5-AMINO-6,8-DIHYDRO-1H-FURO[3,4-d]PYRROLO[3,2-b]PYRIDINE-2-CARBOXAMIDE DERIVATIVES AS MTA-COOPERATIVE INHIBITORS OF PRMT5
This disclosure provides 5-amino-6,8-dihydro-1H-furo[3,4-d]pyrrolo[3,2-b]pyridine-2-carboxamide derivatives, the use thereof for selectively inhibiting the activity of PRMT5 in cooperation with MTA in tumors bearing MTAP DEL mutation, and pharmaceutical compositions comprising the compounds, e.g., for treatment of various diseases including cancer.
1 - 70 . (canceled)
71 . A pharmaceutical composition comprising a compound of claim 78 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
72 . A method of inhibiting PRMT5 activity or treating a disease modulated by PRMT5, comprising administering to a subject in need thereof an effective amount of a compound of claim 78 , or a pharmaceutically acceptable salt thereof.
73 . (canceled)
74 . A method of treating cancer, comprising administering to a subject in need thereof an effective amount of a compound of claim 78 , or a pharmaceutically acceptable salt thereof.
75 - 77 . (canceled)
78 . A compound or pharmaceutically acceptable salt thereof selected from:
79 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
80 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
81 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
82 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
83 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
84 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
85 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
86 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
87 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
88 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
89 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
90 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
91 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
92 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
93 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
94 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
95 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
96 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
97 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
98 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
99 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
100 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
101 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
102 . The compound of claim 78 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.