ISSN:0365-6233    

DOI:10.1002/ardp.19953281102

出版商:WILEY‐VCH Verlag    

年代:1995

数据来源: WILEY

摘要:

AbstractDirect chiral separation of aminoglutethimide (1), an anticancer agent, and its major metabolite — acetylaminoglutethimide (2), on tris(3,5‐dimethylphenyl‐carbamoyl)cellulose working in the reverse‐phase mode with the use of aqueous‐methanolic mobile phases is

ISSN:0365-6233    

DOI:10.1002/ardp.19953281103

出版商:WILEY‐VCH Verlag    

年代:1995

数据来源: WILEY

摘要:

AbstractA group of racemic alkyl 1,4‐dihydro‐2,6‐dimethyl‐4‐(pyridinyl or 2‐trifluoromethylphenyl)‐5‐(1H‐tetrazol‐5‐yl)‐3‐pyridinecarboxylates11–14were prepared using the Hantzsch reaction that involved the condensation of 2‐, 3‐ or 4‐pyridinecarboxaldehyde, or 2‐trifluoromethylbenzaldehyde,8a–dwith isopropyl or methyl 3‐aminocrotonate (9a–b) and 5‐(2‐oxopropyl)‐1H‐tetrazole (10a) or 5‐(2‐oxopropyl)‐1‐methyl‐1H‐tetrazole (10b).In vitrocalcium channel (CC) antagonist and agonist activities were determined using guinea pig ileum longitudinal smooth muscle (GPILSM) and guinea pig left atrium (GPLA) assays, respectively. In the series of compounds11–14, only compounds14aand14bexhibited some weak CC antagonist activity (10−6M range) relative to the reference drug nifedipine (IC50= 1.43 × 10−8M). Compounds11b‐14bhaving a 1‐methyl‐1H‐tetrazol‐5‐yl substituent were inactive CC agonists on GPLA. In contrast, compounds12a‐14ahaving a 1H‐tetrazol‐5‐yl substituent exhibited CC agonist activity on GPLA, but the C‐4 2‐pyridinyl analog11aexhibited a mild negative inotropic effect. The approximately equipotent CC agonist activity (GPLA) exhibited by the C‐4 pyridinyl13aand 4‐(2‐trifluoromethylphenyl)14acompounds compared favorably with that of the reference drug (±)‐Bay K 8644 (EC50= 7.7 × 10−7M) indicating that the 1H‐tetrazol‐5‐yl moiety is a suitable replacement for the nitro group present in Bay K 8644 with respect to cardiac CC agonist activity. These latter com

ISSN:0365-6233    

DOI:10.1002/ardp.19953281104

出版商:WILEY‐VCH Verlag    

年代:1995

数据来源: WILEY

摘要:

AbstractThe propionamides5and6have been synthesized and tested for stimulation of antitumor drug activity.5and6bincrease vincristine cytotoxicity in drug‐sensitive murine tumor cells;5also increases the toxicity in multidrug resistant cells. Dissimilar trends in sensitive and resistant cells have been observed for the stimulating activity of several propionamides of this family and structurally related verapamil with their molar refractivity, suggesting different size requirements for the sensitizers in sensitive and resistant cell

ISSN:0365-6233    

DOI:10.1002/ardp.19953281105

出版商:WILEY‐VCH Verlag    

年代:1995

数据来源: WILEY

摘要:

AbstractIn order to develop a specific TLC‐fluorescence detection, drugs such as Quinethazone (1a), Fenquizone (1b), Diazoxide (7), Bendroflumethiazide (11a), Hydrochlorothiazide (11b) and their derivatives were hydrolysed to provideo‐aminobenzamide2ando‐aminobenzenesulfonamides8, 12, and13. The reaction of these 1,5‐N‐bisnucleophiles with phthalaldehyde (3a) and analogues3b–eresulted in weak up to intensive fluorescent products5, 9, 14, 15, Applying this method to Diazoxide capsules, 5 ng of Diazoxide (7) could be detected by pre‐ and postchromatographic derivatisation with 3‐benzoylpyridine‐2‐carbaldehyde (3e) on TLC plates. The reaction ofo‐aminobenzenesulfonamide8with 3,4‐dimethoxyphthalaldehyde (3b) in CD3OD/DCI provided a monodeuterated compound10b,N,N‐Acetals17,18, and19were obtained from the reaction of furan‐3,4‐dicarbaldehyde (16) witho‐aminobenzenesulfo

ISSN:0365-6233    

DOI:10.1002/ardp.19953281106

出版商:WILEY‐VCH Verlag    

年代:1995

数据来源: WILEY

摘要:

AbstractTwenty pyrazol‐4‐one 1,2‐dioxides and eleven 4‐hydroxyiminopyrazole 1,2‐dioxides were prepared and tested for their antiplatelet activity (Born test with collagen). Six compounds which all belong to the pyrazolone series inhibited the platelet aggregation half‐maximally in submicromolar concentrations (200–800 nmol/L). In positions 3 and 5, these compounds bear at least one (15, 16, 24, 31) or two substituents (7, 29) with electron‐withdrawing groups. Among them are aromatic moieties like 4‐hydroxysulfonylphenyl (7), 4‐cyanophenyl (16), 4‐chlorophenyl (15), phenyl (24) or carboxylic acid esters (29). Two compounds were investigated in anin vivothrombosis model (1, 31). 2h after oral administration of 60 mg/kg1to rats in arterioles 69 % inhibition of thrombus formation (venul

ISSN:0365-6233    

DOI:10.1002/ardp.19953281107

出版商:WILEY‐VCH Verlag    

年代:1995

数据来源: WILEY

摘要:

AbstractCycloalkanecarboxamido)ethyl‐1‐(2‐methoxyphenyl)piperazin es8a–c,8e, and8hwere obtained by acylation of 4‐(2‐aminoethyl)‐1‐(2‐methoxyphenyl)piperazine, and their 5‐HT1A, 5‐HT1A, 5‐HT2Aand α receptor affinities were determined. It was found that the terminal cycloalkane moiety strongly stabilizes both the 5‐HT1Aand 5‐HT2Areceptor‐ligand complexes. It was demonstrated that the most active 5‐HT1Aligands8eand8h(Ki= 2.1 and 0.21 nM, respectively) behaved as potent agonists of these receptors,i.e.both derivatives mimicked 8‐OH‐DPAT in the lower lip retraction (LLR) model and the effect was susceptible to blockade by reasonable doses of the selective 5‐

ISSN:0365-6233    

DOI:10.1002/ardp.19953281108

出版商:WILEY‐VCH Verlag    

年代:1995

数据来源: WILEY

摘要:

AbstractA radioimmunoassay has been developed for the quantitation of triamcinolone‐acetonide (TAAc) at the picogram level. For use of TAAc as an antigenic epitope, first the drug was hemisuccinoylated at C‐21 as confirmed by13C‐NMR‐ and mass spectroscopy after derivatization. This hapten was conjugated to the carrier‐protein bovine serum albumin (BSA) or keyhole limpet hemocyanin (KLH) by different amide‐bond generating methods (imidazolide‐, carbodiimide‐, carbodiimide/sulfo‐N‐hydroxysuccinimde‐, mixed anhydride‐method) yielding antigens of quite different conjugation number, solubility and usefulness. The mixed anhydride‐method yielded most useful soluble conjugates bearing 0.3–31.5 mol TAAc per mol carrier‐protein. Coupling by the carbodiimide‐method yielded insoluble conjugates, inappropriate for antigen synthesis in hapten immunoassays because of formation of coupling agent modified residues and crosslinking of the carrier‐protein. Specificity of the antisera obtained by immunization with TAAc‐BSA and TAAc‐KLH was assessed by isolation of the soluble hapten‐antibody complex and a RIA protocol was developed providing a detection lim

ISSN:0365-6233    

DOI:10.1002/ardp.19953281109

出版商:WILEY‐VCH Verlag    

年代:1995

数据来源: WILEY

ISSN:0365-6233    

DOI:10.1002/ardp.19953281110

出版商:WILEY‐VCH Verlag    

年代:1995

数据来源: WILEY

ISSN:0365-6233    

DOI:10.1002/ardp.19953281101

出版商:WILEY‐VCH Verlag    

年代:1995

数据来源: WILEY