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1. WO2020231713 - AGONISTS OF ROR GAMMAt

Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

[ EN ]

WE CLAIM:

1. A compound of the formula


wherein

A is -CH- or -N-;

Ra is H or CO-Rb,

Rb is a C3-8 cycloalkyl or a -(CH2)r-3-7 membered heterocycle either of which is substituted with 0-3 Rc;

Rc is halogen, Ci-6 alkyl, COOH or CONH2,

R1 and R2 are independently 0-4 hydrogen, halogen, Ci-6 alkyl or CF3;

r is 0, 1 or 2;

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 of the formula


wherein

R1 and R2 are independently 0-4 hydrogen, halogen, Ci-6 alkyl or CF3;

or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 of the formula


wherein

Ra is CO-Rb,

Rb is a C3-8 cycloalkyl or a -(CH2)r-3-7 membered heterocycle either of which is substituted with 0-3 Rc;

Rc is hydrogen, halogen, Ci-6 alkyl, COOH or CONH2,

R1 and R2 are independently 0-4 hydrogen, halogen, Ci-6 alkyl or CF3;

r is 0, 1 or 2;

or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 3 wherein

Ra is CO-Rb,

Rb is a C3-8 cycloalkyl substituted with 0-3 Rc;

Rc is hydrogen, halogen, Ci-6 alkyl, COOH or CONH2,

R1 and R2 are independently 0-4 hydrogen, halogen, Ci-6 alkyl or CF3;

or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 3 wherein

Ra is CO-Rb,

Rb is a -(CH2)r-3-7 membered heterocycle substituted with 0-3 Rc;

Rc is hydrogen, halogen, Ci-6 alkyl, COOH or CONH2,

R1 and R2 are independently 0-4 hydrogen, halogen, Ci-6 alkyl or CF3;

r is 0, 1 or 2;

or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 5 wherein

Ra is CO-Rb,

Rb is a -(CH2)r-3-7 membered heterocycle substituted with 0-3 Rc;

Rc is hydrogen, halogen, Ci-6 alkyl, COOH or CONH2,

R1 and R2 are independently 0-4 hydrogen, halogen, Ci-6 alkyl or CF3;

r is 1;

or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 5 wherein

Ra is CO-Rb,

Rb is a -(CH2)r-3-7 membered heterocycle substituted with 0-3 Rc, wherein the heterocycle is selected from the group consisting of oxanyl, pyridinyl, triazolyl, thiolane-1,1-dione, thiazolidine-2,4-dione or thiane-l,l-dione;

Rc is hydrogen, halogen, Ci-6 alkyl, COOH or CONH2,

R1 and R2 are independently 0-4 hydrogen, halogen, Ci-6 alkyl or CF3;

r is 1;

or a pharmaceutically acceptable salt thereof.

8. A compound according to claim 1 which is

l-(benzyloxy)-4-(l-((4-fluorophenyl)sulfonyl)cyclopentyl)benzene,

4-{3-[4-(benzyloxy)phenyl]-3-(4-fluorobenzenesulfonyl)pyrrolidine-l-carbonyl}- llambda6-thiane-l,l-dione, (2)

4-[(3R)-3-(4-{[2-fluoro-6-(trifluoromethyl)phenyl]methoxy}phenyl)-3-(4-fluorobenzenesulfonyl)pyrrolidine- 1 -carbonyl]- 1 lambda6-thiane- 1 , 1 -dione, (3)

1 -[ 1 -(4-11 uorobenzenesulfonyl )cyclopentyl]-4-(2-phenyl ethoxy )benzene, (4)

1 -(benzyloxy)-4-[ 1 -(3 -chlorobenzenesulfonyl)cyclopentyl]benzene,

1 -[ 1 -(benzenesulfonyl)cyclopentyl]-4-(benzyloxy)benzene,

1 -[ 1 -(4-fluorobenzenesulfonyl)cyclopentyl]-4-[(2-fluorophenyl)methoxy]benzene,

l-(benzyloxy)-4-{ l-[3-(trifluoromethyl)benzenesulfonyl]cyclopentyl}benzene,

1 -(benzyloxy)-4-[ 1 -(4-chlorobenzenesulfonyl)cyclopentyl]benzene,

1 -[ 1 -(benzenesulfonyl)cyclopentyl]-4-(cyclohexylmethoxy)benzene, (10)

1 -[ 1 -(benzenesulfonyl)cyclopentyl]-4-[(3 -fluorophenyl)methoxy]benzene,

1 -[ 1 -(benzenesulfonyl)cyclopentyl]-4-[(4-fluorophenyl)methoxy]benzene,

1 -[ 1 -(benzenesulfonyl)cyclopentyl]-4-[(2-fluorophenyl)methoxy]benzene, l-[l-(benzenesulfonyl)cyclopentyl]-4-(2-cyclopropylethoxy)benzene, (14) l-{3-[4-(benzyloxy)phenyl]-3-(4-fluorobenzenesulfonyl)pyrrolidin-l-yl}-2-(oxan-4-yl)ethan- 1 -one,

l-{3-[4-(benzyloxy)phenyl]-3-(4-fluorobenzenesulfonyl)pyrrolidin-l-yl}-2-(pyridin-4-yl)ethan- 1 -one,

l-{3-[4-(benzyloxy)phenyl]-3-(4-fluorobenzenesulfonyl)pyrrolidin-l-yl}-2-(lH-1 ,2,3 -triazol- 1 -yl)ethan- 1 -one,

3-[4-(benzyloxy)phenyl]-3-(4-fluorobenzenesulfonyl)-l-(oxane-4-carbonyl)pyrrolidine,

3-{3-[4-(benzyloxy)phenyl]-3-(4-fluorobenzenesulfonyl)pyrrolidine-l-carb ony 1 } - 1 6-thi ol ane- 1 , 1 -di one,

5-(2-{3-[4-(benzyloxy)phenyl]-3-(4-fluorobenzenesulfonyl)pyrrolidin-l-yl}-2-oxoethyl)-l,3-thiazolidine-2,4-dione,

4-{3-[4-(benzyloxy)phenyl]-3-[3-(trifluoromethyl)benzenesulfonyl]pyrrolidine-1 -carb ony 1 } - 1 6-thi ane- 1 , 1 -di one,

l-{3-[4-(benzyloxy)phenyl]-3-[3-(trifluoromethyl)benzenesulfonyl]pyrrolidin-l-yl } -2-(pyridin-4-yl)ethan- 1 -one,

4-[3-(benzenesulfonyl)-3-{4-[(2,6-dichlorophenyl)methoxy]phenyl}pyrrolidine-1 -carbonyl]- 1 6-thiane- 1 , 1 -dione,

(1 r,4r)-4-[3 -(benzenesulfonyl)-3 - {4-[(2,6-dichlorophenyl)methoxy]phenyl }pyrrolidine- 1 -carbonyl] cyclohexane- 1 -carboxylic acid, 4-[3-(benzenesulfonyl)-3-{4-[(2,6-dichlorophenyl)methoxy]phenyl}pynOlidine-1 -carbonyl]piperidine- 1 -carboxamide,

l-[3-(benzenesulfonyl)-3-{4-[(2,6-dichlorophenyl)methoxy]phenyl}pynOlidin-l-yl]-2-(pyridin-4-yl)ethan- 1 -one,

4-[3 -(benzenesulfonyl)-3 - { 4- [(2-chloro-3 , 6-difluorophenyl)methoxy]phenyl }pyrrolidine- 1 -carbonyl]- 1 //’-thiane- 1 , 1 -dione,

4-[3-(benzenesulfonyl)-3-{4-[(2-chlorophenyl)methoxy]phenyl}pyrrolidine-l-carb ony 1 ] - 1 6-thi ane- 1 , 1 -di one,

4-[3-(benzenesulfonyl)-3-{4-[(2-chloro-6-fluorophenyl)methoxy]phenyl }pyrrolidine- 1 -carbonyl]- 1 //’-thiane- 1 , 1 -dione,

4-[3-(benzenesulfonyl)-3-(4-{[2-fluoro-6- (trifluoromethyl)phenyl]methoxy }phenyl)pyrrolidine- 1 -carbonyl]- 1 //’-thiane- 1 , 1 -dione, 4-[3-(benzenesulfonyl)-3-{4-[(2-chloro-4-fluorophenyl)methoxy]phenyl }pyrrolidine- 1 -carbonyl]- 1 //’-thiane- 1 , 1 -dione,

4-[3 -(benzenesulfonyl)-3 -(4-{ [2- (trifluoromethyl)phenyl]methoxy}phenyl)pyrrolidine-l -carbonyl]- l /2’-thiane- l , l -dione, 4-[(3R)-3-(benzenesulfonyl)-3-{4-[(2,6-dichlorophenyl)methoxy]phenyl }pyrrolidine- 1 -carbonyl]- 1 /7-th i an e- 1 , 1 -dione,

(lr,4r)-4-[(3R)-3-(benzenesulfonyl)-3-{4-[(2,6-dichlorophenyl)methoxy]phenyl }pyrrolidine- 1 -carbonyl] cyclohexane- 1 -carboxylic acid, (lr,4r)-4-[(3R)-3-{4-[(2,6-dichlorophenyl)methoxy]phenyl}-3-(4-fluorobenzenesulfonyl)pynOlidine-l-carbonyl]cyclohexane-l-carboxylic acid,

4-[(3R)-3-{4-[(2,6-dichlorophenyl)methoxy]phenyl}-3-(4-fluorobenzenesulfonyl)pyrrolidine- l -carbonyl]-! /7-thiane- l , 1 -dione,

4-[(3R)-3-(4-fluorobenzenesulfonyl)-3-{4-[(l S)-l-phenylethoxy]phenyl }pyrrolidine- 1 -carbonyl]- 1 /7-th i an e- 1 , 1 -dione, (37)

4-[(3R)-3 -(4-fluorobenzenesulfonyl)-3 -(4- { [2-(trifluoromethyl)phenyl]methoxy}phenyl)pyrrolidine-l -carbonyl]- l /7’-thiane- l , l -dione, 4-[(3R)-3-(4-{[2-chloro-6-(trifluoromethyl)phenyl]methoxy}phenyl)-3-(4-fluorobenzenesulfonyl)pyrrolidine- l -carbonyl]-! //’-thiane- l , 1 -dione,

4-[(3R)-3-(benzenesulfonyl)-3-(4-{[2-fluoro-6-(trifluoromethyl)phenyl]methoxy}phenyl)pyrrolidine-l-carbonyl]-4-hydroxy-l 6-thiane-1,1 -dione,

(lr,4r)-4-[(3R)-3-(benzenesulfonyl)-3-(4-{[2-fluoro-6-(trifluoromethyl)phenyl]methoxy }phenyl)pyrrolidine- 1 -carbonyl]cyclohexane- 1 -carboxylic acid,

(lr,4r)-4-[(3R)-3-(4-{[2-fluoro-6-(trifluoromethyl)phenyl]methoxy}phenyl)-3-(4-fluorobenzenesulfonyl)pynOlidine-l-carbonyl]cyclohexane-l-carboxylic acid,

4-[(3R)-3-(4-{[2-fluoro-6-(trifluoromethyl)phenyl]methoxy}phenyl)-3-(4-fluorobenzenesulfonyl)pynOlidine- 1 -carbonyl] -4-hydroxy- 1 //’-thiane- 1 , 1 -dione,

(lr,4r)-4-[(3R)-3-(4-{[2-fluoro-6-(trifluoromethyl)phenyl]methoxy}phenyl)-3-(4-fluorobenzenesulfonyl)pynOlidine-l-carbonyl]cyclohexane-l-carboxamide,

(lr,4r)-4-[(3R)-3-(4-{[2-chloro-6-(trifluoromethyl)phenyl]methoxy}phenyl)-3-(4-fluorobenzenesulfonyl)pyrrolidine- 1 -carbonyl]cyclohexane- 1 -carboxamide,

4-[(3R)-3-(4-{[2-chloro-6-(trifluoromethyl)phenyl]methoxy}phenyl)-3-(4-fluorobenzenesulfonyl)pynOlidine- 1 -carbonyl] -4-hydroxy- 1 //’-thiane- 1 , 1 -dione, (lr,4r)-4-[(3R)-3-(4-{[2-chloro-6-(trifluoromethyl)phenyl]methoxy}phenyl)-3-(4-fluorobenzenesulfonyl)pyrrolidine- 1 -carbonyl ]cy cl ohexane- 1 -carboxylic acid

or a pharmaceutically acceptable salt thereof.

9. A compound which is

l-[l-(4-fluorobenzenesulfonyl)cyclopentyl]-4-(2-phenylethoxy)benzene, (4)

1 -[ 1 -(benzenesulfonyl)cyclopentyl]-4-(cyclohexylmethoxy)benzene, (10) l-[l-(benzenesulfonyl)cyclopentyl]-4-(2-cyclopropylethoxy)benzene, (14) 4-[(3R)-3-(4-fluorobenzenesulfonyl)-3-{4-[(lS)-l-phenylethoxyjphenyl (pyrrolidine- 1 -carbonyl]- 1 /f-thiane- 1 , 1 -dione, (37)

or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition comprising one or more compounds according to claim 1 or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers, diluents or excipients.