Cathinone derivatives, pharmaceutical formulations, and methods
Compounds, such as cathinone derivatives, and pharmaceutical formulations that include the compounds. The compounds may have a first selectivity for a first receptor subtype that is at least 10 times greater than a second selectivity for a second receptor subtype from the same class of receptors. Methods of treating patients, which may include administering to a patient a pharmaceutical formulation that includes a compound, such as a cathinone derivative.
1. A compound of formula (I), formula (II), or formula (III), or a salt of formula (I), formula (II), or formula (III):
wherein R 1 is a C 1 -C 10 hydrocarbyl comprising a nitrogen atom;
wherein R 2 , R 3 , R 4 , R 5 , and R 6 are independently selected from the group consisting of hydrogen, methyl, methoxy, hydroxy, a first halogen, and a C 1 -C 6 hydrocarbyl comprising a covalent bond between R 2 and R 3 , R 3 and R 4 , R 4 and R 5 , or R 5 and R 6 ; and
wherein X is selected from the group consisting of hydrogen, methyl, ethyl, hydroxy, and a second halogen; and
wherein (i) R 1 is an 8-methyl-8-azabicyclo[3.2.1]octanyl, or (ii) the compound of formula (I), formula (II), or formula (III) is a structure, or a salt thereof, selected from the group consisting of—
2. The compound of claim 1 , wherein the nitrogen atom is a tertiary nitrogen atom.
3. The compound of claim 1 , wherein—
(i) R 1 is 8-methyl-8-azabicyclo[3.2.1]octan-3-yl,
(ii) R 2 , R 3 , R 4 , R 5 , and R 6 are hydrogen,
(iii) X is methyl, and the compound is 2-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-1-phenylhexan-1-one:
4. The compound of claim 1 , wherein R 1 is an unsubstituted or substituted piperidinyl.
5. The compound of claim 1 , wherein—
(A)(i) R 1 is an unsubstituted piperidin-1-yl,
(ii) R 2 , R 3 , R 4 , R 5 , and R 6 are hydrogen,
(iii) X is hydroxy, and the compound is 5-hydroxy-1-phenyl-2-(piperidin-1-yl)pentan-1-one:
or
(B) (i) R 1 is 1-methylpiperidin-2-yl,
(ii) R 2 , R 3 , R 4 , R 5 , and R 6 are hydrogen,
(iii) X is methyl, and the compound is 2-(1-methylpiperidin-2-yl)-1-phenylhexan-1-one:
or
(C) (i) R 1 is 1-methylpiperidin-2-yl,
(ii) R 2 , R 3 , R 4 , R 5 , and R 6 are hydrogen,
(iii) X is hydroxy, and the compound is 5-hydroxy-2-(1-methylpiperidin-2-yl)-1-phenylpentan-1-one:
6. The compound of claim 1 , wherein R 1 is an unsubstituted or substituted azepanyl.
7. The compound of claim 1 , wherein—
(A) (i) R 1 is azepan-1-yl,
(ii) R 2 , R 3 , R 4 , R 5 , and R 6 are hydrogen,
(iii) X is methyl, and the compound is 2-(azepan-1-yl)-1-phenylhexan-1-one:
or
(B) (i) R 1 is azepan-1-yl,
(ii) R 2 , R 3 , R 4 , R 5 , and R 6 are hydrogen,
(iii) X is hydroxy, and the compound is 2-(azepan-1-yl)-5-hydroxy-1-phenylpentan-1-one:
8. The compound of claim 1 , wherein R 1 is (i) an 8,8-dimethyl-8λ 4 -azabicyclo[3.2.1]octanyl, (ii) a 9-methyl-3-oxa-9-azatricyclo[3.3.1.0 2,4 ]nonanyl, or (iii) a 9,9-dimethyl-3-oxa-W-azatricyclo[3.3.1.0 2,4 ]nonanyl.
9. A pharmaceutical formulation comprising the compound of claim 1 .
10. A method of treating a patient having a disorder linked to the muscarinic acetylcholine receptor, the method comprising:
administering to the patient a therapeutically effective amount of the pharmaceutical formulation of claim 9 .
11. The compound of claim 1 , wherein—
(i) R 1 is 8-methyl-8-azabicyclo[3.2.1]octan-3-yl,
(ii) R 2 , R 3 , R 4 , R 5 , and R 6 are hydrogen,
(iii) X is hydroxy, and the compound is 5-hydroxy-2-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-1-phenylpentan-1-one:
12. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
13. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
14. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
15. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
16. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
17. The compound of claim 1 , wherein R 1 is the 8-methyl-8-azabicyclo[3.2.1]octanyl.
18. The compound of claim 1 , wherein the nitrogen atom is a quaternary nitrogen atom.
19. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
20. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
21. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
22. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
23. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
24. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
25. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
26. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
27. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
28. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
29. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
30. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
31. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
32. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
33. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
34. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
35. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
36. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
37. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
38. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
39. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
40. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
41. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof:
42. The compound of claim 1 , wherein the compound of formula (I), formula (II), or formula (III) is the following structure or a salt thereof: