IP Library › Granted Patent US 7,632,832

Granted Patent B2

US 7,632,832 · App. 11/795,678 · Granted Dec 15, 2009

CGRP receptor antagonists

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Patent No.: US 7,632,832
App. No.: 11/795,678
Granted: Dec 15, 2009
Kind: B2

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Abstract

Compounds of Formula I: (where variables R1, R2, R3, R7, G, J, Q, T, W, X and Y are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache, and pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

Claims (441)

1. A compound of Formula I:

wherein:

R1is selected from:

1) H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3-6 cycloalkyl, and heterocycle, unsubstituted or substituted with one or more substituents independently selected from:

a) C 1-6 alkyl,

b) C 3-6 cycloalkyl,

c) aryl, unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from R 4 ,

d) heteroaryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

e) heterocycle, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

f) (F) p C 1-3 alkyl,

g) halogen,

h) OR 4 ,

i) O(CH 2 ) s OR 4 ,

j) CO 2 R 4 ,

k) (CO)NR 10 R 11 ,

l) O(CO)NR 10 R 11 ,

m) N(R 4 )(CO)NR 10 R 11 ,

n) N(R 10 )(CO)R 11 ,

o) N(R 10 )(CO)OR 11 ,

p) SO 2 NR 10 R 11 ,

q) N(R 10 )SO 2 R 11 ,

r) S(O) m R 10 ,

s) CN,

t) NR 10 R 11 ,

u) N(R 10 )(CO)NR 4 R 11 , and

v) O(CO)R 4 ; and

2) aryl or heteroaryl, unsubstituted or substituted with one or more substituents independently selected from:

a) C 1-6 alkyl,

b) C 3-6 cycloalkyl,

c) aryl, unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from R 4 ,

d) heteroaryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

e) heterocycle, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

f) (F) p C 1-3 alkyl,

g) halogen,

h) OR 4 ,

i) O(CH 2 ) s OR 4 ,

j) CO 2 R 4 ,

k) (CO)NR 10 R 11 ,

l) O(CO)NR 10 R 11 ,

m) N(R 4 )(CO)NR 10 R 11 ,

n) N(R 10 )(CO)R 11 ,

o) N(R 10 )(CO)OR 11 ,

p) SO 2 NR 10 R 11 ,

q) N(R 10 )SO 2 R 11 ,

r) S(O) m R 10 ,

s) CN,

t) NR 10 R 11 ,

u) N(R 10 )(CO)NR 4 R 11 , and

v) O(CO)R 4 ; and

R 2 is independently selected from H and:

1) C 1-6 alkyl,

2) C 3-6 cycloalkyl,

3) aryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

4) heteroaryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

5) heterocycle, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

6) (F) p C 1-3 alkyl,

7) halogen,

8) OR 4 ,

9) O(CH 2 ) s OR 4 ,

10) CO 2 R 4 ,

11) (CO)NR 10 R 11 ,

12) O(CO)NR 10 R 11 ,

13) N(R 4 )(CO)NR 10 R 11 ,

14) N(R 10 )(CO)R 11 ,

15) N(R 10 )(CO)OR 11 ,

16) SO 2 NR 10 R 11 ,

17) N(R 10 ) SO 2 R 11 ,

18) S(O) m R 10 ,

19) CN,

20) NR 10 R 11 ,

21) N(R 10 )(CO)NR 4 R 11 , and

22) O(CO)R 4 ;

R 7 is selected from:

1) H, C 0 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3-6 cycloalkyl and heterocycle, unsubstituted or substituted with one or more substituents independently selected from:

a) C 1-6 alkyl,

b) C 3-6 cycloalkyl,

c) aryl, unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from R 4 ,

d) heteroaryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

e) heterocycle, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

f) (F) p C 1-3 alkyl,

g) halogen,

h) OR 4 ,

i) O(CH 2 ) s OR 4 ,

j) CO 2 R 4 ,

k) (CO)NR 10 R 11 ,

l) O(CO)NR 10 R 11 ,

m) N(R 4 )(CO)NR 10 R 11 ,

n) N(R 10 )(CO)R 11 ,

o) N(R 10 )(CO)OR 11 ,

p) SO 2 NR 10 R 11 ,

q) N(R 10 ) SO 2 R 11 ,

r) S(O) m R 10 ,

s) CN,

t) NR 10 R 11 ,

u) N(R 10 )(CO)NR 4 R 11 ,

v) O(CO)R 4 ; and

2) aryl or heteroaryl, unsubstituted or substituted with one or more substituents independently selected from:

a) C 1-6 alkyl,

b) C 3-6 cycloalkyl,

c) aryl, unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from R 4 ,

d) heteroaryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

e) heterocycle, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

f) (F) p C 1-3 alkyl,

g) halogen,

h) OR 4 ,

i) O(CH 2 ) s OR 4 ,

j) CO 2 R 4 ,

k) (CO)NR 10 R 11 ,

l) O(CO)NR 10 R 11 ,

m) N(R 4 )(CO)NR 10 R 11 ,

n) N(R 10 )(CO)R 11 ,

o) N(R 10 )(CO)OR 11 ,

p) SO 2 NR 10 R 11 ,

q) N(R 10 ) SO 2 R 11 ,

r) S(O) m R 10 ,

s) CN,

t) NR 10 R 11 ,

u) N(R 10 )(CO)NR 4 R 11 , and

v) O(CO)R 4 ;

R 10 and R 11 are independently selected from: H, C 1-6 alkyl, (F)pC 1-6 alkyl, C 3-6 cycloalkyl, aryl, heteroaryl, and benzyl, unsubstituted or substituted with halogen, hydroxy or C 1 -C 6 alkoxy, where R 10 and R 11 may be joined together to form a ring selected from: azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, which is unsubstituted or substituted with 1-5 substituents independently selected from R 4 ;

R 4 is independently selected from: H, C 1-6 alkyl, (F) p C 1-6 alkyl, C 3-6 cycloalkyl, aryl, heteroaryl and benzyl, unsubstituted or substituted with halogen, hydroxy or C 1 -C 6 alkoxy;

W is O, NR 4 or C(R 4 ) 2 ;

X is C or S;

Y is O, (R4) 2 , NCN, NSO 2 CH 3 or NCONH 2 , or Y is O 2 when X is S;

R5 is independently selected from H and:

1) C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3-6 cycloalkyl and heterocycle, unsubstituted or substituted with one or more substituents independently selected from:

a) C 1-6 alkyl,

b) C 3-6 cycloalkyl,

c) aryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

d) heteroaryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

e) heterocycle, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

f) (F) p C 1-3 alkyl,

g) halogen,

h) OR 4 ,

i) O(CH 2 ) s OR 4 ,

j) CO 2 R 4 ,

k) (CO)NR 10 R 11 ,

l) O(CO)NR 10 R 11 ,

m) N(R 4 )(CO)NR 10 R 11 ,

n) N(R 10 )(CO)R 11 ,

o) N(R 10 )(CO)OR 11 ,

p) SO 2 NR 10 R 11 ,

q) N(R 10 ) SO 2 R 11 ,

r) S(O) m R 10 ,

s) CN,

t) NR 10 R 11 ,

u) N(R 10 )(CO)NR 4 R 11 , and,

v) O(CO)R 4 ;

2) aryl or heteroaryl, unsubstituted or substituted with one or more substituents independently selected from:

a) C 1-6 alkyl,

b) C 3-6 cycloalkyl,

c) aryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

d) heteroaryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

e) heterocycle, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

f) (F) p C 1-3 alkyl,

g) halogen,

h) OR 4 ,

i) O(CH 2 ) s OR 4 ,

j) CO 2 R 4 ,

k) (CO)NR 10 R 11 ,

l) O(CO)NR 10 R 11 ,

m) N(R 4 )(CO)NR 10 R 11 ,

n) N(R 10 )(CO)R 11 ,

o) N(R 10 )(CO)OR 11 ,

p) SO 2 NR 10 R 11 ,

q) N(R 10 ) SO 2 R 11 ,

r) S(O) m R 10 ,

s) CN,

t) NR 10 R 11 ,

u) N(R 10 )(CO)NR 4 R 11 , and

v) O(CO)R 4 ;

3) C 1-6 alkyl,

4) C 3-6 cycloalkyl,

5) heterocycle, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

6) (F) p C 1-3 alkyl,

7) halogen,

8) OR 4 ,

9) O(CH 2 ) s OR 4 ,

10) CO 2 R 4 ,

11) (CO)NR 10 R 11 ,

12) O(CO)NR 10 R 11 ,

13) N(R 4 )(CO)NR 10 R 11 ,

14) N(R 10 )(CO)R 11 ,

15) N(R 10 )(CO)OR 11 ,

16) SO 2 NR 10 R 11 ,

17) N(R 10 ) SO 2 R 11 ,

18) S(O)mR 10 ,

19) CN,

20) NR 10 R 11 ,

21) N(R 10 )(CO)NR 4 R 11 , and,

22) O(CO)R 4 ,

or two R 5 attached to the same carbon form the substituent ═O, such that C(R 5 ) 2 may be C═O,

where the number of R 5 substituents that are not H, can range from zero to three;

R 6 is independently selected from: H, C 1-6 alkyl, (F) p C 1-6 alkyl, C 3-6 cycloalkyl, aryl, heteroaryl and benzyl, unsubstituted or substituted with

a) (F) p C 1-3 alkyl,

b) halogen,

c) OR 4 ,

d) O(CH 2 ) s OR 4 ,

e) CO 2 R 4 ,

f) (CO)NR 10 R 11 ,

g) O(CO)NR 10 R 11 ,

h) N(R 4 )(CO)NR 10 R 11 ,

i) N(R 10 )(CO)R 11 ,

j) N(R 10 )(CO)OR 11 ,

k) SO 2 NR 10 R 11 ,

l) N(R 10 ) SO 2 R 11 ,

m) S(O) m R 10 ,

n) CN,

o) NR 10 R 11 ,

p) N(R 10 )(CO)NR 4 R 11 , and

q) O(CO)R 4 ;

G_J is selected from: N, C(R 5 ), C═C(R 5 ), N—C(R 5 ) 2 , C═N, C(R 5 )-C(R 5 ) 2 , C(R 5 )-N(R 6 ), and N—N(R 6 );

Q-T is selected from: C(R 5 ) 2 -C(R 5 ) 2 , C(R 5 )═C(R 5 ), N═C(R 5 ), C(R 5 )═N, N═N, N(R 6 ), C(R 5 ) 2 -(C═O), N(R 6 )-(C═O), and C(R 5 ) 2 -N(R 6 );

R 3 is independently selected from H, substituted or unsubstituted C 1 -C 3 alkyl, CN, F, OR 4 and CO 2 R 4 ;

p is 0 to 2q+1, for a substituent with q carbons; m is 0, 1 or 2; s is 1, 2 or 3;

“heteroaryl” means a stable 5- to 7-membered monocyclic- or stable 9- to 10-membered fused bicyclic heterocyclic ring system which contains an aromatic ring, any ring of which may be saturated, partially saturated, or unsaturated, and which consists of carbon atoms and from one to four heteroatoms selected from the group consisting of N, O and S, and wherein the nitrogen and sulfur heteroatoms may optionally be oxidized, and the nitrogen heteroatom may optionally be quaternized, and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring;

“heterocycle” means a stable 5- to 7-membered monocyclic- or stable 8- to 11-membered bicyclic heterocyclic ring system which is either saturated or unsaturated, and which consists of carbon atoms and from one to four heteroatoms selected from the group consisting of N, O and S, and wherein the nitrogen and sulfur heteroatoms may optionally be oxidized, and the nitrogen heteroatom may optionally be quaternized, and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring;

or a pharmaceutically acceptable salt or diastereomer thereof.

2. The compound of claim 1 of the Formula Ia:

or a pharmaceutically acceptable salt or diastereomer thereof.

3. The compound of claim 1 of the Formula Ib

or a pharmaceutically acceptable salt or diastereomer thereof.

4. The compound of claim 1 , wherein:

R 1 is selected from:

1) H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3-6 cycloalkyl, and heterocycle, unsubstituted or substituted with one or more substituents independently selected from:

a) C 1-6 alkyl,

b) C 3-6 cycloalkyl,

c) aryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

d) heteroaryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

e) heterocycle, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

f) (F) p C 1-3 alkyl,

g) halogen,

h) OR 4 ,

i) O(CH) s OR 4 ,

j) COR 4 ,

k) (CO)NR 10 R 11 ,

l) O(CO)NR 10 R 11 ,

m) N(R 4 )(CO)NR 10 R 11 ,

n) N(R 10 )(CO)R 11 ,

o) N(R 10 )(CO)OR 11 ,

p) SO 2 NR 10 R 11 ,

q) N(R 10 ) SO 2 R 11 ,

r) S(O) m R 10 ,

s) CN,

t) NR 10 R 11 ,

u) N(R 10 )(CO)NR 4 R 11 , and

v) O(CO)R 4 ; and

2) aryl or heteroaryl, unsubstituted or substituted with one or more substituents independently selected from:

a) C 1-6 alkyl,

b) C3-6 cycloalkyl,

c) aryl, unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from R 4 ,

d) heteroaryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

e) heterocycle, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

f) (F) p C1-3 alkyl,

g) halogen,

h) OR 4 ,

i) O(CH 2 ) s OR 4 ,

j) CO2R 4 ,

k) (CO)NR 10 R 11 ,

l) O(CO)NR 10 R 11 ,

m) N(R 4 )(CO)NR 10 R 11 ,

n) N(R 10 )(CO)R 11 ,

o) N(R 10 )(CO)OR 11 ,

p) SO 2 NR 10 R 11 ,

q) N(R 10 ) SO 2 R 11 ,

r) S(O)Mr 10 ,

s) CN,

t) NR 10 R 11 ,

u) N(R 10 )(CO)NR 4 R 11 , and

v) O(CO)R 4 ; and

R2 is independently selected from H and:

1) C 1-6 alkyl,

2) C 3-6 cycloalkyl,

3) aryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

4) heteroaryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

5) heterocycle, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

6) (F) p C 1-3 alkyl,

7) halogen,

8) OR 4 ,

9) O(CH 2 ) s OR 4 ,

10) CO 2 R 4 ,

11) (CO)NR 10 R 11 ,

12) O(CO)NR 10 R 11 ,

13) N(R 4 )(CO)NR 10 R 11 ,

14) N(R 10 )(CO)R 11 ,

15) N(R 10 )(CO)OR 11 ,

16) SO 2 NR 10 R 11 ,

17) N(R 10 ) SO 2 R 11 ,

18) S(O) m R 10 ,

19) CN,

20) NR 10 R 11 ,

21) N(R 10 )(CO)NR 4 R 11 , and

22) O(CO)R 4 ;

R 7 is selected from:

1) H, C 0 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3-6 cycloalkyl and heterocycle, unsubstituted or substituted with one or more substituents independently selected from:

a) C 1-6 alkyl,

b) C 3-6 cycloalkyl,

c) aryl, unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from R 4 ,

d) heteroaryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

e) heterocycle, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

f) (F) p C 1-3 alkyl,

g) halogen,

h) OR 4 ,

i) O(CH 2 ) s OR 4 ,

j) CO 2 R 4 ,

k) (CO)NR 10 R 11 ,

l) O(CO)NR 10 R 11 ,

m) N(R 4 )(CO)NR 10 R 11 ,

n) N(R 10 )(CO)R 11 ,

o) N(R 10 )(CO)OR 11 ,

p) SO 2 NR 10 R 11 ,

q) N(R 10 ) SO 2 R 11 ,

r) S(O) m R 10 ,

s) CN,

t) NR 10 R 11 ,

u) N(R 10 )(CO)NR 4 R 11 ,

v) O(CO)R 4 ; and

2) aryl or heteroaryl, unsubstituted or substituted with one or more substituents independently selected from:

a) C 1-6 alkyl,

b) C 3-6 cycloalkyl,

c) aryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

d) heteroaryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

e) heterocycle, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

f) (F) p C 1-3 alkyl,

g) halogen,

h) OR 4 ,

i) O(CH 2 ) s OR 4 ,

j) CO 2 R 4 ,

k) (CO)NR 10 R 11 ,

l) O(CO)NR 10 R 11 ,

m) N(R 4 )(CO)NR 10 R 11 ,

n) N(R 10 )(CO)R 11 ,

o) N(R 10 )(CO)OR 11 ,

p) SO 2 NR 10 R 11 ,

q) N(R 10 ) SO 02 R 11 ,

r) S(O) m R 10 ,

s) CN,

t) NR 10 R 11 ,

u) N(R 10 )(CO)NR 4 R 11 , and

v) O(CO)R 4 ;

R 10 and R 11 are independently selected from: H, C 1-6 alkyl, (F)pC 1-6 alkyl, C 3-6 cycloalkyl, aryl, heteroaryl and benzyl, unsubstituted or substituted with halogen, hydroxy or C 1 -C 6 alkoxy, where R 10 and R 11 may be joined together to form a ring selected from: azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl and morpholinyl, which is unsubstituted or substituted with 1-5 substituents independently selected from R 4

R 4 is independently selected from: H, C 1-6 alkyl, (F)pC 1-6 alkyl, C 3-6 cycloalkyl, aryl, heteroaryl and benzyl, unsubstituted or substituted with halogen, hydroxy or C 1 -C 6 alkoxy;

W is O, NR 4 or C(R 4 ) 2 ;

G_J is N and Q-T is C(R 5 ) 2 -C(R 5 ) 2 , or,

G-J is N and Q-T is C(R 5 )═C(R 5 ), or,

G-J is N and Q-T is N═C(R 5 ), or,

G-J is N and Q-T is C(R 5 )═N, or,

G-J is N and Q-T is N═N, or,

G-J is C═C(R 5 ) and Q-T is N(R 6 ), or,

G-J is N and Q-T is C(R 5 ) 2 -(C═O), or,

G-J is N—C(R 5 ) 2 and Q-T is C(R 5 ) 2 -C(R 5 ) 2 , or,

G-J is C═C(R 5 ) and Q-T is C(R 5 )═C(R 5 ), or,

G-J is C═C(R 5 ) and Q-T is C(R 5 )═N, or,

G-J is C═C(R 5 ) and Q-T is N═C(R 5 ), or,

G-J is C═N and Q-T is C(R 5 )═C(R 5 ), or,

G-J is N—C(R 5 ) 2 and Q-T is C(R 5 ) 2 -(C═O), or,

G-J is C(R 5 )-C(R 5 )2 and Q-T is N(R 6 )-(C═O), or,

G-J is C(R 5 )-C(R 5 ) 2 and Q-T is C(R 5 ) 2 -C(R 5 ) 2 , or,

G-J is C(R 5 )-C(R 5 ) 2 and Q-T is C(R 5 ) 2 -N(R 6 ), or,

G-J is C(R 5 )-N(R 6 ) and Q-T is C(R 5 ) 2 -C(R 5 ) 2 , or,

G-J is C(R 5 )-C(R 5 )2 and Q-T is N═C(R 5 ), or,

G-J is N—C(R 5 ) 2 and Q-T is C(R 5 ) 2 -N(R 6 ), or,

G-J is N-N(R 6 ) and Q-T is C(R 5 ) 2 -C(R 5 ) 2 , or,

G-J is N—C(R 5 ) 2 and Q-T is N═C(R 5 );

R 5 is independently selected from H and:

1) C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3-6 cycloalkyl and heterocycle, unsubstituted or substituted with one or more substituents independently selected from:

a) C 1-6 alkyl,

b) C 3-6 cycloalkyl,

c) aryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

d) heteroaryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

e) heterocycle, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

f) (F) p C 1-3 alkyl,

g) halogen,

h) OR 4 ,

i) O(CH 2 ) s OR 4 ,

j) CO 2 R 4 ,

k) (CO)NR 10 R 11 ,

l) O(CO)NR 10 R 11 ,

m) N(R 4 )(CO)NR 10 R 11 ,

n) N(R 10 )(CO)R 11 ,

o) N(R 10 )(CO)OR 11 ,

p) SO 2 NR 10 R 11 ,

q) N(R 10 ) SO 2 R 11 ,

r) S(O) m R 10 ,

s) CN,

t) NR 10 R 11 ,

u) N(R 10 )(CO)NR 4 R 11 , and,

v) O(CO)R 4 ;

2) aryl or heteroaryl, unsubstituted or substituted with one or more substituents independently selected from:

a) C 1-6 alkyl,

b) C 3-6 cycloalkyl,

c) aryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

d) heteroaryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

e) heterocycle, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

f) (F) p C 1-3 alkyl,

g) halogen,

h) OR 4 ,

i) O(CH 2 ) s OR 4 ,

j) CO 2 R 4 ,

k) (CO)NR 10 R 11 ,

l) O(CO)NR 10 R 11 ,

m) N(R 4 )(CO)NR 10 R 11 ,

n) N(R 10 )(CO)R 11 ,

o) N(R 10 )(CO)OR 11 ,

p) SO 2 NR 10 R 11 ,

q) N(R 10 ) SO 2 R 11 ,

r) S(O) m R 10 ,

s) CN,

t) NR 10 R 11 ,

u) N(R 10 )(CO)NR 4 R 11 , and

v) O(CO)R 4 ;

3) C 1-6 alkyl,

4) C 3-6 cycloalkyl,

5) aryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

6) heteroaryl, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

7) heterocycle, unsubstituted or substituted with 1-5 substituents independently selected from R 4 ,

8) (F) p C 1-3 alkyl,

9) halogen,

10) OR 4 ,

11) O(CH 2 ) s OR 4 ,

12) CO 2 R 4 ,

13) (CO)NR 10 R 11 ,

14) O(CO)NR 10 R 11 ,

15) N(R 4 )(CO)NR 10 R 11 ,

16) N(R 10 )(CO)R 11 ,

17) N(R 10 )(CO)OR 11 ,

18) SO 2 NR 10 R 11 ,

19) N(R 10 ) SO 2 R 11 ,

20) S(O)mR 10 ,

21) CN,

22) NR 10 R 11 ,

23) N(R 10 )(CO)NR 4 R 11 , and

24) O(CO)R 4 ,

or two R 5 attached to the same carbon form the substituent ═O, such that C(R 5 )2 may be C═O,

where the number of R 5 substituents that are not H, can range from zero to three;

R 3 is independently selected from H, substituted or unsubstituted C 1 -C 3 alkyl, CN and CO 2 R 4 ;

p is 0 to 2q+1, for a substituent with q carbons; m is 0 to 2; s is 1 to 3;

or a pharmaceutical acceptable salt or diasteromer thereof.

5. A compound selected from:

or a pharmaceutically acceptable salt or diastereomer thereof.

6. A pharmaceutical composition which comprises an inert carrier and the compound of claim 1 .

Assignments (5)

MERGER Recorded Aug 8, 2022

From: MERCK SHARP & DOHME CORP.

To: MERCK SHARP & DOHME LLC

Reel/Frame 061102/0145 →

CHANGE OF NAME Recorded Aug 29, 2012

From: SCHERING CORPORATION

To: MERCK SHARP & DOHME CORP.

Reel/Frame 028866/0511 →

MERGER Recorded Aug 27, 2012

From: MERCK SHARP & DOHME CORP.

To: SCHERING CORPORATION

Reel/Frame 028850/0515 →

CHANGE OF NAME Recorded Jan 26, 2010

From: MERCK & CO., INC.

To: MERCK SHARP & DOHME CORP.

Reel/Frame 023906/0803 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 30, 2008

From: BURGEY, CHRISTOPHER S.; WILLIAMS, THERESA M.; DENG, ZHENGWU J.; STUMP, CRAIG A.

To: MERCK & CO., INC.

Reel/Frame 021319/0555 →