PYRROLIDINE ARYL-ETHER AS NK3 RECEPTOR ANTAGONISTS.

摘要

The invention relates to a compound of general formula (I) wherein is aryl or a five or six membered heteroaryl; is a six to nine membered mono or bi-heterocyclic group, wherein X may be a carbon atom, SO₂ or a further hetero atom, selected from the group consisting of N or O; if X is a carbon atom, O, SO₂ or unsubstituted N, then R₁ is hydrogen, hydroxy, cyano, -(CH ₂ ) _q -OH, -(CH ₂ ) _q -NRR', -(CH ₂ )_q-CN, lower alkyl, -S(O)₂ -lower alkyl, -NR-S(O) ₂ -lower alkyl, -C(O)-lower alkyl, -NR-C(O)-lower alkyl, phenyl, or is a heterocyclic group selected from piperidinyl-₂-one; if X is a N-atom, substituted by R ₁, then R ₁ is hydrogen, -(CH ₂ ) _q -OH, -(CH ₂ ) _q -NRR', -(CH ₂ )_q-CN, lower alkyl, -S(O) ₂ - lower alkyl, aryl or a five or six membered heteroaryl or -C(O)-lower alkyl, provided that q is 2 or 3. R/R' are independently from each other hydrogen or lower alkyl; R ₂ is hydrogen, halogen, lower alkyl, cyano, lower alkoxy substituted by halogen, lower alkyl substituted by halogen or is a five or six membered heteroaryl; R ₃ is hydrogen or halogen; R ₄ is hydrogen or lower alkyl; n is 1 or 2; in case n is 2, R ₁ may be the same or different; o is 1 or 2; in case o is 2, R₂ may be the same or different; p is 1 or 2; in case p is 2, R ₃ may be the same or different; _q is 1, 2 or 3; s is 0, 1, 2, 3 or 4; or to a pharmaceutically active salt thereof, including all stereoisomeric forms, individual diastereoisomers and enantiomers of the compound of formula (I) as well as racemic and non-racemic mixtures thereof. It has been found that the present compounds are high potential NK-3 receptor antagonists for the treatment of depression, pain, psychosis, Parkinson's disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD).