Substituted asymmetric ureas as modulators of ghrelin receptor activity

Abstract

or pharmaceutically acceptable salts thereof.

1 . A compound of Formula I: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 a dashed line indicates an optional bond; 
 X is CH or N; 
 Z is NR 9 , CR 10 R 11 , or 0; 
 R 1  is H, C 1-6  alkyl, benzyl, OH, or C 1-6  alkoxy, wherein said C 1-6  alkyl, benzyl, or C 1-6  alkoxy is optionally substituted with 1-3 substituents selected from halo, OH, C 1-6  alkyl, C 1-6  alkoxy, C 1-6  hydroxyalkyl, CO(C 1-6  alkyl), CHO, CO 2 H, CO 2 (C 1-6  alkyl), and C 1-6  haloalkyl; 
 R 2  is H or C 1-6  alkyl; 
 R 3  and R 4  are each, independently, H, CN, halo, CHO, or CO 2 H, or optionally substituted C 1-6  alkyl, C 1-6  hydroxyalkyl, C 1-6  alkylcycloalkyl, C 1-6  haloalkyl, C 1-6  alkoxy, CO(C 1-6  alkyl), CO 2 (C 1-6  alkyl), or CONR 12 R 13 ; 
 or R 3  and R 4  taken together with the C atom to which they are attached form a 3-6-membered ring; 
 R 5  is halo, CN, CHO, CO 2 H, CO(C 1-6  alkyl), CO 2 (C 1-6  alkyl), NR 14 R 15 , NHCONR 14 R 1 , CONR 14 R 15 , C 1-6  alkyl, C 1-6  alkoxy, C 1-6  haloalkyl, C 1-6  hydroxyalkyl, C 2-6  alkenyl, C 2-6  alkynyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl, wherein said CO(C 1-6  alkyl), CO 2 (C 1-6  alkyl), NR 14 R 15 , NHCONR 14 R 15 , CONR 14 R 15 , C 1-6  alkyl, C 1-6  alkoxy, C 1-6  haloalkyl, C 1-6  hydroxyalkyl, C 2-6  alkenyl, C 2-6  alkynyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl is optionally substituted with 1-3 substituents selected from halo, CN, OH, NO 2 , Si(CH 3 ) 4 , CHO, and CO 2 H, or optionally substituted CO(C 1-6  alkyl), CO 2 (C 1-6  alkyl), NR 14 R 15 , NHCONR 14 R 15 , CONR 14 R 15 , CH═NOH, C 1-6  alkyl, C 1-6  alkoxy, C 1-6  haloalkyl, C 1-6  hydroxyalkyl, C 2-6  alkenyl, C 2-6  alkynyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl; 
 R 6  is absent or H; 
 R 7  is H, CN, or halo; 
 or two R 7  can be taken together with the atoms to which they are attached form a 5-6-memebered ring; 
 or R 5  and R 7  taken together with the atoms to which they are attached form an optionally substituted 5-6-membered ring; 
 R 8  is H or C 1-6  alkyl; 
 R 9  is H, C 1-6  alkyl, CO(C 1-6  alkyl), CHO, CO 2 H, or CO 2 (C 1-6  alkyl); 
 R 10  and R 11  are each, independently, H, C 1-6  alkyl, or halo; 
 R 12  and R 13  are each, independently, H or C 1-6  alkyl; 
 R 14  and R 15  are each, independently H, C 1-6  alkyl, CO(C 1-6  alkyl), CO(heteroaryl), heteroaryl, or cycloalkyl; 
 r is 1 or 2; 
 s is 0-4; and 
 n is 0-3. 
 
     
     
         2 - 51 . (canceled) 
     
     
         52 . A method of modulating ghrelin receptor activity in a human subject comprising administering to said subject an effective amount of a compound of  claim 1 . 
     
     
         53 . A method of treating a disease associated with expression or activity of a ghrelin receptor in a human subject comprising administering to said subject an effective amount of a compound of  claim 1 . 
     
     
         54 - 61 . (canceled)