Biomedical subjects
Publications and source records attributed to S Rádl.
A series of epibatidine analogues and their positional isomers bearing an 8-azabicyclo[3.2.1]octane moiety is described. Some of the compounds, especially those containing 8-azabicyclo[3.2.1]oct-2-ene moiety show high affinity for the nicotinic cholinergic receptor.
New derivatives of anpirtoline and deazaanpirtoline modified in the side chain have been synthesized. The series includes compounds 3 with side-chains containing piperidine or pyrrolidine rings, compounds 4 containing 8-azabicyclo[3.2.1]octane moiety, and compounds 5 having piperazine ring in their side-chains. Their receptor binding profiles (5-HT1A, 5-HT1B) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. Optimized structures (PM3-MOPAC, Alchemy 2000, Tripos Inc.) of the synthesized compounds 3-5 were compared with that of anpirtoline.
New condensed derivatives of anpirtoline, in which the pyridine ring is replaced with quinoline, quinazoline, 7-chloroquinoline, and 7-chloroquinazoline nuclei, have been synthesized. Their receptor binding profiles (5-HT1A, 5-HT1B) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. The analgesic activity of compounds 4e-4g, and 4l are at least comparable to that of clinically used drugs flupirtine and tramadol under the same conditions.
A series of epibatidine analogs and their positional isomers bearing an 8-azabicyclo[3.2.1]octane moiety is described. Also some of their simplified analogs bearing a 3-piperidine moiety are reported. Their receptor binding profiles (5-HT1A, 5-HT1B, M1, M2, neuronal nicotinic receptor) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. Some of the compounds, especially those containing an 8-azabicyclo[3.2.1]oct-2-ene moiety possess high afinity for the nicotinic cholinergic receptor. The most analgesically active compounds are also highly toxic. Optimized structures (PM3-MOPAC, Alchemy 2000, Tripos Inc.) of compounds 1-9 were compared with that of epibatidine.
New deaza derivatives of anpirtoline have been synthesized by three different methods. Their receptor binding profiles (5-HT1A, 5-HT1B) and analgesic activity (hot plate, acetic acid induced writhing) have been studied.
New condensed derivatives of anpirtoline, in which the pyridine ring is replaced with quinoline, isoquinoline, quinazoline, and phthalazine nuclei, have been synthesized. Their receptor binding profiles (5-HT1A, 5-HT1B) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. The analgesic activity of compounds 7d, 8b, 8c, and 8e are at least comparable to that of the clinically used drugs flupirtine and tramadol under the same conditions.
IBC's International Conference on Integrating Combinatorial Chemistry into the Discovery Pipeline was held September 14-15, 1998. The program started with a pre-conference workshop on High-Throughput Compound Characterization and Purification. The agenda of the main conference was divided into sessions of Synthesis, Automation and Unique Chemistries; Integrating Combinatorial Chemistry, Medicinal Chemistry and Screening; Combinatorial Chemistry Applications for Drug Discovery; and Information and Data Management. This meeting was an excellent opportunity to see how big pharma, biotech and service companies are addressing the current bottlenecks in combinatorial chemistry to speed drug discovery.
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Chemotherapy has not only proved valuable in treating many diseases but the history of discovery of some drugs makes exciting reading. The aim of this article is to outline one such story.
Oxidation of 3-acetyl derivatives of 3-acetyl-1-ethyl-1,4-dihydro-6,7-methylenedioxyquinoline-4-one (VIc) and 3-acetyl-7-chloro-1-ethyl-6-fluoro-1,4-dihydroquinoline-4-one (VId) with selenium dioxide provided the corresponding acids, [1-ethyl-1,4-dihydro-6,7-methylenedioxy-4-oxoquinoline-3-yl]glyoxylic acid (VIe) and [7-chloro-1-ethyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-yl]glyoxylic acid (VIf), respectively. Reactions of compounds VIc--VIf with thiosemicarbazide yielded the respective thiosemicarbazones of 3-acetyl-1-ethyl-1,4-dihydro-6,7-methylenedioxyquinoline-4-one (VIIa), 3-acetyl-7-chloro-1-ethyl-6-fluoro-1,4-dihydroquinoline-4-one (VIIb), [1-ethyl-1,4-dihydro-6,7-methylenedioxy-4-oxoquinoline-3-yl]glyoxylic acids (VIId). The compounds showed no significant in vitro antibacterial activity.
The review brings the status of research into DNA gyrase inhibitors up to date. Structure-activity relationships in both coumarin antibiotics, like novobiocin or coumermycins, and quinolones are discussed. In the section dealing with the quinolones, promising drugs under further evaluation are pointed out. Recently discovered new types of DNA gyrase inhibitors, i.e. tetramic acid derivatives and biphenyl dicarboxylic acid monoamides, are also briefly mentioned.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.