Claims for Patent: 8,247,411

Summary for Patent: 8,247,411

Title:	Sulfonyl amide derivatives for the treatment of abnormal cell growth
Abstract:	The present invention relates to a compound of the formula I wherein R1 to R6, A, B, n and m are as defined herein. Such novel sulfonyl amide derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.
Inventor(s):	Michael Joseph Luzzio, Kevin Daniel Freeman-Cook, Samit Kumar Bhattacharya, Matthew Merrill Hayward, Catherine Angela Hulford, Christopher Lowell Autry, Xumiao Zhao, Jun Xiao, Kendra Louise Nelson
Assignee:	Pfizer Inc
Application Number:	US13/045,923
Patent Claims:	1. A compound of formula I: or a pharmaceutically acceptable salt thereof; wherein A is phenyl; B is phenyl or a 5- to 6-membered heteroaryl; K is CH; each R1 is independently selected from the group consisting of —H, halo, —CF3, —CN, —NO2, —NR7R8, —NR7C(NR7R8)(═CR9), —CR7(NR7R8)(═NR7), —NR7C(NR7R8)(═NR7), —NR7C(O)R9, —C(O)NR7R8, —C(O)R9, —C(O)C(O)R9, —C(O)OR10, —OC(O)R9, —OR10, —OC(O)OR10, —S(O)jR11, —S(O)(═NR7)R8, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C1-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C10)aryl and —(C1-C9)heteroaryl moieties of said R1 is optionally independently substituted by one to three R12 groups; R2 and R3 are each independently selected from the group consisting of —H, -halo, —OR10, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C10)aryl and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, (C4-C9)heterocycloalkenyl, —(C6-C10)aryl and —(C1-C9)heteroaryl moieties of said R2 and R3 is optionally substituted by one to three R12 groups; R4 and R5 are each independently selected from the group consisting of —H, —NR7R8, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C10)aryl and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C10)aryl and —(C1-C9)heteroaryl moieties of said R4 and R5 is optionally substituted by one to three R12 groups; R6 is —CF3; R7 and R8 are each independently selected from the group consisting of —H, —OR10, —S(O)jR11, —NO2, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl —(C6-C10)aryl, and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, (C4-C9)heterocycloalkenyl, —(C6-C10)aryl and —(C1-C9)heteroaryl moieties of said R7 and R8 is optionally substituted by one to three R12 groups; each R9 is independently selected from the group consisting of —H, -halo, —NR13R14, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl —(C6-C10)aryl, and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, (C4-C9)heterocycloalkenyl, —(C6-C10)aryl and —(C1-C9)heteroaryl moieties of said R9 is optionally substituted by one to three R12 groups; each R10 is independently selected from the group consisting of —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl —(C6-C10)aryl, and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, (C4-C9)heterocycloalkenyl, —(C6-C10)aryl and —(C1-C9)heteroaryl moieties of said R10 is optionally substituted by one to three R12 groups; each R11 is independently selected from the group consisting of —H, —NR13R14, —C(O)R13, —CF3, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl —(C6-C10)aryl, and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, (C4-C9)heterocycloalkenyl, —(C6-C10)aryl and —(C1-C9)heteroaryl moieties of said R11 is optionally substituted by one to three R12 groups; each R12 is independently selected from the group consisting of —H, —OR13, —C(O)R13, —C(O)OR13, —OC(O)R13, —OC(O)OR13, —C(O)NR13R14, —NR13C(O)NR13R14, —NR13R14, —NR13C(NR13R14)(═NR13), —NR13C(NR13R14)(═N—C(O)R13), —NR13C(O)R14, —NR13S(O)jR13, —S(O)jR13, —CF3, —CN, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl; wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl of said R12 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF3, —CN, —NO2, —OH, —O((C1-C6)alkyl), —C(O)R15, —C(O)NR15R16, —S(O)jR15, and —S(O)jNR15R16, —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —SH, —S((C1-C6)alkyl), —NH2, —NH((C1-C6)alkyl) and —N((C1-C6)alkyl)2; R13 and R14 are each independently selected from the group consisting of —H, —NR15C(O)R16, —CF3, —CN, —S(O)jR15, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl of said R13 and R14 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF3, —CN, —NO2, —OH, —O((C1-C6)alkyl), —C(O)((C1-C6)alkyl), —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl,—SH, —S((C1-C6)alkyl), —NH2, —NH((C1-C6)alkyl) and —N((C1-C6)alkyl)2; R15 and R16 are each independently selected from the group consisting of —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl of said R15 and R16 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF3, —CN, —NO2, —OH, —O((C1-C6)alkyl), —C(O)((C1-C6)alkyl), —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —SH, —S((C1-C6)alkyl), —NH2, —NH((C1-C6)alkyl) and —N((C1-C6)alkyl)2; wherein one or two carbon ring atoms in each of the aforementioned —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl and —(C6-C9)heterobicycloalkenyl in said R1-R14 groups may optionally and independently be replaced with —C(O)— or —C(S)—; wherein two groups attached to the same tetravalent carbon atom in each of the aforementioned —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl and —(C6-C9)heterobicycloalkenyl of said R1 to R14 groups may optionally join to form a ring system selected from the group consisting of a —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, and —(C4-C9)heterocycloalkenyl; and wherein j is an integer from 0 to 2; n is an integer from 1 to 3; and m is an integer from 0 to 3. 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is —C(O)NR7R8 and R7 and R8 and each independently selected from the group consisting —H and —(C1-C6)alkyl. 3. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 and R3 are —H. 4. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R4 and R5 are methyl. 5. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein m is 1 or 2 and n is 1. 6. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the moiety represents a moiety selected from the group consisting of: 7. A compound of formula Ia: or a pharmaceutically acceptable salt thereof; wherein A is phenyl; B is phenyl or a 5- to 6-membered heteroaryl; K is CH; each R1 is independently selected from the group consisting of —H, halo, —CF3, —CN, —NO2, —NR7R8, —NR7C(NR7R8)(═CR9), —CR7(NR7R8)(═NR7), —NR7C(NR7R8)(═NR7), —NR7C(O)R9, —C(O)NR7R8, —C(O)R9, —C(O)C(O)R9, —C(O)OR10, —OC(O)R9, —OR10, —OC(O)OR10, —S(O)jR11, —S(O)(═NR7)R8, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C1-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C10)aryl and —(C1-C9)heteroaryl moieties of said R1 is optionally independently substituted by one to three R12 groups; R2 and R3 are each independently selected from the group consisting of —H, -halo, and —OR10; R4 and R5 are each independently selected from the group consisting of —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, and —(C2-C6)alkynyl moieties of said R4 and R5 is optionally substituted by one to three R12 groups; R6 is —CF3; R7 and R8 are each independently selected from the group consisting of —H, —OR10, —S(O)jR11, —NO2, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl —(C6-C10)aryl, and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, (C4-C9)heterocycloalkenyl, —(C6-C10)aryl and —(C1-C9)heteroaryl moieties of said R7 and R8 is optionally substituted by one to three R12 groups; each R9 is independently selected from the group consisting of —H, -halo, —NR13R14, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl —(C6-C10)aryl, and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, (C4-C9)heterocycloalkenyl, —(C6-C10)aryl and —(C1-C9)heteroaryl moieties of said R9 is optionally substituted by one to three R12 groups; each R10 is independently selected from the group consisting of —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl —(C6-C10)aryl, and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, (C4-C9)heterocycloalkenyl, —(C6-C10)aryl and —(C1-C9)heteroaryl moieties of said R10 is optionally substituted by one to three R12 groups; each R11 is independently selected from the group consisting of —H, —NR13R14, —C(O)R13, —CF3, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl —(C6-C10)aryl, and —(C1-C9)heteroaryl; land wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, (C4-C9)heterocycloalkenyl, —(C6-C10)aryl and —(C1-C9)heteroaryl moieties of said R11 is optionally substituted by one to three R12 groups; each R12 is independently selected from the group consisting of —H, —OR13, —C(O)R13, —C(O)OR13, —OC(O)R13, —OC(O)OR13, —C(O)NR13R14, —NR13C(O)NR13R14, —NR13R14, —NR13C(NR13R14)(═NR13), —NR13C(NR13R14)(═N—C(O)R13), —NR13C(O)R14, —NR13S(O)jR13, —S(O)jR13, —CF3, —CN, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl; wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl of said R12 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF3, —CN, —NO2, —OH, —O((C1-C6)alkyl), —C(O)R15, —C(O)NR15R16, —S(O)jR15, and —S(O)jNR15R16, —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —SH, —S((C1-C6)alkyl), —NH2, —NH((C1-C6)alkyl and —N((C1-C6)alkyl)2; R13 and R14 are each independently selected from the group consisting of —H, —NR15C(O)R16, —CF3, —CN, —S(O)jR15, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl of said R13 and R14 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF3, —CN, —NO2, —OH, —O((C1-C6)alkyl), —C(O)((C1-C6)alkyl), —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —SH, —S((C1-C6)alkyl), —NH2, —NH((C1-C6)alkyl) and —N((C1-C6)alkyl)2; R15 and R16 are each independently selected from the group consisting of —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl of said R15 and R16 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF3, —CN, —NO2, —OH, —O((C1-C6)alkyl), —C(O)((C1-C6)alkyl), —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —SH, —S((C1-C6)alkyl), —NH2, —NH((C1-C6)alkyl) and —N((C1-C6)alkyl)2; wherein one or two carbon ring atoms in each of the aforementioned —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl and —(C6-C9)heterobicycloalkenyl in said R1-R14 groups may optionally and independently be replaced with —C(O)— or —C(S)—; wherein two groups attached to the same tetravalent carbon atom in each of the aforementioned —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl and —(C6-C9)heterobicycloalkenyl of said R1 to R14 groups may optionally join to form a ring system selected from the group consisting of a —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, and —(C4-C9)heterocycloalkenyl; and wherein j is an integer from 0 to 2; n is 1 ;and m is 1. 8. A compound of formula Id: or a pharmaceutically acceptable salt thereof; wherein A is phenyl; B is selected from the group consisting of phenyl, pyridyl, pyrimidinyl and pyrazinyl; each R1 is independently selected from the group consisting of —H, halo, —CF3, —CN, —C(O)NR7R8, —C(O)R9, —OR10, and —(C1-C6)alkyl; and wherein the —(C1-C6)alkyl moiety of said R1 is optionally independently substituted by one to three R12 groups; R2 and R3 are each independently selected from the group consisting of —H and —(C1-C6)alkyl; R4 and R5 are each independently selected from the group consisting of —H and —(C1-C6)alkyl; R7 and R8 are each independently selected from the group consisting of —H, —OR10, —S(O)jR11, —NO2, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl —(C6-C10)aryl, and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, (C4-C9)heterocycloalkenyl, —(C6-C10)aryl and —(C1-C9)heteroaryl moieties of said R7 and R8 is optionally substituted by one to three R12 groups; each R9 is independently selected from the group consisting of —H, -halo, —NR13R14, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl —(C6-C10)aryl, and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, (C4-C9)heterocycloalkenyl, —(C6-C10)aryl and —(C1-C9)heteroaryl moieties of said R9 is optionally substituted by one to three R12 groups; each R10 is independently selected from the group consisting of —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl —(C6-C10)aryl, and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, (C4-C9)heterocycloalkenyl, —(C6-C10)aryl and —(C1-C9)heteroaryl moieties of said R10 is optionally substituted by one to three R12 groups; each R11 is independently selected from the group consisting of —H, —NR13R14, —C(O)R13, —CF3, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl —(C6-C10)aryl, and —(C1-C9)heteroaryl; land wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C2-C9)heterocycloalkyl, (C4-C9)heterocycloalkenyl, —(C6-C10)aryl and —(C1-C9)heteroaryl moieties of said R11 is optionally substituted by one to three R12 groups; each R12 is independently selected from the group consisting of —H, —OR13, —C(O)R13, —C(O)OR13, —OC(O)R13, —OC(O)OR13, —C(O)NR13R14, —NR13C(O)NR13R14, —NR13R14, —NR13C(NR13R14)(═NR13), —NR13C(NR13R14)(═N—C(O)R13), —NR13C(O)R14, —NR13S(O)jR13, —S(O)jR13, —CF3, —CN, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl; wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl of said R12 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF3, —CN, —NO2, —OH, —O((C1-C6)alkyl), —C(O)R15, —C(O)NR15R16, —S(O)jR15, and —S(O)jNR15R16, —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —SH, —S((C1-C6)alkyl), —NH2, —NH((C1-C6)alkyl and —N((C1-C6)alkyl)2; R13 and R14 are each independently selected from the group consisting of —H, —NR15C(O)R16, —CF3, —CN, —S(O)jR15, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl of said R13 and R14 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF3, —CN, —NO2, —OH, —O((C1-C6)alkyl), —C(O)((C1-C6)alkyl), —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —SH, —S((C1-C6)alkyl), —NH2, —NH((C1-C6)alkyl) and —N((C1-C6)alkyl)2; R15 and R16 are each independently selected from the group consisting of —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl; and wherein each of the foregoing —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C10)cycloalkyl, —(C5-C10)cycloalkenyl, —(C6-C10)bicycloalkyl, —(C6-C10)bicycloalkenyl, —(C2-C9)heterocycloalkyl, —(C4-C9)heterocycloalkenyl, —(C6-C9)heterobicycloalkyl, —(C6-C9)heterobicycloalkenyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl of said R15 and R16 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF3, —CN, —NO2, —OH, —O((C1-C6)alkyl), —C(O)((C1-C6)alkyl), —(C3-C10)cycloalkyl, —(C2-C9)heterocycloalkyl, —SH, —S((C1-C6)alkyl), —NH2, —NH((C1-C6)alkyl) and —N((C1-C6)alkyl)2; j is an integer from 0 to 2; and m is an integer from 1 to 3. 9. The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein the moiety represents a moiety selected from the group consisting of: 10. The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein R1 is —C(O)NR7R8 and R7 and R8 are each independently selected from the group consisting —H and —(C1-C6)alkyl. 11. The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein the moiety represents a moiety selected from the group consisting of: R1 is —C(O)NH2 or —C(O)NHCH3; and R1a is selected from the group consisting of fluoro, chloro, methyl and —OCH3. 12. The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein R2 and R3 are —H. 13. The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein R4 and R5 are methyl. 14. The compound of claim 1 which is selected from the group consisting of 4-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; 4-({4-[({3-[methyl(methylsulfonyl)amino]pyridin-2-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; 4-{[4-({3-[methyl(methylsulfonyl)amino]benzyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzamide; 3-({4-[({3-[methyl(methylsulfonyl)amino]pyrazin-2-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; 4-methoxy-3-({4-[({3-[methyl(methylsulfonyl)amino]pyrazin-2-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; N-methyl-4-({4-[({3-[methyl(methylsulfonyl)amino]pyridin-2-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; N-methyl-4-({4-[({3-[methyl(methylsulfonyl)amino]pyrazin-2-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; 3-fluoro-4-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; 2-fluoro-4-({4-[({3-[methyl(methylsulfonyl)amino]pyridin-2-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; 2-fluoro-4-{[4-({3-[methyl(methylsulfonyl)amino]benzyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzamide; 2-methyl-4-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; 2-methyl-4-({4-[({3-[methyl(methylsulfonyl)amino]pyridin-2-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; 2-methyl-4-({4-[({3-[methyl(methylsulfonyl)amino]pyrazin-2-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; 3-methyl-4-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; 3-methyl-4-({4-[({3-[methyl(methylsulfonyl)amino]pyridin-2-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; 3-methyl-4-({4-[({3-[methyl(methylsulfonyl)amino]pyrazin-2-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; 2-chloro-4-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; 2-chloro-4-({4-[({3-[methyl(methylsulfonyl)amino]pyridin-2-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; 2-chloro-4-({4-[({3-[methyl(methylsulfonyl)amino]pyrazin-2-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; 3-fluoro-N-methyl-4-({4-[({3-[methyl(methylsulfonyl)amino]pyrazin-2-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; 2-fluoro-N-methyl-4-({4-[({3-[methyl(methylsulfonyl)amino]pyrazin-2-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; N,2-dimethyl-4-({4-[({3-[methyl(methylsulfonyl)amino]pyrazin-2-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; N,3-dimethyl-4-({4-[({3-[methyl(methylsulfonyl)amino]pyrazin-2-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; N,3-dimethyl-4-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; (R)—N-(3-((2-(4-(1-aminoethyl)phenylamino)-5-(trifluoromethyl)pyrimidin-4-ylamino)methyl)pyridin-2-yl)-N-methylmethane-sulfonamide; N-(3-((2-(4-(aminomethyl)phenylamino)-5-(trifluoromethyl)pyrimidin-4-ylamino)methyl)pyridin-2-yl)-N-methylmethane-sulfonamide; N-[4-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]acetamide; N-(3-((2-(4-(hydroxymethyl)phenylamino)-5-(trifluoromethyl)pyrimidin-4-ylamino)methyl)pyridin-2-yl)-N-methylmethane-sulfonamide; N-(3-((2-(4-(chloromethyl)phenylamino)-5-(trifluoromethyl)pyrimidin-4-ylamino)methyl)pyridin-2-yl)-N-methylmethane-sulfonamide; N-(3-((2-(4-((1,3-dihydroxypropan-2-ylamino)methyl)phenylamino)-5-(trifluoromethyl)pyrimidin-4-ylamino)methyl)pyridin-2-yl)-N-methylmethane-sulfonamide; tert-butyl 3-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzoate; 3-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzoic acid; N-cyclopropyl-3-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; and N-(3-((2-(4-(1-hydroxyethyl)phenylamino)-5-(trifluoromethyl)pyrimidin-4-ylamino)methyl)pyridin-2-yl)-N-methylmethanesulfonamide; or a pharmaceutically acceptable salt thereof. 15. The compound of claim 1 which is selected from the group consisting of 2-fluoro-4-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; 3-fluoro-4-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; and N-methyl-4-({4-[({3-[methyl(methylsulfonyl)amino]pyrazin-2-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; or a pharmaceutically acceptable salt thereof. 16. The compound of claim 1 which is selected from the group consisting of 2-fluoro-4-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide formate; 3-fluoro-4-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide formate; and N-methyl-4-({4-[({3-[methyl(methylsulfonyl)amino]pyrazin-2-yl}methyl)amino]-5-(trifluoromethyppyrimidin-2-yl}amino)benzamide hydrochloride. 17. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.