摘要:

AbstractA series of 5‐aminomethinimino‐3‐methyl‐4‐isoxazolecarboxylic acid phenylamides4has been prepared by condensation of 5‐amino‐3‐methyl‐4‐isoxazolecarboxylic acid phenylamides1with trichloroacetic aldehyde. Alcoholysis of trichloro derivatives2gave 5‐alkoxymethine derivatives3which, on reaction with an appropriate amine, formed the corresponding compounds4. The compounds obtained were evaluated for their immunological activity. The properties of three compounds, described in this report, permitted inhibition of the immune response in all possible ways: diminishing both types of immune response (4d), humoral immune response (4a), or cellular immune response (4c). Preparation4dis comparable in its effectiveness to CsA, so it may be potentially used as an agent for prolongation of the function of transplanted organs. Two other compounds may potentially be used in cases where only one type the immune response is required for combat

ISSN:0365-6233    

DOI:10.1002/ardp.19973301102

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

Abstract3,5‐Disubstituted tetrahydro‐2H‐1,3,5‐thiadiazine‐2‐thione (THTT) derivatives;4a–gwere prepared and found to be a promising prodrug approach for peptide drugs. The pH profile for their degradation in aqueous buffer solutions was determined using HPLC technique and accounted for, in terms of specific base‐catalyzed reactions. All of the compounds however, showed high acid‐stability. Enzymatic (human serum) hydrolysis of the different derivatives offered an advantageous range oft1/2's, the property that permits controlling onset and duration of

ISSN:0365-6233    

DOI:10.1002/ardp.19973301103

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractPotent arpromidine‐type histamine H2receptor agonists such as BU‐E‐76 (He 90481) were among the first non‐peptides reported to display weak neuropeptide Y (NPY) Y1receptor antagonist activity. In search of new chemical leads for the development of more potent NPY antagonists, a series ofN,N‐disubstituted ω‐guanidino and ω‐aminoalkanoic acid amides were synthesized on the basis of structure‐activity relationships and molecular modeling studies of arpromidine and related imidazolylpropylguanidines. In one group of compounds the imidazole ring was retained whereas in the second group it was replaced with a phenol group representing a putative mimic of Tyr36in NPY. Although the substitution patterns have not yet been optimized, the title compounds are NPY Y1antagonists in human erythroleukemia (HEL) cells (Ca2+assay) achieving pKB values in the range of 6.3–6.6. For representative new substances tested in the isolated guinea pig right atrium histamine H2receptor agonism could not be found. In theN‐(diphenylalkyl)amide series, compounds with a trimethylene chain were more active Y1antagonists than the ethylene homologs. Concerning the spacer in the ω‐amino or ω‐guanidinoalkanoyl portion, the best activity was found in compounds with a four‐ or five‐membered alkyl chain or a 1,4‐cyclohexylene group. Surprisingly, in contrast to the phenol series, in the imidazole series the compounds with a side chain amino group turned out to be considerably more potent than the corresponding strongly basic guanidines. Thus, the structure‐activity relationships appear to be different for the diphenylalkylamide NPY antag

ISSN:0365-6233    

DOI:10.1002/ardp.19973301104

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractA series of 5‐hydroxy and 5‐benzyloxy analogs of the antiarrhythmic and multidrug resistance (MDR) modulating drug propafenone was synthesized and the MDR‐modulating activity of the compounds was evaluated using a daunomycin efflux assay system. The key step of the synthesis is the selective reduction of the double bond in 1 without cleavage of the benzyl group thus leading to the phenol3. Alkylation with epichlorohydrine followed by nucleophilic epoxide ring opening gave the benzylated target compounds5a–d. Subsequent cleavage of the benzyl group gave the 5‐hydroxy analogs6a–d. Structure activity relationship studies showed, that the 5‐hydroxy derivates6a–dfit the logP/log potency correlation line previously established for a series of propafenone analogs. In contrast, all four 5‐benzyloxy analogs5a–dshowed almost identical EC50values, independent

ISSN:0365-6233    

DOI:10.1002/ardp.19973301105

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractFluoride impurities in pharmaceutical grade calcium ascorbate were determined analytically by capillary gas chromatography (GC) and ion‐selective electrode potentiometry (ISE). In the GC method, the amount of fluoride impurities was quantitatively analyzed following the conversion of fluoride to its corresponding trimethylsilane derivative using trimethylchlorsilane. The derivatization procedure was performed under acidic conditions and the generated trimethylfluorsilane was subsequently extracted withn‐hexane prior to GC analysis using isopentane as an internal standard.In the potentiometric method, the fluoride content was determined by relating the potential of the sample solution at different concentrations to a calibration curve. A comparative evaluation between the two methods was validated according to their linearity, precision, and accuracy. The fluoride concentrations found by means of GC and ISE were (0.94 ± 0.04) ppm and (0.85 ± 0.12) ppm, respectively. The student's t‐test (error of the first kind α = 0.1) indicated that there was no significant difference between the results obtained by the two

ISSN:0365-6233    

DOI:10.1002/ardp.19973301106

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractThe synthesis and biological evaluation as potential CCK‐B receptor ligands of a number of 1‐isopentyl‐3‐aryloxycarbamoyl‐5‐aryl‐1,5‐benzodiazepines substituted with halogen atoms on the benzo‐fused ring is here

ISSN:0365-6233    

DOI:10.1002/ardp.19973301107

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractThe synthesis and biological evaluation ofZ‐ andE‐1‐methyl‐2‐(1‐hydroximinoethyl)‐6‐methoxy‐3,4‐dihydro‐naphthalene (Z‐1andE‐1) as nonsteroidal inhibitors of 17α‐hydroxylase‐C17,20‐lyase (P450 17, CYP17) is described.Z‐1andE‐1were separated by column chromatography and identified by1H NMR. The synthesis of the key compound3was accomplished by a new reaction acetylating the 1‐methyl‐6‐methoxy‐3,4‐dihydronaphthalene compound2under Friedel‐Crafts conditions. Compound2was obtained from the 1‐tetralone via Wittig reaction. Using a microsomal fraction of human testicular enzyme,Z

ISSN:0365-6233    

DOI:10.1002/ardp.19973301108

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractAminoalcohols related to the opioid tramadol (1) were synthesised. Their binding capacities to subtypes of the opioid receptor were tested.

ISSN:0365-6233    

DOI:10.1002/ardp.19973301109

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

ISSN:0365-6233    

DOI:10.1002/ardp.19973301101

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY