6522-02-7Relevant articles and documents
TRUNCATED ITRACONAZOLE ANALOGUES AND METHODS OF USE THEREOF
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Paragraph 0097; 0126, (2021/02/19)
Disclosed herein are analogues of itraconazole that are potent hedgehog signaling pathway inhibitors. The compounds are expected to be useful in the treatment of cell proliferation disorders such as cancer, particularly cancers that are dependent upon the hedgehog signaling pathway such as basal cell carcinoma and medulloblastoma.
Synthesis of Albicidin Derivatives: Assessing the Role of N-terminal Acylation on the Antibacterial Activity
Kerwat, Dennis,Gr?tz, Stefan,Kretz, Julian,Seidel, Maria,Kunert, Maria,Weston, John B.,Süssmuth, Roderich D.
, p. 1899 - 1903 (2016/10/12)
The peptide antibiotic albicidin, which is synthesized by the plant pathogenic bacterium, Xanthomonas albilineans, represents the most prominent member of a new class of antibacterial gyrase inhibitors. It shows remarkable antibacterial activities against Gram-positive and Gram-negative microorganisms. Its unique structure potentially represents a new lead structure for the development of an antibacterial drug. Here we report the synthesis of 14 albicidin derivatives with structural variations at the N-terminus, primarily investigating the effects of variation of cinnamoyl, phenylpropanoyl, and benzoyl residues. Gyrase inhibition in vitro and determination of minimal inhibitory concentrations were assessed in parallel. Activities in a nanomolar range and the importance of N-acylation were demonstrated.
Macrocyclic protease inhibitors with reduced peptide character
Chua, Krystle C. H.,Pietsch, Markus,Zhang, Xiaozhou,Hautmann, Stephanie,Chan, Hon Y.,Bruning, John B.,Guetschow, Michael,Abell, Andrew D.
, p. 7828 - 7831 (2014/08/05)
There is a real need for simple structures that define a β-strand conformation, a secondary structure that is central to peptide-protein interactions. For example, protease substrates and inhibitors almost universally adopt this geometry on active site binding. A planar pyrrole is used to replace two amino acids of a peptide backbone to generate a simple macrocycle that retains the required geometry for active site binding. The resulting β-strand templates have reduced peptide character and provide potent protease inhibitors with the attachment of an appropriate amino aldehyde to the C-terminus. Picomolar inhibitors of cathepsin L and S are reported and the mode of binding of one example to the model protease chymotrypsin is defined by X-ray crystallography. The incorporation of a pyrrole into a peptide backbone generates simple macrocycles that adopt a β-strand geometry. The attachment of a P1 amino aldehyde to these templates then gives rise to potent protease inhibitors (see example, top, which has Ki values of 440 pM and 920 pM against the cysteine cathepsins L and S, respectively). A crystal structure of a related derivative bound to chymotrypsin (see picture, bottom) confirms the design.
