Continued exploration of the triazolopyridine scaffold as a platform for p38 MAP kinase inhibition
Graphical abstract
The structure based drug design, synthesis and structure–activity relationship of a series of C6 sulfur linked triazolopyridine based p38 inhibitors are described. The metabolic deficiencies of this series were overcome through changes in the C6 linker from sulfur to methylene, which was predicted by molecular modeling to be bioisosteric. X-ray of the ethylene linked compound 61 confirmed the predicted binding orientation of the scaffold in the p38 enzyme.
References and notes (16)
Curr. Opin. Invest. Drugs
(2001)- et al.
Exp. Opin. Ther. Pat.
(2005) - et al.
Drug News Perspect.
(2000)et al.Nature
(1994) - et al.
Arthritis Rheum.
(1990)et al.J. Immunol.
(1990)et al.Gastroenterology
(1999)et al.Arthritis Rheum.
(2000) - et al.
Drugs
(1999)et al.Br. J. Clin. Pharmacol.
(2001)Aliment. Pharmacol. Ther.
(1999)Curr. Opin. Anti-Inflamm. Immunomodulat. Invest. Drugs
(2000) - et al.
Bioorg. Med. Chem. Lett.
(2006) - et al.
J. Med. Chem.
(2005)
Cited by (21)
Triazolopyridine, a leitmotif of synthetic methods and pharmacological attributes: An extensive review
2023, Arabian Journal of ChemistryA review of synthetic methods of 1,2,4-triazolopyridines and their therapeutic properties
2023, Results in ChemistrySynthesis and biological evaluation of (1,2,4)triazole[4,3-a]pyridine derivatives as potential therapeutic agents for concanavalin A-induced hepatitis
2019, European Journal of Medicinal ChemistryCitation Excerpt :In our continued concern about new potential small molecules that can be used as anti-inflammation agents, screening of our small molecule library was carried out, leading to the discovery of compound 3b (Fig. 1), which is a triazolopyridine derivative. The triazolopyridines have been identified as one of the promising scaffolds in medicinal chemistry, which possess a wide range of biological activities, such as p38 inhibitors [22–25], c-Met inhibitors [26], protein tyrosine kinase modulators [27] and dipeptidyl peptidase IV inhibitors [28]. We focused our attention on the (1,2,4)triazole[4,3-a]pyridine (TZP) motif owing to the (1,2,4)triazole core structure being able to serve as a suitable hydrogen bonding acceptor, which is thought to be essential for its pharmacological activity.
One-pot synthesis of N-fused 1,2,4-triazoles and related heterocycles via I<inf>2</inf>/TBHP-mediated oxidative C–N bond formation
2018, Tetrahedron LettersCitation Excerpt :1,2,4-Triazole-fused heterocycles are widely found in natural products and drugs with a broad spectrum of biological activities, such as antibacterial [1], anti-HIV [2], anti-inflammatory [3], and antiepileptic activities [4], (Fig. 1).
Facile one-pot synthesis of new [1,2,4]triazolo[1,5-a]pyridine derivatives by ultrasonic irradiation
2017, Synthetic Communications
- †
Present address: Genomics Institute of the Novartis Research Foundation (GNF), 10675 John Jay Hopkins Dr., San Diego, CA 92121, USA.
- ‡
Present address: Johnson & Johnson PRD-La Jolla, 3210 Merryfield Row, San Diego, CA 9212, USA.
- §
Present address: Pfizer Global Research and Development, La Jolla Laboratories, 10770 Science Center Drive, San Diego, CA 92121, USA.