Organic compounds

Patent metadata

Field	Value
Publication number	US-11427587-B2
Application number	US-201816634059-A
Country	US
Kind code	B2
Filing date	Jul 20, 2018
Priority date	Jul 26, 2017
Publication date	Aug 30, 2022
Grant date	Aug 30, 2022

Abstract

The invention relates to particular prodrugs of substituted heterocycle fused gamma-carbolines, in free, solid, pharmaceutically acceptable salt and/or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving the 5-HT2A receptor, the serotonin transporter (SERT), pathways involving the dopamine D1 and D2 receptor signaling system, and/or the μ-opioid receptor.

First claim

What is claimed:

1. A compound of a Formula I:

wherein:
R is —C(O)—O—C(R a )(R b )(R c ), —C(O)—O—CH 2 —O—C(R a )(R b )(R c ) or —C(R 6 )(R 7 )—O—C(O)—R 8 ;
Z is O, or —C(O)—;
R 8 is —C(R a )(R b )(R c ), —O—C(R a )(R b )(R c ), or —N(R d )(R e );
R a , R b and R c are each independently selected from H and C 1-24 alkyl;
R d and R e are each independently selected from H and C 1-24 alkyl;
R 6 and R 7 are each independently selected from H, C 1-6 alkyl, carboxy and C 1-6 alkoxycarbonyl;
in free or salt form;

or
a compound of a Formula II:

wherein:
Z is O, or —C(O)—:
R 1 , R 2 , R 3 and R 4 are each independently selected from H and C 1-6 alkyl;
n is an integer from 1 to 23;
in free or salt form.

2. A compound of Formula I according to claim 1 , wherein Z is O.

3. A compound of Formula I according to claim 1 , wherein Z is —C(O).

4. A compound of Formula I according to claim 1 , wherein R 5 is —C(O)—O—C(R a )(R b )(R c ).

5. A compound of Formula I according to claim 1 , wherein R 5 is —C(O)—O—CH 2 —O—C(R a )(R b )(R c ).

6. A compound of Formula I according to claim 1 , wherein R 5 is —C(R 6 )(R 7 )—O—C(O)—R 8 , and R 8 is —C(R a )(R b )(R c ).

7. A compound of Formula I according to claim 1 , wherein R 5 is —C(R 6 )(R 7 )—O—C(O)—R 8 , and R 8 is —O—C(R a )(R b )(R c ).

8. A compound of Formula I according to claim 1 , wherein R 5 is —C(R 6 )(R 7 )—O—C(O)—R 8 , and R 8 is —N(R d )(R e ).

9. A compound of a Formula II according to claim 1 :

wherein:
Z is O, or —C(O)—;
R 1 , R 2 , R 3 and R 4 are each independently selected from H and C 1-6 alkyl;
n is an integer from 1 to 23;
in free or salt form.

10. A compound according to claim 1 in the form of a salt.

11. A pharmaceutical composition comprising a compound according to claim 1 , in free or pharmaceutically acceptable salt form, in admixture with a pharmaceutically acceptable diluent or carrier.

12. The pharmaceutical composition of claim 11 , wherein the composition is formulated as a long acting injectable.

13. The pharmaceutical composition according to claim 12 , wherein the composition comprises the compound in free or pharmaceutically acceptable salt form or in crystal form, wherein said compound is formed into particles or crystals having a volume-based particle size of 0.5-100 microns; and optionally, wherein the particles have a surface area of 0.1 to 5 m 2 /g.

Assignees

• Intra Cellular Therapies Inc

Inventors

• Li Peng
• Zheng Hailin
• Davis Robert
• Mates Sharon
• Vanover Kimberly
• Snyder Gretchen

Classifications

• A61K31/485

  Morphinan derivatives, e.g. morphine, codeine · CPC title

• C07D471/18

  Bridged systems · CPC title

• A61P25/36

  Opioid-abuse · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title