Novel 17.beta.-hydroxysteroid dehydrogenase type i inhibitors

C - Chemistry – Metallurgy – 07 – J

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Details

C07J 1/00 (2006.01) A61K 31/565 (2006.01)

Patent

CA 2545704

The present invention relates to novel 3, 15 substituted estrone derivatives which represent inhibitory compounds of the 17.beta.-hydroxysteroid dehydrogenase type I (17.beta.-HSD1), to their salts, to pharmaceutical preparations containing these compounds and to processes for the preparation of these compounds. Furthermore, the invention concerns the therapeutic use of said novel 3, 15 substituted estrone derivatives, particularly their use in the treatment or prevention of steroid hor~mone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of 17.beta.-hydroxysteroid dehydrogenase type I enzymes and/or requiring the lowering of the endogenous 17.beta.-estradiol concentration. In addition, the present invention relates to the general use of selective 17.beta.-hydroxysteroid dehydrogenase type 1 inhibitors which possess in addition no or only pure antagonistic binding affinities to the estrogen receptor for the treatment and prevention of benign gynaecological disorders, in particular endometriosis.

La présente invention concerne de nouveaux dérivés d'estrone substitués en positions 3 et 15, lesquels constituent des composés inhibiteurs de la 17.beta.-hydroxystéroïde déshydrogénase de type I (17.beta.-HSD1), leurs sels, des préparations pharmaceutiques contenant ces composés, ainsi que des procédés de préparation de ces composés. En outre, l'invention concerne l'utilisation thérapeutique de ces nouveaux dérivés d'estrone substitués en position 3 et 15, en particulier leur utilisation dans le traitement de la prévention de maladies ou de troubles dépendant des hormones stéroïdes, telles que les maladies ou troubles dépendant des hormones stéroïdes nécessitant l'inhibition de l'enzyme 17.beta.-hydroxystéroïde déshydrogénase de type I et/ou nécessitant l'abaissement de la concentration de 17.beta.-estradiol endogène. De plus, l'invention concerne l'utilisation générale d'inhibiteurs sélectifs de la 17.beta.-hydroxystéroïde déshydrogénase de type I qui, de surcroît, ne présentent pas d'affinité ou seulement une affinité purement antagoniste vis-à-vis du récepteur d'oestrogène, pour le traitement et la prévention de troubles gynécologiques bénins, en particulier de l'endométriose.

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