a broad spectrum of side effects, specific inhibitors of histone deacetylase 6 (HDAC6i) are supposed to have less side effects. We present the synthesis and biological evaluation of Marbostats, novel HDAC6i that contain the hydroxamic acid moiety linked to tetrahydro-β-carboline derivatives. Our lead compound Marbostat-100 is a more potent and more selective HDAC6i than previously established well-characterized compounds in vitro as well as in cells. Moreover, Marbostat-100 is well tolerated by mice and effective against collagen type II induced arthritis. Thus, Marbostat-100 represents a most selective known HDAC6i and the possibility for clinical evaluation of a HDAC isoform-specific drug.
MK-7622: A First-in-Class M1 Positive Allosteric Modulator Development Candidate
Beshore, Douglas C.,Di Marco, Christina N.,Chang, Ronald K.,Greshock, Thomas J.,Ma, Lei,Wittmann, Marion,Seager, Matthew A.,Koeplinger, Kenneth A.,Thompson, Charles D.,Fuerst, Joy,Hartman, George D.,Bilodeau, Mark T.,Ray, William J.,Kuduk, Scott D.
supporting information, p. 652 - 656 (2018/05/14)
Identification of ligands that selectively activate the M1 muscarinic signaling pathway has been sought for decades to treat a range of neurological and cognitive disorders. Herein, we describe the optimization efforts focused on addressing key physicochemical and safety properties, ultimately leading to the clinical candidate MK-7622, a highly selective positive allosteric modulator of the M1 muscarinic receptor that has entered Phase II studies in patients with Alzheimer's disease.
DIHYDROBENZOQUINAZOLINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
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Page/Page column 32-33, (2012/04/23)
The present invention is directed to dihydrobenzoquinazilinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease
