Pyrrolidine compounds which modulate the CB2 receptor

1. A compound of the formula (I)

X is NH;

Ar 1 is chosen

phenyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, dioxanyl, tetrahydrofuranyl, oxazolyl, isoxazolyl, thiazolyl, pyrazolyl, pyrrolyl, imidazolyl, thienyl, thiadiazolyl, triazolyl, thiomorpholinyl, 1,1-Dioxo-1λ 6 -thiomorpholinyl, morpholinyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrrolidinyl, piperidinyl, piperazinyl, purinyl, quinolinyl, Dihydro-2H-quinolinyl, isoquinolinyl, quinazolinyl, indazolyl, indolyl, isoindolyl, benzofuranyl, benzopyranyl and benzodioxolyl each optionally substituted by 1-3 C 1-6 alkyl, C 1-6 alkoxy, CN, halogen, NO 2 , —S(O) 2 —C 1-3 alkyl, —CO 2 —C 1-4 alkyl, C(O)—NH(C 1-3 alkyl), —C(O)—N(C 1-3 alkyl) 2 , —N(C 1-3 alkyl), —N(C 1-3 alkyl)—C(O)—C 1-4 alkyl, —N(C 1-3 alkyl)—S(O) 2 —C 1-3 alkyl, morpholinyl or piperazinyl;

Ar 2 is chosen from

benzoxazolyl, benzothiazolyl, benzimidazolyl, oxazolyl, isoxazolyl, thiazolyl, pyrazolyl, pyrrolyl, imidazolyl, thienyl, thiadiazolyl, triazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, quinolinyl, isoquinolinyl, quinazolinyl, indazolyl, thieno[2,3-d]pyrimidinyl, indolyl, isoindolyl and benzofuranyl, each optionally substituted by 1-3 C 1-6 alkyl, cyclopropyl, cyclohexyl, phenyl, CN, halogen, pyrimidinyl, acetyl or oxo (═O);

L 1 is a bond;

L 2 is chosen from a bond, —CH 2 — and —CH 2 —CH 2 —;

wherein L 2 where possible is optionally substituted by halogen or C 1-3 alkyl;

R 1 is chosen from oxo (═O );

m is 0, 1 or 2;

wherein each Ar 1 and Ar 2 , or the substituents thereof are optionally partially or fully halogenated;

the stereogenic carbon indicated with an arrow is in the (S) configuration;

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 and wherein:

Ar 1 is chosen from phenyl , thienyl, pyridinyl, pyrimidinyl, pyrazine and triazine each optionally substituted by 1-3 C 1-6 alkyl, C 1-6 alkoxy, CN, halogen, NO 2 , —S(O) 2 —C 1-3 alkyl, —CO 2 —C 1-4 alkyl, —NH(C 1-3 alkyl)—CO 2 —C 1-4 alkyl, —C(O)—NH(C 1-3 alkyl), —C(O)—N(C 1-3 alkyl) 2 , —NH(C 1-3 alkyl), —N(C 1-3 alkyl)—C(O)—C 1-4 alkyl, —N(C 1-3 alkyl)—S(O) 2 —C 1-3 alkyl, morpholinyl or piperazinyl;

Ar 2 is oxazolyl, isoxazolyl, thiadiazolyl, pyrazolyl, triazolyl, thiazolyl, pyridinyl, benzimidazolyl, benzothiazolyl and benzoxazolyl, each optionally substituted by 1-3 C 1-5 alkyl, cyclopropyl, cyclohexyl, phenyl, CN, halogen, pyrimidinyl, acetyl or oxo (═O);

L 2 is chosen from a bond and —CH 2 —.

3. The compound according to claim 2 and wherein:

Ar 1 is chosen from pyridinyl, phenyl and thienyl each optionally substituted by 1-3 C 1-6 alkyl, C 1-6 alkoxy, CN, halogen, NO 2 , —S(O) 2 —C 1-3 alkyl,—CO 2 —C 1-4 alkyl, —NH(C 1-3 alkyl)—CO 2 —C 1-4 alkyl, —C(O)—NH(C 1-3 alkyl), —C(O)—N(C 1-3 alkyl) 2 , —NH(C 1-3 alkyl), —N(C 1-3 alkyl)—C(O)—C 1-4 alkyl or —N(C 1-3 alkyl)—S(O) 2 —C 1-3 alkyl;

Ar 2 is chosen from isoxazolyl optionally substituted by 1-3 C 1-5 alkyl and cyclopropyl.

4. The compound according to claim 3 and wherein:

Ar 2 is chosen from

5. A compound of the formula (III)

wherein

of the formula (III) is chosen from A1 - A56 of Table I, and

of the formula (III) is chosen from B1 -B25 of 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

A27

A28

A29

A30

A31

A32

A33

A34

A35

A36

A37

A38

A39

A40

A41

A42

A43

A44

A45

A46

A47

A48

A49

A50

A51

A52

A53

A54

A55

A56

B1

B2

B3

B4

B5

B6

B7

B8

B9

B10

B11

B12

B13

B14

B15

B16

B17

B18

B19

B20

B21

B22

B23

B24

B25

or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 5 wherein the stereogenic carbon indicated with an arrow formula (III) is in the (S) configuration.

7. A compound chosen from

or a pharmaceutically acceptable salt thereof.

8. 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.

9. A method of treating pain comprising administering a therapeutically effective amount of a compound according to claim 1 .

10. The method according to claim 9 wherein the pain is chosen from acute pain, visceral pain, neuropathic pain, inflammatory and nociceptive pain, cancer pain, and headache.