US 7,547,724 B2
IAP BIR domain binding compounds
Alain Laurent, Montreal (Canada); Kim E. Hewitt, Montreal (Canada); Stephen Morris, Beaconsfield (Canada); Patrick Bureau, Kirkland (Canada); Alain Boudreault, Dorval (Canada); Scott Jarvis, Longueuil (Canada); and James Jaquith, Pincourt (Canada)
Assigned to Aegera Therpeutics, Inc., Verdum, Quebec (US)
Filed on Dec. 01, 2006, as Appl. No. 11/606,883.
Application 11/606883 is a continuation of application No. 11/583816, filed on Oct. 20, 2006.
Claims priority of provisional application 60/830662, filed on Jul. 14, 2006.
Claims priority of provisional application 60/729727, filed on Oct. 25, 2005.
Prior Publication US 2008/0014207 A1, Jan. 17, 2008
Int. Cl. A61K 31/427 (2006.01); C07D 417/04 (2006.01)
U.S. Cl. 514—423  [514/422; 548/518] 15 Claims
 
1. A compound represented by formula:

OG Complex Work Unit Drawing
or a salt thereof,
wherein:
m is 0, 1 or 2;
p is 1 or 2;
Y is NH, O or S;
A and A1 are independently selected from
1) —CH2—,
2) —CH2CH2—,
3) —C(CH3)2—,
4) —CH(C1-C6 alkyl)-,
5) —CH(C3-C7 cycloalkyl)-,
6) —C3-C7 cycloalkyl-,
7) —CH(C1-C6 alkyl-C3-C7 cycloalkyl)-, or
8) —C(O)—;
B and B1 are independently C1-C6 alkyl;
X and X1 are independently selected from

OG Complex Work Unit Drawing
R1, R100, R2 and R200 are independently selected from:
1) H, or
2) C1-C6 alkyl optionally substituted with one or more R6 substituents;
Q and Q1 are each independently
1) NR4R5,
2) OR11, or
3) S(O)mR11; or
Q and Q1 are each independently

OG Complex Work Unit Drawing
wherein G is a 5, 6 or 7 membered ring which optionally incorporates one or more heteroatoms chosen from S, N or O, the ring being optionally substituted with one or more R12 substituents;
R4 and R5 are each independently
1) H,
2) haloalkyl,
3) C1-C6 alkyl,
4) C2-C6 alkenyl,
5) C2-C4 alkynyl,
6) C3-C7 cycloalkyl,
7) C3-C7 cycloalkenyl,
8) aryl,
9) heteroaryl,
10) heterocyclyl,
11) heterobicyclyl,
12) C(O)—R11,
13) C(O)O—R11,
14) C(═Y)NR8R9, or
15) S(O)2—R11,
wherein the alkyl, alkenyl, alkynyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more R6 substituents; and wherein the aryl, heteroaryl, heterocyclyl, and heterobicyclyl is optionally substituted with one or more R10 substituents;
R6 is
1) halogen,
2) NO2,
3) CN,
4) haloalkyl,
5) C1-C6 alkyl,
6) C2-C6 alkenyl,
7) C2-C4 alkynyl,
8) C3-C7 cycloalkyl,
9) C3-C7 cycloalkenyl,
10) aryl,
11) heteroaryl,
12) heterocyclyl,
13) heterobicyclyl,
14) OR 7,
15) S(O)mR7,
16) NR8R9,
17) NR8S(O)2R11,
18) COR7,
19) C(O)OR7,
20) CONR8R9,
21) S(O)2NR8R9
22) OC(O)R7,
23) OC(O)Y—R11,
24) SC(O)R7, or
25) NC(Y)NR8R9,
wherein the aryl, heteroaryl, heterocyclyl, and heterobicyclyl is optionally substituted with one or more R10 substituents;
R7 is
1) H,
2) haloalkyl,
3) C1-C6 alkyl,
4) C2-C6 alkenyl,
5) C2-C4 alkynyl,
6) C3-C7 cycloalkyl,
7) C3-C7 cycloalkenyl,
8) aryl,
9) heteroaryl,
10) heterocyclyl,
11) heterobicyclyl,
12) R8R9NC(═Y), or
13) C1-C6 alkyl-C2-C4 alkenyl, or
14) C1-C6 alkyl-C2-C4 alkynyl,
wherein the alkyl, alkenyl, alkynyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more R6 substituents; and wherein the aryl, heteroaryl, heterocyclyl, and heterobicyclyl is optionally substituted with one or more R10 substituents;
R8 and R9 are each independently
1) H,
2) haloalkyl,
3) C1-C6 alkyl,
4) C2-C6 alkenyl,
5) C2-C4 alkynyl,
6) C3-C7 cycloalkyl,
7) C3-C7 cycloalkenyl,
8) aryl,
9) heteroaryl,
10) heterocyclyl,
11) heterobicyclyl,
12) C(O)R11,
13) C(O)Y—R11, or
14) S(O)2—R11,
wherein the alkyl, alkenyl, alkynyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more R6 substituents; and wherein the aryl, heteroaryl, heterocyclyl, and heterobicyclyl is optionally substituted with one or more R10 substituents;
or R8 and R9 together with the nitrogen atom to which they are bonded form a five, six or seven membered heterocyclic ring optionally substituted with one or more R6 substituents;
R10 is
1) halogen,
2) NO2,
3) CN,
4) B(OR13)(OR14),
5) C1-C6 alkyl,
6) C2-C6 alkenyl,
7) C2-C4 alkynyl,
8) C3-C7 cycloalkyl,
9) C3-C7 cycloalkenyl,
10) haloalkyl,
11) OR7,
12) NR8R9,
13) SR7,
14) COR7,
15) C(O)OR7,
16) S(O)mR7,
17) CONR8R9,
18) S(O)2NR8R9,
19) aryl,
20) heteroaryl,
21) heterocyclyl, or
22) heterobicyclyl,
wherein the alkyl, alkenyl, alkynyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more R6 substituents;
R11 is
1) haloalkyl,
2) C1-C6 alkyl,
3) C2-C6 alkenyl,
4) C2-C4 alkynyl,
5) C3-C7 cycloalkyl,
6) C3-C7 cycloalkenyl,
7) aryl,
8) heteroaryl,
9) heterocyclyl, or
10) heterobicyclyl,
wherein the alkyl, alkenyl, alkynyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more R6 substituents; and wherein the aryl, heteroaryl, heterocyclyl, and heterobicyclyl is optionally substituted with one or more R10 substituents;
R12 is
1) haloalkyl,
2) C1-C6 alkyl,
3) C2-C6 alkenyl,
4) C2-C4 alkynyl,
5) C3-C7 cycloalkyl,
6) C3-C7 cycloalkenyl,
7) aryl,
8) heteroaryl,
9) heterocyclyl,
10) heterobicyclyl,
11) C(O)—R11,
12) C(O)O—R11,
13) C(O)NR8R9,
14) S(O)m—R11, or
15) C(═Y)NR8R9,
wherein the alkyl, alkenyl, alkynyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more R6 substituents; and wherein the aryl, heteroaryl, heterocyclyl, and heterobicyclyl is optionally substituted with one or more R10 substituents;
R13 and R14 are each independently
1) H, or
2) C1-C6 alkyl; or
R13 and R14 are combined to form a heterocyclic ring or a heterobicyclic ring.