Novel Lactam Derivatives

Abstract

The invention thus provides compounds of formula (I) a salt, or solvate thereof.

1 . A compound of formula (I) comprising:  
     
       
         
         
             
             
         
       
     
     a salt or solvate thereof, wherein 
 M is a group selected from the group consisting of O, S, C═O, NH and CH 2 ;  
 L is a 2- or 3-membered alkylene chain;  
 wherein together M-L may be optionally substituted by at least one moiety selected from the group consisting of methyl, ethyl, hydroxy and C 1-3  alkoxy;  
 R 1  and R 2  are each independently selected from the group consisting of hydrogen, C 1-6  straight or branched alkyl which may be optionally substituted by phenyl, and C 3-6  cycloalkyl optionally substituted by one or more C 1-6  alkyl groups;  
 each R 6  is the same or different and is independently selected from the group consisting of hydroxy, C 1-2 alkyl, C 1-3 alkoxy, halo, C 2-3 alkenyl, benzyl, and —C(R a )NOR b , wherein R a  and R b  are each independently selected from the group consisting of hydrogen, methyl, methoxymethyl, methoxymethoxy, and methoxyethoxy and n is 1, 2, 3, or 4;  
 QY is a bicyclic fused heterocyclic ring wherein Q and Y are each one ring of said bicyclic fused heterocyclic group, wherein said Y ring contains from 1 to 3 nitrogens and is bound to the phenyl ring of formula (I) via a nitrogen atom, and said Q ring is a 5- or 6-membered aryl or heterocyclic ring having a group ZR 3 ; Z is bound to the Q ring;  
 Z is selected from the group consisting of a direct bond, NH, NCH 3 , O, S, and CH 2 ; and  
 R 3  is a group selected from the group consisting of aryl, alk-2-en-1-yl, cycloalkyl and cycloalk-2-en-1-yl and wherein said aryl, alk-2-en-1-yl, cycloalkyl, and cycloalk-2-en-1-yl are optionally substituted from 1 to 3 times with a subsituent selected from the group consisting of C 1-3  alkyl, halo, amino, alkylamino, dialkylamino, hydroxy, C 1-3  alkoxy, cyano, trifluoromethyl, and methylthio groups.  
 
   
   
       2 . The compound of  claim 1  wherein M is O or CH 2 .  
   
   
       3 . The compound of  claim 2  wherein M is O.  
   
   
       4 . The compound of  claim 1  wherein L is (CH 2 ) 2 .  
   
   
       5 . The compound of  claim 1  wherein L is linked to the phenyl ring of formula (I) via an R 6  substituent located in the ortho position relative to the group M to form a bicyclic structure.  
   
   
       6 . The compound of  claim 5  wherein said bicyclic structure is selected from the group consisting of 1,4-benzodioxan, benzopyran, 1,2-dihydrobenzopyran, 1,2,3,4-tetrahydronaphthalene, and 1,2-dihydronaphthalene.  
   
   
       7 . The compound of  claim 1  wherein (i) R 1  and R 2  independently are a C 1-6  alkyl.  
   
   
       8 . The compound of  claim 7  wherein R 1  and R 2  independently are methyl and isopropyl.  
   
   
       9 . The compound of  claim 1  wherein QY is a 5,5; 5,6; 6,5; or 6,6 bicyclic fused heterocyclic ring.  
   
   
       10 . The compound of  claim 1  wherein QY is a group selected from isoindole-1,3-dione, 2,3-dihydro-isoindole-1-one, 3-H-benzo(1,2,3)triazin-4-one, 3-H-quinazolin-4-one, 1-H-quinazoline-2,4-dione, 3-H-thieno[2,3-d]-1-triazine-4-one, 3-H-thieno[2,3d]pyrimidin-4-one, 3-H-thieno[3,2-d]pyrimidin-4-one, 2-thioxo-2,3-dihydro-1-H-thieno[3,2-d]pyrimidine-4-one, 2-methylthio-3H-thieno[3,2-d]pyrimidin-4-one.  
   
   
       11 . The compound of  claim 1  wherein at least one R 6  is in the ortho position with respect to the group M.  
   
   
       12 . The compound of  claim 1  wherein R 6  is methoxy.  
   
   
       13 . The compound of  claim 1  wherein Z is a bond or an oxygen atom.  
   
   
       14 . The compound of  claim 1  wherein R 3  is selected from the group consisting of (i) phenyl which is optionally substituted by halogen, hydroxy, C 1-3  alkoxy, C 1-4  alkyl, cyano or trifluoromethyl, (ii) C 5-7  cycloakyl, (iii) C 5-7  2-cycloakenyl, and (iv) C 3-6  alk-2-en-1-yl.  
   
   
       15 . The compound of  claim 1  wherein R 3  represents phenyl.  
   
   
       16 . A pharmaceutical composition comprising a compound of  claim 1  or a physiologically acceptable salt or solvate thereof and one or more pharmaceutically acceptable carriers or excipients.  
   
   
       17 . A method of treating one or more Disorders which comprises administering to a mammal suffering from one or more of the Disorders an effective amount of a compound of  claim 1  or a physiologically acceptable salt or solvate thereof, wherein said Disorders are selected from the group consisting of obesity, diabetes, depression, schizophrenia, sleep disorder, and anxiety.  
   
   
       18 . The method of  claim 17  wherein said mammal is a human.