US2022048922A1PendingUtilityA1
Compounds targeting prmt5
Est. expiryApr 2, 2039(~12.7 yrs left)· nominal 20-yr term from priority
Inventors:Koen VandyckPierre Jean-Marie Bernard RaboissonJerome DevalLeonid BeigelmanDavid Craig McgowanYannick Debing
C07D 495/04C07D 513/04C07D 471/04C07D 473/26A61P 35/00A61K 31/53A61K 31/52C07D 519/00A61K 45/06C07D 487/04A61K 31/437A61K 31/519A61K 31/522C07D 473/30C07K 16/22C07D 498/04C07D 473/34
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Claims
Abstract
Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions that include a compound described herein (including pharmaceutically acceptable salts of a compound described herein) and methods of synthesizing the same. Also provided herein are methods of treating diseases and/or conditions with a compound of Formula (I), or a pharmaceutically acceptable salt thereof.
Claims
exact text as granted — not AI-modified1 . A compound of Formula (I), or a pharmaceutically acceptable salt thereof, having the structure:
wherein:
B 1 is an optionally substituted
,
wherein X 1 is CR C1 ; X 2 is CR C2 ; X 3 is CR C3 ; and R C1 , R C2 , R C3 , R C4 and R C5 are independently hydrogen or halogen or an unsubstituted C 1-4 alkyl;
R 1B is hydrogen, halogen, hydroxy, an unsubstituted C 1-4 alkyl, an unsubstituted C 2-4 alkenyl, an unsubstituted C 3 -C 6 cycloalkyl, an unsubstituted C 1-4 alkoxy or NR A1 R A2 ; and
R A1 and R A2 are each hydrogen;
R 1 is hydrogen;
R 2A is hydrogen;
R 2B is OH or —O—C(═O)—C 1-4 alkyl;
R 3A is hydrogen;
R 3B is OH or —O—C(═O)—C 1-4 alkyl;
R 4A is —(CR D1 R E1 )(CR D2 R E2 )n-R F1 ;
wherein R D1 , R E1 , R D2 and R E2 are independently selected from the group consisting of hydrogen, halogen, hydroxy and an unsubstituted C 1-3 alkyl; n is 1; and R F1 is an unsubstituted or a substituted aryl, an unsubstituted or a substituted heteroaryl or an unsubstituted or a substituted heterocyclyl;
R 4B is an unsubstituted C 1-4 alkyl,
Z 1 is CR 5A R 5B;
R 5A and R 5B are each hydrogen.
2 .- 18 . (canceled)
19 . The compound of claim 1 , wherein R 2B is OH.
20 . The compound of claim 1 , wherein R 2B is —O—C(═O)—C 1-4 alkyl.
21 .- 31 . (canceled)
32 . The compound of claim 1 , wherein R 3B is OH.
33 . The compound of claim 1 , wherein R 3B is —O—C(═O)—C 1-4 alkyl.
34 .- 45 . (canceled)
46 . The compound of claim 1 , wherein R D1 , R E1 , R D2 and R E2 are each hydrogen.
47 .- 56 . (canceled)
57 . The compound of claim 1 , wherein R F1 is an unsubstituted or a substituted heteroaryl.
58 . (canceled)
59 . The compound of claim 57 , wherein R F1 is pyridinyl.
60 . (canceled)
61 . The compound of claim 59 , wherein R F1 is substituted with one, two or three substituents independently selected from the group consisting of halogen, cyano, an unsubstituted C 1-4 alkyl, an unsubstituted C 1-4 haloalkyl, an unsubstituted monocyclic C 3-6 cycloalkyl, an optionally substituted C-carboxy, an optionally substituted N-amido, amino, a mono-substituted amine, a di-substituted amine, —NH—C(═O)-unsubstituted C 1-8 alkyl, —NH—C(═O)—O-unsubstituted C 1-8 alkyl, —NH—C(═O)-unsubstituted C 3-6 cycloalkyl and —NH—C(═O)—O-unsubstituted C 3-6 cycloalkyl.
62 . The compound of claim 1 , wherein R F1 is selected from the group consisting of:
63 .- 105 . (canceled)
106 . The compound of claim 1 , wherein R 4B is CH 3 .
107 .- 134 . (canceled)
135 . The compound of claim 1 , wherein R 1B is NR A1 R A2 , wherein R A1 and R A2 are each hydrogen.
136 .- 142 . (canceled)
143 . The compound of claim 1 , wherein B 1 is
144 .- 147 . (canceled)
148 . The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
149 .- 154 . (canceled)
155 . The compound of claim 148 , wherein B 1 is
156 . (canceled)
157 . (canceled)
158 . The compound of claim 148 , wherein R F1 is pyridinyl.
159 . (canceled)
160 . The compound of claim 158 , wherein R F1 is substituted with one, two or three substituents independently selected from the group consisting of halogen, cyano, an unsubstituted C 1-4 alkyl, an unsubstituted C 1-4 haloalkyl, an unsubstituted monocyclic C 3-6 cycloalkyl, an optionally substituted C-carboxy, an optionally substituted N-amido, amino, a mono-substituted amine, a di-substituted amine, —NH—C(═O)-unsubstituted C 1-8 alkyl, —NH—C(═O)—O-unsubstituted C 1-8 alkyl, —NH—C(═O)-unsubstituted C 3-6 cycloalkyl and —NH—C(═O)—O-unsubstituted C 3-6 cycloalkyl.
161 . The compound of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt of any of the foregoing.
162 . A pharmaceutical composition comprising an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and excipient.
163 - 174 . (canceled)
175 . A method for treating a cancer comprising administering an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, to a subject in need thereof.
176 . (canceled)
177 . A method for modulating PRMT5 comprising contacting the PRMT5 enzyme with an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.
178 . A method for inhibiting PRMT5 comprising contacting the PRMT5 enzyme Use of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.
179 . The method of claim 175 , further comprises the use of an additional agent selected from the group consisting of a kinase inhibitor, a checkpoint inhibitor/modulator and an anti-VEGF antibody.
180 . (canceled)Join the waitlist — get patent alerts
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