| US 7,566,716 B2 | ||
| Imidazopyrazines as Raf inhibitor compounds | ||
| Ellen Laird, Longmont, Colo. (US); George Topalov, Superior, Colo. (US); Joseph P. Lyssikatos, Superior, Colo. (US); Mike Welch, Westminster, Colo. (US); Jonas Grina, Superior, Colo. (US); Josh Hansen, Longmont, Colo. (US); and Brad Newhouse, Broomfield, Colo. (US) | ||
| Assigned to Array Biopharma Inc., Boulder, Colo. (US) | ||
| Filed on May 18, 2006, as Appl. No. 11/436,353. | ||
| Claims priority of provisional application 60/683175, filed on May 20, 2005. | ||
| Prior Publication US 2006/0281751 A1, Dec. 14, 2006 | ||
| Int. Cl. A61K 31/497 (2006.01) | ||
| U.S. Cl. 514—252.1 [544/106; 544/350; 546/152; 546/184; 546/348; 548/127; 548/146; 548/373.1; 548/490; 549/29] | 21 Claims |
1. A compound of Formula I, stereoisomers, tautomers or pharmaceutically acceptable salts thereof,
 X is NR5;
R1 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, cycloalkyl, heterocycloalkyl, Zn-aryl, or heteroaryl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl portions are
optionally substituted with one or more groups independently selected from F, Cl, Br, I, NO2, oxo (with the proviso that it is not on said aryl or heteroaryl), alkyl, Zn-aryl, Zn-heterocycloalkyl, Zn-heteroaryl, Zn-CN, Zn-OR12, Zn-C(O)R12, Zn-C(O)OR12, Zn-C(O)-heterocycloalkyl, Zn-NR15R15, Zn-NR12C(O)R13, Zn-NR12C(O)OR13, Zn-SR12, Zn-SOR12, Zn-SO2R12, Zn-O—(C1-C6 alkyl)-C(O)NR12R13, Zn-O—(C1-C6 alkyl)-C(O)OR12, Zn-O—(C1-C6 alkyl)-heterocycloalkyl, Zn-O—(C1-C6 alkyl)-C(O)-heterocycloalkyl, Zn-C(O)NR12R13, Zn-NR12—(C1-C6 alkyl)-C(O)NR12R13, Zn-NR12—(C1-C6 alkyl)-C(O)OR12, Zn-NR12—(C2-C6 alkyl)-OC(O)NR12R13, Zn-NR12C(═O)NR13Zn-R16, and Zn-NR12—(C2-C6 alkyl)-NR12C(O)NR12R13;
R2, R3 and R4 are;
R5 is H, or C1-C10 alkyl;
 (i) R7 and R8 form a 5 or 6 membered fused carbocyclic ring substituted with ═Y, and R9, R10 and R11 are independently selected from H, F, Cl, Br, and I, or
(ii) R8 and R9 form a 5 or 6 membered fused carbocyclic ring substituted with ═Y, and R7, R10 and R11 are independently selected from H, F, Cl, Br, and I;
Y is O or N—OH;
R12, R13 and R14 are independently selected from H, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, heterocycloalkyl,
aryl and heteroaryl, wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, heterocycloalkyl,
aryl and heteroaryl are optionally substituted with one or more groups independently selected from halogen, OH, O-alkyl, amino,
alkylamino and dialkylamino;
R15 is H, —SO2-alkyl, —SO2NR13R14, (C1-C6 alkyl)-OH, —C(O)O-alkyl, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, heterocycloalkyl,
aryl or heteroaryl, wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, heterocycloalkyl,
aryl and heteroaryl portions are optionally substituted with one or more groups independently selected from halogen, OH, O-alkyl,
amino, alkylamino and dialkylamino;
R16, is heteroaryl that is substituted with one or more alkyl, alkenyl, or alkynyl;
Z is alkylene having from 1 to 4 carbons, or alkenylene or alkynylene each having from 2 to 4 carbons, wherein said alkylene,
alkenylene and alkynylene are optionally substituted with one or more groups independently selected from halogen, OH, O-alkyl,
and amino; and
n is 0, 1, 2, 3 or 4.
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