US 7,495,102 B2
Azaindole inhibitors of aurora kinases
Martha A. Sarpong, Collegeville, Pa. (US); Nicholas D. Adams, Collegeville, Pa. (US); Jeffrey Michael Axten, Collegeville, Pa. (US); Amita M. Chaudhari, Collegeville, Pa. (US); Dashyant Dhanak, Collegeville, Pa. (US); Toshihiro Hamajima, Tsukuba (Japan); Kenneth Allen Newlander, Collegeville, Pa. (US); Cynthia A. Parrish, Collegeville, Pa. (US); Jerry Leroy Adams, Collegeville, Pa. (US); Domingos J. Silva, Collegeville, Pa. (US); and Jun Tang, Durham, N.C. (US)
Assigned to SmithKline Beecham Corporation, Philadelphia, Pa. (US)
Filed on Sep. 14, 2007, as Appl. No. 11/855,183.
Application 11/835434 is a division of application No. 11/612531, filed on Dec. 19, 2006, granted, now 7,282,588.
Application 11/855183 is a continuation of application No. 11/835434, filed on Aug. 08, 2007, granted, now 7,419,988.
Claims priority of provisional application 60/753383, filed on Dec. 23, 2005.
Prior Publication US 2008/0081808 A1, Apr. 03, 2008
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 453/02 (2006.01)
U.S. Cl. 546—133 12 Claims
 
1. A compound of the following formula:

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt thereof, wherein:
A is >C═Y or >S(O)x wherein Y is O, S, or N—R1; wherein x is 1 or 2;
R1 is independently H, C1-C3-alkyl, or cyclopropyl;
R2 is H, C1-C6 alkyl, halo-C1-C6-alkyl, C3-C6-cycloalkyl, C1-C6 alkoxy, hydroxy-C1-C6-alkyl, amino-C1-C6 alkyl, C1-C6 alkoxymethyl, hydroxy, —(CH2)y—Ar—(R7)z, or NR8R9, with the proviso that when A is S(O)x, R2 is not H; wherein y is 0, 1, or 2; and z is a non-negative integer not greater than the number of positions available on Ar for substitution;
Ar is phenyl or heteroaryl;
R3 is independently H, C1-C6-alkyl, C2-C6-alkenyl, halo-C1-C6-alkyl, hydroxy-C1-C6-alkyl, amino-C1-C6-alkyl, C1-C6-alkylamino-C1-C6-alkyl, di-C1-C6-alkylamino-C1-C6-alkyl, —(CH2)w—R10; wherein w is 1 or 2;
R4 is independently C1-C6-alkyl, halo, halo-C1-C6-alkyl, or Ar—(R7)z;
R5 is independently C1-C6-alkyl, halo, halo-C1-C6-alkyl, Ar—(R7)z, —(CH2)aNR13R14, —Ar—(CH2)aNR13R14, -A′-NR1—(CH2)b-A″, —CH2CH2C(O)-A′″, or —Ar′—(C(O)(CH2)aNR13R14)c;
wherein A′ is C(O) or CH2; A″ is H, NR13R14, C1-C6-thioalkyl, C1-C6-alkoxy, —SO2CH3, or —OH;
A′″ is —OH, C1-C6-alkoxy, or —NR13R14; and Ar′ is a 5- or 6-membered heterocycloalkyl ring;
wherein a is independently 0, 1, or 2; b is 1, 2, or 3, with the proviso that when b is 1, A″ is H;
and c is 0 or 1;
R6 and each R7 are each independently halo, cyano, nitro, C1-C6-alkyl, COOH, C1-C6-alkylcarbonyl, C1-C6-alkyl-carbonyl-C1-C6-alkyl, amino, C1-C6-alkylamino, di-C1-C6-alkylamino, amino-C1-C6-alkyl, C1-C6-alkylamino-C1-C6-alkyl, di-C1-C6-alkylamino-C1-C6-alkyl, OH, halo-C1-C6-alkyl, hydroxy-C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkoxy-C1-C6-alkyl, heteroaryl, or phenyl;
R8 is H or C1-C6-alkyl;
R9 is H, C1-C6-alkyl, halo-C1-C6-alkyl, C3-C6cycloalkyl, C1-C6 alkoxy, —(CH2)y—Ar—(R7)z; or R8 and R9, together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring optionally substituted with C1-C6-alkyl, halo, amino, cyano, C1-C6-alkoxy, or OH;
R10 is heterocycloalkyl, Ar—(R7)z, COOH, or C(O)—NR11R12
R11 is H or C1-C3-alkyl;
R12 is H, C1-C6-alkyl, halo-C1-C3-alkyl, or hydroxy-C1-C3-alkyl; or R11 and, together with the nitrogen atom to which they are attached form 5- or 6-membered heterocycloalkyl ring optionally substituted with C1-C6-alkyl, halo, amino, cyano, C1-C6-alkoxy, or hydroxy;
R13 is H, C1-C6-alkyl, or hydroxy-C1-C6-alkyl;
R14 is H, C1-C6-alkyl, halo-C1-C6-alkyl, hydroxy-C1-C6-alkyl, C1-C6-alkylamino, or SO2CH3; or R13 and R14, together with the nitrogen atom to which they are attached form 5- or 6-membered heterocycloalkyl ring optionally substituted with C1-C6-alkyl, halo, amino, cyano, C1-C6-alkoxy, hydroxy-C1-C6-alkyl, or OH; and
R15 and R16 are each independently H, C1-C6-alkyl, or halo, or R15 and R16, together with the carbon atom to which they are attached form cyclopropyl, C═O, C═S, or C═NR1;
m is 0 or 1;
n, o, and q are each independently 0, 1, or 2; and
p is 0, 1, 2, 3, or 4.