Compounds, compositions, and methods for the treatment of disease
Disclosed are compounds and compositions for inhibiting the expression of a pattern recognition receptor (e.g., STING), and methods of use thereof.
1 . A compound of formula I:
or a pharmaceutically acceptable salt thereof;
wherein
M is Cl or F;
Z is SR 1 , SO 2 R 1 , or N(R 1 )(R 2 )
R 1 and R 2 are each independently H or alkyl;
R 3 is H, alkyl, methyl, haloalkyl, chloromethyl, alkyloxyalkyl, methoxymethyl, hydroxyalkyl, hydroxymethyl, aminoalkyl, diethylamino, aryl, phenyl, alkynyl, ethynyl, alkyne substituted with cycloalkyl, heterocyclylalkyl or morpholinylalkyl;
L 1 is C 7 -C 15 alkyl;
each R 4 is independently halo, CN, SR 7 , OR 7 , NHCOR 7 , NR 8 CO 2 R 7 , N(R 7 )(R 8 ), COR 7 , CO 2 R 7 , OC(O)R 7 , CON(R 7 )(R 8 ), heteroaryl, or heterocyclyl;
R 7 and R 8 are each independently selected from the group consisting of hydrogen, and alkyl; and
n is an integer from 0-18.
2 . The compound of claim 1 , wherein M is Cl.
3 . The compound of claim 1 , wherein Z is SO 2 R 1 .
4 . The compound of claim 1 , wherein R 1 is methyl, ethyl, isopropyl, or hexyl.
5 . The compound of claim 1 , wherein L 1 is C 7 alkylenyl, C 9 alkylenyl, C 10 alkylenyl, or C 15 alkylenyl.
6 . The compound of claim 1 , wherein each R 4 is independently CO 2 R 7 , COR 7 , heterocyclyl, OR 7 , heteroaryl, or CON(R 7 )(R 8 ).
7 . The compound of claim 1 , wherein each R 4 is independently CO 2 R 7 , heterocyclyl, or COR 7 .
8 . The compound of claim 1 , wherein n is 0, 1, or 2.
9 . A compound selected from the group consisting of:
Compound
Number
Structure
9
24
28
69
74
96
97
109
111
112
114
118
121
122
124
125
128
131
132
133
134
135
136
137
138
139
140
142
143
144
145
146
147
148
149
150
152
158
159
160
162
164
165
167
168
10 . A pharmaceutical composition, comprising a compound of claim 1 and a pharmaceutically acceptable excipient.
11 . A pharmaceutical composition, comprising a compound of claim 9 and a pharmaceutically acceptable excipient.