ISSN:0365-6233    

DOI:10.1002/ardp.19973300102

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractThein vitroandin vivoeffect of guaiazulene, a natural azulene derivative, on rat hepatic cytochrome P450 (CYP) is investigated. Furthermore, paracetamol hepatotoxicity is induced in rats and the activity of specific cytochrome P450 forms, involved in the metabolic activation of paracetamol to the toxic metaboliteN‐acetyl‐p‐benzoquinone imine (NAPQI) is examined, after the administration of guaiazulene, using diagnostic cytochrome P450 substrates. It is found that guaiazulene inhibited considerably CYP1A2 and CYP2B1 and had a weak effect on CYP1A1 in rat hepatic microsomal fractions. Guaiazulene administered to rats did not produce any macroscopic toxic effect and caused no change of liver weight, microsomal protein and total cytochrome P450 content. Guaiazulene inhibited CYP1A2 activity in rats with or without paracetamol intoxication. Considering that CYP1A2 participates in the formation of NAPQI, as well as in the metabolic activation of several toxic and carcinogenic compounds, these results, in combination with the antioxidant activity of guaiazulene that we have found in previous investigations, indicate potential useful applications of guaiaz

ISSN:0365-6233    

DOI:10.1002/ardp.19973300103

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

Abstract1,4‐Epidioxy‐bisabola‐2,12‐diene (3) and aromatic hydroperoxides (4, 5) were prepared by photoxidation of γ‐curcumene (1). Reduction and esterification of6and7afforded compounds9to10. All compounds were testedin vitrofor antimalarial activity. The activity could not be increased significantly, compared with3. The most active compounds,3and9, did not showin vivoantimalarial activi

ISSN:0365-6233    

DOI:10.1002/ardp.19973300104

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractCompound10b, 6‐acetamido‐6,8‐dideoxy‐D‐erythro‐β‐D‐galacto‐octopyranosyl‐1‐oxyacetic acid sodium salt, was synthesised by hydrazinolysis of Lincomycin, acetylation of methylthiolincosaminide (MTL)9a, and by subsequent glycosylation of acetate9bwith methyl glycolate under mild conditions (NIS/TfOH). The methyl ester10awas hydrolysed by treatment with Amberlite Ira‐4OO (OH−) resin and aqueous sodium hydroxide, followed by neutralisation with Dowex‐50 W × 8 (H+) resin and lyophilisation to give10b. This carboxylate may represent the first derivative in a novel series of sialidase inhibitors utilising carbohydrate natural products. The phosphonate11c, prepared under the same experimental conditions with dibenzyl(hydroxy‐methyl) phosphonate as acceptor, also displays an inhibitory activity towardsClostridium perfringenssialidase

ISSN:0365-6233    

DOI:10.1002/ardp.19973300105

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractThe stereoisomers of amidinomycin7and their intermediates1–6, which are produced from homochiral 3‐oxocyclopentanecarboxylic acids by asymmetric synthesis, are tested for their antimicrobial effects by agar diffusion test and by Bouillon serial dilution assay. Their antibiotic activities againstBacillus subtilis, Staphylococcus aureus, andMicrococcus luteus, respectively, are reported. Structure‐activity relationships depend on the type and combination of functional groups, on only the relative stereochemistry as well as on the grade of lipophilia of the tested comp

ISSN:0365-6233    

DOI:10.1002/ardp.19973300106

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractWith an aim of creating new, high affinity dopaminergic ligands, six different 3‐ and 4‐substituted 1‐{2‐[5‐(1H‐benzimidazole‐2‐thione)]ethyl}piperidines and nine related heterocyclic congeners were synthesized and evaluated forin vitrobinding affinity at D1and D2dopamine receptors. Synaptosomal membranes prepared from fresh bovine caudate nuclei were used as a source of the dopamine receptors. Only 4‐[bis‐(4‐fluorophenyl)methylene]‐piperidines, compounds9e, 10d, and11d, expressed moderate affinity for the D1receptors, while all other compounds were inactive competitors of [3H]SCH 23390. Compounds9c, 9d, 10c, 11a, and11cwere inactive in the D2receptor binding assay, as well. Derivatives of 4‐phenylpiperidine (9–11b) and 3‐phenyl‐piperidine (10a) expressed a moderate to low affinity for the D2receptors. However, racemic (±)‐1‐{2‐[5‐(1H‐benzimidazole‐2‐thione)]ethyl}‐3‐phenylpiperidine9aand its enantiomer (+)‐9abehaved as selective, high affinity D2receptor ligands, the latter

ISSN:0365-6233    

DOI:10.1002/ardp.19973300107

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractStarting from 3,6‐dichloro‐N‐(2−chloro‐5‐nitrophenyl)‐pyrid‐azine‐4‐carboxamide (7) a series of 6,11‐dialkylated pyridazino‐[3,4‐b][1,5]benzodiazepin‐5‐ones with a 3−chloro‐8‐nitro, 8‐amino, 8‐acetylamino, or 8−chloro substitution pattern was preparedvia N‐alkyl‐3‐alkylamino‐6−chloro‐N‐(2−chloro‐5‐nitro‐phenyl)‐pyridazine‐4‐carboxamides. The new compounds were screened as non‐nucleoside reverse transcriptase inhibitors. The influence of the s

ISSN:0365-6233    

DOI:10.1002/ardp.19973300108

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractA group of 3‐alkyl 5‐isopropyl 4‐aryl‐1,4‐dihydro‐2,6‐dimethyl‐3,5‐pyridinedicarboxylates10–20containing an amine, quaternary ammonium, aryl(heteroaryl)alkenyl, 4 ‐ (4‐fluorophenyl)‐piperazin‐1‐yl or methoxy moiety in the C‐3 alkyl ester R‐substituent in combination with a C‐4 phenyl ring bearing a 2,3‐Cl2, 3‐NO2, 3‐NMe2, 4‐NMe2or 3,4,5‐(OMe)3X‐substituent were prepared using the Hantzsch 1,4‐dihydropyridine reaction.In vitrocalcium channel antagonist activity (CCA) was determined using a guinea pig ileum longitudinal smooth muscle assay. In the C‐4 3‐nitrophenyl series of compounds, the C‐3 ester R‐substituent was a determinant of CCA activity where the relative potency order was −CH2CH2CH=C‐(2‐methylphenyl)2± −CH2CH2NMe2.HCl>−CH2CH2CH=C‐(3‐methyl‐2‐thienyl)2>−CH2CH2+NMe3I−. The position and nature of the C‐4 phenyl X‐substituent, were also determinants of CCA activity where the relative activity order was 3‐NMe2>4‐NMe2>3,4,5‐(OMe)3. Anticonvulsant activities were determined in mice using the subcutaneous metrazol (scMet) and maximal electroshock (MES) screens. The compounds investigated were generally not effective for protecting againist scMet induced seizures, except for10{X = 2,3‐Cl2, R = 2‐[4‐(4‐fluorophenyl)piperazin‐1‐yl]ethyl} and14a(X = 3‐NMe2.HCl, R = CH2CH2OMe), which exhibited modest activity. Compound11a(X = 3‐NO2, R = −CH2CH2NMe2.HCl) was the most effective agent in the MES screen. All of the compounds investigated, except for11b(X = 3‐NO2, R = −CH2CH2+NMe3I−,Kp = 0.15), are lipophilic withn‐octanol/aqueous phosphate buffer (pH = 7.4) partition coefficients (Kp) in the 121–424 range relative to the reference drug nimodipine (Kp = 187). The structure‐activity relation

ISSN:0365-6233    

DOI:10.1002/ardp.19973300109

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

ISSN:0365-6233    

DOI:10.1002/ardp.19973300101

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY