Substituted heteroaryls as inhibitors of the BCL6 BTB domain protein-protein interaction
The present application relates to compounds of Formula I or pharmaceutically acceptable salts, solvates and/or prodrugs thereof, to compositions comprising these compounds or pharmaceutically acceptable salts, solvates and/or prodrugs thereof, and various uses in the treatment of diseases, disorders or conditions that are treatable by inhibiting interactions with BCL6 BTB, such as cancer.
1. A compound of formula (I):
or a pharmaceutically acceptable salt or stereoisomer thereof,
wherein:
X 3 is CR 6 or N;
X 4 is CR 7 or N;
X 5 is CR 8 or N;
R 1 is H, C 1-6 alkyl, C 1-6 alkylene-C(O)—C 3-6 cycloalkyl, C 1-6 alkylene-C(O)—C 3-6 heterocycloalkyl, C 1-6 alkylene-C(O)-phenyl, C 1-6 alkylene-C(O)—C 5-6 heteroaryl, C 1-6 alkylene-O—C 1-6 alkyl, C 1-6 alkylene-C 3-6 cycloalkcyl, C 1-6 alkylene-C 3-6 heterocycloalkyl, C 1-6 alkylene-phenyl, C 1-6 alkylene-C 5-6 heteroaryl, C 2-6 alkenylene-O—C 1-6 alkyl, C 2-6 alkenylene-C 3-6 cycloalkyl, C 2-6 alkenylene-C 3-6 heterocycloalkyl, C 2-6 alkenylene-phenyl, C 2-6 alkenylene-C 5-6 heteroaryl, C 2-6 alkynylene-O—C 1-6 alkyl, C 2-6 alkynylene-C 3-6 cycloalkyl, C 2-6 alkynylene-C 3-6 heterocycloalkcyl, C 2-6 alkynylene-phenyl, or C 2-6 alkynylene-C 5-6 heteroaryl, wherein each C 3-6 cycloalkyl, C 3-6 heterocycloalkyl, phenyl, or C 5-6 heteroaryl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo and C 1-4 alkyl;
R 2 is H, halo, C 1-6 alkyl, NH 2 , NH 1-6 alkyl, N(C 1-6 alkyl)(C 1-6 alkyl), OH, OC 1-6 alkyl, SH, Z 1 —C 1-6 alkylene-O—C 1-6 alkyl, Z 1 —C 1-6 alkylene-C 3-6 cycloalkyl, Z 1 —C 1-6 alkylene-C 3-6 heterocycloalkyl, Z 1 —C 1-6 alkylene-phenyl, Z 1 —C 1-6 alkylene-C 5-6 heteroaryl, Z 1 —C 2-6 alkenylene-O—C 1-6 alkyl, Z 1 —C 2-6 alkenylene-C 3-6 cycloalkyl, Z 1 —C 2-6 alkenylene-C 3-6 heterocycloalkyl, Z 1 —C 2-6 alkenylene-phenyl, Z 1 —C 2-6 alkenylene-C 5-6 heteroaryl, Z 1 —C 2-6 alkynylene-O—C 1-6 alkyl, Z 1 —C 2-6 alkynylene-C 3-6 cycloalkyl, Z 1 —C 2-6 alkynylene-C 3-6 heterocycloalkyl, Z 1 —C 2-6 alkynylene-phenyl, Z 1 —C 2-6 alkynylene-C 5-6 heteroaryl, Z 1 —C 3-6 cycloalkyl, Z 1 —C 3-6 heterocycloalkyl, Z 1 -phenyl, or Z 1 —C 5-6 heteroaryl, wherein each C 3-6 cycloalkyl, C 3-6 heterocycloalkyl, phenyl, or C 5-6 heteroaryl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, NH 2 , NHC 1-6 alkyl, N(C 1-6 alkyl)(C 1-6 alkyl), OH, and SH;
R 3 is C 6-10 cycloalkyl, C 6-10 heterocycloalkyl, C 6-10 aryl, or C 6-10 heteroaryl, wherein the C 6-10 cycloalkyl, C 6-10 heterocycloalkyl, C 6-10 aryl, or C 6-10 heteroaryl is optionally substituted with 1 Z 2 —R 9 substituent, and optionally further substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halo, CN, NO 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, OC 1 alkyl, and ═O;
R 4 is H or C 1-6 alkyl;
R 5 is OH;
R 6 is H or halo;
R 7 is H, halo, C 1-6 alkyl, OC 1-6 alkyl, or S(O) 2 NH 2 ;
R 8 is H, halo, C 1-6 alkyl, OC 1-6 alkyl, or S(O) 2 NH 2 ; or
R 7 and R 8 , taken together with the carbon atoms to which they are attached, form a 3- to 8-membered heterocycloalkyl or heteroaryl, wherein the 3- to 8-membered heterocycloalkyl or heteroaryl contains 1 or 2 heteroatoms or heteroatomic groups independently selected from the group consisting of NH, N(C 1-6 alkyl), O, S, S(O), and S(O) 2 ;
R 9 is C 1-6 alkyl, NR 10 R 11 , C 3-10 cycloalkyl, C 3-10 heterocycloalkyl, C 6-10 aryl, or C 5-10 heteroaryl, wherein the C 3-10 cycloalkyl, C 3-10 heterocycloalkyl, C 6-10 aryl, or C 5-10 heteroaryl is optionally substituted with 1 substituent selected from the group consisting of C 1-6 alkylene-OH, C 1-6 alkylene-(diOH), C 1-6 alkylene-O—C 1-6 alkyl, S(O) 2 C 1-4 alkyl, Z 3 —C 3-10 cycloalkyl, Z 3 —C 3-10 heterocycloalkyl, Z 3 —C 6-10 aryl, and Z 3 —C 5-10 heteroaryl, wherein the Z 3 —C 3-10 cycloalkyl, Z 3 —C 3-10 heterocycloalkyl, Z 3 —C 6-10 aryl, or Z 3 —C 5-10 heteroaryl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halo and C 1-6 alkyl, and optionally further substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from the group consisting of halo, CN, C 1-6 alkyl, and OC 1-6 alkyl;
R 10 is H, C 1-6 alkyl, C 1-6 alkylene-OH, C 1-6 alkylene-(diOH), C 1-6 alkylene-O—C 1-6 alkyl, S(O) 2 C 1-6 alkyl, Z 4 —C 3-10 cycloalkyl, Z 4 —C 3-10 heterocycloalkyl, Z 4 —C 6-10 aryl, or Z 4 —C 5-10 heteroaryl, wherein the Z 4 —C 3-10 cycloalkyl, Z 4 —C 3-10 heterocycloalkyl, Z 4 —C 6-10 aryl, or Z 4 —C 5-10 heteroaryl is optionally substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from the group consisting of halo and C 1-6 alkyl;
R 11 is H, C 1-6 alkyl, C 1-6 alkylene-OH, C 1-6 alkylene-(diOH), C 1-6 alkylene-O—C 1-6 alkyl, S(O) 2 C 1-6 alkyl, Z 4 —C 3-10 cycloalkyl, Z 4 —C 3-10 heterocycloalkyl, Z 4 —C 6-10 aryl, or Z 4 —C 5-10 heteroaryl, wherein the Z 4 —C 3-10 cycloalkyl, Z 4 —C 3-10 heterocycloalkyl, Z 4 —C 6-10 aryl, or Z 4 —C 5-10 heteroaryl is optionally substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from the group consisting of halo and C 1-6 alkyl;
Z 1 is a direct bond, —NH—, —NC 1-6 alkyl-, —O—, —S(O)—, or —S(O) 2 —;
Z 2 is a direct bond, —C 1-6 alkylene-, —C(O)—, —O—, —S—, —S(O)—, or —S(O) 2 —
Z 3 is a direct bond or —C 1-6 alkylene-; and
Z 4 is a direct bond or —C 1-6 alkylene-;
wherein each C 1-6 alkyl and C 1-6 alkylene is optionally and independently substituted with 1 or more substituents independently selected from the group consisting of D and F.
2. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 1 is H, CH 3 , CF 3 , CH 2 OCH 3 , CH 2 OCF 3 , CH 2 —C 3-6 cycloalkyl, CH 2 —C 3-6 heterocycloalkyl, CH 2 -phenyl, CH 2 —C 5-6 heteroaryl, CH 2 CH 2 —C(O)—C 3-6 cycloalkyl, CH 2 CH 2 —C(O)—C 3-6 heterocycloalkyl, CH 2 CH 2 —C(O)-phenyl, CH 2 CH 2 —C(O)—C 5-6 heteroaryl, CH 2 C≡C—C 3-6 cycloalkyl, CH 2 C≡C—C 3-6 heterocycloalkyl, CH 2 C≡C-phenyl, and CH 2 C≡C—C 5-6 heteroaryl, wherein each C 3-6 cycloalkyl, C 3-6 heterocycloalkyl, phenyl, or C 3-6 heteroaryl is optionally substituted with 1 or 2 substituents independently selected from the group consisting of F, Cl, CH 3 , and CF 3 .
3. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein the heteroaryl of R 1 is a C 5 heteroaryl, wherein 1 or 2 C atoms of the C 5 heteroaryl of R 1 is replaced with 1 or 2 N heteroatoms, and further wherein the C 5 heteroaryl of R 1 is optionally substituted with 1 or 2 CH 3 substituents.
4. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 2 is H, F, Cl, CH 3 , CF 3 , NH 2 , NHCH 3 , N(CH 3 ) 2 , N(CH 3 )(CH 2 CH 3 ), OH, OCH 3 , Z 1 —C 1-2 alkylene-OCH 3 , Z 1 —C 1-2 alkylene-C 3-6 cycloalkyl, Z 1 —C 1-2 alkylene-C 3-6 heterocycloalkyl, Z 1 —C 1-4 alkylene-phenyl, Z 1 —C 1-4 alkylene-C 5-6 heteroaryl, Z 1 —C 2-3 alkenylene-O—C 1-4 alkyl, Z 1 —C 2-3 alkenylene-C 3-6 cycloalkyl, Z 1 —C 2-3 alkenylene-C 3-6 heterocycloalkyl, Z 1 —C 2-3 alkenylene-phenyl, Z 1 —C 2-3 alkenylene-C 5-6 heteroaryl, Z 1 —C 3-6 cycloalkyl, Z 1 —C 3-6 heterocycloalkyl, Z 1 -phenyl, or Z 1 —C 5-6 heteroaryl, wherein each C 3-6 cycloalkyl, C 3-6 heterocycloalkyl, phenyl, or C 5-6 heteroaryl is optionally substituted with 1 or 2 substituents independently selected from the group consisting of F, Cl, and N(CH 3 ) 2 .
5. The compound of claim 4 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 2 is H, Cl, CH 3 , CF 3 , CH═CH-cyclopropyl, NH 2 , NHCH 3 , NH—CH 2 -cyclopropyl, NH 2 —CH 2 -(p-F-phenyl), N(CH 3 ) 2 , N(CH 3 )(CH 2 CH 3 ), OH, OCH 3 , O—CH 2 CH 2 —OCH 3 , azetidin-1-yl, phenyl, or NH-[5-chloro-2-(dimethylamino)pyridin-4-yl].
6. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 3 is C 6-10 aryl or C 6-10 heteroaryl, wherein the C 6-10 aryl or C 6-10 heteroaryl is monocyclic or bicyclic, and further wherein the C 6-10 aryl or C 6-10 heteroaryl is optionally substituted with 1 Z 2 —R 9 substituent, and optionally further substituted with 1, 2, or 3 substituents independently selected from the group consisting of F, Cl, CN, NO 2 , C 1-2 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, OC 1-2 alkyl, and ═O.
7. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
Z 2 is a direct bond; and
R 9 is:
wherein:
is the point of attachment to R 3 ;
X 6 is —CH 2 —, —CHF—, —CF 2 —, —CH(C 1-4 alkyl)-, —CH(C 1-4 alkylene-O—C 1-4 alkyl)-, —CH(C 1-4 alkylene-C 3-6 cycloalkyl)-, —CH(C 1-4 alkylene-C 3-6 heterocycloalkyl)-, —CH(C 3-6 cycloalkyl)-, —CH(C 3-6 heterocycloalkyl)-, —C(C 1-4 alkyl)(C 1-4 alkyl)-, —NH—, —N(C 1-4 alkyl)-, —N(C 1-4 alkylene-O—C 1-4 alkyl)-, —N(C 1-4 alkylene-C 3-6 cycloalkyl)-, —N(C 1-4 alkylene-C 3-6 heterocycloalkyl)-, —N(C 3-6 cycloalkyl)-, —N(C 3-6 heterocycloalkyl)-, or —O—;
R 12 is H, F, C 1-4 alkyl, or C 1-4 alkylene-O—C 1-4 alkyl;
R 13 is H, F, C 1-4 alkyl, or C 1-4 alkylene-O—C 1-4 alkyl;
R 14 is H, F, C 1-4 alkyl, or C 1-4 alkylene-O—C 1-4 alkyl; and
R 15 is H, F, C 1-4 alkyl, or C 1-4 alkylene-O—C 1-4 alkyl; or
R 12 and R 14 form a C 1-3 alkylene bridge linking the carbon atoms to which they are attached; or
R 13 and R 15 form a C 1-3 alkylene bridge linking the carbon atoms to which they are attached;
wherein each C 1-4 alkyl and C 1-4 alkylene is optionally and independently substituted with 1 or more F substituents.
8. The compound of claim 7 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
X 6 is —CH 2 —, —CHF—, —CF 2 —, —CH(CH 2 -cyclopropyl)-, —CH(CH 2 -cyclobutyl)-, —NH—, —N(CH 3 )—, —N(CH 2 CH 3 )—, —N[CH(CH 3 ) 2 ]—, N(CH 2 CH 2 —O—CH 3 )—, —N(CH 2 -cyclopropyl)-, N[CH(CH 3 )-cyclopropyl]-, N(CH 2 -cyclobutyl)-, —N(cyclopropyl)-, —N(cyclobutyl)-, —N(oxetanyl)-, or —O—;
R 12 is H, F, CH 3 , CF 3 , or C 1-2 alkylene-O—CH 3 ;
R 13 is H, F, CH 3 , CF 3 , or C 1-2 alkylene-O—CH 3 ;
R 14 is H, F, CH 3 , CF 3 , or C 1-2 alkylene-O—CH 3 ; and
R 15 is H, F, CH 3 , CF 3 , or C 1-2 alkylene-O—CH 3 ; or
R 12 and R 14 form a —CH 2 CH 2 — bridge linking the carbon atoms to which they are attached; or
R 13 and R 15 form a —CH 2 CH 2 — bridge linking the carbon atoms to which they are attached.
9. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
R 7 is H, F, Cl, CH 3 , CF 3 , CH 2 CH 3 , OCH 3 , OCF 3 , or S(O) 2 NH 2 ; and
R 8 is H, F, Cl, CH 3 , CF 3 , CH 2 CH 3 , OCH 3 , OCF 3 , or S(O) 2 NH 2 .
10. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 7 and R 8 , taken together with the carbon atoms to which they are attached, form a 3- to 6-membered heterocycloalkyl or heteroaryl, wherein the 3- to 6-membered heterocycloalkyl or heteroaryl contains 1 or 2 heteroatoms or heteroatomic groups independently selected from the group consisting of NH, N(CH 3 ), O, and S.
11. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 9 is C 1-4 alkyl, NR 10 R 11 , C 3-10 cycloalkyl, C 3-10 heterocycloalkyl, C 6-10 aryl, or C 5-10 heteroaryl, wherein the C 3-10 cycloalkyl, C 3-10 heterocycloalkyl, C 6-10 aryl, or C 5-10 heteroaryl is optionally substituted with 1 substituent selected from the group consisting of C 1-4 alkylene-OH, C 1-4 alkylene-(diOH), C 1-4 alkylene-O—C 1-4 alkyl, S(O) 2 C 1-4 alkyl, Z 3 —C 3-10 cycloalkyl, Z 3 —C 3-10 heterocycloalkyl, Z 3 —C 6-10 aryl, and Z 3 —C 5-10 heteroaryl, wherein the Z 3 —C 3-10 cycloalkyl, Z 3 —C 3-10 heterocycloalkyl, Z 3 —C 6-10 aryl, or Z 3 —C 5-10 heteroaryl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of F, Cl, and C 1-4 alkyl, and optionally further substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from the group consisting of halo, CN, C 1-4 alkyl, and OC 1-4 alkyl.
12. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
R 10 is H, C 1-4 alkyl, C 1-4 alkylene-OH, C 1-4 alkylene-(diOH), C 1-4 alkylene-O—C 1-6 alkyl, S(O) 2 C 1-4 alkyl, Z 4 —C 3-10 cycloalkyl, Z 4 —C 3-10 heterocycloalkyl, Z 4 —C 6-10 aryl, or Z 4 —C 5-10 heteroaryl, wherein the Z 4 —C 3-10 cycloalkyl, Z 4 —C 3-10 heterocycloalkyl, Z 4 —C 6-10 aryl, or Z 4 —C 5-10 heteroaryl is optionally substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from the group consisting of halo and C 1-6 alkyl; and
R 11 is H, C 1-4 alkyl, C 1-4 alkylene-OH, C 1-4 alkylene-(diOH), C 1-4 alkylene-O—C 1-6 alkyl, S(O) 2 C 1-4 alkyl, Z 4 —C 3-10 cycloalkyl, Z 4 —C 3-10 heterocycloalkyl, Z 4 —C 6-10 aryl, or Z 4 —C 5-10 heteroaryl, wherein the Z 4 —C 3-10 cycloalkyl, Z 4 —C 3-10 heterocycloalkyl, Z 4 —C 6-10 aryl, or Z 4 —C 5-10 heteroaryl is optionally substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from the group consisting of halo and C 1-6 alkyl.
13. The compound of claim 1 , or a stereoisomer thereof, wherein the compound, or stereoisomer thereof, is selected from the group consisting of:
Compound
Structure
I-1
I-2
I-3
I-4
I-5
I-6
I-7
I-8
I-9
I-10
I-11
I-12
I-13
I-14
I-15
I-16
I-17
I-18
I-19
I-20
I-21
I-22
I-23
I-24
I-25
I-26
I-27
I-28
I-29
I-30
I-31
I-32
I-33
I-34
I-35
I-36
I-37
I-38
I-39
I-40
I-41
I-42
I-43
I-44
I-45
I-46
I-47
I-48
I-49
I-50
I-51
I-52
I-53
I-54
I-55
I-56
I-57
I-58
I-59
I-60
I-61
I-62
I-63
I-64
I-65
I-66
I-67
I-68
I-69
I-70
I-71
I-72
I-73
I-74
I-75
I-76
I-77
I-78
I-79
I-80
I-81
I-82
I-83
I-84
I-85
I-86
I-87
I-88
I-89
I-90
I-91
I-92
I-93
I-94
I-95
I-96
I-97
I-98
I-99
I-100
I-101
I-102
I-103
I-104
I-105
I-106
I-107
I-108
I-109
I-110
I-111
I-112
I-113
I-114
I-115
I-116
I-117
I-118
I-119
I-120
I-121
I-122
I-123
I-124
I-125
I-126
I-127
I-128
I-129
I-130
I-131
I-132
I-133
I-134
I-135
I-136
I-137
I-138
I-139
I-140
I-141
I-142
I-143
I-144
I-145
I-146
I-147
I-148
I-149
I-150
I-151
I-152
I-153
I-154
I-155
I-156
I-157
I-158
I-159
I-160
I-161
I-162
I-163
I-164
I-165
I-166
I-167
I-168
I-169
I-170
I-171
I-172
I-173
I-174
I-175
I-176
I-177
I-178
I-179
I-180
I-181
I-182
I-183
I-184
I-185
I-186
I-187
I-188
I-189
I-190
I-191
I-192
I-193
I-194
I-195
I-196
I-197
I-198
I-199
I-200
I-201
I-202
I-203
I-204
I-205
I-206
I-207
I-208
I-209
I-210
I-211
I-212
I-213
I-214
I-215
I-216
I-217
I-218
I-219
I-220
I-221
I-222
I-223
I-224
I-225
I-226
I-227
I-228
I-229
I-230
I-231
I-232
I-233
I-234
I-235
I-236
I-237
I-238
I-239
I-240
I-241
I-242
I-243
I-244
I-245
I-246
I-247
I-248
I-249
I-250
I-251
I-252
I-253
I-254
I-255
I-256
Enantiomer 1
I-257
I-258
Enantiomer
I-259
I-260
I-261
I-262
I-263
I-264
I-265
I-266
I-267
I-268
I-269
I-270
I-271
I-272
I-273
I-274
I-275
I-276
I-277
I-278
I-279
I-280
I-281
I-282
I-283
I-284
I-285
I-286
I-287
I-288
I-289
I-290
I-291
I-292
I-293
I-294
I-295
I-296
I-297
I-298
I-299
I-300
I-301
I-302
I-303
I-304
I-305
I-306
I-307
I-308
I-309
I-310
I-311
I-312
I-313
I-314
I-315
I-316
I-317
I-318
I-319
I-320
I-321
I-322
I-323
I-324
I-325
I-326
I-327
I-328
I-329
I-330
I-331
I-332
I-333
I-334
I-335
I-336
I-337
I-338
I-339
I-340
I-341
I-342
I-343
I-344
I-345
I-346
I-347
I-348
I-349
I-350
I-351
I-352
I-353
I-354
I-355
I-356
I-357
I-358
I-359
I-360
I-361
I-362
I-363
I-364
I-365
I-366
I-367
I-368
I-369
I-370
I-371
I-372
I-373
I-374
I-375
I-376
I-377
I-378
I-379
I-380
I-381
I-382
I-383
I-384
I-385
I-386
I-387
I-388
I-389
I-390
I-391
I-392
I-393
I-394
I-395
I-396
I-397
I-398
I-399
I-400
I-401
I-402
I-403
I-404
I-405
I-406
I-407
I-408
I-409
I-410
I-411
I-412
I-413
I-414
I-415
I-416
I-417
I-418
I-419
I-420
I-421
I-422
I-423
I-424
I-425
I-426
I-427
I-428
I-429
I-430
I-431
I-432
I-433
I-434
I-435
I-436
I-437
I-438
I-439
I-440
I-441
I-442
I-443
I-444
I-445
I-446
I-447
I-448
I-449
I-450
I-451
I-452
I-453
I-454
I-455
I-456
I-457
I-458
I-459
I-460
I-461
I-462
I-463
I-464
I-465
I-466
I-467
I-468
I-469
I-470
I-471
I-472
I-473
I-474
I-475
I-476
I-477
I-478
I-479
I-480
I-481
I-482
I-483
I-484
I-485
I-486
I-487
I-488
or a pharmaceutically acceptable salt thereof.
14. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof.
15. A method for treating lymphoma in a subject, wherein the method comprises administering to the subject in need thereof a therapeutically effective amount of at least one compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof.
16. The method of claim 15 , wherein the lymphoma is selected from the group consisting of a B-cell lymphoma, a follicular lymphoma, and a non-Hodgkins lymphoma.
17. The method of claim 16 , wherein the B-cell lymphoma is diffuse large B-cell lymphoma (DLBCL).
18. The method of claim 15 , wherein the method further comprises administering to the subject in need thereof a therapeutically effective amount of at least one compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, in combination with at least one additional lymphoma treatment.