- Marbostat-100 Defines a New Class of Potent and Selective Antiinflammatory and Antirheumatic Histone Deacetylase 6 Inhibitors
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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.
- 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
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supporting information
p. 3454 - 3477
(2018/05/01)
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- NOVEL HDAC6 INHIBITORS AND THEIR USES
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The present invention relates to small molecule compounds and their use as HDAC inhibitors and in the treatment of various diseases, such as cancer. The present invention further relates to methods of synthesizing the compounds and methods of treatment. H ? L(HA), H is a head group selected from (head group 1), (head group 2), (head group 3), (head group 4), (head group 5) and (head group 6).
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Page/Page column 54-55
(2016/05/02)
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- Synthesis of 3-Amino-2-(3-indolyl)propanol and propanoate derivatives and preliminary cardiovascular evaluation in rats
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A series of tryptamine analogues has been prepared and tested for their 5-HT1 receptor agonist properties. The incorporation of an alkoxy group at the C-5 position of the indole nucleus resulted in a short-lived and dose-dependent immediate ant
- Perez-Alvarez, Victor,Morales-Rios, Martha S.,Hong, Enrique,Joseph-Nathan, Pedro
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p. 246 - 252
(2007/10/03)
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- SYNTHESE BREVE DE L'INDORENATE
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A short synthesis of the potential anti-hypertensive drug indorenate 1 is described.
- Morales-Rios, Martha S.,Zepeda, L. Gerardo,Joseph-Nathan Pedro
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p. 2825 - 2826
(2007/10/02)
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- Process for the preparation of 3-amino-2-(5-fluoro and 5-methoxy-1H-indol-3-yl)propanoic acid derivatives
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The compounds having Formula I, STR1 wherein X is a fluorine or methoxy group, and R is a hydrogen or methyl group, such that R is hydrogen only when X is fluorine are novel. The compounds having Formula I and their acid addition salts are useful for the treatment of hypertension. Processes for the preparation of the compounds having Formula I and useful intermediates are described.
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- 3-Amino or amido-2-(1H-indol-3-yl) propanoic acid derivatives
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Disclosed are compounds characterized by the structural formula: STR1 Various compounds circumscribed by the foregoing formula in which: R is H, CH3 or CH2 CH3, R' is H, or STR2 X is H, F or OCH3, Y is H or Cl, and Z is H or STR3 are therapeutically useful as anti-hypertensive agents.
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