Switching "on" and "off" the adhesion in stimuli-responsive elastomers.

The present work aims at the preparation of dry adhesives with switchable bonding properties by using the reversible nature of the [4πs+4πs] cycloaddition of anthracenes. Photo-responsive hydrogenated carboxylated nitrile butadiene rubber with photo-responsive pendant anthracene groups is prepared by one-pot synthesis. The formation of 3D networks relies on the photodimerization of the anthracene moieties upon UV exposure (λ > 300 nm). Controlled cleavage of the crosslink sites is achieved by either deep UV exposure (λ = 254 nm) or thermal dissociation at 70 °C. The kinetics of the optical and thermal cleavage routes are compared in thin films using UV-vis spectroscopy and their influence on the reversibility of the network is detailed. Going from thin films to free standing samples the modulation of the network structure and thermo-mechanical properties over repeated crosslinking and cleavage cycles are characterized by low-field NMR spectroscopy and dynamic mechanical analysis. The applicability of the stimuli-responsive networks as adhesives with reversible bonding properties is demonstrated. The results evidence that the reversibility of the crosslinking reaction enables a controlled switching "on" and "off" of adhesion properties. The recovery of the adhesion force amounts to 75 and 80% for photo- and thermal dissociation, respectively. Spatial control of adhesion properties is evidenced by adhesion force mapping experiments of photo-patterned films.

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, 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 side-chain modified anpirtoline derivatives.

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.

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.

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.

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.

Use of combinatorial chemistry to speed drug discovery.

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.

From chloroquine to antineoplastic drugs? the story of antibacterial quinolones.

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.

[Synthesis and antibacterial activity of thiosemicarbazones of 3-acylquinolones]. / Syntéza a antibakteriální aktivita thiosemikarbazonu nekterých 3-acylchinolonu.

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.

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.