The synthesis of water soluble hydrochlorides of indazole derivatives 1b, 8 and 9 is described. By treating of 2,5-dinitroindazole with thiomorpholine 3-thiomorpholino-5-nitroindazole (10) and 3,5-dinitroindazole (11) in the form of the molecular compound 11a are obtained. The known indazole derivatives 1 and 7 as well as the newly synthesized hydrochlorides of 1b, 8 and 9 are, except of 8.HCl, less toxic than benzydamine hydrochloric (BZD). The same compounds show with some excepts a comparable or greater antiinflammatory effect than BZD in the carrageenin induced oedema test.
Download full-text PDF |
Source |
---|
Molecules
January 2025
Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 32 Vavilov St., Moscow 119991, Russia.
In recent years, a number of synthetic potentiators of antibiotics have been discovered. Their action can significantly enhance the antibacterial effect and limit the spread of antibiotic resistance through inhibition of bacterial cystathionine-γ-lyase. To expand the known set of potentiators, we developed methods for the synthesis of five new representatives of 6-bromoindole derivatives-potential inhibitors of bacterial cystathionine-γ-lyase-namely potassium 3-amino-5-((6-bromoindolyl)methyl)thiophene-2-carboxylate () and its 6-bromoindazole analogs ( and ), along with two 6-broindazole analogs of the parent compound .
View Article and Find Full Text PDFCurr Pharm Des
January 2025
Department of Pharmacy Practice and Pharmacotherapeutics, University of Sharjah, Sharjah, UAE.
Background: Synthetic cannabinoids are one of the most identified abused drugs nowadays. Their popularity is due to their psychoactive effects, which resemble delta 9 tetrahydrocannabinol. This study investigates the genotoxic potential of three synthetic cannabinoids of indazole-passed drugs, AB-Fubinaca, AMBFubinaca, and EMB-Fubinaca (at a final concentration of 200 nM).
View Article and Find Full Text PDFACS Med Chem Lett
January 2025
Bristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, California 92121, United States.
In recent years, targeted protein degradation (TPD) has emerged as a powerful therapeutic modality utilizing both heterobifunctional ligand-directed degraders (LDDs) and molecular glues (e.g., CELMoDs) to recruit E3 ligases for inducing polyubiquitination and subsequent proteasomal degradation of target proteins.
View Article and Find Full Text PDFEur J Med Chem
December 2024
Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address:
Concurrent inhibition of HDAC and BRD4, two well-established epigenetic targets for anti-tumor therapy, demonstrates the potential to enhance anti-tumor effects synergistically. The present study involves the development of a series of novel HDAC3/BRD4 dual inhibitors, followed by evaluation of their antitumor efficacy against several tumor models. Guided by scaffold hopping strategy, key pharmacophore of BRD4 inhibitor I-BET-151 was incorporated into an in-house developed HDAC3-selective inhibitor 17h.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.
The design of dualsteric/bitopic receptor ligands as compounds capable of simultaneously interacting with both the orthosteric and an allosteric binding site has gained importance to achieve enhanced receptor specificity and minimize off-target effects. In this work, we reported the synthesis and biological evaluation of a new series of compounds, namely, the series, obtained by chemically combining the CB1R ago-positive allosteric modulators (PAM) with the cannabinoid receptors (CBRs) orthosteric agonist . Therefore, compounds were designed as dualsteric/bitopic ligands for CB1R with the aim of obtaining stronger CB1R agonists or ago-PAMs, with improved receptor subtype selectivity and reduction of central side effects.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!