Anesthetic compounds and related methods of use

Patent metadata

Field	Value
Publication number	US-9522136-B2
Application number	US-201514808413-A
Country	US
Kind code	B2
Filing date	Jul 24, 2015
Priority date	Jan 13, 2012
Publication date	Dec 20, 2016
Grant date	Dec 20, 2016

Abstract

Provided herein are compounds according to formula (I): provided herein is also a pharmaceutical composition comprising a compound according to formula (I) and a pharmaceutically acceptable carrier, and a method for providing anesthesia in a subject by administering such a pharmaceutical composition.

First claim

The invention claimed is:

1. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound according to formula (I)

wherein,
R 1 is L 1 C(O)OL 2 -[C(R 7 R 8 )] p —C(R 9 R 10 )—C(O)OT;
R 2 is R 1 , optionally substituted linear or branched C 1 -C 10 alkyl, optionally substituted linear or branched C 2 -C 10 alkenyl, or optionally substituted linear or branched C 2 -C 10 alkynyl, wherein the backbone of C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 2 -C 10 alkynyl optionally comprises one or more heteroatoms;
each R 3 is independently halogen, CN, CF 3 , SR 2 , SOR 2 , SO 2 R 2 , OR 2 , CO 2 H, CO 2 R 2 , N(R 2 ) 2 , NHR 2 , NO 2 , or R 2 ;
Z is N or CR 6 ;
R 4 , R 5 , and R 6 are independently hydrogen, halogen, CN, CF 3 , SR 2 , SOR 2 , SO 2 R 2 , OR 2 , CO 2 H, CO 2 R 2 , N(R 2 ) 2 , NHR 2 , NO 2 , or R 2 ;
R 7 and R 8 are independently hydrogen, optionally substituted linear or branched C 1 -C 10 alkyl, optionally substituted linear or branched C 2 -C 10 alkenyl, optionally substituted linear or branched C 2 -C 10 alkynyl, or R 7 and R 8 together with the carbon they are attached to form an optionally substituted 3-8 membered cyclyl or heterocyclyl;
R 9 and R 10 are independently hydrogen, optionally substituted linear or branched C 1 -C 10 alkyl, optionally substituted linear or branched C 2 -C 10 alkenyl, optionally substituted linear or branched C 2 -C 10 alkynyl, optionally substituted C 4 -C 8 cyclyl, optionally substituted C 3 -C 8 heterocyclyl, or R 9 and R 10 together with the carbon they are attached to form an optionally substituted 3-8 membered cyclyl or heterocyclyl, or
R 7 and R 9 together with the carbons they are attached to form an optionally substituted 3-8 membered cyclyl, heterocyclyl, aryl or heteroaryl;
L 1 and L 2 are independently a bond, optionally substituted linear or branched C 1 -C 10 alkylene, optionally substituted linear or branched C 2 -C 10 alkenylene, or optionally substituted linear or branched C 2 -C 10 alkynylene, wherein the backbone of C 1 -C 10 alkylene, C 2 -C 10 alkenylene, or C 2 -C 10 alkynylene optionally comprises one or more heteroatoms;
T is H, a linear or branched, substituted or unsubstituted C 1 -C 10 alkyl, linear or branched, substituted or unsubstituted C 2 -C 10 alkenyl, linear or branched, substituted or unsubstituted C 2 -C 10 alkynyl, optionally substituted cyclyl, optionally substituted heterocylcyl, optionally substituted aryl, optionally substituted heteroaryl, or PEG, wherein the backbone of C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl optionally comprises one or more heteroatoms;
n is an integer from 0-5; and
p is 0 or 1, provided that at least one of R 7 , R 8 , R 9 and R 10 is not hydrogen,

or a salt, solvate, or ester thereof.

2. The pharmaceutical composition of claim 1 , wherein R 9 and R 10 together with the carbon they are attached to form an optionally substituted 3-8 membered cyclyl or heterocyclyl.

3. The pharmaceutical composition of claim 2 , wherein Z is N.

4. The pharmaceutical composition of claim 2 , wherein R 4 and R 5 are each hydrogen.

5. The pharmaceutical composition of claim 2 , wherein R 2 is methyl, ethyl, n-propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, pentyl, neopentyl, hexyl, 2-methylpentyl, 3-methylpentyl, 2,3-dimethylbutyl, or 2,2-dimethylbutyl.

6. The pharmaceutical composition of claim 2 , wherein T is methyl or ethyl.

7. The pharmaceutical composition of claim 1 , wherein the compound has a structure of formula (IA):

or a salt, solvate, or ester thereof.

8. The pharmaceutical composition of claim 1 , wherein the compound has a structure of formula (IB):

or a salt, solvate, or ester thereof.

9. The pharmaceutical composition of claim 8 , wherein Z is N.

10. The pharmaceutical composition of claim 8 , wherein R 9 and R 10 together with the carbon they are attached to form a 3-, 4-, 5, or 6-membered cyclyl.

11. The pharmaceutical composition of claim 1 , wherein the compound has a structure of formula (IC):

or a salt, solvate, or ester thereof.

12. The pharmaceutical composition of claim 1 , wherein the compound of formula (I) is selected from the group consisting of

or a salt, solvate or ester thereof.

13. The pharmaceutical composition of claim 1 , wherein the compound of formula (I) is selected from the group consisting of

or a salt, solvate or ester thereof.

14. The pharmaceutical composition of claim 1 , wherein the compound is selected from the group consisting of

or a salt, solvate, or ester thereof.

15. A pharmaceutical composition comprising a compound having a structure

or a salt, solvate, or ester thereof, and a pharmaceutically acceptable excipient.

Assignees

• Massachusetts Gen Hospital
• Annovation Biopharma Llc
• Annovation Biopharma Inc

Inventors

• Raines Douglas E
• Husain Syed Shaukat
• Randle John C R

Classifications

• A61P25/20

  Hypnotics; Sedatives · CPC title

• A61K31/454

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone · CPC title

• A61K31/40

  having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil · CPC title

• C07D233/54

  having two double bonds between ring members or between ring members and non-ring members · CPC title

• C07D401/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title