| 摘要 |
The present invention relates to a series of substituted compounds having the general formula (I), including their stereoisomers and/or their pharmaceutically acceptable salts, wherein R1, R2, R3, R4, R5, and R6 are as defined herein. This invention also relates to methods of making these compounds including intermediates. The compounds of this invention are effective at the kappa (κ) opioid receptor (KOR) site. Therefore, the compounds of this invention are useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of central nervous system disorders (CNS), including but not limited to acute and chronic pain, and associated disorders, particularly functioning peripherally at the CNS.; |
| 主权项 |
1. A compound of formula (I), stereoisomers thereof or pharmaceutically acceptable salts thereof; wherein,
R1 represents hydrogen, alkyl, haloalkyl or —(CH2)m-cycloalkyl;R2 represents (1) cycloalkyl (2) an group selected from heterocyclyl, heteroaryl, or aryl, wherein such group is optionally substituted with 1 to 3 substituents selected independently from cyano, hydroxyl, alkyl, alkynyl, alkoxy, halogen, haloalkyl, haloalkoxy, —COORa, —CONRaRf, —O—(CH2)n—R7 or R11;R3 is an optionally substituted group selected from Optional substituent on R3, in each occurrence, independently selected from halogen, alkyl or haloalkyl;R4 is selected from hydrogen, hydroxyl, halogen, alkyl, alkoxy, or haloalkyl;R5 and R6, each are independently selected from hydrogen or alkyl;R7 is selected from cyano, tetrazolyl, —COORa, —CONRaRf or R8, in each occurrence, is independently selected from hydrogen, halogen, alkyl or —(CH2)q—R9;R9is —COORa or R10 is selected from hydrogen, cyano, —COORa, —CONRaRf or tetrazolyl;R11 is selected from (1) (C3-C6)cycloalkyl, benzyl,or (2) 5-6 membered heteroaryl optionally substituted with 1 to 2 substituents selected independently from alkyl, haloalkyl, haloalkoxy or —(CH2)m—(C3-C6)cycloalkyl;
Ra and Rb, in each occurrence, independently selected from hydrogen, alkyl, heterocyclyl or heteroaryl;Rb, in each occurrence, independently selected from hydrogen, alkyl or alkoxy,Ra, in each occurrence, independently selected from hydrogen, alkyl, haloalkyl or —S(O)2-alkyl;Rf in each occurrence, independently selected from hydrogen or alkyl;m is selected from 0, 1, 2, 3 or 4;n and q, each independently selected from 1 or 2;provided that when R2 is phenyl optionally substituted with alkyl, alkoxy or halogen, R1 is alkyl and one of R5 and R6 represents hydrogen, then R3 does not represent the following ringswherein Ri, in each occurrence, represents hydrogen or alkyl. |
