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Titolo:
SYNTHESIS AND EVALUATION OF SULFUR-CONTAINING GLUTETHIMIDE DERIVATIVES FOR AROMATASE AND DESMOLASE INHIBITORY ACTIVITY
Autore:
BEDNARSKI PJ; HARTMANN RW;
Indirizzi:
UNIV REGENSBURG,LEHRSTUHL PHARMAZEUT CHEM 2 W-8400 REGENSBURG GERMANY UNIV SAARLAND,FACHRICHTUNG PHARMAZEUT CHEM W-6600 SAARBRUCKEN GERMANY
Titolo Testata:
Archiv der pharmazie
fascicolo: 7, volume: 326, anno: 1993,
pagine: 391 - 394
SICI:
0365-6233(1993)326:7<391:SAEOSG>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
THIOL-CONTAINING ANDROGENS; MICROSOMAL CYTOCHROME-P-450; SELECTIVE-INHIBITION; LIGAND-BINDING; AMINOGLUTETHIMIDE; ANALOGS; MODEL; SITE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
26
Recensione:
Indirizzi per estratti:
Citazione:
P.J. Bednarski e R.W. Hartmann, "SYNTHESIS AND EVALUATION OF SULFUR-CONTAINING GLUTETHIMIDE DERIVATIVES FOR AROMATASE AND DESMOLASE INHIBITORY ACTIVITY", Archiv der pharmazie, 326(7), 1993, pp. 391-394

Abstract

Novel sulfur-containing glutethimide derivatives, substituted with either thiol or methylsulfide groups in the ortholpara positions of the aromatic ring, were synthesized and tested for both human placental aromatase and bovine adrenocortical desmolase inhibitory activities. Thesynthesis was achieved by the chlorosulfonation of gluthethimide, which yielded a 3:1 mixture of the para to ortho sulfonyl chlorides 2a/b. The sulfonyl chlorides of gluthethimide were reduced with Zn/H2SO4 togive the thioglutethimides 3a/b, which in turn were methylated with MeI/EtOH to give the corresponding methylsulfides 4a/b. In comparison to aminoglutethimide (AG), 3a/b and 4a/b were weak inhibitors of aromatase, with 3a/b being more potent than 4a/b. Aromatase inhibition by the thiol compound was pH-dependent; 3a/b was most potent at higher pH (7.4) than at lower (6.6). This suggested that the thiolate form of 4 coordinates with the ferric heme of aromatase. Likewise, both 3a/b and 4a/b were less potent at inhibiting bovine adrenal desmolase than AG. Possible reasons for the surprisingly poor aromatase inhibitor activity of these compounds are discussed.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 09:46:46