Triazacyclododecansulfonamide (“TCD”)-based protein secretion inhibitors
AssigneeKezar Life Sciences
InventorHenry Johnson
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Abstract
Provided herein are triazacyclododecansulfonamide (“TCD”)-based protein secretion inhibitors, such as inhibitors of Sec61, methods for their preparation, related pharmaceutical compositions, and methods for using the same. For example, provided herein are compounds of Formula (I) and pharmaceutically acceptable salts and compositions including the same. The compounds disclosed herein may be used, for example, in the treatment of diseases including inflammation and/or cancer.
Claims32
A compound of Formula (I), or a pharmaceutically acceptable salt thereof:
- wherein:
- each of Ra and Rb is independently H or C1-3alkyl;
- R1 is H, OH, C1-3alkyl, OC1-3alkyl, ═CH2, or ═NOR5;
- or R1 is C3-6cycloalkyl or C3-6 heterocycloalkyl and forms a spiro group with the ring carbon to which it is attached;
- each of R1a and R1b is independently H or C1-3 alkyl;
- R2 is C3-9heterocycloalkyl or C3-9heterocycloalkenyl;
- R3 is H, C1-6alkyl, C3-8cycloalkyl, C3-8cycloalkenyl, C3-7heterocycloalkyl, or C2-6heteroaryl;
- R4 is C3-8cycloalkyl, C3-9heterocycloalkyl, C6-10aryl, or C2-6heteroaryl;
- each R5 independently is H, C1-3alkyl, or C0-2alkylene-C6-10aryl;
- X is absent, C1-3alkylene, C═O, or (C═O)O;
- each Y is independently SO or SO2;
- and
- each heterocycloalkyl, heterocycloalkenyl, and heteroaryl group independently has 1, 2, or 3 ring heteroatoms selected from N, O, and S.
A compound listed in Table A, or a pharmaceutically acceptable salt thereof.
- TABLE A
- No.
- Structure
- A5
- A13
- A17
- A19
- A20
- A21
- A22
- A23
- A24
- A25
- A26
- A27
- A28
- A29
- A30
- A31
- A32
- A33
- A34
- A35
- A36
- A37
- A38
- A39
- A40
- A41
- A42
- A43
- A44
- A46
- A47
- A48
- A49
- A50
- A51
- A52
- A53
- A54
- A55
- A56
- A57
- A58
- A59
- A60
- A61
- A63
- A64
- A65
- A66
- A67
- A68
- A69
- A70
- A71
- A72
- A73
- A74
- A75
- A76
- A77
- A78
- A79
- A80
- A81
- A82
- A83
- A84
- A85
- A86
- A87
- A88
- A89
- A90
- A91
- A92
- A93
- A94
- A95
- A96
- A97
- A98
- A99
- A100
- A101
- A102
- A104
- A105
- A106
- A107
- A108
- A109
- A110
- A111
- A112
- A113
- A114
- A115
- A116
- A117
- A118
- A119
- A120
- A121
- A122
- A123
- A124
- A125
- A126
- A127
- A128
- A129
- A130
- A134
- A135
- A136
- A137
- A138
- A140
- A141
- A142
- A143
- A144
- A145
- A146
- A147
- A148
- A149
- A150
- A151
- A152
- A153
- A154
- A155
- A157
- A160
- A161
- A162
- A163
- A164
- A165
- A166
- A167
- A168
- A169
- A170
- A171
- A172
- A173
- A174
- A175
- A176
- A177
- A178
- A179
- A180
- A181
- A182
- A183
- A185
- A188
- A190
- A191
- A193
- A194
- A195
- A196
- A197
- A198
- A199
- A200
- A201
- A202
- A203
- A204
- A206
- A207
- A208
- A209
- A210
Dependencies are inferred from the claim text.