The Design of Local Anesthetics

Büchi, J; Perlia, X

doi:10.1016/b978-0-12-060303-9.50012-4

Cited by 15 publications

(12 citation statements)

References 154 publications

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“…(17) was also involved in the synthesis of antitumor and antifolate analogues of methotrexate [185,186], but no biological activity has been reported for it. (18) is a N-alkylated procaine analogue having a 3.5-fold local anesthetic potency compared to the parent compound [187]. Its effect on the glucose transport in human erythrocite [188] and eel electroplax and cobra venom acetylcholinesterase [189] have been investigated, but it is not listed as a drug in Negwer database.…”

Section: -Diethylaminoethyl 4-aminobenzoate (Procaine)mentioning

confidence: 99%

Drug Evolution Concept in Drug Design: 2. Chimera Method

Roman¹,

Popek²,

Lazar³

et al. 2006

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The drug evolution method represents a novel approach towards efficient rational drug design by implementing the drug evolution concept to the creation and development of general chemical libraries with the purpose of allowing the identification of drug candidates with improved odds and lesser costs than the traditional drug design strategies. As another example of successful translation of the biological evolution into chemical evolution, the chimera method comprises the grafting of selected building blocks, identified through a basic search within a drug library, onto the same substitution sites on a rationally chosen scaffold. The method allows the creation of a library containing both drugs and prospective drug candidates without any priorly required knowledge on the pursued disease or molecular target. Two libraries having scaffolds derived from para-aminobenzoic acid and salicylic acid have exemplified the application of the chimera method. The validation of the method has been achieved through the high number of recognized drugs within the library, which exhibit in the same time a wide variety of therapeutic activities and interact with a broad spectrum of molecular targets. The drug-enriched chimera libraries are expected to provide a highly efficient access to novel drug candidates whose unspecified therapeutic effects should be further revealed through high-throughput screening.

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Section: -Diethylaminoethyl 4-aminobenzoate (Procaine)mentioning

confidence: 99%

Drug Evolution Concept in Drug Design: 2. Chimera Method

Roman¹,

Popek²,

Lazar³

et al. 2006

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“…Die Vorstellung von Bfichi u. Perlia (1962), derzufolge EAP als Baustein der Phospholipoide Poren in dem Lipidbestandteil der Zellmembran sehlieBt, dfirfte wohl lediglich ein Teilvorgang beim Proze[~ der Membranabdiehtung sein. Auf den aktiven Vesikeltransport l~l]t sit sieh nieht anwenden.…”

Section: Zur Wirkung Der Mg-und Ca-chelateunclassified

Electronmicroscopic studies on the influence of magnesium and calcium chelates upon the capillary permeability in mouse heart muscle

1972

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Electronmicroscopic Studies on the Influence o/ Magnesium and Calcium Chelates upon the Capillary Perrrleability in Mouse Heart MuscleSummary. Electronmicroscopic studies revealed thc influence of Magnesium and Calcium Chelates on the capillary permeability of mouse heart muscle. Horseradish peroxidase was best suited as tracer substance. After intraperitoneal application of high dosages of Magnesium-aspartate and Ca-Phosphorylthreonine (0.4 ml of a 20(~) solution) a marked inhibition of the capillary permeability could be observed. Smaller dosages (0.4 ml of a 4°Jo solution intraperitoneally administered) of Mgaspartate, Ca-Phosphory]threonine and Ca-EAP which could only be obtained as a 4(y() solution, showed an inhibition of the transcapillary peroxidase transportation, too. These observations are considered to be due to a block in the enzyme system of the membrane ATP-ases caused by high concentrations of Magnesium and Calcium ions. Key words: Capillary permeabilityPeroxidase --Mg-aspartate Ca-EAP. Zusammen/assung. in einer elektronenmikroskopischen Studie wird der EinfluBvon Magnesium-und Calcium-Chelaten auf die Capillarpermeabilit/it im Herzmuskel der Maus experimentell untersucht. Als Markierungssubstanz erwies sich die Meerrettichperoxidase als besonders geeignet. Es zeigt sich, dab nach hohen Dosen Magnesiumaspartat and Ca-Phosphorylthreonin (jeweils 0,4 ml 20°/oige L6sung i.p.) eine deutliche Hemmung der Capillarpermeabilit/~t eintritt. Auch in geringerer Dosierung (jeweils 0,4 ml 4°/oige L6sung i.p.) zeigen Mg-aspartat, Ca-Phosphorylthreonin und auch Ca-EAP, das nur als 4°/oige L6sung erhalten werden konnte, eine Hemmung des transcapill~ren Peroxidastransportes. Die Befunde werden auf eine Blockierung des Enzymsystems der Membran-ATP-asen durch fiberschieBende Magnesium-bzw. Calciumkonzentrationen zuriickgefiihrt.Schliisselw6rter: Capillarpermeabilit~,t --Peroxidase --Mg-aspartat --Ca-EAP.

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“…Introduction of bulky grotp on amino functicn inhibit's rotation of N-glycosidic linkage and ilaces N in the groove of 5 '-OH and heterocyclic base. This is the reason why bulky groups are sought for depurArnation resistivity (31). In the case of N-MPB derivatives of both 2 '-deoxyadenosine as viell as 2'-deoxyguanosine (figure-6) protonation at N7 is inhibited in all probability due tQ two main factors (i) the bulky nature of the group which prevents free rotation of the glycosyl bond and (ii) its hydrophobicity which inhibits approach of H 0+ at N7.…”

Section: Purification Of the Tetramer D(twtc)mentioning

confidence: 99%

Improved synthesis of oligodeoxyribonucleotide using 3-methoxy-4-phenoxybenzoyl group for amino protection

Mishra¹,

Misra²

1986

Nucl Acids Res

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3-Methoxy-4-phenoxybenzoyl group has been used for the protection of exocyclic amino group of nucleosides. In case of 2'-deoxycytidine it has been found to be highly selective under controlled conditions. The N-protected derivatives of 2'-deoxyadenosine and 2 '-deoxyguanosine have been found to be suf ficiently stable towards acids minimising depurination under conditions of synthesis of oligodeoxyribonucleotide on solid support via phosphotriester approach. The high lipophilicity of the group and milder deprotection conditions are additional advantages.

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The Design of Local Anesthetics

Cited by 15 publications

References 154 publications

Drug Evolution Concept in Drug Design: 2. Chimera Method

Drug Evolution Concept in Drug Design: 2. Chimera Method

Electronmicroscopic studies on the influence of magnesium and calcium chelates upon the capillary permeability in mouse heart muscle

Improved synthesis of oligodeoxyribonucleotide using 3-methoxy-4-phenoxybenzoyl group for amino protection

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