The Relationship between Structure and Anticonvulsant Activity in a Series of Benzenesulfonamides

Hh, Keasling; El, Schumann; Veldkamp, W.

doi:10.1021/jm00328a038

Cited by 11 publications

(6 citation statements)

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“…In the benzene-sulphonamide derivatives 47 (Table XIII) a bilinear approach, correlated the biological response with the overall lipophilicity, was the best correlation as in the cases of many other CNS drugs 14 (as protection against maximal electroshock-induced seizures). 50 values, the greatest deviation being noted for compounds 1 and 10 whose Clog P values were lowest.…”

Section: B In Vivo Qsar Of Anticonvulsantsmentioning

confidence: 99%

Review, reevaluation, and new results in quantitative structure-activity studies of anticonvulsants

Hadjipavlou‐Litina

1998

Med. Res. Rev.

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Section: B In Vivo Qsar Of Anticonvulsantsmentioning

confidence: 99%

Review, reevaluation, and new results in quantitative structure-activity studies of anticonvulsants

Hadjipavlou‐Litina

1998

Med. Res. Rev.

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“…A careful survey of the literature identified several factors that limit the scope of classical sulfonylation reactions with NH 2 OH [ 31 , 58 ]. In fact, the sulfonylation of weakly nucleophilic amines, such as hydroxylamine, is difficult and sulfohydroxamic acids are often obtained in low yields after several elaborate and tedious purification steps [ 60 , 61 ]. On the other hand, the use of activated sulfohydroxamic acids with better leaving groups than chlorine does not improve the yield due to the high reactivity of sulfonyl chlorides.…”

Section: Resultsmentioning

confidence: 99%

“…A 180 μm diameter carbon-composite disk electrode (area: 2.5 × 10 −4 cm 2 ) was then fabricated by mixing 840 mg of graphite with 500 mg of Araldite-M and 200 mg of hardener and filling the silica capillary tubing with the mixture. After 24 h at 40 °C, the sensor surface was polished using a high speed drill (Dremel ® 300, Dremel Europe, Breda, the Nederlands) equipped with an aluminum oxide grinding wheel [ 60 ]. The surface of the fabricated sensors was then polished with alumina.…”

Section: Methodsmentioning

confidence: 99%

Synthesis of Nitric Oxide Donors Derived from Piloty’s Acid and Study of Their Effects on Dopamine Secretion from PC12 Cells

et al. 2017

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This study investigated the mechanisms and kinetics of nitric oxide (NO) generation by derivatives of Piloty’s acid (NO-donors) under physiological conditions. In order to qualitatively and quantitatively measure NO release, electron paramagnetic resonance (EPR) was carried out with NO spin trapping. In addition, voltammetric techniques, including cyclic voltammetry and constant potential amperometry, were used to confirm NO release from Piloty’s acid and its derivatives. The resulting data showed that Piloty’s acid derivatives are able to release NO under physiological conditions. In particular, electron-withdrawing substituents favoured NO generation, while electron-donor groups reduced NO generation. In vitro microdialysis, performed on PC12 cell cultures, was used to evaluate the dynamical secretion of dopamine induced by the Piloty’s acid derivatives. Although all the studied molecules were able to induce DA secretion from PC12, only those with a slow release of NO have not determined an autoxidation of DA itself. These results confirm that the time-course of NO-donors decomposition and the amount of NO released play a key role in dopamine secretion and auto-oxidation. This information could drive the synthesis or the selection of compounds to use as potential drugs for the therapy of Parkinson’s disease (PD).

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“…To synthesize the precursor, 1-Boc-piperazine 4 was reacted with 4-bromobenzenesulfonyl chloride 5 , using Keasling’s procedure [18], to generate 6 . Attempts to convert bromide 6 to the corresponding boronic acid 7 using the procedure of Berg et al proved problematic in our hands [17], and so a modified procedure based upon Berg and Hellberg’s use of boron tri-isopropoxide [19], and subsequent hydrolysis, was employed to obtain 7 .…”

Section: Resultsmentioning

confidence: 99%

Synthesis and evaluation of [11C]PyrATP-1, a novel radiotracer for PET imaging of glycogen synthase kinase-3β (GSK-3β)

Cole

Shao

Sherman

et al. 2014

Nuclear Medicine and Biology

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Introduction The dysfunction of glycogen synthase kinase-3β(GSK-3β) has been implicated in a number of diseases, including Alzheimer’s disease. The ability to non-invasively quantify GSK-3βactivity in vivo is therefore of critical importance, and this work is focused upon development of inhibitors of GSK-3βradiolabeled with carbon-11 to examine quantification of the enzyme using positron emission tomography (PET) imaging. Methods [11C]PyrATP-1 was prepared from the corresponding desmethyl-piperazine precursor in an automated synthesis module. In vivo rodent and primate imaging studies were conducted on a Concorde MicroPET P4 scanner to evaluate imaging properties, and in vitro autoradiography studies with rat brain samples were carried out to examine specific binding. Results 2035 ± 518 MBq (55 ± 14 mCi) of [11C]PyrATP-1 were obtained (1–2% noncorrected radiochemical yield at end-of-synthesis based upon [11C]CO2) with high chemical (>95%) and radiochemical (>99%) purities, and good specific activities (143 ± 52 GBq/µmol (3874 ± 1424 Ci/mmol)), n = 5. In vivo microPET imaging studies revealed poor brain uptake in rodents and non-human primates. Pretreatment of rodents with cyclosporin A resulted in moderately increased brain uptake suggesting Pgp transporter involvement. Autoradiography demonstrated high levels of specific binding in areas of the rodent brain known to be rich in GSK-3β. Conclusion [11C]PyrATP-1 is readily synthesized using standard carbon-11 radiochemistry. However, the poor brain uptake in rodents and non-human primates indicates that the radiotracer is not suitable for the purposes of quantifying GSK-3βin neurological and psychiatric disorders.

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The Relationship between Structure and Anticonvulsant Activity in a Series of Benzenesulfonamides

Cited by 11 publications

References 0 publications

Review, reevaluation, and new results in quantitative structure-activity studies of anticonvulsants

Review, reevaluation, and new results in quantitative structure-activity studies of anticonvulsants

Synthesis of Nitric Oxide Donors Derived from Piloty’s Acid and Study of Their Effects on Dopamine Secretion from PC12 Cells

Synthesis and evaluation of [11C]PyrATP-1, a novel radiotracer for PET imaging of glycogen synthase kinase-3β (GSK-3β)

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