sGC stimulators

1. A compound of Formula I-c, or pharmaceutically acceptable salt thereof:

wherein:

ring A is a 5-membered heteroaryl ring; each instance of X is independently C or N and the bond between each two instances of X is either a single or a double bond so as to make ring A an aromatic heterocycle; wherein a minimum of 2 instances of X and a maximum of 3 instances of X in ring A can simultaneously be N;

ring B is selected from a phenyl, a 5 or 6-membered heteroaryl ring, containing 1 or 2 ring heteroatoms independently selected from N, O and S, a C 3-7 cycloalkyl ring and a 4 to 7-membered heterocyclic ring, containing up to 3 heteroatoms independently selected from O, N and S;

n is 0 or an integer selected from 1, 2 and 3;

each J B is independently selected from halogen, —CN, a C 1-6 aliphatic, —OR B and a C 3-8 cycloaliphatic group; wherein each said C 1-6 aliphatic and each said C 3-8 cycloaliphatic group is optionally and independently substituted with up to 3 instances of R 3 ;

each R B is independently selected from hydrogen, a C 1-6 aliphatic and a C 3-8 cycloaliphatic; wherein each of said R B that is a C 1-6 aliphatic and each of said R B that is a C 3-8 cycloaliphatic ring is optionally and independently substituted with up to 3 instances of R 3a ;

each R 3 is independently selected from halogen, —CN, C 1-4 alkyl, C 1-4 haloalkyl, —O(C 1-4 alkyl) and —O(C 1-4 haloalkyl);

each R 3a is independently selected from halogen, —CN, C 1-4 alkyl, C 1-4 haloalkyl, —O(C 1-4 alkyl) and —O(C 1-4 haloalkyl);

Z 1 in ring D is CH or N; Z is C or N; wherein if Z 1 is CH, then Z must be C; and if Z 1 is N, then Z may be C or N;

each J D is independently selected from J A , —CN, —NO 2 , —OR D , —SR D , —C(O)R D , —C(O)OR D , —OC(O)R D , —C(O)N(R D ) 2 , —N(R D ) 2 , —N(R d )C(O)R D , —N(R d )C(O)OR D , —N(R d )C(O)N(R D ) 2 , —OC(O)N(R D ) 2 , —SO 2 R D , —SO 2 N(R D ) 2 , —N(R d )SO 2R D , —N(R d )SO 2 NHR D , —N(R d )SO 2 NHC(O)OR D , —N(R d )SO 2 NHC(O)R D , a C 1-6 aliphatic, —(C 1-6 aliphatic)-R D , a C 3-8 cycloaliphatic ring, a 6 to 10-membered aryl ring, a 4 to 8-membered heterocyclic ring and a 5 to 10-membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring and each said 5 to 10-membered heteroaryl ring contains between 1 and 3 heteroatoms independently selected from O, N and S; and wherein each said C 1-6 aliphatic, each said C 1-6 aliphatic portion of the —(C 1-6 aliphatic)-R D moiety, each said C 3-8 cycloaliphatic ring, each said 6 to 10-membered aryl ring, each said 4 to 8-membered heterocyclic ring and each said 5 to 10-membered heteroaryl ring is optionally and independently substituted with up to 5 instances of R 5d ;

J A is selected from a lone pair on nitrogen, hydrogen, halogen, oxo, methyl, hydroxyl, methoxy, trifluoromethyl, trifluoromethoxy and —NR a R b ; wherein R a and R b are each independently selected from hydrogen, C 1-6 alkyl and a 3-6 cycloalkyl ring; or wherein R a and R b , together with the nitrogen atom to which they are both attached, form a 4-8 membered heterocyclic ring, or a 5-membered heteroaryl ring optionally containing up to two additional heteroatoms selected from N, O and S; wherein each of said 4-8 membered heterocyclic ring and 5-membered heteroaryl ring is optionally and independently substituted by up to 6 instances of fluorine;

each R D is independently selected from hydrogen, a C 1-6 aliphatic, —(C 1-6 aliphatic)-R f , a C 3-8 cycloaliphatic ring, a 4 to 10-membered heterocyclic ring, and a 5 to 6-membered heteroaryl ring; wherein each said 4 to 10-membered heterocyclic ring and each said 5 to 6-membered heteroaryl ring contains between 1 and 3 heteroatoms independently selected from O, N and S; and wherein each said C 1-6 aliphatic, each said C 1-6 aliphatic portion of the —(C 1-6 aliphatic)-R f moiety, each said C 3-8 cycloaliphatic ring, each said 4 to 10-membered heterocyclic ring, each said phenyl and each said 5 to 6-membered heteroaryl ring is optionally and independently substituted with up to 5 instances of R 5a ; wherein when any R D is one of a C 1-6 aliphatic or a —(C 1-6 aliphatic)-R f group, one or two —CH 2 — units that form said C 1-6 aliphatic chains may, optionally, be replaced by a group independently selected from —N(R d )—, —CO— and −O—;

each R d is independently selected from hydrogen, a C 1-6 aliphatic, —(C 1-6 aliphatic)-R f , a C 3-8 cycloaliphatic ring, a 4 to 8-membered heterocyclic ring, phenyl and a 5 to 6-membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring and each said 5 or 6-membered heteroaryl ring contains between 1 and 3 heteroatoms independently selected from O, N and S; and wherein each said C 1-6 aliphatic, each said C 1-6 aliphatic portion of the —(C 1-6 aliphatic)-R f moiety, each said C 3-8 cycloaliphatic ring, each said 4 to 8-membered heterocyclic ring, each said phenyl and each said 5 to 6-membered heteroaryl ring is optionally and independently substituted by up to 5 instances of R 5b ; wherein when any R d is one of a C 1-6 aliphatic or a —(C 1-6 aliphatic)-R f group, one or two —CH 2 — units that form said C 1-6 aliphatic chains may, optionally, be replaced by a group independently selected from —N(R dd )—, —CO— and —O—;

each R dd is independently selected from hydrogen, a C 1-6 aliphatic, —(C 1-6 aliphatic)-R f , a C 3-8 cycloaliphatic ring, a 4 to 8-membered heterocyclic ring, phenyl and a 5 to 6-membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring and each said 5 or 6-membered heteroaryl ring contains between 1 and 3 heteroatoms independently selected from O, N and S; and wherein each said C 1-6 aliphatic, each said C 1-6 aliphatic portion of the —(C 1-6 aliphatic)-R f moiety, each said C 3-8 cycloaliphatic ring, each said 4 to 8-membered heterocyclic ring, each said phenyl and each said 5 to 6-membered heteroaryl ring is optionally and independently substituted by up to 5 instances of R 5b ;

each R f is independently selected from a C 1-3 alkyl, a C 3-8 cycloaliphatic ring, a 4 to 10-membered heterocyclic ring, phenyl and a 5 to 6-membered heteroaryl ring; wherein each said 4 to 10-membered heterocyclic ring and each said 5 to 6-membered heteroaryl ring contains between 1 and 4 heteroatoms independently selected from O, N and S; and wherein each said C 3-8 cycloaliphatic ring, each said 4 to 10-membered heterocyclic ring, each said phenyl and each said 5 to 6-membered heteroaryl ring is optionally and independently substituted by up to 5 instances of R 5c ;

when J D is —C(O)N(R D ) 2 , —N(R D ) 2 , —N(R d )C(O)N(R D ) 2 , —OC(O)N(R D ) 2 or —SO 2 N(R D ) 2 , the two R D groups together with the nitrogen atom attached to the two R D groups may form a 4 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally contains up to 3 additional heteroatoms independently selected from N, O and S, in addition to the nitrogen atom to which the two R D groups are attached; and wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring is optionally and independently substituted by up to 5 instances of R 5 ;

when J D is —N(R d )C(O)R D , the R D group together with the carbon atom attached to the R D group, with the nitrogen atom attached to the R d group, and with the R d group may form a 4 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally contains up to 2 additional heteroatoms independently selected from N, O and S, in addition to the nitrogen atom to which the R d group is attached; and wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring is optionally and independently substituted by up to 5 instances of R 5 ;

when J D is —N(R d )C(O)OR D , the R D group together with the oxygen atom attached to the R D group, with the carbon atom of the —C(O)— portion of the —N(R d )C(O)OR D group, with the nitrogen atom attached to the R d group, and with said R d group, may form a 4 to 8-membered heterocyclic ring; wherein said 4 to 8-membered heterocyclic ring optionally contains up to 2 additional heteroatoms independently selected from N, O and S, and is optionally and independently substituted by up to 5 instances of R 5 ;

when J D is —N(R d )C(O)N(R D ) 2 , one of the R D groups attached to the nitrogen atom, together with said nitrogen atom, and with the N atom attached to the R d group and said R d group may form a 4 to 8-membered heterocyclic ring; wherein said 4 to 8-membered heterocyclic ring optionally contains up to 2 additional heteroatoms independently selected from N, O and S, and is optionally and independently substituted by up to 5 instances of R 5 ;

when J D is —N(R d )SO 2 R D , the R D group together with the sulfur atom attached to the R D group, with the nitrogen atom attached to the R d group, and with said R d group may combine to form a 4 to 8-membered heterocyclic ring; wherein said 4 to 8-membered heterocyclic ring optionally contains up to 2 additional heteroatoms independently selected from N, O and S, and is optionally and independently substituted by up to 5 instances of R 5 ;

each R 5 is independently selected from halogen, —CN, C 1-6 alkyl, —(C 1-6 alkyl)-R 6 , —OR 6 , —SR 6 , —COR 6 , —OC(O)R 6 , —C(O)OR 6 , —C(O)N(R 6 ) 2 , —C(O)N(R 6 )SO 2 R 6 , —N(R 6 )C(O)R 6 , —N(R 6 )C(O)OR 6 , —N(R 6 )C(O)N(R 6 ) 2 , —N(R 6 ) 2 , —SO 2 R 6 , —SO 2 OH, —SO 2 NHOH, —SO 2 N(R 6 ) 2 , —SO 2 N(R 6 )COOR 6 , —SO 2 N(R 6 )C(O)R 6 , —N(R 6 )SO 2 R 6 , —(C═O)NHOR 6 , a C 3-8 cycloalkyl ring, a 4 to 7-membered heterocyclic ring, a 5 or 6-membered heteroaryl ring, phenyl, benzyl, an oxo group and a bicyclic group; wherein each of said 5 or 6-membered heteroaryl ring or 4 to 7-membered heterocyclic ring contains up to 4 ring heteroatoms independently selected from N, O and S; and wherein each of said C 1-6 alkyl, C 1-6 alkyl portion of the —(C 1-6 alkyl)-R 6 moiety, C 3-8 cycloalkyl ring, 4 to 7-membered heterocyclic ring, 5 or 6-membered heteroaryl ring, benzyl or phenyl group is optionally and independently substituted with up to 3 instances of halogen, C 1-4 alkyl, —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —COOH, —CONH 2 , —COO(C 1-4 alkyl), —O(C 1-4 alkyl), —O(C 1-4 haloalkyl) or oxo; wherein said bicyclic group contains ring one and ring two in a fused or bridged relationship, said ring one is a 4 to 7-membered heterocyclic ring, a 5 or 6-membered heteroaryl ring, phenyl or benzyl, and said ring two is a phenyl ring or a 5 or 6-membered heteroaryl ring containing up to 3 ring heteroatoms selected from N, O and S; and wherein said bicyclic group is optionally and independently substituted by up to six instances of halogen, C 1-4 alkyl, —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —COOH, —CONH 2 , —COO(C 1-4 alkyl), —O(C 1-4 alkyl), —O(C 1-4 haloalkyl) or oxo;

two instances of R 5 , attached to the same or different atoms of J D , together with said atom or atoms to which they are attached, may optionally form a C 3-8 cycloalkyl ring, a 4 to 6-membered heterocyclic ring; a phenyl or a 5 or 6-membered heteroaryl ring, resulting in a bicyclic system wherein the two rings of the bicyclic system are in a spiro, fused or bridged relationship, wherein said 4 to 6-membered heterocycle or said 5 or 6-membered heteroaryl ring contains up to four ring heteroatoms independently selected from N, O and S; and wherein said C 3-8 cycloalkyl ring, 4 to 6-membered heterocyclic ring, phenyl or 5 or 6-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, oxo, —C(O)O(C 1-4 alkyl), —C(O)OH, —NR(CO)O(C 1-4 alkyl), —CONH 2 , —OH or halogen; wherein R is hydrogen or a C 1-2 alkyl;

each R 5a is independently selected from halogen, —CN, C 1-6 alkyl, —(C 1-6 alkyl)R 6a , —OR 6a , —SR 6a , —COR 6a , —OC(O)R 6a , —C(O)OR 6a , —C(O)N(R 6a ) 2 , —C(O)N(R 6a )SO 2 R 6a , —N(R 6a )C(O)R 6a , —N(R 6a )C(O)OR 6a , —N(R 6a )C(O)N(R 6a ) 2 , —N(R 6a ) 2 , —SO 2 R 6a , —SO 2 OH, —SO 2 NHOH, —SO 2 N(R 6a ) 2 , —SO 2 N(R 6a )COOR 6a , —SO 2 N(R 6a )C(O)R 6a , —N(R 6a )SO 2 R 6a , —(C═O)NHOR 6a , a C 3-8 cycloalkyl ring, a 4 to 7-membered heterocyclic ring, a 5 or 6-membered heteroaryl ring, phenyl, benzyl, an oxo group and a bicyclic group; wherein each 5 or 6-membered heteroaryl ring or 4 to 7-membered heterocyclic ring contains up to 4 ring heteroatoms independently selected from N, O and S, wherein each of said C 1-6 alkyl, C 1-6 alkyl portion of the —(C 1-6 alkyl)R 6a moiety, C 3-8 cycloalkyl ring, 4 to 7-membered heterocyclic ring, 5 or 6-membered heteroaryl ring, benzyl or phenyl group is optionally and independently substituted with up to 3 instances of halogen, C 1-4 alkyl, C 1-4 haloalkyl, —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —COOH, —CONH 2 , —COO(C 1-4 alkyl), —O(C 1-4 alkyl), —O(C 1-4 haloalkyl) or oxo; wherein said bicyclic group contains ring one and ring two in a fused or bridged relationship, said ring one is a 4 to 7-membered heterocyclic ring, a 5 or 6-membered heteroaryl ring, phenyl or benzyl, and said ring two is a phenyl ring or a 5 or 6-membered heteroaryl ring containing up to 3 ring heteroatoms selected from N, O and S; and wherein said bicyclic group is optionally and independently substituted by up to six instances of halogen, C 1-4 alkyl, —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —COOH, —CONH 2 , —COO(C 1-4 alkyl), —O(C 1-4 alkyl), —O(C 1-4 haloalkyl) or oxo;

each R 5b is independently selected from halogen, —CN, C 1-6 alkyl, —(C 1-6 alkyl)R 6a , —OR 6a , —SR 6a , —COR 6a , —OC(O)R 6a , —C(O)OR 6a , —C(O)N(R 6a ) 2 , —C(O)N(R 6a )SO 2 R 6a , —N(R 6a )C(O)R 6a , —N(R 6a )C(O)OR 6a , —N(R 6a )C(O)N(R 6a ) 2 , —N(R 6a ) 2 , —SO 2 R 6a , —SO 2 OH, —SO 2 NHOH, —SO 2 N(R 6a ) 2 , —SO 2 N(R 6a )COOR 6a , —SO 2 N(R 6a )C(O)R 6a , —N(R 6a )SO 2 R 6a , —(C═O)NHOR 6a , a C 3-8 cycloalkyl ring, a 4 to 7-membered heterocyclic ring, a 5 or 6-membered heteroaryl ring, phenyl, benzyl, an oxo group and a bicyclic group; wherein each 5 or 6-membered heteroaryl ring or 4 to 7-membered heterocyclic ring contains up to 4 ring heteroatoms independently selected from N, O and S, wherein each of said C 1-6 alkyl, C 1-6 alkyl portion of the —(C 1-6 alkyl)R 6a moiety, C 3-8 cycloalkyl ring, 4 to 7-membered heterocyclic ring, 5 or 6-membered heteroaryl ring, benzyl or phenyl group is optionally and independently substituted with up to 3 instances of halogen, C 1-4 alkyl, C 1-4 haloalkyl, —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —COOH, —CONH 2 , —COO(C 1-4 alkyl), —O(C 1-4 alkyl), —O(C 1-4 haloalkyl) or oxo; wherein said bicyclic group contains ring one and ring two in a fused or bridged relationship, said ring one is a 4 to 7-membered heterocyclic ring, a 5 or 6-membered heteroaryl ring, phenyl or benzyl, and said ring two is a phenyl ring or a 5 or 6-membered heteroaryl ring containing up to 3 ring heteroatoms selected from N, O and S; and wherein said bicyclic group is optionally and independently substituted by up to six instances of halogen, C 1-4 alkyl, —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —COOH, —CONH 2 , —COO(C 1-4 alkyl), —O(C 1-4 alkyl), —O(C 1-4 haloalkyl) or oxo;

two instances of R 5a or two instances of R 5b attached to the same or different atoms of R D or R d , respectively, together with said atom or atoms to which they are attached, may optionally form a C 3-8 cycloalkyl ring, a 4 to 6-membered heterocyclic ring; a phenyl or a 5 or 6-membered heteroaryl ring, resulting in a bicyclic system wherein the two rings of the bicyclic system are in a spiro, fused or bridged relationship with respect to each other; wherein said 4 to 6-membered heterocycle or said 5 or 6-membered heteroaryl ring contains up to four ring heteroatoms independently selected from N, O and S; and wherein said C 3-8 cycloalkyl ring, 4 to 6-membered heterocyclic ring, phenyl or 5 or 6-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, oxo, —C(O)O(C 1-4 alkyl), —C(O)OH, —C(O)NH 2 , —NR(CO)O(C 1-4 alkyl), —OH or halogen; wherein R is hydrogen or a C 1-2 alkyl;

each R 5c is independently selected from halogen, —CN, C 1-6 alkyl, —(C 1-6 alkyl)-R 6b , —OR 6b , —SR 6b , —COR 6b , —OC(O)R 6b , —C(O)OR 6b , —C(O)N(R 6b ) 2 , —C(O)N(R 6b )SO 2 R 6b , —N(R 6b )C(O)R 6b , —N(R 6b )C(O)OR 6b , —N(R 6b )C(O)N(R 6b ) 2 , —N(R 6b ) 2 , —SO 2 R 6b , —SO 2 OH, —SO 2 NHOH, —SO 2 N(R 6b ) 2 , —SO 2 N(R 6b )COOR 6b , —SO 2 N(R 6b )C(O)R 6b , —N(R 6b )SO 2 R 6b , —(C═O)NHOR 6b , a C 3-8 cycloalkyl ring, a 4 to 7-membered heterocyclic ring, a 5 or 6-membered heteroaryl ring, phenyl, benzyl, an oxo group, and a bicyclic group; wherein each of said 5 or 6-membered heteroaryl ring and each of said 4 to 7-membered heterocyclic ring contains up to 4 ring heteroatoms independently selected from N, O and S; and wherein each of said C 1-6 alkyl, C 1-6 alkyl portion of said —(C 1-6 alkyl)-R 6b moiety, each of said C 3-8 cycloalkyl ring, each of said 4 to 7-membered heterocyclic ring, each of said 5 or 6-membered heteroaryl ring, each of said benzyl and each of said phenyl group is optionally and independently substituted with up to 3 instances of halogen, C 1-4 alkyl, —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —COOH, —CONH 2 , —COO(C 1-4 alkyl), —O(C 1-4 alkyl), —O(C 1-4 haloalkyl) or oxo; wherein said bicyclic group contains a first ring and a second ring in a fused or bridged relationship, said first ring is a 4 to 7-membered heterocyclic ring, a 5 or 6-membered heteroaryl ring, phenyl or benzyl, and said second ring is a phenyl ring or a 5 or 6-membered heteroaryl ring containing up to 3 ring heteroatoms selected from N, O and S; and wherein said bicyclic group is optionally and independently substituted by up to six instances of halogen, C 1-4 alkyl, —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —COOH, —CONH 2 , —COO(C 1-4 alkyl), —O(C 1-4 alkyl), —O(C 1-4 haloalkyl) or oxo;

two instances of R 5c attached to the same or different atoms of R f , together with said atom or atoms to which it is attached, may optionally form a C 3-8 cycloalkyl ring, a 4 to 6-membered heterocyclic ring; a phenyl or a 5 or 6-membered heteroaryl ring, resulting in a bicyclic system wherein the two rings of the bicyclic system are in a spiro, fused or bridged relationship with respect to each other; wherein said 4 to 6-membered heterocycle or said 5 or 6-membered heteroaryl ring contains up to four ring heteroatoms independently selected from N, O and S; and wherein said C 3-8 cycloalkyl ring, 4 to 6-membered heterocyclic ring, phenyl or 5 or 6-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, oxo, —C(O)O(C 1-4 alkyl), —C(O)OH, —CONH 2 , —NR(CO)O(C 1-4 alkyl), —OH or halogen; wherein R is hydrogen or a C 1-2 alkyl;

each R 5d is independently selected from halogen, —CN, C 1-6 alkyl, —(C 1-6 alkyl)-R 6 , —OR 6 , —SR 6 , —COR 6 , —OC(O)R 6 , —C(O)OR 6 , —C(O)N(R 6 ) 2 , —N(R 6 )C(O)R 6 , —N(R 6 )C(O)OR 6 , —N(R 6 )C(O)N(R 6 ) 2 , —N(R 6 ) 2 , —SO 2 R 6 , —SO 2 OH, —SO 2 NHOH, —SO 2 N(R 6 )COR 6 , —SO 2 N(R 6 ) 2 , —N(R 6 )SO 2 R 6 , a C 7-12 aralkyl, a C 3-8 cycloalkyl ring, a 4 to 7-membered heterocyclic ring, a 5 or 6-membered heteroaryl ring, phenyl or an oxo group; wherein each 5 or 6-membered heteroaryl ring and 4 to 7-membered heterocyclic ring contains up to four ring heteroatoms independently selected from N, O and S, wherein each of said C 1-6 alkyl, C 1-6 alkyl portion of the —(C 1-6 alkyl)-R 6 moiety, C 7-12 aralkyl, C 3-8 cycloalkyl ring, 4 to 7-membered heterocyclic ring, 5 or 6-membered heteroaryl ring or phenyl group is optionally and independently substituted with up to 3 instances of halogen, C 1-4 alkyl, C 1-4 (haloalkyl), —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —COOH, —CONH 2 , —COO(C 1-4 alkyl), —O(C 1-4 alkyl), —O(C 1-4 haloalkyl) or oxo;

two instances of R 5d attached to the same or different atoms of J D , together with said atom or atoms of J D to which they are attached, may optionally form a C 3-8 cycloalkyl ring, a 4 to 6-membered heterocyclic ring; a phenyl or a 5 or 6-membered heteroaryl ring, resulting in a bicyclic system wherein the two rings of the bicyclic system are in a spiro, fused or bridged relationship with respect to each other; wherein said 4 to 6-membered heterocycle or said 5 or 6-membered heteroaryl ring contains up to four ring heteroatoms independently selected from N, O and S; and wherein said C 3-8 cycloalkyl ring, 4 to 6-membered heterocyclic ring, phenyl or 5 or 6-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, oxo, —C(O)O(C 1-4 alkyl), —C(O)OH, —NR(CO)O(C 1-4 alkyl), —C(O)NH 2 , —OH or halogen; wherein R is hydrogen or a C 1-2 alkyl;

each R 6 is independently selected from hydrogen, a C 1-6 alkyl, phenyl, benzyl, a C 3-8 cycloalkyl ring, a 4 to 7-membered heterocyclic ring and a 5 or 6-membered heteroaryl ring, wherein each of said C 1-6 alkyl, each of said phenyl, each of said benzyl, each of said C 3-8 cycloalkyl group, each of said 4 to 7-membered heterocyclic ring and each of said 5 or 6-membered heteroaryl ring is optionally and independently substituted with up to 3 instances of halogen, C 1-4 alkyl, —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —COOH, —C(O)NH 2 , —COO(C 1-4 alkyl), —O(C 1-4 alkyl), —O(C 1-4 haloalkyl) or oxo, wherein each of said 5 or 6-membered heteroaryl ring or 4 to 7-membered heterocyclic ring contains up to 4 ring heteroatoms independently selected from N, 0 and S;

each R 6a is independently selected from hydrogen, a C 1-6 alkyl, phenyl, benzyl, a C 3-8 cycloalkyl ring, a 4 to 7-membered heterocyclic ring and a 5 or 6-membered heteroaryl ring, wherein each of said C 1-6 alkyl, each of said phenyl, each of said benzyl, each of said C 3-8 cycloalkyl group, each of said 4 to 7-membered heterocyclic ring and each of said 5 or 6-membered heteroaryl ring is optionally and independently substituted with up to 3 instances of halogen, C 1-4 alkyl, —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —COOH, —C(O)NH 2 , —C(O)N(C 1-6 alkyl) 2 , —C(O)NH(C 1-6 alkyl), —C(O)N(C 1-6 haloalkyl) 2 , —C(O)NH(C 1-6 haloalkyl), C(O)N(C 1-6 alkyl)(C 1-6 haloalkyl), —COO(C 1-6 alkyl), —COO(C 1-6 haloalkyl), —O(C 1-4 alkyl), —O(C 1-4 haloalkyl) or oxo, wherein each of said 5 or 6-membered heteroaryl ring or 4 to 7-membered heterocyclic ring contains up to 4 ring heteroatoms independently selected from N, O and S;

each R 6b is independently selected from hydrogen, a C 1-6 alkyl, phenyl, benzyl, a C 3-8 cycloalkyl ring, a 4 to 7-membered heterocyclic ring and a 5 or 6-membered heteroaryl ring, wherein each of said C 1-6 alkyl, each of said phenyl, each of said benzyl, each of said C 3-8 cycloalkyl group, each of said 4 to 7-membered heterocyclic ring and each of said 5 or 6-membered heteroaryl ring is optionally and independently substituted with up to 3 instances of halogen, C 1-4 alkyl, —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —COOH, —C(O)NH 2 , —COO(C 1-4 alkyl), —O(C 1-4 alkyl), —O(C 1-4 haloalkyl) or oxo, wherein each of said 5 or 6-membered heteroaryl ring or 4 to 7-membered heterocyclic ring contains up to 4 ring heteroatoms independently selected from N, 0 and S;

two instances of R 6 linked to the same nitrogen atom of R 5 or R 5d , together with said nitrogen atom of R 5 or R 5d , respectively, may form a 5 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 5 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally contains up to 2 additional heteroatoms independently selected from N, O and S;

two instances of R 6a linked to a nitrogen atom of R 5a or R 5b , together with said nitrogen, may form a 5 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 5 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally contains up to 2 additional heteroatoms independently selected from N, O and S;

two instances of R 6b linked to a nitrogen atom of R 5c , together with said nitrogen, may form a 5 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 5 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally contains up to 2 additional heteroatoms independently selected from N, O and S;

ring E is a 5 to 7-membered heterocycle or a 5-membered heteroaryl ring; said heterocycle or heteroaryl ring containing up to 4 heteroatoms independently selected from N and O;

o is 0 or an integer selected from 1, 2, and 3;

Y is either absent or is a C 1-6 alkyl chain, optionally substituted by up to 6 instances of fluoro; and wherein Y is a C 1-6 alkyl chain, up to 3 methylene units of this alkyl chain, can be replaced by a group selected from —O—, —C(O)— and —N((Y 1 )—R 90 )—, wherein

Y 1 is either absent or is a C 1-6 alkyl chain, optionally substituted by up to 6 instances of fluoro; and:

when Y 1 is absent, each R 90 is independently selected from hydrogen, —COR 10 , —C(O)OR 10 , —C(O)N(R 10 ) 2 , —C(O)N(R 10 )SO 2 R 10 , —SO 2 R 10 , —SO 2 N(R 10 ) 2 , —SO 2 N(R 10 )COOR 10 , —SO 2 N(R 10 )C(O)R 10 , —(C═O)NHOR 10 a C 3-6 cycloalkyl ring, a 4-8-membered heterocyclic ring, a phenyl ring and a 5-6 membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring or 5 to 6-membered heteroaryl ring contains up to 4 ring heteroatoms independently selected from N, O and S; and wherein each of said C 3-6 cycloalkyl rings, each of said 4 to 8-membered heterocyclic rings, each of said phenyl and each of said 5 to 6-membered heteroaryl rings is optionally and independently substituted with up to 3 instances of R 11 ; and

when Y 1 is present, each R 90 is independently selected from hydrogen, halogen, —CN, —OR 10 , —COR 10 , —OC(O)R 10 , —C(O)OR 10 , —C(O)N(R 10 ) 2 , —C(O)N(R 10 )SO 2 R 10 , —N(R 10 )C(O)R 10 , —N(R 10 )C(O)OR 10 , —N(R 10 )C(O)N(R 10 ) 2 , —N(R 10 ) 2 , —SO 2 R 10 , —SO 2 N(R 10 ) 2 , —SO 2 N(R 10 )COOR 10 , —SO 2 N(R 10 )C(O)R 10 , —N(R 10 )SO 2 R 10 , —(C═O)NHOR 10 , C 3-6 cycloalkyl ring, a 4-8-membered heterocyclic ring, a phenyl ring and a 5-6 membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring or 5 to 6-membered heteroaryl ring contains up to 4 ring heteroatoms independently selected from N, O and S; and wherein each of said C 3-6 cycloalkyl rings, each of said 4 to 8-membered heterocyclic rings, each of said phenyl and each of said 5 to 6-membered heteroaryl rings is optionally and independently substituted with up to 3 instances of R 11 ;

each R 9 is independently selected from hydrogen, halogen, a C 1-6 alkyl, —CN, —OR 10 , —COR 10 , —OC(O)R 10 , —C(O)OR 10 , —C(O)N(R 10 ) 2 , —C(O)N(R 10 )SO 2 R 10 , —N(R 10 )C(O)R 10 , —N(R 10 )C(O)OR 10 , —N(R 10 )C(O)N(R 10 ) 2 , —N(R 10 ) 2 , —SO 2 R 10 , —SO 2 N(R 10 ) 2 , —SO 2 N(R 10 )COOR 10 , —SO 2 N(R 10 )C(O)R 10 , —N(R 10 )SO 2 R 10 , —(C═O)NHOR 10 , C 3-6 cycloalkyl ring, a 4-8-membered heterocyclic ring, a phenyl ring and a 5-6 membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring or 5 to 6-membered heteroaryl ring contains up to 4 ring heteroatoms independently selected from N, O and S; and wherein each of said C 1-6 alkyl, each of said C 3-6 cycloalkyl rings, each of said 4 to 8-membered heterocyclic rings, each of said phenyl and each of said 5 to 6-membered heteroaryl rings is optionally and independently substituted with up to 3 instances of R 11 ;

each R 10 is independently selected from hydrogen, a C 1-6 alkyl, —(C 1-6 alkyl)-R 13 , phenyl, benzyl, a C 3-8 cycloalkyl ring, a 4 to 7-membered heterocyclic ring and a 5 or 6-membered heteroaryl ring, wherein each 5 or 6-membered heteroaryl ring or 4 to 7-membered heterocyclic ring contains up to 4 ring heteroatoms independently selected from N, O and S; and wherein each of said C 1-6 alkyl, C 1-6 alkyl portion of said —(C 1-6 alkyl)-R 13 moiety, each said phenyl, each said benzyl, each said C 3-8 cycloalkyl group, each said 4 to 7-membered heterocyclic ring and each 5 or 6-membered heteroaryl ring is optionally and independently substituted with up to 3 instances of R 11a ;

each R 13 is independently selected from a phenyl, a benzyl, a C 3-6 cycloalkyl ring, a 4 to 7-membered heterocyclic ring or a 5 or 6-membered heteroaryl ring, wherein each 5 or 6-membered heteroaryl ring and 4 to 7-membered heterocyclic ring contains up to 4 ring heteroatoms independently selected from N, O and S; and wherein each said phenyl, each of said benzyl, each said C 3-8 cycloalkyl group, each said 4 to 7-membered heterocyclic ring and each 5 or 6-membered heteroaryl ring is optionally and independently substituted with up to 3 instances of R 11b ;

each R 11 is independently selected from halogen, C 1-6 alkyl, —CN, —OR 12 , —COR 12 , —C(O)OR 12 , —C(O)N(R 12 ) 2 , —N(R 12 )C(O)R 12 , —N(R 12 )C(O)OR 12 , —N(R 12 )C(O)N(R 12 ) 2 , —N(R 12 ) 2 , —SO 2 R 12 , —SO 2 N(R 12 ) 2 and —N(R 12 )SO 2 R 12 ; wherein each of said C 1-6 alkyl is optionally and independently substituted by up to 6 instances of fluoro and/or 3 instances of R 121 ;

each R 11 independently selected from halogen, oxo, C 1-6 alkyl, —CN, —OR 12 , —COR 12 , —C(O)OR 12 , —C(O)N(R 12 ) 2 , —N(R 12 )C(O)R 12 , —N(R 12 )C(O)OR 12 , —N(R 12 )C(O)N(R 12 ) 2 , —N(R 12 ) 2 , —SO 2 R 12 , —SO 2 N(R 12 ) 2 and —N(R 12 )SO 2 R 12 ; wherein each of said C 1-6 alkyl is optionally and independently substituted by up to 6 instances of fluoro and/or 3 instances of R 121 ; and

each R 11b is independently selected from halogen, C 1-6 alkyl, oxo, —CN, —OR 12 , —COR 12 , —C(O)OR 12 , —C(O)N(R 12 ) 2 , —N(R 12 )C(O)R 12 , —N(S)C(O)OR 12 , —N(R 12 )C(O)N(R 12 ) 2 , —N(R 12 ) 2 , —SO 2 R 12 , —SO 2 N(R 12 ) 2 and —N(R 12 )SO 2 R 12 ; wherein each of said C 1-6 alkyl is optionally and independently substituted by up to 6 instances of fluoro and/or 3 instances of R 121 ;

each R 12 is selected from hydrogen, a C 1-6 alkyl, phenyl, benzyl, a C 3-8 cycloalkyl ring, a 4 to 7-membered heterocyclic ring and a 5 or 6-membered heteroaryl ring, wherein each 5 or 6-membered heteroaryl ring or 4 to 7-membered heterocyclic ring contains up to 4 ring heteroatoms independently selected from N, O and S; and wherein each of said C 1-6 alkyl, each said phenyl, each said benzyl, each said C 3-8 cycloalkyl group, each said 4 to 7-membered heterocyclic ring and each 5 or 6-membered heteroaryl ring is optionally and independently substituted with up to 3 instances of halogen, C 1-4 alkyl, C 1-4 (fluoroalkyl), —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —COOH, —CONH 2 , —COO(C 1-4 alkyl), —O(C 1-4 alkyl), —O(C 1-4 fluoroalkyl) or oxo;

each R 121 is selected from hydrogen, a C 1-6 alkyl, phenyl, benzyl, a C 3-8 cycloalkyl ring, a 4 to 7-membered heterocyclic ring and a 5 or 6-membered heteroaryl ring, wherein each 5 or 6-membered heteroaryl ring or 4 to 7-membered heterocyclic ring contains up to 4 ring heteroatoms independently selected from N, O and S; and wherein each of said C 1-6 alkyl, each said phenyl, each said benzyl, each said C 3-8 cycloalkyl group, each said 4 to 7-membered heterocyclic ring and each 5 or 6-membered heteroaryl ring is optionally and independently substituted with up to 3 instances of halogen, C 1-4 alkyl, C 1-4 (fluoroalkyl), —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —COOH, —CONH 2 , —COO(C 1-4 alkyl), —O(C 1-4 alkyl), —O(C 1-4 fluoroalkyl) or oxo;

R C1 is either

i) a ring C; or

ii) is selected from hydrogen, halogen, oxo, —CN, C 1-6 aliphatic, —(C 1-6 aliphatic)-R N , —OR 7 , —OC(O)R 7 , —O(R 7 )C(O)N(R 7 ) 2 , —COR 7 , —C(O)OR 7 , —C(O)N(R 7 ) 2 , —N(R 7 )C(O)R 7 , —N(R 7 )C(O)OR 7 , —N(R 7 )C(O)N(R 7 ) 2 , —N(R 7 ) 2 , —SR 7 , —S(O)R 7 , —SO 2 R 7 , —SO 2 N(R 7 ) 2 , —C(O)N(R 7 )SO 2 R 7 , —SO 2 N(R 7 )COOR 7 , —SO 2 N(R 7 )C(O)R 7 and —N(R 7 )SO 2 R 7 ; wherein each said C 1-6 aliphatic, each C 1-6 aliphatic portion of said —(C 1-6 aliphatic)-R N , is optionally and independently substituted with up to 6 instances of fluoro and up to 2 instances of —CN, —OR 8 , oxo, —N(R 8 ) 2 , —N(R 8 )C(O)R 8 , —N(R 8 )C(O)R 8 , —N(R 8 )C(O)N(R 8 ) 2 , —SO 2 R 8 , —SO 2 N(R 8 ) 2 , —NHOR 8 , —SO 2 N(R 8 )COOR 8 , —SO 2 N(R 8 )C(O)R 8 , —N(R 8 )SO 2 R 8 ;

wherein each R 7 is independently selected from hydrogen, C 1-6 alkyl, C 1-6 fluoroalkyl, a C 3-8 cycloalkyl ring, phenyl, a 4 to 7-membered heterocyclic ring and a 5 or 6-membered heteroaryl ring; wherein each of said 5 or 6-membered heteroaryl ring or 4 to 7-membered heterocyclic ring contains up to 4 ring heteroatoms independently selected from N, O and S; and wherein each of said C 1-6 alkyl, each of said phenyl, each of said C 3-8 cycloalkyl group, each of said 4 to 7-membered heterocyclic ring and each of said 5 or 6-membered heteroaryl ring is optionally and independently substituted with up to 3 instances of halogen, C 1-4 alkyl, —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —COOH, —COO(C 1-4 alkyl), —O(C 1-4 alkyl), —O(C 1-4 haloalkyl) or oxo;

each R 8 is independently selected from hydrogen, C 1-6 alkyl, C 1-6 fluoroalkyl, a C 3-8 cycloalkyl ring, a 4 to 7-membered heterocyclic ring and a 5 or 6-membered heteroaryl ring; wherein each of said 5 or 6-membered heteroaryl ring or 4 to 7-membered heterocyclic ring contains up to 4 ring heteroatoms independently selected from N, O and S; and wherein each of said C 1-6 alkyl, each of said phenyl, each of said C 3-8 cycloalkyl group, each of said 4 to 7-membered heterocyclic ring and each of said 5 or 6-membered heteroaryl ring is optionally and independently substituted with up to 3 instances of halogen, C 1-4 alkyl, —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —COOH, —COO(C 1-4 alkyl), —O(C 1-4 alkyl), —O(C 1-4 haloalkyl) or oxo;

each R N is independently selected from a phenyl ring, a monocyclic 5 or 6-membered heteroaryl ring, a monocyclic C 3-6 cycloaliphatic ring, and a monocyclic 4 to 6-membered heterocycle; wherein said monocyclic 5 or 6-membered heteroaryl ring or said monocyclic 4 to 6-membered heterocycle contain between 1 and 4 heteroatoms selected from N, O and S; wherein said monocyclic 5 or 6-membered heteroaryl ring is not a 1,3,5-triazinyl ring; and wherein said phenyl, said monocyclic 5 to 6-membered heteroaryl ring, said monocyclic C 3-6 cycloaliphatic ring, or said monocyclic 4 to 6-membered heterocycle is optionally and independently substituted with up to 6 instances of fluoro and/or up to 3 instances of J M ;

each J M is independently selected from —CN, a C 1-6 aliphatic, —OR M , —SR M , —N(R M ) 2 , a C 3-8 cycloaliphatic ring and a 4 to 8-membered heterocyclic ring; wherein said 4 to 8-membered heterocyclic ring contains 1 or 2 heteroatoms independently selected from N, O and S; wherein each said C 1-6 aliphatic, each said C 3-8 cycloaliphatic ring and each said 4 to 8-membered heterocyclic ring, is optionally and independently substituted with up to 3 instances of R 7c ;

each R M is independently selected from hydrogen, a C 1-6 aliphatic, a C 3-8 cycloaliphatic ring and a 4 to 8-membered heterocyclic ring; wherein each said 4 to 8-membered heterocyclic ring contains between 1 and 3 heteroatoms independently selected from O, N and S; and wherein

ring C is a phenyl ring, a monocyclic 5 or 6-membered heteroaryl ring, a bicyclic 8 to 10-membered heteroaryl ring, a monocyclic 3 to 10-membered cycloaliphatic ring, or a monocyclic 4 to 10-membered heterocycle; wherein said monocyclic 5 or 6-membered heteroaryl ring, said bicyclic 8 to 10-membered heteroaryl ring, or said monocyclic 4 to 10-membered heterocycle contain between 1 and 4 heteroatoms selected from N, O and S; wherein said monocyclic 5 or 6-membered heteroaryl ring is not a 1,3,5-triazinyl ring; and wherein said phenyl, monocyclic 5 to 6-membered heteroaryl ring, bicyclic 8 to 10-membered heteroaryl ring, monocyclic 3 to 10-membered cycloaliphatic ring, or monocyclic 4 to 10-membered heterocycle is optionally and independently substituted with up to p instances of J C ; wherein p is 0 or an integer selected from 1, 2 and 3;

each J C is independently selected from halogen, —CN, —NO 2 , a C 1-6 aliphatic, —OR H , —SR H , —N(R H ) 2 , a C 3-8 cycloaliphatic ring and a 4 to 8-membered heterocyclic ring; wherein said 4 to 8-membered heterocyclic ring contains 1 or 2 heteroatoms independently selected from N, O and S; wherein each said C 1-6 aliphatic, each said C 3-8 cycloaliphatic ring and each said 4 to 8-membered heterocyclic ring, is optionally and independently substituted with up to 3 instances of R 7d ; or

alternatively, two J C groups attached to two vicinal ring C atoms, taken together with said two vicinal ring C atoms, form a 5 to 7-membered heterocycle that is a new ring fused to ring C; wherein said 5 to 7-membered heterocycle contains from 1 to 2 heteroatoms independently selected from N, O and S;

each R H is independently selected from hydrogen, a C 1-6 aliphatic, a C 3-8 cycloaliphatic ring and a 4 to 8-membered heterocyclic ring; wherein each said 4 to 8-membered heterocyclic ring contains between 1 and 3 heteroatoms independently selected from O, N and S; alternatively, two instances of R H linked to the same nitrogen atom of —N(R H ) 2 , together with said nitrogen atom of —N(R H ) 2 , form a 4 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally contains up to 2 additional heteroatoms independently selected from N, O and S;

each R 7c is independently selected from halogen, —CN, —NO 2 , C 1-4 alkyl, C 1-4 haloalkyl, C 3-8 cycloalkyl ring, —OR 8b , —SR 8b , —N(R 8b ) 2 , —C(O)O(C 1-4 alkyl), —C(O)OH, —NR(CO)CO(C 1-4 alkyl) and an oxo group; wherein each said cycloalkyl group is optionally and independently substituted with up to 3 instances of halogen;

each R 7d is independently selected from halogen, —CN, —NO 2 , C 1-4 alkyl, C 1-4 haloalkyl, C 3-8 cycloalkyl ring, —C(O)O(C 1-4 alkyl), —C(O)OH, —OR 8c , —SR 8c , —N(R 8c ) 2 , and an oxo group; wherein each said cycloalkyl group is optionally and independently substituted with up to 3 instances of halogen;

each R 8b is independently selected from hydrogen, C 1-6 alkyl, C 1-6 fluoroalkyl, a C 3-8 cycloalkyl ring, a 4 to 7-membered heterocyclic ring and a 5 or 6-membered heteroaryl ring; wherein each of said 5 or 6-membered heteroaryl ring or 4 to 7-membered heterocyclic ring contains up to 4 ring heteroatoms independently selected from N, O and S; and wherein each of said C 1-6 alkyl, each of said phenyl, each of said C 3-8 cycloalkyl group, each of said 4 to 7-membered heterocyclic ring and each of said 5 or 6-membered heteroaryl ring is optionally and independently substituted with up to 3 instances of halogen, C 1-4 alkyl, —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —COOH, —COO(C 1-4 alkyl), —O(C 1-4 alkyl), —O(C 1-4 haloalkyl) or oxo;

each R 8c is independently selected from hydrogen, C 1-6 alkyl, C 1-6 fluoroalkyl, a C 3-8 cycloalkyl ring, a 4 to 7-membered heterocyclic ring and a 5 or 6-membered heteroaryl ring; wherein each of said 5 or 6-membered heteroaryl ring or 4 to 7-membered heterocyclic ring contains up to 4 ring heteroatoms independently selected from N, O and S; and wherein each of said C 1-6 alkyl, each of said phenyl, each of said C 3-8 cycloalkyl group, each of said 4 to 7-membered heterocyclic ring and each of said 5 or 6-membered heteroaryl ring is optionally and independently substituted with up to 3 instances of halogen, C 1-4 alkyl, —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —CN, —COOH, —COO(C 1-4 alkyl), —O(C 1-4 alkyl), —O(C 1-4 haloalkyl) or oxo; and

R C2 is selected from hydrogen, halogen, —OH, —O(C 1-6 alkyl), —O(haloC 1-6 alkyl), —O(C 1-6 haloalkyl), —O(cyclopropyl), cyclopropyl, C 1-6 alkyl, C 1-6 haloalkyl and —CN;

provided that the compound is not one represented by Formula C-1 or Formula C-2 depicted below:

wherein

Z 2 is N or C; wherein when Z 2 is C, R 102 is selected from either —NH 2 , —OH, halogen and hydrogen; or, alternatively, when Z 2 is N, R 102 is a lone pair on N;

Z 5 is C or N; wherein when Z 5 is C, each R 100 is independently selected from hydrogen, —CH 3 , —CF 3 , —CONH 2 , —CONH(cyclopropyl), —COOH, —CN, —COO(C 1-3 alkyl), —NHCOOCH 3 and

or, alternatively, when Z 5 is N, one of R 100 is hydrogen and the other is a lone pair on said N;

R 101 is selected from an isoxazole ring, oxo, —C(O)CH 3 and —CH 2 OMe; wherein R 104 is selected from hydrogen, methyl, ethyl and isopropyl, said methyl optionally substituted with up to 3 fluorines;

R 103 is selected from hydrogen, methyl and —CN;

Z 6 is selected from NH or C; said C optionally substituted by methyl and ethyl ester;

also, provided that the compound is not one represented by Formula B represented below or a pharmaceutically acceptable salt thereof,

wherein ring E is a 5-membered, nitrogen containing, heteroaryl ring;

R 201 is an isoxazole, oxazole or thiazole ring;

Z 3 is a ring atom selected from N and C; wherein when Z 3 is N, R 202 is a lone pair on said N or hydrogen or methyl; when Z 3 is C, R 202 is a substituent selected from hydrogen, —OH, —NH 2 , —OCO(tert-Bu), —NHCOMe and oxo;

Z 4 is a ring atom selected from N and C; wherein when Z 4 is N, R 203 is selected from a lone pair on said N, hydrogen and methyl; and wherein when Z 4 is C, R 203 is hydrogen, methyl or —CONH(tert-Bu);

Z 5 is a ring atom selected from N and CH;

R 204 is selected from hydrogen and —NH 2 ;

and provided the compound is not one of the compounds depicted below:

2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein ring B is phenyl or a 5 to 6-membered heteroaryl ring containing 1 or 2 ring heteroatoms selected from N, O and S.

3. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R C1 is selected from hydrogen, halogen, oxo, —CN, C 1-6 aliphatic, —OR 7 , —COR 7 , —C(O)OR 7 , —C(O)N(R 7 ) 2 , —N(R 7 )C(O)R 7 , —N(R 7 ) 2 , —SR 7 , —S(O)R 7 , —SO 2 R 7 , and —SO 2 N(R 7 ) 2 ; wherein each said C 1-6 aliphatic is optionally and independently substituted with up to 6 instances of fluoro and up to 2 instances of —OR 8 or oxo; and

R C2 is selected from hydrogen and halogen.

4. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is represented by Formula I-e:

wherein p is 0 or an integer selected from 1 and 2;

ring C is a 5-membered heteroaryl ring containing up to 4 ring heteroatoms selected from N, O and S; wherein said 5-membered heteroaryl ring is not a 1,3,5-triazinyl ring; or

alternatively, ring C is selected from a C 4-6 cycloalkyl ring and a 4 to 6-membered heterocyclic ring containing up to 2 ring heteroatoms selected from N, O and S;

each J C is independently selected from halogen or a C 1-4 aliphatic optionally and independently substituted by up to 3 instances of C 1-4 alkoxy, C 1-4 fluoroalkoxy, oxo, —C(O)O(C 1-4 alkyl), —C(O)OH, —OH and halogen; and

W is a phenyl and each J is hydrogen.

5. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is represented by Formula I-f or Formula I-g:

wherein W is ring B and each J is hydrogen.

6. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein J D is J A , —N(R D ) 2 , —N(R d )SO 2 NHR D , —N(R d )SO 2 NHCO(O)OR D , or —N(R d )SO 2 NHC(O)R D .

7. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is represented by Formula I-h or Formula I-j:

or Formula I-k or Formula I-m:

wherein W is ring B and each J is hydrogen.

8. The compound according to claim 1 , wherein the compound is one selected from those depicted in Table I:

TABLE I

I-1

I-2

I-3

I-4

I-5

I-6

I-7

I-8

I-9

I-10

I-11

I-12

I-13

I-14

I-45

I-46

I-49

I-66

I-69

I-71

I-72

I-73

I-74

I-75

I-76

I-77

I-78

I-79

I-80

I-81

I-84

I-85

I-86

I-90

9. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and one or more excipients.