	US 7,468,371 B2
	Tricyclic pyrazole kinase inhibitors
Lee D. Arnold, Niantic, Conn. (US); Jürgen Dinges, Grayslake, Ill. (US); Richard W. Dixon, Jefferson, Mass. (US); Stevan W. Djuric, Libertyville, Ill. (US); Anna M. Ericsson, Schrewsbury, Mass. (US); Kimba Fischer, Longmont, Colo. (US); Alan F. Gasiecki, Vernon Hills, Ill. (US); Vijaya J. Gracias, Lindenhurst, Ill. (US); James H. Holms, Gurnee, Ill. (US); Makoto Takeshita, Fukui (Japan); Michael R. Michaelides, Libertyville, Ill. (US); Melanie A. Muckey, Trevor, Wis. (US); Paul Rafferty, Westborough, Mass. (US); Douglas H. Steinman, Morton Grove, Ill. (US); Carol K. Wada, Gurnee, Ill. (US); Zhiren Xia, Gurnee, Ill. (US); Irini Akritopoulou-Zanze, Lake Bluff, Ill. (US); and Henry Q. Zhang, Grayslake, Ill. (US)
Assigned to Abbott Laboratories Inc., Abbott Park, Ill. (US)
Filed on Mar. 24, 2005, as Appl. No. 11/89,473.
Claims priority of provisional application 60/556005, filed on Mar. 24, 2004.
Prior Publication US 2006/0014816 A1, Jan. 19, 2006
Int. Cl. A61K 31/496 (2006.01); A61K 31/415 (2006.01); C07D 231/54 (2006.01); C07D 409/14 (2006.01)

U.S. Cl. 514—254.05 [544/358; 544/359; 544/366; 544/371; 548/356.1; 548/358.1; 548/359.1; 514/252.12; 514/254.01; 514/403; 514/406]

20 Claims

1. A compound of formula (I)

or a therapeutically acceptable salt thereof, wherein

X¹is selected from the group consisting of C and N;

X²is selected from the group consisting of CH₂, C═O, and O;

R^A, R^B, and R^Care independently selected from the group consisting of hydrogen, alkoxyalkoxy, alkoxyalkoxyalkyl, alkoxyalkyl, alkoxycarbonyl, carboxy, halogen, heteroaryl, heteroarylalkoxy, heteroarylalkyl, heteroarylcarbonyl, heteroaryloxy, heterocycle, heterocyclealkoxy, heterocyclealkyl, heterocyclecarbonyl, heterocycleoxy, R^aR^bN—, (R^aR^bN)alkoxy, (R^aR^bN)alkyl, (R^aR^bN)carbonyl, and (NR^aR^bN)carbonylalkoxy, and (R^aR^bN)carbonylalkyl;

R^Dis absent or selected from the group consisting of hydrogen, alkoxyalkoxy, alkoxyalkoxyalkyl, alkoxyalkyl, alkoxycarbonyl, carboxy, halogen, heteroaryl, heteroarylalkoxy, heteroarylalkyl, heteroarylcarbonyl, heteroaryloxy, heterocycle, heterocyclealkoxy, heterocyclealkyl, heterocyclecarbonyl, heterocycleoxy, R^aR^bN—, (R^aR^bN)alkoxy, (R^aR^bN)alkyl, (R^aR^bN)carbonyl, and (NR^aR^bN)carbonylalkoxy, and (R^aR^bN)carbonylalkyl;

R^aand R^bare independently selected from the group consisting of hydrogen, alkoxyalkyl, alkyl, alkylcarbonyl, formyl, heteroarylalkyl, heterocyclealkyl, and (Z¹Z²N)alkyl;

Z¹and Z²are independently selected from the group consisting of hydrogen, alkyl, formyl, and alkylcarbonyl;

R⁴is selected from the group consisting of heteroaryl, C≡CR⁵, (CH₂)_nNR⁶C(O)NR⁷R⁸, (CH₂)_nNR⁶C(O)OR⁸, (CH₂)_nNR⁶C(NCN)NR⁷R⁸, (CH₂)_nOC(O)NR⁷R⁸, CH═NNR⁶C(O)NR⁷R⁸, CH═NOR⁸, and CH═NOCH₂C(O)NR⁷R⁸;

n is 1, 2, 3, 4, or 5;

R⁵is selected from the group consisting of alkoxyalkoxyalkyl, alkoxyalkyl, alkoxycarbonylalkoxyalkyl, alkyl, aryl, aryloxyalkyl, arylthioalkyl, arylsulfinylalkyl, arylsulfonylalkyl, cycloalkyl, cycloalkylalkoxyalkyl, cycloalkylalkyl, cycloalkyloxyalkyl, haloalkoxyalkyl, haloalkoxyalkoxyalkyl, heteroaryl, heteroarylalkoxyalkyl, heteroarylalkyl, heteroaryloxyalkyl, heterocycle, heterocyclealkoxyalkyl, heterocyclealkyl, heterocyclecarbonylalkyl, heterocyclecarbonyloxyalkyl, heterocycleoxyalkyl, (NR^aR^b)carbonylalkoxyalkyl, (NR^cR^d)alkyl, (CH₂)_nNR⁶C(O)NR⁷R⁸, (CH₂)_nNR⁶C(O)OR⁸, (CH₂)_nNR⁶C(NCN)NR⁷R⁸, (CH₂)_nOC(O)NR⁷R⁸, and CH═NNR⁶C(O)NR⁷R⁸;

R^cis selected from the group consisting of hydrogen and alkyl;

R^dis selected from the group consisting of alkylsulfonyl, arylsulfonyl, heteroarylcarbonyl, and heteroarylcarbonyl;

R⁶and R⁷are each independently selected from the group consisting of hydrogen, alkoxy, alkoxyalkyl, alkyl, aryl, arylalkyl, cycloalkyl, and cycloalkylalkyl; and

R⁸is selected from the group consisting of hydrogen, alkoxyalkoxyalkyl, alkoxyalkyl, alkoxycarbonylalkoxyalkyl, alkoxycarbonylalkyl, alkyl, aryl, arylalkoxyalkyl, arylalkyl, aryloxyalkyl, arylthioalkyl, arylsulfinylalkyl, arylsulfonylalkyl, cyanoalkyl, cycloalkyl, cycloalkylalkyl, haloalkoxyalkoxyalkyl, haloalkoxyalkyl, haloalkyl, heteroaryl, heteroarylalkoxyalkyl, heteroarylalkyl, heteroaryloxyalkyl, heterocycle, heterocyclealkoxyalkyl, heterocyclecarbonylalkyl, heterocyclecarbonyloxyalkyl, heterocycleoxyalkyl, heterocyclealkyl, hydroxyalkyl, (R^aR^bN)alkyl, (R^aR^bN)carbonylalkoxyalkyl, and (R^aR^bN)carbonylalkyl; or

R⁷and R⁸, together with the nitrogen atom to which they are attached, form a heterocycle ring selected from the group consisting of piperazine, piperidine, and morpholine.