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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 2 AbstractLowering local estradiol concentration by inhibition of the estradiol-synthesizing enzyme 17β-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) has been proposed as a promising new therapeutic option to treat estrogen dependent diseases like endometriosis and breast cancer. Based on a molecular modelling approach we designed and synthesized novel C15-substituted estrone derivatives. Subsequent biological evaluation revealed that potent inhibitors of human 17beta-HSD1 can be identified in this compound class. The best, compound 21, inhibited recombinant human 17beta-HSD1 with an IC50 of 10 nM and had no effect on the activity of recombinant human 17β-hydroxysteroid dehydrogenase type 2 (17beta-HSD2), the enzyme catalyzing estradiol inactivation. These properties were retained in a cell-based enzyme activity assays. In spite of the estrogen backbone compound 21 did not show estrogen receptor mediated effects in vitro or in vivo.In conclusion, estrone C15 derivative compound 21 can be regarded as a promising lead compound for further development as a 17beta-HSD1 inhibitor.

Reactions between distibanes of the type Sb 2 R 4 and trialkylalanes and -gallanes R′ 3 M in 1:2 stoichiometry yield eight bisadducts of the type [Sb 2 R 4 ][MR′ 3 ] 2 (R ) Me, R′ ) t-Bu, M ) Al 1, Ga 2; R ) Et, M ) Al, R′ ) Me 3, Et 4, t-Bu 5; M ) Ga, R′ ) Me 6, Et 7, t-Bu 8), which were characterized by multinuclear NMR studies and elemental analysis. In addition, 1, 2, 5, and 8 are the first structurally characterized neutral main group Lewis acid-distibane bisadducts. 1-8 are unstable in solution toward the formation of heterocycles of the type [R 2 SbMR′ 2 ] x . [Me 2 SbGa(t-Bu) 2 ] 3 (9) and [Et 2 SbGa(t-Bu) 2 ] 2 (10) have been isolated and their solid state structures determined by single-crystal X-ray diffraction.