Carboxylic acid, acyl sulfonamide and acyl sulfamide-derivatized bicyclic aza-heteroaromatics as selective Mcl-1 inhibitors and as dual Mcl-1/Bcl-2 inhibitors

1. A compound of formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, or prodrug thereof:

wherein:

A is a substituted heterocycle selected from:

L is —C(O)NR a SO 2 — or —C(O)O—; and

R, R 1 , R a , and Z are independently selected at each occurrence from H, halogen, optionally substituted alkyl, optionally substituted alkylaryl, optionally substituted alkylhetaryl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted haloalkyl, optionally substituted alkoxy, and optionally substituted heteroaryl,

wherein one of Z is

with the proviso that when A is

 and Z bonded to the carbon atom is

 the compound of formula (I) is limited by at least one of i) or ii):

i) R 1 is

 or the optional substituent of R 1 is selected from

ii) R 1 is a group selected from:

2. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, or prodrug thereof, wherein R 1 is selected from H, alkyl, and substituted aryl.

3. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, or prodrug thereof, wherein when A is

one Z is H.

4. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, or prodrug thereof, wherein R 1 comprises a group selected from:

5. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, or prodrug thereof, wherein R 1 comprises a group selected from:

6. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, or prodrug thereof, wherein Z is

7. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, or prodrug thereof, wherein Z comprises a group selected from:

8. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, or prodrug thereof, wherein the compound of formula (I) is selected from Table 1, wherein R is independently selected from H, a halogen, and —COCH 3 ; and Z is independently selected from H, halogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aralkyl, and optionally substituted heteroaryl, wherein one of Z is

TABLE 1

Compound #

A

L

R 1

1002

—C(O)O—

H

1008

—C(O)NHSO 2 —

1014

—C(O)NHSO 2 —

1026

—C(O)NHSO 2 —

1032

—C(O)NHSO 2 —

1038

—C(O)NHSO 2 —

1044

—C(O)NHSO 2 —

1050

—C(O)NHSO 2 —

1056

—C(O)NHSO 2 —

1062

—C(O)NHSO 2 —

1068

—C(O)NHSO 2 —

1074

—C(O)NHSO 2 —

1080

—C(O)NHSO 2 —

1086

—C(O)NHSO 2 —

1092

—C(O)NHSO 2 —

1097

—C(O)O—

H

1098

—C(O)NHSO 2 —

1099

—C(O)NHSO 2 —

1100

—C(O)NHSO 2 —

1101

—C(O)NHSO 2 —

1102

—C(O)NHSO 2 —

1103

—C(O)NHSO 2 —

1104

—C(O)NHSO 2 —

1105

—C(O)NHSO 2 —

1106

—C(O)NHSO 2 —

1107

—C(O)NHSO 2 —

1108

—C(O)NHSO 2 —

1109

—C(O)NHSO 2 —

1110

—C(O)NHSO 2 —

1111

—C(O)NHSO 2 —

1112

—C(O)NHSO 2 —

1114

—C(O)O—

—CH 3

1119

—C(O)O—

—CH 3 .

9. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, or prodrug thereof, wherein the compound of formula (I) is selected from Table 2:

TABLE 2

NB-1-070

NB-1-084

NB-1-086

NB-1-087

NB-1-088

NB-1-089

CG-1-016

CG-1-018

CG-1-019

CG-1-022

CG-1-023

GV-1-028

BD-3-173

BD-3-180

BD-3-181

BD-3-183

BD-3-184

BD-3-187

BD-3-190

BD-3-190-b

BD-3-187-b

BD-3-180-b

2005

2006

10. A pharmaceutical composition for treating leukemia, the pharmaceutical composition comprising one or more compounds according to claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, or prodrug thereof, and a pharmaceutically acceptable carrier.

11. A pharmaceutical composition for treating lymphoma, the pharmaceutical composition comprising one or more compounds according to claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, or prodrug thereof, and a pharmaceutically acceptable carrier.

12. The pharmaceutical composition of claim 11 , wherein the lymphoma is non-Hodgkin's lymphoma.

13. The pharmaceutical composition of claim 10 , wherein the leukemia is selected from myeloid leukemia, acute myeloid leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, chronic granulocytic leukemia, acute granulocytic leukemia, and hairy cell leukemia.

14. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, or prodrug thereof, wherein Z is

15. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, or prodrug thereof, wherein the compound of formula (I) is selected from Table 1, wherein R is independently selected from H, a halogen, and —COCH 3 ; and Z is independently selected from H, halogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aralkyl, and optionally substituted heteroaryl, wherein one of Z is

TABLE 1

Compound #

A

L

R 1

]1002

—C(O)O—

H

1008

—C(O)NHSO 2 —

1014

—C(O)NHSO 2 —

1020

—C(O)NHSO 2 —

1026

—C(O)NHSO 2 —

1032

—C(O)NHSO 2 —

1038

—C(O)NHSO 2 —

1044

—C(O)NHSO 2 —

1050

—C(O)NHSO 2 —

1056

—C(O)NHSO 2 —

1062

—C(O)NHSO 2 —

1068

—C(O)NHSO 2 —

1074

—C(O)NHSO 2 —

1080

—C(O)NHSO 2 —

1086

—C(O)NHSO 2 —

1092

—C(O)NHSO 2 —

1098

—C(O)NHSO 2 —

1099

—C(O)NHSO 2 —

1100

—C(O)NHSO 2 —

1101

—C(O)NHSO 2 —

1102

—C(O)NHSO 2 —

1103

—C(O)NHSO 2 —

1104

—C(O)NHSO 2 —

1105

—C(O)NHSO 2 —

1106

—C(O)NHSO 2 —

1107

—C(O)NHSO 2 —

1108

—C(O)NHSO 2 —

1109

—C(O)NHSO 2 —

1110

—C(O)NHSO 2 —

1111

—C(O)NHSO 2 —

1112

—C(O)NHSO 2 —

1114

—C(O)O—

—CH 3

1119

—C(O)O—

—CH 3 .