Synthesis of 2-guanidinyl pyridines and their trypsin inhibition and docking.
Enzymology
Halogen bonding
Hydrogen bonding
Inhibitor
Molecular docking
Pyridin-2-yl guanidine
Serine protease
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
15 08 2020
15 08 2020
Historique:
received:
11
05
2020
revised:
18
06
2020
accepted:
23
06
2020
entrez:
22
7
2020
pubmed:
22
7
2020
medline:
11
6
2021
Statut:
ppublish
Résumé
A range of guanidine-based pyridines, and related compounds, have been prepared (19 examples). These compounds were evaluated in relation to their competitive inhibition of bovine pancreatic trypsin. Results demonstrate that compounds in which the guanidinyl substituent can form an intramolecular hydrogen bond (IMHB) with the pyridinyl nitrogen atom (6a-p) are better trypsin inhibitors than their counterparts (10-13) that are unable to form an IMHB. Among the compounds 6a-p, examples containing a 5-halo substituent were, generally, found to be better trypsin inhibitors. This trend was inversely related to electronegativity, thus, 1-(5-iodopyridin-2-yl)guanidinium ion 6e (K
Identifiants
pubmed: 32690267
pii: S0968-0896(20)30442-9
doi: 10.1016/j.bmc.2020.115612
pii:
doi:
Substances chimiques
Pyridines
0
Trypsin Inhibitors
0
Trypsin
EC 3.4.21.4
Guanidine
JU58VJ6Y3B
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
115612Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.