Thiazoles in Peptides and Peptidomimetics

Abstract

This perspective article describes important properties of thiazoles in synthetic peptidomimetics and highlights key examples, including some from the last five years.

Potent Thiophene Antagonists of Human Complement C3a Receptor with Anti-Inflammatory Activity

“…Thiophenes are frequently occurring scaffolds in heterocyclic drugs, − for example, in the antidepressant Duloxetine, anti-hypertensive Eprosartan, oral anticoagulant Rivaroxban, antipsychotic Olanzapine, antiplatelet agents Clopidogrel, Preasugrel, and Ticlopidine, and there are many other thiophene-containing compounds with demonstrated efficacy in vitro or in animal models of diseases. − The present study has described structure–activity relationships centered around thiophene-based scaffolds with diverse substitution that has indicated some structural requirements for potent C3aR antagonism. In vitro, thiophene compounds potently inhibited intracellular Ca 2+ release in human macrophages (e.g., 10a , IC 50 85 nM; 10l , 30 nM; 14a , 10 nM; 14b , 7 nM), without inhibiting the agonist effects in the same concentration range as the related Complement protein C5a.…”

Biocompatible strategies for peptide macrocyclisation

“…165 The thiazole unit in the peptide backbone can inuence the folding architecture of peptides. [166][167][168][169] Flow-on effects from the small thiazole gra can stabilise the 2D structure by improving the intramolecular Hbond networks, 164,170 as well as increasing cell membrane permeability by reducing the number of H-bond donors and minimise water solvation of amide bonds. 171 In nature, thiazole crosslinks are formed through a post-translational transformation of cysteine via the mechanism shown in Scheme 8A.…”

Anticancer evaluation of di- and trifunctional substituted 1,3-thiazoles

“…It has been demonstrated that 1,3-thiazoles are widely used for creation of dyes, insecticides, herbicides, and pharmaceuticals. Di-and trisubstituted 1,3-thiazole are effective anti-inflammatory, anthelmintic, antiviral, and bactericidal agents [1][2][3][4][5][6]. The nature of the chemical groups in the heterocycle can significantly affect their pharmacological properties.…”