ABSTRACT
A series of new pyrrole derivatives, pyrrolo[2,3-d]pyrimidine derivatives, pyrrolotriazolopyrimidines and pyrrolotetrazolopyrimidines were synthesized. The evaluation of their antimicrobial activities against Staphylococcus aureus, Escherichia coli, and Candida albicans were carried out. Pyrrolo[2,3-d]pyrimidines 3a-d, 7a,e, 11d exhibited excellent activity against C. albicans with MIC 0.31-0.62 mg/mL. These compounds displayed better antifungal activity than that of standard drug (fluconazole with MIC 1.5 mg/mL). Furthermore, pyrrolo[2,3-d]pyrimidines 3b,c, 7e exhibited the best activity against S. aureus with MIC 0.31 mg/mL, compared with the standard drug (ampicillin with MIC 0.62 mg/mL). The rest of the compounds were found to be inactive against bacteria and fungi.
Subject(s)
Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/pharmacology , Pyridines/chemical synthesis , Pyridines/pharmacology , Pyrroles/chemical synthesis , Pyrroles/pharmacology , Anti-Infective Agents/chemistry , Candida albicans/drug effects , Escherichia coli/drug effects , Magnetic Resonance Spectroscopy , Mass Spectrometry , Microbial Sensitivity Tests , Pyridines/chemistry , Pyrroles/chemistry , Spectrophotometry, Infrared , Staphylococcus aureus/drug effectsABSTRACT
A series of non-nucleosides 9-47 were synthesized. Compounds 1-4 were reacted with formic acid (85%) to afford compounds 5-8. Then, the latter compounds were reacted with alkyl halides a-f (2-bromopropane, 2-bromobutane, benzyl bromide, benzyl chloromethyl ether, chloromethyl ethyl ether, phenacyl bromide) in the presence of NaH in dry DMF to give the desired compounds 9-47, which were evaluated for activity against herpes simplex virus type-II (HSV-II).
Subject(s)
Antiviral Agents/pharmacology , Herpesvirus 2, Human/drug effects , Pyrimidinones/pharmacology , Pyrroles/pharmacology , Animals , Antiviral Agents/chemical synthesis , Chlorocebus aethiops , Herpesvirus 2, Human/growth & development , Microbial Sensitivity Tests , Pyrimidinones/chemical synthesis , Pyrroles/chemical synthesis , Structure-Activity Relationship , Vero Cells , Viral Plaque AssayABSTRACT
The MAP kinase p38 plays a key role in the biosynthesis of the inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and 1L-1beta. Accordingly, new pyrrolo[2, 3-]pyridine derivatives 5a-d were prepared from 2-amino-3-cyanopyrroles 3a-d via the intermediate propenylaminopyrroles 4a-d. Then the compounds 5a-d were tested for their ability to inhibit the production of TNF-alpha in vivo in rats. The most potent compounds 5a and 5b possess enhanced ability to inhibit the production of TNF-alpha stimulated with bacterial lipopolysaccharide.
