PYRROLO[2,3-d]PYRIMIDINE TROPOMYSIN-RELATED KINASE INHIBITORS

A compound of Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein
• R1 is H, or C1-5 alkyl optionally substituted by up to 3 substituents independently selected from OH, CON(R5R6), SO2R7, SR7, OR7, CH2OH, CO2R5, SONR7R7, NR7SO2R5, CN, NO2 and R8, or a ring system selected from C3-5 cycloalkyl, propellanyl, or a 4-6 membered saturated heterocyclyl ring, which ring system has up to 3 ring hetero-atoms selected from N, O and S, and which ring system is optionally substituted by up to 3 substituents independently selected from methyl, OH, CON(R5R6), SO2R7, OR7, CH2OH, CO2R5, SONR7R7, NR7SO2R5, CN, NO2 and R8;
• R2 is H or methyl;
• R3 is H, NH2 or NH(C1-3 alkyl optionally substituted with up to 3 substituents independently selected from OH and O(C1-3 alkyl));
• R101 is H, OH, methyl, cyclopropyl, methoxy, ethyl, ethoxy or CN,
• X is a bond, O, (CH—R4)n, NR104, OCH2 or CH2O;
• R4 is independently H, CH3, CH2OH, CH2OCH3, OH, NH2, NHCH3, N(CH3)2, CH2NH2, CH2NHCH3, or CH2N(CH3)2;
• R104 is H, C1-3 alkyl or a C4-6 saturated carbocycle, each of which is optionally substituted by up to 3 substituents independently selected from C1-3 alkyl, CH2OH and NH2;
• n is 1 or 2;
• R102 is a ring system which is a 3-7 membered monocyclic carbocyclic or heterocyclic system, or an 8-14-membered bicyclic system, which ring system may be saturated or partially or fully unsaturated, wherein the heterocyclic ring system may have up to 5 ring hetero-atoms selected from N, S, and O, wherein the bicyclic ring system can be 2 rings (carbocyclic-carbocyclic, carbocyclic-heterocyclic, heterocyclic-carbocyclic or heterocyclic-heterocyclic) fused or linked by a single bond, which ring system is optionally substituted by up to 3 substituents independently selected from, where possible—halo, CN, NR5R6, SO2R7, SR7, C1-4 alkyl optionally substituted by up to 3 OH and/or C1-3 alkoxy groups, C3-6 cycloalkyl optionally substituted by up to 3 OH and/or C1-3 alkoxy groups, C1-3 alkyl substituted by up to 3 halogen, OH, O(C1-3 alkyl), O(C3-6 cycloalkyl optionally substituted by up to 3 OH and/or C1-3 alkoxy groups, O(C1-3 alkyl substituted by up to 3 halogen), O(C1-3 alkyl substituted by up to 3 OH and/or C1-3 alkoxy groups), NR5SO2R7, ═O, R8, C(O)R8, NO2, NR5CO2R7, NR5COR7, OR8, S(O)R7, and CH2R8;
• R5 and R6 are each independently H, or C1-5 alkyl optionally substituted by up to 3 substituents independently selected from OH, CONR7R7, SO2R7, OR7, CH2OH, CO2R7, SONR7R7, NR7SO2R7, CN, NO2 and R9, or a ring system selected from C3-5 cycloalkyl, propellanyl, or a 4-6 membered saturated heterocyclyl ring, which ring system is optionally substituted by up to 3 substituents independently selected from OH, CON(R7R7), SO2R7, CO2R7, SONR7R7, NR7SO2R7, CN, NO2, halo, NR7R7, SR7, C1-4 alkyl optionally substituted by up to 3 OH and/or C1-3 alkoxy groups, C3-6 cycloalkyl optionally substituted by up to 3 OH and/or C1-3 alkoxy groups, C1-3 alkyl substituted by 1 to 3 halogen, O(C3-6 cycloalkyl optionally substituted by up to 3 OH and/or C1-3 alkoxy groups, O(C1-3 alkyl substituted by up to 3 halogen, O(C1-3 alkyl substituted by up to 3 OH and/or C1-3 alkoxy, NR7SO2R7, ═O, NO2, NR7CO2R7, and S(O)R7, or R5 and R6 together with the N to which they are attached can be a 4-7 membered ring optionally including up to 2 further ring hetero-atoms independently selected from N, O, S, which ring is optionally substituted by C1-3 alkoxy and/or C1-3 alkyl;
• R7 is H, C1-5 alkyl or C1-5 alkoxy, which C1-5 alkyl or C1-5 alkoxy is optionally substituted by up to 3 substituents independently selected from halogen;
• R8 is a is a ring system which is a 3-7 membered monocyclic carbocyclic or heterocyclic system, or an 8-14-membered bicyclic system, which ring system may be saturated or partially or fully unsaturated, wherein the heterocyclic ring system may have up to 5 ring hetero-atoms selected from N, S, and O,
• wherein the bicyclic ring system can be 2 rings (carbocyclic-carbocyclic, carbocyclic-heterocyclic, heterocyclic-carbocyclic or heterocyclic-heterocyclic) fused or linked by a single bond, which ring system is optionally substituted by up to 3 substituents independently selected from, where possible—halo, CN, NR5R6, SO2R7, SR7, C1-4 alkyl optionally substituted by up to 3 OH and/or C1-3 alkoxy groups, C3-6 cycloalkyl optionally substituted by up to 3 OH and/or C1-3 alkoxy groups, C1-3 alkyl substituted by 1 to 3 halogen, OH, O(C1-3 alkyl), O(C3-6 cycloalkyl optionally substituted by up to 3 OH and/or C1-3 alkoxy groups, O(C1-3 alkyl substituted by up to 3 halogen, O(C1-3 alkyl substituted by up to 3 OH and/or C1-3 alkoxy, NR5SO2R7, ═O, NO2, NR7COR7, NR5CO2R7, and S(O)R7;
• R9 is a is a ring system which is a 3-7 membered monocyclic carbocyclic or heterocyclic system, or an 8-14-membered bicyclic system, which ring system may be saturated or partially or fully unsaturated, wherein the heterocyclic ring system may have up to 5 ring hetero-atoms selected from N, S, and O, wherein the bicyclic ring system can be 2 rings (carbocyclic-carbocyclic, carbocyclic-heterocyclic, heterocyclic-carbocyclic or heterocyclic-heterocyclic) fused or linked by a single bond, which ring system is optionally substituted by up to 3 substituents independently selected from, where possible—halo, CN, NR7R7, SO2R7, SR7, C1-4 alkyl optionally substituted by up to 3 OH and/or C1-3 alkoxy groups, C3-6 cycloalkyl optionally substituted by up to 3 OH and/or C1-3 alkoxy groups, C1-3 alkyl substituted by 1 to 3 halogen, OH, O(C1-3 alkyl), O(C3-6 cycloalkyl optionally substituted by up to 3 OH and/or C1-3 alkoxy groups, O(C1-3 alkyl substituted by up to 3 halogen, O(C1-3 alkyl substituted by up to 3 OH and/or C1-3 alkoxy, NR7SO2R7, ═O, NO2, NR7CO2R7, NR7COR7, and S(O)R7;
• wherein each CH moiety can be replaced by a CF moiety.