106928-50-1Relevant articles and documents
Amino [13]-macrodilactones: Synthesis, derivatization, and structural motifs
Chen, Chengsheng,Lawrence, Jean-Marc,Peczuh, Mark W.
, (2020)
Macrocycles draw their usefulness from an ability to balance size, shape, and functionality according to general principles. These structural parameters manifest as the conformations of macrocycles and ultimately their functions. Reported here are results of an investigation on [13]-macrodilactones that take up unique folded conformations based on the interplay of multi-atom planar units and sterics. The defining feature of this group of [13]-macrodilactones is the pendant amine group attached to the ring. Amidation of the ring generated analogs that were designed to imitate features of the macrocyclic natural product Teixobactin. We also show that intramolecular interactions, and the A-value of an acylated amine can explain the conformational preferences in macrocycles.
New histone deacetylase inhibitors based on 4-fluoro-2-amino acid esters: Synthesis and activity
Lübke, Martin,Jung, Manfred,Haufe, Günter
, p. 144 - 156 (2013/11/06)
A series of twelve fluorinated and non-fluorinated potential histone deacetylase inhibitors 25 was synthesized and their inhibitory activity was tested against rat liver histone deacetylase. The new inhibitors involve an enzyme binding element consisting of asparagine, glutamine or different short chain fluorinated or unfluorinated amino acids, a suberoyl spacer and a hydroxamic acid functionality, which is responsible for the inhibitory activity. The 4-fluoro-2-aminobutyric acid esters 1a,b, their 2-methyl derivatives 2a,b and the 2-amino-4-fluoropent-4-enoic acid esters 3a,b were synthesized by alkylation of glycine or alanine ester imides with bromofluoroethane or 2-fluoroallylbromide, respectively. Methyl 2-amino-5-fluorohex-5-enoate (4a) was prepared using 3-fluorobut-3-enyl tosylate or the iodide as alkylating reagents. An alternative pathway starting from Boc protected 3-iodo-L-alanine was more efficient. The latter method was also applied to synthesize the parent unfluorinated compound 4c using allylbromide as the alkylating reagent. The fluorinated compounds, tested as histone deacetylase inhibitors were slightly less active than comparable (S)-valine, (S)-phenylalanine or (S)-allylglycine derivatives that do not contain a fluorine atom. Interestingly, it was shown for the first time that the fluoro vinyl group which was proposed to be an aprotic amide mimic due to its electronic properties may serve as a bioisosteric replacement of a primary amide function. For the fluorinated analogs 25f (IC50 0.88 μM) and 25i (IC50 1.02 μM) a similar or an even enhanced inhibitory activity was observed compared to the unfluorinated parents 25g (IC50 0.67 μM) and 25j (IC50 1.79 μM) or the (S)-asparagine or (S)-glutamine derivatives 25l (IC50 2.10 μM) and 25m (IC50 3.90 μM).
THERAPEUTIC OR PROPHYLACTIC AGENT FOR MULTIPLE SCLEROSIS
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Page/Page column 37, (2009/04/23)
A therapeutic or prophylactic agent for multiple sclerosis is disclosed. The therapeutic or prophylactic agent comprises as an effective ingredient a glycine derivative having a specific structure or a pharmaceutically acceptable salt thereof, for example, the below-described compound [(E)-2-(2,6-dichlorobenzamido)-5-[4-(isopropyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid]. The therapeutic or prophylactic agent for multiple sclerosis according to the present invention shows the excellent absorbability and in vivo stability when orally administered, and exhibits high therapeutic or prophylactic effects.