Compounds useful in therapy

Abstract

There is provided a compound of formula I, wherein A, D, R 1 , R 2 , R 3 , X and n have meanings given in the description, which are useful in the prophylaxis and in the treatment of diseases mediated by opiate receptors, such as pruritus.

1 . A compound of formula I,  
       
         
           
           
               
               
           
         
       
       wherein A represents a single bond, C 1-4  alkylene, C 2-4  alkenylene or C 2-4  alkynylene, which alkylene, alkenylene or alkynylene groups are optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, halo or OH; 
 D represents H, OH, CN, N(R 4 )(R 5 ), N(H)R 6 , C(O)OR 7 , C(O)R 8 , C(═NR 9a )R 8 , or C(═NOR 9b )R 8 ;  
 provided that when A represents C 2-4  alkenylene or C 2-4  alkynylene, and D represents OH, N(R 4 )(R 5 ) or N(H)R 6 , then D is not directly attached to an unsaturated carbon atom;  
 and provided that when A represents a single bond, then D does not represent H, OH, N(R 4 )(R 5 ) or N(H)R 6 ;  
 R 4  and R 5  independently represent H, C 1-6  alkyl, C 3-8  cycloalkyl, aryl, C 1-4  alkylphenyl, which latter four groups are optionally substituted by one or more substituents selected from nitro, halo, C 1-4  alkyl and C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms), or R 4  and R 5 , together with the N-atom to which they are attached, form a 4- to 7-membered heterocyclic ring, which ring optionally contains one or more additional heteroatoms selected from oxygen, nitrogen and sulfur and which ring is optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, OH, ═O, nitro, amino or and halo;  
 R 6  represents C(O)R 10a , C(O)OR 10b  or S(O) 2 R 10c ;  
 R 10a  to R 10c  independently represent C 1-4  alkyl, C 3-8  cycloalkyl, aryl, C 1-4  alkylphenyl (which four groups are all optionally substituted by or one or more substituents selected from nitro, halo, C 1-4  alkyl or C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms)), or R 10a  represents H;  
 R 7  and R 8  independently represent H, C 1-6  alkyl, C 3-8  cycloalkyl, aryl or C 1-4  alkylphenyl, which latter four groups are optionally substituted by one or more substituents selected from nitro, halo, C 1-4  alkyl or C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms);  
 R 9a  and R 9b  independently represent C 1-6  alkyl, C 3-8  cycloalkyl, aryl, C 1-4  alkylphenyl, which latter four groups are optionally substituted by one or more substituents selected from nitro, halo, C 1-4  alkyl or C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms), or R 9b  represents H;  
 R 1  and R 2  are each independently H or C 1-4  alkyl;  
 R 3  represents aryl (optionally substituted by one or more substituents selected from OH, nitro, halo, CN, CH 2 CN, CONH 2 , C 1-4  alkyl, C 1-4  alkoxy, C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms) and —N(R 11a )(R 11b )), C 1-10  alkyl, C 3-10  alkenyl or C 3-10  alkynyl wherein said alkyl, alkenyl or alkynyl groups are optionally substituted and/or terminated by one or more substituents selected from OR 11c , S(O) p R 11d , CN, halo, C 1-6  alkoxy carbonyl, C 2-6  alkanoyl, C 2-6  alkanoyloxy, C 3-8  cycloalkyl, C 4-9  cycloalkanoyl, N(R 12a )S(O) 2 R 13 , Het 1 , aryl, or adamantyl (which latter two groups are optionally substituted by one or more substituents selected from OH, nitro, amino, halo, CN, CH 2 CN, CONH 2 , C 1-4  alkyl, C, 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms)), or —W-A 1 -N(R 12b )(R 12c );  
 p is 0, 1 or 2;  
 W represents a single bond, C(O) or S(O) q ;  
 A 1  represents a single bond or C 1-10  alkylene;  
 provided that when both W and A 1  represent single bonds, then the group —N(R 12b )(R 12c ) is not directly attached to an unsaturated carbon atom;  
 q is 0, 1 or 2;  
 R 11a  to R 11d  each independently represent H, C 1-10  alkyl, C 3-10  alkenyl, C 3-10 alkynyl, C   3-8  cycloalkyl, C 1-4  alkylphenyl, aryl (which latter six groups are optionally substituted by or one or more substituents selected from OH, nitro, amino, halo, CN, CH 2 CN, CONH 2 , C 1-4  alkyl, C 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms)) or Het 2 ;  
 provided that R 11d  does not represent H when p represents 1 or 2;  
 R 12a  to R 12c  each independently represent H, C 1-10  alkyl, C 3-10  alkenyl, C 3-10  alkynyl, C 3-8  cycloalkyl, C 1-4  alkylphenyl, aryl (which latter six groups are optionally substituted by or one or more substituents selected from OH, nitro, amino, halo, CN, CH 2 CN, CONH 2 , C 14  alkyl, C 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms)), or Het 3 , or R 12b  and R 12c  together represent unbranched C 2-6  alkylene which alkylene group is optionally interrupted by O, S and/or an N(R 14 ) group and is optionally substituted by one or more C 1-4  alkyl groups;  
 R 13  represents C 1-6  alkyl, C 3-8  cycloalkyl, C 1-4  alkylphenyl or aryl, which four groups are optionally substituted by or one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, OH, nitro, amino or halo;  
 R 14  represents H, C 1-6  alkyl, C 3-8  cycloalkyl, A 2 -(C 3-8  cycloalkyl) or  
 A 2 -aryl;  
 A 2  represents C 1-6  alkylene;  
 Het 1 , Het 2  and Het 3  independently represent 3- to 8-membered heterocyclic groups, which groups contain at least one heteroatom selected from oxygen, sulfur and/or nitrogen, which groups are optionally fused to a benzene ring, and which groups are optionally substituted in the heterocyclic and/or fused benzene ring part by one or more substituents selected from OH, ═O, nitro, amino, halo, CN, aryl, C 1-4  alkyl, C 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms);  
 X is H, halo, C 1-4  alkyl or C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms);  
 n is 0, 1 or 2;  
 or pharmaceutically, or veterinarily, acceptable derivatives thereof.  
 
     
     
         2 . The compound as claimed in any one of claims  1 ,  21  or  22  wherein the group A-D is attached in the meta-position relative to the piperidine ring.  
     
     
         3 . The compound as claimed in any one of claims  1 ,  21  or  22  wherein R 1  represents C 1-2  alkyl.  
     
     
         4 . The compound as claimed in claims  1 ,  21  or  22  wherein R 2  represents H or C 1-2  alkyl.  
     
     
         5 . The compound as claimed in  claim 1  or  21  wherein R 3  represents saturated C 1-10  alkyl, optionally substituted by one or more substituents selected from OR 11c , CN, halo, C 2-4  alkanoyl, C 1-4  alkoxy carbonyl, N(R 12a )SO 2 R 13 , Het 1 , aryl (which latter group is optionally substituted by one or more substituents selected from OH, C 1-4  alkyl, C 1-4  alkoxy, C 2-5  alkanoyl, halo, nitro, amino, CN and CONH 2 ), and —W-A 1 -N(R  12b )(R 12c ).  
     
     
         6 . The compound as claimed in  claim 1  or  21  wherein R 11c  represents H, C 1-6  alkyl or aryl (which latter groups is optionally substituted by one or more substituents selected from OH, C 1-4  alkyl, C 1-4  alkoxy, C 2-5  alkanoyl, halo, nitro, amino, CN and CONH 2 ); R 2a  to R 12c  independently represent H, C  1-4  alkyl, C 1-2  alkylphenyl or aryl (which latter three groups are optionally substituted by one or more substituents selected from halo, C 1-4  alkyl and C 1-4  alkoxy); W represents C(O); and A 1  represents a single bond.  
     
     
         7 . The compound as claimed in  claim 1  or  21  wherein R 13  represents C 1-4  alkyl, C 1-2  alkylphenyl or aryl (which three groups are all optionally substituted by one or more substituents selected from halo, C 1-4  alkyl and C 1-4  alkoxy).  
     
     
         8 . The compound as claimed in any one of claims  1  or  22  wherein A represents a single bond, C 1-4  alkylene, C 2-4  alkenylene or C 2-4  alkynylene, which alkylene, alkenylene or alkynylene groups are optionally substituted by one or more OH or methyl groups.  
     
     
         9 . The compound as claimed in any one of claims  21  or  22  wherein D represents H, OH, CN, N(H)R 4 , N(H)C(O)R 10a , N(H)C(O)OR 10b , N(H)S(O) 2 R 10c , C(O)N(R 4 )(R 5 ), C(O)OR 7 , C(O)R 8  or C(═NOH)R 8 ; R 4  and R 5  independently represent H, C 1-4  alkyl or C 1-3  alkylphenyl, which latter two groups are optionally substituted by C 1-4  alkoxy; R 7  and R 8  independently represent H or C 1-4  alkyl; and/or R 10a  to R 10c  independently represent C 1-4  alkyl, which group is optionally substituted by one or more halo atoms.  
     
     
         10 . The compound as claimed in  claim 1  or  21  wherein R 3  represents saturated C 1-7  alkyl, optionally substituted by one or more substituents selected from CN, O—(C 1-6  alkyl), phenyl, and O-(phenyl).  
     
     
         11 . The A compound as claimed  claim 1  or  21  wherein R 3  represents saturated C 1-7  alkyl, optionally substituted by one or more substituents selected from CN, O—(C 1-6  alkyl), phenyl, and O-(phenyl).  
     
     
         12 . The compound as claimed in any one of claims  1 ,  21  or  22  wherein n represents 0 or 1.  
     
     
         13 . (canceled)  
     
     
         14 . (canceled)  
     
     
         15 . A pharmaceutical composition comprising a therapeutically effective amount of a compound as defined in any one of claims  1 ,  21  or  22  in admixture with a pharmaceutically, or a veterinarily, acceptable adjuvant, diluent or carrier.  
     
     
         16 . The pharmaceutical composition as claimed in  claim 15 , which is a veterinary composition.  
     
     
         17 . (canceled)  
     
     
         18 . (canceled)  
     
     
         19 . A method of treating or preventing a disease mediated by an opiate receptor, which comprises administering a therapeutically effective amount of a compound as defined in any one of claims  1  to a patient in need of such treatment, said compound having the formula:  
       
         
           
           
               
               
           
         
       
       wherein A represents a single bond, C 1-4  alkylene. C 2-4  alkenylene or C 2-4  alkynylene, which alkylene, alkenylene or alkynylene groups are optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, halo and OH; 
 D represents H, OH, CN, N(R 4 )(R 5 ), N(H)R 6 , C(O)N(R 4 )(R 5 ), C(O)OR 7 , C(O)R 8 , C(═NR 9a )R 8 , or C(═NOR 9b )R 8 ;  
 provided that when A represents C 2-4  alkenylene or C 2-4  alkynylene, and D represents OH, N(R 4 )(R 5 ) or N(H)R 6 , then D is not directly attached to an unsaturated carbon atom;  
 and provided that when A represents a single bond, then D does not represent H, OH, N(R 4 )(R 5 ) or N(H)R 6 ;  
 R 4  and R 5  independently represent H, C 1-6  alkyl, C 3-8  cycloalkyl, aryl, C 1-4  alkylphenyl, which latter four groups are optionally substituted by one or more substituents selected from nitro, halo, C 1-4  alkyl and C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms), or R 4  and R 5 , together with the N-atom to which they are attached, form a 4- to 7-membered heterocyclic ring, which ring optionally contains one or more additional heteroatoms selected from oxygen, nitrogen and sulfur and which ring is optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, OH, ═O, nitro, amino and halo;  
 R 6  represents C(O)R 10a , C(O)OR 10b  or S(O) 2 R 10c ;  
 R 10a  to R 10c  independently represent C 1-4  alkyl, C 3-8  cycloalkyl, aryl, C 1-4  alkylphenyl (which four groups are all optionally substituted by or one or more substituents selected from nitro, halo, C 1-4  alkyl and C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms)), or R 10a  represents H,  
 R 7  and R 8  independently represent H, C 1-6  alkyl, C 3-8  cycloalkyl, aryl or C 1-4  alkylphenyl, which latter four groups are optionally substituted by one or more substituents selected from nitro, halo, C 1-4  alkyl and C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms);  
 R 9a  and R 9b  independently represent C 1-6  alkyl, C 3-8  cycloalkyl, aryl, C 1-4  alkylphenyl, which latter four groups are optionally substituted by one or more substituents selected from nitro, halo, C 1-4  alkyl and C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms), or R 9b  represents H;  
 R 1  and R 2  are each independently H or C 1-4  alkyl;  
 R 3  represents aryl (optionally substituted by one or more substituents selected from OH, nitro, halo, CN, CH 2 CN, CONH 2  ,C 1-4  alkyl, C 1-5  alkoxy, C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms) and —N(R 11a )(R 11b )), C 1-10  alkyl, C 1-10  alkenyl or C 3-10  alkynyl wherein said alkyl, alkenyl or alkynyl groups are optionally substituted and/or terminated by one or more substituents selected from OR 11c , S(O) p R 11d , CN, halo, C 1-6  alkoxy carbonyl, C 2-6  alkanoyl, C 2-6  alkanoyloxy, C 3-8  cycloalkyl, C 4-9  cycloalkanoyl, N(R 12a )S(O) 2 R 13 , Het 1 , aryl, adamantyl (which latter two groups are optionally substituted by one or more substituents selected from OH, nitro, amino, halo, CN, CH 2 CN, CONH 2 ,C 1-4  alkyl, C 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms)), or —W-A 1 -N(R 12b )(R 12c ).  
 p is 0, 1 or 2;  
 W represents a single bond, C(O) or S(O) q ,  
 A 1  represents a single bond or Cup alkylene,  
 provided that when both W and A 1  represent single bonds, then the group —N(R 12b )(R 12c ) is not directly attached to an unsaturated carbon atom;  
 q is 0, 1 or 2;  
 R 11a  to R 11d  each independently represent H, C 1-10  alkyl, C 3-10  alkenyl C 3-8  alkynyl, C 3-8  cycloalkyl, C 1-4  alkylphenyl, aryl (which latter six groups are optionally substituted by or one or more substituents selected from OH, nitro, amino, halo, CN, CH 2 CN, CONH 2  , C 1-4  alkyl, C 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms)) or Het 2 ;  
 provided that R 11d  does not represent H when p represents 1 or 2;  
 R 12a  to R 12c  each independently represent H, C 1-10  alkyl, C 3-10  alkenyl, C 3-10  alkynyl, C 3-8  cycloalkyl, C 1-4  alkylphenyl, aryl (which latter six groups are optionally substituted by or one or more substituents selected from OH, nitro, amino, halo, CN, CH 2 CN, CONH 2 , C 1-4  alkyl, C 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms)), Het 3 , or R 12b  and R 12c  together represent unbranched C 2-6  alkylene which alkylene group is optionally interrupted by O, S and/or an N(R 14 ) group and is optionally substituted by one or more C 1-4  alkyl groups;  
 R 13  represents C 1-6  alkyl, C 3-8  cycloalkyl, C 1-4  alkylphenyl or aryl, which four groups are optionally substituted by or one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, OH, nitro, amino and halo;  
 R 14  represents H, C 1-6  alkyl, C 3-8  cycloalkyl, A 2 -(C 3-8  cycloalkyl) or A 2 -aryl;  
 A 2  represents C 1-6  alkylene;  
 Het 1 , Het 2  and Het 3  independently represent 3- to 8-membered heterocyclic groups, which groups contain at least one heteroatom selected from oxygen, sulfur and/or nitrogen, which groups are optionally fused to a benzene ring, and which groups are optionally substituted in the heterocyclic and/or fused benzene ring part by one or more substituents selected from OH, ═O, nitro. amino, halo, CN, aryl, C 1-4  alkyl, C 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms);  
 X is H, halo, C 1-4  alkyl or C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms);  
 n is 0, 1 or 2;  
 or pharmaceutically or veterinarily, acceptable derivatives thereof.  
 
     
     
         20 . A process for the preparation of a compound of the formula:  
       
         
           
           
               
               
           
         
       
       wherein A represents a single bond, C 1-4  alkylene, C 2-4  alkenylene or C 2-4  alkynylene, which alkylene, alkenylene or alkynylene groups are optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, halo and OH; 
 D represents H, OH, CN, N(R 4 )(R 5 ), N(H)R 6 , C(O)N(R 4 )(R 5 ), C(O)OR 7 , C(O)R 8 , C(═NR 9a )R 8 , or C(═NOR 9b )R 8 ;  
 provided that when A represents C 2-4  alkenylene or C 2-4  alkynylene, and D represents OH, N(R 4 )(R 5 ) or N(H)R 6 , then D is not directly attached to an unsaturated carbon atom;  
 and provided that when A represents a single bond. then D does not represent H, OH, N(R 4 )(R 5 ) or N(H)R 6 ;  
 R 4  and R 5  independently represent H, C 1-6  alkyl, C 3-8  cycloalkyl, aryl, C 1-4  alkylphenyl, which latter four groups are optionally substituted by one or more substituents selected from nitro, halo, C 1-4  alkyl and C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms), or R 4  and R 5 , together with the N-atom to which they are attached, form a 4- to 7-membered heterocyclic ring, which ring optionally contains one or more additional heteroatoms selected from oxygen, nitrogen and sulfur and which ring is optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, OH, ═O, nitro, amino and halo;  
 R 6  represents C(O)R 10a , C(O)OR 10b  or S(O) 2 R 10c ;  
 R 10a  to R 10c  independently represent C 1-4  C 1-4  alkyl, C 3-8  cycloalkyl, aryl, C 1-4  alkylphenyl (which four groups are all optionally substituted by or one or more substituents selected from nitro, halo, C 1-4  alkyl and C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms)), or R 10a  represents H;  
 R 7  and R 8  independently represent H, C 1-6  alkyl, C 3-8  cycloalkyl, aryl or C 1-4  alkylphenyl, which latter four groups are optionally substituted by one or more substituents selected from nitro, halo, C 1-4  alkyl and C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms),  
 R 9a  and R 9b  independently represent C 1-6  alkyl, C 3-8  cycloalkyl, aryl, C 1-4  alkylphenyl, which latter four groups are optionally substituted by one or more substituents selected from nitro, halo, C 1-4  alkyl and C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms), or R 9b  represents H;  
 R 1  and R 2  are each independently H or C 1-4  alkyl;  
 R 3  represents aryl (optionally substituted by one or more substituents selected from OH, nitro, halo, CN, CH 2 CN, CONH 2 , C 1-4  alkyl, C 1-4  alkoxy, C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms) and —N(R 11a )(R 11b )), C 1-10  alkyl, C 3-10  alkenyl or C 3-10  alkynyl wherein said alkyl, alkenyl or alkynyl groups are optionally substituted and/or terminated by one or more substituents selected from OR 11c , S(O) p R 11d , CN, halo, C 1-6  alkoxy carbonyl, C 2-6  alkanoyl, C 2-6  alkanoyloxy, C 3-8  cycloalkyl, C 4-9  cycloalkanoyl, N(R 12a )S(O) 2 R 13 , Het 1 , aryl, adamantyl (which latter two groups are optionally substituted by one or more substituents selected from OH, nitro, amino, halo, CN, CH 2 CN, CONH 2 ,C 1-4  alkyl, C 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms)), or —W-A 1 -N(R 12b )(R 12c );  
 p is 0, 1 or 2;  
 W represents a single bond, C(O) or S(O) q ;  
 A 1  represents a single bond or C 1-10  alkylene;  
 provided that when both W and A 1  represent single bonds, then the group —N(R 12b)(R   12c ) is not directly attached to an unsaturated carbon atom;  
 q is 0, 1 or 2;  
 R 11a  to R 11d  each independently represent H, C 1-10  alkyl, C 3-10  alkenyl, C 3-10  alkynyl, C 3-8  cycloalkyl, C 1-4  alkylphenyl, aryl (which latter six groups are optionally substituted by or one or more substituents selected from OH, nitro, amino, halo, CN, CH 2 CN, CONH 2  , C 1-4  alkyl, C 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms)) or Het 2 ;  
 provided that R 11d  does not represent H when p represents 1 or 2;  
 R 12a  to R 12c  each independently represent H, C 1-10  alkyl, C 3-10  alkenyl, C 3-10  alkynyl, C 3-8  cycloalkyl, C 1-4  alkylphenyl, aryl (which latter six groups are optionally substituted by or one or more substituents selected from OH, nitro, amino, halo, CN, CH 2 CN, CONH 2 ,C 1-4  alkyl, C 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms)), Het 3 , or R 12b  and R 12c  together represent unbranched C 2-6  alkylene which alkylene group is optionally interrupted by O, S and/or an N(R 14 ) group and is optionally substituted by one or more C 1-4  alkyl groups;  
 R 13  represents C 1-6  alkyl, C 3-8  cycloalkyl, C 1-4  alkylphenyl or aryl, which four groups are optionally substituted by or one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, OH, nitro, amino and halo;  
 R 14  represents H, C 1-6  alkyl, C 3-8  cycloalkyl, A 2 -(C 3-8  cycloalkyl) or A 2 aryl;  
 A 2  represents C 1-6  alkylene,  
 Het 1 , Het 2  and Het 3  independently represent 3- to 8-membered heterocyclic groups, which groups contain at least one heteroatom selected from oxygen, sulfur and/or nitrogen, which groups are optionally fused to a benzene ring, and which groups are optionally substituted in the heterocyclic and/or fused benzene ring part by one or more substituents selected from OH, ═O, nitro, amino, halo, CN, aryl, C 1-4  alkyl, C 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms);  
 X is H, halo, C 1-4  alkyl or C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms);  
 n is 0, 1 or 2;  
 or pharmaceutically, or veterinarily, acceptable derivatives thereof, which process comprises:  
 a) for compounds of formula I in which A represents C 2-4  alkynylene (in which group the carbon-carbon triple bond is α,β to the benzene ring), which alkynylene group is optionally substituted at the 3- and/or the 4-C (relative to the benzene ring) by one or more substituents defined in above in respect of A, and/or one of the groups defined above in respect of D, or (when D is not attached at the 3- or 4-C) which alkynylene group is substituted at the 2-C (relative to the benzene ring) by CN, C(O)N(R 4 )(R 5 ), C(O)OR 7 , C(O)R 8 , C(═NR 9a )R 8 , or C(═NOR 9b )R 8 , reaction of a corresponding compound of formula II,  
                     
 wherein L 1  is a leaving group, and R 1 , R 2 , R 3 , X and n are as defined above, with a compound of formula III,  
                     
 wherein M represents (as appropriate) H, a tin-containing moiety, a boron derivative, a zinc halide, a magnesium halide or an alkali metal, A 3  represents a single bond or C 1-2  alkylene (optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, OH and halo), and D is as defined above, provided that when A 3  represents a single bond, then D does not represent H, OH, N(R 4 )(R 5 ) or N(H)R 6 , wherein R 4 , R 5  and R 6  are as defined above;  
 b) for compounds of formula I in which A represents C 2-4  alkenylene (in which group the carbon-carbon double bond is β,β to the benzene ring), which alkenylene group is optionally substituted at the 2-C (relative to the benzene ring) by C 1-4  alkyl, and also optionally substituted at the 3-and/or 4-C (relative to the benzene ring) by one or more of the substituents defined above in respect of A and/or one of the groups defined above in respect of D, or which alkenylene group is substituted at the 2-C (relative to the benzene ring) by CN, C(O)N(R 4 )(R 5 ), C(O)OR 7 , C(O)R 8 , C(═NR 9a )R 8 , or C(═NOR 9b )R 8 , reaction of a corresponding compound of formula II, as defined above, with a compound of formula IV,  
                     
 wherein the dashed bond represent optional cis- or trans- geometry, R 15  represents H or C 1-4  alkyl A 3 , D and M are as defined above;  
 c) for compounds of formula I in which A represents a single bond and D represents CN, reaction of a compound of formula V,  
                     
 wherein R 1 , R 2 , R 3 , X and n are as defined above, with an alkali metal cyanide;  
 d) for compounds of formula I in which A represents C 1-4  alkylene, C 2-4  alkenylene or C 2-4  alkynylene, which alkylene, alkenylene or alkynylene groups are optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, halo or OH, and D represents NH 2  (which is attached to a CH 2  group), reduction of a corresponding compound of formula I in which A represents (as appropriate) a single bond, C 1-3  alkylene, C 2-3  alkenylene or C 2-3  alkynylene, which alkylene, alkenylene or alkynylene groups are optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, halo and OH, and D represents CN;  
 e) for compounds of formula I in which D represents C(O)NH 2 , controlled hydrolysis of a corresponding compound of formula I in which D represents CN;  
 f) for compounds of formula I in which A represents a single bond and D represents C(O)—(C 1-6  alkyl) or C(O)—(C 1-4  alkylphenyl), which alkyl and alkylphenyl groups are both optionally substituted by one or more of the substituents defined above in respect of R 8 , hydrolysis of a corresponding compound of formula IX,  
                     
 wherein R 15  represents C 1-6  alkyl, R 16  represents H, C 1-5  alkyl, phenyl or C 1-3  alkylphenyl which latter three groups are all optionally substituted by one or more substituents selected from nitro, halo, C 1-4  alkyl and C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms), the dashed bond indicates optional cis- or trans- geometry, and R 1 , R 2 , R 3 , X and n are as defined above;  
 g) for compounds of formula I in which D represents C(O)R 8 , wherein R 8  is as defined above provided that it does not represent H, reaction of a corresponding compound of formula I in which D represents CN with an organometallic compound capable of delivering an R 8a — containing anion, wherein R 8a  is defined as for R 8  above provided that it does not represent H;  
 h) for compounds of formula I in which A represents a single bond and D represents C(O)OR 7 , wherein R 7  is as defined above provided that it does not represent H, reaction of a corresponding compound of formula V, as defined above, with carbon monoxide and an alcohol of formula R 7a OH, wherein R 7a  is defined as for R 7  above provided that it does not represent H;  
 i) for compounds of formula I in which A represents C 1-4  alkylene, C 2-4  alkenylene or C 2-4  alkynylene, which alkylene, alkenylene or alkynylene groups are optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, halo and OH, and D represents OH (which is attached to a CH 2  group), reduction of a corresponding compound of formula I in which A represents (as appropriate) a single bond, C 1-3  alkylene, C 2-3  alkenylene or C 2-3  alkynylene, which alkylene, alkenylene or alkynylene groups are optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, halo and OH, and D represents C(O)OR 7a , wherein R 7a  is as defined above;  
 j) for compounds of formula I in which A represents C 1-4  alkylene, C 2-4  alkenylene or C 2-4  alkynylene, which alkylene, alkenylene or alkynylene groups are gem-disubstituted with two C 1-4  alkyl groups (α to D) and are optionally substituted by one or more further substituents selected from C 1-4  alkyl, C 1-4  alkoxy, halo and OH, and D represents OH, reaction of a corresponding compound of formula I in which A represents (as appropriate) a single bond, C 1-3  alkylene, C 2-3  alkenylene or C 2-3  alkynylene, which alkylene, alkenylene or alkynylene groups are optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, halo and OH, and D represents C(O)OR 7a , wherein R 7a  is as defined above, with a C 1-4  alkyl-delivering organometallic compound;  
 k) for compounds of formula I in which D represents C(O)N(R 4 )(R 5 ), wherein R 4  and R 5  are as defined above: 
 A) reaction of a corresponding compound of formula I in which D represents C(O)OR 7a , wherein R 7a  is as defined above, with a compound of formula XI,  
   HN(R 4 )(R 5 )   XI  
 or an acid addition salt thereof, wherein R 4  and R 5  are as defined above;  
 B) reaction of a corresponding compound of formula I in which D represents C(O)OH with a compound of formula XI, as defined above.  
 
 l) for compounds of formula I in which D represents C(O)OH, hydrolysis of a corresponding compound of formula I in which D represents C(O)OR 7a , wherein R 7a  is as defined above;  
 m) for compounds of formula I in which D represents N(H)R 6 , wherein R 6  is as defined above, reaction of a corresponding compound of formula I in which D represents NH 2  with a compound of formula XII,  
   R 6 -L 1    XII  
 wherein R 6  is as defined above and L 1  is as defined above;  
 n) for compounds of formula I in which A represents C 1-4  alkyl and D represents N(R 4 )(R 5 ) or N(H)C(O)R 10a  attached at the 1-, 2- or 3-C (relative to the benzene ring), wherein R 4 , R 5  and R 10a  are as defined above, reaction of a corresponding compound of formula I in which A represents C 1-4  alkenylene unsaturated α,β-, β,γ- or γ,δ- (respectively) relative to the benzene ring and D represents H, with a compound of formula XI, as defined above, or a compound of formula XIII,  
   NC—R 10a    XIII  
 wherein R 10a  is as defined above;  
 o) for compounds of formula I in which A represents C 2-4  alkylene optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, halo and OH, and D represents OH, oxidation of a corresponding borane adduct of formula XIV,  
                     
 wherein x is 1, 2 or 3, y is (as appropriate) (3-x) or 1, R 17  is (as appropriate) H, halo, an alkyl, or a cycloalkyl group providing one or two bonds to boron, A represents (as appropriate) C 2-4  alkylene optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, halo or OH, and R 1 , R 2 , R 3 , X and n are as defined above;  
 p) for compounds of formula I in which A represents a C 2-4  alkylene group substituted (a to D) with an OH group and D represents OH, reaction of a corresponding compound of formula I in which A represents a C 2-4  alkenylene group and D represents H with a dihydroxylating reagent;  
 q) for compounds of formula I in which A represents a single bond or a C 1-2  alkylene group (as appropriate) and D represents C(O)H, reaction of a corresponding compound of formula I in which A represents a C 2-4  alkylene group substituted (α to D) with an OH group and D represents OH with a reagent that effects 1,2-diol oxidative cleavage;  
 r) for compounds of formula I in which D represents C(═NR 9a )R 8  or C(═NOR 9b )R 8 , wherein R 8 , R 9a  and R 9b  are as defined above, reaction of a corresponding compound of formula I in which D represents C(O)R 8  with a compound of formula XV,  
   H 2 N—R 9a    XV  
 or a compound of formula XVI,  
   H 2 N—OR 9b    XVI  
 wherein R 9a  and R 9b  are as defined above;  
 s) for compounds of formula I in which A represents C 1-4  alkylene substituted (α to D) with an OH group and D represents N(H)CH 3  (at the alkylene chain terminus), reduction of a corresponding compound of formula XVII,  
                     
 wherein r is 0, 1 or 2, L 2  represents H or a group capable, when attached to a C 2  alkylene unit, of undergoing 1,2-elimination (relative to L 2 ), and R 1 , R 2 , R 3 , X and n are as defined above;  
 t) for compounds of formula I wherein R 3  represents C 1  alkyl optionally substituted by C 3-8  cycloalkyl, Het 1 , aryl, adamantyl, (which latter two groups are optionally substituted by one or more substituents selected from OH, nitro, amino, halo, CN, CH 2 CN, CONH 2 , C 1-4  alkyl, C 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms)), or R 3  represents C 2-10  alkyl, C 3-10  alkenyl or C 3-10  alkynyl (which three groups are all optionally substituted by one or more of the relevant substituents identified above in respect to R 3 ), which alkyl, alkenyl or alkynyl groups are attached to the piperidine nitrogen atom via a CH 2  group, wherein Het 1  is as defined in  claim 1 , reduction of a corresponding compound of formula XIX,  
                     
 wherein R 31  represents H, C 3-8  cycloalkyl, Het 1 , aryl, adamantyl, (which latter two groups are optionally substituted by one or more substituents selected from OH, nitro, amino, halo, CN, CH 2 CN, CONH 2 , C 1-4  alkyl, C, 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms)), C 1-9  alkyl, C 2-9  alkenyl or C 2-9  alkynyl, which alkyl, alkenyl or alkynyl groups are optionally substituted and/or terminated by one or more substituents selected from OR 11c , S(O) p R 11d , CN, halo, C 1-6  alkoxy carbonyl, C 2-6  alkanoyl, C 2-6  alkanoyloxy, C 3-8  cycloalkyl, C 4-9  cycloalkanoyl, N(R 12a )S(O) 2 R 13 , Het 1 , aryl, adamantyl (which latter two groups are optionally substituted by one or more substituents selected from OH, nitro, amino, halo, CN, CH 2 CN, CONH 2 , C 1-4  alkyl, C 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms)), and —W-A 1 -N(R 12b )(R 12c ), and R 1 , R 2 , R 11c , R 11d , R 12a  to R 12c , R 13 , Het 1 , n, p, W, X, A 1 , A and D are as defined above;  
 u) reaction of a corresponding compound of formula XX,  
                     
 wherein R 1 , R 2 , A, D, X and n are as defined above, with a compound of formula VIII,  
   R 3 -L 1    VIII  
 wherein R 3  and L 1  are as defined above;  
 v) for compounds of formula I wherein R 3  represents C 1  alkyl, which, is optionally substituted by R 31 , wherein R 31  is as defined above, reaction of a corresponding compound of formula XX, as defined above, with a compound of formula XXII,  
   R 31 CHO   XXII  
 wherein R 31  is as defined above, in the presence of a reducing agent;  
 w) for compounds of formula I wherein R 3  is a C 1-10  alkyl, C 4-10  alkenyl or C 4-10  alkynyl group that is fully saturated from 1- to 3-C (relative to the piperidine N-atom), and which R 3  group is substituted at 2-C (relative to the piperidine N-atom) by S(O) 2 R 11d , S(O) 2 R 11d , alkanoyl, cycloalkanoyl, alkoxy carbonyl, CN, —C(O)-A 1 -N(R 12b )(R 12c ), —S(O)-A 1 -N(R 12b )(R 12c ), or —S(O) 2 -A 1 -N(R 12b )(R 12 c), wherein R 11d , R 12b , R 12c  and A 1  are as defined above in, reaction of a corresponding compound of formula XX, as defined above, with a compound of formula XXIII,  
   R 3a -Z   XXIII  
 wherein R 3a  represents R 3  as defined above except that it does not represent aryl, and that the R 3a  chain contains an additional carbon-carbon double bond α,β to the Z-substituent, and Z represents S(O)R 11d , S(O) 2 R 11d , alkanoyl, cycloalkanoyl, alkoxy carbonyl, CN, —C(O)-A 1 -N(R 12b )(R 12c ), —S(O)-A 1 -N(R 12b )(R 12c ), or —S(O) 2 -A 1 -N(R 12b )(R 12c ), wherein R 11d , R 12b , R 12c  and A 1  are as defined above;  
 x) for compounds of formula I in which A represents C 2-4  alkylene substituted (α to D) with an OH group and D represents N(R 4 )(R 5 ) (at the alkylene chain terminus), and R 4  and R 5  are as defined above, reaction of a compound of formula XXIV,  
                     
 wherein R 1 , R 2 , R 3 , X, r and n are as defined above, with a compound of formula XI, as defined above;  
 y) for compounds of formula I in which D represents N(H)R 4 , wherein R 4  is as defined above provided that it does not represent aryl, reduction of a corresponding compound of formula XXV,  
                     
 wherein R 4b  and R 4c , together with the carbonyl group to which they are attached, form a C 1-6  alkanal, C 3-6  alkanone, C 3-8  cycloalkanone, phenyl(C 1-4 )alkanal or phenyl(C 2-4 )alkanone group, which five groups are optionally substituted by one or more substituents selected from nitro, halo, C 1-4  alkyl or C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms), and R 1 , R 2 , R 3 , A, X and n are as defined above (provided that the —N═C(R 4b )(R 4c ) group is not directly attached to an unsaturated carbon atom);  
 z) for compounds of formula I in which A represents C 1-4  alkylene, C 2-4  alkenylene or C 2-4  alkynylene, which alkylene, alkenylene or alkynylene groups are optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, halo and OH, and D represents N(R 4 )(R 5 ) (attached to a CH 2  group), wherein R 4  and R 5  are as defined above, reduction of a corresponding compound of formula I in which A represents (as appropriate) a single bond, C 1-3  alkylene, C 2-3  alkenylene or C 2-3  alkynylene, which alkylene, alkenylene or alkynylene groups are optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, halo or OH, and D represents C(O)N(R 4 )(R 5 );  
 aa) conversion of one functional group on an alkyl, heterocyclic or aryl group in a compound of formula I to another.  
 
     
     
         21 . A compound of formula I,  
       
         
           
           
               
               
           
         
       
       wherein A represents C 1-4  alkylene, C 2-4  alkenylene or C 2-4  alkynylene, which alkylene, alkenylene or alkynylene groups are optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, halo and OH; 
 D represents H, OH, CN, N(R 4 )(R 5 ), N(H)R 6 , C(O)N(R 4 )(R 5 ), C(O)OR 7 , C(O)R 8 , C(═NR 9a )R 8 , or C(═NOR 9b )R 8 ;  
 provided that when A represents C 2-4  alkenylene or C 2-4  alkynylene, and D represents OH, N(R 4 )(R 5 ) or N(H)R 6 , then D is not directly attached to an unsaturated carbon atom;  
 R 4  and R 5  independently represent H, C 1-6  alkyl, C 3-8  cycloalkyl, aryl, C 1-4  alkylphenyl, which latter four groups are optionally substituted by one or more substituents selected from nitro, halo, C 1-4  alkyl and C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms), or R 4  and R 5 , together with the N-atom to which they are attached, form a 4- to 7-membered heterocyclic ring, which ring optionally contains one or more additional heteroatoms selected from oxygen, nitrogen and sulfur and which ring is optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, OH, ═O, nitro, amino and halo;  
 R 6  represents C(O)R 10a , C(O)OR 10b  or S(O) 2 R 10c ;  
 R 10a  to R 10c  independently represent C 1-4  alkyl, C 3-8  cycloalkyl, aryl, C 1-4  alkylphenyl (which four groups are all optionally substituted by or one or more substituents selected from nitro, halo, C 1-4  alkyl and C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms)), or R 10a  represents H;  
 R 7  and R 8  independently represent H, C 1-6  alkyl C 3-8  cycloalkyl, aryl or C 14  alkylphenyl, which latter four groups are optionally substituted by one or more substituents selected from nitro, halo, C 1-4  alkyl or C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms),  
 R 9a  and R 9b  independently represent C 1-6  alkyl C 3-8  cycloalkyl, aryl, C 1-4  alkylphenyl, which latter four groups are optionally substituted be one or more substituents selected from nitro, halo, C 1-4  alkyl or C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms), or R 9b  represents H;  
 R 1  and R 2  are each independently H or C 1-4  alkyl;  
 R 3  represents aryl (optionally substituted by one or more substituents selected from OH, nitro, halo, CN, CH 2 CN, CONH 2 ,C 1-4  alkyl, C 1-4  alkoxy, C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms) and —N(R 11a )(R 11b )), C 1-10  alkyl, C 3-10  alkenyl and C 3-10  alkynyl wherein said alkyl, alkenyl or alkynyl groups are optionally substituted and/or terminated by one or more substituents selected from OR 11c , S(O) p R 11d , CN, halo, C 1-6  alkoxy carbonyl, C 2-6  alkanoyl, C 2-6  alkanoyloxy, C 3-8  cycloalkyl, C 4-9  cycloalkanoyl, N(R 12a )S(O) 2 R 13 ,  
 Het 1  aryl, adamantyl (which latter two groups are optionally substituted by one or more substituents selected from OH, nitro, amino, halo, CN, CH 2 CN, CONH 2 ,C 1-4  alkyl, C 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms)), or —W-A 1 -N(R 12b )(R 12c );  
 p is 0, 1 or 2;  
 W represents a single bond, C(O) or S(O) q ;  
 A 1  represents a single bond or C 1-10  alkylene;  
 provided that when both W and A 1  represent single bonds, then the group —N(R 12b )(R 12c ) is not directly attached to an unsaturated carbon atom,  
 q is 0, 1 or 2;  
 R 11a  to R 11d  each independently represent H, C 1-10  alkyl, C 3-10  alkenyl, C 3-10  alkynyl, C 3-8  cycloalkyl, C 1-4  alkylphenyl, aryl (which latter six groups are optionally substituted by or one or more substituents selected from OH, nitro, amino, halo, CN, CH 2 CN, CONH 2 , C 1-4  alkyl, C 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms)) and Het 2 ;  
 provided that R 11d  does not represent H when p represents 1 or 2;  
 R 12a  to R 12 c each independently represent H, C 1-10  alkyl, C 3-10  alkenyl, C 3-10  alkynyl, C 3-8  cycloalkyl, C 1-4  alkylphenyl, aryl (which latter six groups are optionally substituted by or one or more substituents selected from OH, nitro, amino, halo, CN, CH 2 CN, CONH 2 , C 1-4  alkyl, C 1-4 alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms)), Het 3 , or R 12b  and R 12c  together represent unbranched C 2-6  alkylene which alkylene group is optionally interrupted by O, S and/or an N(R 14 ) group and is optionally substituted by one or more C 1-4 alkyl groups;  
 R 13  represents C 1-6 alkyl, C 3-8 cycloalkyl, C 1-4 alkylphenyl or aryl, which four groups are optionally substituted by or one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, OH, nitro, amino and halo;  
 R 14  represents H, C 1-6  alky, C 3-8  cycloalkyl, A 2 -(C 3-8  cycloalkyl) or A 2 -aryl;  
 A 2  represents C 1-6  alkylene;  
 Het 1 , Het 2  and Het 3  independently represent 3- to 8-membered heterocyclic groups, which groups contain at least one heteroatom selected from oxygen, sulfur and/or nitrogen, which groups are optionally fused to a benzene ring, and which groups are optionally substituted in the heterocyclic and/or fused benzene ring part by one or more substituents selected from OH, ═O, nitro, amino, halo, CN, aryl, C 1-4  alkyl, C 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms);  
 X is H, halo, C 1-4  alkyl or C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms);  
 n is0, 1 or 2;  
 or pharmaceutically, or veterinarily, acceptable derivatives thereof.  
 
     
     
         22 . A compound of formula I,  
       
         
           
           
               
               
           
         
       
       wherein A represents a single bond, C 1-4  alkylene, C 2-4  alkenylene or C 2-4  alkynylene, which alkylene, alkenylene or alkynylene groups are optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, halo and OH; 
 D represents H, OH, CN, N(R 4 )(R 5 ), N(H)R 6 , C(O)N(R 4 )(R 5 ), C(O)OR 7 , C(O)R 8 , C(═NR 9a ),R 8  , or C(═NOR 9b )R 8 ;  
 provided that when A represents C 2-4  alkenylene or C 2-4  alkynylene, and D represents OH, N(R 4 )(R 5 ) or N(H)R 6 , then D is not directly attached to an unsaturated carbon atom;  
 and provided that when A represents a single bond, then D does not represent H, OH, N(R 4 )(R 5 ) or N(H)R 6 ;  
 R 4  and R 5  independently represent H, C 1-6  alkyl, C 3-8  cycloalkyl, aryl, C 1-4  alkylphenyl, which latter four groups are optionally substituted by one or more substituents selected from nitro, halo, C 1-4  alkyl and C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms), or R 4  and R 5 , together with the N-atom to which they are attached, form a 4- to 7-membered heterocyclic ring, which ring optionally contains one or more additional heteroatoms selected from oxygen. nitrogen and sulfur and which ring is optionally substituted by one or more substituents selected from C 1-4  alkyl, C 1-4  alkoxy, OH, ═O, nitro, amino or halo;  
 R 6  represents C(O)R 10a , C(O)OR 10b  or S(O) 2 R 10c ;  
 R 10a  to R 10c  independently represent C 1-4  alkyl, C 3-8  cycloalkyl, aryl, C 1-4  alkylphenyl (which four groups are all optionally substituted by or one or more substituents selected from nitro, halo, C 1-4  alkyl and C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms)), or R 10a  represents H;  
 R 7 and R 8  independently represent H, C 1-6  alkyl, C 3-8  cycloalkyl, aryl or C 1-4  alkylphenyl, which latter four groups are optionally substituted by one or more substituents selected from nitro, halo, C 1-4  alkyl or C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms);  
 R 9a  and R 9b  independently represent C 1-6  alkyl, C 3-8  cycloalkyl, aryl, C 1-4  alkylphenyl, which latter four groups are optionally substituted by one or more substituents selected from nitro, halo, C 1-4  alkyl and C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms), or R 9b  represents H;  
 R 1  and R 2  are each independently H or C 1-4  alkyl;  
 R 3  represents C 1-10  alkyl, C 3-10  alkenyl or C 3-10  alkynyl, wherein said alkyl, alkenyl or alkynyl groups are substituted all or terminated by WA 1  (NR 12A ) (R 12C ) W represents a single bond, C(O) or SO q ;  
 A 1  represents a single bond or C 1-10  alkylene;  
 provided that when both W and A 1  represent single bonds, then the group —N(R 12b )(R 12c ) is not directly attached to an unsaturated carbon atom;  
 q is 0, 1 or 2;  
 R 12b  and R 12c  each independently represent H, C 1-10  alkyl, C 3-10  alkenyl, C 3-10  alkynyl, C 3-8  cycloalkyl, C 1-4  alkylphenyl, aryl (which latter six groups are optionally substituted by or one or more substituents selected from OH, nitro, amino, halo, CN, CH 2 CN, CONH 2 , C 1-4  alkyl, C 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms)), Het 3 , or R 12b  and R 12c  together represent unbranched C 2-6  alkylene which alkylene group is optionally interrupted by O, S and/or an N(R 14 ) group and is optionally substituted by one or more C 1-4  alkyl groups;  
 R 14  represents H, C 1-6  alkyl, C 3-8  cycloalkyl, A 2 -(C 3-8  cycloalkyl) or A 2 -aryl;  
 A 2  represents C 1-6  alkylene;  
 Het 1 , and Het 3  represents 3- to 8-membered heterocyclic groups, which groups contain at least one heteroatom selected from oxygen, sulfur and/or nitrogen, which groups are optionally fused to a benzene ring and which groups are optionally substituted in the heterocyclic and/or fused benzene ring part by one or more substituents selected from OH, ═O, nitro, amino, halo, CN, aryl, C 1-4  alkyl, C 1-4  alkoxy and C 1-5  alkanoyl (which latter three groups are optionally substituted by one or more halo atoms);  
 X is H, halo, C 1-4  alkyl or C 1-4  alkoxy (which latter two groups are optionally substituted by one or more halo atoms);  
 n is 0, 1 or 2;  
 or pharmaceutically, or veterinarily, acceptable derivatives thereof.