Cardioprotective delta opioid receptor agonists and methods of using same
AssigneeMount Cook Biosciences, Inc.
InventorsKwen-Jen Chang, William Pendergast, Peter J. Gengo, Xin Ma
Life of this patent
Estimating the term…
Abstract
The present invention relates to compositions and methods of treatment for cardioprotection through the use of non-peptidic delta opioid receptor agonist compound(s) that mediate cardioprotective effects of ischemic preconditioning. The compounds are used to reduce injury associated with ischemia and reperfusion of cardiac tissue. Further, the compounds may be used in solutions preserving the viability of an isolated organ.
Claims40
A therapeutic composition for combating ischemic damage, the composition comprising an effective amount of a diarylmethylpiperazine compound of the general formula:
- 12
- wherein:
- Z is selected from the group consisting of:
- hydrogen;
- halogen;
- C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl;
- C1-C6 haloalkyl;
- C1-C6 alkoxy;
- C3-C6 cycloalkoxy;
- sulfides of the formula SR8 where R8 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, arylalkyl having a C5-C10 aryl moiety and an C1-C6 alkyl moiety, or C5-C10 aryl;
- sulfoxides of the formula SOR8 where R8 is the same as above;
- sulfones of the formula SO2R8 where R8 is the same as above;
- nitrile;
- C1-C6 acyl;
- alkoxycarbonylamino (carbamoyl) of the formula NHCO2R8 where R8 is the same as above;
- carboxylic acid, or an ester, amide, or salt thereof;
- aminomethyl of the formula CH2NR9R10 where R9 and R10 may be the same or different, and may be hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C2-C6 hydroxyalkyl, C2-C6 methoxyalkyl, C3-C6 cycloalkyl, or C5-C10 aryl, or R9 and R10 together may form a ring of 5 or 6 atoms, the ring atoms selected from the group consisting of N and C;
- carboxamides of the formula CONR9R10 where R9 and R10 are the same as above, or C2-C30 peptide conjugates thereof;
- and
- sulfonamides of the formula SO2NR9R10 where R9 and R10 are the same as above;
- and
- X is selected from the group consisting of hydrogen, hydroxyl, halogen and alkoxy,
- or a pharmaceutically acceptable ester or salt thereof.
A therapeutic composition for combating ischemic damage, the composition comprising an effective amount of a non-analgesic diarylmethylpiperazine compound of the formula:
- 13
- or a pharmaceutically acceptable ester or salt thereof.
A method of reducing ischemic damage in a subject comprising:
- administering an effective amount of a therapeutic composition comprising a non-analgesic diarylmethylpiperazine compound of the formula:
- 14
- or a pharmaceutically acceptable salt or ester thereof.
A therapeutic composition for combating ischemic damage, the composition comprising an effective amount of a non-analgesic diarylmethylpiperazine compound of the formula:
- 15
- or a pharmaceutically acceptable ester or salt thereof.
A method of reducing ischemic damage in cardiac tissue, the method comprising:
- administering to said mammal an effective amount of a non-analgesic diarylmethylpiperazine compound of the formula:
- 16
- or a pharmaceutically acceptable salt or ester thereof.
A preserving solution for an isolated organ comprising a compound of the formula:
- 17
- or a pharmaceutically acceptable salt or ester thereof.
A method of protecting against ischemia and reperfusion injury in a mammal comprising administering to the mammal an effective amount of a delta opioid receptor agonist of the formula:
- 18
- or pharmaceutically acceptable esters and salts thereof, and a second compound that effectuates an anti-ischemic effect.
A method of effectuating ischemic preconditioning of cardiac tissue in a subject, the method comprising:
- administering to the subject an effective amount of a diarylmethylpiperazine compound of the formula:
- 19
- or pharmaceutically acceptable esters and salts thereof.
Dependencies are inferred from the claim text.