US 6,982,270 B1 | ||
3,4-dihydro-(1H)quinazolin-2-one compounds as CSBP/p38 kinase inhibitors | ||
Jerry L. Adams, Wayne, Pa. (US); Michael J. Bower, Audubon, Pa. (US); Jeffrey C. Boehm, King of Prussia, Pa. (US); Don Edgar Griswold, North Wales, Pa. (US); and David C. Underwood, Ambler, Pa. (US) | ||
Assigned to SmithKline Beecham Corporation, Philadelphia, Pa. (US) | ||
Appl. No. 10/129,863 PCT Filed Nov. 21, 2000, PCT No. PCT/US00/31874 § 371(c)(1), (2), (4) Date May 10, 2002, PCT Pub. No. WO01/38313, PCT Pub. Date May 31, 2001. |
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Claims priority of provisional application 60/166972, filed on Nov. 23, 1999. | ||
Int. Cl. C07D 239/80 (2006.01); A61K 31/517 (2006.01) |
U.S. Cl. 514—266.3 | 26 Claims |
1. A compound of the formula: ![]() wherein R1 is phenyl, naphth-1-yl, naphth-2-yl, heterocyclic or heteroaryl ring, which ring is optionally substituted independently by
one to three substituents selected from halogen, C1-4 alkyl, halo-substituted-C1-4 alkyl, cyano, nitro, (CR10R20)vNR4R14, (CR10R20)vC(Z)NR4R14, (CR10R20)vC(Z)OR8, (CR10R20)vCOR3, (CR10R20)vC(O)H, SR5, S(O)R5, S(O)2R5, (CR10R20)vOR8, ZC(Z)R11, NR10C(Z)R11, or NR10S(O)2R7;
R2 is C1-10 alkyl, aryl, arylC1-10 alkyl, heteroaryl, heteroarylC1-10 alkyl, heterocyclic, heterocyclylC1-10 alkyl moiety which moieties are optionally substituted one or more times independently with C1-10 alkyl, halo-substituted C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-7 cycloalkyl, C3-7 cycloalkylC1-10 alkyl, C5-7 cycloalkenyl, C5-7 cycloalkenyl C1-10 alkyl, halogen, (CR10R20)nOR6, (CR10R20)nSH, (CR10R20)nS(O)mR7, (CR10R20)nNHS(O)2R7, (CR10R20)nNR4R14, (CR10R20)nCN, (CR10R20)nS(O)2NR4R14, (CR10R20)nC(Z)R6, (CR10R20)nOC(Z)R6, (CR10R20)nC(Z)OR6, (CR10R20)nC(Z)NR4R14, (CR10R20)nNR10C(Z)R6, (CR10R20)nNR10C(═NR10)NR4R14, (CR10R20)nOC(Z)NR4R14, (CR10R20)nNR10C(Z)NR4R14, or (CR10R20)nNR10C(Z)OR7;
Z is oxygen or sulfur;
n is 0, or an integer having a value of 1 to 10;
m is 0, or the integer 1 or 2;
v is 0, or an integer having a value of 1 or 2;
t is an integer having a value of 1 to 3;
R3 is C1-4 alkyl, halo-substituted C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-7 cycloalkyl C5-7 cycloalkenyl, aryl, arylC1-4 alkyl, heteroaryl, heteroarylC1-4 alkyl, heterocyclyl, heterocyclylC1-4 alkyl, (CR10R20)vOR7, (CR10R20)vS(O)mR7, (CR10R20)vNHS(O)2R7, or (CR10R20)vNR4R14; and wherein the aryl, arylalkyl, heteroaryl, heteroaryl alkyl may be optionally substituted;
R4 and R14 is each independently selected from hydrogen or optionally substituted C1-4 alkyl, optionally substituted aryl or optionally substituted aryl-C1-4 alkyl, or together with the nitrogen which they are attached form a heterocyclic ring of 5 to 7 members which ring optionally
contains an additional heteroatom selected from oxygen, sulfur or NR9;
R5 is hydrogen, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl or NR4R14, excluding the moieties SR5 being SNR4R14, S(O)2R5 being SO2H and S(O)R5 being SOH;
R6 is hydrogen, C1-10 alkyl, C3-7 cycloalkyl, heterocyclyl, heterocyclyl C1-10 alkyl, aryl, arylC1-10 alkyl, heteroaryl or heteroarylC1-10 alkyl, wherein these moieties may be optionally substituted;
R7 is C1-6alkyl, aryl, arylC1-6 alkyl, heterocyclic, heterocyclylC1-6 alkyl, heteroaryl, or heteroarylC1-6alkyl; and wherein each of these moieties may be optionally substituted;
R8 is hydrogen, C1-4 alkyl, halo-substituted C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, cycloalkyl, C5-7 cycloalkenyl, aryl, arylC1-4 alkyl, heteroaryl, heteroarylC1-4 alkyl, heterocyclyl, heterocyclylC1-4 alkyl, (CR10R20)tOR7, (CR10R20)tS(O)mR7, (CR10R20)tNHS(O)2R7, or (CR10R20)tNR4R14; and wherein the aryl, arylalkyl, heteroaryl, heteroaryl alkyl may be optionally substituted;
R9 is hydrogen, C(Z)R6 or optionally substituted C1-10 alkyl, optionally substituted aryl or optionally substituted aryi-C1-4 alkyl;
R10 and R20 are each independently selected from hydrogen or C1-4 alkyl;
R11 is C1-4 alkyl, halo-substituted C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-7 cycloalkyl, C5-7 cycloalkenyl, aryl, arylC1-4 alkyl, heteroaryl, heteroarylC1-4 alkyl, heterocyclyl, heterocyclylC1-4 alkyl, (CR10R20)tOR7, (CR10R20)tS(O)mR7, (CR10R20)tNHS(O)2R7, or (CR10R20)vNR4R14; and wherein the aryl, arylalkyl, heteroaryl, heteroaryl alkyl may be optionally substituted;
or a pharmaceutically acceptable salt thereof.
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