Rapafucin derivative compounds and methods of use thereof

Patent metadata

Field	Value
Publication number	US-11945827-B2
Application number	US-202117332331-A
Country	US
Kind code	B2
Filing date	May 27, 2021
Priority date	Feb 4, 2016
Publication date	Apr 2, 2024
Grant date	Apr 2, 2024

Abstract

The present disclosure provides macrocyclic compounds inspired by the immunophilin ligand family of natural products FK506 and rapamycin. The generation of a Rapafucin library of macrocyles that contain FK506 and rapamycin binding domains should have great potential as new leads for developing drugs to be used for treating diseases.

First claim

What is claimed is:

1. A compound of Formula (V)

or an optically pure stereoisomer or pharmaceutically acceptable salt thereof,
wherein L is optionally substituted (CH 2 ) n NR 20 C 1-6 alkylene;
A is NH, NMe, O, S(O) 2 or S;
each X is O;
E is CH or N;
R 1 is H;
R 2 is C 1-20 alkoxy;
R 3 is C 1-20 alkyl;
R 4 is independently selected from the group consisting of H;
or R 4 forms a cyclic structure formed with R 3 , the cyclic structure is C 2-10 heterocyclyl R 20 is H;
n is 0;
m is an integer selected from 2;
p is 2; and
q is 4.

2. The compound of claim 1 , wherein R 2 is methoxy.

3. The compound of claim 1 , wherein E is CH.

4. A pharmaceutical composition comprising the compound of claim 1 or an optically pure stereoisomer or pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.

Assignees

• Univ Johns Hopkins
• Rapafusyn Pharmaceuticals Inc

Inventors

• Liu Jun
• Hong Sam
• Ullman Brett R
• Semple Joseph E
• Yamamoto Kana
• Kumar Puneet
• Sadagopan Magesh
• Schmitt Jennifer C

Classifications

• C07D498/14 Primary

  Ortho-condensed systems · CPC title

• C07D498/04 Primary

  Ortho-condensed systems · CPC title

• C07F9/3258

  the ester moiety containing a substituent or a structure which is considered as characteristic · CPC title

• C07F9/6561

  containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings · CPC title