Granted Patent B2

US 12,558,356 · App. 18/957,502 · Granted Feb 24, 2026

Inventors: Kevan M. Shokat (San Francisco, CA); Ziyang Zhang (San Francisco, CA); William A. Weiss (San Francisco, CA); QiWen Fan (San Francisco, CA)

Assignee: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

A61K31/506A61K31/444A61K31/496A61K31/517

Abstract

Claims (39)

1 . A compound having the formula:

A B -L B1 -R B1 , or a pharmaceutically acceptable salt thereof;

wherein

A B is an immunophilin-binding moiety having the formula

 or a stereoisomeric form thereof;

L B1 -R B1 is L B4 -L B3 -L B2 -R B1 ;

L B2 is —S(O) 2 —;

L B3 is a bond;

L B4 is unsubstituted, fully saturated or mono-unsaturated, C 3 -C 6 alkylene;

R B1 is —NR B1A R B1B ; and

R B1A and R B1B are independently hydrogen, halogen, —CCl 3 , —CBr 3 , —CF 3 , —CI 3 , —CH 2 Cl, —CH 2 Br, —CH 2 F, —CH 2 I, —CHCl 2 , —CHBr 2 , —CHF 2 , —CHI 2 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCCl 3 , —OCBr 3 , —OCF 3 , —OCI 3 , —OCH 2 Cl, —OCH 2 Br, —OCH 2 F, —OCH 2 I, —OCHCl 2 , —OCHBr 2 , —OCHF 2 , —OCHI 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or R B1A and R B1B substituents bonded to the same nitrogen atom are joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl.

2 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each of R B1A and R B1B is independently hydrogen or substituted or unsubstituted, C 1 -C 4 alkyl.

3 . A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

4 . A compound having the formula:

A B -L B1 -R B1 , or a pharmaceutically acceptable salt thereof;

wherein

A B is an immunophilin-binding moiety having the formula

 or a stereoisomeric form thereof;

L B1 is

Z is —S— or —SO 2 —;

R B1 is —NR B1A R B1B or —NHC(O)CH 2 R B1C ; and

each of R B1A , R B1B , and R B1C is independently substituted or unsubstituted pyridyl.

5 . A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 4 , or a pharmaceutically acceptable salt thereof.

6 . A compound of the formula:

A B -L B1 -R B1 , or a pharmaceutically acceptable salt thereof,

wherein

A B is an immunophilin-binding moiety having the formula

 or a stereoisomeric form thereof;

L B1 -R B1 is L B4 -L B3 -L B2 -R B1 ;

L B2 is —N(R B2 )—;

L B3 is a bond;

L B4 is unsubstituted, fully saturated or mono-unsaturated, C 3 -C 6 alkylene;

R B2 is hydrogen, halogen, —CCl 3 , —CBr 3 , —CF 3 , —CI 3 , —CH 2 Cl, —CH 2 Br, —CH 2 F, —CH 2 I, —CHCl 2 , —CHBr 2 , —CHF 2 , —CHI 2 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHC(NH)H, —NHC(NH)NH 2 , —NHOH, —OCCl 3 , —OCBr 3 , —OCF 3 , —OCI 3 , —OCH 2 Cl, —OCH 2 Br, —OCH 2 F, —OCH 2 I, —OCHCl 2 , —OCHBr 2 , —OCHF 2 , —OCHI 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R B1 is —SO nB1 R B1D ;

R B1D is hydrogen, halogen, —CCl 3 , —CBr 3 , —CF 3 , —CI 3 , —CH 2 Cl, —CH 2 Br, —CH 2 F, —CH 2 I, —CHCl 2 , —CHBr 2 , —CHF 2 , —CHI 2 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCCl 3 , —OCBr 3 , —OCF 3 , —OCI 3 , —OCH 2 Cl, —OCH 2 Br, —OCH 2 F, —OCH 2 I, —OCHCl 2 , —OCHBr 2 , —OCHF 2 , —OCHI 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and

nB1 is an integer from 0 to 4.

7 . A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 6 , or a pharmaceutically acceptable salt thereof.

8 . A compound, or a pharmaceutically acceptable salt thereof, wherein the compound is of the formula:

9 . A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 8 , or a pharmaceutically acceptable salt thereof.

Assignments (1)

Continuity (3)

References Cited (196)