摘要:

AbstractSyntheses of New Bridged Heterocycles by 1,3‐Dipolar CycloadditionCycloaddition of bridged Quinonehydrazones 1, 4, 5 with mesoionic reagents are studied; thep‐nitrophenylhydrazone 1 reacts with 3‐phenylsydnone (2) under elimination of CO2and dehydrogenation yielding the linearly annulated heterocyclic cycloadduct 3; as opposed to this reaction cycloaddition of phenylsydnone 2 withN‐methyl‐(4)‐ andN‐benzyl‐(5)‐hydrazone derivatives produces the methanobridged heterocycles 6 an

ISSN:0365-6233    

DOI:10.1002/ardp.2503240901

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY

摘要:

AbstractIn the present study, the A‐ring of estradiol was converted to an acetylsalicylic structure which was further complexed with Cu(II). The aim was to combine the anti‐inflammatory properties of estrogens with those of Cu(II) complexes. Key intermediate of the synthesis was 2‐formyl‐estradiol (2) which was prepared in quantitative yield through reaction of the phenoxymagnesium bromide of estradiol with formaldehyde in the presence of HMPA. For a successful reaction, an excess of ethylmagnesium bromide was required, and the mechanism is discussed. The target complex 5 exhibited potent anti‐inflammatory properties, comparable to those of indomethacin, in the carrageenan‐induced rat paw edema. This biological activity was not due either to the steroidal ligand or to the complexed C

ISSN:0365-6233    

DOI:10.1002/ardp.2503240902

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY

摘要:

AbstractBased on the analysis of Quantitative Structure ‐ Activity Relationships (QSAR) three representatives of imidazo[4,5‐b]pyridine derivatives of predicted high antibacterial activity againstMycobacterium tuberculosiswere synthetized and tested bacteriologically. Excellent agreement of the predicted and experimentally observed bioactivity was noted. Additional new derivatives of 4‐methyl‐4H‐2‐cyanomethylimidazo[4,5‐b]pyridine (7) and 2‐(α‐methylcyanomethyl)imidazo[4,5‐b]pyridine (22) were also synthesized and some of them were tested for tuberculostatic activity. The compounds synthesized according to a standard “trial and error” approach app

ISSN:0365-6233    

DOI:10.1002/ardp.2503240903

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY

摘要:

AbstractSynthesis, Biotransformation, and Pharmacodynamics of a New Theophylline Derivative7‐[(RS)2‐((RS)‐1‐Methyl‐2‐phenyl‐ethylamino)propyl]‐theophylline (3) was not described until now. This fenetylline analogue is available by reaction of 7 with an excess of 2 at 150°C. If 2 reacts with 4, an E2‐elimination overwhelms SN‐nucleophilic displacement yielding compound 5.In vivostudies with male White‐Wistar rats, comparing biotransformation of 3 and 1, demonstrate, that the amount of 2 is decreased from 4.7% of (RS)‐2 to 1%, probably due to steric hindrance of the attacking monooxygenases by the methyl group at C‐11 of 3. Pharmacodynamic studies of 3, tested with mice, gave similar result

ISSN:0365-6233    

DOI:10.1002/ardp.2503240904

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY

摘要:

AbstractSynthesis and Hydrolysis of Acyloxy‐2‐oxopropanes2‐Oxopropylesters are examined as potential prodrugs of acidic non‐steroidal anti‐inflammatory drugs. The esters are characterized by a high degree of chemical lability at pH 7.4 (37°C) while exhibiting a higher stability at pH<7. The rate of the non‐enzymatic hydrolysis at pH 7.4 is dependent on steric and electronic effects which can be contributed to the particular

ISSN:0365-6233    

DOI:10.1002/ardp.2503240905

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY

摘要:

AbstractThe synthesis of enantiomerically pure β‐arnino acids (1a‐c)viaan O‐activated equivalent of β‐homoserine is discussed. The chiral synthon 2 was planned to be represented by (S)‐3‐N,N‐dibenzylamino‐4‐mesyloxybutanoic acid methyl ester (3) or by (S)‐3‐N,N‐dibenzylamino‐4‐mesyloxybutanenitrile (6). Both intermediates should be approached from L‐aspartic acid 4 or L‐asparagine 5 through selective reduction of the α‐carboxyl group. It turned out that only nitrile 6 was suitable for the envisioned β‐amino acid synthesis, since alcohol 14 ‐ the synthetic precursor of 3 ‐ was unstable towards intramolecular nucleophilic attack to accomplish the chiral building block 15. Reaction of mesylate 6 with different‘Gilmancuprates’ afforded the 3‐N,N‐dibenzylamino nitrile derivatives 22a‐c, which could be readily deprotected to give the target compounds 1a‐c in 23‐36% overall yield from asparagine. In contrast Me2Cu(CN)Li2as an example for higher order‘Lipshutzcuprates’ did not afford the desired substitution product 22a. The optical integrity of the synthesis was established by coupling of the methyl ester 24 with chiral 1‐phenylethyl

ISSN:0365-6233    

DOI:10.1002/ardp.2503240906

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY

摘要:

AbstractThe synthesis and preliminary assays as hypocholesterolemic agents of fiveN‐diphenylmethylpiperazines are described. The evaluations were carried out in hypercholesterolemic mice and two of these compounds were more effective than bezafibrate in the test employed. The di‐p‐chlorosubstituted compounds showed higher activity than their corresponding dechlorinated an

ISSN:0365-6233    

DOI:10.1002/ardp.2503240907

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY

摘要:

AbstractThe (E)‐1‐hetaryl‐2‐propen‐1‐ones 3 and 4 are prepared by condensation of 2‐acetylthiophenes (1a,1c,1d) or 2‐acetylfuran (1b) with aldehydes. TheMichaeladducts 5/6 are obtained from 3/4 by reaction with malononitrile/LDA in THF at −78°C, or in DMSO with NaH at room temp. Reaction of 3/4 with malononitrile and methylate in methanol yielded the substituted nicotinonitriles 7/8. From terephthalaldehyde, the diketones 9 are prepared, which yield with malononitrile the phenylene‐bis[(thienyl/furyl)nicotinonitrile] derivatives 10 under similiar conditions. Structural and spectra

ISSN:0365-6233    

DOI:10.1002/ardp.2503240908

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY

摘要:

AbstractThree boron derivatives,i.e.trimethylamine‐carbomethoxyborane, tetrakis‐μ‐(trimethylamine‐boranecarboxylato)‐bis(trimethylamine‐carboxyborane)‐dicopper(II), andN,N‐dimethyl‐n‐octadecylamine borane were evaluated for acute toxicity in male mice, at 1, 2 or 5 x their therapeutic dose in rodents for pharmacological activity. Based on organ weights, clinical chemistry, hematopoietic parameters and tissue morphology, the trimethylamine‐carbomethoxyborane was shown to be free of toxicity. The dicopper(II) complex andN,N‐dimethyl‐n‐octadecylamine borane demonstrated slight toxicity with marginal disturbance in hepatic and kidney morphology. The dicopper(II) complex may cause marginal myocardial damage and theN,N‐dimethyl‐n‐octadecylamine borane caused elevations in cholic acid. All three derivatives dem

ISSN:0365-6233    

DOI:10.1002/ardp.2503240909

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY

摘要:

AbstractSynthesis of [b]‐Fused Azepinediones by DealkoxycarbonylationThe 2,3,4,5‐tetrahydro‐1H‐1‐benzazepinediones 2 and 5,6,7,8‐tetrahydro‐4H‐thieno[3,2‐b]azepine‐5,8‐dione (11) are obtained by dealkoxycarbonylation in wet dimethylsulfoxide from fused azepinecarboxylic esters 3 and 10, respectively, 3b and 10 are prepared byDieckmannreaction with KH in DMF/toluene from diesters

ISSN:0365-6233    

DOI:10.1002/ardp.2503240910

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY