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US 8,138,338 B2Granted
Aurora kinase inhibitors from an encoded small molecule library
AssigneeGlaxoSmithKline LLC
InventorMatthew Clark
Life of this patent
Estimating the term…
Abstract
The present invention provides, at least in part, compounds of formula (I): or a pharmaceutically acceptable salt thereof, wherein Z1, Z2, Z3, R1, x, y, R2, R3, R4a, R4b, R5, R6 and R7 are described herein, as well as methods for their identification, their preparation, pharmaceutical compositions containing them, and their use as Aurora A kinase inhibitors in treatment, e.g., of cancer and other proliferative disorders.
Claims13
A compound of formula I-3:
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 is aryl, heteroaryl, aralkyl, heteroaralkyl, optionally substituted on carbon with 1, 2, or 3 R6;
- x and y are each independently 1;
- R2 is hydrogen, (C1-C6)alkyl, cyano, —CO2H, —C(═O)(C1-C6)alkyl, —C(═N)(C1-C6)alkyl, —CO2(C1-C6)alkyl, —CONH2, —C(═N)NH2, —C(═N)NH(C1-C6)alkyl), —C(═N)N(C1-C6)alkyl)2, —CONH(C1-C6)alkyl, CON((C1-C6)alkyl)2, wherein the (C1-C6)alkyl, —C(═O)(C1-C6)alkyl, —C(═N)(C1-C6)alkyl, —CO2(C1-C6)alkyl, —C(═N)NH(C1-C6)alkyl), —C(═N)N(C1-C6)alkyl)2, —CONH(C1-C6)alkyl, or —CON((C1-C6)alkyl)2 may be optionally substituted on carbon with 1, 2, or 3 R6;
- R3 is selected from
- R4a is hydrogen, (C1-C6)alkyl, or (C3-C6)cycloalkyl wherein the (C1-C6)alkyl, or (C3-C6)cycloalkyl may be optionally substituted on carbon with 1, 2, or 3 R6;
- R4b is hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, aryl, heteroaryl, aralkyl, or heteroaralkyl, wherein the (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, aryl, heteroaryl, aralkyl, or heteroaralkyl may be optionally substituted on carbon with 1, 2, or 3 R6;
- or
- R4a and R4b, together with the carbon to which they are attached, form an aryl or heteroaryl group;
- R5 is hydrogen, (C1-C6)alkyl, or (C3-C6)cycloalkyl;
- R6 is halogen, trifluoromethyl, trifluoromethoxy, cyano, nitro, hydroxy, amino, —NH(C1-C6)alkyl, —N((C1-C6)alkyl)2, aryl, heteroaryl, (C3-C7)cycloalkyl, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C2-C6)alkenyloxy, (C2-C6)alkynyloxy, (C1-C6)alkylthio, (C1-C6)alkylsulfinyl, (C1-C6)alkylsulfonyl, amino, (C1-C6)alkylamino, di-[(C1-C6) alkyl]amino, formyl, —C(═O)(C1-C6)alkyl, —C(═N)(C1-C6)alkyl, carboxy, —CO2(C1-C6)alkyl, —CONH2, —C(═N)NH2, —C(═N)NH(C1-C6)alkyl), —C(═N)N(C1-C6)alkyl)2, —CONH(C1-C6)alkyl, —CON((C1-C6)alkyl)2, —OC(O)(C1-C6)alkyl, —OC(O)NH2, —OC(O)NH(C1-C6)alkyl, —OC(O)NH((C1-C6)alkyl)2, —NHC(O)(C1-C6)alkyl, —N(C1-C6)alkyl-C(O)(C1-C6)alkyl, —NH—C(O)NH2, —N(C1-C6)alkyl-C(O)NH2, —N(C1-C6)alkyl-C(O)NH(C1-C6)alkyl, N(C1-C6)alkyl-C(O)NH(C1-C6)alkyl)2, —NH—C(O)NH(C1-C6)alkyl)2, —NH—(C1-C6)alkylsulfamoyl, N,N-di-[(C1-C6)alkyl]sulfamoyl, (C1-C6)alkylsulfonylamino, or —N—(C1-C6)alkyl-(C1-C6)alkylsulfonylamino, wherein the —NH(C1-C6)alkyl, —N((C1-C6)alkyl)2, aryl, heteroaryl, (C3-C7)cycloalkyl, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C2-C6)alkenyloxy, (C2-C6)alkynyloxy, (C1-C6)alkylthio, (C1-C6)alkylsulfonyl, (C1-C6)alkylamino, di-[(C1-C6)alkyl]amino, —C(═O)(C1-C6)alkyl, —C(═N)(C1-C6)alkyl, carboxy, —CO2(C1-C6)alkyl, —C(═N)NH(C1-C6)alkyl), —C(═N)N(C1-C6)alkyl)2, —CONH(C1-C6)alkyl, —CON((C1-C6)alkyl)2, —OC(O)(C1-C6)alkyl, —OC(O)NH(C1-C6)alkyl, —OC(O)NH((C1-C6)alkyl)2, —NHC(O)(C1-C6)alkyl, —N(C1-C6)alkyl-C(O)(C1-C6)alkyl, —N(C1-C6)alkyl-C(O)NH2, —N(C1-C6)alkyl-C(O)NH(C1-C6)alkyl, N(C1-C6)alkyl-C(O)NH(C1-C6)alkyl)2, —NH—C(O)NH(C1-C6)alkyl)2, —NH—(C1-C6)alkylsulfamoyl, N,N-di-[(C1-C6)alkyl]sulfamoyl, (C1-C6)alkylsulfonylamino, or —N—(C1-C6)alkyl-(C1-C6)alkylsulfonylamino may be optionally substituted on carbon with R7;
- and
- R7 is halogen, trifluoromethyl, trifluoromethoxy, (C1-C6)alkyl , (C1-C6)alkoxy, cyano, nitro, or hydroxyl.
10 more elements
A compound selected from the group consisting of:
- and pharmaceutically acceptable salts thereof.
Dependencies are inferred from the claim text.