SUBSTITUTED B-AMINO ACID DERIVATIVES AS CXCR3 RECEPTOR ANTAGONISTS

摘要

The present invention relates to compounds of formula 1;;that are useful for the preventive and/or therapeutic treatment of diseases caused by abnormal activation of CXCR3 chemokines. The invention relates furthermore to a process for the preparation of said compounds, to pharmaceutical compositions containing said compounds and to novel intermediates used in the preparation of said compounds.

主权项

1. A compound of formula 1 wherein
R represents hydrogen, —C1-4 alkyl, —C3-8 cycloalkyl, —C1-4 halogenalkyl or halogenphenyl group;R′ represents hydrogen orR and R′ represent together with the carbon atom attached a C4 aliphatic ring; andR1 represents a group selected from the group consisting of wherein
A represents a direct bond or CH2, CH(CH3), C(CH3)2 or C(CH2)2 group;R2 represents Cl, Me or —CF3;R3 represents hydrogen, Cl or F;R4 represents hydrogen or a —C1-4 alkyl group;R5 represents a heteroaryl group selected from the group consisting of X represents O, S or CH2; Y represents hydrogen, halogen or a —C1-4 alkyl, —C1-4 alkoxy or —C1-4 hydroxyalkyl group; and Z represents a C1-4 aliphatic hydrocarbon bridge optionally containing one double bond, and/or one or more heteroatom selected from O, S, NH and N(CH3) or represents a C2-4 aliphatic hydrocarbon bridge optionally containing N fused with a C3-6 cycloalkyl ring optionally containing one or more double bonds or with a phenyl ring or represents a C1-4 aliphatic hydrocarbon bridge substituted with a spiro C3-6 cycloalkyl ring optionally containing one or more double bonds; or a pharmaceutically acceptable salt thereof, stereoisomer thereof or a pharmaceutically acceptable salt of the stereoisomer.