- Synthesis and in Vitro and in Vivo Biological Evaluation of Tissue-Specific Bisthiazole Histone Deacetylase (HDAC) Inhibitors
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A series of bisthiazole-based hydroxamic acids as novel potent HDAC inhibitors was developed during our previous work. In the present work, a new series of highly potent bisthiazole-based compounds were designed and synthesized. Among the prepared compounds, compound H13, which contains an α-(S)-methyl-substituted benzyl group, displays potent inhibitory activity toward human HDACs and several cancer cells lines. Compound H13 has a favorable PK profile and high tissue distribution specificity in the colon, as well as good efficacy in the AOM-DSS mouse model for colitis-associated colonic tumorigenesis.
- Zhang, Shu-Wei,Gong, Chao-Jun,Su, Ming-Bo,Chen, Fei,He, Ting,Zhang, Yang-Ming,Shen, Qian-Qian,Su, Yi,Ding, Jian,Li, Jia,Chen, Yi,Nan, Fa-Jun
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p. 804 - 815
(2020/02/04)
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- SUBSTITUTED HYDROXAMIC ACIDS AND USES THEREOF
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This invention provides compounds of formula (I): wherein ring A, X1, X2, X3, R2, R4b, R10, and G have values as described in the specification, useful as inhibitors of HDAC6. The invention also provides pharmaceutical compositions comprising the compounds of the invention, and methods of using the compositions in the treatment of proliferative, inflammatory, infectious, neurological or cardiovascular diseases or disorders.
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- Novel small molecule bradykinin B1 receptor antagonists. Part 1: Benzamides and semicarbazides
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The synthesis and SAR of two series of bradykinin B1 receptor antagonists is described. The benzamide moiety proved to be a suitable replacement for the aryl ester functionality of biaryl based antagonists. In addition, it was found that semica
- Schaudt, Marco,Locardi, Elsa,Zischinsky, Gunther,Stragies, Roland,Pfeifer, Jochen R.,Gibson, Christoph,Scharn, Dirk,Richter, Uwe,Kalkhof, Holger,Dinkel, Klaus,Schnatbaum, Karsten
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scheme or table
p. 1225 - 1228
(2010/06/15)
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- Efficient synthesis of chiral phenethylamines: preparation, asymmetric hydrogenation, and mild deprotection of ene-trifluoroacetamides
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A mild and efficient route to enantioenriched aryl alkyl amines from ketones has been developed. The first successful synthesis and asymmetric hydrogenation of ene-trifluoroamides from oximes gave highly enantioenriched trifluoroacetamides (94-98% ee). The corresponding phenethyl amides are liberated under mild conditions (K2CO3, MeOH/H2O). In addition, a new application of Josiphos ligands toward the asymmetric hydrogenation of both ene-acetamides and ene-trifluoroacetamides was discovered.
- Allwein, Shawn P.,McWilliams, J. Christopher,Secord, Elizabeth A.,Mowrey, Dale R.,Nelson, Todd D.,Kress, Michael H.
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p. 6409 - 6412
(2007/10/03)
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- Piperazine compounds and medicinal use thereof
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The present invention relates to a piperazine compound of the formula wherein R1and R2are each hydrogen, halogen, lower alkyl, lower alkoxy, amino, substituted amino, nitro, hydroxy or cyano, R3, R4and R5are each hydrogen, halogen, lower alkyl, lower alkoxy, nitro, amino, substituted amino or hydroxy, R6and R7are each hydrogen, lower alkyl, lower alkyl substituted by halogen, aralkyl, acyl or lower acyl substituted by halogen, R8and R9are each hydrogen or lower alkyl, Y is lower alkylene and the like, and ring A is phenyl, pyrimidyl, thiazolyl, pyridyl, pyrazyl or imidazolyl, a pharmaceutically acceptable salt thereof and pharmaceutical agents containing these compounds. The compound of the present invention has superior TNF-α production inhibitory effect and/or IL-10 production promoting effect, and, since it is free of or shows only strikingly reduced expression of an effect on the central nervous system, the compound is useful as a highly safe and superior TNF-α production inhibitor an/or IL-10 production promoter and is useful as an agent for the prophylaxis or treatment of various diseases caused by abnormal TNF-α production, diseases curable with IL-10, such as chronic inflammatory diseases, acute inflammatory diseases, inflammatory diseases due to infection, autoimmune diseases, allergic diseases, and TNF-α mediated diseases.
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