Compounds which selectively modulate the CB2 receptor

1. A compound of the formula (I)

wherein:

Het is a 5-membered heteroaryl ring;

R 1 is C 1-10 alkyl, C 1-10 alkoxy, C 3-10 cycloalkyl, 3-10 membered saturated heterocyclic ring, 5-10 membered mono or bicyclic heteroaryl ring or phenyl each optionally independently substituted with 1-3 substituents chosen from C 1-4 alkyl, C 1-4 alkoxy, C 3-10 cycloalkyl, C 1-4 alkylsulfonyl, acyl, oxo, cyano, phenyl, hydroxyl and halogen;

R 2 and R 3 are C 1 -C 4 alkyl or hydrogen with the proviso that both R 2 and R 3 cannot be hydrogen; or R 2 and R 3 together with the carbon atom to which they are attached form a 3- to 6-membered cycloalkyl or heterocyclic ring;

R 4 is hydrogen or methyl;

R 5 is chosen from

m is 0, 1, 2 or 3

R 6 is hydrogen or C 1-4 alkyl;

wherein R 7 and R 8 are each independently hydrogen or C 1-4 alkyl with the proviso that both R 7 and R 8 cannot be hydrogen; and wherein R 7 and R 8 optionally can cyclize to form a C 3-7 cycloalkyl ring;

n is 0, 1 or 2;

wherein any carbon atom on the formula (I) or any R substituent listed above is optionally partially or fully halogenated where possible;

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , and wherein

Het is

R 1 is C 1-4 alkyl, phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, piperidinyl; benzoxazolyl, benzothiazolyl, benzimidazolyl, dioxanyl, oxazolyl, isoxazolyl, thiazolyl, pyrazolyl, pyrrolyl, imidazolyl, thienyl, thiomorpholinyl, 1,1-Dioxo-1λ 6 -thiomorpholinyl, morpholinyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrrolidinyl, piperazinyl, purinyl, quinolinyl, Dihydro-2H-quinolinyl, isoquinolinyl, quinazolinyl, indazolyl, indolyl, benzofuranyl, benzopyranyl or benzodioxolyl each optionally substituted by a substituent chosen from halogen, C 1-4 alkyl, C 1-4 alkylsulfonyl and oxo;

R 2 and R 3 are independently methyl, ethyl, n-propyl, isopropyl or hydrogen with the proviso that both R 2 and R 3 cannot be hydrogen; or R 2 and R 3 together with the carbon to which they are attached form a cyclopropyl, cyclobutyl or cyclopentyl ring;

R 4 is hydrogen;

R 5 is chosen from

R 6 is hydrogen or C 1-3 alkyl;

wherein R 7 and R 8 are each C 1-3 alkyl or C 3-6 cycloalkyl

or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 2 , and wherein

R 1 is C 1-4 alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, piperidinyl, dioxanyl, thiomorpholinyl, 1,1-Dioxo-1λ 6 -thiomorpholinyl, morpholinyl, pyrrolidinyl or piperazinyl, each optionally substituted by a substituent chosen from halogen, C 1-4 alkyl, C 1-4 alkylsulfonyl and oxo or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 , and wherein

R 1 is C 1-4 alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, piperidinyl, dioxanyl, thiomorpholinyl, 1,1-Dioxo-1λ 6 -thiomorpholinyl, morpholinyl, pyrrolidinyl or piperazinyl, optionally substituted by a substituent chosen from halogen, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylsulfonyl and oxo

or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 2 , and wherein

Het is

R 1 is phenyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, oxazolyl, isoxazolyl, thiazolyl, pyrazolyl, pyrrolyl, imidazolyl, thienyl, thiadiazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, purinyl, quinolinyl, Dihydro-2H-quinolinyl, isoquinolinyl, quinazolinyl, indazolyl, indolyl, benzofuranyl, benzopyranyl or benzodioxolyl each optionally substituted by a substituent chosen from halogen, C 1-4 alkyl, C 1-4 alkylsulfonyl and oxo;

R 2 and R 3 are independently methyl, ethyl, n-propyl, isopropyl or hydrogen with the proviso that both R 2 and R 3 cannot be hydrogen; or R 2 and R 3 together with the carbon to which they are attached form a cyclopropyl, cyclobutyl or cyclopentyl ring

or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 5 , and wherein

Het is

R 1 is phenyl or benzimidazoyl each optionally substituted by a substituent chosen from halogen, C 1-4 alkyl, C 1-4 alkylsulfonyl and oxo;

R 2 and R 3 are methyl; or R 2 and R 3 together with the carbon to which they are attached form a cyclopropyl or cyclobutyl ring;

R 6 is hydrogen or C 1-2 alkyl;

R 7 and R 8 are each C 1-2 alkyl

or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 3 , and wherein

Het is

R 1 is C 1-2 alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydropyranyl, tetrahydrofuranyl, azetidinyl, pyrrolidinyl or piperidinyl each optionally substituted by a substituent chosen from by halogen, C 1-4 alkyl, C 1-4 alkylsulfonyl and oxo;

R 2 and R 3 are methyl, or R 2 and R 3 together with the carbon to which they are attached form a cyclopropyl or cyclobutyl ring;

R 6 is hydrogen or C 1-2 alkyl;

R 7 and R 8 are each C 1-2 alkyl

or a pharmaceutically acceptable salt thereof.

8. The compound according claim 6 and wherein

Het is

R 1 is phenyl optionally substituted by a substituent chosen from by halogen, C 1-4 alkyl and C 1-4 alkylsulfonyl

or a pharmaceutically acceptable salt thereof.

9. The compound according to claim 7 , and wherein

Het is

R 1 is cyclopropyl, cyclobutyl, tetrahydropyranyl, tetrahydrofuranyl or azetidinyl each optionally substituted by a substituent chosen from by halogen, C 1-4 alkyl, C 1-4 alkylsulfonyl and oxo

or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 3 , and wherein

Het is

R 2 and R 3 are methyl

or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 10 , and wherein

Het is

and

R 5 is

or a pharmaceutically acceptable salt thereof.

12. The compound according to claim 11 , and wherein

Het is

or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 11 , and wherein

R 5 is

or a pharmaceutically acceptable salt thereof.

14. The compound according to claim 11 , and wherein

R 1 is C 1-4 alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydropyranyl, tetrahydrofuranyl, azetidinyl, piperidinyl or pyrrolidinyl each optionally substituted by a substituent chosen from by halogen, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylsulfonyl and oxo or a pharmaceutically acceptable salt thereof.

15. The compound according to claim 11 , and wherein

R 1 is CF 3 —CH 2 —CH 2 —CH 2 — or tetrahydropyranyl

or a pharmaceutically acceptable salt thereof.

16. A compound of the formula (I)

wherein

of the formula (I) is chosen from column A1-A26 in Table I, and

of the formula (I) is chosen from column B1-B20 in Table I,

TABLE I

A1

A2

A3

A4

A5

A6

A7

A8

A9

A10

A11

A12

A13

A14

A15

A16

A17

A18

A19

A20

A21

A22

A23

A24

A25

A26

B1

B2

B3

B4

B5

B6

B7

B8

B9

B10

B11

B12

B13

B14

B15

B16

B17

B18

B19

B20

or a pharmaceutically acceptable salt thereof.

17. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 and one or more pharmaceutically acceptable carriers and/or adjuvants.

18. A compound wherein the compound is

or a pharmaceutically acceptable salt thereof.

19. A compound wherein the compound is

or a pharmaceutically acceptable salt thereof.

20. A compound wherein the compound is

or a pharmaceutically acceptable salt thereof.

21. A compound wherein the compound is

or a pharmaceutically acceptable salt thereof.

22. A compound wherein the compound is

or a pharmaceutically acceptable salt thereof.

23. A compound wherein the compound is

or a pharmaceutically acceptable salt thereof.

24. A compound wherein the compound is

or a pharmaceutically acceptable salt thereof.

25. A compound wherein the compound is

or a pharmaceutically acceptable salt thereof.

26. A compound wherein the compound is

or a pharmaceutically acceptable salt thereof.

27. A compound wherein the compound is

or a pharmaceutically acceptable salt thereof.

28. A compound wherein the compound is

or a pharmaceutically acceptable salt thereof.

29. A compound wherein the compound is

or a pharmaceutically acceptable salt thereof.

30. A compound wherein the compound is

or a pharmaceutically acceptable salt thereof.

31. A compound wherein the compound is

or a pharmaceutically acceptable salt thereof.

32. A compound wherein the compound is

or a pharmaceutically acceptable salt thereof.