摘要:

AbstractA series of potent HIV‐protease inhibitors has been prepared. Several of the newly synthesized compounds showed high plasma levels after oral administration to animals. Based on the overall biological profile, CGP 61755 was chosen for further preclinical evaluation. For this compound, a 10 step synthesis potentially suitable for large scale production was develope

ISSN:0365-6233    

DOI:10.1002/ardp.19963290602

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractDecyldimethylamine reacts readily with chloromethylalkyl ethers or sulfides, chloromethylbezyl ethers or sulfides and chloromethylcycloalkyl ethers to give quaternary ammonium chlorides in very good yields. All the chlorides studied showed antimicrobial activity. The relationship between the chemical structure and antimicrobial activity was analyzed by rough sets.

ISSN:0365-6233    

DOI:10.1002/ardp.19963290603

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractA series of new 3‐(ω‐aminoalkyl)‐5,5‐disubstituted hydantoins, containing 1‐phenylpiperazine, 1‐(o‐methoxyphenyl)piperazine or 1,2,3,4‐tetrahydroisoquinoline fragments, were synthesized by standard alkylation procedures and their 5‐HT1Aand 5‐HT2Areceptor affinities were determined. It has been shown that the investigated derivatives are recognized by 5‐HT1Aand 5‐HT2Areceptors due to the presence of a 1‐arylpiperazine fragment; however, the terminal hydantoin moiety plays an important role in stabilization of the receptor‐ligand complex. It has also been found that the two 1‐phenylpiperazine derivatives32and36are new, selective 5‐HT2Areceptor ligands (Ki= 34 and 37 nM, respectively), whereas the derivative of 1‐(o‐methoxyphenyl)piperazine (38) is a new, highly potent 5‐HT1Areceptor ligand (Ki= 0.51 nM) with a moderate aff

ISSN:0365-6233    

DOI:10.1002/ardp.19963290604

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractThe natural amidinomycin ((1R, 3S)‐14) and its three stereoisomers are synthesized from homochiral 3‐oxocyclopentanecarboxylic acids (1a) by asymmetric methods, which are based on an asymmetric reductive amination to produce methylcis‐N‐(1‐phenylethyl)‐3‐aminocyclo‐pentanecarboxylates (3b) via optically active methylN‐(1‐phenylethyl)‐3‐iminocyclopentane‐carboxylates (2b) for thecis‐isomers of14.Optically puretrans‐3‐aminocyclopentane‐carboxylic acids (4a) are obtained from the homochiral keto acids1avia asymmetric reductive amination of 3‐hydroxy‐iminocyclopentanecarboxylic acids (

ISSN:0365-6233    

DOI:10.1002/ardp.19963290605

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractThe delay of onset of irritation phenomena at the chorioallantoic membrane of incubated hen's eggs, a parameter for anti‐inflammatory activity, was determined for the pharmaceutical substances diclofenac, flufenamic acid, ibuprofen, indomethacin, ketoprofen, piroxicam, phenylbutazone, salicylic acid, and sodium salicylate. Alongside questions relating to the dose‐effect ratio, metabolisation, recovery, and diffusion of the substances to their site of action were investigated. The reproducibility of the procedure and its selectivity with regard to substances with a different mechanism of action is proven. The method allows classification of the substances according to their anti‐inflammatory potency. However, correlation with the results of enzyme inhibition orin vivoresults is only possible to a limited e

ISSN:0365-6233    

DOI:10.1002/ardp.19963290606

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractSeveral heterocyclic bicyclo[3.3.1]nonan‐9‐ones were found to have a high affinity to k opioid receptors. 3,7‐Diazabicyclononanones with 2,4‐dipyridyl side chains were the most potent agonists whereas the corresponding 3‐oxa‐7‐azabicyclo[3.3.1]nonan‐9‐one and compounds with phenyl substituents in 2 and 4 position are almost inactive. The purpose of this study was to unravel the active conformation of the bicyclononanones using well‐known k‐selective agonists such as ketocyclacocine, arylacetamides, several isoquinolines, CI‐977, and four stereoisomers of EMD‐61753 for comparison. In order to determine the geometry of the diazabicycles in solution pH‐dependent NMR measurements of the bicycles were recorded and the results were related to the geometries of the aforementioned k agonists obtained from semiempirical PM3 calculations. A chair‐boat conformation and a protonation at the N7nitrogen atom of the diazabicyclononanones were found to be the pharmacophoric conformation. Comparison of the spatial arrangements, electrostatic, hydrophobic, and hydrogen bonding potentials of all k‐selective agonists led to a model of structure‐activity relationships of ligands of the k‐receptor. The arrangement of the pharmacophoric elements is characterized by an almost parallel orientation of a carbonyl and a protonated NH function in conjunction with at least one aromatic ring. Ketocyclazocine is only able to adopt this parallel orientation when the nitrogen is inverted relative to the X‐ray structure. Furthermore, two binding sites for the aromatic rings are discussed. The pharmacological results of all considered bicyclononanone derivatives as well as of the four enantiomers of EMD‐61753 can be understood

ISSN:0365-6233    

DOI:10.1002/ardp.19963290607

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

ISSN:0365-6233    

DOI:10.1002/ardp.19963290608

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

ISSN:0365-6233    

DOI:10.1002/ardp.19963290601

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY