Stanislav Radl

Recent advances in the synthesis of antibacterial quinolones

This review surveys the main synthetic approaches used for the construction of antibacterial quinolones, including aza analogs (naphthyridones, cinnolones) and condensed polycyclic analogs, with an emphasis on the more versatile methods which are potentially useful in other fields of heterocyclic chemistry. Simpler non-condensed monocyclic analogs, i.e., pyridone and pyridazinone carboxylic acids are also briefly mentioned

Structure-activity relationships in DNA gyrase inhibitors

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.

An improved synthesis of 1,1-dimethylethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate, a key intermediate for atorvastatin synthesis

An improved synthesis of 1,1-dimethylethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate, a key intermediate for the synthesis of an effective HMG-CoA reductase inhibitor atorvastatin, is described. The synthesis is based on the iodolactonization of hepta-1,6-dien-4-ol to 4-allyl-6-iodomethyl-1,3-dioxan-2-one, which was converted in several steps to (6-allyl-2,2-dimethyl-1,3-dioxan-4-yl)-acetonitrile. This intermediate provided (6-cyanomethyl-2,2-dimethyl-1,3-dioxan-4-yl)acetic acid either via the corresponding aldehyde or via (2,2-dimethyl-6-oxiranylmethyl-1,3-dioxan-4-yl)acetonitrile.

Synthesis and Binding Studies of Some Epibatidine Analogues

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.

A New Way to tert-Butyl [(4R,6R)-6-Aminoethyl-2,2-dimethyl-1,3-dioxan-4-yl]acetate, a Key Intermediate of Atorvastatin Synthesis

Abstract A new synthesis of tert-butyl [(4R,6R)-6-aminoethyl-2,2-dimethyl-1,3-dioxan-4-yl]acetate, a key intermediate of the synthesis of an effective HMG-CoA reductase inhibitor atorvastatin, is described. The synthesis is based on the Henry reaction of nitromethane and tert-butyl [(4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl] acetate. The formed nitroaldol was then O-acetylated and the sodium borohydride reduction of the intermediate provided tert-butyl [(4R,6R)-2,2-dimethyl-6-nitroethyl-1,3-dioxan-4-yl] acetate. Catalytic hydrogenation of the nitro group led to the title compound.

Synthesis and Analgesic Activity of Some Quinazoline Analogs 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.

Synthesis and analgesic activity of some condensed analogs of anpirtoline.

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.

SYNTHETIC STUDIES CONNECTED WITH THE PREPARATION OF N-[3-(3-CYANOPYRAZOLO[1,5-a] PYRIMIDIN-5-YL)PHENYL]-N-ETHYLACETAMIDE, A ZALEPLON REGIOISOMER

N-[3-(3-Cyanopyrazolo[1,5-a]pyrimidin-5-yl)phenyl]-N-ethylacetamide, a principal impurity of zaleplon, is prepared by Suzuki-Miyaura cross coupling reaction of the corresponding boronic acid and/or boronates with 5-chloropyrazolo[1,5-a]pyrimidin-3-carbonitrile (7). Various methods of preparation of both components are described, as well as approaches based on the final modification of the 5-(3-aminophenyl)-pyrazolo[1,5-a]pyrimidine-3-carbonitrile moiety prepared by Suzuki-Miyaura cross coupling. All the prepared compounds were unambiguouesly identified by NMR techniques. Spectral characteristics (IR, UV, MS) of these compounds are also given.

Synthesis, analgesic activity, and binding properties of some epibatidine analogs with a tropine skeleton

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.

Synthesis and Analgesic Activity of Some Deaza Derivatives of Anpirtoline

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.