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1. (WO2010072352) 1, 2, 4 -OXADIAZOLE DERIVATIVES AND THEIR THERAPEUTIC USE
Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

CLAIMS

1. A compound of general formula (I)1 or a pharmaceutically acceptable salt or N- oxide thereof:


Formula (I) wherein

either (i) A is selected from the group consisting of -N-, -O- and -S-; B and C are independently selected from the group consisting of -N- and -O-, with the proviso that two of A, B and C are nitrogen atoms, or (ii) two of A, B and C are -N- and one of A, B and C is -NH-;

G1 is selected from the group consisting of -CH2-, -NH- and -O-;

G2 is selected from the group consisting of -NR4- and -O-;

R1 represents: > a 8 to 10 membered bicyclic N-containing heteroaryl group optionally substituted with a Ci-4 carboxyalkyl group or a C1-4 aminoalkyl group,

> a pyridyl group optionally substituted with one or more substituents selected from hydroxy groups, C1-4 alkyl groups, C1^, carboxyalkyl groups, C1-4 haloalkyl groups, C1-4 alkoxy groups, amino groups, C1-4 aminoalkyl groups and Ci-4 aminoalkoxy groups,

> a pyridone group substituted with one or more C1-4 alkyl groups; C1^, haloalkyl groups or C1^ aminoalkyl groups, or

> a group of formula:
wherein:

• Ra represents a hydrogen atom, a halogen atom, a C1-4 alkyl group, C3-4 cycloalkyl group or a -CF3 group; • Rb represents a hydrogen atom, a halogen atom, a Ci-4 alkyl group, a -CF3 group or a Ci-4 alkoxy group;

• Rd represents a hydrogen atom, a C1-4 alkyl group or a C1-4 alkoxy group;

• Rc represents: o a hydrogen atom, a C1-4 hydroxyalkyl group, a C1-4 aminoalkyl group which is optionally substituted with one or more substituents selected from halogen atoms, hydroxy groups and -CF3 groups; o a 4 to 6-membered saturated N-containing heterocyclic ring optionally substituted with a C1-2 carboxyalkyl group; o -(CH2)(M)-C(O)OR1, -(CH2)(CM)-C(O)NR1R", -(CH2)(M)-NHC(O)R", -S(O)2NR1R", -0-(CH2)(^)NR1R", -O-(CH2)(1-4)C(O)OR", -O-(CH2)(1-4)- C(O)NR1R", -(CH2)(O-4J-NR1R", -(CH2)(M)-CONHS(O)2R1, -(CH2)(M)- NHS(O)2R' or -(CH2)(0-3rNH-(CH2)(1-3)-(NH)(0-1)S(O)2R' wherein,

R1 represents a hydrogen atom or a C1-4 alkyl group,

R" represents a hydrogen atom, a C1-4 alkyl group, a C3-4 cycloalkyl group, a C1-4 carboxyalkyl group, a C1-4 haloalkyl group, a C1-4 hydroxyalkyl group or a 6 membered, saturated N- containing heterocyclic ring, or

R' and R" together with the nitrogen atom to which they are attached form a 4 to 6 membered heterocyclic group which contains, as heteroatoms, one N atom and, optionally, one further atom selected from N and O, and which is optionally substituted with a carboxy or a C1-4 carboxyalkyl group,

or Rc together with Rd form a C5-6 cycloalkyl group optionally substituted by a -NHRf group, wherein Rf is selected from the group consisting of a hydrogen atom and a carboxyrnethy! group;

R2 and R3 are independently selected from the group consisting of hydrogen atoms, halogen atoms and C1-4 alkyi groups; and

R4 is selected from the group consisting of a hydrogen atom, a phenyl group, a C3-4 cycloalkyl-C1-4 alkyl group, Ci-4 aminoalkyl group, C1-4 haloalkyl group and a linear or branched C1-4 alkyl group which is optionally substituted by a phenyl or a pyridyl group.

2. A compound according to claim 1 , wherein A is selected from the group consisting of -N- and -O-.

3. A compound according to claim 2, wherein A represents -N-.

4. A compound according to any one of claims 1 to 3, wherein both A and B represent -N- and C represents -O-.

5. A compound according to any one of the preceding claims, wherein G1 represents a -CH2- or a -O- group.

6. A compound according to claim 5, wherein G1 represents a -CH2- group.

7. A compound according to any one of the preceding claims, wherein R2 and R3 are independently selected from the group consisting of hydrogen atoms, fluorine atoms and methyl groups.

8. A compound according to claim 7, wherein both R2 and R3 are methyl groups.

9. A compound according to any one of claims 1 to 8, wherein R4 is selected from the group consisting of a C3-4 cycloalkyl-C1-4 alkyl group, C1-4 haloalkyl group and a linear or branched unsubstituted C1-4 alkyl group.

10. A compound according to claim 9, wherein G2 represents-NR4-, and wherein R4 is selected from the group consisting of a methyl group, ethyl group, t-butyl group, cyclopropylmethyl group and 2,2,2-trifluoroethyl group.

11. A compound according to claim 10, wherein R4 represents a methyl or an ethyl group.

12. A compound according to any one of the preceding claims, wherein R1 represents:

> a pyridyl group substituted with one, two or three substituents selected from hydroxy groups and C1-4 alkyl groups;

> a pyridone group substituted with one or two C1-2 alkyl groups; or

> a group of formula:


wherein:

• Ra represents a hydrogen atom or a C1-4 alkyl group; " R" represents a hydrogen atom or C1-4 alkyl group;

• Rd represents a hydrogen atom or a C1-4 alkyl group;

• Rc represents: o a C1-4 hydroxyalkyl group or a C1^ aminoalkyl substitued by one or more halogen atoms; o -(CH2WC(O)OR1, -(CH2WC(O)NR1R", -O-(CH2)(2.3)NR'R", -(CH2W

NHC(O)R", -S(O)2NR1R", -(CH2WNR1R" or -(CH2)(1-2)-CONHS(O)2R' wherein,

R1 represents a hydrogen atom or a methyl group,

R" represents a hydrogen atom, a C1-4 alkyl group, Ci-4 carboxyalkyl group, C1-4 haloalkyl group or a C1-4 hydroxyalkyl group, or

R1 and R" together with the nitrogen atom to which they are attached from a 4 to 6 membered heterocyclic group which contains, as heteroatoms, one N atom and, optionally, one further N atom, and which is optionally substituted with a carboxy or a C1-2 carboxyalkyl group, or Rc together with Rd form a cyclohexyl group substituted with a carboxymethylamino group.

13. A compound according to claim 12, wherein R1 represents:

> a pyridyl group substituted with two or three substituents selected from hydroxy groups, methyl and ethyl groups, or

> a group of formula:
wherein:

• Ra represents a hydrogen atom or a methyl group;

• Rb represents a hydrogen atom, a methyl group; • Rd represents a hydrogen atom or a methyl group;

• Rc represents: -(CH2)(Z-3J-C(O)OR1, -(CHa)2-C(O)NR1R" or -(CH2)(^)-NR1R", wherein o R' represents a hydrogen atom; o R" represents a hydrogen atom, a C1-2 carboxyalkyl group, a C1-4 haloalkyl group or a C1-2 hydroxyalkyl group; or o R' and R" together with the nitrogen atom to which they are attached form a 4 membered saturated heterocyclic group, which contains as heteroatom, one nitrogen atom and which is substituted with a carboxy group.

14. A compound according to claim 13, wherein R1 represents a group of formula:


wherein: o Ra represents a hydrogen atom; o both Rb and Rd represent methyl groups; and o Rc represents -(CH2)(2-3rC(O)OH or -(CH2)(2-3)-NHR", wherein R" is selected from a hydrogen atom, a C1-2 carboxyalkyl group, and C1-2 hydroxyalkyl group.

15. A compound according to any one of the preceding claims wherein: G1 represents a -CH2- group,

G2 represents a -NR4- group, wherein R4 represents a methyl or ethyl group, both R2 and R represent a methyl group, and R1 represents: > a pyridyl group substituted with two or three substituents selected from hydroxy groups, methyl or ethyl groups, or

> a group of formula:


wherein:

• Ra represents a hydrogen atom or a methyl group;

• Rb represents a hydrogen atom, a methyl group,

• Rd represents a hydrogen atom or a methyl group,

• Rc represents: -(CH2)(2.3)-C(O)OR1, -(CH2)Z-C(O)NR1R" or -(CH2)(2.3)-NR'R", wherein: o R' represents a hydrogen atom; o R" represents a hydrogen atom, a C1-2 carboxyalkyl group, a C1-4 haloalkyl group or a Ci-2 hydroxyalkyl group, or o R' and R" together with the nitrogen atom to which they are attached form a 4 membered saturated heterocyclic group, which contains as heteroatom, one nitrogen atom and which is substituted with a carboxy group.

16. A compound according to claim 15, wherein R1 represents a group of formula:


wherein o Ra represents a hydrogen atom; o both Rb and Rd represents a methyl group and o Rc represents -(CH2)(2.3)-C(O)OH or -(CH2)(2.3)-NHR", wherein R" is selected from a hydrogen atom, a C1-2 carboxyalkyl group and Ci-2 hydroxyalkyl group.

17. A compound of according to claim 1 , wherein R1 represents: > an imidazo[1 ,2-a]pyridyl group or a 3/-/-pyrrolo[2,3-b]pyridyl group which are optionally substituted with a carboxyethyl group;

> a pyridyl group optionally substituted with one or more substituents selected from hydroxy groups, methyl groups, ethyl groups, carboxyethyl groups, -CF3 groups, methoxy groups and amino groups

> a pyridone group substituted with one or more substituents selected from methyl and ethyl groups; or

> a group of formula:


wherein:

• Ra represents a hydrogen atom, a methyl group, cyclopropyl group or a CF3 group;

• Rb represents a hydrogen atom, a chlorine atom or a methyl group;

• Rd represents a hydrogen atom or a methyl group; • Rc represents: o a C1^ hydroxyalkyl group or a C1-4 aminoalkyl group substituted with one or more substituents selected from fluorine atoms and hydroxy groups; o a 4 to 6-membered saturated N-containing heterocyclic ring which is optionally substituted with a C1-2 carboxyalkyl group o -(CH2)(CM)-C(O)OR1, -(CH2)(O-4J-C(O)NR1R", -(CH2)(0_4)-NHC(O)R",

-S(O)2NR1R", -0-(CH2)(M)NR1R", -O-(CH2)(1-4)C(O)OR", -O-(CH2)(1-4)- C(O)NR1R" -(CH2)(O-4J-NR1R", -(CH2WCONHS(O)2R1 -(CH2)(O-4,- NHS(O)2R' or -(CH2)(o-3)-NH-(CH2)(1.3)-(NH)(o-1)S(0)2R' wherein o R' represents a hydrogen atom or a methyl group, o R" represents a hydrogen atom, a methyl group, a cyclopropyl group, a piperidyl group, a C1-2 carboxyalkyl group, a CF3 group, C1-4 hydroxyalkyl group, or o R1 and R" together with the nitrogen atom to which they are attached from a 4 to 6 membered heterocyclic group which contains, as heteroatoms, one N atom and, optionally, one further atom selected frnm N and O, and which is optionally substituted with a carboxy or a C1- 4 carboxyalkyl group, or Rc together with Rd form a cyclohexyl group optionally substituted by a -NHRf group, wherein Rf is selected from the group consisting of a hydrogen atom and a carboxymethyl group;

R2 and R3 are independently selected from the group consisting of hydrogen atoms, fluorine atoms and methyl groups; and

R4 is selected from the group consisting of a hydrogen atom, a phenyl group, a C3-4 cycloalkyl-Ci.2 alkyl group, C1-2 aminoalkyl group, C1-2 haloalkyl group or R4 represents a linear or branched C1^, alkyl group which is optionally substituted by a phenyl group or a pyridyl group.

18. A compound according to any one of claims 1 to 11 , wherein R1 represents a group of formula:


wherein:

• Ra represents a hydrogen atom,

• Rb represents a methyl group or a CF3 group,

• Rd represents a hydrogen atom or a methyl group; • Rc represents a -(CH2)(CM)-C(O)NR1R", -(CH2WNHC(O)R" or -(CH2W

NR1R", wherein o R' represents a hydrogen atom or a methyl group, o R" represents a hydrogen atom, a methyl group, a C1-2 carboxyalkyl group or a C1., hydroxyalkyl group, or o R' and R" together with the nitrogen atom to which they are attached from a 4 to 6 membered heterocyclic group which contains, as heteroatoms, one N atom and, optionally, one further atom selected from N and O, and which is optionally substituted with a carboxy or a C1- 4 carboxyalkyl group

19. A compound according to claim 18, wherein Rc represents a -(CH2)(2-3)-NR'R", wherein R' and R" together with the nitrogen atom to which they are attached from a 4 to 6 membered heterocyclic group which contains, as heteroatoms, one N atom, and which is substituted with a carboxy or a C1-2 carboxyalkyl group.

20. A compound according to claim 1, which is a compound of general formula (I1), or a pharmaceutically acceptable salt or N-oxide thereof:


Formula (I1) wherein,

G1 is selected from the group consisting of -CH2-, and -O-;

G2 is selected from the group consisting of -NR4- and -O-;

R1 represents:

> a pyrrolopyhdyl group, which is unsubstituted or substituted with a C1-2 carboxyalkyl group;

> a pyridyl group optionally substituted with 1 , 2 or 3 substituents selected from hydroxy groups, C1-2 alkyl groups, C1-2 carboxyalkyl groups, C1-2 haloalkyl groups, C1-2 alkoxy groups, and amino groups;

> a pyridone group substituted with 1 , 2 or 3 C1-2 alkyl groups; or

> a group of formula:


wherein: • Ra represents a hydrogen atom, a C1-2 alkyl group, a cyclopropyl group or a

-CF3 yrυuμ;

Rb represents a hydrogen atom, a chlorine atom, or a C1-2 alkyl group;

• Rd represents a hydrogen atom, or a CL2 alkyl group;

• Rc represents: o a d.3 hydroxyalkyl group; o a carboxyethylpiperazine group; o -(CH2)(0.2)-C(O)ORI, -(CH2)^-C(O)NR1R", -S(O)2NR1R", or -(CH2W

NR'R", wherein,

R1 represents a hydrogen atom,

R" represents a hydrogen atom, a Ci-2 alkyl group, a cyclopropyl group, a C1-2 carboxyalkyl group, a C1-2 haloalkyl group, a C1-2 hydroxyalkyl group or a piperidyl group, or

R' and R" together with the nitrogen atom to which they are attached from a 4 to 6 membered heterocyclic group which contains, as heteroatoms, one N atom and, optionally, one further atom selected from N and O, and which is optionally substituted with a carboxy or a C1-2 carboxyalkyl group, or Rc together with Rd forms a cyclohexyl group substituted by a -NHRf group, wherein Rf is a carboxymethyl group;

R2 and R3 are independently selected from the group consisting of hydrogen atoms, fluorine atoms and C1-2 alkyl groups; and

R4 is selected from the group consisting of hydrogen atoms, phenyl groups, cyclopropyl-C1-2 alkyl groups, C1-2 aminoalkyl groups, C1-2 haloalkyl groups and linear or branched C1^ alkyl groups which are optionally substituted by a phenyl or a pyridyl group.

21. A compound accroding to claim 1 which is one of:

4-(5-(6,6-Dimethyl-4,5,6,7-tetrahydro-2H-indazol-3-yl)-1 ,2,4-oxadiazol-3- yl)benzenesulfonamide (4-(5-(6,6-Dimethyl-4,5,6,7-tetrahydro-2H-indazol-3-yl)-1 ,2,4-oxadiazol-3- yl)phenyl)metanol

(4-(5-(1 ,6,6-Trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3- yl)phenyl)methanol

4-(5-(1 ,6,6-Trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3- yl)benzenesulfonamide

4-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1,2,4-oxadiazol-3- yl)benzenesulfonamide 5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-3-(pyridin-4-yl)-1 ,2,4-oxadiazole

S-C^δ^i-Ethyl-θ.e-dimethyM.S.e.y-tetrahydro-I H-indazol-a-yO-i ^^-oxadiazol-S-yl)-2,6-dimethylphenyl)propanoic acid 3-(4-(4-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol- 3-yl)phenyl)piperazin-1 -yl)propanoic acid

4-(5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)benzoic acid

4-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)benzamide

5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-3-(4-(piperazin-1 -yl)phenyl)-1 ,2,4-oxadiazole

2-(4-(5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenyl)acetic acid 1-(4-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid

2-(4-(5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenyl)acetamide

4-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)pyridine 1 -oxide

N-(4-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)piperidin-4-amine

5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-3-(6-methoxypyridin-3-yl)-1 ,2,4-oxadiazole 5-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)pyridin-2-ol

4-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)pyridin-2-ol

3-(4-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-2,6-dimethylphenyl)propanamide

4-(5-(1-Benzyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)benzamide

4-(5-(1 -tert-Butyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol- 3-yl)benzamide 5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-3-(2-methoxypyridin-4-yl)-1 ,2,4-oxadiazole 4-(5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)- 1 -methylpyridin-2(1 H)-one

1 -(4-(5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenyl)piperidine-4-carboxylic acid (4-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenyl)methanol

4-(5-(6,6-Dimethyl-1-phenyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)benzamide

3-Ethyl-5-(5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-6-methylpyridin-2-ol

5-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)- 3-methylpyridin-2-ol

4-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)- 3-methylbenzamide 4-(4-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)benzyl)morpholine

S-Ethyl-δ-CS^I-ethyl-θ.β-dimethyl^.S.ej-tetrahydro-IH-indazol-S-yO-i^^-oxadiazol-3-yl)-1 ,6-dimethylpyridin-2(1 H)-one

5-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-1 ,3-dimethylpyridin-2(1 H)-one

N-Cyclopropyl^S^I-ethyl-e.β-dimethyM.S.βJ-tetrahydro-I H-indazol-S-yO-i ^^-oxadiazol-3-yl)benzamide

1-(4-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenyl)-N-methylmethanamine S-CI-Ethyl-e.θ-dimethyM.S.θy-tetrahydro-IH-indazol-S-yO-S-CS-methylpyridin^-yl)- 1,2,4-oxadiazole

4-(5-(6,6-Dimethyl-1 -(2,2,2-trifluoroethyl)-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)benzamide

(4-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenyl)methanamine

5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-3-(3-methylpyridin-2-yl)- 1 ,2,4-oxadiazole

2-(4-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-2,6-dimethylphenyl)ethanamine 5-(5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2.4-oxadiazol-3-yl)- 4-methylpyridin-2-ol 3-(4-(5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoic acid

5-(5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)- 6-methylpyridin-2-ol 5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-3-(4-methylpyridin-3-yl)- 1 ,2,4-oxadiazole

5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-3-(4- (trifluoromethyl)pyridin-3-yl)-1 ,2,4-oxadiazole

5-(1-Ethyl-6,6-dimethyl-4,5l6,7-tetrahydro-1 H-indazol-3-yl)-3-(imidazo[1 ,2-a]pyridin-6-yl)-1 ,2,4-oxadiazole

3-(4-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-3-methylphenyl)propanamide

2-(4-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-3-methylphenyl)ethanamine 3-(4-(5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-2,6-dimethylphenyl)propan-1 -amine

4-(5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)- 3-(trifluoromethyl)benzoic acid

4-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-3-(trifluoromethyl)benzamide

5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-3-(2-methylpyridin-3-yl)- 1 ,2,4-oxadiazole

5-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)- 6-(trifluoromethyl)pyridin-2-amine 3-Cyclopropyl-4-[5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]benzamide

5-[5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]- 6-(trifluoromethyl)pyridin-2-ol

5-(5-(6,6-Dimethyl-1 -(2,2,2-trifluoroethyl)-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-3-ethyl-6-methylpyridin-2-ol

3-(4-(5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-3-(trifluoromethyl)phenyl)propanoic acid

S^-CS^I-Ethyl-β.β-dimethyl^.S.ΘJ-tetrahydro-IH-indazol-S-yO-i ^^-oxadiazol-S-yl)-3-(trifluoromethyl)phenyl)propanamide 3-Ethyl-5-[5-(1-ethyl-6,6-dimethyl-1 ,4,6,7-tetrahydropyrano[4.3-c]pyrazol-3-yl)- 1 ,2,4-oxadiazol-3-yl]-6-methylpyridin-2-ol 3-(4-(5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-3-methylphenyl)propan-1 -amine

3-(4-(5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-3-(trifluoromethyl)phenyl)propan-1 -amine 6-(5-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)- 1 ,2,3,4-tetrahydronaphthalen-2-amine

2-(4-(5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-3-(trifluoromethyl)phenyl)ethanamine

3-(2,6-Dimethyl-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenyl)propanoic acid

3-(2,6-Dimethyl-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenyl)propanamide

3-(4-(5-(6,6-Dimethyl-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-yl)-1 ,2,4-oxadiazol-3-yl)- 2,6-dimethylphenyl)propanoic acid 3-(4-(5-(6,6-Dimethyl-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-yl)-1 ,2,4-oxadiazol-3-yl)- 2,6-dimethylphenyl)propanamide

2-(6-(5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-1 ,2,3,4-tetrahydronaphthalen-2-ylamino)ethanoic acid

3-(2,6-Dimethyl-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenyl)propan-1 -amine

3-(4-(5-(6,6-Dimethyl-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-yl)-1 ,2,4-oxadiazol-3-yl)- 2,6-dimethylphenyl)propan-1-amine

2-(2,6-Dimethyl-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenyl)ethanamine 2-(4-(5-(6,6-Dimethyl-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-yl)-1 ,2,4-oxadiazol-3-yl)- 2,6-dimethylphenyl)ethanamine

S-CS-Ce.e-Dimethyl-i-Cpyridin-S-ylmethyO-^.δ.θJ-tetrahydro-I H-indazol-S-yl)-! ^^-oxadiazol-3-yl)-3-ethyl-6-methylpyridin-2(1 H)-one

2-(Dimethyl-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-2,6-dimethylphenethylamino)ethanoic acid

2-(3-(4-(5-(6,6-Dimethyl-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-2,6-dimethylphenyl)propylamino)ethanoic acid

3-(Dimethyl-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-2,6-dimethylphenethylamino)propanoic acid 3-Ethyl-5-(5-(1-ethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 :2:4-oxadia7o!-3-y!)-6-methylpyridin-2(1 H)-one 3-Ethyl-6-methyl-5-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)pyridin-2-ol

5-(5-(6,6-Dimethyl-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-3-ethyl-6-methylpyridin-2(1 H)-one 5-(5-(1 -(2-Aminoethyl)-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-3-ethyl-6-methylpyridin-2-ol

3-Ethyl-5-(5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-6-methylpyridin-2-amine

2-(4-(5-(6,6-Dimethyl-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-2,6-dimethylphenyl)-N,N-dimethylethanamine

3-(4-(4-(5-(6,6-Dimethyl-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenyl)piperazin-1 -yl)propanoic acid

3-Ethyl-5-(5-(1-ethyl-6,6-difluoro-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1,2,4-oxadiazol-3-yl)-6-methylpyridin-2(1 H)-one 3-(3-Ethyl-5-(5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-6-methylpyridin-2-yl)propanoic acid

5-(5-(1 -(Cyclopropylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-3-ethyl-6-methylpyridin-2(1H)-one

3-(2,6-Dimethyl-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenyl)propane-1 ,2-diol

N-(2,6-Dimethyl-4-(5-(1 ,6,6-trinnethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenethyl)-2,2,2-trifluoroethanamine

2-(2,6-Dimethyl-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydrc-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenethylamino)ethanol 2-(2,6-Dimethyl-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenethylamino)ethanoic acid

1-(2,6-Dimethyl-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-S-ylJphenethylJazetidine-S-carboxylic acid

3-(2-Methyl-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenyl)propanoic acid

4-(2,6-Dimethyl-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenethyl)morpholine

3-(4-(5-(6,6-Dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-2,6-dimethylphenyl)propane-1 ,2-diol 3-(4-(5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1.2:4-oxadiazo!-3-yl)phenylamido)propanoic acid 3-(4-(5-(6,6-Dimethyl-1-(pyridin-3-ylmethyl)-4,5,6,7-tetrahydro-1 H-indazol-3-yl)- 1 ,2,4-oxadiazol-3-yl)-2,6-dimethylphenyl)propane-1 ,2-diol

3-(2-Chloro-4-(5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenylsulfonamido)propanoic acid 3-(4-(5-(6,6-Dimethyl-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-yl)-1 ,2,4-oxadiazol-3-yl)- 2,6-dimethylphenyl)propane-1 ,2-diol

3-(1-Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-5-(pyridin-4-yl)-1 ,2,4-oxadiazole

5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-3-o-tolyl-1 ,2,4-oxadiazole

3-(5-(5-(1 -Ethyl-6,6-dimethyl-4,5,6,7-tetrahydrc-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-1 H-pyrrolo[2,3-b]pyridin-1 -yl)propanoic acid

3-(5-(5-(6,6-Dimethyl-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-yl)-1 ,2,4-oxadiazol-3-yl)- 1 H-pyrrolo[2,3-b]pyridin-1-yl)propanoic acid 1 -amino-3-{2,6-dimethyl-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)- 1 ,2,4-oxadiazol-3-yl]phenyl}propan-2-ol,

N-(2-{2,6-dimethyl-4-[5-(1.e.e-trimethyKS.ej-tetrahydro-i H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]phenyl}ethyl)-2-methylpropan-2-amine,

S^-IS-CI-ethyl-e.e-dimethyM.S.βy-tetrahydro-I H-indazol-S-yO-i ^^-oxadiazol-S-yl]-3-methylphenyl}propanoic acid,

[2-(4-{5-[6,6-dimethyl-1-(pyridin-3-ylmethyl)-4,5,6,7-tetrahydro-1 H-indazol-3-yl]- 1 ,2,4-oxadiazol-3-yl}-2,6-dimethylphenyl)ethyl]amine,

3-(4-{5-[1-(cyclopropylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl]- 1 ,2,4-oxadiazol-3-yl}-2,6-dimethylphenyl)propanoic acid, (2-{4-[3-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-5-yl]-3-methylphenyl}ethyl)amine,

N-[2-(4-{5-[6,6-dimethyl-1-(pyridin-3-ylmethyl)-4,5,6,7-tetrahydro-1 H-indazol-3-yl]- 1 ,2,4-oxadiazol-3-yl}-2,6-dimethylphenyl)ethyl]glycine,

3-{4-[5-(1 -ethyl-6,6-difluoro-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]-2,6-dimethylphenyl}propanoic acid,

3-(4-{5-[6,6-dimethyl-1-(pyridin-3-ylmethyl)-4,5,6,7-tetrahydro-1 H-indazol-3-yl]- 1 ,2,4-oxadiazol-3-yl}-2,6-dimethylphenyl)propanoic acid,

N-(2-{2,6-dimethyl-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]phenyl}ethyl)-2-hydroxyacetamide, 3-{4-[5-(1 -ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]-2,6-dimethylphenyl}-N-(methylsulfonyl)propanamide, a^-tS-CI-ethyl-e.e-dimethyM.S.βy-tetrahydro-IH-indazol-S-yO-i ^^-oxadiazol-S-yl]-2-methylphenyl}propanoic acid,

3-{4-[5-(1 -ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]-2,6-dimethylphenyl}propane-1,2-diol, N-(2-{4-[5-(6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]- 2,6-dimethylphenyl}ethyl)-2,2,2-trifluoroethanamine,

N-^Iδ-ti-ethyl-β.β-dimethyM.S.βJ-tetrahydro-IH-indazol-a-yO-I .Z^-oxadiazol-S-yl]-3-methylphenyl}sulfonyl)-beta-alanine,

N-(3-{4-[5-(1 -ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]-2,6-dimethylphenyl}propyl)methanesulfonamide,

N-(3-{2,6-dimethyl-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]phenyl}propanoyl)glycine,

(2-{4-[5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]-2-methylphenyl}ethyl)amine, N-({4-[5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]-3-methylphenyl}sulfonyl)glycine,

1-ethyl-6,6-dimethyl-3-[3-(2-methyl-4-piperidin-4-ylphenyl)-1 ,2,4-oxadiazol-5-yl]- 4,5,6,7-tetrahydro-1 H-indazole,

(4-{4-[5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]-3-methylphenyl}pipeιϊdin-1-yl)acetic acid,

3-(4-{4-[5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol- 3-yl]-3-methylphenyl}piperidin-1 -yl)propanoic acid,

(2-{4-[3-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-5-yl]-2,6-dimethylphenoxy}ethyl)amine, S^-IS-CI-ethyl-β.β-dimethyl^.S.βJ-tetrahydro-IH-indazol-S-yO-i^^-oxadiazol-S-yl]-2,5-dimethylphenyl}propanoic acid,

{4-[3-(1 -ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-5-yl]- 2,6-dimethylphenoxy}acetic acid,

3-{4-[3-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-5-yl]-2,6-dimethoxyphenyl}propanoic acid,

S^-chloro^-^-CI-ethyl-β.e-dimethyl^.S.ej-tetrahydro-IH-indazol-S-yO-i ^^-oxadiazol-5-yl]-6-methoxyphenyl}propanoic acid,

(2-{2,6-dimethyl-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]phenyl}ethyl)[2-(methylsulfonyl)ethyl]amine, 3-{2-ethyl-4-[5-(1 -ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 :2:4-oxadiazol-3-yl]-6-methylphenyl}propanoic acid, (2-{3-(trifluoromethyl)-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydiO-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]phenyl}ethyl)amine,

{4-[5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]- 2,6-dimethylphenyl}acetic acid, [3-({3-ethyl-5-[5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]-6-methylpyridin-2-yl}oxy)propyl]amine,

1 ,6,6-trimethyl-3-[3-(2-methyl-4-piperidin-4-ylphenyl)-1 ,2,4-oxadiazol-5-yl]-4,5,6,7-tetrahydro-1 H-indazole,

2-{4-[5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]-2,6-dimethylphenyl}acetamide,

2-{4-[5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]-2,6-dimethylphenyl}acetamide,

(2-{3-ethyl-5-[5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]-6-methylpyridin-2-yl}ethyl)amine, (2-{2,6-dimethyl-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,3,4-thiadiazol-2-yl]phenoxy}ethyl)amine,

{2-[4-[5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]-2-(trifluoromethyl)phenyl]ethyl}amine,

2-{2,6-dimethyl-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]phenyl}ethanol,

1-(2-{2,6-dimethyl-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-S-ylJphenylJethylJpiperidine^-carboxylic acid,

[1-(2-{2,6-dimethyl-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-S-ylJpheny^ethyOpiperidin^-ylJacetic acid, 1-(2-{2,6-dimethyl-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1,2,4-oxadiazol-S-ylJphenylJethyQpyrrolidine-S-carboxylic acid,

(3S)-1-(2-{2,6-dimethyl-4-[5-(1,6,6-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)- 1 ,2,4-oxadiazol-3-yl]phenyl}ethyl)pyrrolidine-3-carboxylic acid,

N-(2-{2,6-dimethyl-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydrc~1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]phenyl}ethyl)-L-alanine,

N-(2-{2,6-dimethyl-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]phenyl}ethyl)-2-methylalaniπe,

N-(2-{2,6-dimethyl-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]phenyl}ethyl)-D-alanine, 2-((2,6-dimethyl-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ;2,4-oxadiazol-3-yl)phenethyl)(methyl)amino)acetic acid, (2-{2,6-dimethyl-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,3,4-oxadiazol-2-yl]phenoxy}ethyl)amine,

{2-[4-[5-(1 -ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]-2-(trifluoromethyl)phenoxy]ethyl}amine, (2-{2-(trifluoromethyl)-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]phenyl}ethyl)amine,

(2-{2-(trifluoromethyl)-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]phenoxy}ethyl)amine,

(2,2-difluoro-2-{2-methyl-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]phenyl}ethyl)amine,

1-{2,6-dimethyl-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]phenyl}propan-2-ol,

3-{2,6-dimethyl-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]phenyl}propan-1-ol,, [4-(2-{2,6-dimethyl-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]phenyl}ethyl)piperazin-1 -yl]acetic acid,

1 -(2-{4-[5-(1 -ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol- S-yll^.θ-dimethylpheny^ethylJpiperidine^-carboxylic acid,

1-(2-{4-[5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]-2-methylphenyl}ethyl)piperidine-4-carboxylic acid,

1 -(2-{4-[3-(1 -ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol- 5-yl]-2-methylphenyl}ethyl)piperidine-4-carboxylic acid,

1-{2-[4-[5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol- S-ylJ^-^rifluoromethyOphenyllethylJpiperidine^-carboxylic acid, N-{2-[4-[5-(1 -ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol- 3-yl]-2-(trifluoromethyl)phenyl]ethyl}glycine,

4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]benzoic acid,

1-(2-{3-methyl-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl]phenyl}ethyl)piperidine-4-carboxylic acid,

(1-{2-[4-[5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol- 3-yl]-2-(trifluoromethyl)phenyl]ethyl}piperidin-4-yl)acetic acid,

2-[(2-{4-[5-(6,6-dimethyl-4,5,6,7-tetrahydro-1 ,2-benzisoxazol-3-yl)-1 ,2,4-oxadiazol- 3-yl]-2,6-dimethylphenyl}ethyl)amino]ethanol, N-{2-[(2-{4-[5-(6,6-dimethyl-4,5,6,7-tetrahydro-1 ,2-benzisoxazol-3-yl)-1 ,2,4-oxadiazol-3-yl]-2,6-dimethylphenyl}ethyl)amino]ethyl}methane-sulfonamide, N-(2-{4-[5-(6,6-dimethyl-4,5l6,7-tetrahydro-1,2-benzisoxazol-3-yl)-1,2,4-oxadiazol- 3-yl]-2,6-dimethylphenyl}ethyl)-2,2,2-trifluoroethanamine1

1 -(2-{4-[5-(6,6-dimethyl-4,5,6,7-tetrahydro-1 ,2-benzisoxazol-3-yl)-1 ,2,4-oxadiazol-3-yll^.e-dimethylphenylJethyOpiperidine^-carboxylic acid, 3-{4-[5-(6,6-dimethyl-4,5,6,7-tetrahydro-1 ,2-benzisoxazol-3-yl)-1 ,2,4-oxadiazol-3-yl]-2,6-dimethylphenyl}propane-1 ,2-diol,

1 -(2-{2-(trifluoromethyl)-4-[5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazoI-3-yl)-i ^^-oxadiazol-S-ylJphenytyethylJpiperidine^-carboxylic acid,

2-(2-(trifluoromethyl)-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenethylamino)acetic acid,

2-(methyl(2-(trifluoromethyl)-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenethyl)amino)acetic acid,

1-(2-(trifluoromethyl)-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenethyl)azetidine-3-carboxylic acid, 2-(1-(2-(trifluoromethyl)-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)- 1 ,2,4-oxadiazol-3-yl)phenethyl)piperidin-4-yl)acetic acid,

1 -(2,6-dimethyl-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-4H-1 ,2,4-triazol-3-yl)phenethyl)piperidine-4-carboxylic acid,

1-(2,6-dimethyl-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,3,4-oxadiazol-2-yl)phenethyl)piperidine-4-carboxylic acid,

1-(2,6-dimethyl-4-(5-(1,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,3,4-thiadiazol^-yljphenethyljpiperidine^-carboxylic acid,

2-(1-(2,6-dimethyl-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,3,4-thiadiazol-2-yl)phenethyl)piperidin-4-yl)acetic acid, 1-(2-(trifluoromethyl)-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,3,4-oxadiazol-2-yl)phenethyl)piperidine-4-carboxylic acid,

1-(2-(trifluoromethyl)-4-(5-(1.e.β-trimethyl^.S.ej-tetrahydro-i H-indazol-3-yl)-1 ,3,4-thiadiazol^-yOphenethylJpiperidine^-carboxylic acid,

2-(1-(2-(trifluoromethyl)-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,3,4-thiadiazol-2-yl)phenethyl)piperidin-4-yl)acetic acid,

2-(5-(5-(1 -ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-1 H-pyrrolo[2,3-b]pyridin-1 -yl)ethanamine,

5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-3-(1 H-pyrrolo[2,3-b]pyridin-5-yl)-1 ,2,4-oxadiazole, 2-(5-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydrc~1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-1 H-pyrrolo[2,3-b]pyridin-1-yl)ethanamine, 3-(1 H-indazol-5-yl)-5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazole,

5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-3-(1H-indol-4-yl)-1 ,2,4-oxadiazole, 3-(1 H-indol-4-yl)-5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazole,

5-(1 -ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-3-(1 H-indol-5-yl)-1 ,2,4-oxadiazole,

3-(1H-benzo[d]imidazol-5-yl)-5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazole,

2-(4-(5-(1-ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-1 H-indol-1-yl)acetic acid,

2-(5-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-1 H-indol-1-yl)acetic acid, 3-(4-(5-(1 -ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-1 H-indol-1 -yl)propanoic acid,

2-(5-(5-(1 -ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-1 H-indol-1 -yl)acetic acid,

3-(5-(5-(1 -ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-1 H-indol-1 -yl)propanoic acid,

2-(1-(2-(trifluoromethyl)-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)- 1 ,3,4-oxadiazol-2-yl)phenethyl)piperidin-4-yl)acetic acid,

2-(2-(trifluoromethyl)-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,3,4-thiadiazol-2-yl)phenethylamino)acetic acid, 1 -(2-(trifluoromethyl)-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,3,4-thiadiazol^-yOphenethyOazetidine-S-carboxylic acid,

1-(2-(trifluoromethyl)-4-(3-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-S-yOphenethylJpiperidine^-carboxylic acid

2-(1 -(2-(trifluoromethyl)-4-(3-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-5-yl)phenethyl)piperidin-4-yl)acetic acid

3-(3-(trifluoromethyl)-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenyl)propanoic acid,

3-(4-(5-(1 -ethyl-6,6-dimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)-2-(trifluoromethyl)phenyl)propanoic acid, and 3-(2-(trifluoromethyl)-4-(5-(1 ,6,6-trimethyl-4,5,6,7-tetrahydro-1 H-indazol-3-yl)-1 ,2,4-oxadiazol-3-yl)phenyl)propanoic acid or a pharmaceutically acceptable salt or N-oxide thereof

22. A compound according to any one of claims 1 to 21 for use in the treatment of a pathological condition or disease susceptible to amelioration by sphingosine-1- phosphate receptors (S1 P1) agonists.

23. A compound according to claim 22, wherein the pathological condition or disease is selected from autoimmune diseases, chronic immune and inflammatory diseases, transplant rejection, malignant neoplastic diseases, angiogenic-related disorders, pain, neurological diseases, viral and infectious diseases.

24. A compound according to claim 23 wherein the pathological condition or disease is selected from multiple sclerosis, transplant rejection, systemic lupus erythematosus, asthma, psoriasis, rheumatoid arthritis, psoriatic arthritis and Crohn's disease,

25. A pharmaceutical composition comprising a compound as defined in any one of claims 1 to 21 in association with a pharmaceutically acceptable diluent or carrier.

26. Use of a compound as defined in any one of claims 1 to 21 in the manufacture of a ..■edicament for the treatment of a pathological condition or disease as defined in claims 22 to 24.

27. A method for treating a subject afflicted with a pathological condition or disease as defined in claims 22 to 24, which comprises administering to said subject a therapeutically effective amount of a compound as defined in any one of claims 1 to 21.

28. A combination product comprising (i) a compound according to any one of claims 1 to 21; and (ii) another compound selected from: a) Beta interferons such as Betaseron, Avonex or Rebif b) lmmunomodulators such as glatiramer acetate c) Inhibitors of DNA synthesis and repair, such as Mitoxantrone d) Anti-alpha 4 integrin antibodies, such as Natalizumab (Tysabri) e) Alpha 4 integrin antagonists such as R-1295 , TBC-4746. CDP-323;

ELND-002, Firategrast and TMC-2003 f) Dyhydrofolate reductase inhibitors, such as Methotrexate or CH- 1504 g) Glucocorticoids such as prednisone or methylprednisolone h) DHODH inhibitors such as teriflunomide i) Fumaric acid esters, such as BG-12 j) lmmunomodulators such as Laquinimod k) Anti-CD20 monoclonal antibodies such as Rituximab, Ocrelizumab

Ofatumumab or TRU-015

I) Anti-CD52 such as alemtuzumab m) Anti-CD25 such as daclizumab n) Anti-CD88, such as eculizumab or pexilizumab o) Calcineurin inhibitors such as cyclosporine A or tacrolimus p) IMPDH inhibitors, such as mycophenolate mophetyl q) Cannabinoid receptor agonists such as Sativex r) Chemokine CCR1 antagonists such as MLN-3897 or PS-031291 s) Chemokine CCR2 antagonists such as INCB-8696 t) Interferon alpha such as Sumiferon MP u) NF-kappaB activation inhibitors such as FAE and MLN-0415 v) JAK inhibitors such as CP-690550 or INCB018424 w) Syk inhibitors, such as R-112 x) PKC inhibitors, such as NVP-AEB071 y) Phosphosdiesterase IV inhibitors such as GRC-4039 z) P38 Inhibitors such as ARRY-797 aa) MEK inhibitors, such as ARRY-142886 or ARRY-438162