Heterocyclic benzodiazepine CGRP receptor antagonists
View Patent ↗Compounds of formula I: (where variables R 2 , R 7 , D, W, X, Y and Z are as described herein) which are antagonists of CGRP receptors and which are useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. 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.
1. A compound of the Formula I:
wherein:
Z is selected from:
D is independently selected from N and C(R 1 );
R 1 is independently 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 each independently selected from:
a) C 1-6 alkyl,
b) C 3-6 cycloalkyl,
c) aryl, unsubstituted or substituted with 1-5 substituents each independently selected from R 4 ,
d) heteroaryl, unsubstituted or substituted with 1-5 substituents each independently selected from R 4 ,
e) heterocycle, unsubstituted or substituted with 1-5 substituents each 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 each independently selected from:
a) C 1-6 alkyl,
b) C 3-6 cycloalkyl,
c) aryl, unsubstituted or substituted with 1-5 substituents each independently selected from R 4 ,
d) heteroaryl, unsubstituted or substituted with 1-5 substituents each independently selected from R 4 ,
e) heterocycle, unsubstituted or substituted with 1-5 substituents each 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 ;
where any two independent R 1 and the atom or atoms to which they are attached optionally join to form a ring selected from C 3-6 cycloalkyl, aryl, heterocycle, and heteroaryl;
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 where the substituents are independently selected from R 4 ,
4) heteroaryl, unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from R 4 ,
5) heterocycle, unsubstituted or substituted with 1-5 substituents where the substituents are 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 ;
where any two independent R 2 on the same or adjacent atoms optionally join 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 7 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 ,
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 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 ;
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;
M is —NH— or is a bond;
K is —CH 2 — or is a bond;
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 or 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 each independently selected from R 4 ,
e) heterocycle, unsubstituted or substituted with 1-5 substituents each 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 ;
J is a bond, C(R 6 ) 2 , O or NR 6 ;
V is selected from a bond, C(R 6 ) 2 , O, S(O) m , NR 6 , C(R 6 ) 2 —C(R 6 ) 2 , C(R 6 )═C(R 6 ), C(R 6 ) 2 —N(R 6 ), C(R 6 )═N,N(R 6 )—C(R 6 ) 2 , N═C(R 6 ), and N(R 6 )—N(R 6 );
G-L is selected from: N, N—C(R 6 ) 2 , C═C(R 6 ), C═N, C(R 6 ), C(R 6 )—C(R 6 ) 2 , C(R 6 )—C(R 6 ) 2 —C(R 6 ) 2 , C═C(R 6 )—C(R 6 ) 2 , C(R 6 )—C(R 6 )═C(R 6 ), C(R 6 )—C(R 6 ) 2 —N(R 6 ), C═C(R 6 )—N(R 6 ), C(R 6 )—C(R 6 )═N, C(R 6 )—N(R 6 )—C(R 6 ) 2 , C═N—C(R 6 ) 2 , C(R 6 )—N═C(R 6 ), C(R 6 )—N(R 6 )—N(R 6 ), C═N—N(R 6 ), N—C(R 6 ) 2 —C(R 6 ) 2 , N—C(R 6 )═C(R 6 ), N—C(R 6 ) 2 —N(R 6 ), N—C(R 6 )═N, N—N(R 6 )—C(R 6 ) 2 and N—N═C(R 6 );
Q is independently selected from:
(1) ═C(R 7a )—,
(2) —C(R 7a ) 2 —,
(3) —C(═O)—,
(4) —S(O) m —,
(5) ═N—,
(6) —N(R 7a )—, and,
(7) a bond;
T is independently selected from:
(1) ═C(R 7b )—,
(2) —C(R 7b ) 2 —,
(3) —C(═O)—,
(4) —S(O) m —,
(5) ═N—,
(6) —N(R 7b )—, and
(7) a bond;
R 3 is independently selected from H, substituted or unsubstituted C 1 -C 3 alkyl, F, CN and CO 2 R 4 ;
R 7a and R 7b are each independently selected from R 2 , where R 7a and R 7b and the atom or atoms to which they are attached optionally join to form a ring selected from C 3-6 cycloalkyl, aryl, heterocycle, and heteroaryl, which ring is unsubstituted or substituted with 1-10 substituents each independently selected from R 6 ;
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 optionally join to form a ring selected from: azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, which is ring is unsubstituted or substituted with 1-5 substituents each independently selected from 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;
the dashed line indicates the optional presence of a double bond;
and pharmaceutically acceptable salts and individual diastereomers thereof.
2. A compound of the Formula Ib:
wherein:
D is independently selected from N and C(R 1 );
R 1 is independently 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 each independently selected from:
a) C 1-6 alkyl,
b) C 3-6 cycloalkyl,
c) aryl, unsubstituted or substituted with 1-5 substituents each independently selected from R 4 ,
d) heteroaryl, unsubstituted or substituted with 1-5 substituents each independently selected from R 4 ,
e) heterocycle, unsubstituted or substituted with 1-5 substituents each 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 each independently selected from:
a) C 1-6 alkyl,
b) C 3-6 cycloalkyl,
c) aryl, unsubstituted or substituted with 1-5 substituents each independently selected from R 4 ,
d) heteroaryl, unsubstituted or substituted with 1-5 substituents each independently selected from R 4 ,
e) heterocycle, unsubstituted or substituted with 1-5 substituents each 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 ;
where any two independent R 1 and the atom or atoms to which they are attached optionally join to form a ring selected from C 3-6 cycloalkyl, aryl, heterocycle, and heteroaryl;
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 where the substituents are independently selected from R 4 ,
4) heteroaryl, unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from R 4 ,
5) heterocycle, unsubstituted or substituted with 1-5 substituents where the substituents are 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 ;
where any two independent R 2 on the same or adjacent atoms optionally join 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 7 is selected from:
1) aryl 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 ;
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;
Q is independently selected from:
(1) ═C(R 7a )—,
(2) —C(R 7a ) 2 —,
(3) —C(═O)—,
(4) —S(O) m —,
(5) ═N—, and
(6) —N(R 7a )—;
T is independently selected from:
(1) ═C(R 7b )—,
(2) —C(R 7b ) 2 —,
(3) —C(═O)—,
(4) —S(O) m —,
(5) ═N—, and
(6) —N(R 7b )—;
R 3 is independently selected from H, substituted or unsubstituted C 1 -C 3 alkyl, F, CN and CO 2 R 4 ;
R 7a and R 7b are each independently selected from R 2 , where R 7a and R 7b and the atom or atoms to which they are attached optionally join to form a ring selected from C 3-6 cycloalkyl, aryl, heterocycle, and heteroaryl, which ring is unsubstituted or substituted with 1-10 substituents each independently selected from R 6 ;
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 optionally join to form a ring selected from: azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, which is ring is unsubstituted or substituted with 1-5 substituents each independently selected from 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;
and pharmaceutically acceptable salts and individual diastereomers thereof.
3. A compound of the Formula Ic:
wherein:
D is independently selected from N and C(R 1 );
R 1 is independently 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 each independently selected from:
a) C 1-6 alkyl,
b) C 3-6 cycloalkyl,
c) aryl, unsubstituted or substituted with 1-5 substituents each independently selected from R 4 ,
d) heteroaryl, unsubstituted or substituted with 1-5 substituents each independently selected from R 4 ,
e) heterocycle, unsubstituted or substituted with 1-5 substituents each 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 each independently selected from:
a) C 1-6 alkyl,
b) C 3-6 cycloalkyl,
c) aryl, unsubstituted or substituted with 1-5 substituents each independently selected from R 4 ,
d) heteroaryl, unsubstituted or substituted with 1-5 substituents each independently selected from R 4 ,
e) heterocycle, unsubstituted or substituted with 1-5 substituents each 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 ;
where any two independent R 1 and the atom or atoms to which they are attached optionally join to form a ring selected from C 3-6 cycloalkyl, aryl, heterocycle, and heteroaryl;
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;
Q is independently selected from:
(1) ═C(R 7a )—,
(2) —C(R 7a ) 2 —,
(3) —C(═O)—,
(4) —S(O) m —,
(5) ═N—, and
(6) —N(R 7a )—;
T is independently selected from:
(1) ═C(R 7b )—,
(2) —C(R 7b ) 2 —,
(3) —C(═O)—,
(4) —S(O) m —,
(5) ═N—, and
(6) —N(R 7b )—;
R 7a and R 7a are each independently selected from R 2 , where R 7a and R 7a and the atom or atoms to which they are attached optionally join to form a ring selected from C 3-6 cycloalkyl, aryl, heterocycle, and heteroaryl, which ring is unsubstituted or substituted with 1-10 substituents each independently selected from R 6 ;
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 optionally join to form a ring selected from: azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, which is ring is unsubstituted or substituted with 1-5 substituents each independently selected from 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;
and pharmaceutically acceptable salts and individual diastereomers thereof.
4. The compound of claim 1 , wherein J is a bond, V is a bond and Z is Z1.
5. The compound of claim 1 , wherein J is a bond, V is a bond, Z is Z1 and T is —C(═O)—.
6. The compound of claim 1 , wherein G-L is N, and Z is Z2.
7. The compound of claim 1 , wherein G-L is N—C(R 6 ) 2 , and Z is Z2.
8. The compound of claim 1 , wherein G-L is C═C(R 6 ), and Z is Z2.
9. The compound of claim 1 , wherein G-L is C═N, and Z is Z2.
10. The compound of claim 1 , wherein G-L is N—C(R 6 ) 2 —C(R 6 ) 2 and Z is Z2.
11. The compound of claim 1 , wherein J is a bond, V is a bond, Z is Z1, Q is —N(R 7a )—, and T is —C(═O)—.
12. The compound of claim 1 , wherein J is a bond, V is a bond, Z is Z1, Q is —C(R 7a ) 2 —, and T is —C(═O)—.
13. The compound of claim 1 , wherein J is a bond, Visa bond, Z is Z1, Q is —N═, and T is ═C(R 7a )—.
14. The compound of claim 1 , wherein J is a bond, V is a bond, Z is Z1, Q is —C(R 7a ) 2 —, and T is —C(R 7b ) 2 —.
15. The compound of claim 1 , wherein J is a bond, Visa bond, Z is Z1, Q is —C(R 7a )═, T is ═C(R 7b )—, and the atoms to which R 7a and R 7b are attached are joined together to form a benzene, pyridine, or diazine ring.
16. The compound of claim 1 , wherein J is a bond, V is C(R 6 ) 2 , Z is Z1, Q is —C(R 7a )═, T is ═C(R 7b )—, and the atoms to which R 7a and R 7b are attached are joined together to form a benzene or pyridine ring.
17. A compound of claim 1 which is selected from:
and pharmaceutically acceptable salts and individual stereoisomers thereof.
18. A pharmaceutical composition which comprises an inert carrier and the compound of claim 1 .