Substituted fluoroethyl ureas as alpha 2 adrenergic agents

1. A compound having the formula

or a pharmaceutically acceptable salt thereof;

wherein n is 0 or 1; and

A is 5 to 7-membered cycloalkenyl optionally fused to an aromatic ring;

wherein A has 0, 1, 2, 3, or 4 substituents;

said substituents each independently consisting of: a moiety consisting of from 0 to 8 carbon atoms, 0 or 1 nitrogen atoms, 0 or 1 oxygen atoms, 0 or 1 sulfur atoms, 0 to 3 fluorine atoms, and from 0 to 22 hydrogen atoms; F; Cl; Br; or I;

provided that A is not unsubstituted 2-cyclohexen-1-yl.

2. The compound of claim 1 having the formula

or a pharmaceutically acceptable salt thereof;

wherein R 1 and R 2 are substituents which independently consist of: a moiety consisting of from 0 to 3 carbon atoms, 0 or 1 oxygen atoms, and from 0 to 9 hydrogen atoms; F; Cl; Br; or I.

3. The compound of claim 1 having the formula

or a pharmaceutically acceptable salt thereof;

wherein R 1 and R 2 are substituents which independently consist of: a moiety consisting of from 0 to 3 carbon atoms, 0 or 1 oxygen atoms, and from 0 to 9 hydrogen atoms; F; Cl; Br; or I; and

m is 1, 2, or 3.

4. The compound according to claim 1 having the formula

or a pharmaceutically acceptable salt thereof;

wherein X is S, N, or O;

R 1 and R 2 are substituents which independently consist of: a moiety consisting of from 0 to 3 carbon atoms, 0 or 1 oxygen atoms, and from 0 to 9 hydrogen atoms;

F; Cl; Br; or I; and

m is 1, 2, or 3.

5. The compound according to claim 1 wherein A is cyclopentenyl optionally fused to an aromatic ring.

6. The compound according to claim 1 wherein A is cyclohexenyl optionally fused to an aromatic ring.

7. The compound according to claim 1 wherein A is tetrahydronaphthylenyl.

8. The compound according to claim 1 wherein A is cycloheptenyl optionally fused to an aromatic ring.

9. The compound according to claim 1 wherein A has 0, 1, or 2 substituents.

10. The compound of claim 9 wherein the substituents are independently C 1-3 alkyl, C 1-3 alkoxy, F, Cl, Br, I, or NH 2 .

11. The compound according to claim 1 wherein n is 0.

12. The compound according to claim 1 wherein n is 1.

13. The compound according to claim 1 selected from

1-(2-fluoro-ethyl)-3-indan-2-yl-urea;

1-(2-Fluoro-ethyl)-3-indan-1-yl-urea;

(R)-(−)-1-(2-Fluoro-ethyl)-3-indan-1-yl-urea;

(S)-(−)-1-(2-Fluoro-ethyl)-3-indan-1-yl-urea;

1-(2-fluoroethyl)-3-(3-methylindan-1-yl)urea;

1-(2-fluoro-ethyl)-3-(2-methyl-indan-1-yl)-urea;

1-(2-fluoro-ethyl)-3-(4-methyl-indan-1-yl)-urea;

1-(2-fluoro-ethyl)-3-(6-methyl-indan-1-yl)-urea;

1-(2-fluoro-ethyl)-3-(6-methoxy-indan-1-yl)-urea;

1-(2-fluoro-ethyl)-3-(5-fluoro-indan-1-yl)-urea;

1-(2-fluoro-ethyl)-3-(4-methoxy-indan-1-yl)-urea;

1-(2-fluoro-ethyl)-3-(5-methoxy-indan-1-yl)-urea;

1-(5-chloro-indan-1-yl)-3-(2-fluoro-ethyl)-urea;

1-(5-bromo-indan-1-yl)-3-(2-fluoro-ethyl)-urea;

1-(2-fluoro-ethyl)-3-(6-fluoro-indan-1-yl)-urea;

1-(4-chloro-indan-1-yl)-3-(2-fluoro-ethyl)-urea;

1-(4-bromo-indan-1-yl)-3-(2-fluoro-ethyl)-urea;

1-(2-fluoro-ethyl)-3-(4-fluoro-indan-1-yl)-urea;

1-(2-fluoro-ethyl)-3-(7-methoxy-indan-1-yl)-urea;

1-(6-bromo-indan-1-yl)-3-(2-fluoro-ethyl)-urea;

1-(6-chloro-indan-1-yl)-3-(2-fluoro-ethyl)-urea;

1-(2-fluoro-ethyl)-3-(7-methyl-indan-1-yl)-urea;

1-(2-fluoro-ethyl)-3-(5-methyl-indan-1-yl)-urea;

1-(4-ethyl-indan-1-yl)-3-(2-fluoro-ethyl)-urea;

1-(2-fluoro-ethyl)-3-(7-fluoro-indan-1-yl)-urea;

1-(7-bromo-indan-1-yl)-3-(2-fluoro-ethyl)-urea;

1-(7-chloro-indan-1-yl)-3-(2-fluoro-ethyl)-urea;

1-(6,7-dichloro-indan-1-yl)-3-(2-fluoro-ethyl)-urea;

1-(6,7-difluoro-indan-1-yl)-3-(2-fluoro-ethyl)-urea;

1-(6,7-dimethyl-indan-1-yl)-3-(2-fluoro-ethyl)-urea;

1-(6-chloro-7-methyl-indan-1-yl)-3-(2-fluoro-ethyl)-urea;

1-(6-bromo-7-methyl-indan-1-yl)-3-(2-fluoro-ethyl)-urea;

1-(2-fluoro-ethyl)-3-(5-methoxy-indan-2-yl)-urea;

1-(2-fluoro-ethyl)-3-(4-methyl-indan-2-yl)-urea;

1-(2-fluoro-ethyl)-3-(4-methoxy-indan-2-yl)-urea;

1-(2-fluoro-ethyl)-3-(5-methyl-indan-2-yl)-urea;

1-(4-bromo-indan-2-yl)-3-(2-fluoro-ethyl)-urea;

1-(2-fluoro-ethyl)-3-(4-fluoro-indan-2-yl)-urea;

1-(2-fluoro-ethyl)-3-(5-fluoro-indan-2-yl)-urea;

1-(4-Chloro-indan-2-yl)-3-(2-fluoro-ethyl)-urea;

1-(5-chloro-indan-2-yl)-3-(2-fluoro-ethyl)-urea;

1-({[(2-fluoroethyl)amino]carbonyl}amino)-2,3-dihydro-1H-inden-4-yl benzoate;

1-(2-fluoroethyl)-3-(4-hydroxy-2,3-dihydro-1H-inden-1-yl)urea;

1-(4-amino-indan-1-yl)-3-(2-fluoro-ethyl)-urea;

1-(6,7-dihydro-5H-[1]pyrindin-7-yl)-3-(2-fluoro-ethyl)-urea;

1-(6,7-dihydro-5H-[1]pyrindin-5-yl)-3-(2-fluoro-ethyl)-urea;

1-(2-Fluoro-ethyl)-3-indan-1-ylmethyl-urea;

1-(2-fluoro-ethyl)-3-(5-methoxy-1,2,3,4-tetrahydro-naphthalen-1-yl)-urea;

1-(2-fluoro-ethyl)-3-(7-methoxy-1,2,3,4-tetrahydro-naphthalen-1-yl)-urea;

1-(2-fluoro-ethyl)-3-(4-methyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-urea;

1-(5,7-Dimethyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-3-(2-fluoro-ethyl)-urea;

1-(2-fluoro-ethyl)-3-(5-methyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-urea;

1-(5-chloro-1,2,3,4-tetrahydro-naphthalen-1-yl)-3-(2-fluoro-ethyl)-urea;

1-(5-ethyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-3-(2-fluoro-ethyl)-urea;

1-(5-bromo-1,2,3,4-tetrahydro-naphthalen-1-yl)-3-(2-fluoro-ethyl)-urea;

1-(2-fluoro-ethyl)-3-(5-fluoro-1,2,3,4-tetrahydro-naphthalen-1-yl)-urea;

1-(2-fluoroethyl)-3-(4,5,6,7-tetrahydro-1-benzofuran-4-yl)urea;

1-(2-fluoroethyl)-3-(4,5,6,7-tetrahydro-1-benzothien-4-yl)urea;

1-(2-fluoro-ethyl)-3-(1,2,3,4-tetrahydro-naphthalen-2-yl)-urea;

1-(2-fluoro-ethyl)-3-(6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl)-urea;

1-(2-fluoro-ethyl)-3-(3-fluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl)-urea;

1-(2-fluoro-ethyl)-3-(3-methyl-cyclopent-2-enyl)-urea;

1-(2,3-Dimethyl-cyclopent-2-enyl)-3-(2-fluoro-ethyl)-urea;

1-(3-ethyl-2-methyl-cyclopent-2-enyl)-3-(2-fluoro-ethyl)-urea;

1-(2-fluoro-ethyl)-3-(2-methyl-cyclohex-2-enyl)-urea;

1-(2-ethyl-cyclohex-2-enyl)-3-(2-fluoro-ethyl)-urea;

1-(2-fluoro-ethyl)-3-(3-methyl-cyclohex-2-enyl)-urea;

1-(3-Ethyl-cyclohex-2-enyl)-3-(2-fluoro-ethyl)-urea;

1-(2,3-dimethyl-cyclohex-2-enyl)-3-(2-fluoro-ethyl)-urea;

1-(2-Fluoro-ethyl)-3-(3-hydroxymethyl-cyclohex-2-enyl)-urea;

1-(2-fluoro-ethyl)-3-(3-formyl-2-methyl-cyclohex-2-enyl)-urea; and

1-(2-fluoro-ethyl)-3-(2R-propyl-1R-cyclohexyl)-urea.

14. A method of treating pain comprising administering a compound according to claim 1 to a mammal in need thereof.

15. The method of claim 14 wherein the pain is chronic pain.

16. The method of claim 14 wherein the pain is neuropathic pain.

17. The method of claim 14 wherein the pain is visceral pain.

18. The method of claim 14 wherein the pain is associated with allodynia.

19. The method of claim 14 wherein the pain is associated with muscle spasticity.

20. The method of claim 14 wherein the pain is associated with diarrhea.

21. A dosage form comprising a compound of claim 1 and a pharmaceutically acceptable excipient.