US 7,541,367 B2
3-benzoimidazolyl-pyrazolopyridines useful in treating kinase disorders
George Chiu, Bridgewater, N.J. (US); Peter J. Connolly, New Providence, N.J. (US); Stuart Emanuel, Doylestown, Pa. (US); Shenlin Huang, San Diego, Calif. (US); Shengjian Li, Belle Mead, N.J. (US); Ronghui Lin, East Brunswick, N.J. (US); Yanhua Lu, Greenbrook, N.J. (US); and Steven A. Middleton, Flemington, N.J. (US)
Assigned to Janssen Pharmaceutica, N.V., Beerse (Belgium)
Filed on May 31, 2006, as Appl. No. 11/443,994.
Claims priority of provisional application 60/686056, filed on May 31, 2005.
Prior Publication US 2009/0048249 A1, Feb. 19, 2009
Int. Cl. A01N 43/42 (2006.01); A61K 31/44 (2006.01); C07D 471/02 (2006.01); C07D 491/02 (2006.01); C07D 498/02 (2006.01); C07D 513/02 (2006.01); C07D 515/02 (2006.01)
U.S. Cl. 514—303  [546/119] 38 Claims
 
1. A compound of formula (I):

OG Complex Work Unit Drawing
or a pharmaceutically acceptable form thereof, wherein
R1 is hydrogen or C1-8alkyl,
R2 is hydrogen, halogen, C3-12cycloalkyl-R7, heterocyclyl-R8, aryl-R9, heteroaryl-R10, C1-8alkyl-C3-12cycloalkyl-R7, C1-8alkyl-heterocyclyl-R8, C1-8alkyl-aryl-R9, C1-8alkyl-heteroaryl-R10, C1-8alkyl-O—C1-8alkyl-C3-12cycloalkyl-R7, C1-8alkyl-O—C1-8alkyl-heterocyclyl-R8, C1-8alkyl-O—C1-8alkyl-aryl-R9, C1-8alkyl-O—C1-8alkyl-heteroaryl-R10, C(O)—C3-12cycloalkyl-R7, C(O)-heterocyclyl-R8, C(O)-aryl-R9, C(O)-heteroaryl-R10, C(O)NH—C3-12cycloalkyl-R7, C(O)NH-heterocyclyl-R8, C(O)NH-aryl-R9 or C(O)NH-heteroaryl-R10,
R3, R4, R5 and R6 is each selected from hydrogen, halogen, nitro, cyano, C1-8alkyl, C1-8alkoxy, C1-8alkyl(halogen)1-3, C1-8alkoxy(halogen)1-3, C1-8alkyl-O—C1-8alkyl, C1-8alkyl-O—C1-8alkyl-O—C1-8alkyl, OH, OC(O)C1-8alkyl, C1-8alkyl-OH, C1-8alkoxy-OH, C(O)H, C(O)C1-8alkyl, C(O)OH, C(O)O—C1-8alkyl, NH2, NH—C1-8alkyl, N(C1-8alkyl)2, NHC(O)C1-8alkyl, NHC(O)NHC1-8alkyl, N(C1-8alkyl)C(O)C1-8alkyl, C1-8alkyl-NH2, C1-8alkyl-NH—C1-8alkyl, C1-8alkyl-N(C1-8alkyl)2, C1-8alkyl-NH(OH), C1-8alkyl=N(OH), C1-8alkyl-NH—C1-8alkyl-NH2, C1-8alkyl-N(C1-8alkyl-NH2)2, C1-8alkyl-N(C1-8alkyl)-C1-8alkyl-NH2, C(O)NH2, C(O)NH—C1-8alkyl, C(O)N(C1-8alkyl)2, C(O)NH—C1-8alkyl-NH2, C(O)NH—C1-8alkyl-NH—C1-8alkyl, C(O)NH—C1-8alkyl-N(C1-8alkyl)2, C(O)N(C1-8alkyl-NH2)2, C(O)N(C1-8alkyl)-C1-8alkyl-NH2, C(O)N(C1-8alkyl)-C1-8alkyl-NH—C1-8alkyl, C(O)N(C1-8alkyl)-C1-8alkyl-N(C1-8alkyl)2, C3-12cycloalkyl-R11, heterocyclyl-R12, aryl-R13, heteroaryl-R14, C1-8alkyl-C3-12cycloalkyl-R11, C1-8alkyl-heterocyclyl-R12, C1-8alkyl-aryl-R13, C1-8alkyl-heteroaryl-R14, C1-8alkyl-O—C1-8alkyl-C3-12cycloalkyl-R11, C1-8alkyl-O—C1-8alkyl-heterocyclyl-R12, C1-8alkyl-O—C1-8alkyl-aryl-R13, C1-8alkyl-O—C1-8alkyl-heteroaryl-R14, C(O)—C3-12cycloalkyl-R11, C(O)-heterocyclyl-R12, C(O)-aryl-R13, C(O)-heteroaryl-R14, C(O)NH—C3-12cycloalkyl-R11, C(O)NH-heterocyclyl-R12, C(O)NH-aryl-R13 or C(O)NH-heteroaryl-R14,
alternatively, one of each R3 and R4, R4 and R5 or R5 and R6 are taken together to form —O—CH2—O— or —O—(CH2)2—O— which, together with the benzoimidazolyl ring of formula (I), form a 5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl, 6H-1,3-dioxa-6,8-diaza-as-indacen-7-yl, 8H-1,3-dioxa-6,8-diaza-as-indacen-7-yl, 6,7-dihydro-1H-5,8-dioxa-1,3-diaza-cyclopenta[b]naphthalen-2-yl, 7,8-dihydro-1H-6,9-dioxa-1,3-diaza-cyclopenta[a]naphthalen-2-yl or a 7,8-dihydro-3H-6,9-dioxa-1,3-diaza-cyclopenta[a]naphthalen-2-yl ring system, wherein the —O—CH2—O— or —O—(CH2)2—O— portion is each optionally substituted on one or two carbon atoms with one or two substituents each selected from halogen, nitro, cyano, C1-8alkyl, C1-8alkoxy, C1-8alkyl(halogen)1-3, C1-8alkoxy(halogen)1-3, OH or C1-8alkyl-OH,
R7, R8, R9 and R10 is each one, two, three, four or five substituents each selected from hydrogen, halogen, nitro, cyano, C1-8alkyl, C1-8alkoxy, C1-8alkyl(halogen)1-3, C1-8alkoxy(halogen)1-3, OH, C1-8alkyl-OH, C1-8alkoxy-O—C1-8alkyl, C1-8alkoxy-OH, C(O)H, C(O)C1-8alkyl, C(O)OH, C(O)O—C1-8alkyl, NH2, NH—C1-8alkyl, N(C1-8alkyl)2, C1-8alkyl-NH2, C1-8alkyl-NH—C1-8alkyl, CH(C1-8alkyl)-NH—C1-8alkyl, C(C1-8alkyl)2-NH—C1-8alkyl, C1-8alkyl-N(C1-8alkyl)2, C1-8alkyl-NH—C1-8alkyl-O—C1-8alkyl, C1-8alkyl-NH—C1-8alkyl-NH2, C1-8alkyl-NH—C(O)C1-8alkyl, C1-8alkyl-NH—C(O)NHC1-8alkyl, C1-8alkyl-NH—C1-8alkyl-NH—C1-8alkyl, C1-8alkyl-NH—C1-8alkyl-N(C1-8alkyl)2, C1-8alkyl=N(OH), C1-8alkyl-NH—C1-8alkyl-OH, SO2NH2, SO2NH—C1-8alkyl, SO2N(C1-8alkyl)2, C3-12cycloalkyl-R15, heterocyclyl-R16, aryl-R17, heteroaryl-R18, C1-8alkyl-C3-12cycloalkyl-R15, C1-8alkyl-heterocyclyl-R16, C1-8alkyl-aryl-R17, C1-8alkyl-heteroaryl-R18, C1-8alkyl-NH—C3-12cycloalkyl-R15, C1-8alkyl-NH-heterocyclyl-R16, C1-8alkyl-NH-aryl-R17, C1-8alkyl-NH-heteroaryl-R18, C1-8alkyl-NH—C1-8alkyl-C3-12cycloalkyl-R15, C1-8alkyl-NH—C1-8-alkyl-heterocyclyl-R16, C1-8alkyl-NH—C1-8alkyl-aryl-R17, C1-8alkyl-NH—C1-8alkyl-heteroaryl-R18, SO2—C3-12cycloalkyl-R15, SO2-heterocyclyl-R16, SO2-aryl-R17 or SO2-heteroaryl-R18,
R11, R12, R13 and R14 is each one, two, three, four or five substituents each selected from hydrogen, halogen, nitro, cyano, C1-8alkyl, C1-8alkoxy, C1-8alkyl(halogen)1-3, C1-8alkoxy(halogen)1-3, OH, C1-8alkyl-OH, C1-8alkoxy-OH, NH2, NH—C1-8alkyl or N(C1-8alkyl)2, and
R15, R16, R17 and R18 is each one, two, three, four or five substituents each selected from hydrogen, halogen, nitro, cyano, C1-8alkyl, C1-8alkoxy, C1-8alkyl(halogen)1-3, C1-8alkoxy(halogen)1-3, OH, C1-8alkyl-OH, C1-8alkoxy-OH, C(O)H, C(O)C1-8alkyl, C(O)OH, C(O)O—C1-8alkyl, NH2, NH—C1-8alkyl or N(C1-8alkyl)2.