US2023142883A1PendingUtilityA1
Compounds and uses thereof
Est. expiryJan 29, 2039(~12.5 yrs left)· nominal 20-yr term from priority
C07D 498/10C07D 401/14A61K 31/4545C07D 471/04A61K 47/545A61P 35/00C07D 519/00A61K 31/5386A61K 31/496A61K 47/55C07D 471/10C07D 487/04C07D 487/10
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Claims
Abstract
The present invention relates to compositions and methods for the treatment of BAF-related disorders, such as cancers and viral infections.
Claims
exact text as granted — not AI-modified1 . A compound having the structure of Formula I:
A-L-B Formula I,
wherein A is:
wherein
A 1 is a bond between A and L;
R 4 is H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 9 alkenyl, optionally substituted C 1 -C 6 heteroalkyl, or optionally substituted C 3 -C 10 carbocyclyl;
R 5 is H, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 10 carbocyclyl, or optionally substituted C 6 -C 10 aryl;
R 6a is H, halogen, cyano, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 10 carbocyclyl, optionally substituted C 2 -C 9 heterocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 2 -C 9 heteroaryl, optionally substituted C 2 -C 9 alkenyl, optionally substituted C 2 -C 9 heteroalkenyl, hydroxy, thiol, or optionally substituted amino;
R 6b is H, halogen, cyano, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 10 carbocyclyl, optionally substituted C 2 -C 9 heterocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 2 -C 9 heteroaryl, optionally substituted C 2 -C 9 alkenyl, optionally substituted C 2 -C 9 heteroalkenyl, hydroxy, thiol, or optionally substituted amino;
or R 6a and R 6b , together with the carbon atoms to which each is attached, combine to form optionally substituted C 6 -C 10 aryl or optionally substituted C 2 -C 9 heteroaryl;
s is 0, 1, 2, 3, or 4;
each R 9 is, independently, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 10 carbocyclyl, optionally substituted C 2 -C 9 heterocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 2 -C 9 heteroaryl, optionally substituted C 2 -C 9 alkenyl, optionally substituted C 2 -C 9 heteroalkenyl, hydroxy, thiol, or optionally substituted amino;
B is:
wherein
A 2 is a bond between the degradation moiety and the linker,
v1 is 0, 1, 2, 3, 4, or 5;
u1 is 1, 2, or 3;
T 1 is a bond or
R 5A is H, optionally substituted C 1 -C 6 alkyl, or optionally substituted C 1 -C 6 heteroalkyl;
each R J1 is, independently, halogen, optionally substituted C 1 -C 6 alkyl, or optionally substituted C 1 -C 6 heteroalkyl;
J A is absent, O, optionally substituted amino, optionally substituted C 1 -C 6 alkyl, or optionally substituted C 1 -C 6 heteroalkyl; and
J is absent, optionally substituted C 3 -C 10 carbocyclylene, optionally substituted C 6 -C 10 arylene, optionally substituted C 2 -C 9 heterocyclylene, or optionally substituted C 2 -C 9 heteroarylene;
L is:
A 1 -(E 1 )-(F 1 )-(C 3 ) m -(E 3 ) n -(F 2 ) o1 -(F 3 ) o2 -(E 2 ) p -A 2 , Formula II
wherein
A 1 is a bond between the linker and A;
A 2 is a bond between B and the linker,
each of m, n, o1, o2, and p is, independently, 0 or 1;
each of E 1 and E 2 is, independently, O, S, NR N , optionally substituted C 1-19 alkylene, optionally substituted C 2-10 alkenylene, optionally substituted C 2-10 alkynylene, optionally substituted C 2 -C 10 polyethylene glycol, or optionally substituted C 1-10 heteroalkylene;
E 3 is optionally substituted C 1 -C 6 alkylene, optionally substituted C 1 -C 6 heteroalkylene, O, S, or NR N ;
each R N is, independently, H, optionally substituted C 1-4 alkyl, optionally substituted C 2-4 alkenyl, optionally substituted C 2-4 alkynyl, optionally substituted C 2-6 heterocyclyl, optionally substituted C 6-12 aryl, or optionally substituted C 1-7 heteroalkyl;
C 3 is carbonyl, thiocarbonyl, sulphonyl, or phosphoryl; and
each of F 1 , F 2 , and F 3 is, independently, optionally substituted C 3 -C 10 carbocyclylene, optionally substituted C 2-10 heterocyclylene, optionally substituted C 6 -C 10 arylene, or optionally substituted C 2 -C 9 heteroarylene,
or a pharmaceutically acceptable salt thereof.
2 . The compound of claim 1 , wherein R 4 is an optionally substituted C 1 -C 6 alkyl and R 3 is H.
3 . The compound of claim 1 , wherein R 8a and Rob are H or an optionally substituted Cr Ce alkyl.
4 . The compound of claim 1 , wherein R 8a and Rob, together with the carbon atoms to which each is attached, combine to form optionally substituted C 6 -C 10 aryl or optionally substituted C 2 -C 9 heteroaryl.
5 . The compound of claim 1 , wherein the structure of Formula IIIb has the structure of Formula IVc:
wherein
each of R 10a , R 10c , and R 10d is, independently, H, halogen, hydroxy, optionally substituted C 1 -C 6 alkyl,
optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 10 carbocyclyl, optionally substituted C 2 -C 9 heterocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 2 -C 9 heteroaryl, optionally substituted C 2 -C 9 alkenyl, optionally substituted C 2 -C 9 heteroalkenyl, hydroxy, thiol, or optionally substituted amino.
6 . The compound of claim 5 , wherein R 4 is an optionally substituted C 1 -C 6 alkyl and R 5 is H.
7 . The compound of claim 5 , wherein s is 2.
8 . The compound of claim 5 , wherein each R 9 is, independently, halogen,
9 . The compound of claim 5 , wherein the structure of Formula Pic has the structure of Formula IVd:
or a pharmaceutically acceptable salt thereof.
10 . The compound of claim 9 , wherein R 4 is an optionally substituted C 1 -C 6 alkyl and R 5 is H.
11 . The compound of claim 1 , wherein the structure of Formula Y1 has the structure of Formula AA0:
or a pharmaceutically acceptable salt thereof.
12 . The compound of claim 11 , wherein the structure of Formula AA0 has the structure of:
or a pharmaceutically acceptable salt thereof.
13 . The compound of claim 11 , wherein J A is optionally substituted amino.
14 . The compound of claim 11 , wherein the structure of Formula AA0 has the structure of:
15 . The compound of claim 1 , wherein the structure of Formula Y1 has the structure of Formula A10:
or a pharmaceutically acceptable salt thereof.
16 . The compound of claim 15 , wherein the structure of Formula A10 is:
17 . The compound of claim 1 , wherein E 1 is optionally substituted C 1-10 alkylene.
18 . The compound of claim 17 , wherein E 1 is
19 . The compound of claim 1 , wherein each of F 1 or P is, independently, optionally substituted C 5 -C 8 heterocyclylene.
20 . The compound of claim 19 , wherein the C 2 -C 6 heterocyclylene is monocyclic.
21 . The compound of claim 19 , wherein the C 2 -C 6 heterocyclylene is
q1 is 0, 1, 2, 3, or 4;
q2 is 0, 1, 2, 3, 4, 5, or 6;
q3 is 0, 1, 2, 3, 4, 5, 6, 7, or 8;
each R h is, independently, 2 H, halogen, optionally substituted C 1 -C 6 alkyl, OR i2 , or NR i3 R i4 ; or two R h groups, together with the carbon atom to which each is attached, combine to form optionally substituted C 3 -C 10 carbocyclyl or optionally substituted C 2 -C 9 heterocyclyl; or two R h groups, together with the carbon atoms to which each is attached, combine to form optionally substituted C 3 -C 10 carbocyclyl or optionally substituted C 2 -C 9 heterocyclyl;
R i1 is H or optionally substituted C 1 -C 6 alkyl;
R i2 is H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, or optionally substituted C 3 -C 9 carbocyclyl.
22 . The compound of claim 19 , wherein the C 2 -C 9 heterocyclylene is
23 . The compound of claim 19 , wherein the C 5 -C 8 heterocyclylene is polycyclic.
24 . The compound of claim 19 , wherein the C 2 -C 6 heterocyclylene is bicyclic.
25 . The compound of claim 19 , wherein the C 2 -C 6 heterocyclylene is bridged.
26 . The compound of claim 25 , wherein the C 2 -C 6 heterocyclylene is
27 . The compound of claim 19 , wherein the C 2 -C 6 heterocyclylene is fused.
28 . The compound of claim 27 , wherein the C 2 -C heterocyclylene is
29 . The compound of 19 , wherein the C 2 -C 6 heterocyclylene is spirocyclic.
30 . The compound of claim 29 , wherein the C 2 -C 6 heterocyclylene is
31 . The compound of claim 1 , wherein F 3 is optionally substituted C 6 -C 10 arylene.
32 . The compound of claim 1 , wherein F 3 is optionally substituted C 2 -C 9 heteroarylene.
33 . The compound of claim 1 , wherein:
F 1 is
F 2 is
and
F 3 is optionally substituted C 6 -C 10 arylene.Cited by (0)
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