Cardiac sarcomere inhibitors

1. A compound of Formula (I), or a pharmaceutically acceptable salt thereof:

wherein:

G 1 is —O—;

G 2 is a bond;

G 3 is —CR 8 —;

R 1 , R 3 , and R 8 are each independently H, C 1 -C 6 alkyl, halo, or hydroxyl;

R 2 is H, C 2 -C 6 alkyl, halo, or hydroxyl;

Z is selected from the group consisting of a bond, C 1 -C 6 alkyl, —O—, —N(R 9 )—, —R x O—, —OR y —, and —R z S—;

R 9 is H, C 1 -C 6 alkyl, or cycloalkyl;

A is selected from the group consisting of substituted C 2 alkynyl, unsubstituted C 2 alkynyl, phenyl, and 5- or 6-membered heteroaryl comprising at least one annular N atom, wherein the phenyl or 5- or 6-membered heteroaryl of A is unsubstituted or substituted with one or more R 10 substituents;

each R 10 is independently selected from the group consisting of substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 2 -C 6 alkenyl, substituted or unsubstituted C 2 -C 6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, and —C(O)OR a ;

B is selected from the group consisting of H, C 1 -C 6 alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl, wherein the C 1 -C 6 alkyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl of B is unsubstituted or substituted with one or more R 11 substituents;

each R 11 is independently selected from the group consisting of substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, unsubstituted C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted with one or more R 12 substituents, substituted or unsubstituted C 2 -C 6 alkenyl, substituted or unsubstituted C 2 -C 6 alkynyl, halo, —OR b , —C(O)R c , —C(O)OR d , oxo, and —NR e R f ;

each R 12 is independently selected from the group consisting of halo, —OR b , —C(O)R g , —C(O)OR h , and —C(O)NR i R j ;

each R a , R b , R c , R d , R e , R f , R g , R h , R i , and R j is independently H or C 1 -C 6 alkyl; and

R x , R y , and R z are each C 1 -C 6 alkyl,

wherein when A is unsubstituted phenyl or 5-trifluoromethyl-1,2,4-oxadiazolyl, the —Z—B moiety is not —OC(CH 3 ) 3 or 1-ethyl-3-hydroxy-1,5-dihydro-2H-pyrrol-2-onyl.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) is a compound of Formula (If):

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , and R 8 are each H.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein G 3 is —CH—.

5. The compound of claim 1 , wherein R 1 , R 2 , and R 3 are each H.

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

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

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is —N(R 9 )—.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is selected from the group consisting of phenyl and 5- or 6-membered heteroaryl comprising at least one annular N atom, wherein the phenyl or 5- or 6-membered heteroaryl is unsubstituted or substituted with one or more R 10 substituents.

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is selected from the group consisting of phenyl, pyrazolyl, oxazolyl, oxadiazolyl, isoxazolyl, tetrazolyl, triazolyl, thiazolyl, pyrimidinyl, pyridinyl, pyrazinyl, and pyridazinyl, each of which is unsubstituted or substituted with one or more R 10 substituents.

11. The compound of claim, or a pharmaceutically acceptable salt thereof, wherein A is selected from the group consisting of:

each of which is unsubstituted or substituted with one or more R 10 substituents.

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each C 1 -C 6 alkyl, cycloalkyl, or heterocycloalkyl of R 10 is independently unsubstituted or substituted with one more substituents independently selected from the group consisting of —OR k and —OC(O)R m , wherein R k and R m are each independently H or C 1 -C 6 alkyl.

13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is oxadiazolyl, which is unsubstituted or substituted with one substituent selected from the group consisting of methyl, ethyl, isopropyl, difluoromethyl, cyclopropyl, and cyclobutyl.

14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is isoxazolyl, which is unsubstituted or substituted with one or more substituents selected from the group consisting of methyl, ethyl, and difluoromethyl.

15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein B is selected from the group consisting of H, C 1 -C 6 alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl, wherein the C 1 -C 6 alkyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl of B is unsubstituted or substituted with one or more R 11 substituents;

each R 11 is independently selected from the group consisting of heterocycloalkyl, heteroaryl, cycloalkyl, aryl, C 1 -C 6 alkyl, halo, fluoroalkyl, —OR b , —C(O)R c , —C(O)OR d , oxo, and —NR e R f , wherein each heterocycloalkyl and heteroaryl of R 11 is unsubstituted or substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —C(O)R n , —C(O)OR p , and —C(O)NR q R r ; and

each R b , R c , R d , R e , R f , R n , R p , R q , and R r is independently H or C 1 -C 6 alkyl.

16. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein B is selected from the group consisting of C 1 -C 4 alkyl, C 3 -C 5 cycloalkyl, 6- to 10-membered aryl, 4- to 6-membered heterocycloalkyl comprising at least one annular N or 0 atom, 5- or 6-membered monocyclic heteroaryl comprising at least one annular N atom, and 8-or 9-membered bicyclic heteroaryl comprising at least one annular N atom, each of which is substituted or unsubstituted.

17. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein B selected from the group consisting of C 1 -C 4 alkyl, C 3 -C 5 cycloalkyl, 6- to 10-membered aryl, 4- to 6-membered heterocycloalkyl comprising at least one annular N or O atom, 5- or 6-membered monocyclic heteroaryl comprising at least one annular N atom, or 8- or 9-membered bicyclic heteroaryl comprising at least one annular N atom, each of which is unsubstituted or substituted with one or more R 11 substituents;

each R 11 is independently selected from the group consisting of heterocycloalkyl, heteroaryl, cycloalkyl, aryl, C 1 -C 6 alkyl, halo, fluoroalkyl, —OR b , —C(O)R c , —C(O)OR d , oxo, and —NR e R f , wherein each heterocycloalkyl and heteroaryl of R 11 is unsubstituted or substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —C(O)R n , —C(O)OR p , and —C(O)NR q R r , and wherein each C 1 -C 6 alkyl of R 11 is unsubstituted or substituted with —OR b ; and

each R b , R c , R d , R e , R f , R n , R p , R q , and R r is independently H or C 1 -C 6 alkyl.

18. The compound of claim, or a pharmaceutically acceptable salt thereof, wherein each R 11 is independently selected from the group consisting of methyl, ethyl, isopropyl, cyclopropyl, difluoromethyl, trifluoromethyl, oxo, —C(O)CH 3 , —C(O)OtBu, —OCH 3 , —OH, —NH 2 , —Cl, oxetanyl, oxadiazolyl, and azetidinyl, wherein each oxadiazolyl and azetidinyl of R 11 is unsubstituted or substituted with one or more substituents selected from the group consisting of ethyl, —C(O)CH 3 , —C(O)OtBu, —C(O)OCH 3 , —C(O)NHCH 3 , —C(O)NH 2 , and —OCH 3 , and wherein each methyl, ethyl, and isopropyl of R 11 is unsubstituted or substituted with —OH.

19. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein B is selected from the group consisting of:

each of which is unsubstituted or substituted with one or more R 11 substituents;

each R 11 is independently selected from the group consisting of heterocycloalkyl, heteroaryl, halo, C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted with one or two R 12 substituents, cycloalkyl, cycloalkyl substituted with one or two R 12 substituents, fluoroalkyl, —OR b , —C(O)R c , —C(O)OR d , oxo, and —NR e R f ;

each R 12 is independently selected from the group consisting of halo, —OR b , —C(O)R g , —C(O)OR h , and —C(O)NR i R j ; and

each R b , R c , R d , R e , and R f , R g , R h , R i , and R j is independently H or C 1 -C 6 alkyl.

20. A compound, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of

Structure

Name

N-(6-(5-methyl-1,2,4-oxadiazol-3-yl)- 2,3-dihydrobenzofuran-3- yl)benzamide;

2-methyl-N-(6-(5-methyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3- yl)isonicotinamide;

1-methyl-N-(6-(5-methyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-5-carboxamide;

(S)-1-methyl-N-(6-(5-methyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-5-carboxamide;

N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1-methyl- 1H-pyrazole-5-carboxamide;

(S)-N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1-methyl- 1H-pyrazole-5-carboxamide;

1,3-dimethyl-N-(6-(5-methyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-5-carboxamide;

(S)-1,3-dimethyl-N-(6-(5-methyl- 1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-5-carboxamide;

1,3-dimethyl-N-(6-(5-methyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-4-carboxamide;

(S)-1,3-dimethyl-N-(6-(5-methyl- 1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-4-carboxamide;

2,4-dimethyl-N-(6-(5-methyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)oxazole-5- carboxamide;

(R)-2,4-dimethyl-N-(6-(5-methyl- 1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)oxazole-5- carboxamide;

(S)-2,4-dimethyl-N-(6-(5-methyl- 1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)oxazole-5- carboxamide;

1,5-dimethyl-N-(6-(5-methyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-4-carboxamide;

(S)-1,5-dimethyl-N-(6-(5-methyl- 1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-4-carboxamide;

2-methyl-N-(6-(5-methyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)oxazole-5- carboxamide;

(S)-2-methyl-N-(6-(5-methyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)oxazole-5- carboxamide;

2-methyl-N-(6-(5-methyl-1,2,4- oxadiazol-3-yl)-2,3-dihydrofuro[3,2- b]pyridin-3-yl)isonicotinamide;

(S)-2-methyl-N-(6-(5-methyl-1,2,4- oxadiazol-3-yl)-2,3-dihydrofuro[3,2- b]pyridin-3-yl)isonicotinamide;

N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1,3- dimethyl-1H-pyrazole-5- carboxamide;

(S)-N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1,3- dimethyl-1H-pyrazole-5- carboxamide;

N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-2,4- dimethyloxazole-5-carboxamide;

(S)-N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-2,4- dimethyloxazole-5-carboxamide;

N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3-dihydrofuro[3,2- b]pyridin-3-yl)-2- methylisonicotinamide;

(S)-N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3-dihydrofuro[3,2- b]pyridin-3-yl)-2- methylisonicotinamide;

N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-2-methyl- 2H-tetrazole-5-carboxamide;

(S)-N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-2-methyl- 2H-tetrazole-5-carboxamide;

2-methyl-N-(6-(5-methyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-2H- tetrazole-5-carboxamide;

(S)-2-methyl-N-(6-(5-methyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-2H- tetrazole-5-carboxamide;

N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-2- methyloxazole-5-carboxamide;

(S)-N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-2- methyloxazole-5-carboxamide;

N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1,3- dimethyl-1H-pyrazole-4- carboxamide;

(S)-N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1,3- dimethyl-1H-pyrazole-4- carboxamide;

N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1,5- dimethyl-1H-pyrazole-4- carboxamide;

(S)-N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1,5- dimethyl-1H-pyrazole-4- carboxamide;

(S)-1-methyl-N-(6-(5-methyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-4-carboxamide;

1-methyl-N-(6-(5-methyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-4-carboxamide;

(S)-N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1-methyl- 1H-pyrazole-4-carboxamide;

N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1-methyl- 1H-pyrazole-4-carboxamide;

(R)-N-(6-(5-cyclopropyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1-methyl- 1H-pyrazole-5-carboxamide;

N-(6-(5-cyclopropyl-1,2,4-oxadiazol- 3-yl)-2,3-dihydrobenzofuran-3-yl)-1- methyl-1H-pyrazole-5-carboxamide;

(S)-N-(6-(5-cyclopropyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1-methyl- 1H-pyrazole-5-carboxamide;

N-(6-(5-(methoxymethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1-methyl- 1H-pyrazole-5-carboxamide;

(S)-N-(6-(5-(methoxymethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1-methyl- 1H-pyrazole-5-carboxamide;

(R)-N-(6-(5-(methoxymethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1,3- dimethyl-1H-pyrazole-5- carboxamide;

N-(6-(5-(methoxymethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1,3- dimethyl-1H-pyrazole-5- carboxamide;

(S)-N-(6-(5-(methoxymethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1,3- dimethyl-1H-pyrazole-5- carboxamide;

(S)-N-(6-(5-ethyl-1,2,4-oxadiazol-3- yl)-2,3-dihydrobenzofuran-3-yl)-1- methyl-1H-pyrazole-5-carboxamide;

N-(6-(5-ethyl-1,2,4-oxadiazol-3-yl)- 2,3-dihydrobenzofuran-3-yl)-1- methyl-1H-pyrazole-5-carboxamide;

N-(6-(5-ethyl-1,2,4-oxadiazol-3-yl)- 2,3-dihydrobenzofuran-3-yl)-1,3- dimethyl-1H-pyrazole-5- carboxamide;

(S)-N-(6-(5-ethyl-1,2,4-oxadiazol-3- yl)-2,3-dihydrobenzofuran-3-yl)-1,3- dimethyl-1H-pyrazole-5- carboxamide;

N-(6-(5-cyclopropyl-1,2,4-oxadiazol- 3-yl)-2,3-dihydrobenzofuran-3-yl)- 1,3-dimethyl-1H-pyrazole-5- carboxamide;

(S)-N-(6-(5-cyclopropyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1,3- dimethyl-1H-pyrazole-5- carboxamide;

N-(6-(5-cyclopropyl-1,2,4-oxadiazol- 3-yl)-2,3-dihydrobenzofuran-3-yl)-2- methyl-2H-tetrazole-5-carboxamide;

(S)-N-(6-(5-cyclopropyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-2-methyl- 2H-tetrazole-5-carboxamide;

(S)-N-(6-(5-cyclopropyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1-methyl- 1H-pyrazole-4-carboxamide;

N-(6-(5-cyclopropyl-1,2,4-oxadiazol- 3-yl)-2,3-dihydrobenzofuran-3-yl)-1- methyl-1H-pyrazole-4-carboxamide;

(S)-N-(6-(5-ethyl-1,2,4-oxadiazol-3- yl)-2,3-dihydrobenzofuran-3-yl)-1- methyl-1H-pyrazole-4-carboxamide;

N-(6-(5-ethyl-1,2,4-oxadiazol-3-yl)- 2,3-dihydrobenzofuran-3-yl)-1- methyl-1H-pyrazole-4-carboxamide;

(S)-1-methyl-N-(6-(5-(methyl-d3)- 1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-5-carboxamide;

(S)-1-methyl-N-(6-(5-(methyl-d3)- 1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-4-carboxamide;

(S)-1,3-dimethyl-N-(6-(5-(methyl- d3)-1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-5-carboxamde;

(S)-2-methyl-N-(6-(5-(methyl-d3)- 1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)oxazole-5- carboxamide;

(S)-2,4-dimethyl-N-(6-(5-(methyl- d3)-1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)oxazole-5- carboxamide;

(S)-1,5-dimethyl-N-(6-(5-(methyl- d3)-1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-4-carboxamide;

(S)-1,3-dimethyl-N-(6-(5-(methyl- d3)-1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-4-carboxamide;

(S)-2-methyl-N-(6-(5-(methyl-d3)- 1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-2H- tetrazole-5-carboxamide;

(S)-1-methyl-N-(6-(3-(methyl-d3)- 1,2,4-oxadiazol-5-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-4-carboxamide;

(S)-1-methyl-N-(6-(3-(methyl-d3)- 1,2,4-oxadiazol-5-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-5-carboxamide;

(S)-1-methyl-N-(6-(3-methyl-1,2,4- oxadiazol-5-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-4-carboxamide;

(S)-1-methyl-N-(6-(3-methyl-1,2,4- oxadiazol-5-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-5-carboxamide;

(S)-N-(6-(5-ethyl-1,2,4-oxadiazol-3- yl)-2,3-dihydrobenzofuran-3-yl)-3- methylisoxazole-5-carboxamide;

(S)-N-(6-(5-ethyl-1,2,4-oxadiazol-3- yl)-2,3-dihydrobenzofuran-3-yl)-3- methylisoxazole-4-carboxamide;

(S)-1,5-dimethyl-N-(6-(3-(methyl- d3)-1,2,4-oxadiazol-5-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-4-carboxamide;

(S)-2-methyl-N-(6-(3-(methyl-d3)- 1,2,4-oxadiazol-5-yl)-2,3- dihydrobenzofuran-3-yl)-2H- tetrazole-5-carboxamide;

(S)-1,5-dimethyl-N-(6-(3-methyl- 1,2,4-oxadiazol-5-yl)-2,3- dihydrobenzofuran-3-yl)-1H- pyrazole-4-carboxamide;

(S)-2-methyl-N-(6-(3-methyl-1,2,4- oxadiazol-5-yl)-2,3- dihydrobenzofuran-3-yl)-2H- tetrazole-5-carboxamide;

(S)-3-methyl-N-(6-(5-methyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)isoxazole-5- carboxamide;

(S)-3-methyl-N-(6-(5-methyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)isoxazole-4- carboxamide;

methyl (S)-(6-(5-cyclopropyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)carbamate;

methyl (S)-6-(5-ethyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)carbamate;

(S)-2-methyl-N-(6-(5-methylisoxazol- 3-yl)-2,3-dihydrobenzofuran-3-yl)- 2H-tetrazole-5-carboxamide;

(S)-N-(6-(5-ethylisoxazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-2-methyl- 2H-tetrazole-5-carboxamide;

(S)-N-(6-(5-ethylisoxazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1-methyl- 1H-pyrazole-5-carboxamide;

(S)-N-(6-(5-ethylisoxazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-2- methyloxazole-5-carboxamide;

(S)-N-(6-(5-ethylisoxazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-1-methyl- 1H-pyrazole-4-carboxamide;

(S)-N-(6-(5-ethylisoxazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-4- methyloxazole-5-carboxamide;

(S)-N-(6-(5-ethylisoxazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-2- methylisonicotinamide;

(S)-1-methyl-N-(6-(5-methylisoxazol- 3-yl)-2,3-dihydrobenzofuran-3-yl)- 1H-pyrazole-4-carboxamide;

(S)-1-methyl-N-(6-(5-methylisoxazol- 3-yl)-2,3-dihydrobenzofuran-3-yl)- 1H-pyrazole-5-carboxamide;

(S)-2-methyl-N-(6-(5-methylisoxazol- 3-yl)-2,3-dihydrobenzofuran-3- yl)oxazole-5-carboxamide;

(S)-4-methyl-N-(6-(5-methylisoxazol- 3-yl)-2,3-dihydrobenzofuran-3- yl)oxazole-5-carboxamide;

(S)-2-methyl-N-(6-(5-methylisoxazol- 3-yl)-2,3-dihydrobenzofuran-3- yl)isonicotinamide;

(S)-N-(6-(5-ethylisoxazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-5-methyl- 1H-pyrazole-4-carboxamide;

(S)-5-methyl-N-(6-(5-methylisoxazol- 3-yl)-2,3-dihydrobenzofuran-3-yl)- 1H-pyrazole-4-carboxamide;

(S)-N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-2,2- difluoroacetamide;

(S)-N-(6-(5-ethyl-1,2,4-oxadiazol-3- yl)-2,3-dihydrobenzofuran-3- yl)acetamide;

(S)-N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)acetamide;

(S)-N-(6-(5-ethyl-1,2,4-oxadiazol-3- yl)-2,3-dihydrobenzofuran-3- yl)acetamide-2,2,2-d3;

(S)-N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)acetamide- 2,2,2-d3;

(S)-N-(6-(5-methyl-1,2,4-oxadiazol- 3-yl)-2,3-dihydrobenzofuran-3- yl)acetamide;

(S)-N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-4- methyloxazole-5-carboxamide;

(S)-4-methyl-N-(6-(5-methyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)oxazole-5- carboxamide;

(S)-N-(6-(5-ethyl-1,2,4-oxadiazol-3- yl)-2,3-dihydrobenzofuran-3-yl)-4- methyloxazole-5-carboxamide;

(S)-N-(6-(5-cyclopropyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-4- methyloxazole-5-carboxamide;

(S)-N-(6-(5-cyclopropyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)acetamide;

(S)-N-(6-(5-cyclobutyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)acetamide;

(S)-N-(6-(5-(1-methylcyclopropyl)- 1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)acetamide;

(S)-4-methyl-N-(6-(5-(1- methylcyclopropyl)-1,2,4-oxadiazol- 3-yl)-2,3-dihydrobenzofuran-3- yl)oxazole-5-carboxamide;

(S)-N-(6-(5-cyclopropyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-2- methyloxazole-5-carboxamide;

(S)-N-(6-(5-ethyl-1,2,4-oxadiazol-3- yl)-2,3-dihydrobenzofuran-3-yl)-2- methyloxazole-5-carboxamide;

(S)-2-methyl-N-(6-(5-(1- methylcyclopropyl)-1,2,4-oxadiazol- 3-yl)-2,3-dihydrobenzofuran-3- yl)oxazole-5-carboxamide;

(S)-N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-3- (hydroxymethyl)benzamide;

(S)-N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-4- (hydroxymethyl)picolinamide;

(S)-N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-4- (hydroxymethyl)picolinamide;

(S)-N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-2- (hydroxymethyl)isonicotinamide;

(S)-N-(6-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-2- (hydroxymethyl)isonicotinamide;

(S)-3-(hydroxymethyl)-N-(6-(5- (methoxymethyl)-1,2,4-oxadiazol-3- yl)-2,3-dihydrobenzofuran-3- yl)benzamide;

(S)-3-(hydroxymethyl)-N-(6-(5- (methoxymethyl)-1,2,4-oxadiazol-3- yl)-2,3-dihydrobenzofuran-3- yl)benzamide;

(S)-4-(hydroxymethyl)-N-(6-(5- (methoxymethyl)-1,2,4-oxadiazol-3- yl)-2,3-dihydrobenzofuran-3- yl)picolinamide;

(S)-2-(hydroxymethyl)-N-(6-(5- (methoxymethyl)-1,2,4-oxadiazol-3- yl)-2,3-dihydrobenzofuran-3- yl)isonicotinamide;

(S)-3-(hydroxymethyl)-N-(6-(5- methyl-1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)benzamide;

(S)-4-(hydroxymethyl)-N-(6-(5- methyl-1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)picolinamide;

(S)-2-(hydroxymethyl)-N-(6-(5- methyl-1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3- yl)isonicotinamide;

3-((S)-1-hydroxyethyl)-N-((S)-6-(5- methyl-1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)benzamide;

3-((R)-1-hydroxyethyl)-N-((S)-6-(5- methyl-1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)benzamide;

3-((S)-1-hydroxyethyl)-N-((S)-6-(5- (methoxymethyl)-1,2,4-oxadiazol-3- yl)-2,3-dihydrobenzofuran-3- yl)benzamide;

3-((R)-1-hydroxyethyl)-N-((S)-6-(5- (methoxymethyl)-1,2,4-oxadiazol-3- yl)-2,3-dihydrobenzofuran-3- yl)benzamide;

2-(1-hydroxyethyl)-N-((S)-6-(5- methyl-1,2,4-oxadiazol-3-yl)-2,3- dihydrobenzofuran-3- yl)isonicotinamide;

(S)-N-((S)-6-(5-ethyl-1,2,4-oxadiazol- 3-yl)-2,3-dihydrobenzofuran-3-yl)-3- hydroxypyrrolidine-1-carobxamide;

(R)-N-((S)-6-(5-ethyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-3- hydroxypyrrolidine-1-carboxamide;

(S)-N-(6-(5-ethyl-1,2,4-oxadiazol-3- yl)-2,3-dihydrobenzofuran-3-yl)-3- hydroxyazetidine-1-carboxamide;

(S)-N-((S)-6-(5-ethyl-1,2,4-oxadiazol- 3-yl)-2,3-dihydrobenzofuran-3-yl)-3- fluoropyrrolidine-1-carboxamide;

(R)-N-((S)-6-(5-ethyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)-3- fluoropyrrolidine-1-carboxamide;

2-hydroxyethyl (S)-(6-(4-ethyl-1,2,4- oxadiazol-3-yl)-2,3- dihydrobenzofuran-3-yl)carbamate;

(S)-1-(6-(5-ethyl-1,2,4-oxadiazol-3- yl)-2,3-dihydrobenzofuran-3-yl)-3-(2- hydroxyethyl)urea; and

(S)-3-(6-(5-ethyl-1,2,4-oxadiazol-3- yl)-2,3-dihydrobenzofuran-3-yl)-1-(2- hydroxyethyl)-1-methylurea.

21. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

22. A method of treating heart disease in a subject in need thereof, comprising administering to the subject a compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the heart disease is hypertrophic cardiomyopathy (HCM) or heart failure with preserved ejection fraction (HFpEF).

23. The method of claim 22 , wherein the heart disease is hypertrophic cardiomyopathy (HCM).

24. The method of claim 23 , wherein the HCM is obstructive or nonobstructive or is associated with a sarcomeric and/or non-sarcomeric mutation.

25. The method of claim 22 , wherein the heart disease is heart failure with preserved ejection fraction (HFpEF).

26. A method of inhibiting the cardiac sarcomere, comprising contacting the cardiac sarcomere with a compound of claim 1 , or a pharmaceutically acceptable salt thereof.