Novel substituted thiophenepyrimidinone derivatives as inhibitors of 17beta-hydroxysteroid dehydrogenase

A hydroxyl and substituent technology, applied in the field of thienyl pyrimidone derivatives, can solve the problems of membrane permeability difficulties and insolubility

CN101087793AInactive Publication Date: 2007-12-12SOLVAY PHARMA GMBH
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Patent Information

Authority / Receiving Office
CN · China
Current Assignee / Owner
Publication Date
2007-12-12
Estimated Expiration
Not applicable · inactive patent

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Abstract

This invention relates to novel substituted thiophenepyrimidinone derivatives and their use in therapy, especially for use in the treatment and / or prevention of a steroid hormone dependent diseases or disorder, such as steroid hormone dependent diseases or disorders requiring inhibition of 17beta-hydroxysteroid dehydrogenase enzymes.
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Description

field of invention

[0001] The present invention relates to novel substituted compounds representing inhibitors of 17β-hydroxysteroid dehydrogenase, preferably type 1 (17β-HSD1), type 2 (17β-HSD2) or type 3 (17β-HSD3) 17β-hydroxysteroid dehydrogenase The thienopyrimidinone derivatives, their salts, pharmaceutical preparations containing these compounds and the preparation methods of these compounds. Furthermore, the present invention also relates to the therapeutic use of said benzothienone derivatives, in particular their use in the treatment or prevention of steroid hormone-dependent diseases or conditions, for example where inhibition of 17β-hydroxysteroid dehydrogenase, in particular type I 17β - HSD enzyme and / or use in steroid hormone-dependent diseases or conditions requiring regulation of endogenous 17[beta]-estradiol and / or testosterone concentrations. Background of the invention

[0002] The publications and other materials used herein to illustrate the background ...

Examples

Embodiment

[0382] In order to more fully illustrate the nature of the invention and the mode of carrying it out, the following examples are provided but should not be construed as limiting.

[0383] Preparation of the following No.1 to No.17 compounds falling within the scope of general formula (I):

[0384] Compound No.1: 3-Benzyl-5-methyl-2-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydro-3H-benzo[4,5 ]thieno[2,3-d]pyrimidin-4-one

[0385]

[0386] 2-Amino-4-methyl-4,5,6,7-tetrahydro-benzo[b]-thiophene-3-carboxylic acid ethyl ester (26.6mmol, 100mol-%) and N-benzyl-3, 4,5-Trimethoxy-benzamide (34.6 mmol, 130 mol-%) was dissolved in anhydrous 1,2-dichloroethane. Cool the reaction mixture with an ice-salt bath, add POCl 3 (1.7ml, 24.6mmol, 130mol-%). The reaction mixture was refluxed for 24 hours. Add POCl twice during reflux 3 (340 μl). The reaction mixture was poured into ice water, and after neutralization with sodium acetate, the product was extracted into dichloromethane. The ...