3-aryl-3-hydroxy-2-amino-propionic acid amides, 3-heteroaryl-3-hydroxy-2-aminopropionic acid amides and related compounds having analgesic and/or immuno stimulant activity
Compounds of Formulas 1 and 2 where the variables have the meaning disclosed in the specification, have analgesic and in some cases immunostimulant activity.
1. A method for treating chronic pain in a mammal, comprising administering to said mammal at least one compound of the formula:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is H or alkyl of 1 to 6 carbons;
R 2 is selected from the group consisting of H, and alkyl of 1 to 6 carbons; or the R 1 and R 2 groups together with the nitrogen atom to which they are shown attached form a saturated or unsaturated 4, 5, 6 or 7 membered ring that optionally additionally includes one or two heteroatoms independently selected from the group consisting of N, O and S, said 4, 5, 6 or 7 membered ring optionally being substituted with one or two COOH, CH 2 OH, OH, B(OH) 2 , halogen groups, cyano groups or with one or two alkyl groups having 1 to 6 carbons;
R 3 is H, CO—R 7 or CO—O—R 7 where R 7 is H, alkyl of 1 to 20 carbons, cycloalkyl of 3 to 6 carbons, aryl or heteroaryl, aryl-alkyl, aryl(hydroxy)alkyl, heteroaryl-alkyl or heteroalkyl(hydroxy)alkyl where the alkyl moiety has 1 to 4 carbons, said aryl or heteroaryl groups being optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons;
R 4 is H, alkyl of 1 to 6 carbons, or CO—R 8 where R 8 is alkyl of 1 to 6 carbons;
R 5 and R 6 are independently selected from the group consisting of H, halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons; or
R 5 and R 6 together with the atoms to which they are attached jointly form a carbocyclic or a heterocyclic ring, the carbocyclic ring having 5 or 6 atoms in the ring, the heterocyclic ring having 5 or 6 atoms in the ring and 1 to 3 heteroatoms independently selected from N, O and S;
said carbocyclic or heterocyclic ring jointly formed by R 5 and R 6 being optionally substituted with 1 to 6 R 9 groups where R 9 is independently selected from halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons, and
the wavy lines represent bonds of the alpha or beta configuration
with the proviso that the formula excludes the compound of the formula below:
2. A method for treating chronic pain in a mammal, comprising administering to said mammal at least one compound of the formula:
or a pharmaceutically acceptable salt of said compound, wherein:
R 1 and R 2 groups together with the nitrogen atom to which they are shown attached form a saturated 5 or 6 membered ring, said ring optionally being substituted with one or two COOH, CH 2 OH, OH, B(OH) 2 , halogen groups, cyano groups or with one or two alkyl groups having 1 to 6 carbons;
R 3 is H or alkyl of 1 to 20 carbons; and
R 4 is H or alkyl of 1 to 6 carbons.
3. A method for treating chronic pain in a mammal, comprising administering to said mammal a compound of the formula:
or any other pharmaceutically acceptable salt of
4. A method for treating chronic pain in a mammal, comprising administering to said mammal a compound of the formula:
or a pharmaceutically acceptable salt thereof.
5. A compound of the formula:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is H or alkyl of 1 to 6 carbons;
R 2 is selected from the group consisting of H, and alkyl of 1 to 6 carbons; or the R 1 and R 2 groups together with the nitrogen atom to which they are shown attached form a saturated or unsaturated 4, 5, 6 or 7 membered ring that optionally additionally includes one or two heteroatoms independently selected from the group consisting of N, O and S, said 4, 5, 6 or 7 membered ring optionally being substituted with one or two COOH, CH 2 OH, OH, B(OH) 2 , halogen groups, cyano groups or with one or two alkyl groups having 1 to 6 carbons;
R 3 is H, CO—R 7 or CO—O—R 7 where R 7 is H, alkyl of 1 to 20 carbons, cycloalkyl of 3 to 6 carbons, aryl or heteroaryl, aryl-alkyl, aryl(hydroxy)alkyl, heteroaryl-alkyl or heteroalkyl(hydroxy)alkyl where the alkyl moiety has 1 to 4 carbons, said aryl or heteroaryl groups being optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons;
R 4 is H, alkyl of 1 to 6 carbons, or CO—R 8 where R 8 is alkyl of 1 to 6 carbons;
R 5 and R 6 are independently selected from the group consisting of H, halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons; or
R 5 and R 6 together with the atoms to which they are attached jointly form a carbocyclic or a heterocyclic ring, the carbocyclic ring having 5 or 6 atoms in the ring, the heterocyclic ring having 5 or 6 atoms in the ring and 1 to 3 heteroatoms independently selected from N, O and S;
said carbocyclic or heterocyclic ring jointly formed by R 5 and R 6 being optionally substituted with 1 to 6 R 9 groups where R 9 is independently selected from halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons, and
the wavy lines represent bonds of the alpha or beta configuration
with the proviso that the formula excludes the compound of the formula below:
6. A compound of the formula:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 and R 2 groups together with the nitrogen atom to which they are shown attached form a saturated 5 or 6 membered ring, said ring optionally being substituted with one or two COOH, CH 2 OH, OH, B(OH) 2 , halogen groups, cyano groups or with one or two alkyl groups having 1 to 6 carbons;
R 3 is H or alkyl of 1 to 20 carbons; and
R 4 is H or alkyl of 1 to 6 carbons.
7. The compound of claim 6 , or a pharmaceutically acceptable salt thereof, wherein the compound has the formula:
8. The compound of claim 6 , or a pharmaceutically acceptable salt thereof, wherein the compound has the formula:
9. A pharmaceutical composition comprising at least one compound of claim 5 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.
10. A pharmaceutical composition comprising at least one compound of claim 6 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.