Macrocyclic urea orexin receptor agonists

1 . A compound of the formula I:

wherein:

A is N or C(R 8 ) n ;

D is N or C(R 8 ) n ;

E is N or C(R 8 ) n ;

G is N or C(R 8 ) n ;

J is Nor C(R 8 ) n ;

W is N or C(R 8 ) n ;

when J is N, m is 1 but when J is C(R 8 ) n , m is 1 or 2;

n is 0 or 1;

X is —O— or —CH 2 —;

Y is phenyl, pyridyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyridofuranyl, oxazolyl, thiazolyl, which is unsubstituted or substituted with one to three groups selected from R 4 ;

Z is

R is independently selected from H or C 1-6 alkyl;

R 1 is selected from:

1) Hydrogen,

2) CN,

3) —C(O)NR 2 —,

4) —CH 2 OCH 2 CF 3 —,

5) —CH 2 OCH 2 CHCF 2 —, and

6) C 1-6 alkyl, which is substituted with 0, 1, or 3 independently selected from:

a) C 1-6 alkyl,

b) halogen,

c) hydroxyl,

d) —O—C 1-6 alkyl which is substituted with 0, 1, or 3 substituents selected from halogen, or C 3-6 cycloalkyl which is unsubstituted or substituted with halogen, C 1-6 alkyl, or C 1-6 alkylfluoro,

e) C 3-6 cycloalkyl, which is which is substituted with 0, 1, or 3 of R 4 ,

f) Heteroaryl, which is substituted with 0, 1, or 3 of R 4 ,

g) Heterocyclyl, which is substituted with 0, 1, or 3 R 4 ,

h) CN, and

i) S(O) 2 R;

R 2 is selected from

1) Linear or branched C 1-10 alkyl or C 4-8 alkenyl, 2) —(CR 2 ) 1-6 —O—(CR 2 ) 1-6 —;

3) —(CR 2 ) 1-6 —N(R 9 )—(CR 2 ) 1-6 —, wherein R 9 is hydrogen or —C 1-6 alkyl, where the —C 1-6 alkyl is unsubstituted or substituted with halogen,

4) —(CR 2 ) 1-6 C 3-6 cycloalkyl-(CR 2 ) 1-6 —, where the —C 3-6 cycloalkyl is unsubstituted or substituted with —C 1-6 alkyl or halogen, and

5) Piperidinyl, pyrrolidinyl, oxaxolyl, oxadiazolyl or thiazolyl ring, which is unsubstituted or substituted with —C 1-6 alkyl or halogen;

R 3 is selected from a direct bond, —S—, —NR—, —O—C 1-6 alkyl-, —S—C 1-6 alkyl-, and —S(O) 2 —C 1-6 alkyl-;

R 4 is selected from:

(1) hydrogen,

(2) hydroxyl,

(3) halogen,

(4) —C 1-6 alkyl, which is unsubstituted or substituted with one to six fluoro,

(5) —O—C 1-6 alkyl, which is unsubstituted or substituted with one to six fluoro, and

(6) C 3-6 cycloalkyl;

R 5 and R 6 are independently selected from:

(1) hydrogen, and

(2) —C 1-6 alkyl, where the alkyl is unsubstituted or substituted with one to six substituents independently selected from halogen,

or R 5 and R 6 and the carbon atom to which they are attached may be joined together to form a —C 3-6 cycloalkyl group;

R 7 is selected from:

(1) hydrogen,

(2) —C 1-6 alkyl, where the alkyl is unsubstituted or substituted with one to six substituents independently selected from halogen, and

(3) —C 3-6 cycloalkyl, where the —C 3-6 cycloalkyl is unsubstituted or substituted with —C 1-6 alkyl or halogen;

R 8 is selected from:

(1) hydrogen,

(2) halogen, and

(3) —C 1-6 alkyl, where the alkyl is unsubstituted or substituted with one to six substituents independently selected from halogen;

or a pharmaceutically acceptable salt thereof.

2 . The compound according to claim 1 , having structure of Formula I′:

wherein:

A is C;

D is N or C(R 8 ) n ;

E is N or C(R 8 ) n ;

G is N or C(R 8 ) n ;

J is Nor C(R 8 ) n ;

W is N or C(R 8 ) n ;

with the proviso that one, two, three or four of D, E, G, J and W are N, and the remainder of D, E, G, J and W are other than N;

n is 0 or 1;

X is —O— or —CH 2 —;

Y is phenyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, pyridofuranyl, oxazolyl, thiazolyl, which is unsubstituted or substituted with one to three groups selected from R 4 ;

Z is

R is independently selected from H or C 1-6 alkyl;

R 1 is selected from:

1) hydrogen,

2) CN,

3) —C(O)NR 2 —,

4) —CH 2 OCH 2 CF 3 —,

5) —CH 2 OCH 2 CHCF 2 —, and

6) C 1-6 alkyl, which is substituted with 0, 1, or 3 substituents independently selected from:

a) C 1-6 alkyl,

b) halogen,

c) hydroxyl,

d) —O—C 1-6 alkyl which is substituted with 0, 1, or 3 substituents selected from halogen, or C 3-6 cycloalkyl which is unsubstituted or substituted with halogen, C 1-6 alkyl, or C 1-6 alkylfluoro,

e) C 3-6 cycloalkyl, which is substituted with 0, 1, or 3 of R 4 ,

f) Heteroaryl, which is substituted with 0, 1, or 3 of R 4 ,

g) Heterocyclyl, which is substituted with 0, 1, or 3 of R 4 ,

h) CN, and

i) S(O) 2 R;

R 2 is selected from

1) Linear or branched C 1-10 alkyl or C 4-8 alkenyl,

2) —(CR 2 ) 1-6 —O—(CR 2 ) 1-6 —,

3) —(CR 2 ) 1-6 —N(R 9 )—(CR 2 ) 1-6 —, wherein R 9 is hydrogen or —C 1-6 alkyl, where the —C 1-6 alkyl is unsubstituted or substituted with halogen,

4) —(CR 2 ) 1-6 C 3-6 cycloalkyl-(CR 2 ) 1-6 , where the —C 3-6 cycloalkyl is unsubstituted or substituted with —C 1-6 alkyl or halogen, and

5) Piperidinyl, pyrrolidinyl, oxaxolyl, oxadiazolyl or thiazolyl ring, which is unsubstituted or substituted with —C 1-6 alkyl or halogen;

R 3 is selected from a direct bond, —O—C 1-6 alkyl-, —S—C 1-6 alky-1, and —S(O) 2 —C 1-6 alkyl-;

R 4 is selected from:

(1) hydrogen,

(2) hydroxyl,

(3) fluoro,

(4) —C 1-6 alkyl, which is unsubstituted or substituted with one to six fluoro, and

(5) —O—C 1-6 alkyl, which is unsubstituted or substituted with one to six fluoro;

R 5 and R 6 are independently selected from:

(1) hydrogen, and

(2) —C 1-6 alkyl, where the alkyl is unsubstituted or substituted with one to six substituents independently selected from halogen,

or R 5 and R 6 and the carbon atom to which they are attached may be joined together to form a —C 3-6 cycloalkyl group;

R 7 is selected from:

(1) —C 1-6 alkyl, where the alkyl is unsubstituted or substituted with one to six substituents independently selected from halogen, and

(2) —C 3-6 cycloalkyl, where the —C 3-6 cycloalkyl is unsubstituted or substituted with —C 1-6 alkyl or halogen;

R 8 is selected from:

(1) hydrogen,

(2) halogen, and

(3) —C 1-6 alkyl, where the alkyl is unsubstituted or substituted with one to six substituents independently selected from halogen;

or a pharmaceutically acceptable salt thereof.

3 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the group:

is selected from:

4 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the group:

is:

5 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is —O—.

6 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Y is phenyl, pyridyl, pyridazinyl, pyrazinyl, or pyrimidinyl.

7 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is

and R 1 is selected from hydrogen, —C(O)NR 2 , CH 2 OCH 2 CF 3 , CH 2 OCH 2 CHCF 2 , and —C 1-6 alkyl, which is substituted with 0, 1, or 3 substituents independently selected from C 1-6 alkyl, halogen, hydroxyl, CN, and C 3-6 cycloalkyl, which is substituted with 0, 1, or 3 of R 4 , and —O—C 1-6 alkyl which is substituted with 0, 1, or 3 substituents selected from halogen, or C 3-6 cycloalkyl which is unsubstituted or substituted with halogen, C 1-6 alkyl, or C 1-6 alkylfluoro;

R 2 is selected from

1) Linear or branched C 1-10 alkyl or C 4-8 alkenyl,

2) (CR 2 ) 1-6 —O—(CR 2 ) 1-6 —;

3) (CR 2 ) 1-6 —N(R 9 )—(CR 2 ) 1-6 —, wherein R 9 is hydrogen or —C 1-6 alkyl, where the —C 1-6 alkyl is unsubstituted or substituted with halogen,

4) —(CR 2 ) 1-6 C 3-6 cycloalkyl-(CR 2 ) 1-6 , where the —C 3-6 cycloalkyl is unsubstituted or substituted with —C 1-6 alkyl or halogen, and

5) Piperidinyl, pyrrolidinyl, oxaxolyl, oxadiazolyl or thiazolyl ring, which is unsubstituted or substituted with —C 1-6 alkyl or halogen; and

R 3 is selected from a direct bond, —S—, —NR—, —O—C 1-6 alkyl, —S—C 1-6 alkyl, and —S(O) 2 —C 1-6 alkyl.

8 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is selected from:

(1) C 1-6 alkyl, and

(2) —O—C 1-6 alkyl.

9 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 and R 6 are independently selected from:

(1) hydrogen, and

(2) —C 1-6 alkyl, where the alkyl is unsubstituted or substituted with one to six substituents independently selected from fluoro.

10 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is selected from:

(1) hydrogen, and

(2) —C 1-6 alkyl.

11 . A compound which is selected from:

(10R,E)-9-ethyl-10-methyl-3-oxa-7,9-diaza-2(6,8)-imidazo[1,2-a]pyrazina-1(1,3)-benzena-4(1,3)-cyclopentanacyclodecaphan-8-one;

(12R)-13-ethyl-12-methyl-12,13,16,17,19,20-hexahydro-6,22-(azeno)-11,7-(metheno)imidazo[1,2-o][1,18,4,6, 15]dioxatriazacycloicosin-14(15H)-one;

(12R)-13-ethyl-12-methyl-18-(propan-2-yl)-12,13,15,16,17,18,19,20-octahydro-14H-6,22-(azeno)-11,7-(metheno)imidazo[1,2-r][1,4,7,9,18]oxatetraazacycloicosin-14-one;

(12R)-13-ethyl-12-methyl-12,13,15,16,17,18,21,22,22a,23-decahydro-14H,20H-6,25-(azeno)-11,7-(metheno)imidazo[1,2-s]pyrrolo[2,1-c][1,4,8,10,19]oxatetraazacyclohenicosin-14-one;

(7R)-8-ethyl-7-methyl-18-oxa-8,10,13,21,24,26-hexaazapentacyclo-[17.6.1.1-2,6-1-13,17.0-20,24-]octacosa-1(25),2(28),3,5,19(26),20,22-heptaen-9-one;

(12R)-13-ethyl-8-methoxy-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,15,16,17,18,20,21-octahydro-14H-6,23-(azeno)-11,7-(metheno)imidazo[2,1-f][1,4,7,13,16,18]dioxatetraazacyclohenicosin-14-one;

(12R)-13-ethyl-8-methoxy-12-methyl-12,13,15,16,17,18,20,21-octahydro-14H-6,23-(azeno)-11,7-(metheno)imidazo[2,1-f][1,4,7,13,16,18]dioxatetraazacyclohenicosin-14-one;

(12R)-13-ethyl-8-methoxy-12-methyl-12,13,16,17,20,21-hexahydro-19H-6,23-(azeno)-11,7-(metheno)imidazo[1,2-o][1,18,4,6,9,15]dioxatetraazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-8-methoxy-12,16-dimethyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(R,E)-4-ethyl-3-methyl-13-oxa-4,6,9-triaza-1(6,8)-imidazo[1,2-a]pyrazina-2(1,3)-benzenacyclotridecaphan-5-one;

(12R)-13-ethyl-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[1,2-s][1,4,8,10,19]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,13, 15]oxatriazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-12,19,19-trimethyl-12,13,15,16,17,18,19,20-octahydro-14H-6,22-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,13,15]oxatriazacycloicosin-14-one;

(12R)-13-ethyl-12-methyl-12,13,15,16,17,18,20,21-octahydro-14H-6,23-(azeno)-11,7-(metheno)imidazo[2,1-f][1,4,7,16,18]dioxatriazacyclohenicosin-14-one;

(12R)-13,18-diethyl-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,13,15,18]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-12,18,21-trimethyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,13,15,18]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-12-methyl-12,13,16,17,20,21-hexahydro-19H-6,23-(azeno)-11,7-(metheno)imidazo[1,2-o][1,18,4,6,15]dioxatriazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-12,16-dimethyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,13,15]oxatriazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-12-methyl-16-(1,3-thiazol-4-yl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,13,15]oxatriazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-12-methyl-16-(1,2-oxazol-3-yl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,13,15]oxatriazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-8-methoxy-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,20,21-hexahydro-19H-6,23-(azeno)-11,7-(metheno)imidazo[1,2-o][1,18,4,6,9,15]dioxatetraazacyclohenicosin-14(15H)-one;

(R,2 7 E,6 2 Z)-10-ethyl-11-methyl-3-oxa-8,10-diaza-6(4,2)-thiazola-2(6,8)-imidazo[1,2-a]pyrazina-1(1,3)-benzenacycloundecaphan-9-one;

(R,2 7 E,5 4 Z)-10-ethyl-11-methyl-3-oxa-8,10-diaza-5(3,5)-oxadiazola-2(6,8)-imidazo[1,2-a]pyrazina-1(1,3)-benzenacycloundecaphan-9-one;

(3R,E)-4-ethyl-3,9-dimethyl-8-(trifluoromethyl)-12-oxa-4,6,9-triaza-1(6,8)-imidazo[1,2-a]pyrazina-2(1,3)-benzenacyclododecaphan-5-one;

(3R,E)-4-ethyl-3,9-dimethyl-8-(trifluoromethyl)-13-oxa-4,6,9-triaza-1(6,8)-imidazo[1,2-a]pyrazina-2(1,3)-benzenacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-2 2 -methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-12-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(3,5)-pyridinacyclododecaphan-5-one;

(3R,7R,E)-4-ethyl-2 2 -methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(3,5)-pyridinacyclotridecaphan-5-one;

(12S,16R)-13-ethyl-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,15,16,17,18,19,20-octahydro-14H-6,22-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacycloicosin-14-one;

(12R,16R)-13-ethyl-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,15,16,17,18,19,20-octahydro-14H-6,22-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13, 15]oxatetraazacycloicosin-14-one;

(12S,16R)-13-ethyl-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(1 7 E,3R,7S,9Z)-4-ethyl-3-methyl-7-(3,3,3-trifluoropropyl)-12-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(1,3)-benzenacyclododecaphan-9-en-5-one;

(3R,7R,E)-4-ethyl-3-methyl-7-(3,3,3-trifluoropropyl)-12-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(1,3)-benzenacyclododecaphan-5-one;

(16S,18Z)-13-ethyl-8-methoxy-12-(trifluoromethyl)-16-(3,3,3-trifluoropropyl)-12,13,15,16,17,20-hexahydro-14H-6,22-(azeno)-11,7-(metheno)[1,2,4]triazolo[5,1-c][1,4,10,13,15]oxatetraazacycloicosin-14-one;

(16R)-13-ethyl-8-methoxy-12-(trifluoromethyl)-16-(3,3,3-trifluoropropyl)-12,13,15,16,17,18,19,20-octahydro-14H-6,22-(azeno)-11,7-(metheno)[1,2,4]triazolo [5,1-c][1,4,10,13,15]oxatetraazacycloicosin-14-one;

(16R)-13-ethyl-8-methoxy-12-(trifluoromethyl)-16-(3,3,3-trifluoropropyl)-12,13,15,16,17,18,19,20-octahydro-14H-6,22-(azeno)-11,7-(metheno)[1,2,4]triazolo[5,1-c][1,4,10,13, 15]oxatetraazacycloicosin-14-one;

13-ethyl-8-methoxy-12-(trifluoromethyl)-12,13,15,16,17,18,19,20-octahydro-14H-6,22-(azeno)-11,7-(metheno)[1,2,4]triazolo[5,1-c][1,4,10,13,15]oxatetraazacycloicosin-14-one;

(16R)-13-ethyl-8-methoxy-2-methyl-12-(trifluoromethyl)-16-(3,3,3-trifluoropropyl)-12,13,15,16,17,18,19,20-octahydro-14H-6,22-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacycloicosin-14-one;

(16R)-13-ethyl-8-methoxy-12,16-bis (trifluoromethyl)-12,13,15,16,17,18,19,20-octahydro-14H-6,22-(azeno)-11,7-(metheno)[1,2,4]triazolo[5,1-c][1,4,10,13,15]oxatetraazacycloicosin-14-one;

(16R)-13-ethyl-8-methoxy-16-(2,2,2-trifluoroethyl)-12-(trifluoromethyl)-12,13,15,16,17,18,19,20-octahydro-14H-6,22-(azeno)-11,7-(metheno)[1,2,4]triazolo[5,1-c][1,4,10,13,15]oxatetraazacycloicosin-14-one;

(16R)-13-ethyl-8-methoxy-12,16-bis (trifluoromethyl)-12,13,15,16,17,18,19,20-octahydro-14H-6,22-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacycloicosin-14-one;

(12S,16R)-13-ethyl-8-methoxy-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,15,16,17,18,19,20-octahydro-14H-6,22-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacycloicosin-14-one;

(12R,18Z)-13-ethyl-12,17-dimethyl-16-(3,3,3-trifluoropropyl)-12,13,15,16,17,20-hexahydro-14H-6,22-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,13,15]oxatriazacycloicosin-14-one;

(12R)-13-ethyl-12,17-dimethyl-16-(3,3,3-trifluoropropyl)-12,13,15,16,17,18,19,20-octahydro-14H-6,22-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,13, 15]oxatriazacycloicosin-14-one;

(16R)-13-ethyl-16-(3,3,3-trifluoropropyl)-12,13,15,16,17,18,19,20-octahydro-14H-6,22-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,13,15]oxatriazacycloicosin-14-one;

(16R)-13-ethyl-8-methoxy-16-(3,3,3-trifluoropropyl)-12,13,15,16,17,18,19,20-octahydro-14H-6,22-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,13,15]oxatriazacycloicosin-14-one;

(16R)-13-ethyl-8-methoxy-16-(3,3,3-trifluoropropyl)-12,13,15,16,17,18,19,20-octahydro-14H-6,22-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacycloicosin-14-one;

(3R,7R,E)-4-ethyl-2 2 -methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-12-oxa-4,6-diaza-1(2,4)-imidazo[2,1-f][1,2,4]triazina-2(3,5)-pyridinacyclododecaphan-5-one;

(3R,7R,E)-4-ethyl-2 2 -methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(2,4)-imidazo[2,1-f][1,2,4]triazina-2(3,5)-pyridinacyclotridecaphan-5-one;

(3R,E)-4-ethyl-3,9-dimethyl-7-(3,3,3-trifluoropropyl)-12-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(1,3)-benzenacyclododecaphan-5-one;

(12R)-13-ethyl-12-methyl-12,13,15,16,17,18,19,20-octahydro-14H-6,22-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,13,15]oxatriazacycloicosin-14-one;

(7R)-8-ethyl-14,14-difluoro-3-methoxy-7-methyl-11-(3,3,3-trifluoropropyl)-17-oxa-5,8,10,20,23,25-hexazatetracyclo(12R)[16.6.1.12,6.019,23]hexacosa-1(24),2(26),3,5,18(25), 19,21-heptaen-9-one;

(3R,7R,E)-4-ethyl-23-methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]yridine-2(2,6)-pyridinacyclotridecaphan-5-one;

(16R)-13-ethyl-8-methoxy-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,9,13, 15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-13,16-diethyl-8-methoxy-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-8-methoxy-12-methyl-16-(2-methylpropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-8-methoxy-12-methyl-16-propyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-16-(cyclopropylmethyl)-13-ethyl-8-methoxy-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-8-methoxy-16-(2-methoxyethyl)-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-16-cyclopropyl-13-ethyl-8-methoxy-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-8-methoxy-16-(methoxymethyl)-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-16-[(2,2-difluorocyclopropyl) methyl]-13-ethyl-8-methoxy-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclo henicosin-14(15H)-one;

(12R)-13-ethyl-8-methoxy-16-(3-methoxypropyl)-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-16-(cyclobutylmethyl)-13-ethyl-8-methoxy-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-16-(ethoxymethyl)-13-ethyl-8-methoxy-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-16-tert-butyl-13-ethyl-8-methoxy-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-16-(2-ethylbutyl)-8-methoxy-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-16-(cyclopentylmethyl)-13-ethyl-8-methoxy-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-8-methoxy-12-methyl-16-{[1-(trifluoromethyl)cyclopropyl]methyl}-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-8-methoxy-12-methyl-16-[(oxolan-3-yl)methyl]-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-8-methoxy-12-methyl-16-(oxan-4-yl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-16-[(3,3-difluorocyclobutyl) methyl]-13-ethyl-8-methoxy-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-16-{[1-(difluoromethyl)cyclopropyl]methyl}-13-ethyl-8-methoxy-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-16-(3-fluoro-3-methylbutyl)-8-methoxy-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-16-(3-fluorobutyl)-8-methoxy-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-8-methoxy-12-methyl-16-[2-(trifluoromethoxy)ethyl]-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(9R,E)-12-ethyl-13-methyl-9-(3,3,3-trifluoropropyl)-3-oxa-10,12-diaza-1(7,5)-furo[3,2-b]pyridina-2(6,8)-imidazo[1,2-a]pyrazinacyclotridecaphan-11-one;

(10R)-7-ethyl-6,19-dimethyl-10-(3,3,3-trifluoropropyl)-6,7,10,11,12,13,14,15-octahydro-23,17-(azeno)-5,24-(metheno)furo[2,3-h]imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-8(9H)-one;

(10R)-7-ethyl-6,19-dimethyl-10-(3,3,3-trifluoropropyl)-6,7,10,11,12,13,14, 15-octahydro-23,17-(azeno)-5,24-(metheno)furo[2,3-h]imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-8(9H)-one;

(10R)-7-ethyl-6,20-dimethyl-10-(3,3,3-trifluoropropyl)-6,7,10,11,12,13,14,15-octahydro-23,17-(azeno)-5,24-(metheno)furo[2,3-h]imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-8(9H)-one;

(10R)-7-ethyl-6,20-dimethyl-10-(3,3,3-trifluoropropyl)-6,7,10,11,12,13,14,15-octahydro-23,17-(azeno)-5,24-(metheno)furo[2,3-h]imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-8(9H)-one;

(12R,16R)-13-ethyl-8-methoxy-12-methyl-16-(trifluoromethyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R,16R)-13-ethyl-8,12-dimethyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,9,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R,16R)-13-ethyl-8,12-dimethyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(15R)-12-ethyl-7-methoxy-11-methyl-15-(3,3,3-trifluoropropyl)-11,12,15,16,17,18,19,20-octahydro-10,6-(azeno)-5,22-(metheno)pyrazolo[1,5-c][1,3,9,13,15]oxatetraazacyclohenicosin-13(14H)-one;

(12R,16R)-13-ethyl-8-methoxy-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,15,16,17,18,19,20,21,22-decahydro-14H-6,23-(azeno)-11,7-(metheno)imidazo[1,2-1][1,3,6,12]tetraazacyclohenicosin-14-one;

(12R,16R)-13-ethyl-8-methoxy-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)[1,2,4]triazolo[5,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R,16R)-16-(3,3-difluorobutyl)-13-ethyl-8-methoxy-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,9,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R,16R)-16-(3,3-difluorobutyl)-13-ethyl-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R)-13-ethyl-8-methoxy-12-methyl-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R,16R)-13-ethyl-8-methoxy-5,12-dimethyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,9,13, 15]oxatetraazacyclohenicosin-14(15H)-one;

(12R,16R)-13-ethyl-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,5,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(15R)-12-ethyl-7-methoxy-11-methyl-15-(3,3,3-trifluoropropyl)-11,12,15,16,17,18,19,20-octahydro-5,22-(azeno)-10,6-(metheno)pyrazolo[1,5-c][1,3,10,13,15]oxatetraazacyclohenicosin-13(14H)-one;

(12R,16R)-13-ethyl-8-methoxy-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23:11,7-di(metheno)imidazo[2,1-c][1,4,5,9,13, 15]oxapentaazacyclohenicosin-14(15H)-one;

(16R)-13-ethyl-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23:11,7-di(azeno)imidazo[2,1-c][1,4,13,15]oxatriazacyclohenicosin-14(15H)-one;

(12R,16R)-13-ethyl-8-methoxy-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23:11,7-di(metheno)imidazo[2,1-c][1,4,9,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(16R)-13-ethyl-10,12-dimethyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,8,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12S,16R)-13-ethyl-8,12-dimethyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23:11,7-di(azeno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(15R)-12-ethyl-11-methyl-15-(3,3,3-trifluoropropyl)-11,12,15,16,17,18,19,20-octahydro-6,22-(azeno)-7,10-epithioimidazo[2,1-c][1,4,8,12,14]oxatetraazacycloicosin-13(14H)-one;

(16R)-13-ethyl-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23:11,7-di(metheno)imidazo[2,1-c][1,4,8,10,13,15]oxapentaazacyclohenicosin-14(15H)-one;

(16R)-13-ethyl-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23:11,7-di(metheno)imidazo[2,1-c][1,4,8,10,13,15]oxapentaazacyclohenicosin-14(15H)-one;

(12R,16R)-13-ethyl-8-methoxy-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23:11,7-di(azeno)imidazo[2,1-c][1,4,13,15]oxatriazacyclohenicosin-14(15H)-one;

(11R,15R)-12-ethyl-7-methoxy-11-methyl-15-(3,3,3-trifluoropropyl)-11,12,15,16,17,18,19,20-octahydro-5,22-(azeno)-10,6-(metheno)pyrazolo[1,5-c][1,3,5,10,13,15]oxapentaazacyclohenicosin-13 (14H)-one;

(12R,16R)-13-ethyl-8-methoxy-12-methyl-16-(2,2,2-trifluoroethyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,5,9,13,15]oxapentaazacyclohenicosin-14(15H)-one;

(11R,15R)-12-ethyl-7-methoxy-11-methyl-15-(3,3,3-trifluoropropyl)-11,12,15,16,17,18,19,20-octahydro-5,22:10,6-di(metheno)pyrazolo[1,5-c][1,3,5,10,13,15]oxapentaazacyclohenicosin-13(14H)-one;

(12R,16R)-13-ethyl-12-methyl-16-(2,2,2-trifluoroethyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,5,10,13,15]oxapentaazacyclohenicosin-14(15H)-one;

(12R,16R)-13-ethyl-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,5,10,13,15]oxapentaazacyclohenicosin-14(15H)-one;

(12R,16R)-13-ethyl-12-methyl-16-(2,2,2-trifluoroethyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(15R)-12-ethyl-11-methyl-15-(3,3,3-trifluoropropyl)-11,12,15,16,17,18,19,20-octahydro-6,22-(azeno)-7,10-epoxyimidazo[2,1-c][1,4,8,12,14]oxatetraazacycloicosin-13(14H)-one;

(15R)-12-ethyl-11-methyl-15-(3,3,3-trifluoropropyl)-11,12,15,16,17,18,19,20-octahydro-6,22:10,7-di(azeno)imidazo[2,1-c][1,8,4,12,14]dioxatriazacycloicosin-13(14H)-one;

(12R,16R)-13-ethyl-8-methoxy-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,15,16,17,18,19,20,21,22-decahydro-14H-11,7-(azeno)-6,23-(metheno)imidazo[1,2-1][1,3,12]triazacyclohenicosin-14-one;

(12S,16R)-13-ethyl-9,12-dimethyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R,16R)-13-ethyl-9,12-dimethyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(15R)-12-ethyl-11-methyl-15-(3,3,3-trifluoropropyl)-11,12,15,16,17,18,19,20-octahydro-6,22-(azeno)-7,10-epoxyimidazo[2,1-c][1,4,9,12,14]oxatetraazacycloicosin-13(14H)-one;

(3R,7R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-14-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotetradecaphan-5-one;

(3R,7R,E)-4-ethyl-3-methyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(12R,16R)-13-ethyl-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,8,10,13,15]oxapentaazacyclohenicosin-14(15H)-one;

(16R)-13-ethyl-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,8,10,13,15]oxapentaazacyclohenicosin-14(15H)-one;

(12S,16R)-13-ethyl-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,8,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R,16R)-13-ethyl-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,8,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R,16R)-13-ethyl-8-methoxy-12-methyl-16-(2,2,2-trifluoroethyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R,16S)-13-ethyl-8-methoxy-12-methyl-16-(trifluoromethyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R,16R)-13-ethyl-8-methoxy-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,9,10,13, 15]oxapentaazacyclohenicosin-14(15H)-one;

(12S,16R)-13-ethyl-8-methoxy-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23:11,7-di(azeno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R,16R)-13-ethyl-8-methoxy-12-methyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23:11,7-di(azeno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12S,16R)-13-ethyl-9,12-dimethyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,8,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12R,16R)-13-ethyl-9,12-dimethyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,8,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(12S,16R)-13-ethyl-9,12-dimethyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,8,10,13,15]oxapentaazacyclohenicosin-14(15H)-one;

(12R,16R)-13-ethyl-9,12-dimethyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,8,10,13,15]oxapentaazacyclohenicosin-14(15H)-one;

(16R)-13-ethyl-16-(3,3,3-trifluoropropyl)-12,13,16,17,18,19,20,21-octahydro-6,23-(azeno)-11,7-(metheno)imidazo[2,1-c][1,4,10,13,15]oxatetraazacyclohenicosin-14(15H)-one;

(3R,E)-7-(2,2-difluorobutyl)-4-ethyl-25,3-dimethyl-10,13-dioxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-2 5 -methoxy-16,3-dimethyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(2,4)-imidazo[2,1-f][1,2,4]triazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-2 5 -methoxy-17,3-dimethyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(2,4)-imidazo[2,1-f][1,2,4]triazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(R,E)-7-(3,3-difluorobutyl)-4-ethyl-2 2 -methoxy-13-oxa-4,6-diaza-1(2,4)-imidazo[2,1-f][1,2,4]triazina-2(3,5)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-7-(fluoromethyl)-2 5 -methoxy-3-methyl-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7S,E)-7-(3,3-difluoropropyl)-4-ethyl-2 5 -fluoro-3-methyl-10,13-dioxa-4,6-diaza-1(2,4)-imidazo[2,1-f][1,2,4]triazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-2 5 -chloro-7-(3,3-difluoropropyl)-4-ethyl-3-methyl-13-oxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7S,E)-7-(3,3-difluorobutyl)-4-ethyl-25,3-dimethyl-10,13-dioxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-((R)-3,3,3-trifluoro-2-hydroxypropyl)-13-oxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-((S)-3,3,3-trifluoro-2-hydroxypropyl)-13-oxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-((R)-3,3,3-trifluoro-1-hydroxypropyl)-13-oxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-((S)-3,3,3-trifluoro-1-hydroxypropyl)-13-oxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7S,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-13-oxa-10-thia-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7S,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-13-oxa-10-thia-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one 10,10-dioxide;

(3R,7S,E)-4-ethyl-3-methyl-7-(3,3,3-trifluoropropyl)-10,13-dioxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-10-hydroxy-22,3-dimethyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(3,5)-pyridinacyclotridecaphan-5-one;

(3R,7R,Z)-4-ethyl-23-methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-4,6-diaza-1(6,8)-imidazo[1,2-a]pyridina-2(2,6)-pyridinacyclododecaphan-5-one;

(3R,7R,E)-4-ethyl-23-methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(2,6)-pyrazinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-26-methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(5,7)-pyrazolo[1,5-a]pyridina-2(5,3)-pyridazinacyclotridecaphan-5-one;

(3R,7S,E)-4-ethyl-8,8-difluoro-2 5 -methoxy-3,7-dimethyl-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-3-methyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(R,E)-4-ethyl-3,3-dimethyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-12-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-4-ethyl-2 5 -methoxy-3-methyl-12-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridina-7(1,2)-cyclopropanacyclododecaphan-5-one;

(3R,7R,E)-7-(3,3-difluorobutyl)-4-ethyl-22,3-dimethyl-13-oxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(3,5)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyrimidinacyclotridecaphan-5-one;

(3R,7S,E)-7-(3,3-difluorobutyl)-4-ethyl-2 2 -methoxy-3-methyl-10,13-dioxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(3,5)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-b]pyridazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7S,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-10,13-dioxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyridina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-7-(2,2-difluoropropyl)-4-ethyl-2 5 -methoxy-3-methyl-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(3-methylpyrazin-2-yl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7S,E)-7-(3,3-difluorobutyl)-4-ethyl-25,3-dimethyl-9,13-dioxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(2-(methylsulfonyl) ethyl)-13-oxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7S,E)-7-(3,3-difluorobutyl)-4-ethyl-2 5 -methoxy-3-methyl-10,13-dioxa-4,6-diaza-1(2,4)-imidazo[2,1-f][1,2,4]triazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-3-methyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(5,7)-pyrazolo[1,5-a]pyridina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R)-4-ethyl-2 5 -methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(6,8)-quinolina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-3,4-dimethyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-3-methyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(5,3)-pyridazinacyclotridecaphan-5-one;

(3R,7R,E)-7-(3,3-difluorobutyl)-4-ethyl-15,3-dimethyl-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(2,4)-pyridinacyclotridecaphan-5-one;

(3R,7S,E)-4-ethyl-3-methyl-7-(3,3,3-trifluoropropyl)-10,13-dioxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(2,4)-pyridinacyclotridecaphan-5-one;

(3R,7R)-4-ethyl-2 5 -methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(6,8)-naphthyridina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7S,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(6,8)-naphthyridina-2(4,2)-pyridinacyclotridecaphan-9-en-5-one;

(3R,7S,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-10,13-dioxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7S,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-10,13-dioxa-4,6-diaza-1(5,7)-pyrazolo[1,5-c]pyrimidina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-2 5 -methoxy-12,3-dimethyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-b]pyridazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7S,E)-7-(3,3-difluorobutyl)-4-ethyl-2 5 -methoxy-3-methyl-10,13-dioxa-4,6-diaza-1(5,7)-pyrazolo[1,5-c]pyrimidina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-4-ethyl-2 5 -methoxy-13,3-dimethyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-b]pyridazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-7-(3,3-difluorobutyl)-4-ethyl-2 5 -methoxy-3-methyl-10,13-dioxa-4,6-diaza-1(7,5)-[1,2,4]triazolo[1,5-c]pyrimidina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7S,E)-7-(3,3-difluorobutyl)-4-ethyl-2 5 -methoxy-3-methyl-9,13-dioxa-4,6-diaza-1(5,7)-pyrazolo[1,5-c]pyrimidina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-7-(3,3-difluorobutyl)-4-ethyl-2 5 -methoxy-15,3-dimethyl-13-oxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7S,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-9,13-dioxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7S,E)-4-ethyl-23-fluoro-3-methyl-7-(3,3,3-trifluoropropyl)-9,13-dioxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7R,E)-7-(3,3-difluorobutyl)-4-ethyl-2 5 -methoxy-3-methyl-13-oxa-4,6-diaza-1(7,5)-[1,2,4]triazolo[1,5-c]pyrimidina-2(4,2)-pyridinacyclotridecaphan-5-one;

(R,E)-4-ethyl-2 5 -methoxy-3-methyl-14-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotetradecaphan-5-one;

(R,E)-4-ethyl-2 5 -methoxy-3-methyl-11-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacycloundecaphan-5-one;

(7S,E)-4-ethyl-23-fluoro-2 5 -methoxy-3-methyl-7-(3,3,3-trifluoropropyl)-10,13-dioxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7S,E)-7-(3,3-difluorobutyl)-4-ethyl-3-methyl-10,13-dioxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,7S,E)-7-(3,3-difluorobutyl)-4-ethyl-3-methyl-10,13-dioxa-4,6-diaza-1(5,7)-pyrazolo[1,5-c]pyrimidina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-7-(2-(difluoromethoxy) ethyl)-4-ethyl-2 5 -methoxy-3-methyl-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-4-ethyl-7-((1-fluorocyclopropyl) methyl)-2 5 -methoxy-3-methyl-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-7-(4,4-difluorobutyl)-4-ethyl-2 5 -methoxy-3-methyl-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-4-ethyl-7-(isopropoxymethyl)-2 5 -methoxy-3-methyl-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-7-(2,2-difluoroethyl)-4-ethyl-2 5 -methoxy-3-methyl-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(2,2,3,3-tetrafluoropropyl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-((2,2,2-trifluoroethoxy) methyl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(tetrahydrofuran-3-yl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-7-((2,2-difluoroethoxy) methyl)-4-ethyl-2 5 -methoxy-3-methyl-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-4-ethyl-2 5 -methoxy-7-(1-methoxyethyl)-3-methyl-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-7-(2,2-difluorocyclopropyl)-4-ethyl-2 5 -methoxy-3-methyl-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(tetrahydrofuran-2-yl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

2-((3R,E)-4-ethyl-2 5 -methoxy-3-methyl-5-oxo-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphane-7-yl)acetonitrile;

(3R,E)-7-(3,3-difluorocyclobutyl)-4-ethyl-2 5 -methoxy-3-methyl-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

3-((3R,E)-4-ethyl-2 5 -methoxy-3-methyl-5-oxo-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphane-7-yl)propanenitrile;

(3R,E)-2 5 -cyclopropyl-7-(3,3-difluoropropyl)-4-ethyl-3-methyl-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-2 5 -chloro-4-ethyl-3-methyl-7-(3,3,3-trifluoropropyl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-4-ethyl-2 5 -fluoro-7-(methoxymethyl)-3-methyl-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-7-(3,3-difluorobutyl)-4-ethyl-2 5 -methoxy-3-methyl-13-oxa-4,6-diaza-1(2,4)-imidazo[2,1-f][1,2,4]triazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-7-(3,3-difluoropropyl)-4-ethyl-25,3-dimethyl-13-oxa-4,6-diaza-1(6,8)-[1,2,4]triazolo[1,5-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-7-(3,3-difluoropropyl)-4-ethyl-2 5 -methoxy-3-methyl-13-oxa-4,6-diaza-1(2,4)-imidazo[2,1-f][1,2,4]triazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-7-(bicyclo[1.1.1]pentan-1-ylmethyl)-4-ethyl-2 5 -methoxy-3-methyl-13-oxa-4,6-diaza-1(2,4)-imidazo[2,1-f][1,2,4]triazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-7-(3,3-difluoropropyl)-4-ethyl-2 5 -fluoro-3-methyl-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-b]pyridazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-4-cyclopropyl-7-(3,3-difluoropropyl)-2 5 -fluoro-3-methyl-13-oxa-4,6-diaza-1(2,4)-imidazo[2,1-f][1,2,4]triazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-((1-methylcyclopropyl) methyl)-13-oxa-4,6-diaza-1(2,4)-imidazo[2,1-f][1,2,4]triazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-7-(2,2-difluoropropyl)-4-ethyl-2 5 -methoxy-3-methyl-13-oxa-4,6-diaza-1(2,4)-imidazo[2,1-f][1,2,4]triazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3S,E)-7-(3,3-difluoropropyl)-4-ethyl-2 5 -methoxy-3-(trifluoromethyl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(9R,13R,E)-14-Cyclopropyl-12-ethyl-13-methyl-9-(3,3,3-trifluoropropyl)-3-oxa-10,12-diaza-1(5,2)-thiazola-2(6,8)-imidazo[1,2-a]pyrazinacyclotridecaphan-11-one;

(16E,22E,7R)-2 5 -cyclopropyl-4-ethyl-3-methyl-7-(3,3,3-trifluoropropyl)-21H-13-oxa-4,6-diaza-1(5,7)-pyrazolo[1,5-a]pyridina-2(1,3)-pyrazolacyclotridecaphan-5-one;

(9R,13R,E)-14-Cyclopropyl-12-ethyl-13-methyl-9-(3,3,3-trifluoropropyl)-3-oxa-10,12-diaza-1(5,2)-oxazola-2(6,8)-imidazo[1,2-a]pyrazinacyclotridecaphan-11-one;

(3R,E)-4-ethyl-2 5 -methoxy-3-methyl-7 4 -(trifluoromethyl)-11-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridina-7 (3,1)-pyrrolidinacycloundecaphan-5-one;

(3R,E)-4-ethyl-74,74-difluoro-3-methyl-11-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-7(3,1)-pyrrolidina-2(1,3)-benzenacycloundecaphan-5-one;

(3R,E)-4-ethyl-2 5 -methoxy-3-methyl-7 4 -(trifluoromethyl)-12-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridina-7(3,1)-pyrrolidinacyclododecaphan-5-one;

(3R,E)-4-ethyl-2 2 -methoxy-3-methyl-7-(2-methylthiazol-4-yl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(3,5)-pyridinacyclotridecaphan-5-one;

(3R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(2-methylthiazol-5-yl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(1-methyl-1H-tetrazol-5-yl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(4-methylthiazol-2-yl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3R,E)-4-ethyl-2 5 -methoxy-3-methyl-7-(1-methyl-1H-1,2,4-triazol-5-yl)-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(1 7 E,3R,8E)-4-ethyl-11,11-difluoro-2 5 -methoxy-3,7-dimethyl-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-8-en-5-one;

(3R,7S,E)-4-ethyl-11,11-difluoro-2 5 -methoxy-3,7-dimethyl-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan-5-one;

(3′R,7'S,7′E,8′E)-4′-ethyl-5′-methoxy-3′,7′-dimethyl-2,3,5,6-tetrahydrospiro[pyran-4,11′-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphanen]-8′-en-5′-one;

(3′R,7'S,E)-4′-ethyl-5′-methoxy-3′,7′-dimethyl-2,3,5,6-tetrahydrospiro[pyran-4,11′-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphan]-5′-one;

(3R,E)-4-ethyl-2 5 -methoxy-3-methyl-5-oxo-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphane-7-carbonitrile; and

(3R,E)-4-ethyl-2 5 -fluoro-3-methyl-5-oxo-13-oxa-4,6-diaza-1(6,8)-imidazo[1,2-a]pyrazina-2(4,2)-pyridinacyclotridecaphane-7-carboxamide;

or a pharmaceutically acceptable salt thereof.

12 . A pharmaceutical composition which comprises an inert carrier and a compound of claim 1 or a pharmaceutically acceptable salt thereof.

13 . A method for treating narcolepsy in a mammalian subject which comprises administering to the patient an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.

14 . A method for treating hypersomnia in a mammalian subject which comprises administering to the patient an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.