Amide compounds useful in therapy

Abstract

A compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined herein: and compositions, processes for the preparation, and uses thereof, e.g. in the treatment of endometriosis or uterine fibroids.

1 . A compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof: 
       
         
           
           
               
               
           
         
         wherein, 
         R 1  and R 2  each independently represent H, halogen, CF 3 , C 1-3  alkyl or C 1-3  alkoxy; 
         R 3  represents C 1-6  alkyl, C 3-6  cycloalkyl, phenyl (optionally substituted by one or more substituents each independently selected from R a ) or Het (optionally substituted by one or more substituents each independently selected from OH, oxo, or C 1-4  alkyl);
 R a  represents halogen, CF 3 , or CN; 
 Het represents a 5- or 6-membered, saturated, partially saturated, or aromatic, heterocyclic ring comprising (a) from 1 to 4 nitrogen atoms, or (b) 1 or 2 nitrogen atoms and 1 oxygen atom or 1 sulphur atom, or (c) 1 oxygen atom or 1 sulphur atom; 
 
         R 4  represents H or C 1-3  alkyl; 
         R 5  represents C 1-6  alkyl (optionally substituted by one or more substituents each independently selected from R b ), C 3-6  cycloalkyl (optionally substituted by one or more substituents each independently selected from oxo or OH), or Het 2  (optionally substituted by one or more substituents each independently selected from R d ); where
 R b  represents OH, halogen, C m  cycloalkyl, OC 1-4  alkyl, COR c , NR d   2 , or 
 Het 1 ; where
 R c  independently represents —NH 2 , —NHC 1-4  alkyl, —N(C 1-4  alkyl) 2 , —OC 1-4  alkyl or —C 1-4  alkyl; 
 R d  independently represents H or C 1-4  alkyl; and 
 Het 1  independently represents a 5- or 6-membered, saturated, partially saturated, or aromatic, heterocyclic ring comprising (a) from 1 to 4 nitrogen atoms, or (b) 1 or 2 nitrogen atoms and 1 oxygen atom or 1 sulphur atom, or (c) 1 oxygen atom or 1 sulphur atom, (optionally substituted by one or more substituents each independently selected from OH, oxo or C 1-4  alkyl); 
 
 Het 2  represents a 4- to 6-membered, saturated, partially saturated, or aromatic, monocyclic heterocyclic ring, or a 7- to 12-membered saturated, partially saturated, or aromatic, bicyclic heterocyclic ring, comprising (a) from 1 to 4 nitrogen atoms, or (b) 1 or 2 nitrogen atoms and 1 oxygen atom or 1 sulphur atom, or (c) 1 oxygen atom or 1 sulphur atom; and 
 R d  represents C 1-4  alkyl, oxo, OH, COC 1-4  alkyl, COOC 1-4  alkyl, SO 2 C 1-4  alkyl, NH 2 , CONHC 1-4  alkyl, or CON(C 1-4  alkyl) 2 ; and 
 
         R 6  represents C 1-3  alkyl (optionally substituted by one or more substituents each independently selected from R f ), C 3-5  cycloalkyl (optionally substituted by one or more halogen), CN or halogen; where
 R f  represents halogen or phenyl. 
 
       
     
     
         2 . A compound according to  claim 1 , wherein R 1  represents H or C 1-3  alkyl. 
     
     
         3 . A compound according to  claim 1 , wherein R 1  represents H or methyl. 
     
     
         4 . A compound according to  claim 1 , wherein R 2  represents H. 
     
     
         5 . A compound according to  claim 1 , wherein R 3  represents C 1-6  alkyl, C 3-6  cycloalkyl, or Het. 
     
     
         6 . A compound according to  claim 1 , wherein R 3  is isopropyl, butan-2-yl, cyclopropyl, cyclobutyl or 3-tetrahydrofuranyl. 
     
     
         7 . A compound according to  claim 1 , wherein R 3  is isopropyl, cyclobutyl or butan-2-yl. 
     
     
         8 . A compound according to  claim 1 , wherein R 4  is H or methyl. 
     
     
         9 . A compound according to  claim 1 , wherein R 4  is H. 
     
     
         10 . A compound according to  claim 1 , wherein R 5  is C 1-6  alkyl optionally substituted by hydroxy, fluoro, methoxy, C 1-4  alkanoyl, C 1-4  alkylaminocarbonyl, amino, C 1-4  alkoxycarbonyl, C 3-6  cycloalkyl or Het 1 ; Het 2 ; or C 3-6  cycloalkyl optionally substituted by hydroxy: and preferably is C 1-6  alkyl optionally substituted by hydroxy. 
     
     
         11 . A compound according to  claim 1 , wherein R 5  is methyl, ethyl, n-propyl, isopropyl, t-butyl, 2-butyl, 2,2-dimethylprop-1-yl, 2-methyl-2-hydroxyprop-1-yl, 2-hydroxyprop-1-yl, 3-hydroxy-2-methylprop-2-yl, 2,2,2-trifluoroethyl, 3-methoxyprop-1-yl, 2-methoxyethyl, 3,3,3-trifluoroprop-1-yl, acetylmethyl, methylaminocarbonylmethyl, ethylaminocarbonylmethyl, 2-aminoethyl, 2-amino-2-methylprop-1-yl, 2-methoxycarbonylprop-2-yl, cyclopropylmethyl, 2-cyclopropylethyl, tetrahydrofuran-2-ylmethyl, 1-(1-methyl-1H-pyrazol-4-yl)ethyl, pyrimidin-4-ylmethyl, 1-(1H-pyrazol-1-yl)prop-2-yl, 3-(2-oxopyrrolidin-1-yl)prop-1-yl, (1-methyl-1H-pyrazol-4-yl)methyl, 1-t-butoxycarbonylpyrrolidin-3-yl, 1-t-butoxycarbonylazetidin3-yl, pyrrolidin-3-yl, azetidin-3-yl, 1-isopropylcarbonylpyrrolidin-3-yl, 1-ethylcarbonyl pyrrolidin-3-yl, 1-methanesulphonylpyrrolidin-3-yl, 1-isopropylcarbonylazetidin-3-yl, 1-ethylcarbonylazetidin-3-yl, 1-methanesulphonylazetidin-3-yl, 1-acetylazetidin-3-yl, 2-oxotetrahydrofuran-3-yl, 6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-6-yl, tetrahydro-2H-pyran-3-yl, tetrahydro-2H-pyran-4-yl, 1-methyl-6-oxopiperidin-3-yl, 5-oxopyrrolidin-3-yl, tetrahydrofuran-3-yl, 1,1-dioxidotetrahydro-3-thienyl, cyclopentyl, cyclobutyl, 3-hydroxycyclobutyl or 3-hydroxycyclopentyl. 
     
     
         12 . A compound according to  claim 1 , wherein R 5  is 2-methyl-2-hydroxyprop-1-yl, 2-hydroxyprop-1-yl or methylaminocarbonylmethyl. 
     
     
         13 . A compound according to  claim 1 , wherein R 6  represents C 1-3  alkyl (optionally substituted by one or more phenyl substituents), C 3-5  cycloalkyl (optionally substituted by one or more halogen), CN or halogen. 
     
     
         14 . A compound according to  claim 1 , wherein R 6  is methyl, ethyl, cyclopropyl, 3,3-difluorocyclobutyl, benzyl, cyano or chloro. 
     
     
         15 . A compound according to  claim 1 , wherein R 6  is methyl, cyclopropyl, cyano or chloro. 
     
     
         16 . A compound as claimed in  claim 1  of Formula (Ia), or a pharmaceutically acceptable salt or solvate thereof: 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2  and R 5  are as defined in  claim 1 . 
       
     
     
         17 . A compound of the formula (Ia) as claimed in  claim 16  wherein R 1  and R 2  are both H. 
     
     
         18 . A compound selected from:
 3-(4-cyanophenyl)-4-cyclopropyl-N-(2-hydroxy-2-methylpropyl)-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-N-[(2S)-2-hydroxypropyl]-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-N-[(2R)-2-hydroxypropyl]-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-N,1-diisopropyl-1H-pyrazole-5-carboxamide;   tert-butyl (3R)-3-({[3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-1H-pyrazol-5-yl]carbonyl}amino)pyrrolidine-1-carboxylate;   tert-butyl (3S)-3-({[3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-1H-pyrazol-5-yl]carbonyl}amino)pyrrolidine-1-carboxylate;   tert-butyl 3-({[3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-1H-pyrazol-5-yl]carbonyl}amino)azetidine-1-carboxylate;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-[(3R)-pyrrolidin-3-yl]-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-[(3S)-pyrrolidin-3-yl]-1H-pyrazole-5-carboxamide;   N-azetidin-3-yl-3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-N-[(3R)-1-isobutyrylpyrrolidin-3-yl]-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-Cyanophenyl)-4-cyclopropyl-1-isopropyl-N-[(3S)-1-propionylpyrrolidin-3-yl]-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-[(3R)-1-(methylsulfonyl)pyrrolidin-3-yl]-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-N-[(3S)-1-isobutyrylpyrrolidin-3-yl]-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-[(3S)-1-propionylpyrrolidin-3-yl]-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-N-(1-isobutyrylazetidin-3-yl)-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-(1-propionylazetidin-3-yl)-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-[1-(methylsulfonyl)azetidin-3-yl]-1H-pyrazole-5-carboxamide;   N-(1-acetylazetidin-3-yl)-3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-propyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-(3-methoxypropyl)-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-(3,3,3-trifluoropropyl)-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-(pyrimidin-4-ylmethyl)-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-[(3S)-2-oxotetrahydrofuran-3-yl]-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-[2-(methylamino)-2-oxoethyl]-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-[3-(2-oxopyrrolidin-1-yl)propyl]-1H-pyrazole-5-carboxamide;   methyl N-{[3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-1H-pyrazol-5-yl]carbonyl}-2-methylalaninate;   N-(2-aminoethyl)-3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-1H-pyrazole-5-carboxamide;   N-(2-amino-2-methylpropyl)-3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-[(1-methyl-1H-pyrazol-4-yl)methyl]-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-N-[(1R,3S)-3-hydroxycyclopentyl]-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-N-(cis-3-hydroxycyclobutyl)-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-[(1S)-1-methylpropyl]-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-N-(2,2-dimethylpropyl)-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-[(1R)-1-methylpropyl]-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-(tetrahydrofuran-2-ylmethyl)-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-N-[(6S)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-6-yl]-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-N-[(6R)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-6-yl]-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-[1-(1-methyl-1H-pyrazol-4-yl)ethyl]-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-(tetrahydro-2H-pyran-3-yl)-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-(1-methyl-6-oxopiperidin-3-yl)-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-N-[2-(ethylamino)-2-oxoethyl]-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-[1-methyl-2-(1H-pyrazol-1-yl)ethyl]-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-[(3R)-5-oxopyrrolidin-3-yl]-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-N-ethyl-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-(2,2,2-trifluoroethyl)-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-N-(cyclopropylmethyl)-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-N-cyclobutyl-4-cyclopropyl-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-N-(cyclopropylmethyl)-1-isopropyl-N-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-(tetrahydrofuran-3-yl)-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-[(2R)-tetrahydrofuran-2-ylmethyl]-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-N-(2-cyclopropylethyl)-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-[(2S)-tetrahydrofuran-2-ylmethyl]-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-N-(2-hydroxy-1,1-dimethylethyl)-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-N-(1,1-dioxidotetrahydro-3-thienyl)-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-N,4-dicyclopropyl-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-(2-methoxyethyl)-1H-pyrazole-5-carboxamide;   N-tert-butyl-3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-cyclopropyl-1-isopropyl-N-(2-oxopropyl)-1H-pyrazole-5-carboxamide;   3-(4-cyano-3-methylphenyl)-N-(cyclopropylmethyl)-1-isopropyl-4-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyano-3-methylphenyl)-N-[(2S)-2-hydroxypropyl]-1-isopropyl-4-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyano-3-methylphenyl)-N-[(2R)-2-hydroxypropyl]-1-isopropyl-4-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyano-3-methylphenyl)-N-ethyl-1-isopropyl-4-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyano-3-methylphenyl)-N,1-diisopropyl-4-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyano-3-methylphenyl)-N-cyclopropyl-1-isopropyl-4-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyano-3-methylphenyl)-N-(2-hydroxy-2-methylpropyl)-1-isopropyl-4-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-1-cyclobutyl-N-(cyclopropylmethyl)-4-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-1-cyclobutyl-N,4-dimethyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-1-cyclobutyl-N-cyclopropyl-4-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-1-cyclobutyl-N-[(2S)-2-hydroxypropyl]-4-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-1-cyclobutyl-N-[(2R)-2-hydroxypropyl]-4-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-1-cyclobutyl-N-(2-hydroxy-2-methylpropyl)-4-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-1-cyclobutyl-4-methyl-N-[2-(methylamino)-2-oxoethyl]-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-N-ethyl-4-methyl-1-(tetrahydrofuran-3-yl)-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-N-isopropyl-4-methyl-1-(tetrahydrofuran-3-yl)-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-N-[(2S)-2-hydroxypropyl]-4-methyl-1-(tetrahydrofuran-3-yl)-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-N-[(2R)-2-hydroxypropyl]-4-methyl-1-(tetrahydrofuran-3-yl)-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-N-(2-hydroxy-2-methylpropyl)-4-methyl-1-(tetrahydrofuran-3-yl)-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-1-cyclopropyl-N,4-dimethyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-1-cyclopropyl-N-(cyclopropylmethyl)-4-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-1-cyclopropyl-N-ethyl-4-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-N,1-dicyclopropyl-4-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-1-cyclopropyl-N-isopropyl-4-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-1-cyclopropyl-N-[(2S)-2-hydroxypropyl]-4-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-1-cyclopropyl-N-[(2R)-2-hydroxypropyl]-4-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-1-cyclopropyl-N-(2-hydroxy-2-methylpropyl)-4-methyl-1H-pyrazole-5-carboxamide;   4-cyano-3-(4-cyanophenyl)-N-ethyl-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyano-3-methylphenyl)-1-isopropyl-N,4-dimethyl-1H-pyrazole-5-carboxamide;   4-cyano-3-(4-cyanophenyl)-N,1-diisopropyl-1H-pyrazole-5-carboxamide;   4-cyano-3-(4-cyanophenyl)-1-isopropyl-N-methyl-1H-pyrazole-5-carboxamide;   4-cyano-3-(4-cyanophenyl)-N-(cyclopropylmethyl)-1-isopropyl-1H-pyrazole-5-carboxamide;   4-cyano-3-(4-cyanophenyl)-N-cyclopropyl-1-isopropyl-1H-pyrazole-5-carboxamide;   4-benzyl-3-(4-cyanophenyl)-N,1-diisopropyl-1H-pyrazole-5-carboxamide;   4-benzyl-3-(4-cyanophenyl)-N-cyclopropyl-1-isopropyl-1H-pyrazole-5-carboxamide;   4-benzyl-3-(4-cyanophenyl)-N-ethyl-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-N-cyclopropyl-4-(3,3-difluorocyclobutyl)-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-(3,3-difluorocyclobutyl)-1-isopropyl-N-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-(3,3-difluorocyclobutyl)-N-ethyl-1-isopropyl-1H-pyrazole-5-carboxamide;   1-sec-butyl-3-(4-cyanophenyl)-N-(cyclopropylmethyl)-4-ethyl-1H-pyrazole-5-carboxamide;   1-sec-butyl-3-(4-cyanophenyl)-4-ethyl-N-isopropyl-1H-pyrazole-5-carboxamide;   1-sec-butyl-3-(4-cyanophenyl)-N,4-diethyl-1H-pyrazole-5-carboxamide;   1-sec-butyl-3-(4-cyanophenyl)-N-cyclopropyl-4-ethyl-1H-pyrazole-5-carboxamide;   1-sec-butyl-3-(4-cyanophenyl)-4-ethyl-N-methyl-1H-pyrazole-5-carboxamide;   1-sec-butyl-3-(4-cyanophenyl)-4-ethyl-N-(2-hydroxy-2-methylpropyl)-1H-pyrazole-5-carboxamide;   1-sec-butyl-3-(4-cyanophenyl)-4-ethyl-N-[(2R)-2-hydroxypropyl]-1H-pyrazole-5-carboxamide;   1-sec-butyl-3-(4-cyanophenyl)-4-ethyl-N-[(2S)-2-hydroxypropyl]-1H-pyrazole-5-carboxamide;   1-sec-butyl-3-(4-cyanophenyl)-4-ethyl-N-[2-(methylamino)-2-oxoethyl]-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-N-(cyclopropylmethyl)-4-ethyl-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-N-cyclopropyl-4-ethyl-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-ethyl-1-isopropyl-N-methyl-1H-pyrazole-5-carboxamide;   3-(4-cyano-3-methylphenyl)-1-isopropyl-4-methyl-N-[2-(methylamino)-2-oxoethyl]-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-ethyl-N-[(2S)-2-hydroxypropyl]-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-ethyl-N-[(2R)-2-hydroxypropyl]-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-N,4-diethyl-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-ethyl-N,1-diisopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-ethyl-N-(2-hydroxy-2-methylpropyl)-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-cyanophenyl)-4-ethyl-1-isopropyl-N-[2-(methylamino)-2-oxoethyl]-1H-pyrazole-5-carboxamide;   3-(4-cyano-3-methylphenyl)-4-cyclopropyl-1-isopropyl-N-[2-(methylamino)-2-oxoethyl]-1H-pyrazole-5-carboxamide;   
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         and the pharmaceutically acceptable salts and solvates of any thereof. 
       
     
     
         19 . A compound selected from:
 3-(4-cyanophenyl)-4-cyclopropyl-N-(2-hydroxy-2-methylpropyl)-1-isopropyl-1H-pyrazole-5-carboxamide;   3-(4-Cyano-3-methylphenyl)-N-[(2S)-2-hydroxypropyl]-1-isopropyl-4-methyl-1H-pyrazole-5-carboxamide;   3-(4-Cyano-3-methylphenyl)-N-(2-hydroxy-2-methylpropyl)-1-isopropyl-4-methyl-1H-pyrazole-5-carboxamide;   4-Cyano-3-(4-cyanophenyl)-N-ethyl-1-isopropyl-1H-pyrazole-5-carboxamide;   4-Cyano-3-(4-cyanophenyl)-N,1-diisopropyl-1H-pyrazole-5-carboxamide;   3-(4-Cyano-3-methylphenyl)-4-cyclopropyl-1-isopropyl-N-[2-(methylamino)-2-oxoethyl]-1H-pyrazole-5-carboxamide;   
       
         
           
           
               
               
           
         
         and the pharmaceutically acceptable salts and solvates of any thereof. 
       
     
     
         20 . A pharmaceutical composition including a compound according to  claim 1 , or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient, diluent, carrier or adjuvant. 
     
     
         21 - 25 . (canceled) 
     
     
         26 . A method of treatment of a mammal to treat a disorder which would benefit from progesterone receptor modulation including treating said mammal with an effective amount of a compound according to  claim 1 , or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         27 . A method of treatment of a mammal to treat endometriosis, uterine fibroids (leiomyomata), menorrhagia, adenomyosis, primary and secondary dysmenorrhoea (including symptoms of dyspareunia, dyschexia and chronic pelvic pain), chronic pelvic pain syndrome, or breast, ovarian or endometrial cancer, including treating said mammal with an effective amount of a compound according to  claim 1 , or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         28 . A combination of a compound according to  claim 1 , or a pharmaceutically acceptable salt or solvate thereof, and another therapeutically active entity. 
     
     
         29 . A compound of the formula (III), (IV), (V), (VI) or (VII): 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , R 3 , and R 6  are as defined in  claim 1  and R E  is a suitable ester-forming group. 
       
     
     
         30 . A compound as claimed in  claim 29  wherein R E  is C 1-10  alkyl, phenyl optionally substituted by from 1 to 3 substituents each independently selected from C 1-6  alkyl, halo and nitro, or phenylmethyl optionally substituted in the phenyl ring by from 1 to 3 substituents each independently selected from C 1-6  alkyl, halo and nitro.