US 7,320,986 B2 | ||
Fused tri and tetra-cyclic pyrazole kinase inhibitors | ||
Yunsong Tong, Grayslake, Ill. (US); Akiyo K. Claiborne, Mundelein, Ill. (US); Gaoquan Li, Park City, Ill. (US); Nan-Horng Lin, Vernon Hills, Ill. (US); Hing L. Sham, Vernon Hills, Ill. (US); Thomas J. Sowin, Wadsworth, Ill. (US); and Zhi-Fu Tao, Gurnee, Ill. (US) | ||
Assigned to Abbott Labortories, Abbott Park, Ill. (US) | ||
Filed on Mar. 03, 2004, as Appl. No. 10/792,564. | ||
Claims priority of provisional application 60/452702, filed on Mar. 07, 2003. | ||
Prior Publication US 2004/0259904 A1, Dec. 23, 2004 | ||
Int. Cl. A61K 31/4745 (2006.01); A61K 31/4162 (2006.01); C07D 487/14 (2006.01) |
U.S. Cl. 514—292 [514/406; 546/82; 548/359.5] | 4 Claims |
1. A compound of formula (I)
![]() R1 and R2 are independently selected from the group consisting of hydrogen, alkenyl, alkenyloxy, alkoxy, alkoxyalkoxy, alkoxyalkoxyalkynyl,
alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkoxysulfonyl, alkyl, alkylcarbonyl, alkylcarbonyloxy, alkylsulfinyl, alkylsulfonyl,
alkylthio, alkylthioalkyl, alkynyl, carboxy, carboxyalkyl, cyano, cycloalkenylalkoxy, cycloalkylalkoxy, cycloalkylalkyl, cycloalkylcarbonyl,
cycloalkyloxy, formyl, haloalkoxy, haloalkoxyalkynyl, haloalkyl, halogen, heteroarylalkoxy, heteroarylalkoxyalkoxy, heteroarylalkyl,
heteroarylalkynyl, heteroaryloxyalkyl, hydroxy, hydroxyalkoxy, hydroxyalkyl, hydroxyalkynyl, hydroxysulfonyl, hydroxysulfonylalkyl,
mercapto, mercaptoalkyl, nitro, —NRARB, (NRARB)alkoxy, (NRARB)alkyl, (NRARB)alkynyl, (NRARB)carbonyl, (NRARB)carbonylalkoxy, (NRARB)carbonylalkyl, and (NRGRH)alkoxy; or
R1 and R2 together with the carbon atoms to which they are attached form a 5, 6, 7, or 8-membered nonaromatic ring wherein the ring
contains 0, 1, or 2 heteroatoms selected from the group consisting of O, N(RC), and N(RD), wherein the nonaromatic ring is substituted with 0, 1, or 2 substituents selected from the group consisting of alkyl and
hydroxy;
R3 is selected from the group consisting of hydrogen, alkenyl, alkenyloxy, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl,
alkyl, alkylcarbonyl, alkylthio, alkylthioalkyl, alkynyl, carboxy, carboxyalkyl, cyano, formyl, haloalkoxy, haloalkyl, halogen,
hydroxy, hydroxyalkyl, mercapto, nitro, —NRERF, (NRERF)alkoxy (NRERF)alkyl, (NRERF)carbonyl, and (NRERF)carbonylalkyl;
R4 is selected from the group consisting of hydrogen, alkoxycarbonyl, alkylcarbonylalkoxy, aryl, arylalkoxy, arylalkyl, aryloxy,
carboxy, cyano, halogen, heteroaryl, heteroarylalkoxy, heteroarylalkyl, heteroaryloxy, hydroxy, —NRERF, and (NRERF)carbonyl;
R5 is selected from the group consisting of hydrogen, alkoxycarbonyl, carboxy, or halogen, heteroaryl, hydroxy, nitro, —NRERF, and (NRERF)carbonyl;
provided that when R5 is hydrogen, R4 is other than hydrogen; or
R4 and R5, together with the atoms to which they are attached, form a phenyl ring optionally substituted with 1, 2, 3, or 4 substituents
independently selected from the group consisting of alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkoxysulfonyl,
alkyl, alkylcarbonyl, alkylcarbonyloxy, alkylsulfmyl, alkylsulfonyl, alkylthio, alkylthioalkyl, alkynyl, carboxy, carboxyalkyl,
cyano, formyl, haloalkoxy, haloalkyl, halogen, hydroxy, hydroxyalkyl, mercapto, nitro, —NRGRH, (NRGRH)alkoxy, (NRGRH)alkyl, (NRGRH)carbonyl, and (NRGRH)sulfonyl; or
R4 and R5, together with the atoms to which they are attached, form a heterocycle optionally substituted with 1, 2, or 3 substituents
independently selected from the group consisting of alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylcarbonyloxy,
alkylthio, alkynyl, carboxy, cyano, formyl, haloalkoxy, haloalkyl, halogen, hydroxy, hydroxyalkyl, mercapto, nitro, oxo, —NRGRH, (NRGRH)alkoxy, (NRGRH)alkyl, and (NRGRH)carbonyl;
R6 is selected from the group consisting of hydrogen, lower alkoxy, lower alkyl, halogen, hydroxy, and —NRERF;
RA and RB are independently selected from the group consisting of hydrogen, alkenyl, alkoxyalkyl, alkoxyalkylcarbonyl, alkoxycarbonyl,
alkoxycarbonylalkyl, alkoxycarbonylalkylcarbonyl, alkoxysulfonyl, alkoxysulfonylalkyl, alkoxysulfonylalkylcarbonyl, alkyl,
alkylcarbonyl, alkynyl, aryl, carboxyalkyl, carboxyalkylcarbonyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkylcarbonyl, cycloalkylcarbonyl,
cycloalkylcarbonylalkyl, cycloalkylcarbonylalkylcarbonyl, heteroaryl, heteroarylalkyl, hydroxyalkyl, hydroxyalkylcarbonyl,
hydroxysulfonyl, hydroxysulfonylalkyl, hydroxysulfonylalkylcarbonyl, (NRERF)alkyl, (NRERF)alkylcarbonyl, (NRERF)carbonyl, (NRERF)carbonylalkyl, (NRERF)carbonylalkylcarbonyl, (NRERF)sulfonyl, (NRERF)sulfonylalkyl, and (NRERF)sulfonylalkylcarbonyl;
RC and RD are independently selected from the group consisting of hydrogen, alkoxycarbonyl, alkyl, and alkylcarbonyl;
RE and RF are independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, cycloalkyl, heteroarylalkyl, and hydroxyalkyl;
X1 and X3, are CH;
X4is N;
X2 is CH(R7);
X5 is C; and
R7 is selected from the group consisting of hydrogen, alkoxy, alkyl, hydroxy, lower alkoxy, lower alkyl, and hydroxyalkyl.
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