Spirohydantoin compounds and their use as selective androgen receptor modulators

摘要

The present invention relates to a compound of formula (I-1) in free form or in pharmaceutically acceptable salt form;;in which the substituents are as defined in the specification; to its preparation, to its use as a medicament and to medicaments comprising it. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

主权项

1. A compound of formula (I-1) in free form or in pharmaceutically acceptable salt formin which
X is O or N(R8); Y is CH2, C(═NH), C(═O), C(═S) or C(H)(OR9); Z is O or S; R1 is C1-C3alkyl; R2 is halogen; A is selected from:
a 4-membered saturated ring which contains zero or one O atom, which ring is unsubstituted or substituted once or twice with RA; ora 5-membered saturated or unsaturated non-aromatic ring which contains zero or one O atom, which ring is unsubstituted or substituted once or twice with RA; RA is, for each occurrence, independently selected from hydroxy, halogen, C1-C3alkyl, hydroxyC1-C3alkyl, or two RA at the same carbon atom form an oxo group R8 is C1-C6alkyl optionally substituted with cyano, hydroxy-C1-C6alkyl, haloC1-C6alkyl, C1-C6alkoxy-C1-C6alkyl wherein the alkoxy portion is optionally substituted with cyano or halogen or R8 is —(CH2)n—B; n is 1 or 2; B is a 5- to 6-membered aromatic or non-aromatic ring which comprises 0, 1, 2, 3, or 4 heteroatoms selected from N, O or S, which ring is unsubstituted or substituted once or twice with RB; RB is, for each occurrence, independently selected from halo, cyano, C1-C6alkyl; and R9 is hydrogen or C1-C3alkyl.