US2015080368A1PendingUtilityA1
Sulfonyl amide derivatives for the treatment of abnormal cell growth
Est. expiryApr 18, 2027(~0.8 yrs left)· nominal 20-yr term from priority
Inventors:Michael Joseph LuzzioKevin Daniel Freeman-CookSamit Kumar BhattacharyaMatthew Merrill HaywardCatherine Angela HulfordChristopher Lowell AutryXumiao ZhaoJun XiaoKendra Louise Nelson
A61P 35/04A61P 35/00A61P 35/02A61P 43/00A61P 29/00A61P 27/02A61P 25/00A61P 17/06A61P 19/02A61P 19/10A61P 19/08A61P 13/08C07D 403/12C07D 239/48C07D 401/12C07D 405/14C07D 241/20C07D 417/14C07D 475/00C07D 417/12C07D 413/14C07D 401/14A61K 31/506A61K 31/505
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Claims
Abstract
The present invention relates to a compound of the formula I wherein R 1 to R 6 , 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.
Claims
exact text as granted — not AI-modifiedWe claim:
1 . A compound of formula I:
or a pharmaceutically acceptable salt thereof; wherein
A is a ring moiety selected from the group consisting of a:
(a) 4- to 7-membered carbocyclyl,
(b) 4- to 7-membered heterocyclyl,
(c) phenyl, and
(d) 5- to 6-membered heteroaryl ring,
wherein each of said 4- to 7-membered carbocyclyl and 4- to 7-membered heterocyclyl of said A group may optionally contain one or two olefinic bonds; and wherein one or two carbon ring atoms in each of said 4- to 7-membered carbocyclyl and 4- to 7-membered heterocyclic of said A group may independently optionally be replaced with one or two moieties independently selected from the group consisting of —C(O)—, —C(S)— and —C(═NR 4 )—;
B is phenyl or a 5- to 6-membered heteroaryl;
K is CH, C(NH 2 ) or N;
each R 1 is independently selected from the group consisting of —H, halo, —CF 3 , —CN, —NO 2 , —NR 7 R 8 , —NR 7 C(NR 7 R 8 )(═CR 9 ), —CR 7 (NR 7 R 8 )(═NR 7 ), —NR 7 C(NR 7 R 8 )(═NR 7 ), —NR 7 C(O)R 9 , —C(O)NR 7 R 8 , —C(O)R 9 , —C(O)C(O)R 9 , —C(O)OR 10 , —OC(O)R 9 , —OR 10 , —OC(O)OR 10 , —S(O) j R 11 , —S(O)(═NR)R 8 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 1 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 1 is optionally independently substituted by one to three R 12 groups;
R 2 and R 3 are each independently selected from the group consisting of —H, -halo, —OR 10 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 2 and R 3 is optionally substituted by one to three R 12 groups;
R 4 and R 5 are each independently selected from the group consisting of —H, —NR 7 R 8 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 4 and R 5 is optionally substituted by one to three R 12 groups;
R 6 is selected from the group consisting of -halo, —NR 7 R 8 , —OR 10 , —C(O)R 9 , —CO 2 R 10 , —CONR 7 R 8 , —S(O) j R 11 , —NR 7 CONR 7 R 8 , and —NR 8 SO 2 R 11 , —NO 2 , —CN, —CF 3 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 2 -C 6 )perfluorinated alkyl, —(C 2 -C 6 )perfluorinated alkenyl, —(C 3 -C 6 )perfluorinated alkynyl, —(C 3 -C 7 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 1 -C 9 )heterocyclyl, —(C 1 -C 10 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, —(C 1 -C 9 )heteroaryl, —(C 6 -C 10 )perfluorinated aryl, and —(C 1 -C 9 )perfluorinated heteroaryl; and wherein each of said —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 7 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 1 -C 9 )heterocyclyl, —(C 1 -C 10 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl moieties of said R 6 is optionally substituted by one to three R 12 groups;
R 7 and R 8 are each independently selected from the group consisting of —H, —OR 10 , —S(O) j R 11 , —NO 2 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 7 and R 8 is optionally substituted by one to three R 12 groups;
each R 9 is independently selected from the group consisting of —H, -halo, —NR 13 R 14 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 9 is optionally substituted by one to three R 12 groups;
each R 10 is independently selected from the group consisting of —H, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 10 is optionally substituted by one to three R 12 groups;
each R 11 is independently selected from the group consisting of —H, —NR 13 R 14 , —C(O)R 13 , —CF 3 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 11 is optionally substituted by one to three R 12 groups;
each R 12 is independently selected from the group consisting of —H, —OR 13 , —C(O)R 13 , —C(O)OR 13 , —OC(O)R 13 , —OC(O)OR 13 , —C(O)NR 13 R 14 , —NR 13 C(O)NR 13 R 14 , —NR 13 R 14 , —NR 13 C(NR 13 R 14 )(═NR 13 ), —NR 13 C(NR 13 R 14 )(═N—C(O)R 13 ), —NR 13 C(O)R 14 , —NR 13 S(O) j R 13 , —S(O) j R 13 , —CF 3 , —CN, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl of said R 12 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF 3 , —CN, —NO 2 , —OH, —O((C 1 -C 6 )alkyl), —C(O)R 15 , —C(O)NR 15 R 16 , —S(O) j R 15 , and —S(O) j NR 15 R 16 , —(C 3 -C 10 )cycloalkyl, —(C 2 -C 9 )heterocycloalkyl, —SH, —S((C 1 -C 6 )alkyl), —NH 2 , —NH((C 1 -C 6 )alkyl) and —N((C 1 -C 6 )alkyl) 2 ;
R 13 and R 14 are each independently selected from the group consisting of —H, —NR 15 C(O)R 16 , CF 3 , —CN, —S(O) j R 15 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl of said R 13 and R 14 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF 3 , —CN, —NO 2 , —OH, —O((C 1 -C 6 )alkyl), —C(O)((C 1 -C 6 )alkyl), —(C 3 -C 10 )cycloalkyl, —(C 2 -C 9 )heterocycloalkyl, —SH, —S((C 1 -C 6 )alkyl), —NH 2 , —NH((C 1 -C 6 )alkyl) and —N((C 1 -C 6 )alkyl) 2 ;
R 15 and R 16 are each independently selected from the group consisting of —H, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl of said R 15 and R 16 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF 3 , —CN, —NO 2 , —OH, —O((C 1 -C 6 )alkyl), —C(O)((C 1 -C 6 )alkyl), —(C 3 -C 10 )cycloalkyl, —(C 2 -C 9 )heterocycloalkyl, —SH, —S((C 1 -C 6 )alkyl), —NH 2 , —NH((C 1 -C 6 )alkyl) and —N((C 1 -C 6 )alkyl) 2 ;
wherein one or two carbon ring atoms in each of the aforementioned —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl and —(C 6 -C 9 )heterobicycloalkenyl in said R 1 -R 14 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 —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl and —(C 6 -C 9 )heterobicycloalkeny of said R 1 to R 14 groups may optionally join to form a ring system selected from the group consisting of a —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, and —(C 4 -C 9 )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 wherein A is a phenyl.
3 . The compound of claim 1 wherein A is a 5- to 6-membered heteroaryl.
4 . The compound of claim 1 wherein each R 1 is independently selected from the group consisting of —H, halo, —CF 3 , —CN, —NO 2 , —NR 7 R 8 , —NR 7 C(NR 7 R 8 )(═CR 9 ), —CR 7 (NR 7 R 8 )(═NR 7 ), —NR 7 C(NR 7 R 8 )(═NR 7 ), —NR 7 C(O)R 9 , —C(O)NR 7 R 8 , —C(O)R 9 , —C(O)C(O)R 9 , —C(O)OR 10 , —OC(O)R 9 , —OR 10 , —OC(O)OR 10 , —S(O) j R 11 , and —S(O)(═NR 7 )R 8 .
5 . The compound of claim 1 wherein each R 1 is independently selected from the group consisting of —H, fluoro, chloro, —CF 3 , —CN, —C(O)NR 7 R 8 , and —OR 10 .
6 . The compound of claim 1 wherein R 1 is —C(O)NR 7 R 8 .
7 . The compound of claim 6 wherein R 7 and R 8 are each independently selected from the group consisting —H and —(C 1 -C 6 )alkyl.
8 . The compound of claim 1 wherein R 1 is —C(O)R 9 .
9 . The compound of claim 8 wherein R 1 is —C(O)R 9 and R 9 is selected from the group consisting of —NR 13 R 14 , —(C 1 -C 6 )alkyl and —(C 3 -C 10 )cycloalkyl; wherein each of said —(C 1 -C 6 )alkyl, and —(C 3 -C 10 )cycloalkyl of said R 9 group is optionally substituted by one to three R 12 groups; and wherein two groups attached to the same tetravalent carbon atom of said —(C 1 -C 6 )alkyl and —(C 3 -C 10 )cycloalkyl of said R 9 may optionally join to form a ring system selected from the group consisting of a —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, and —(C 4 -C 9 )heterocycloalkenyl.
10 . The compound of claim 9 wherein R 1 is —C(O)R 9 and R 9 is —NR 13 R 14 .
11 . The compound of claim 10 wherein R 1 is —C(O)R 9 , R 9 is —NR 13 R 14 , and R 13 and R 14 are each independently selected from the group consisting of —H and —(C 1 -C 6 )alkyl; and wherein said —(C 1 -C 6 )alkyl of said R 13 and R 14 groups is optionally independently substituted with one to three groups selected from the group consisting of -halo, —CF 3 , —CN, —NO 2 , —OH, —O((C 1 -C 6 )alkyl), —C(O)((C 1 -C 6 )alkyl), —(C 3 -C 10 )cycloalkyl, —(C 2 -C 9 )heterocycloalkyl, —SH, —S((C 1 -C 6 )alkyl), —NH 2 , —NH((C 1 -C 6 )alkyl) and —N((C 1 -C 6 )alkyl) 2 .
12 . The compound of claim 1 wherein R 2 and R 3 are each independently selected from the group consisting of —H, -halo, and —OR 10 .
13 . The compound of claim 1 wherein R 2 and R 3 are each independently selected from the group consisting of —H, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, and —(C 2 -C 6 )alkynyl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, and —(C 2 -C 6 )alkynyl moieties of said R 2 and R 3 is optionally independently substituted by one to three R 12 groups.
14 . The compound of claim 1 wherein R 2 , R 3 , R 4 and R 5 are each independently selected from the group consisting of —H and —(C 1 -C 6 )alkyl.
15 . The compound of claim 1 wherein R 2 and R 3 are —H.
16 . The compound of claim 1 wherein R 4 and R 5 are each independently selected from the group consisting of —H, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, and —(C 2 -C 6 )alkynyl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl and —(C 2 -C 6 )alkynyl moieties of said R 4 and R 5 is optionally independently substituted by one to three R 12 groups.
17 . The compound of claim 1 wherein R 4 and R 5 are methyl.
18 . The compound of claim 1 wherein R 6 is —CF 3 , K is CH, m is 1 or 2, and n is 1.
19 . The compound of claim 1 wherein R 6 is —CF 3 , K is CH, m is 1, and n is 1.
20 . The compound of claim 1 wherein the moiety
represents a moiety selected from the group consisting of:
21 . The compound of claim 1 wherein the moiety
represents a moiety selected from the group consisting of:
22 . 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, C(NH 2 ) or N;
each R 1 is independently selected from the group consisting of —H, halo, —CF 3 , —CN, —NO 2 , —NR 7 R 8 , —NR 7 C(NR 7 R 8 )(═CR 9 ), —CR 7 (NR 7 R 8 )(═NR 7 ), —NR 7 C(NR 7 R 8 )(═NR 7 ), —NR 7 C(O)R 9 , —C(O)NR 7 R 8 , —C(O)R 9 , —C(O)C(O)R 9 , —C(O)OR 10 , —OC(O)R 9 , —OR 10 , —OC(O)OR 10 , —S(O) j R 11 , —S(O)(═NR 7 )R 8 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 1 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 1 is optionally independently substituted by one to three R 12 groups;
R 2 and R 3 are each independently selected from the group consisting of —H, -halo, —OR 10 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and (C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 2 and R 3 is optionally substituted by one to three R 12 groups;
R 4 and R 5 are each independently selected from the group consisting of —H, —NR 7 R 8 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 4 and R 5 is optionally substituted by one to three R 12 groups;
R 6 is selected from the group consisting of -halo, —NR 7 R 8 , —OR 10 , —C(O)R 9 , —CO 2 R 10 , —CONR 7 R 8 , —S(O) j R 11 , —NR 7 CONR 7 R 8 , and —NR 8 SO 2 R 11 , —NO 2 , —CN, —CF 3 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 2 -C 6 )perfluorinated alkyl, —(C 2 -C 6 )perfluorinated alkenyl, —(C 3 -C 6 )perfluorinated alkynyl, —(C 3 -C 7 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 1 -C 9 )heterocyclyl, —(C 1 -C 10 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, —(C 1 -C 9 )heteroaryl, —(C 6 -C 10 )perfluorinated aryl, and —(C 1 -C 9 )perfluorinated heteroaryl; and wherein each of said —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 7 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 1 -C 9 )heterocyclyl, —(C 1 -C 10 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl moieties of said R 6 is optionally substituted by one to three R 12 groups;
R 7 and R 8 are each independently selected from the group consisting of —H, —OR 10 , —S(O) j R 11 , —NO 2 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 7 and R 8 is optionally substituted by one to three R 12 groups;
each R 9 is independently selected from the group consisting of —H, -halo, —NR 13 R 14 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 9 is optionally substituted by one to three R 12 groups;
each R 10 is independently selected from the group consisting of —H, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 10 is optionally substituted by one to three R 12 groups;
each R 11 is independently selected from the group consisting of —H, —NR 13 R 14 , —C(O)R 13 , —CF 3 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; land wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 11 is optionally substituted by one to three R 12 groups;
each R 12 is independently selected from the group consisting of —H, —OR 13 , —C(O)R 13 , —C(O)OR 13 , —OC(O)R 13 , —OC(O)OR 13 , —C(O)NR 13 R 14 , —NR 13 C(O)NR 13 R 14 , —NR 13 R 14 , —NR 13 C(NR 13 R 14 )(═NR 13 ), —NR 13 C(NR 13 R 14 )(═N—C(O)R 13 ), —NR 13 C(O)R 14 , —NR 13 S(O) j R 13 , —S(O) j R 13 , —CF 3 , —CN, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl of said R 12 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF 3 , —CN, —NO 2 , —OH, —O((C 1 -C 6 )alkyl), —C(O)R 15 , —C(O)NR 15 R 16 , —S(O) j R 15 , and —S(O) j NR 15 R 16 , —(C 3 -C 10 )cycloalkyl, —(C 2 -C 9 )heterocycloalkyl, —SH, —S((C 1 -C 6 )alkyl), —NH 2 , —NH((C 1 -C 6 )alkyl) and —N((C 1 -C 6 )alkyl) 2 ;
R 13 and R 14 are each independently selected from the group consisting of —H, —NR 15 C(O)R 16 , —CF 3 , —CN, —S(O) j R 15 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl of said R 13 and R 14 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF 3 , —CN, —NO 2 , —OH, —O((C 1 -C 6 )alkyl), —C(O)((C 1 -C 6 )alkyl), —(C 3 -C 10 )cycloalkyl, —(C 2 -C 9 )heterocycloalkyl, —SH, —S((C 1 -C 6 )alkyl), —NH 2 , —NH((C 1 -C 6 )alkyl) and —N((C 1 -C 6 )alkyl) 2 ;
R 15 and R 16 are each independently selected from the group consisting of —H, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl of said R 15 and R 16 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF 3 , —CN, —NO 2 , —OH, —O((C 1 -C 6 )alkyl), —C(O)((C 1 -C 6 )alkyl), —(C 3 -C 10 )cycloalkyl, —(C 2 -C 9 )heterocycloalkyl, —SH, —S((C 1 -C 6 )alkyl), —NH 2 , —NH((C 1 -C 6 )alkyl) and —N((C 1 -C 6 )alkyl) 2 ;
wherein one or two carbon ring atoms in each of the aforementioned —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl and —(C 6 -C 9 )heterobicycloalkenyl in said R 1 -R 14 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 —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl and —(C 6 -C 9 )heterobicycloalkeny of said R 1 to R 14 groups may optionally join to form a ring system selected from the group consisting of a —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, and —(C 4 -C 9 )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.
23 . A compound of formula Ib:
or a pharmaceutically acceptable salt thereof; wherein
A is phenyl;
B is phenyl or a 5- to 6-membered heteroaryl;
K is CH, C(NH 2 ) or N;
at least one R 1 is —(C 1 -C 6 )alkyl optionally independently substituted by one to three R 12 groups;
R 2 and R 3 are each independently selected from the group consisting of —H, -halo, —OR 10 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 2 and R 3 is optionally substituted by one to three R 12 groups;
R 4 and R 5 are each independently selected from the group consisting of —H, —NR 7 R 8 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 4 and R 5 is optionally substituted by one to three R 12 groups;
R 6 is selected from the group consisting of -halo, —NR 7 R 8 , —OR 10 , —C(O)R 9 , —CO 2 R 10 , —CONR 7 R 8 , —S(O) j R 11 , —NR 7 CONR 7 R 8 , and —NR 8 SO 2 R 11 , —NO 2 , —CN, —CF 3 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 2 -C 6 )perfluorinated alkyl, —(C 2 -C 6 )perfluorinated alkenyl, —(C 3 -C 6 )perfluorinated alkynyl, —(C 3 -C 7 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 1 -C 9 )heterocyclyl, —(C 1 -C 10 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, —(C 1 -C 9 )heteroaryl, —(C 6 -C 10 )perfluorinated aryl, and —(C 1 -C 9 )perfluorinated heteroaryl; and wherein each of said —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 7 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 1 -C 9 )heterocyclyl, —(C 1 -C 10 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl moieties of said R 6 is optionally substituted by one to three R 12 groups;
R 7 and R 8 are each independently selected from the group consisting of —H, —OR 10 , —S(O) j R 11 , —NO 2 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 7 and R 8 is optionally substituted by one to three R 12 groups;
each R 9 is independently selected from the group consisting of —H, -halo, —NR 13 R 14 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 9 is optionally substituted by one to three R 12 groups;
each R 10 is independently selected from the group consisting of —H, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 10 is optionally substituted by one to three R 12 groups;
each R 11 is independently selected from the group consisting of —H, —NR 13 R 14 , —C(O)R 13 , —CF 3 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; land wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 11 is optionally substituted by one to three R 12 groups;
each R 12 is independently selected from the group consisting of —H, —OR 13 , —C(O)R 13 , —C(O)OR 13 , —OC(O)R 13 , —OC(O)OR 13 , —C(O)NR 13 R 14 , —NR 13 C(O)NR 13 R 14 , —NR 13 R 14 , —NR 13 C(NR 13 R 14 )(═NR 13 ), —NR 13 C(NR 13 R 14 )(═N—C(O)R 13 ), —NR 13 C(O)R 14 , —NR 13 S(O) j R 13 , —S(O) j R 13 , —CF 3 , —CN, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl of said R 12 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF 3 , —CN, —NO 2 , —OH, —O((C 1 -C 6 )alkyl), —C(O)R 15 , —C(O)NR 15 R 16 , —S(O) j R 15 , and —S(O) j NR 15 R 16 , —(C 3 -C 10 )cycloalkyl, —(C 2 -C 9 )heterocycloalkyl, —SH, —S((C 1 -C 6 )alkyl), —NH 2 , —NH((C 1 -C 6 )alkyl) and —N((C 1 -C 6 )alkyl) 2 ;
R 13 and R 14 are each independently selected from the group consisting of —H, —NR 15 C(O)R 16 , —CF 3 , —CN, —S(O) j R 15 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl of said R 13 and R 14 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF 3 , —CN, —NO 2 , —OH, —O((C 1 -C 6 )alkyl), —C(O)((C 1 -C 6 )alkyl), —(C 3 -C 10 )cycloalkyl, —(C 2 -C 9 )heterocycloalkyl, —SH, —S((C 1 -C 6 )alkyl), —NH 2 , —NH((C 1 -C 6 )alkyl) and —N((C 1 -C 6 )alkyl) 2 ;
R 15 and R 16 are each independently selected from the group consisting of —H, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl of said R 15 and R 16 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF 3 , —CN, —NO 2 , —OH, —O((C 1 -C 6 )alkyl), —C(O)((C 1 -C 6 )alkyl), —(C 3 -C 10 )cycloalkyl, —(C 2 -C 9 )heterocycloalkyl, —SH, —S((C 1 -C 6 )alkyl), —NH 2 , —NH((C 1 -C 6 )alkyl) and —N((C 1 -C 6 )alkyl) 2 ;
wherein one or two carbon ring atoms in each of the aforementioned —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl and —(C 6 -C 9 )heterobicycloalkenyl in said R 1 -R 14 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 —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl and —(C 6 -C 9 )heterobicycloalkeny of said R 1 to R 14 groups may optionally join to form a ring system selected from the group consisting of a —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, and —(C 4 -C 9 )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.
24 . A compound of formula Ic:
or a pharmaceutically acceptable salt thereof; wherein the moiety
represents a moiety selected from the group consisting of:
A is a ring moiety selected from the group consisting of a:
(a) 4- to 7-membered carbocyclyl,
(b) 4- to 7-membered heterocyclyl,
(c) phenyl, and
(d) 5- to 6-membered heteroaryl ring,
wherein each of said 4- to 7-membered carbocyclyl and 4- to 7-membered heterocyclyl of said A group may optionally contain one or two olefinic bonds; and
wherein one or two carbon ring atoms in each of said 4- to 7-membered carbocyclyl and 4- to 7-membered heterocyclic of said A group may independently optionally be replaced with one or two moieties independently selected from the group consisting of —C(O)—, —C(S)— and —C(═NR 4 )—;
K is CH, C(NH 2 ) or N;
each R 1 is independently selected from the group consisting of —H, halo, —CF 3 , —CN, —NO 2 , —NR 7 R 8 , —NR 7 C(NR 7 R 8 )(═CR 9 ), —CR 7 (NR 7 R 8 )(═NR 7 ), —NR 7 C(NR 7 R 8 )(═NR 7 ), —NR 7 C(O)R 9 , —C(O)NR 7 R 8 , —C(O)R 9 , —C(O)C(O)R 9 , —C(O)OR 10 , —OC(O)R 9 , —OR 10 , —OC(O)OR 10 , —S(O) j R 11 , —S(O)(═NR 7 )R 8 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 1 is optionally independently substituted by one to three R 12 groups;
R 6 is selected from the group consisting of -halo, —NR 7 R 8 , —OR 10 , —C(O)R 9 , —CO 2 R 10 , —CONR 7 R 8 , —S(O) j R 11 , —NR 7 CONR 7 R 8 , and —NR 8 SO 2 R 11 , —NO 2 , —CN, —CF 3 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 2 -C 6 )perfluorinated alkyl, —(C 2 -C 6 )perfluorinated alkenyl, —(C 3 -C 6 )perfluorinated alkynyl, —(C 3 -C 7 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 1 -C 9 )heterocyclyl, —(C 1 -C 10 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, —(C 1 -C 9 )heteroaryl, —(C 6 -C 10 )perfluorinated aryl, and —(C 1 -C 9 )perfluorinated heteroaryl; and wherein each of said —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 7 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 1 -C 9 )heterocyclyl, —(C 1 -C 10 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl moieties of said R 6 is optionally substituted by one to three R 12 groups;
R 7 and R 8 are each independently selected from the group consisting of —H, —OR 10 , —S(O) j R 11 , —NO 2 , —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 7 and R 8 is optionally substituted by one to three R 12 groups;
each R 9 is independently selected from the group consisting of —H, -halo, —NR 13 R 14 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 9 is optionally substituted by one to three R 12 groups;
each R 10 is independently selected from the group consisting of —H, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 10 is optionally substituted by one to three R 12 groups;
each R 11 is independently selected from the group consisting of —H, —NR 13 R 14 , —C(O)R 13 , —CF 3 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; land wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 11 is optionally substituted by one to three R 12 groups;
each R 12 is independently selected from the group consisting of —H, —OR 13 , —C(O)R 13 , —C(O)OR 13 , —OC(O)R 13 , —OC(O)OR 13 , —C(O)NR 13 R 14 , —NR 13 C(O)NR 13 R 14 , —NR 13 R 14 , —NR 13 C(NR 13 R 14 )(═NR 13 ), —NR 13 C(NR 13 R 14 )(═N—C(O)R 13 ), —NR 13 C(O)R 14 , —NR 13 S(O) j R 13 , —S(O) j R 13 , —CF 3 , —CN, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl of said R 12 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF 3 , —CN, —NO 2 , —OH, —O((C 1 -C 6 )alkyl), —C(O)R 15 , —C(O)NR 15 R 16 , —S(O) j R 15 , and —S(O) j NR 15 R 16 , —(C 3 -C 10 )cycloalkyl, —(C 2 -C 9 )heterocycloalkyl, —SH, —S((C 1 -C 6 )alkyl), —NH 2 , —NH((C 1 -C 6 )alkyl) and —N((C 1 -C 6 )alkyl) 2 ;
R 13 and R 14 are each independently selected from the group consisting of —H, —NR 15 C(O)R 16 , —CF 3 , —CN, —S(O) j R 15 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl of said R 13 and R 14 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF 3 , —CN, —NO 2 , —OH, —O((C 1 -C 6 )alkyl), —C(O)((C 1 -C 6 )alkyl), —(C 3 -C 10 )cycloalkyl, —(C 2 -C 9 )heterocycloalkyl, —SH, —S((C 1 -C 6 )alkyl), —NH 2 , —NH((C 1 -C 6 )alkyl) and —N((C 1 -C 6 )alkyl) 2 ;
R 15 and R 16 are each independently selected from the group consisting of —H, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl of said R 15 and R 16 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF 3 , —CN, —NO 2 , —OH, —O((C 1 -C 6 )alkyl), —C(O)((C 1 -C 6 )alkyl), —(C 3 -C 10 )cycloalkyl, —(C 2 -C 9 )heterocycloalkyl, —SH, —S((C 1 -C 6 )alkyl), —NH 2 , —NH((C 1 -C 6 )alkyl) and —N((C 1 -C 6 )alkyl) 2 ;
wherein one or two carbon ring atoms in each of the aforementioned —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl and —(C 6 -C 9 )heterobicycloalkenyl in said R 1 and R 6 -R 14 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 —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl and —(C 6 -C 9 )heterobicycloalkenyl of said R 1 and R 6 -R 14 groups may optionally join to form a ring system selected from the group consisting of a —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, and —(C 4 -C 9 )heterocycloalkenyl; and wherein
j is an integer from 0 to 2; and
m is an integer from 0 to 3.
25 . A compound of formula Id:
or a pharmaceutically acceptable salt thereof; wherein
A is phenyl or a 5- to 6-membered heteroaryl;
B is selected from the group consisting of phenyl, pyridyl, pyrimidinyl and pyrazinyl;
each R 1 is independently selected from the group consisting of —H, halo, —CF 3 , —CN, —C(O)NR 7 R 8 , —C(O)R 9 , —OR 10 , and —(C 1 -C 6 )alkyl; and wherein the —(C 1 -C 6 )alkyl moiety of said R 1 is optionally independently substituted by one to three R 12 groups;
R 2 and R 3 are each independently selected from the group consisting of —H and —(C 1 -C 6 )alkyl;
R 4 and R 5 are each independently selected from the group consisting of —H and —(C 1 -C 6 )alkyl;
R 7 and R 8 are each independently selected from the group consisting of —H, —OR 10 , —S(O) j R 11 , —NO 2 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 7 and R 8 is optionally substituted by one to three R 12 groups;
each R 9 is independently selected from the group consisting of —H, -halo, —NR 13 R 14 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 9 is optionally substituted by one to three R 12 groups;
each R 10 is independently selected from the group consisting of —H, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 10 is optionally substituted by one to three R 12 groups;
each R 11 is independently selected from the group consisting of —H, —NR 13 R 14 , —C(O)R 13 , —CF 3 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; land wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, (C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 10 )aryl and —(C 1 -C 9 )heteroaryl moieties of said R 11 is optionally substituted by one to three R 12 groups;
each R 12 is independently selected from the group consisting of —H, —OR 13 , —C(O)R 13 , —C(O)OR 13 , —OC(O)R 13 , —OC(O)OR 13 , —C(O)NR 13 R 14 , —NR 13 C(O)NR 13 R 14 , —NR 13 R 14 , —NR 13 C(NR 13 R 14 )(═NR 13 ), —NR 13 C(NR 13 R 14 )(═N—C(O)R 13 ), —NR 13 C(O)R 14 , —NR 13 S(O) j R 13 , —S(O) j R 13 , —CF 3 , —CN, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl of said R 12 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF 3 , —CN, —NO 2 , —OH, —O((C 1 -C 6 )alkyl), —C(O)R 15 , —C(O)NR 15 R 16 , —S(O) j R 15 , and —S(O) j NR 15 R 16 , —(C 3 -C 10 )cycloalkyl, —(C 2 -C 9 )heterocycloalkyl, —SH, —S((C 1 -C 6 )alkyl), —NH 2 , —NH((C 1 -C 6 )alkyl) and —N((C 1 -C 6 )alkyl) 2 ;
R 13 and R 14 are each independently selected from the group consisting of —H, —NR 15 C(O)R 16 , —CF 3 , —CN, —S(O) j R 15 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl of said R 13 and R 14 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF 3 , —CN, —NO 2 , —OH, —O((C 1 -C 6 )alkyl), —C(O)((C 1 -C 6 )alkyl), —(C 3 -C 10 )cycloalkyl, —(C 2 -C 9 )heterocycloalkyl, —SH, —S((C 1 -C 6 )alkyl), —NH 2 , —NH((C 1 -C 6 )alkyl) and —N((C 1 -C 6 )alkyl) 2 ;
R 15 and R 16 are each independently selected from the group consisting of —H, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl; and wherein each of the foregoing —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 3 -C 10 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 6 -C 10 )bicycloalkyl, —(C 6 -C 10 )bicycloalkenyl, —(C 2 -C 9 )heterocycloalkyl, —(C 4 -C 9 )heterocycloalkenyl, —(C 6 -C 9 )heterobicycloalkyl, —(C 6 -C 9 )heterobicycloalkenyl, —(C 6 -C 10 )aryl, and —(C 1 -C 9 )heteroaryl of said R 15 and R 16 is optionally independently substituted by one to three groups selected from the group consisting of -halo, —CF 3 , —CN, —NO 2 , —OH, —O((C 1 -C 6 )alkyl), —C(O)((C 1 -C 6 )alkyl), —(C 3 -C 10 )cycloalkyl, —(C 2 -C 9 )heterocycloalkyl, —SH, —S((C 1 -C 6 )alkyl), —NH 2 , —NH((C 1 -C 6 )alkyl) and —N((C 1 -C 6 )alkyl) 2 ;
j is an integer from 0 to 2; and
m is an integer from 1 to 3.
26 . The compound of claim 25 wherein A is a phenyl.
27 . The compound of claim 25 wherein the moiety
represents a moiety selected from the group consisting of:
28 . The compound of claim 25 wherein R 1 is —C(O)NR 7 R 8 and R 7 and R 8 are each independently selected from the group consisting —H and —(C 1 -C 6 )alkyl.
29 . The compound of claim 25 wherein R 1 is —OR 10 and R 10 is —(C 1 -C 6 )alkyl.
30 . The compound of claim 25 wherein each R 1 is independently selected from the group consisting of —H, fluoro, chloro, —CF 3 , —CN, methyl, —C(O)NH 2 , —C(O)NHCH 3 , —C(O)NHCH 2 CH 3 , —C(O)N(CH 3 ) 2 , and —OCH 3 .
31 . The compound of claim 25 wherein the moiety
represents a moiety selected from the group consisting of:
R 1 is —C(O)NH 2 or —C(O)NHCH 3 ; and
R 1a is selected from the group consisting of fluoro, chloro, methyl and —OCH 3 .
32 . The compound of claim 25 wherein R 2 and R 3 are —H.
33 . The compound of claim 25 wherein R 4 and R 5 are methyl.
34 . The compound of claim 25 wherein m is 1 or 2.
35 . 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; and
N,3-dimethyl-4-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide; or a pharmaceutically acceptable salt thereof.
36 . A compound of claim 1 which is selected from the group consisting of
(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; and
N-(3-((2-(4-(chloromethyl)phenylamino)-5-(trifluoromethyl)pyrimidin-4-ylamino)methyl)pyridin-2-yl)-N-methylmethane-sulfonamide; or a pharmaceutically acceptable salt thereof.
37 . The compound of claim 1 which is selected from the group consisting of
N-(3-((2-(4-((1,3-dihydroxypropan-2-ylamino)methyl)phenylamino)-5-(trifluoromethyl)pyrimidin-4-ylamino)methyl)pyridin-2-yl)-N-methylmethane-sulfonamide; or a pharmaceutically acceptable salt thereof.
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.
38 . 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.
39 . 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-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide hydrochloride.
40 . A method for the treatment of cancer in a mammal comprising administering to said mammal an amount of a compound of claim 1 that is effective in treating cancer.
41 . The method of claim 40 wherein said cancer is selected from the group consisting of lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, colon cancer, breast cancer, uterine cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, prostate cancer, chronic or acute leukemia, lymphocytic lymphomas, cancer of the bladder, cancer of the kidney or ureter, renal cell carcinoma, carcinoma of the renal pelvis, neoplasms of the central nervous system (CNS), primary CNS lymphoma, spinal axis tumors, brain stem glioma, pituitary adenoma, or a combination of one or more of the foregoing cancers.
42 . A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.Cited by (0)
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