BEDNARSKI, PJ and HARTMANN, RW (1993) SYNTHESIS AND EVALUATION OF SULFUR-CONTAINING GLUTETHIMIDE DERIVATIVES FOR AROMATASE AND DESMOLASE INHIBITORY ACTIVITY. ARCHIV DER PHARMAZIE, 326 (7). pp. 391-394. ISSN 0365-6233,
Full text not available from this repository.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. The synthesis 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 to give 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | THIOL-CONTAINING ANDROGENS; MICROSOMAL CYTOCHROME-P-450; SELECTIVE-INHIBITION; LIGAND-BINDING; AMINOGLUTETHIMIDE; ANALOGS; MODEL; SITE; |
| Depositing User: | Dr. Gernot Deinzer |
| Last Modified: | 19 Oct 2022 08:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/53885 |
Actions (login required)
 |
View Item |
