Showing papers on "Hydroxysteroid dehydrogenase published in 2002"
TL;DR: The results confirm the initial strategy of combining studies of structural biology and enzyme mechanism in the inhibitor design, which may be applied to other steroidogenic enzymes involved in human diseases.
Abstract: SPECIFIC AIMThe goal of this study is to design high-affinity inhibitors for human estrogenic type 1 17β-hydroxysteroid dehydrogenase (17β-HSD1) to block the synthesis of estrogen, which plays an i...
87 citations
TL;DR: A full-length cDNA of mouse type 10 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD10) was cloned from brain, representing the accurate nucleotide sequence information that rendered possible an accurate deduction of the amino acid sequence of the wild-type enzyme.
62 citations
Patent•
05 Sep 2002TL;DR: In this article, a novel class of compounds as inhibitors of type 3 17β-hydroxysteroid dehydrogenase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds and methods of treatment, prevention, inhibition, or amelioration of one of the diseases associated with Type 3 17 β-hydroxylsteroid dehydrogenase using such compounds or pharmaceutical compositions are described.
Abstract: In its many embodiments, the present invention provides a novel class of compounds as inhibitors of type 3 17β-hydroxysteroid dehydrogenase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with type 3 17β-hydroxysteroid dehydrogenase using such compounds or pharmaceutical compositions.
57 citations
TL;DR: The results suggest that AKR1C1 decreases the neurosteroid concentrations in human brain by inactivating 3alpha,5alpha-THP and eliminating the precursors from the synthetic pathways.
Abstract: In this report, we compared kinetic constants and products in the reduction of the neurosteroids, 3α, 5α-tetrahydroprogesterone (3α,5α-THP) and 3α,5α-tetrahydrodeoxycorticosterone (3α,5α-THDOC), and their precursors, 5α-dihydroprogesterone (5α-DHP), 5α-dihydrodeoxycorticosterone (5α-DHDOC) and progesterone, by three isoenzymes (AKR1C1, AKR1C2 and AKR1C3) of human 3α-hydroxysteroid dehydrogenase. AKR1C1 efficiently reduced 3α,5α-THP, 5α-DHP and progesterone to their 20α-hydroxy metabolites, and slowly converted 5α-DHDOC to 3α,5α-THDOC. AKR1C2 exhibited low 20-ketoreductase activity for 3α,5α-THP and moderate 3-ketoreductase activity for 5α-DHP and 5α-DHDOC. 3α,5α-THDOC was not reduced by the two isoenzymes. No significant activity for the steroids was detected with AKR1C3. The results suggest that AKR1C2 is involved in the neurosteroid synthesis, but AKR1C1 decreases the neurosteroid concentrations in human brain by inactivating 3α,5α-THP and eliminating the precursors from the synthetic pathways. In addition, we found that the several benzodiazepines inhibited the three isoenzymes noncompetitively with respect to the substrate. Although cloxazolam was a potent and specific inhibitor of AKR1C3, diazepam, estazolam, flunitrazepam, medazepam and nitrazepam, that inhibited AKR1C1 and AKR1C2, may influence the neurosteroid metabolism.
55 citations
TL;DR: The results point to the possibility that the gonadotropin-induced DHP production and final oocyte maturation in the zebrafish may not involve significant change of CR/20 beta-HSD expression as evidenced in the salmonids, or that there might be other isoforms of 20 beta- HSD whose expression is tightly controlled by endocrine and paracrine factors.
45 citations
TL;DR: Dodecyl-β-d-maltoside was found to be the best detergent for the solubilization, purification, and reconstitution of 17β-hydroxysteroid dehydrogenase 2 and was proved to be a homodimer.
42 citations
TL;DR: It is found that the steroid metabolism of these lung fibroblast cells is oriented toward androgen inactivation, and an allelic variation of the 17 beta-HSD-2 gene is suspected, which would result in familial incidence of respiratory distress.
Abstract: Androgens delay lung maturation through their action on lung fibroblasts. Knowing that testosterone is secreted by the lung epithelial-like cell line A-549, we have studied the metabolism of androgens by several human lung diploid fibroblasts cell lines. No 17-ketosteroid reductase activity was detected. In contrast, testosterone was transformed mainly into androstenedione and androstanedione with no 5α-dihydrotestosterone formed, indicating the presence of 17β- hydroxysteroid dehydrogenase (HSD) type 2 and 5α-reductase activities. The eight cell lines analyzed had either a low or high 17β-HSD type 2 activity level. No correlation between these levels and the sex or age stage of cells was established, but Northern blot analysis of human lung RNA samples of five adult subjects revealed very similar variations between subjects in the level of 17β-HSD type 2 mRNA. The 5α-reductase activity had a marked substrate preference for androstenedione, the product of 17β-HSD type 2. When tritiated testosterone was us...
42 citations
TL;DR: Results demonstrate that the carbonyl reductase of ayu ovary is involved in the production of maturation-inducing hormone, and they provide evidence for a novel physiological role of this enzyme in the final maturation of oocytes.
Abstract: 17α,20β-Dihydroxy-4-pregnen-3-one is the major oocyte maturation-inducing hormone of several teleost species. Gonadotropin-induced increase in ovarian 20β-hydroxysteroid dehydrogenase activity is essential for the synthesis of maturation-inducing hormone. Cloning and expression studies suggest that ayu (Plecoglossus altivelis) ovarian carbonyl reductase can function as 20β-hydroxysteroid dehydrogenase. The amino acid sequence deduced from the isolated cDNA had 276 amino acid residues and shared approximately 60% homology with mammalian and teleostean carbonyl reductases. The sequence data search showed that the ayu cDNA clone belongs to the short-chain dehydrogenase/reductase family. The clear lysate prepared from Escherichia coli harboring the cDNA catalyzed the production of maturation-inducing hormone. Its identification was confirmed by two-dimensional, thin-layer chromatography followed by recrystallization. Purification of the E. coli-expressed cDNA product revealed that it possessed both carbonyl reductase and steroid dehydrogenase activities, and 17α-hydroxyprogesterone, the endogenous immediate precursor of maturation-inducing hormone, was one of the preferred substrates. Furthermore, Northern blot analysis denoted that the transcripts are present both in fully grown, immature ovarian follicles and at higher levels in mature ovarian follicles. These results demonstrate that the carbonyl reductase of ayu ovary is involved in the production of maturation-inducing hormone, and they provide evidence for a novel physiological role of this enzyme in the final maturation of oocytes. Based on its functional properties, the enzyme can be referred to as carbonyl reductase-like 20β-hydroxysteroid dehydrogenase.
41 citations
TL;DR: It is proposed that progesterone produced during the first half of mouse pregnancy in decidua and giant trophoblast cells acts as an immunosuppressant at the fetal maternal interface to prevent rejection of the fetus.
41 citations
TL;DR: Activity from a series of ovarian epithelial tumors was assayed in cytosol and microsomes under conditions which differentiate between isoforms, indicating 17HSD/KSR5 was the predominant isoform.
37 citations
TL;DR: Testing the effect of a variety of dietary phytoestrogens on the activity of human 17beta-hydroxysteroid dehydrogenase type 5 shows that reductive and oxidative activity of the enzyme are inhibited by many compounds, especially zearalenone, coumestrol, quercetin and biochanin A.
Abstract: Phytoestrogens contained in a vegetarian diet are supposed to have beneficial effects on the development and progression of a variety of endocrine-related cancers. We have tested the effect of a variety of dietary phytoestrogens, especially flavonoids, on the activity of human 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD 5), a key enzyme in the metabolism of estrogens and androgens. Our studies show that reductive and oxidative activity of the enzyme are inhibited by many compounds, especially zearalenone, coumestrol, quercetin and biochanin A. Among flavones, inhibitor potency is enhanced with increased degree of hydroxylation. The most effective inhibitors seem to bind to the hydrophilic cofactor binding pocket of the enzyme.
TL;DR: The 7-hydroxycoumarins, umbelliferone and 4-methylumbellifer one (IC 50 =1.4 and 1.9 μM, respectively) were potent inhibitors of human testes microsomal 17 β -HSD (type 3) enzyme whereas 7-methoxycou marin, 4-HydroxycOUmarin and 7-ethoxyCoumarin had little or no inhibitory activity.
Abstract: The 7-hydroxycoumarins, umbelliferone and 4-methylumbelliferone (IC 50 =1.4 and 1.9 μM, respectively) were potent inhibitors of human testes microsomal 17 β -HSD (type 3) enzyme whereas 7-methoxycoumarin, 4-hydroxycoumarin and 7-ethoxycoumarin had little or no inhibitory activity. Analogues of the weak inhibitory triphenylethenes tamoxifen and clomiphene but lacking the basic substituent, were weak inhibitors of the human microsomal enzyme. Inhibitory activity was improved by replacement of the triphenylethene structure with a triphenylmethyl (17, 52.6% inhibition) or phenylpropyl (16, 94.8%, IC 50 =42.1 μM) skeleton. Further studies on tamoxifen using rat testes microsomal 17 β -HSD showed that the inhibition was time-dependent and irreversible but not specifically mechanism-based.
Patent•
15 Oct 2002TL;DR: In this paper, the authors have disclosed compounds of the formula (I), prodrugs thereof, or pharmaceutically acceptable salts of the compounds or of said pro drugs which are useful as inhibitors of Type 3 17β-hydroxysteroid dehydrogenase.
Abstract: There are disclosed compounds of the formula (I), prodrugs thereof, or pharmaceutically acceptable salts of the compounds or of said prodrugs which are useful as inhibitors of Type 3 17β-Hydroxysteroid Dehydrogenase. Also disclosed are pharmaceutical compositions containing said compounds and their use for the treatment or prevention of androgen dependent diseases.
TL;DR: The cells with unique characteristics, TTE1, established from transgenic mice harboring a temperature-sensitive simian virus 40 (tsSV40) large T-antigen gene should serve as a useful model to study the function of Leydig cell.
Abstract: A Leydig cell line, TTE1, has been established from transgenic mice harboring a temperature-sensitive simian virus 40 (tsSV40) large T-antigen gene. The cells grew at a permissive temperature (33°C), but growth was markedly prevented at a nonpermissive temperature (39°C). T-antigen was expressed in the nuclei at 33°C but disappeared at 39°C, indicating that the cells show a temperature-sensitive growth phenotype reflected by the tsSV40 large T-antigen. TTE1 cells did not show any colony-forming activity in soft agar and form tumors in subcutaneous tissue in nude mice, indicating that the cells were not transformed. Alkaline phosphatase and 3 g -hydroxysteroid dehydrogenase (HSD) activities or expression of cytokeratin and vimentin were observed. Reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that TTE1 cells expressed mRNAs encoding 17 g -HSD types 1 and 3, and inhibin- f. The cells with unique characteristics, therefore, should serve as a useful model to study the ...
TL;DR: Cloning a cDNA that encodes a novel short-chain dehydrogenase/reductase, SDR-O, conserved in mouse, human and rat is reported, suggesting that S DR-O may catalyse the metabolism of another class of nuclear receptor ligand and may regulate metabolism by binding substrates/products and/or by serving as a regulatory factor.
01 Jan 2002
TL;DR: Results dem- onstrate that the carbonyl reductase of ayu ovary is involved in the production of maturation-inducing hormone, and they provide evidence for a novel physiological role of this enzyme in the final maturation of oocytes.
Abstract: a,20b-Dihydroxy-4-pregnen-3-one is the major oocyte maturation-inducing hormone of several teleost species. Gonad- otropin-induced increase in ovarian 20b-hydroxysteroid dehy- drogenase activity is essential for the synthesis of maturation- inducing hormone. Cloning and expression studies suggest that ayu (Plecoglossus altivelis) ovarian carbonyl reductase can func- tion as 20b-hydroxysteroid dehydrogenase. The amino acid se- quence deduced from the isolated cDNA had 276 amino acid residues and shared approximately 60% homology with mam- malian and teleostean carbonyl reductases. The sequence data search showed that the ayu cDNA clone belongs to the short- chain dehydrogenase/reductase family. The clear lysate prepared from Escherichia coli harboring the cDNA catalyzed the pro- duction of maturation-inducing hormone. Its identification was confirmed by two-dimensional, thin-layer chromatography fol- lowed by recrystallization. Purification of the E. coli-expressed cDNA product revealed that it possessed both carbonyl reduc- tase and steroid dehydrogenase activities, and 17a-hydroxypro- gesterone, the endogenous immediate precursor of maturation- inducing hormone, was one of the preferred substrates. Fur- thermore, Northern blot analysis denoted that the transcripts are present both in fully grown, immature ovarian follicles and at higher levels in mature ovarian follicles. These results dem- onstrate that the carbonyl reductase of ayu ovary is involved in the production of maturation-inducing hormone, and they pro- vide evidence for a novel physiological role of this enzyme in the final maturation of oocytes. Based on its functional prop- erties, the enzyme can be referred to as carbonyl reductase-like 20b-hydroxysteroid dehydrogenase.
TL;DR: Interestingly, these ADT derivatives do not bind to androgen, estrogen, glucocorticoid, and progestin receptors, suggesting no unsuitable receptor-mediated effects.
Abstract: A series of androsterone (ADT) derivatives substituted at position 16 were efficiently synthesized in short reaction sequences; the ether analogues were also synthesized in the case of the methyl and allyl derivatives. The aim of this study was to develop inhibitors of the steroidogenic enzyme type 3 17 β -hydroxysteroid dehydrogenase and then evaluate their ability to inhibit this activity in transfected HEK-293 cells. For each compound we measured the percentage of inhibition of the transformation of 4-androstene-3,17-dione, the natural substrate of this steroidogenic enzyme, into the active androgen testosterone. The synthesized compounds proved to be weak inhibitors of this enzyme, but interestingly, these ADT derivatives do not bind to androgen, estrogen, glucocorticoid, and progestin receptors, suggesting no unsuitable receptor-mediated effects. One exception, 16 α -(3′-bromopropyl)-5 α -androstane-3 α,17 β -diol (8), the only compound bearing a hydroxy group at position 17 β instead of a ketone, sh...
TL;DR: It was found that RAs repress the growth of RL 95-2 cells, which express all subtypes of RXR and RAR, as examined by RT-PCR, and 17HSD type 2 mRNA expression was not altered by RAs in cultured cells.
Abstract: The effects of E2 are dependent on ERs and local E2 concentration in target cells. Modulation of intracellular E2 concentration involves the action of 17β-hydroxysteroid dehydrogenase (17HSD) type 2, the enzyme converting E2 to estrone. In the present study, the influence of RAs on the growth of endometrial cancer cell line RL 95-2 as well as the expression of ERs and 17HSD type 2 have been investigated. It was found that RAs repress the growth of RL 95-2 cells, which express all subtypes of RXR and RAR, as examined by RT-PCR. Also, quantitative RT-PCR analysis showed that both ERα and ERβ are present in RL 95-2 cells, and Western blot assay further revealed that ERα expression was decreased by all trans-RA treatment. In contrast, RAs induced 17HSD type 2 mRNA expression in a dose- and time-dependent fashion. This stimulatory effect was also detected at the level of in vivo oxidative 17HSD activity in cultured cells. On the other hand, the abundance of 17HSD type 2 mRNA was not altered by RAs in cultured ...
15 Mar 2002
TL;DR: In this article, the absence of the 11beta-hydroxysteroid dehydrogenases (11beta-HSDs) in the Australian koala (Phascolarctos cinereus) was investigated and no activity (either reductive or oxidative) was found in hepatic microsomes.
Abstract: The 11beta-hydroxysteroid dehydrogenases (11beta-HSDs) interconvert 11beta-hydroxysteroids such as cortisol into 11-oxosteroids such as cortisone. In most mammals, 11beta-HSD 1 is expressed predominantly in the liver and is active in both the oxidative (cortisol to cortisone) and dehydrogenase (cortisone to cortisol) directions, whilst 11beta-HSD 2 is expressed predominantly in the kidney and functions as a pure oxidative enzyme. We have investigated 11beta-HSD 1 activity in the Australian koala (Phascolarctos cinereus) and have found no activity (either reductive or oxidative) in hepatic microsomes. Immunoblot analysis of koala hepatic microsomes, using an 11beta-HSD 1 antibody raised against the mouse enzyme, failed to identify immunoreactive protein. Reverse transcriptase-polymerase chain reaction (RT-PCR) of koala liver mRNA and genomic PCR using primers designed against highly conserved regions of 11beta-HSD 1 nucleotide sequences were also negative. Furthermore, Southern and Northern blot analysis of koala genomic DNA and mRNA, respectively, confirmed that the koala lacks the 11beta-HSD 1 gene and gene transcript. These results support the fact that the lack of hepatic 11beta-HSD 1 activity in the koala is due to the absence of the 11beta-HSD 1 gene, and this absence is novel among mammalian species studied to date.
TL;DR: The preparative-scale oxidation of Gd(III) complexes of ligands containing 7,12-dihydroxy and 12-hydroxy substituted cholanoic moieties to the corresponding 12-oxo derivatives was accomplished by means of 12 f -hydroxysteroid dehydrogenase.
Abstract: The preparative-scale oxidation of Gd(III) complexes of ligands containing 7,12-dihydroxy and 12-hydroxy substituted cholanoic moieties to the corresponding 12-oxo derivatives was accomplished by means of 12 f -hydroxysteroid dehydrogenase. The enzymatic transformation appeared preferable to the chemical one because it was highly regioselective and environmentally benign. Other dehydrogenases, namely 3 f - and 7 f -hydroxysteroid dehydrogenases, also proved to be capable of catalysing the regioselective oxidation of the hydroxy groups of a Gd(III) complex containing a subunit of 3,7,12-trihydroxycholanoic acid. The above complexes are of interest as contrast agents for in vivo magnetic resonance imaging.
TL;DR: The data demonstrate that 17HSD type 2 expression in endometrial carcinoma cells is down-regulated by certain growth factors.
Abstract: Estradiol (E2) is the major molecular form of estrogens. Its biological effects are determined by estrogen receptors and intracellular E2 concentration in target cells. Regulation of intracellular E2 concentration involves the action of 17β-hydroxysteroid dehydrogenase (17HSD) type 2, the enzyme inactivating E2 to estrone. It has been demonstrated that 17HSD type 2 is expressed in normal endometrial epithelia and emdometrial carcinoma cells (RL 95-2). However, the regulatory mechanism of 17HSD type 2 expression in emdometrial cancer cells remains unknown. In the present study, the effects of transforming growth factor-β1 (TGF-β1) and epidermal growth factor (EGF) on 17HSD type 2 expression in RL 95-2 cells have been investigated using enzyme activity assay and Northern blot analysis. After stimulation with TGF-β1 or EGF, the in vivo oxidative 17HSD activity in RL 95-2 cells was significantly decreased. It appeared that the inhibitory effect of TGF-β1 and EGF on the enzyme activity of 17HSD type 2 is dose-and time-dependent. Northern blot analysis further revealed that treatment of cells for 48 h with 10 ng/mL TGF-1 β and 50 ng/mL EGF reduced the expression 17HSD type 2 mRNA to 30% and 20% of the control level, respectively. The data demonstrate that 17HSD type 2 expression in endometrial carcinoma cells is down-regulated by certain growth factors.
TL;DR: Two crystal forms of 17beta-HSD5 in an enzyme-testosterone-NADP ternary complex have been obtained under different crystallization conditions and show high sequence homology to 3alpha-hydroxysteroid dehydrogenases (3alpha-HSDs).
Abstract: 17β-Hydroxysteroid dehydrogenases (17β-HSDs) catalyze the last step in the biosynthesis of all androgens and estrogens, thus playing a pivotal role in sex-hormone metabolism. Human 17β-HSD type 5 (17β-HSD5) catalyzes hydride transfer at the 17β-hydroxy position, but possesses high sequence homology to 3α-hydroxysteroid dehydrogenases (3α-HSD). Two crystal forms of 17β-HSD5 in an enzyme–testosterone–NADP ternary complex have been obtained under different crystallization conditions. A form I crystal obtained at pH 8.5 diffracted to 1.32 A. It belonged to space group P21, with unit-cell parameters a = 47.41, b = 77.16, c = 48.67 A, β = 116.32°. Form II crystals obtained at pH 6.5 diffracted to 2.0 A and belonged to space group P63, with unit-cell parameters a = b = 110.58, c = 56.89 A.
TL;DR: It was suggested in porcine oocytes that the metabolic abilities of progesterone, 17α-hydroxyprogesterone, 20 α-hydroxypregnenolone,17α,20β-dihydroxyproGESterone and estradiol-17β in the cytoplasm are closely related to nuclear maturation, and the disappearance of their metabolic abilities could be used as a characteristic for the resumption of meiotic maturation.
Abstract: The activities of hydroxysteroid dehydrogenases (HSDs) were histochemically demonstrated in cultured porcine oocytes, and the changes in steroid metabolism during meiotic maturation and also the relationship between nuclear maturation and changes in steroid metabolism in the cytoplasm were examined The activities of Δ5-3β-HSD, 17 β-HSD, 20α-HSD and 20β-HSD were observed in 91 to 97% of porcine oocytes soon after collection The percentages of oocytes showing the activities of Δ5-3β-HSD (using DHA as the substrate), 17β-HSD (testosterone) and 20β-HSD (20β-hydroxyprogesterone) did not change during maturation culture, while those showing the activities of Δ5-3β-HSD (pregnenolone and 17α-hydroxypregnenolone), 17β-HSD (estradiol-17β), 20α-HSD (20α-hydroxyprogesterone) and 20β-HSD (17α-hydroxyprogesterone) decreased as the time of maturation culture was prolonged and reached 4, 0, 0, 2 and 0%, respectively, after 44 h culture In the oocytes cultured for 22 h with olomoucine, nuclei were all in the germinal vesicle stage, and the activities of Δ5-3β-HSD (pregnenolone and 17α-hydroxypregnenolone), 17β-HSD (estradiol-17β), 20α-HSD (20α-hydroxyprogesterone) and 20β-HSD (17α-hydroxyprogesterone) were observed in 57, 64, 65, 61 and 66% of the treated oocytes, respectively On the other hand, 10, 2, 10, 7 and 2% of control oocytes respectively showed such HSD activities, demonstrating a significantly lower percentage of oocytes showing the HSD activities, compared with the olomoucine-treated oocytes From the present findings, it was suggested in porcine oocytes that the metabolic abilities of progesterone, 17α-hydroxyprogesterone, 20α-hydroxyprogesterone, 17α,20β-dihydroxyprogesterone and estradiol-17β in the cytoplasm are closely related to nuclear maturation, and the disappearance of their metabolic abilities could be used as a characteristic for the resumption of meiotic maturation
Patent•
21 Aug 2002TL;DR: In this article, the high resolution structure of human type III 3α-hydroxysteroid dehydrogenase (3a-HSD) was determined by X-ray diffraction.
Abstract: 3 α-hydroxysteroid dehydrogenase (3a-HSD) plays a central role in the metabolism and action of steroid hormones and neurosteroids (steroids synthesized in the central nervous system). The high resolution structure of human type III 3a-HSD crystallized in complex with cofactor NADP is determined by X-ray diffraction. Furthermore the active site is determined. The structure coordinates of the enzyme may be used to design and select novel classes of modulators to human type III 3a-HSD.
Patent•
14 Jan 2002
TL;DR: In this paper, the authors present a set of reagents which regulate human alpha-hydroxysteroid dehydrogenase-like enzyme and reagents that bind to human alpha -hydroxylsteroid-dehydrogenase gene products.
Abstract: Reagents which regulate human alpha-hydroxysteroid dehydrogenase-like enzyme and reagents which bind to human alpha-hydroxysteroid dehydrogenase-like enzyme gene products can play a role in preventing, ameliorating, or correcting dysfunctions or diseases including, but not limited to, cancer, glaucoma, obesity, colon and prostate cancer and benign prostatic hypertrophy.
Patent•
30 May 2002TL;DR: In this paper, the authors describe a topical and/or dermatological composition for topical application or by oral administration, characterized in that it contains an effective amount of at least one compound inhibiting the enzyme 3.β. -hydroxysteroid dehydrogenase.
Abstract: The invention relates to a cosmetic and / or dermatological and / or pharmaceutical composition for topical application or by oral administration, characterized in that it contains an effective amount of at least one compound inhibiting the enzyme 3.beta. -hydroxysteroid dehydrogenase. This composition is intended for the treatment of certain effects of chronological aging and of photo-aging of the skin.
Patent•
05 Sep 2002
TL;DR: There are compounds of the formula (I) which are useful as inhibitors of Type 3 17beta-Hydroxysteroid Dehydrogenase and pharmaceutical compositions containing said compounds and their use for the treatment or prevention of androgen dependent diseases.
Abstract: There are disclosed compounds of the formula (I): prodrugs thereof, or pharmaceutically acceptable salts of the compounds or of said prodrugs which are useful as inhibitors of Type 3 17beta-Hydroxysteroid Dehydrogenase. Also disclosed are pharmaceutical compositions containing said compounds and their use for the treatment or prevention of androgen dependent diseases.
18 Feb 2002
Journal Article•