Substituted piperidine compounds and methods of their use
View Patent ↗Novel 3,4-disubstituted-4-aryl-piperidine compounds are disclosed. Pharmaceutical compositions containing the 3,4-disubstituted-4-aryl-piperidine compounds and methods of their pharmaceutical uses are also disclosed. The compounds disclosed are useful, inter alia, as antagonists of opioid receptors.
1. A compound of formula I:
wherein:
R 1 is H or alkyl;
R 2a is alkyl;
R 2b is H, or alkyl;
R 3 is H, alkyl,-or aralkyl;
R 4 is
H, or
alkyl
R 5 is —CH 2 P(═O)OR 7b OR 7c ;
R 7b , and R 7c are each independently H, or alkyl
m is the integer 0, 1, 2, 3, or 4;
or a pharmaceutically acceptable salt thereof.
2. A compound according to claim 1 , wherein R 1 is H.
3. A compound according to claim 1 , wherein R 2a and R 2b are trans to each other.
4. A compound according to claim 1 , of formula II:
5. A compound according to claim 1 , wherein R 2a and R 2b are each methyl.
6. A compound according to claim 1 , of formula III:
wherein:
R 3 is aralkyl.
7. A compound according to claim 1 , wherein R 3 is:
8. A compound according to claim 7 , wherein R 1 is H, R 2a and R 2b are each methyl and are trans to each other, m is the integer 1, R 4 is H, and R 7b , and R 7c are each independently H or methyl.
9. A compound according to claim 5 , wherein R 3 is:
10. A compound according to claim 4 , wherein R 2a and R 2b are each methyl.
11. A compound according to claim 1 , of formula IX:
wherein:
R 3 is H, alkyl, or aralkyl.
12. A compound according to claim 1 , wherein R 4 is H.
13. A compound according to claim 1 , wherein m is the integer 1.
14. A pharmaceutical composition, comprising:
a pharmaceutically acceptable carrier; and
an effective amount of a compound according to claim 1 .
15. A pharmaceutical composition according to claim 14 , further comprising an effective amount of at least one opioid.
16. A pharmaceutical composition according to claim 15 , wherein said opioid is alfentanil, buprenorphine, butorphanol, codeine, dezocine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine (pethidine), methadone, morphine, nalbuphine, oxycodone, oxymorphone, pentazocine, propiram, propoxyphene, sufentanil, tramadol or mixtures thereof.
17. A pharmaceutical composition comprising the compound ({2S-Benzyl -3-[4-(3-hydroxyphenyl)-3R,4R-dimethylpiperidin-l-yl]-propionylamino }-methyl)-phosphonic acid or a pharmaceutically acceptable salt thereof.