Synthesis of estrogen sulfamates: Compounds with a novel endocrinological profile

Schwarz, S.; Thieme, Ina; Richter, Margit; Undeutsch, B.; Henkel, H.; Elger, W.

doi:10.1016/s0039-128x(96)00200-0

Cited by 35 publications

(27 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Selective sulfamoylation of compound 3 at the 3b-OH was achieved in good yield (73% of 4) following an improved procedure that used 2,6-di-t-butyl-4-methylpyridine (DBMP) as base in CH 2 Cl 2 . 28 This procedure was used for the synthesis of all the other sulfamoylated derivatives in both steroidal series, except 6. For the latter, sodium hydride and ethylene glycol dimethyl ether were respectively the base and solvent.…”

Section: Chemical Synthesis Of Compounds 3-13mentioning

confidence: 99%

3β-Sulfamate Derivatives of C19 and C21 Steroids Bearing a t -Butylbenzyl or a Benzyl Group: Synthesis and Evaluation as Non-estrogenic and Non-androgenic Steroid Sulfatase Inhibitors

Ciobanu

Boivin

Luu‐The

et al. 2003

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

A series of C19 and C21 steroids bearing one or two inhibiting groups (3b-sulfamate and 17a-or 20(S)-tbutylbenzyl or benzyl) were synthesized and tested for inhibition of steroid sulfatase activity. When only a sulfamate group was added to dehydroepiandrosterone, androst-5-ene-3b,17b-diol, pregnenolone and 20-hydroxy-pregnenolone, no significant inhibition of steroid sulfatase occurred at concentrations of 0.3 and 3 mM. With only a t-butylbenzyl or a benzyl group, a stronger steroid sulfatase inhibition was obtained in the androst-5-ene than in the pregn-5-ene series. Comparative results from the screening tests and the IC 50 values have shown that the effect of a sulfamate moiety as a second inhibiting group can be combined to the t-butylbenzyl or benzyl effect in the C19 and C21 steroid series. The 3b-sulfamoyloxy-17a-t-butylbenzyl-5-androsten-17b-ol (10) was thus found to be the most active compound with IC 50 values of 46 6 8 and 14 6 1 nM; respectively for the transformations of E 1 S to E 1 and DHEAS to DHEA. The IC 50 values of compound 10 are similar to that of 17a-t-butylbenzyl-estradiol, which was previously reported by our group as a good steroid sulfatase reversible inhibitor, but remains higher than that of the potent inactivators estrone-3-O-sulfamate (EMATE) and 17a-t-butylbenzyl-EMATE. However, contrary to these two latter inhibitors, compound 10 did not induce any proliferative effect on estrogensensitive ZR-75-1 cells nor on androgen-sensitive Shionogi cells at concentrations tested, suggesting that this steroid sulfatase inhibitor is non estrogenic and non androgenic.

show abstract

Section: Chemical Synthesis Of Compounds 3-13mentioning

confidence: 99%

3β-Sulfamate Derivatives of C19 and C21 Steroids Bearing a t -Butylbenzyl or a Benzyl Group: Synthesis and Evaluation as Non-estrogenic and Non-androgenic Steroid Sulfatase Inhibitors

Ciobanu

Boivin

Luu‐The

et al. 2003

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

show abstract

“…Next, the sulfamate derivative 3 was obtained in over 95 % yield from the phenol 2 by reaction with sulfamoyl chloride and DBMP as base. [40,47] Initially we intended to use compound 3 as our solid-phase precursor (approach I), because the reduction of an azide to the corresponding amine on solid phase is known in the literature. [48] Indeed, after successful coupling of compound 3 to trityl chloride resin, the reduction of the azide group with tin reagent was completed, and confirmed by IR analysis of a resin sample.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Libraries of 16β‐Aminopropyl Estradiol Derivatives for Targeting Two Key Steroidogenic Enzymes

Ciobanu¹,

Poirier²

2006

ChemMedChem

View full text Add to dashboard Cite

Two libraries, each consisting of 48 16beta-aminopropyl estradiol derivatives, phenols and sulfamates, respectively, were synthesized by solid-phase parallel chemistry through a seven-step reaction sequence. Following the attachment of a C18-steroid sulfamate precursor on a trityl chloride resin, diversity elements were first introduced on the 16beta-aminopropyl chain of the steroid by acylation reactions with eight Fmoc-amino acids. After deprotection, the free amine function of the resulting compounds was reacted with six carboxylic acids for the introduction of a second diversity level. The two variants employed for the cleavage of compounds from the solid support, acidic and nucleophilic, allowed the corresponding libraries of sulfamate and phenol derivatives in yields of 8-50 % and 13-58 % to be obtained with an average HPLC purity of 94 % and 91 %, respectively. Potent steroid sulfatase inhibitors and interesting SAR results were generated from the screening of the sulfamate library. Furthermore, moderate inhibitors of type 1 17beta-HSD resulted from the partial screening of phenol library. Thus, these two categories of compounds were synthesized to rapidly identify potential inhibitors of steroid biosynthesis for the hormonal therapy of estrogen-dependent diseases, and also to demonstrate the versatility and efficiency of the recently developed sulfamate linker.

show abstract

“…A solution of the hydroxy-2-phenylindole (2.77 mmol) in dry DMF (15 ml) was cooled to 10-15 • C. Sulfamoyl chloride [34], 13.9 mmol per hydroxy group, was added in portions. After the addition, the mixture was stirred for 12 h under N 2 .…”

Section: General Procedures For the Preparation Of The Sulfamatesmentioning

confidence: 99%

2-Phenylindole sulfamates: inhibitors of steroid sulfatase with antiproliferative activity in MCF-7 breast cancer cells

Walter

Liebl

Angerer

2004

The Journal of Steroid Biochemistry and Molecular Biology

View full text Add to dashboard Cite

Synthesis of estrogen sulfamates: Compounds with a novel endocrinological profile

Cited by 35 publications

References 18 publications

3β-Sulfamate Derivatives of C19 and C21 Steroids Bearing a t -Butylbenzyl or a Benzyl Group: Synthesis and Evaluation as Non-estrogenic and Non-androgenic Steroid Sulfatase Inhibitors

3β-Sulfamate Derivatives of C19 and C21 Steroids Bearing a t -Butylbenzyl or a Benzyl Group: Synthesis and Evaluation as Non-estrogenic and Non-androgenic Steroid Sulfatase Inhibitors

Synthesis of Libraries of 16β‐Aminopropyl Estradiol Derivatives for Targeting Two Key Steroidogenic Enzymes

2-Phenylindole sulfamates: inhibitors of steroid sulfatase with antiproliferative activity in MCF-7 breast cancer cells

Contact Info

Product

Resources

About