sGC STIMULATORS

A compound according to Formula I, or a pharmaceutically acceptable salt thereof,

• ring A is a 5-membered heteroaryl ring;
• each instance of X is independently selected from 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 a heteroaryl ring;
• wherein a minimum of two instances of X and a maximum of three instances of X in ring A can simultaneously be N;
• W is either
• i) absent, and JB is connected directly to the carbon atom bearing two J groups, each J is independently selected from hydrogen, methyl or fluorine, n is 1 and JB is a C2-6 alkyl chain substituted by between 2 and 9 instances of fluorine;
• or
• ii) a ring B that is a phenyl or a 5 or 6-membered heteroaryl ring, C3-7 cycloalkyl ring, or a 4 to 7-membered heterocyclic ring;
• wherein said heteroaryl or heterocyclic ring contains 1 to 3 ring heteroatoms selected from N, O or S;
• wherein when W is ring B, then
• each J is hydrogen;
• n is 0 or an integer selected from 1, 2 and 3;
• and
• each JB is independently selected from halogen, —CN, a C1-6 aliphatic, —ORB or a C3-8 cycloaliphatic group;
• wherein each said C1-6 aliphatic and each said C3-8 cycloaliphatic group is optionally and independently substituted with up to 3 instances of R3;
• each RB is independently selected from hydrogen, a C1-6 aliphatic or a C3-8 cycloaliphatic;
• wherein each said RB that is a C1-6 aliphatic and each said RB that is a C3-8 cycloaliphatic ring is optionally and independently substituted with up to 3 instances of R3a;
• each R3 is independently selected from halogen, —CN, C1-4 alkyl, C1-4 haloalkyl, —O(C1-4 alkyl) or —O(C1-4 haloalkyl);
• and
• each R3a is independently selected from halogen, —CN, C1-4 alkyl, C1-4 haloalkyl, —O(C1-4 alkyl) or —O(C1-4 haloalkyl);
• ring D is a 6-membered heteroaryl ring;
• the bond between each two atoms of ring D is a double bond or a single bond so as to make ring D a heteroaryl ring;
• each instance of Z1 and each instance of Z2 is independently selected from N or C(JD) or CH;
• wherein a maximum of three instances of Z1 and Z2 combined can simultaneously be N;
• and wherein at least one instance of Z2 is a nitrogen;
• Z3 is selected from C or N;
• o is 0 or an integer selected from 1 and 2;
• each JD is either absent or a substituent on any available C atom of ring D, independently selected from halogen, oxo, —CN, —NO2, —ORD, —SRD, —C(O)RD, —C(O)ORD, —OC(O)RD, —C(O)N(RD)2, —N(RD)2, —N(Rd)C(O)RD, —N(Rd)C(O)ORD, —N(Rd)C(O)N(RD)2, —OC(O)N(RD)2, —SO2RD, —SO2N(RD)2, —N(Rd)SO2RD, a C1-6 aliphatic, —(C1-6 aliphatic)-RD, a C3-8 cycloaliphatic ring, a 6 to 10-membered aryl ring, a 4 to 8-membered heterocyclic ring or 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 or S;
• and wherein each of said C1-6 aliphatic chains, each said C3-8 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 R5;
• each RD is independently selected from hydrogen, a C1-6 aliphatic, —(C1-6 aliphatic)-Rf, a C3-8 cycloaliphatic ring, a 4 to 8-membered heterocyclic ring, phenyl or a 5 to 6-membered heteroaryl ring;
• wherein each said 4 to 8-membered heterocyclic ring and each said 5 to 6-membered heteroaryl ring contains between 1 and 3 heteroatoms independently selected from O, N or S;
• and wherein each of said C1-6 aliphatic chains, each said C3-8 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 with up to 5 instances of R5a;
• wherein when any RD is one of a C1-6 aliphatic or a —(C1-6 aliphatic)-Rf group, one or two —CH2— units that form said C1-6 aliphatic chains may, optionally, be replaced by a group independently selected from —C(O)—, —N(Rd)— or —O—;
• each Rd is independently selected from hydrogen, a C1-6 aliphatic, —(C1-6 aliphatic)-Rf, a C3-8 cycloaliphatic ring, a 4 to 8-membered heterocyclic ring, phenyl or 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 or S;
• and wherein each of said C1-6 aliphatic chains, each said C3-8 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 R5b;
• each Rf is independently selected from a C1-3 alkyl, a C3-8 cycloaliphatic ring, a 4 to 8-membered heterocyclic ring, phenyl or a 5 to 6-membered heteroaryl ring;
• wherein each said 4 to 8-membered heterocyclic ring and each said 5 to 6-membered heteroaryl ring contains between 1 and 4 heteroatoms independently selected from O, N or S;
• and wherein each said C3-8 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 R5c;
• when JD is —C(O)N(RD)2, —N(RD)2, —N(Rd)C(O)N(RD)2, —OC(O)N(RD)2 or —SO2N(RD)2, the two RD groups together with the nitrogen atom attached to the two RD 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 or S, in addition to the nitrogen atom to which the two RD 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 R5d;
• when JD is —N(Rd)C(O)RD, the RD group together with the carbon atom attached to the RD group, with the nitrogen atom attached to the Rd group, and with the Rd 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 or S, in addition to the nitrogen atom to which the Rd 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 R5d;
• when JD is —N(Rd)C(O)ORD, the RD group together with the oxygen atom attached to the RD group, with the carbon atom of the —C(O)— portion of the —N(Rd)C(O)ORD group, with the nitrogen atom attached to the Rd group, and with said Rd 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 or S, and is optionally and independently substituted by up to 5 instances of R5d;
• when JD is —N(Rd)C(O)N(RD)2, one of the RD groups attached to the nitrogen atom, together with said nitrogen atom, and with the N atom attached to the Rd group and said Rd 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 or S, and is optionally and independently substituted by up to 5 instances of R5d;
• when JD is —N(Rd)SO2RD, the RD group together with the sulfur atom attached to the RD group, with the nitrogen atom attached to the Rd group, and with said Rd 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 or S, and is optionally and independently substituted by up to 5 instances of R5d;
• each R5 is independently selected from halogen, —CN, C1-6 alkyl, —(C1-6alkyl)-R6, —OR6, —SR6, —COR6, —OC(O)R6, —C(O)OR6, —C(O)N(R6)2, —N(R6)C(O)R6, —N(R6)C(O)OR6, —N(R6)C(O)N(R6)2, —N(R6)2, —SO2R6, —SO2OH, —SO2NHOH, —SO2N(R6)2, —SO2N(R6)(CO)—R6, —N(R6)SO2R6, a C7-12 aralkyl, a C3-8 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 or 4 to 7-membered heterocyclic ring contains up to four ring heteroatoms independently selected from N, O and S, wherein each of said C1-6 alkyl chains, said C7-12 aralkyl, said C3-8 cycloalkyl ring, said 4 to 7-membered heterocyclic ring, said 5 or 6-membered heteroaryl ring or said phenyl group is optionally and independently substituted with up to 3 instances of halogen, C1-4 alkyl, C1-4(haloalkyl), —OH, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —CN, —COOH, —CONH2, —COO(C1-4 alkyl), —O(C1-4 alkyl), —O(C1-4 haloalkyl) or oxo;
• alternatively, two instances of R5 attached to the same or different atoms of JD, together with said atom or atoms of JD to which they are attached, may form a C3-8 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 or S;
• and wherein said C3-8 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 C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, oxo, —C(O)O(C1-4 alkyl), —C(O)OH, —NR(CO)O(C1-4 alkyl), —CONH2, —OH or halogen;
• wherein R is hydrogen or a C1-2 alkyl;
• each R5a is independently selected from halogen, —CN, C1-6 alkyl, —(C1-6alkyl)-R6a, —OR6a, —SR6a, —COR6a, —OC(O)R6a, —C(O)OR6a, —C(O)N(R6a)2, —N(R6a)C(O)R6a, —N(R6a)C(O)OR6a, —N(R6a)C(O)N(R6a)2, —N(R6a)2, —SO2R6a, —SO2OH, —SO2NHOH, —SO2N(R6a)2, —SO2N(R6a)(CO)—R6a, —N(R6a)SO2R6a, a C7-12 aralkyl, a C3-8 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 or 4 to 7-membered heterocyclic ring contains up to four ring heteroatoms independently selected from N, O and S, wherein each of said C1-6 alkyl chains, each said C7-12 aralkyl, said C3-8 cycloalkyl ring, said 4 to 7-membered heterocyclic ring, said 5 or 6-membered heteroaryl ring or phenyl group is optionally and independently substituted with up to 3 instances of halogen, C1-4 alkyl, C1-4(haloalkyl), —OH, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —CN, —COOH, —COO(C1-4 alkyl), —CONH2, —O(C1-4 alkyl), —O(C1-4 haloalkyl) or oxo;
• each R5b is independently selected from halogen, —CN, C1-6 alkyl, —(C1-6alkyl)-R6a, —OR6a, —SR6a, —COR6a, —OC(O)R6a, —C(O)OR6a, —C(O)N(R6a)2, —N(R6a)C(O)R6a, —N(R6a)C(O)OR6a, —N(R6a)C(O)N(R6a)2, —N(R6a)2, —SO2R6a, —SO2OH, —SO2NHOH, —SO2N(R6a)2, —SO2N(R6a)(CO)—R6a, —N(R6a)SO2R6a, a C7-12 aralkyl, a C3-8 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 or 4 to 7-membered heterocyclic ring contains up to four ring heteroatoms independently selected from N, O and S, wherein each of said C1-6 alkyl chains, each said C7-12 aralkyl, said C3-8 cycloalkyl ring, said 4 to 7-membered heterocyclic ring, said 5 or 6-membered heteroaryl ring or phenyl group is optionally and independently substituted with up to 3 instances of halogen, C1-4 alkyl, C1-4(haloalkyl), —OH, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —CN, —COOH, —COO(C1-4 alkyl), —CONH2, —O(C1-4 alkyl), —O(C1-4 haloalkyl) or oxo;
• alternatively, two instances of R5a or two instances of R5b attached to the same or different atoms of RD or Rd, respectively, together with said atom or atoms to which they are attached, may form a C3-8 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 or S;
• and wherein said C3-8 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 C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, oxo, —C(O)O(C1-4 alkyl), —C(O)OH, —NR(CO)O(C1-4 alkyl), —CONH2, —OH or halogen;
• wherein R is hydrogen or a C1-2 alkyl;
• each R5c is independently selected from halogen, —CN, C1-6 alkyl, —(C1-6alkyl)-R6b, —OR6b, —SR6b, —COR6b, —OC(O)R6b, —C(O)OR6b, —C(O)N(R6b)2, —N(R6b)C(O)R6b, —N(R6b)C(O)OR6b, —N(R6b)C(O)N(R6b)2, —N(R6b)2, —SO2R6b, —SO2OH, —SO2NHOH, —SO2N(R6b)(CO)—R6b, —SO2N(R6b)2, —N(R6b)SO2R6b, a C7-12 aralkyl, a C3-8 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 or 4 to 7-membered heterocyclic ring contains up to four ring heteroatoms independently selected from N, O and S, wherein each of said C1-6 alkyl chains, said C7-12 aralkyl, said C3-8 cycloalkyl ring, said 4 to 7-membered heterocyclic ring, said 5 or 6-membered heteroaryl ring or said phenyl groups is optionally and independently substituted with up to 3 instances of halogen, C1-4 alkyl, C1-4(haloalkyl), —OH, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —CN, —COOH, —CONH2, —COO(C1-4 alkyl), —O(C1-4 alkyl), —O(C1-4 haloalkyl) or oxo;
• alternatively, two instances of R5c attached to the same or different atoms of Rf, together with said atom or atoms to which it is attached, may form a C3-8 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 or S;
• and wherein said C3-8 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 C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, oxo, —C(O)O(C1-4 alkyl), —C(O)OH, —CONH2, —NR(CO)O(C1-4 alkyl), —OH or halogen;
• wherein R is hydrogen or a C1-2 alkyl;
• each R5d is independently selected from halogen, —CN, C1-6 alkyl, —(C1-6alkyl)-R6, —OR6, —SR6, —COR6, —OC(O)R6, —C(O)OR6, —C(O)N(R6)2, —N(R6)C(O)R6, —N(R6)C(O)OR6, —N(R6)C(O)N(R6)2, —N(R6)2, —SO2OH, —SO2NHOH, —SO2N(R6)(CO)—R6, —SO2R6, —SO2N(R6)2, —N(R6)SO2R6, a C7-12 aralkyl, a C3-8 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 or 4 to 7-membered heterocyclic ring contains up to four ring heteroatoms independently selected from N, O and S, wherein each of said C1-6 alkyl chains, said C7-12 aralkyl, said C3-8 cycloalkyl ring, said 4 to 7-membered heterocyclic ring, said 5 or 6-membered heteroaryl ring or said phenyl groups is optionally and independently substituted with up to 3 instances of halogen, C1-4 alkyl, C1-4(haloalkyl), —OH, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —CN, —COOH, —CONH2, —COO(C1-4 alkyl), —O(C1-4 alkyl), —O(C1-4 haloalkyl) or oxo;
• two instances of R5 or two instances of R5d, attached to the same or different atoms of JD, together with said atom or atoms to which they are attached, may optionally form a C3-8 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 or S;
• and wherein said C3-8 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 C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, oxo, —C(O)O(C1-4 alkyl), —C(O)OH, —CONH2, —NR(CO)O(C1-4 alkyl), —OH or halogen;
• wherein R is hydrogen or a C1-2 alkyl;
• each R6 is independently selected from hydrogen, a C1-6 aliphatic, phenyl, benzyl, a C3-8 cycloalkyl ring, a 4 to 7-membered heterocyclic ring or a 5 or 6-membered heteroaryl ring, wherein each of said C1-6 aliphatic, each of said phenyl, each of said benzyl, each of said C3-8 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, C1-4 alkyl, —OH, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —CN, —COOH, —COO(C1-4alkyl), —O(C1-4 alkyl), —O(C1-4 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 R6a is independently selected from hydrogen, a C1-6 aliphatic, phenyl, benzyl, a C3-8 cycloalkyl ring, a 4 to 7-membered heterocyclic ring or a 5 or 6-membered heteroaryl ring, wherein each of said C1-6 aliphatic, each of said phenyl, each of said benzyl, each of said C3-8 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, C1-4 alkyl, —OH, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —CN, —COOH, —COO(C1-4alkyl), —O(C1-4 alkyl), —O(C1-4 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 R6b is independently selected from hydrogen, a C1-6 aliphatic, phenyl, benzyl, a C3-8 cycloalkyl ring, a 4 to 7-membered heterocyclic ring or a 5 or 6-membered heteroaryl ring, wherein each of said C1-6 aliphatic, each of said phenyl, each of said benzyl, each of said C3-8 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, C1-4 alkyl, —OH, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —CN, —COOH, —COO(C1-4alkyl), —O(C1-4 alkyl), —O(C1-4 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;
• wherein
• two instances of R6 linked to the same nitrogen atom of R5 or R5d, together with said nitrogen atom of R5 or R5d, 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 or S;
• two instances of R6a linked to a nitrogen atom of R5a or R5b, 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 or S;
• two instances of R6b linked to a nitrogen atom of R5c, 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 or S;
• ring E is selected from a tetrahydropyridine, a piperazine, a pyrroline or an imidazolidine ring;
• wherein when ring E is a tetrahydropyridine or pyrroline and contains a double bond between two ring carbon atoms, said double bond is the fused bond between ring E and ring F, with one of its atoms being Z3 that is an unsubstituted carbon atom;
• when ring E is a piperazine or an imidazolidine, Z3 is a nitrogen atom situated in a bridge position of the bicyclic ring system formed by ring E and ring F and there is no double bond in ring E;
• ring F is a 5 or 6-membered heteroaryl ring containing up to 4 heteroatoms independently selected from N, O and S;
• r is 0 or an integer selected from 1 and 2;
• s is 0 or an integer selected from 1, 2, 3, 4 and 5;
• each instance of JE is independently selected from:
• halogen, —CONH2, —CONHR13, —CON(R13)2, —CH2OH, —CH(R13)(OH), —C(R13)2OH, C1-6 alkyl, C1-6 haloalkyl, a tetrazole ring, —CONHSO2R13 or oxo;
• each instance of R13 is independently selected from a C1-6 alkyl, C1-6 haloalkyl, or a C3-6 cycloalkyl ring, or two instances of R13 attached to the same N atom can form a 5-6 membered heterocyclic ring containing up to 3 heteroatoms selected from N, O and S;
• each instance of JF is independently selected from oxo or —(Y)—R9;
• wherein Y is either absent or a C1-6 alkyl chain, optionally substituted by up to 6 instances of fluoro;
• and wherein when Y is said C1-6 alkyl chain, up to 3 methylene units of this alkyl chain, can be replaced by a group selected from —O—, —C(O)— or —N((Y1)—R99)—;
• each R9 is independently selected from hydrogen, halogen, C1-6 aliphatic, —CN, —OR10, —COR10, —OC(O)R10, —C(O)OR10, —C(O)N(R10)2, —C(O)N(R10)SO2R, —N(R10)C(O)R10, —N(R10)C(O)OR10, —N(R10)C(O)N(R10)2, —N(R10)2, —SO2R10, —SO2N(R10)2, —SO2N(R10)COOR10, —SO2N(R10)C(O)R10, —N(R10)SO2R10, —SO2OH, —SO2NHOH, —SO2N(R10)(CO)—R10, a C3-6 cycloalkyl ring, a 4 to 8-membered heterocyclic ring, a phenyl ring or 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 or S;
• and wherein each of said C1-6 aliphatic, C3-6 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 R11a;
• each instance of Y1 is either absent or a C1-6 alkyl chain, optionally substituted by up to 6 instances of fluoro;
• wherein
• when Y1 is absent, each R99 is independently selected from hydrogen, —COR10, —C(O)OR10, —C(O)N(R10)2, —C(O)N(R10)SO2R10, —SO2R10, —SO2N(R10)2, —SO2N(R10)COOR10, —SO2N(R10)C(O)R10, —SO2OH, —SO2NHOH, —SO2N(R10)(CO)—R10, a C3-6 cycloalkyl ring, a 4 to 8-membered heterocyclic ring, a phenyl ring or a 5 to 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 or S;
• and wherein each of said C3-6 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 R11a;
• when Y1 is present, each R99 is independently selected from hydrogen, halogen, —CN, —OC(O)R10, —OR10, —COR10, —C(O)OR10, —C(O)OR10, —C(O)N(R10)2, —C(O)N(R10)SO2R10, —SO2R10, —SOR10, —SR10, —SO2N(R10)2, —SO2N(R10)COOR10, —SO2N(R10)C(O)R10, —SO2OH, —SO2NHOH, —SO2N(R10)(CO)—R10, a C3-6 cycloalkyl ring, a 4 to 8-membered heterocyclic ring, a phenyl ring or a 5 to 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 or S;
• and wherein each of said C3-6 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 R11a;
• each R10 is independently selected from hydrogen, a C1-6 alkyl, —(C1-6 alkyl)-R14, phenyl, benzyl, a C3-6 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 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 C1-6 alkyl, each said phenyl, each said benzyl, each said C3-8 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 R11b;
• each R14 is independently selected from a phenyl, a benzyl, a C3-6 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 or 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 C3-8 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 R11c;
• each R11a is independently selected from halogen, C1-6 alkyl, —CN, —OR12, —COR12, —C(O)OR12, —C(O)N(R12)2, —N(R12)C(O)R12, —N(R12)C(O)OR12, —N(R12)C(O)N(R12)2, —N(R12)2, —SO2R12, —SO2N(R12)2 or —N(R12)SO2R12;
• wherein each of said C1-6 alkyl is optionally and independently substituted by up to 6 instances of fluoro and/or 3 instances of R121;
• each R11b is independently selected from halogen, C1-6 alkyl, —CN, —OR12, —COR12, —C(O)OR12, —C(O)N(R12)2, —N(R12)C(O)R12, —N(R12)C(O)OR12, —N(R12)C(O)N(R12)2, —N(R12)2, —SO2R12, —SO2N(R12)2 or —N(R12)SO2R12;
• wherein each of said C1-6 alkyl is optionally and independently substituted by up to 6 instances of fluoro and/or 3 instances of R121;
• each R11c is independently selected from halogen, C1-6 alkyl, —CN, —OR12, —COR12, —C(O)OR12, —C(O)N(R12)2, —N(R12)C(O)R12, —N(R12)C(O)OR12, —N(R12)C(O)N(R12)2, —N(R12)2, —SO2R12, —SO2N(R12)2 or —N(R12)SO2R12;
• wherein each of said C1-6 alkyl is optionally and independently substituted by up to 6 instances of fluoro and/or 3 instances of R121;
• each R12 is selected from hydrogen, C1-4 alkyl, C1-4(fluoroalkyl), —OH, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —CN, —COOH, —COO(C1-4 alkyl), —O(C1-4 alkyl), —O(C1-4 fluoroalkyl) or oxo;
• each R121 is selected from C1-4 alkyl, C1-4(fluoroalkyl), —OH, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —CN, —COOH, —COO(C1-4 alkyl), —O(C1-4 alkyl), —O(C1-4 fluoroalkyl) or oxo;
• RC1 is either a lone pair on N or selected from hydrogen, —OH, C1-2 alkyl, C1-2 haloalkyl, —O(C1-2 alkyl), —O(C1-2 haloalkyl), —COCH3, —CONH2, —NH2, —NH(C1-2 alkyl), —N(C1-2 alkyl)2, —CN, —S(C1-2 alkyl), —S(C1-2 haloalkyl), —C≡CH, —CH═CH2, —C(OH)(Me)H, —S(O)(C1-2 alkyl), —S(O)(C1-2 haloalkyl);
• —S(O)2(C1-2 alkyl), —S(O)2(C1-2 haloalkyl);
• and
• RC2 is either a lone pair on N or selected from hydrogen, halogen, C1-6 alkyl and C1-6 haloalkyl.