IP Library › Granted Patent US 6,953,790

Granted Patent B2

US 6,953,790 · App. 10/838,835 · Granted Oct 11, 2005

CGRP receptor antagonists

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Quick Facts

Patent No.: US 6,953,790
App. No.: 10/838,835
Granted: Oct 11, 2005
Kind: B2

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Abstract

The present invention is directed to compounds of Formula I: and Formula II: (where variables R 1 , R 2 , R 3 , R 4 , A, B, G, J, Q, T, U, V, 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. The invention is also directed to 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 (536)

1. A compound of the Formula I:

wherein:

A is a C(R 2 ) 2 ;

B is C(R 2 ) 2 ;

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 where the substituents are independently selected from R 4 ,

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

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

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

e) heterocycle, unsubstituted or substituted with 1-5 substituents where the substituents are 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,

t) O(CO)R 4 ;

R 2 is independently 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 where the substituents are independently selected from R 4 ,

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

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

e) heterocycle, unsubstituted or substituted with 1-5 substituents where the substituents are 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 ,

or, any two independent R 2 on the same or adjacent atoms may be joined together to form a ring selected from cyclobutyl, cyclopentenyl, cyclopentyl, cyclohexenyl, cyclohexyl, phenyl, naphthyl, thienyl, thiazolyl, thiazolinyl, oxazolyl, oxazolinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, pyrimidyl, pyrazinyl, pyrrolyl, pyrrolinyl, morpholinyl, thiomorpholine, thiomorpholine S-oxide, thiomorpholine S-dioxide, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyridyl, furanyl, dihydrofuranyl, dihydropyranyl and piperazinyl;

R 10 and R 11 are 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, 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 where the substituents are 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, (R 4 ) 2 , NCN, NSO 2 CH 3 , NCONH 2 , or Y is O 2 when X is S;

R 6 is independently selected from H and:

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 where the substituents are independently selected from R 4 ,

e) heterocycle, unsubstituted or substituted with 1-5 substituents where the substituents are 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 ;

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

Q, T, U and V are each independently carbon or nitrogen wherein at least one but no more than three of Q, T, U and V are nitrogen, of which one may be optionally an N-oxide, and wherein when any of Q, T, U, or V is carbon it is unsubstituted or substituted where the substituents are independently selected from R 6 ;

R 5 is independently selected from H, substituted or unsubstituted C 1 -C 3 alkyl, CN, OR 4 , N(R 4 ) 2 and CO 2 R 4 ;

R 3 is independently selected from H, substituted or unsubstituted C 1 -C 3 alkyl, F, CN 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;

or a pharmaceutically acceptable salt or individual diastereomers thereof.

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

wherein:

A is C(R 2 ) 2 ;

B is (C(R 2 ) 2 ;

Y is O or NCN;

or a pharmaceutically acceptable salt or individual diastereomers thereof.

3. The compound of claim 1 of the Formula Ib:

wherein:

A is C(R 2 ) 2 ;

B is (C(R 2 ) 2 ;

or a pharmaceutically acceptable salt or individual diastereomers thereof.

4. The compound of claim 1 of the Formula Ie:

wherein:

A is C(R 2 ) 2 ;

or a pharmaceutically acceptable salt or individual diastereomers thereof.

5. The compound of claim 1 , wherein:

R 1 is selected from:

1) H, C 1 -C 6 alkyl, 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 where the substituents are independently selected from R 4 ,

e) heterocycle, unsubstituted or substituted with 1-5 substituents where the substituents are 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) CN,

l) NR 10 R 11 , and

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

d) halogen,

e) OR 4 ,

f) CO 2 R 4 ,

g) (CO)NR 10 R 11 ,

h) SO 2 NR 10 R 11 ,

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

j) S(O) m R 4 ,

k) CN and

l) NR 10 R 11 , and

m) O(CO)R 4 ; and

R 2 is selected from:

1) H, C 1 -C 6 alkyl, 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 sustituents where the substituents are independently selected from R 4 ,

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

e) heterocycle, unsubstituted or substituted with 1-5 substituents where the substituents are 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) S(O) m R 4 ,

l) CN,

m) NR 10 R 11 , and

n) O(CO)R 4 ; and

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

a) C 1-6 alkyl,

b) C 3-6 cycloalkyl,

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

d) halogen,

e) OR 4 ,

f) CO 2 R 4 ,

g) (CO)NR 10 R 11 ,

h) SO 2 NR 10 R 11 ,

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

j) S(O) m R 4 ,

k) CN,

l) NR 10 R 11 ,

m) O(CO)R 4 ,

G-J is selected from:

N, N—C(R 5 ) 2 , C═C(R 5 ), C═N, C═C(R 5 )—C(R 5 ), C(R 5 )—C(R 5 )═C(R 5 ), N—C(R 5 ) 2 —C(R 5 ) 2 and N—C(R 5 )═C(R 5 );

R 6 is independently selected from H and:

a) C 1-6 alkyl,

b) C 3-6 cycloalkyl,

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

d) halogen,

e) OR 4 ,

f) CO 2 R 4 ,

g) (CO)NR 10 R 11 ,

h) SO 2 NR 10 R 11 ,

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

j) S(O) m R 4 ,

k) CN,

l) NR 10 R 11 , and

m) O(CO)R 4 ;

or a pharmaceutically acceptable salt or individual diastereomers thereof.

6. The compound of claim 5 of the Formula Ia:

wherein:

A is C(R 2 ) 2 ;

B is (C(R 2 ) 2 ;

Y is O or NCN;

or a pharmaceutically acceptable salt or individual diastereomers thereof.

7. The compound of claim 5 of the Formula Ib:

wherein:

A is C(R 2 ) 2 ;

B is (C(R 2 ) 2 ;

or a pharmaceutically acceptable salt or individual diastereomers thereof.

8. The compound of claim 5 of the Formula Ie:

wherein:

A is C(R 2 ) 2 ;

or a pharmaceutically acceptable salt or individual diastereomers thereof.

9. The compound of claim 1 , wherein:

R 1 is selected from:

1) H, C 1 -C 6 alkyl, 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) phenyl, 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 where the substituents are independently selected from R 4 , and where heteroaryl is selected from:

imidazole, isoxazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, and thiazole;

e) heterocycle, unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from R 4 , and where heterocycle is selected from:

azetidine, dioxane, dioxolane, morpholine, oxetane, piperazine, piperidine, pyrrolidine, tetrahydrofuran, and tetrahydropyran;

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) CN, and

l) NR 10 R 11 ; and

2) aryl or heteroaryl, selected from:

phenyl, imidazole, isoxazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, and thiazole; unsubstituted or substituted with one or more substituents independently selected from:

a) C 1-6 alkyl,

b) C 3-6 cycloalkyl,

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

d) halogen,

e) OR 4 ,

f) CO 2 R 4 ,

g) (CO)NR 10 R 11 ,

h) SO 2 NR 10 R 11 ,

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

j) S(O) m R 4 ,

k) CN and

l) NR 10 R 11 ;

R 2 is selected from:

1) H, C 0 -C 6 alkyl, 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) phenyl, 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 where the substituents are independently selected from R 4 , and where heteroaryl is selected from:

benzimidazole, benzothiophene, furan, imidazole, indole, isoxazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, and triazole;

e) heterocycle, unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from R 4 , and where heterocycle is selected from:

azetidine, imidazolidine, imidazoline, isoxazoline, isoxazolidine, morpholine, oxazoline, oxazolidine, oxetane, pyrazolidine, pyrazoline, pyrroline, tetrahydrofuran, tetrahydropyran, thiazoline, and thiazolidine;

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) CN, and

l) NR 10 R 11 ; and

2) aryl or heteroaryl, selected from:

phenyl, benzimidazole, benzothiophene, furan, imidazole, indole, isoxazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, and triazole;

unsubstituted or substituted with one or more substituents independently selected from:

a) C 1-6 alkyl,

b) C 3-6 cycloalkyl,

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

d) halogen,

e) OR 4 ,

f) CO 2 R 4 ,

g) (CO)NR 10 R 11 ,

h) SO 2 NR 10 R 11 ,

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

j) S(O) m R 4 ,

k) CN and

l) NR 10 R 11 ,

R 10 and R 11 are 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, 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 where the substituents are 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 phenyl, unsubstituted or substituted with hydroxy or C 1 -C 6 alkoxy;

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

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

R 6 is independently selected from H and:

a) C 1-6 alkyl,

b) C 3-6 cycloalkyl,

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

d) halogen,

e) OR 4 ,

f) CO 2 R 4 ,

g) (CO)NR 10 R 11 ,

h) SO 2 NR 10 R 11 ,

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

j) S(O) m R 4 ,

k) CN and

l) NR 10 R 11 ;

or a pharmaceutically acceptable salt or individual diastereomers thereof.

10. The compound of claim 9 of the Formula Ia:

or a pharmaceutically acceptable salt or individual diastereomers thereof.

11. The compound of claim 9 of the Formula Ib:

or a pharmaceutically acceptable salt or individual diastereomers thereof.

12. The compound of claim 9 of the Formula Ie:

or a pharmaceutically acceptable salt or individual diastereomers thereof.

13. A compound selected from:

or a pharmaceutically acceptable salt or individual diastereomers thereof.

14. A compound of the formula:

wherein the configuration of the C-3 carbon, the configuration of the C-6 carbon, and R 1 are selected from a single row in the following table:

C-3

C-6

R 1

CH 3

CH 2 CH 3

CH 2 CF 3

CH 2 CO 2 CH 3

CH 2 CO 2 H

(CH 2 ) 2 OCH 2 CH 3

CH 2 CN

(CH 2 ) 2 OH

CH 2 CH 2 F

CH 2 CHF 2

CH 2 CHCF 2

(CH 2 ) 2 OCF 3

or a pharmaceutically acceptable salt or individual diastereomers thereof.

15. A compound of the formula:

wherein the configuration of the C-6 carbon, and R 1 and R 2 are selected from a single row in the following table:

C-6

R 1

R 2

R or S

CH 2 CH 2 F

CH 2 CH 2 OMe

R or S

CH 2 CF 3

or a pharmaceutically acceptable salt or individual diastereomers thereof.

16. A compound of the formula:

wherein the configuration of the C-3 carbon, the configuration of the C-6 carbon, and R 1 are selected from a single row in the following table:

C-3

C-6

R 1

or a pharmaceutically acceptable salt or individual diastereomers thereof.

17. A compound of the formula:

wherein R is selected from:

CH 3 ,

CH 2 CH 2 SO 2 CH 3 ,

CH 2 CH 3 ,

CH 2 CH 2 F,

CH 2 CHF 2 ,

CH 2 CO 2 CH(CH 3 ) 2 ,

CH 2 CH 2 OH,

CH 2 CO 2 CH 3 ,

CH 2 CH 2 CF 3 ,

CH(CH 3 ) 2 ,

CH 2 CO 2 H, and

or a pharmaceutically acceptable salt or individual diastereomers thereof.

18. A compound of the formula:

wherein R is selected from:

CH 3 ,

CH 2 CH 2 SOCH 3 ,

CH 2 CH 2 SCH 3 ,

CH 2 CH 2 SO 2 CH 3 ,

CH 2 CHF 2 ,

CH 2 CH 2 OCH 3 ,

CH 2 CH 2 OCF 3 , and

CH 2 CH 2 OH,

or a pharmaceutically acceptable salt or individual diastereomers thereof.

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

20. A pharmaceutical composition which comprises an inert carrier and the compound of claim 13 .

21. A method of treating migraine headaches, cluster headaches, and headaches, said method comprising the administration, to a person in need of such treatment, of a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.

22. A method of treating migraine headaches, cluster headaches, and headaches, said method comprising the administration, to a person in need of such treatment, of a therapeutically effective amount of the compound of claim 13 or a pharmaceutically acceptable salt thereof.

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