Azaindole structural framework is an integral part of several biologically active natural and synthetic organic molecules; and several FDA approved drugs for various diseases. In the last decade, quite a number of literature reports appeared describing the pharmacology, biological activity and therapeutic applications of a variety of azaindole molecules. This prompted the organic and medicinal chemistry community to develop novel synthetic methods for various azaindoles and test them for a bioactivity against a variety of biological targets. Herein, we have summarized the biological activity of therapeutically advanced clinical candidates and several preclinical candidate drugs that contain azaindole structural moiety.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736151 | PMC |
| http://dx.doi.org/10.1016/j.bmc.2020.115830 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
In Silico Prediction of Alkaline Phosphatase Interaction with the Natural Inhibitory 5-Azaindoles Guitarrin C and D.
Molecules
December 2024
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, Prospect 100-Letya Vladivostoka 152, 690022 Vladivostok, Russia.
The natural 5-azaindoles, marine sponge guitarrin C and D, were observed to exert inhibitory activity against a highly active alkaline phosphatase (ALP) CmAP of the PhoA family from the marine bacterium , with IC values of 8.5 and 110 µM, respectively. The superimposition of CmAP complexes with -nitrophenyl phosphate (NPP), a commonly used chromogenic aryl substrate for ALP, and the inhibitory guitarrins C, D, and the non-inhibitory guitarrins A, B, and E revealed that the presence of a carboxyl group at C6 together with a hydroxyl group at C8 is a prerequisite for the inhibitory effect of 5-azaindoles on ALP activity.
View Article and Find Full Text PDFGeometry Optimization Using the Frozen Domain and Partial Dimer Approaches in the Fragment Molecular Orbital Method: Implementation, Benchmark, and Applications to Protein Ligand-Binding Sites.
J Chem Inf Model
December 2024
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Osaka, Suita 565-0871, Japan.
Article Synopsis
- - The frozen domain (FD) approximation using the fragment molecular orbital (FMO) method allows for efficient partial geometry optimization of large biomolecular systems, including protein-ligand complexes.
- - A new variation called the frozen domain and partial dimer (FDPD) method was developed, which significantly reduces computational time for geometry optimization compared to conventional methods, achieving notable improvements in systems such as the β-adrenergic receptor and estrogen receptor.
- - The FDPD method enhanced the understanding of structure-activity relationships in drug design, as it improved the correlation between ligand binding energy and biological activity by optimizing structures more effectively.
Structure-mutagenicity relationships on quinoline and indole analogues in the Ames test.
Genes Environ
November 2024
Global Drug Safety, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba-shi, Ibaraki, 300-2635, Japan.
Background: Although the in silico predictive ability of the Ames test results has recently made remarkable progress, there are still some chemical classes for which the predictive ability is not yet sufficient due to a lack of Ames test data. These classes include simple heterocyclic compounds. This study aimed to investigate the mutagenicity and structure-mutagenicity relationships for some heterocycles in the Ames test.
View Article and Find Full Text PDFDesign and Synthesis of Potential Multi-Target Antidepressants: Exploration of 1-(4-(7-Azaindole)-3,6-dihydropyridin-1-yl)alkyl-3-(1-indol-3-yl)pyrrolidine-2,5-dione Derivatives with Affinity for the Serotonin Transporter.
Int J Mol Sci
October 2024
Department of Drug Technology and Pharmaceutical Biotechnology, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, 02-097 Warszawa, Poland.
We describe the design, synthesis and structure-activity relationship of a novel series of 1-(4-(7-azaindole)-3,6-dihydropyridin-1-yl)alkyl-3-(1-indol-3-yl)pyrrolidine-2,5-dione derivatives with combined effects on the serotonin (5-HT) and dopamine (D) receptors and the serotonin (5-HT), noradrenaline (NA), and dopamine (DA) transporters as multi-target directed ligands for the treatment of depression. All of the tested compounds demonstrated good affinity for the serotonin transporter (SERT). Among them, compounds and emerged as the lead candidates because of their promising pharmacological profile based on in vitro studies.
View Article and Find Full Text PDFSynthesis of 3-heteroaryl-pyrrolo[2,3-b]pyridines as potent inhibitors of AP-2-associated protein kinase 1 (AAK1) with antiviral activity.
Eur J Med Chem
December 2024
KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Molecular Structural and Translational Virology Research Group, Herestraat 49, box 1043, B-3000 Leuven, Belgium. Electronic address:
Inhibition of AP-2-associated protein kinase 1 (AAK1) has been shown to be a promising avenue for the development of broad-spectrum antiviral agents. On a previously described AAK1 inhibitor based on a pyrrolo[2,3-b]pyridine scaffold, the concept of isosterism was applied, by replacing a carboxamide linker by various five-membered heterocycles. It led to the discovery of a novel series of AAK1 inhibitors with IC values in the low nM range, that also displayed antiviral activity against the dengue virus and Venezuelan equine encephalitis virus.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!