Arylalkene derivatives and use thereof as selective estrogen receptor modulators

A pharmaceutical composition, comprising a compound of formula I:

• wherein
• R1 is
• wherein the 5-membered ring is optionally and independently substituted with one or more groups selected from the group consisting of halogen, —OH, —SH, alkyl, halogenated alkyl and alkoxy;
• and
• R0 is alkyl;
• wherein R0 is optionally and independently substituted with one or more groups selected from the group consisting of halogen, —OH, —NH2, and alkoxy;
• ring A and ring B are each independently selected from aryl and pyridinyl;
• R2 is selected from halogen, —OH, alkyl, alkoxy, alkylsulfanyl, monoalkylamino and dialkylamino, wherein the alkyl, alkoxy, alkylsulfanyl, monoalkylamino and dialkylamino groups are each optionally and independently substituted substituted with —NR4R5, wherein R4 and R5 are each independently hydrogen, alkyl or cycloalkyl, or R4 and R5, together with the nitrogen atom to which they attach, form a heterocyclyl which is optionally substituted with alkyl;
• and
• R3 is selected from the group consisting of halogen, —OH, —NH2, —CN, —SH, —COOH, alkyl, cycloalkyl, alkoxy, alkylsulfanyl, monoalkylamino, and dialkylamino, wherein the alkyl, cycloalkyl, alkoxy, alkylsulfanyl, monoalkylamino, and dialkylamino are each optionally substituted with —OH heterocyclyl or NR4R5, wherein R4 and R5 are each independently hydrogen, alkyl or cycloalkyl, or R4 and R5, together with the nitrogen atom to which they attach, form a heterocyclyl which is optionally substituted with alkyl;
• m and n are the number of groups R2 on ring A and the number of groups R3 on ring B, respectively, and m is selected from 1, 2 or 3 and n is selected from 0, 1, 2 or 3,
• or a pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer or prodrug thereof.

A method for treating estrogen-dependent diseases and conditions in humans, which method comprises administering to a human in need thereof, a therapeutically effective amount of a compound of formula I:

• wherein
• R1 is
• wherein the 5-membered ring is optionally and independently substituted with one or more groups selected from the group consisting of halogen, —OH, —SH, alkyl, halogenated alkyl and alkoxy;
• and
• R0 is alkyl;
• wherein R0 is optionally and independently substituted with one or more groups selected from the group consisting of halogen, —OH, —NH2, and alkoxy;
• ring A and ring B are each independently selected from aryl and pyridinyl;
• R2 is selected from halogen, —OH, alkyl, alkoxy, alkylsulfanyl, monoalkylamino and dialkylamino, wherein the alkyl, alkoxy, alkylsulfanyl, monoalkylamino and dialkylamino groups are each optionally and independently substituted substituted with —NR4R5, wherein R4 and R5 are each independently hydrogen, alkyl or cycloalkyl, or R4 and R5, together with the nitrogen atom to which they attach, form a heterocyclyl which is optionally substituted with alkyl;
• and
• R3 is selected from the group consisting of halogen, —OH, —NH2, —CN, —SH, —COOH, alkyl, cycloalkyl, alkoxy, alkylsulfanyl, monoalkylamino, and dialkylamino, wherein the alkyl, cycloalkyl, alkoxy, alkylsulfanyl, monoalkylamino, and dialkylamino are each optionally substituted with —OH or —NR4R5, wherein R4 and R5 are each independently hydrogen, alkyl or cycloalkyl, or R4 and R5, together with the nitrogen atom to which they attach, form a heterocyclyl which is optionally substituted with alkyl;
• m and n are the number of groups R2 on ring A and the number of groups R3 on ring B, respectively, and m is selected from 1, 2 or 3 and n is selected from 0, 1, 2 or 3,
• or a pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer or prodrug thereof;
• wherein said estrogen-dependent diseases and conditions are selected from the group consisting of menopausal disorders, or postmenopausal disorders, vasomotor symptoms, urogenital atrophy, vulvar vaginal atrophy, atrophic vaginitis, endometriosis, female sexual dysfunction, depression, diabetes, bone demineralization, and osteoporosis.