摘要:

AbstractDie Sulfhydrolyse von 2,5‐Bis(methylthio)‐3,6‐dihydropyrazin (5) liefert 2,5‐Piperazindithion (8) und nicht Glycindithiomethylester (6). Die durch Alkylieren von5erhaltenen Iminiumsalze9werden von H2S in die 1,4‐Dialkyl‐2,5‐piperazindithione10übergeführt.5bildet mit Chlorameisensäuremethylester 2,5‐Bis(methylthio)‐pyrazin (11) und mit Acetanhydrid das 1,4‐Dihydropyrazin12. Die Sulfhydrolyse der 6‐ und 7‐Ring‐Iminiumsalze1

ISSN:0365-6233    

DOI:10.1002/ardp.19933260202

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY

摘要:

AbstractAlkaloids1‐4fromCynanchum vincetoxicum(asclepiadaceae) (Scheme 1) do not have affinity to the oestrogen receptor but they inhibit the growth of the hormone‐independent mammary carcinoma cells MDA‐MB‐231 (Fig. 1) and bind to nucleosides and nucleotides (Table 1). Intercalation was not o

ISSN:0365-6233    

DOI:10.1002/ardp.19933260203

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY

摘要:

AbstractN‐Alkyl (2 ‐ 11) andN‐acyl (18 ‐ 30) derivatives of 2,3‐dihydro‐2‐phenyl‐1,4‐benzoxazepin‐5(4H)‐one (1) have been synthesized. 4‐Alkyl‐2,3‐dihydro‐2‐phenyl‐1,4‐benzoxazepin‐5(4H)‐thiones12 ‐ 15arose from compounds2, 3, 5, and6withLawesson'sreagent. Bis‐[2,3‐dihydro‐2‐phenyl‐1,4‐benzoxazepin‐5(4H)

ISSN:0365-6233    

DOI:10.1002/ardp.19933260204

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY

摘要:

AbstractDie Racemate und die Enantiomere der Hexahydropyrimidin‐2‐one2a‐2e, die man auch als zyklische Harnstoffe auffassen kann, werden aus den Racematen und den Enantiomeren der Barbiturate1a‐1edurch Reduktion mit LiAlH4/AlCl3gewonnen. Die in Ethanol rechtsdrehenden Enantiomere von2a‐2dbesitzen S‐Konfiguration. ‐ Die Prüfung von Ratten ergab. daß alle synthetisierten zyklischen Harnstoffe sedativ‐hypnotische Wirksamkeit besitzen. Die Enantiomere wiesen zum Teil beachtliche enantioselektive Wirkung

ISSN:0365-6233    

DOI:10.1002/ardp.19933260205

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY

摘要:

AbstractA series of hydantoin prostaglandin analogues, in which the hexamethylene moiety of the acid side chain was replaced by other spacing groups possessing either ether, sulphide and/or olefin functionality, were prepared and evaluated for platelet aggregation inhibiting activity. The 4‐thia analogue13proved to be the most potent inhibitor (ca. 22x PGE1) and the 3‐thia‐ and 3‐oxa‐analogues,6and10respectively, are approximately equipotent with BW245C (ca. 14x PGE1). Z‐olefinic analogues (e.g.11) were usually more potent than theirE‐isomers (e.g.12). Structure‐activity relationships are disc

ISSN:0365-6233    

DOI:10.1002/ardp.19933260206

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY

摘要:

AbstractAs an example coadsorption data for a series of 4‐hydroxybenzoic acid alkyl esters with POE‐9.4‐nonylphenol were presented. The mediated adsorption is shown to be increased by increasing the alkyl residue of the 4‐hydroxybenzoic acid ester. The amount of drug which was coadsorbed was found to be up to 75% of the total drug content when propyl 4‐hydroxybenzoate was used as a model compound. For the prediction of such interaction phenomena the use of a liquid chromatographic technique was proposed. This methodology is based on the so called pseudo phase liquid chromatography (PLC). The results obtained by the „dynamic”︁ PLC method were in good agreement with the corresponding data from „static”︁ equilibrium adsorption experiments. On this basis a prediction was made for several other drug molecules. In addition the use of an equilibrium expression approach according toArunyanartandCline‐Lovepermitted calculation of micelle‐solute equilibrium constants from capacity

ISSN:0365-6233    

DOI:10.1002/ardp.19933260207

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY

摘要:

AbstractDie Addition des mit LDA deprotonierten Glycinesters6an das Homophthalaldehydmonoacetal 5 liefert den β‐Hydroxyester7, der sich nach Reduktion zu den racemischen 2,6‐Epoxy‐3‐benzoxocin‐5‐aminen (+/−)‐12und (+/−)‐13cyclisieren läß. Die Schlüsselverbindungen für die Gewinnung von12und13in enantiomerenreiner Form sind die Hydroxyacetale (R,S,R)‐22und (R,S,S)‐23: (R,S,R)‐22läßt sich stereoselektiv durch Addition der Aryllithiumverbindung21bbzw. der Aryltitanverbindung21can das neue Serinal‐Äquivalent (R,S)‐20gewinnen; die Reduktion des Ketons (R,S)‐24mit LiAlH4bei −78°C führt überwiegend (>95%) zu dem diastereomeren Hydroxyacetal (R,S,S)‐23. Mit Säure werden (R,S,R)‐22und (R,S,S)‐23in die tricyclischen Urethane (S,S,R)‐25und (R,S,S)‐30überführt, die sich zu den Dimethylaminen (S,S,R)‐12und (R,S,S)‐13reduzieren und methylieren lassen (ee>97%). Analog werden die enantiomeren Amine (R,R,S)‐12und (S,R,R)‐13ausgehend von (R)‐Serin dargestellt. Die relative Konfiguration von (R,S,R)‐22wird mit Hilfe von Molecular Dynamics Rechnungen (Sybyl 5.4) in Kombination mit NOE‐Messungen bewiesen.‐ Nach Applikation beider Enantiomere von12,13,27und32lassen sich bei Mäusen typische Symptome für eine zentrale Dämpfung beobachten. Im Essigsäure Writhing‐Test sind (S,S,R)‐12, (S,R,R)‐13, (R,S,S)‐13, (S,S,R)‐27, (R,R,S)‐27und (R,S,S)‐32sta

ISSN:0365-6233    

DOI:10.1002/ardp.19933260208

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY

ISSN:0365-6233    

DOI:10.1002/ardp.19933260209

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY

摘要:

AbstractThe relationships between some physiological processes and central nervous system or peripheral activity of serotonin (5‐HT; A) has resulted in extensive studies of the chemistry and biological properties of many serotoninergic (agonists or antagonists) compounds1)and the existence of multiple serotoninergic receptors subtypes is supported by pharmacological evidence2). So, central 5‐HT binding sites can be classified into 5‐HT1(1A, 1B, 1C, 1D), 5‐HT2, 5‐HT3and 5‐HT4subtypes3,4)There is some basis for considering that central serotoninergic agonists might be antihypertensives actingvia5‐HT1Areceptors5,6,7)Indorenate (B), a synthetic indole. closely related to serotonin, has antihypertensive properties resulting from agonist activity at central serotoninergic receptors with a relatively high affinity for 5‐HT1Asites8).A possible approach in the design of new serotoninergic ligands and more generally new drug candidates may consist in the application of the bioisosteric theory. So, the NH group is a classical bioisostere of the vinyl increment and the naphthalene nacleus could be considered as a bioisostere of the indole ring. Few examples of the naphthalene‐indole bioisosterism have emerged in the lit.9,10,11)Here we describe the synthesis of the naphthalenic bioisostere

ISSN:0365-6233    

DOI:10.1002/ardp.19933260210

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY

ISSN:0365-6233    

DOI:10.1002/ardp.19933260212

出版商:WILEY‐VCH Verlag    

年代:1993

数据来源: WILEY