Inhibitors of catechol O-methyl transferase and their use in the treatment of psychotic disorders

摘要

The present invention relates to 4-pyridinone compounds which are inhibitors of catechol O-methyltransferase (COMT), and are useful in the treatment and prevention of neurological and psychiatric disorders and diseases in which COMT enzyme is involved. The present invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which COMT is involved.

主权项

1. A compound of structural formula I: including tautomers or pharmaceutically acceptable salts and individual enantiomers and diastereomers thereof wherein: Y represents C2-6 alkynyl, CH2C5-10 heterocyclyl, (CH2)2C5-10 heterocyclyl, (CH2)3C5-10 heterocyclyl, (CH2)4C5-10 heterocyclyl, (CH2)5C5-10 heterocyclyl, (CH2)nC6-10 aryl, said alkynyl, heterocyclyl and aryl substituted with 1 to 3 groups of Ra; X1, and R1 independently represent hydrogen, halo, CN, C1-6 alkyl, C2-6 alkynyl, (CH2)nC6-10 aryl, (CH2)nC5-10 heterocyclyl, said alkyl, heterocyclyl, and aryl optionally substituted with 1 to 3 groups of Ra; X represents hydrogen, halo, CN, C1-6 alkyl, C2-6 alkynyl, (CH2)nC6-10 aryl, said alkyl and aryl optionally substituted with 1 to 3 groups of Ra; R2 represents H, OH, C1-6 alkyl, N(CH3)2, (CH2)nC3-10 cycloalkyl, (CH2)nC5-10 heterocyclyl, (CH2)nC6-10 aryl, said aryl and heterocyclyl optionally substituted with 1 to 3 groups of Ra; Ra represents C1-6 alkyl, halogen, hydroxyl, C2-4alkynyl, (CH2)nCF3, OCHF2, OCF3, C3-6 cycloalkyl, NR2C(O)R2, C(O)N(R2)2, C(R2)2OR2, C(O)R2, NO2, CN, N(R2)2, (CH2)nC(O)OR2, SO2R2, NHSO2R2, OR2, (CH2)nC5-10 heterocyclyl, C(O)(CH2)nC5-10 heterocyclyl, (CH2)nC6-10 aryl, or C(O)(CH2)nC6-10 aryl, said alkyl, alkynyl, cycloalkyl, heterocyclyl and aryl optionally substituted with 1 to 3 groups of Rb; Rb represents C1-6 alkyl, halogen, CHF2, OCHF2, —O—, N(R2)2, CH2OH, (CH2)nC6-10 aryl, (CH2)nC5-10 heterocyclyl, OR2, C3-6cycloalkyl, (CH2)nCF3, or CN; and n represents 0 to 5.