Abstract:
:Phosphono-analogues of glutathione containing the O = P(OR)2 moiety in place of the cysteinyl residue CH2SH 1a-1d were prepared by solution phase peptide synthesis. Benzyl, benzyloxy-carbonyl, and tert-butyl protecting groups were used to mask the individual amino acid functional groups. The formation of peptide bonds was achieved by the usual peptide synthesis via activation of carboxylic functions with cyclohexylcarbodiimide and subsequent reaction with free amino groups. The thus obtained, fully-protected peptides were each purified by normal phase column chromatography. Deprotection was accomplished by hydrogenolysis and by treatment with HBr/acetic acid yielding the desired phosphonic acid diester 1a-1d. The inhibition of the glutathione conjugation of 1-chloro-2,4-dinitrobenzene by human placental glutathione S-transferase was studied by determining the IC50 values of the new glutathione analogues. The IC50 values were 291 microM, 139 microM, 64 microM, and 21 microM for the dimethyl, diethyl, diisopropyl, and di-n-butyl esters, respectively. The results clearly show that the formal substitution of the glutathione thiol function by phosphonic acid esters leads to a new class of glutathione S-transferase inhibitors. Further investigations directed at the question of whether or not these glutathione analogues are suitable for a modulation in chemotherapy are in progress.
journal_name
Arch Pharm (Weinheim)journal_title
Archiv der Pharmazieauthors
Kunze Tdoi
10.1002/ardp.19963291106subject
Has Abstractpub_date
1996-11-01 00:00:00pages
503-9issue
11eissn
0365-6233issn
1521-4184journal_volume
329pub_type
杂志文章abstract::The regio- and stereospecific synthesis of O-methyl-chiro-inositols and O-methyl-scyllo-inositol was achieved, starting from p-benzoquinone. After preparing dimethoxy conduritol-B as a key compound, regiospecific bromination of the alkene moiety of dimethoxy conduritol-B and acid-catalyzed ring opening of dimethoxydia...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.202000254
更新日期:2020-09-30 00:00:00
abstract::[4-(Adamantane-1-carboxamido)-3-oxo-1-thia-4-azaspiro[4.4]nonan-2-yl]acetic acid (4a) and [4-(adamantane-1-carboxamido)-8-nonsubstituted/substituted-3-oxo-1-thia-4-azas-piro[4.5]decane-2-yl]acetic acid (4b-g) derivatives were synthesized; their structures were verified by elemental analysis, infrared spectroscopy, 1 H...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.202000256
更新日期:2021-01-06 00:00:00
abstract::A series of 3,4-bis-chalcone-N-arylpyrazoles 3a-k was prepared from diacetyl pyrazoles 2a-e. The reaction of 2d and 2e with hydrazine hydrate gave pyrazolo[3,4-d]pyridazine derivatives 4a-b. Furthermore, the reaction of 2a-e with thiosemicarbazide afforded pyrazolo[3,4-d]pyridazine thiocyanate salts 5a-e. The synthesi...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201300193
更新日期:2013-09-01 00:00:00
abstract::The synthesis of new bischromone derivatives (4a-c and 5a-c) as potential anticancer drugs is described. The difference in the reactivity between 4-oxo-4H-chromene-3-carboxylic acid 2 (or its methyl ester 3) and 4-oxo-4H-chromene-3-carbonyl chloride 1 with three different polyamines: 3,3'-diamino-N-methyldipropylamine...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201200220
更新日期:2013-01-01 00:00:00
abstract::Although a few experimental approaches to isolated limb perfusion (ILP) are described in the literature, none of these animal models mimics the clinical perfusion techniques adequately to improve the technique of ILP on the basis of valid preclinical data. Therefore, we developed an ILP setup in rats allowing online m...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200400917
更新日期:2004-12-01 00:00:00
abstract::The chemical reactivity of cytotoxic 5-indolone derivatives is examined in order to get ideas about their behaviour in biological systems. Dienone-phenol-rearrangement preserving the indole ring system could not be achieved, aromatization of 1b gives the phenol derivative 3 alpha. In diluted NaOH ester hydrolysis occu...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19923250904
更新日期:1992-09-01 00:00:00
abstract::This review emphasizes the relationship of breast cancer, estrogen receptor and ligands, especially the centrality of the estrogen receptor, which mediates on one hand the hormone-induced gene transcription and on the other hand the anti-estrogen action against breast cancer. The characterization of the estrogen recep...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章,评审
doi:10.1002/ardp.200800174
更新日期:2009-03-01 00:00:00
abstract::Reaction of K2PtCl4 with the substituted 2-aminomethylpyridines 9, 14, and 22 affords the corresponding dichloroplatinum(II) complexes 3-5. Compounds 3 and 22 show remarkable relative binding affinities for the estrogen receptor. Towards the hormone-independent P388-tumor of the CD2F1-mouse the platinum(II) complexes ...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:
更新日期:1991-10-01 00:00:00
abstract::Rapamycin, a potent antifungal antibiotic, was approved as immunosuppressant, and lately its derivatives have been developed into mTOR targeting anticancer drugs. Structure modification was performed at the C-42 position of rapamycin, and a novel series of rapamycin triazole hybrids (4a-d, 5a-e, 8a-e, and 9a-e) was fa...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201500457
更新日期:2016-06-01 00:00:00
abstract::The oncoprotein cytotoxic associated gene A (CagA) of Helicobacter pylori plays a pivotal role in the development of gastric cancer, so it has been an important target for anti-H. pylori drugs. Conventional drugs are currently being implemented against H. pylori. The inhibitory role of plant metabolites like curcumin ...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201400438
更新日期:2015-08-01 00:00:00
abstract::A number of 7-piperazinylquinolones carrying a functionalized 2-(furan-3-yl)ethyl moiety attached to the piperazine ring have been synthesized and evaluated as antibacterial agents against a panel of Gram-positive and Gram-negative bacteria. Most of the synthesized compounds exhibited significant antibacterial activit...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200600169
更新日期:2007-01-01 00:00:00
abstract::A range of novel pyridine-2,4,6-tricarbohydrazide thiourea compounds (4a-i) were synthesized in good to excellent yields (63-92%). The enzyme inhibitory potentials of these compounds were investigated against α- and β-glucosidases because these enzymes play a crucial role in treating type-2 diabetes mellitus (T2DM). A...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201700236
更新日期:2018-01-01 00:00:00
abstract::A series of oximes deriving from 5-arylidene-pyrrolidine-2,3,4-triones and pyridine-2,3,4-triones has been prepared. The presence of the tautomeric nitrosoenol was proven in solutions of alpha-ketooxime 7a. The binding affinity of the new oximes toward the N-methyl-D-aspartate (glycine site) receptor has been measured...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/(sici)1521-4184(19999)332:9<309::aid-ardp3
更新日期:1999-09-01 00:00:00
abstract::Both 2-nitrooxymethyl-4-phenyl- (2) and 4-nitrooxymethylphenyl-1,4-dihydropyridines (3) represent new combinations of two different vasodilating structures. 2 could not be isolated due to its spontaneous lactonization. Derivatives of 3 were obtained via Hantzsch synthesis using nitrooxymethylated benzaldehydes. The in...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19973300804
更新日期:1997-08-01 00:00:00
abstract::3'-Azidonucleosides 4 have been synthesized by condensation of silylated (Z)-5-ethylidenehydantoin and (Z)-5-benzylidenehydantoin with methyl 3-azido-5-O-tert-butyldiphenylsilyl-2,3-dideoxy-D-erythro-pento furanoside (3). The nucleosides 4 were deblocked on treatment with tetrabutylammonium fluoride. The ethylidene gr...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19943271010
更新日期:1994-10-01 00:00:00
abstract::Three series of imidazolidinium ligands (NHC precursors) substituted with 4-vinylbenzyl, 2-methyl-1,4-benzodioxane, and N-propylphthalimide were synthesized. N-Heterocyclic carbene (NHC) precursors were prepared from N-alkylimidazoline and alkyl halides. The novel NHC precursors were characterized by 1 H NMR, 13 C NMR...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201700045
更新日期:2017-06-01 00:00:00
abstract::A series of bis(benzo[g]indoles) bridged by CX-(CH2)nN(Me)(CH2)n-CX (X = O, S, H2; n = 2,3) was synthesized as bifunctional antitumor agents and evaluated for cytotoxic activity against diverse human cancer cell lines by the National Cancer Institute. The parent compounds 2a,b exhibited a good level of activity and de...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/1521-4184(200112)334:11<337::aid-ardp337>3
更新日期:2001-11-01 00:00:00
abstract::We report in this work the synthesis, cytotoxicity, and antimicrobial activity of ([1,2,4]triazolo[1,5-c]quinazolin-2-ylthio)carboxylic acid amides 4-7 in connection with our previous research in the preparation of triazoloquinazoline derivatives. Due to simplicity, general availability of starting materials, and high...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200900077
更新日期:2009-11-01 00:00:00
abstract::Chemical modification of cinnoxacin was studied with the aim of improving its antibacterial activity and spectrum. A series of 4-imino-1, 4-dihydrocinnoline-3-carboxylic acid derivatives was synthesized and their in vitro antibacterial activity was evaluated. These derivatives were designed as isosteric analogues of f...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200390000
更新日期:2003-03-01 00:00:00
abstract::In an attempt to counteract bacterial pathogenicity, a set of novel imidazolidine-2,4-dione and 2-thioxoimidazolidin-4-one derivatives was synthesized and evaluated as inhibitors of bacterial virulence. The new compounds were characterized and screened for their effects on the expression of virulence factors of Pseudo...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201900352
更新日期:2020-05-01 00:00:00
abstract::Several 4-cyano-1,5-diphenylpyrazoles attached to different heterocyclic ring systems at position 3 were synthesized starting from ethyl 4-cyano-1,5-diphenyl-1H-pyrazole-3-carboxylate 1. The newly synthesized compounds were tested in vivo for their anti-estrogenic effects and evaluated in vitro for their cytotoxic pro...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200900176
更新日期:2010-07-01 00:00:00
abstract::Polyketide-derived macrolactones like zearalenone (1), zearalane (2) or curvularin (3) display a wide range of interesting pharmacological activities. Here, we present a short and efficient approach towards this class of natural products by a combination of the Sonogashira and Mitsunobu reactions. The resulting lacton...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200500132
更新日期:2005-12-01 00:00:00
abstract::New phosphoramide mustards (6-8) have been prepared from the antibiotics 2 and 3, and from 5. The mixture of cyclophosphamides could be separated by preparative layer and column chromatography. The assignments of configuration to the isomeric phosphoramidates was based on the magnetic anisotropy of the P = O bond. The...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/(sici)1521-4184(19989)331:9<265::aid-ardp2
更新日期:1998-09-01 00:00:00
abstract::A novel approach to the pyridoacridine ring system of the ascididemin-type marine alkaloids is presented. This approach allows for the introduction of the ring A of the alkaloids by using a simple aromatic aldehyde building block. The viability of this approach is demonstrated with the synthesis of AK37, a bioactive d...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201200019
更新日期:2012-10-01 00:00:00
abstract::To identify new agents for the treatment of American cutaneous leishmaniasis, a series of eight 1,4-bis(substituted benzalhydrazino)phthalazines was evaluated against Leishmania braziliensis and Leishmania mexicana parasites. These compounds represent a disubstituted version of the 1-chloro-4-(monoaryl/heteroarylhydra...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201800299
更新日期:2019-06-01 00:00:00
abstract::Alzheimer's disease (AD) is a neurodegenerative disorder characterized by dementia, memory impairment, cognitive dysfunction, and speech impairment. The utility of cholinergic replacement by acetylcholinesterase (AChE) inhibitors in AD treatment has been well documented so far. Recently, studies have also evidenced th...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.202000282
更新日期:2020-11-06 00:00:00
abstract::A series of 5-amino-3-methylisoxazole-4-carboxylic acid amides has been prepared by condensation of 5-amino-3-methylisoxazole-4-carboxylic acid with ethyl chloroformate. The resulting mixed anhydride undergoes condensation with appropriate phenylamides to form the corresponding amides 6-16. The compounds obtained were...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/(sici)1521-4184(19995)332:5<158::aid-ardp1
更新日期:1999-05-01 00:00:00
abstract::A series of dialkyl, dicycloalkyl, and diaryl ester analogues of nifedipine, in which the ortho-nitro phenyl group at position 4 is replaced by the 4-(5)-chloro-2-ethyl-5-(4)-imidazolyl substituent, were synthesized and evaluated as calcium channel antagonists using the high K+ contraction of guinea pig ileal longitud...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200600013
更新日期:2006-06-01 00:00:00
abstract::Two new arylnaphthalide lignans, procumphthalide A (1) and 4-O-beta-D-glucopyranosyl-(1"'-->2")-beta-D-apiofuranosyldiphyllin, named procumbenoside B (2), along with cilinaphthalide B (3) and several other known compounds were isolated from the methanolic extracts of Justicia procumbens. By using NMR and other spectra...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200300841
更新日期:2004-04-01 00:00:00
abstract::A series of novel N(1)-[5-(4-substituted phenyl)-1,3,4-thiadiazol-2-yl]-N(4)-(4-substituted benzaldehyde)-semicarbazone 1-12, N(1)-[5-(4-substituted phenyl)-1,3,4-thiadiazol-2-yl]-N(4)-[1-(4-substituted phenyl)ethanone]-semicarbazone 13-16, and N(1)-[5-(4-substituted phenyl)-1,3,4-thiadiazol-2-yl]-N(4)-[1-(4-substitut...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200800213
更新日期:2009-08-01 00:00:00