1. Claim 84
1.1. (Claim 84) The method of claim 83, wherein the anti-apoptosis agent is tretinoin, GGTI 298 TFA salt, BTSA1, AT406, SM-406, elesclomol, STA-4783, Ganetespib, STA-9090, NQDI-1, or zoledronic acid
2. Claim 1
2.1. (Claim 1)A compound of Formula (I) : wherein each Q, Y and Z are independently selected from N and C, and X is N or C-R a; provided that at least one of Q, X, Y and Z is N, and each dashed bond is independently a single or double bond such that the bicycle they form is a heteroaryl; R 1 is selected from alkyl, alkenyl, alkynyl, amino, acylamino, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, and heteroaralkyl; either a) W is N, R 2 is absent, and A 1 and A 2 are each CH 2; b) W is C, R 2 is selected from H, halo, CN, alkyl, alkoxy, hydroxy, acyloxy, and amino, and A 1 and A 2 are each independently selected from CH 2 and O; or c) W is C, and R 1 and R 2 are taken together to form a =CH 2-amido, cycloalkyl, and heterocyclyl, and A 1 and A 2 are each independently selected from CH 2 and O; R a is selected from H, halo, CN and alkyl; R 9 is selected from H, halo, alkyl, alkoxy, hydroxy, acyloxy, and amino; R 10 is H or alkoxy; R 11 is aryloxy, heteroaryloxy, arylalkyl, alkoxycarbonyl, ureido or -C (O) -aryl; and R 12 is selected from H, halo, CN, alkyl, alkoxy, hydroxy, and acyloxy; provided that the compound of Formula (I)
2.1.1. provided that the compound of Formula (I) is not
2.1.1.1. (Not)
2.1.2. if W is C, R 2, R 9 and R 12 are each hydrogen, and R 11 is unsubstituted phenyloxy, then R 1 is not -NHCH 2OH, -NHCH 2COOH, -NHCH 2CONH 2, -NHCH 2CH 2NH 2, -NH (CH 2) 2N (Me) 2, -NHCH 2-pyridinyl, -NHCO-pyridyl, -C (O) OEt, -NH-tetrahydropyran, -NHCH 2pyrrolidinyl, -NH (CH 2) 3imidazolyl, -NHpyrrolidinonyl, wherein R 13 is selected from H, ethyl, isopropyl, t-butyl, -CH 2OCH 3, -CH 2CH 2OH and -CH 2CH 2OCH 3; and if W is N, R 9 and R 12 are each hydrogen, and R 11 is unsubstituted phenyloxy, then R 1 is not piperidinyl.
2.1.2.1. (Not)
2.2. Claim 2~5
2.2.1. Claim 6
2.2.1.1. The compound of any one of claims 1-5, wherein R 1 is V is N or CH; T is N or CH; R 3 is alkyl; and R 4 is H or alkyl.
2.2.2. Claim 7
2.2.2.1. Claim 8
2.2.2.1.1. Claim 9
2.2.2.1.2. (Claim 8) The compound of any one of claims 1-7, wherein Q is C, X is C-R a, R a is H, Y is N and Z is C; Q is C, X is C-R a, R a is halo, Y is N and Z is C; Q is C, X is N, Y is C and Z is N; Q is C, X is N, Y is N and Z is C; Q is N, X is C-R a, R a is H, Y is C and Z is C; Q is C, X is C-R a, R a is H, Y is C and Z is N; or Q is C, X is C-R a, R a is H, Y is N and Z is C.
2.2.2.2. (Claim 7) The compound of any one of claims 1-5, wherein R 1 is V is N or CH; T is N or CH; R 3 is alkyl; and R 4 is H or alkyl
2.2.3. (Claim 2) The compound of claim 1, having the structure: wherein R 2 is H.
2.2.4. (Claim 3) The compound of claim 1, having the structure: wherein R 2 is H.
2.2.5. (Claim 4) The compound of claim 1, having the structure: wherein R 2 is H.
2.2.6. (Claim 5) The compound of claim 1, having the structure: wherein R 2 is H.
3. Claim 71
3.1. Claim 72
3.1.1. Claim 73
3.1.1.1. Claim 74
3.1.1.1.1. Example127
3.1.1.1.2. (Claim 74) The method of claim 73, wherein the HCK inhibitor is and the BCL-2 inhibitor is ABT-199.
3.1.1.2. Claim 75
3.1.1.2.1. Example103
3.1.1.2.2. (Claim 75) The method of claim 73, wherein the HCK inhibitor is and the BCL-2 inhibitor is ABT-199.
3.1.1.3. Claim 76
3.1.1.3.1. Example165
3.1.1.3.2. (Claim 76) The method of claim 73, wherein the HCK inhibitor is and the BCL-2 inhibitor is ABT-199.
3.1.1.4. Claim 77
3.1.1.4.1. Example163
3.1.1.4.2. (Claim 77) The method of claim 73, wherein the HCK inhibitor is and the BCL-2 inhibitor is ABT-199.
3.1.1.5. Claim 78
3.1.1.5.1. (Claim 78) The method of claim 73, wherein the FLT3-ITD inhibitor is AC220 and the BCL-2 inhibitor is ABT-199.
3.1.1.6. (Claim 73) The method of claim 72, wherein the BCL-2 inhibitor is ABT-199.
3.1.2. Claim 79
3.1.2.1. (Claim 79) The method of claim 72, wherein the FLT3-ITD inhibitor is SU5614 and the BCL-2 inhibitor is ABT-737.
3.1.3. (Claim 72) The method of claim 71, wherein the BCL-2 inhibitor is selected from gossypol, obatoclax, ABT-737, ABT-199, and ABT-263.
3.2. (Claim 71) The method of any preceding claim, wherein the BCL-2 inhibitor is selected from AT-101, TW-37, TM-1206, gossypolic acid, gossypolonic acid, apogossypol, apogossypolone, A385358, ABT-737, ABT-263, ABT-199, WEHI-539, BXI-61, BXI-72, obatoclax, JY-1-106, and SAHB peptides.
4. Claim 80
4.1. (Claim 80) The method of any preceding claim, wherein the HCK inhibitor, and/or FLT3-ITD inhibitor, and/or the BCL-2 inhibitor is each present as a pharmaceutically acceptable salt.
5. Claim 81
5.1. (Claim 81) The method of any preceding claim, wherein the HCK inhibitor, and/or FLT3-ITD inhibitor, and/or the BCL-2 inhibitor is each present in a pharmaceutically acceptable composition.
6. Claim 82
6.1. (Claim 82) The method of any preceding claim, wherein the HCK inhibitor, and/or FLT3-ITD inhibitor, and/or the BCL-2 inhibitor is administered conjointly with dexamethasone.
7. Claim 83
7.1. (Claim 83) The method of any preceding claim, wherein the HCK inhibitor, and/or FLT3-ITD inhibitor, and/or the BCL-2 inhibitor is administered conjointly with an anti-apoptosis agent.
8. Claim 85
8.1. Claim 86
8.1.1. (Claim 86) The method of claim 85, wherein the Mcl-1 inhibitor is
8.2. (Claim 85) The method of any preceding claim, wherein the HCK inhibitor, and/or FLT3-ITD inhibitor, and/or the BCL-2 inhibitor is administered conjointly with an Mcl-1 inhibitor.
9. Claim 87
9.1. Claim 88
9.1.1. (Claim 88) The method of claim 87, wherein the IAP antagonist is +AT-406/Debio 1143, GDC-0917/CUDC-427, LCL161, or TL-32711.
9.2. (Claim 87) The method of any preceding claim, wherein the HCK inhibitor, and/or FLT3-ITD inhibitor, and/or the BCL-2 inhibitor is administered conjointly with an IAP antagonist.
10. Claim 89
10.1. Claim 90
10.1.1. (Claim 90) The method of claim 89, wherein the cell cycle inhibitor is selected from palbociclib, ribociclib, abemaciclib, flavopiridol, AT9283, alisertib, and MK-1775.