Heterocyclic compound

Patent metadata

Field	Value
Publication number	US-2020163970-A1
Application number	US-201816482994-A
Country	US
Kind code	A1
Filing date	Feb 2, 2018
Priority date	Feb 3, 2017
Publication date	May 28, 2020
Grant date	—

Abstract

Provided is a novel compound or salt thereof that induces degradation by autophagy of an intracellular molecule. In this compound, a ligand having activity to bind to an intracellular molecule and a structure having activity to induce autophagy of an intracellular molecule are linked via a linker without loss of the activity of the ligand and the structure.

First claim

1 . A compound binding to an intracellular molecule and inducing autophagic degradation of the intracellular molecule, or a salt thereof, with the proviso the compound is not:

2 . The compound according to claim 1 represented by the following formula (I):

wherein
R 1 represents a ligand specifically binding to an intracellular molecule,
L a represents a bond or a chain linker having 1 to 10 atoms in a backbone,
L b represents
i) a bond,
ii) a chain linker having 1 to 13 atoms in a backbone, or
iii) formula (II):
-L 1 -X 1 -L 2 -  (II)

wherein L 1 represents a bond or a chain linker having 1 to 10 atoms in a backbone,
X 1 represents an optionally substituted divalent cyclic group, and
L 2 represents a bond or a chain linker having 1 or 2 atoms in a backbone, and R 2 represents a group selected from the following formulas:

wherein
R A1 , R A2 , R A3 , R A4 , R A5 , R A6 , R A7 , R A8 , R A9 and R A10 each independently represent a hydrogen atom or a substituent, or
R A1 and R A2 are optionally bonded to each other to form an optionally substituted ring, and
R B1 , R B2 , R B3 , R B4 and R B5 each independently represent an optionally substituted hydrocarbon ring group, an optionally substituted unsaturated heterocyclic group, X 2 —R 3 ,
wherein X 2 represents an optionally substituted methylene group, and R 3 represents an optionally substituted cyclic group, or a salt thereof.

3 . The compound according to claim 2 or a salt thereof, wherein R 2 represents the following formula:

wherein
R A1 and R A2 each independently represent a hydrogen atom or a substituent, or
R A1 and R A2 are optionally bonded to each other to form an optionally substituted ring, and
R B1 represents an optionally substituted hydrocarbon ring group, an optionally substituted unsaturated heterocyclic group, or X 2 —R 3 wherein
X 2 represents an optionally substituted methylene group, and R 3 represents an optionally substituted cyclic group.

4 . A medicament comprising a compound or a salt thereof according to claim 1 .

5 . The medicament according to claim 4 , wherein the medicament is a drug inducing degradation of an intracellular molecule.

6 . The medicament according to claim 4 , wherein the medicament is a prophylactic or therapeutic drug for a cancer.

Assignees

• Univ Tohoku

Inventors

• Arimoto Hirokazu
• ITTO Kaori
• Takahashi Daiki
• Cho Nobuo
• Nara Hiroshi
• Shimokawa Kenichiro
• Ohra Taiichi
• Sasaki Shigekazu
• Ishii Naoki

Classifications

• C07D495/14

  Ortho-condensed systems · CPC title

• A61K31/52

  Purines, e.g. adenine · CPC title

• C07D473/06

  with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 · CPC title

• A61K31/5517

  condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam · CPC title

• A61K31/513

  having oxo groups directly attached to the heterocyclic ring, e.g. cytosine · CPC title