摘要:

AbstractThe stability of an aqueous solution of suramin has been determined. The only degradation product detectable by HPLC was the amine precursor2.The decomposition kinetics of suramin at different temperatures are shown. Because of first order kinetics the Arrhenius equation could be used to evaluate the decomposition data. A good correlation was obtained between the reaction constants and the temperature (r= 0.9898). After 42 days at 37 °C, 2% of suramin are hydrolysed. Possible implications of our results for the search for suramin metabolites in patients are discussed

ISSN:0365-6233    

DOI:10.1002/ardp.19963290502

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractA series of new sulfamoylthiophene and sulfamoylpyrazole carboxylic acid derivatives was synthesized. Some of these compounds show interesting analgesic properties and significant nonsteroidal anti‐inflammatory activities in several models of inflammatio

ISSN:0365-6233    

DOI:10.1002/ardp.19963290503

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractAziridine‐2,3‐dicarboxylates andN‐acylated derivatives have been evaluated as potential irreversible inhibitors of the cysteine proteinase papain. Dependence of inhibition activity on stereo‐chemistry of the aziridine moiety has been analyzed. Whereas unsubstituted (R,R)‐ and (S,S)‐ diethyl aziridine‐2,3‐dicarboxylates (5) and (2) show no significant difference in inactivation the derivative acylated with BOC‐(S)‐Phe (BOC‐(S)‐Phe‐(S,S)‐Azi) (10) shows a 6 fold higher activity than the diastereomer BOC‐(S)‐Phe‐(R,R)‐Azi (11). Analogs acylated with Z‐ or BOC‐(S)‐Ala (9, 8) have lower second‐order rate constants, indicating binding of the amino acid moiety of the

ISSN:0365-6233    

DOI:10.1002/ardp.19963290504

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractThe conjugation of indomethacin with chitosan partially substituted with the hydrophilic residues triethylene glycol glutarate and triethylene glycol choline ether glutarate is described. Mucoadhesive conjugates were obtained showing gelling properties both in acid and basic environment. Among the substituents, triethylene glycol choline ether glutarate better enhances the gelling properties of the macromolecules. In all cases the kinetics of drug release from the macromolecules approached zero order.

ISSN:0365-6233    

DOI:10.1002/ardp.19963290505

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractIn search of potential drugs for the treatment of estrogen‐ and androgen‐dependent cancer as well as the prophylaxis of metastases, tetralones, tetralins, and dihydronaphthalenes bearing a OCH3substituent at the benzene nucleus and an imidazol‐4‐yl, imidazol‐1‐yl, or 1,2,4‐triazol‐1‐yl substituent in 2‐position were synthesized with and without C1‐spacer between the rings (compounds2 – 26). The compounds were testedin vitrofor inhibition of the three target enzymes P450 arom (human placental microsomes), P450 17 (rat testicular microsomes), and P450 TxA2(citrated human whole blood). To examine selectivity, some compounds were further testedin vitrofor inhibition of P450 18 (bovine adrenal mitochondria), P450 see (bovine adrenal mitochondria) and corticoid formation (aldosterone, corticosterone; ACTH stimulated rat adrenal tissue).In vivo, selected compounds were examined in Sprague Dawley rats regarding P450 TxA2inhibition, reduction of plasma testosterone concentration, antiuterotrophic activity (inhibition of the uterotrophic activity of androstenedione), reduction of plasma estradiol concentration (pregnant mares' serum gonadotropin‐primed rats), and mammary tumor inhibiting activity (dimethylbenzanthracene‐induced tumor; pre‐ and postmenopausal model).In the series of imidazol‐4‐yl compounds, which represent a novelty in the field of azole inhibitors of steroidogenic P450 enzymes, strong inhibitors of P450 arom and/or P450 17 were found: 7‐OCH3‐2‐(imidazol‐4‐ylmethylene)‐1‐tetralone (4) and 7‐OCH3‐2‐(imidazol‐4‐ylmethyl)‐tetralin (12) are among the most potent inhibitors of P450 aromin vitroknown so far. Compound4is a selective inhibitor, whereas12shows in addition strong inhibition of P450 17. In contrast to12, the 6‐OCH3derivative (compound11) is a selective inhibitor of P450 17, being 50 times more potent than ketoconazole. Some imidazol‐1‐yl compounds show a marked inhibition of P450 TxA2: 2‐(imidazol‐1‐ylmethyl)‐1‐tetralone (13) is a selective inhibitor of P450 TxA2, whereas 7‐OCH3‐2‐(imidazol‐1‐ylmethyl)‐tetralin (17) as well as 2‐(imidazol‐1‐ylmethyl)‐tetralin (16) and 7‐OCH3‐2‐imidazol‐1‐yl‐3,4‐dihydronaphthalene (25) additionally show strong inhibition of P450 arom and P450 17. Regarding the other steroidogenic P450 enzymes as well as corticosterone formation, the compounds show only little inhibitory activity. Aldosterone formation, however, is inhibited at low concentrations. Nevertheless,4and12are more selective, i.e. inhibit aldosterone synthesis less than t

ISSN:0365-6233    

DOI:10.1002/ardp.19963290506

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractThe synthesis of 2‐substituted anthracenonyl acetic acid (2‐AA) derivatives is described. The key step is the Marschalk reaction of 1‐hydroxy‐8‐methoxy‐anthracenedione with glycolic acid. After protection of the resulting 2‐anthracenonyl acetic acid derivative, the 2‐monoalkylated derivatives are selectively obtained by direct alkylation. The methodology proves quite general and allows for the introduction of various substituents onto the 2‐position of the carboxylic side chain. Reduction of the anthracenediones proceeds with concomitant protecting group removal and provides final 2‐AA products in good yields. The results of initial biological studies demonstrate enhanced 5‐lipoxygenase inhibition

ISSN:0365-6233    

DOI:10.1002/ardp.19963290507

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractThe reaction of 2‐benzoylbenzaldehyde (1) with primary diamine2, generated by rearrangement and hydrolysis of Oxazepam, in CD3OD leads to intensely fluorescing deuterated isoindoloquinazolines3and4.Reduction of ethyl 2‐benzoylbenzoate (5) with LiAlD4followed by oxidation with MnO2yields 2‐benzoylbenz[D]aldehyde (7). The condensation of7with diamine2leads to isoindoloquinazoline12, free of deuterium. On the basis of these experiments a plausible pathway is proposed for the “fluorescence re

ISSN:0365-6233    

DOI:10.1002/ardp.19963290508

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

ISSN:0365-6233    

DOI:10.1002/ardp.19963290501

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY