Compound with analgesic effect for use in prevention and treatment of pain
AssigneeAcademia Sinica
InventorsChih-Cheng Chen, Jim-Min Fang, Cheng-Han Lee, Jen-Yao Chang
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Abstract
Compounds for use in prevention and/or treatment of pain are disclosed. The compounds are derived by conjugation of N6-(4-hydroxybenzyl)adenosine and analogous compounds with amino acids or peptides. In one embodiment of the invention, the compound is 5′-O-(glycine-N-carbonyl-N6-(4-hydroxybenzyl)adenosine (I-a1). In another embodiment of the invention, the compound is 5-deoxy-5′-(glycine-N-amido)-N6-(4-hydroxybenzyl)adenosine (I-d1). Also disclosed are methods of making and using the same.
Claims16
A compound of formula (I):
- wherein;
- n is 0, 1, 2 or 3;
- X is NH, O or S;
- Y is O, NH or S;
- wherein when n is 1, R1 is OH, NH2, NO2, halogen, alkyl, haloalkyl, hydroxyalkyl, unsubstituted or substituted alkoxy, alkoxyalkyl, alkenyl or alkynyl;
- when n is 2 or 3, R1 is independently selected from:
- OH, NH2, NO2, halogen, alkyl, haloalkyl, hydroxyalkyl, unsubstituted or substituted alkoxy, alkoxyalkyl, alkenyl or alkynyl;
- R2 and R3 are each independently OH, NH2, NO2, haloalkyl, hydroxyalkyl or alkylamino;
- and
- R4 is selected from an amino acid or a peptide,
- wherein when R4 is an amino acid, R4 is linked to the C(═O) in the structure via the backbone amino group or side chain amino group, and the carboxy group of the amino acid is optionally a methyl or ethyl ester, and
- wherein when R4 is a peptide, R4 is linked to the C(═O) in the structure via the N-terminal amino group of said peptide, or a side chain amino group of an amino acid in the peptide, wherein the C-terminal of the peptide is optionally modified;
- a tautomer or stereoisomer thereof;
- and
- a pharmaceutically acceptable salt of the foregoing.
A method of treating acid-induced muscle pain, pain associated with tissue acidosis, or fibromyalgia in a subject in need thereof, the method comprising administering to said subject a compound of formula (I):
- wherein X is NH and Y is O, n is 1, R1, R2 and R3 are each OH,
- R4 is selected from an amino acid or a peptide,
- wherein when R4 is an amino acid, R4 is linked to the C(═O) in the structure via the backbone amino group or side chain amino group, and the carboxy group of the amino acid is optionally a methyl or ethyl ester, and
- wherein when R4 is a peptide, R4 is linked to the C(═O) in the structure via the N-terminal amino group of said peptide, or a side chain amino group of an amino acid in the peptide, wherein the C-terminal of the peptide is optionally modified, a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of the foregoing.
A method of reducing neurokinin 1 receptor (NK1R) signaling in a cell, the method comprising contacting said cell with a compound of formula (I):
- wherein X is NH and Y is O, n is 1, R1, R2 and R3 are each OH,
- R4 is selected from an amino acid or a peptide,
- wherein when R4 is an amino acid, R4 is linked to the C(═O) in the structure via the backbone amino group or side chain amino group, and the carboxy group of the amino acid is optionally a methyl or ethyl ester, and
- wherein when R4 is a peptide, R4 is linked to the C(═O) in the structure via the N-terminal amino group of said peptide, or a side chain amino group of an amino acid in the peptide, wherein the C-terminal of the peptide is optionally modified.
Dependencies are inferred from the claim text.