An efficient synthetic route to a series of substituted 2-aminopyrimidine (2-AP) derivatives has been developed. Subsequent biofilm screening has allowed comparison between the biological activity of these new derivatives and that of the 2-aminoimidazole class of anti-biofilm compounds. Several derivatives displayed the ability to modulate bacterial biofilm formation, exhibiting greater activity against Gram-positive strains than Gram-negative strains. Additionally some 2-aminopyrmidines were able to suppress MRSA resistance to conventional antibiotics.
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http://dx.doi.org/10.1039/c2ob06871k | DOI Listing |
Biochem Biophys Res Commun
January 2025
Molecular Biophysics and Structural Biology (MBSB) Group, Department of Biochemistry, University of Johannesburg, Auckland Park Kingsway Campus, 2006, South Africa. Electronic address:
To address microbial infections and combat drug resistance, we designed, synthesized, and evaluated three novel s-triazine clubbed pharmacophores: 1-acetylpyrazoline (5a-e), 2-aminopyrimidine (6a-e), and 1,5-benzodiazepine (7a-e). These were derived from chalcone (4a-e), showing improved pharmacological profiles. The compounds underwent characterization by FTIR, NMR, and Mass Spectroscopy, and their antimicrobial activities, along with structure-activity relationships (SAR), were assessed using in silico and in vitro methods.
View Article and Find Full Text PDFArch Pharm (Weinheim)
January 2025
Fluoro & Agro Chemicals Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, India.
This report explores the potential of novel 6-aryloxy-2-aminopyrimidine-benzonitrile scaffolds as promising anti-infective agents in the face of the increasing threat of infectious diseases. Starting from 2-amino-4,6-dichloropyrimidine, a series of 24 compounds inspired from the antiviral drugs dapivirine, etravirine, and rilpivirine were designed and synthesized via a two-step reaction sequence in good yields. Biological testing of synthetic analogs revealed potent inhibition against both viral and tuberculosis targets.
View Article and Find Full Text PDFJ Med Chem
September 2024
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
Eur J Med Chem
November 2024
Eye Institute, Nankai University, 94 Weijin Road, Tianjin, 300071, China; School of Medicine, Nankai University, 94 Weijin Road, Tianjin, 300071, China. Electronic address:
To overcome C797S mutation, the latest and most common resistance mechanism in the clinical treatment of third-generation EGFR inhibitor, a novel series of substituted 6-(2-aminopyrimidine)-indole derivatives were designed and synthesized. Through the structure-activity relationship (SAR) study, compound 11eg was identified as a novel and potent EGFR inhibitor (IC = 0.053 μM) but had a weak effect on EGFR (IC = 1.
View Article and Find Full Text PDFEur J Med Chem
April 2024
Nerviano Medical Sciences S.r.l., Viale Pasteur 10, 20014, Nerviano, MI, Italy.
Spleen tyrosine kinase (Syk) is a key signal transduction mediator of the B cell receptor (BCR) signaling pathway. Abnormal BCR signaling plays a key role in initiation and development of B-cell-derived hematological malignancies, therefore, Syk represents a potential target for inhibiting the BCR signaling resulting in a therapeutic effect in these cancers. Herein, we describe a novel series of SYK inhibitors with 4-(3'-pyrazolyl)-2-amino-pyrimidine scaffold.
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