61471-45-2Relevant articles and documents
NOVEL SMALL MOLECULE SHC BLOCKERS FOR TREATING LIVER DISEASE AND METABOLIC DISEASE
-
Paragraph 00254; 00264, (2021/07/10)
The subject matter disclosed herein is directed to novel She inhibitors of Formula (II). These compounds are useful for treating impaired insulin sensitivity, glucose tolerance, obesity, diabetes, metabolic syndrome, NAFLD, NASH, PSC, PBC, or other metabo
Design, synthesis, and biological evaluation of N-carboxyphenylpyrrole derivatives as potent HIV fusion inhibitors targeting gp41
Liu, Kun,Lu, Hong,Hou, Ling,Qi, Zhi,Teixeira, Cátia,Barbault, Florent,Fan, Bo-Tao,Liu, Shuwen,Jiang, Shibo,Xie, Lan
experimental part, p. 7843 - 7854 (2009/11/30)
On the basis of the structures of small-molecule hits targeting the HIV-1 gp41, N-(4-carboxy-3-hydroxy)phenyl-2,5-dimethylpyrrole (2, NB-2), and N-(3-carboxy-4-chloro)phenylpyrrole (A1, NB-64), 42 N-carboxyphenylpyrrole derivatives in two categories (A and B series) were designed and synthesized. We found that 11 compounds exhibited promising anti-HIV-1 activity at micromolar level and their antiviral activity was correlated with their inhibitory activity on gp41 six-helix bundle formation, suggesting that these compounds block HIV fusion and entry by disrupting gp41 core formation. The structure-activity relationship and molecular docking analysis revealed that the carboxyl group could interact with either Arg579 or Lys574 to form salt bridges and two methyl groups on the pyrrole ring were favorable for interaction with the residues in gp41 pocket. The most active compound, N-(3-carboxy-4-hydroxy)phenyl-2,5-dimethylpyrrole (A12), partially occupied the deep hydrophobic pocket, suggesting that enlarging the molecular size of A12 could improve its binding affinity and anti-HIV-1 activity for further development as a small-molecule HIV fusion and entry inhibitor.
