# US 10,501,449 B2 · Substituted nitrogen containing compounds

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- Number: US 10,501,449 B2
- Document ID: US10501449B2
- Status: Granted
- Kind: B2
- Application number: 15/993,683
- Filed: 2018-05-31
- Published: 2018-12-06
- Granted: 2019-12-10
- Earliest claimed: 2018-05-31
- Assignees: Bristol-Myers Squibb Company
- Applicants: Bristol-Myers Squibb Company
- Inventors: Navnath Dnyanoba Yadav; Rajeev S. Bhide; Rajesh Onkardas Bora; Prashantha Gunaga; Manoranjan Panda; Eldon Scott Priestley; Jeremy Richter
- Web page: https://patentgrep.com/patent/US10501449B2

## CPC

- C07D 405/14: containing three or more hetero rings
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/12: Antihypertensives
- C07D 413/14: containing three or more hetero rings
- C07D 417/14: containing three or more hetero rings
- C07D 487/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed are compounds of Formula (I) or a salt thereof, wherein R1 is: each W is independently NR1b or O; Z is a bond or CHR1d; and R1, R2, Rd, R3a, R3b, L1, B, V, Y, and n are defined herein. Also disclosed are methods of using such compounds as inhibitors of ROMK, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating cardiovascular diseases.

## Claims

### Claim 1

A compound having the structure of Formula (I)
or a salt thereof, wherein:
R1 is:
each W is independently NR1b or O;
Z is a bond or CHR1d;
X is independently N or CR1a, wherein X is N at only 0, 1, or 2 positions;
each R1a is independently H, F, Cl, —OH, —CN, C1-3 alkyl, C1-3 fluoroalkyl, C3-6 cycloalkyl, C1-3 alkoxy, or C1-3 fluoroalkoxy;
each R1b is independently H, C1-3 alkyl, C2-3 fluoroalkyl, C3-6 cycloalkyl
R1c is independently H, deuterium, C1-4 alkyl, C1-4 fluoroalkyl, or C3-6 cycloalkyl;
R1d is H, C1-3 alkyl, C1-4 fluoroalkyl, or C3-6 cycloalkyl;
Y is —C(R6)2—, —C(R6)2—C(R6)2—, —C(O)—, —C(O)—C(R6)2—, —C(R6)2—C(O)—, or SO2—;
V is —O—, —NR4—, —CR5R5—, —S—, —S(O)—, —SO2—, or —C(O)—; wherein if V is —O—, —S—, —S(O)—, —SO2—, or —C(O)—, then Y is not —SO2—, and wherein if V is —O—, —S—, or NR4, then Y is not C(R6)2, and wherein if V is —S(O)—, —SO2—, or C(═O)—, then Y is not —C(═O)—, —C(═O)—C(R6)2—;
L1 is —C(R)2—, —C(O)—, or —C(R)2—C(R)2—; wherein R is independently H, F, OH, C1-3 alkyl, C1-3 hydroxyalkyl, C1-3 alkoxyalkyl, or C1-3 fluoroalkyl; wherein R is not —OH or F if it is attached to a carbon atom that is adjacent to a nitrogen atom:
Ring B is phenyl, pyridinyl, pyrimidinyl, pyrrazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, isoxazolyl, isothiazolyl, pyrrolyl, pyrazinyl, oxazolyl, pyridazinyl, pyrrolidinyl, or imidazolidinyl;
R2 is a C6-10 aryl, or a 5 to 10 membered heterocycle ring containing 1 to 4 heteroatoms selected from N, O, and S, the heterocycle ring optionally containing an oxo substitution, the aryl or heterocycle ring are substituted with 0-3 R2a;
R2a is independently OH, ═O, CN, halo, C1-4 alkyl, C1-4 deuteroalkyl, C1-4 fluoroalkyl, C1-4 alkoxy, C1-4 deuteroalkoxy, C1-4 fluoroalkoxy, C3-6 cycloalkyl, C3-6 cycloalkoxy, C(═O)NR4bR4b, C(═O)C1-4 alkyl, SO2Re, NR4bSO2R4b, or a 4 to 6 membered heterocycle having 1, 2, 3, or 4 heteroatoms selected from O, S, and N, the heterocycle optionally containing an oxo substitution and is substituted with 0-3 R2b;
R2b is independently C1-3 alkyl, C1-3 fluoralkyl, C1-3 hydroxyalkyl, C3-6 cycloalkyl, or C3-6 fluorocycloalkyl;
R3a is H, halo, OH, CN, C1-3 alkyl, C1-3 hydroxyalkyl, C1-3 fluoroalkyl, C1-3 alkoxy, or C3-6 cycloalkyl, wherein if V is —O—, —NR4—, —S—, —S(O)—, —SO2—, or —C(═O)—, then R3a is not halo, and wherein if V is —O—, —NR4—, —S—, then R3a is not OH, CN;
R3b is H, ═O, C1-3 alkyl, C1-3 hydroxyalkyl, C1-3 fluoroalkyl, C1-3 alkoxy, or C3-6 cycloalkyl;
R4 is H, C1-3 alkyl, C2-3 fluoroalkyl, C2-3 hydroxyalkyl, CO2R4a, C(O)R4a, SO2R4a, C(O)N(R4bR4b), SO2N(R4bR4b), or OH;
R4a is C1-3 alkyl, C1-3 fluoroalkyl, C3-6 cycloalkyl, C3-6 fluorocycloalkyl, C6-10 aryl or a 4 to 10 membered heterocycle having 1, 2, 3 or 4 heteroatoms selected from O, S, and N, the aryl or heterocycle being substituted with 0-3 R4c;
R4b is independently H, C1-3 alkyl, C2-3 fluoroalkyl, C3-6 cycloalkyl, C3-6 fluorocycloalkyl, C6-10 aryl or a 4 to 10 membered heterocycle having 1, 2, 3 or 4 heteroatoms selected from O, S, and N;
alternatively, 2 R4bs, along with the atom to which they are attached, join to form a 3 to 6 membered saturated ring containing an additional 0-2 heteroatoms selected from O, S, and N;
R4c is independently H, F, Cl, or C1-3 alkyl;
R5 is independently H, F, OH, C1-3 alkoxy, C1-3 fluoroalkoxy, C1-3 alkyl, C1-3 fluoroalkyl, C1-3 hydroxyalkyl, C3-6 cycloalkyl, C3-6 fluorocycloalkyl, NR5bR5b, O—R5c, or 2 R5s are ═O; wherein if one R5 is F, OH or NR5bR5b, then the other R5 is not OH, or NR5bR5b;
R5b is independently H, C1-3 alkyl, C3-6 cycloalkyl, C(O)Ra, SO2Ra, or C(O)NRbRb;
alternatively, 2 R5bs, along with the atom to which they are attached, join to form a 3 to 6 membered saturated ring containing 0-2 heteroatoms selected from O, S, or N;
R5c is independently H, C1-3 alkyl, C3-6 cycloalkyl, or C(O)NRbRb;
R6 is independently H, OH, F, C1-3 alkyl, C1-3 deuteroalkyl, C1-3 fluoroalkyl, C3-6 cycloalkyl, C3-6 fluorocycloalkyl, C1-3 alkoxy, C1-3 hydroxyalkyl, C1-3 hydroxydeuteroalkyl, C1-3 alkoxyalkyl, or C1-3 fluoroalkoxyalkyl, or NR6bR6b; wherein if one R6 on one carbon atom is F, OH or NR6bR6b, then the other R6 on the same carbon atom is not OH or NR6bR6b;
R6b is independently H, C1-3 alkyl, C3-6 cycloalkyl, C(O)Ra, SO2Ra, or C(O)NRbRb; alternatively, 2 R6s along with the same atom to which they are attached can form a 3 to 6 membered saturated ring containing 0-2 heteroatoms selected from O, S, and N;
Ra is independently H, C1-3 alkyl, C2-3 fluoroalkyl, C3-6 cycloalkyl, C3-6 fluorocycloalkyl, C6-10 aryl or a 4 to 10 membered heterocycle having 1, 2, 3, or 4 heteroatoms selected from O, S, and N;
Rb is independently H, C1-3 alkyl, C2-3 fluoroalkyl, C3-6 cycloalkyl, C3-6 fluorocycloalkyl, C6-10 aryl or a 4 to 10 membered heterocycle having 1, 2, 3 or 4 heteroatoms selected from O, S, and N;
alternatively, 2 Rb's along with the atom to which they are attached, join to form a 3 to 6 membered saturated ring, containing 0-2 heteroatoms selected from O, S, and N;
each Rd is independently H, F, C1-3 alkyl, C1-3 fluoroalkyl, C1-3 alkoxy, C1-3 fluoroalkoxy, C1-3 hydroxyalkyl, C3-6 cycloalkyl, halo, OH, ═O, CN, OCF3, OCHF2, CHF2CF3, or C(O)NReRe;
each Re is independently H, C1-3 alkyl, C2-3 fluoroalkyl, C3-6 cycloalkyl, C2-3 hydroxyalkyl, C2-3 alkoxyalkyl, C6-10 aryl, or a 5 to 10 membered heteroaryl having 1, 2, 3, or 4 heteroatoms selected from O, S, and N;
alternatively, 2 Res along with the atom to which they are attached, join to form a 3 to 6 membered saturated ring, containing 0-2 heteroatoms selected from O, S, or N; and
n is 0, 1, or 2.

### Claim 2 (depends on 1)

A compound of claim 1, or salt thereof, wherein:
R1 is:
each R1a is independently selected from F, Cl, C1-3 alkyl, C1-3 fluoroalkyl, and C3-6 cycloalkyl;
R1c is independently H, deuterium, C1-2 alkyl, or C3-6 cycloalkyl; and
n is zero, 1, or 2.

### Claim 3 (depends on 2)

A compound of claim 2, or salt thereof, wherein:
R2 is phenyl, pyridinyl, indolyl, indazolyl, benzo[d]oxazol-onyl, pyrazolo[4,3-b]pyridinyl, pyridin-2-onyl, pyrazolyl, [1,2,4]triazolo[1,5-a]pyridinyl, imidazo[1,2-b]pyridazinyl, pyrazinyl, pyrazolo[1,5-a]pyrimidinyl, thiazolyl, thiophenyl, 1,2,3-triazolyl, benzo[d][1,2,3]triazolyl, [1,2,4]triazolo[4,3-b]pyridazinyl, benzo[d]imidazolyl, imidazolyl, pyrazolo[3,4-b]pyridinyl, pyrazolo[3,4-c]pyridinyl, pyrazolo[4,3-c]pyridinyl, pyrrolyl, pyrrolo[2,3-b]pyridinyl, pyrrolo[2,3-c]pyridinyl, pyrrolo[3,2-b]pyridinyl, pyrrolo[3,2-c]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, tetrazolyl, 1,2,4-triazolyl, isothiazolyl, isoxazolyl, oxazolyl, pyridazinyl, pyrimidinyl, or benzo[d]oxazol-2-onyl, triazolyl, oxadiazolyl, or pyrrolopyridinyl, each being substituted with 0-3 R2a.

### Claim 4 (depends on 3)

A compound of claim 3, or salt thereof, wherein:
Ring B is pyridinyl, pyrimidinyl, pyrrazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, isoxazolyl, pyrazinyl, oxazolyl, or pyridazinyl.

### Claim 5 (depends on 4)

A compound of claim 4, or salt thereof, wherein:
V is —O—, —CR5R5—, or —C(═O)—;
wherein if V is —O—, or NR4, then Y is not C(R6)2;
Y is —C(R6)2—, —C(R6)2—C(R6)2—, —C(═O)—, —C(═O)—C(R6)2—, or —C(R6)2—C(O)—; and
L1 is —C(R)2—, —C(O)—, or —CH2—C(R)2—; wherein R is independently from hydrogen, F, OH, C1-3 alkyl, C1-3 hydroxyalkyl, C1-3 alkoxyalkyl, or C1-3fluoroalkyl.

### Claim 6 (depends on 5)

A compound of claim 5, or salt thereof, wherein:
R2 is phenyl, pyridinyl, indolyl, indazolyl, benzo[d]oxazol-2(3H)-onyl, pyrazolo[4,3-b]pyridinyl, pyridin-2(1H)-onyl, pyrazolyl, pyrimidinyl, imidazolyl, pyrazolyl, triazolyl, oxadiazolyl, thiadiazolyl, [1,2,4]triazolo[1,5-a]pyridinyl, imidazo[1,2-b]pyridazinyl, pyrazinyl, pyrazolo[1,5-a]pyrimidinyl, thiophenyl, [1,2,4]triazolo[4,3-b]pyridazinyl, pyrazolo[1,5-a]pyrimidinyl, or benzo[d]oxazol-2(3H)-only, each being substituted with 0-3 R2a; and
R2a is OH, ═O, CN, halo, C1-4 alkyl, SO2C1-4 alkyl, oxazolidin-2-one substituted with 0-1 R2b;
R2b is C1-3alkyl, C1-3 fluoroalkyl, C1-3 alkoxy, or C1-3 fluoroalkoxy.

### Claim 7 (depends on 6)

A compound of claim 6, or salt thereof, wherein:
R1 is
R1a is independently H or —CH3.

### Claim 8 (depends on 7)

The compound according to claim 7, or salt thereof, wherein:
Ring B is pyridinyl, triazolyl, thiazolyl, oxadiazolyl, imidazolyl, or pyrrazolyl; and
R2 is phenyl, pyridinyl, pyrimidinyl, benzo[d]oxazol-2(3H)-onyl, imidazolyl, pyrazolyl, triazolyl, or oxadiazolyl, each being substituted with 0-3 R2a.

### Claim 9 (depends on 8)

The compound according to claim 8, or salt thereof, wherein:
V is —O—, —NR4—, or —CR5R5—;
Y is —C(R6)2—C(R6)2— or —C(R6)2—;
L1 is —C(R)2—; wherein R is independently hydrogen, F, OH, C1-3 alkyl, C1-3 hydroxyalkyl, C1-3 alkoxyalkyl, or C1-3 fluoroalkyl; and
R6 is independently H, C1-3-alkyl, C1-3-fluoroalkyl, or C3-6-cycloalkyl.

### Claim 10 (depends on 1)

A compound of claim 1, or salt thereof, wherein the compound is selected from
(R)-4-methyl-6-(4-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-4-methyl-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-3-methyl-5-(5-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)pyridin-2-yl)benzo[d]oxazol-2(3H)-one;
5-(4-((4,4-difluoro-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-1H-pyrazol-1-yl)-3-methylbenzo[d]oxazol-2(3H)-one;
6-(4-((4,4-difluoro-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile;
(R)-6-(5-methoxy-4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile;
(R)-4-methyl-5-(4-((1-(2-methylthiazol-5-yl)-1H-pyrazol-4-yl)methyl)morpholin-2-yl)isobenzofuran-1(3H)-one;
(R)-4-cyclopropyl-6-(4-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-4-methyl-6-(4-((5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-2-oxooxazolidin-3-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-4-methyl-6-(4-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-5-oxomorpholino)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-4-methoxy-6 (4 (2 (2 (4 methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)ethyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-6-(5-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1,3,4-oxadiazol-2-yl)nicotinonitrile;
(R)-4-methyl-6-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1,3,4-oxadiazol-2-yl)nicotinonitrile;
(R)-4-methoxy-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-imidazol-1-yl)nicotinonitrile;
(R)-4-methyl-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-5-oxopiperazin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-4-methyl-5-(4-((6-(4-methyl-1H-imidazol-1-yl)pyridin-3-yl)methyl)morpholin-2-yl)isobenzofuran-1(3H)-one;
(R)-4-methoxy-5′-((5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-2-oxooxazolidin-3-yl)methyl)-[2,2′-bipyridine]-5-carbonitrile;
6-(4-(1-hydroxy-2-((R)-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)ethyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile (Diastereomer-I & II);
(R)-3-methyl-5-(5-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)thiazol-2-yl)benzo[d]oxazol-2(3H)-one;
(R)-3-methyl-5-(5-(2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholine-4-carbonyl)thiazol-2-yl)benzo[d]oxazol-2(3H)-one;
(R)-1-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)thiazol-2-yl)-1H-imidazole-4-carbonitrile;
(R)-4-methyl-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2H-1,2,3-triazol-2-yl)nicotinonitrile;
(R)-4-methyl-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)nicotinonitrile;
Methyl-(R)-4-((1-(5-cyano-4-methylpyridin-2-yl)-1H-pyrazol-4-yl)methyl)-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazine-1-carboxylate;
(S)-4-methyl-6-(4-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-3-methyl-5-(4-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-pyrazol-1-yl)benzo[d]oxazol-2(3H)-one;
(R)-6-(5-methoxy-4-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile;
(R)-4-methoxy-6-(4-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-imidazol-1-yl)nicotinonitrile;
(R)-6-(4-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-imidazol-1-yl) nicotinonitrile;
(R)-3-methyl-5-(4-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-imidazol-1-yl)benzo[d]oxazol-2(3H)-one;
(R)-4-methyl-6-(5-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1,3,4-oxadiazol-2-yl)nicotinonitrile;
(R)-4-methyl-6 (4 (2 (2 (4 methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)ethyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-4-methoxy-6-(5-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)thiazol-2-yl)nicotinonitrile;
(R)-4-methyl-6-(5-(2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholine-4-carbonyl)thiazol-2-yl)nicotinonitrile;
(R)-4-methoxy-6-(5-(2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholine-4-carbonyl)thiazol-2-yl)nicotinonitrile;
(R)-4-methoxy-5′-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-[2,2′-bipyridine]-5-carbonitrile;
(R)-4-methyl-5-(4-((2-(4-methyl-1H-imidazol-1-yl)thiazol-5-yl)methyl)morpholin-2-yl)isobenzofuran-1(3H)-one;
(R)-1-(5-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)pyridin-2-yl)-1H-imidazole-4-carbonitrile;
(R)-4-methyl-5-(4-((1-(thiophen-3-yl)-1H-pyrazol-4-yl)methyl)morpholin-2-yl)isobenzofuran-1(3H)-one;
(R)-4-methyl-5-(4-((1-(pyrazin-2-yl)-1H-pyrazol-4-yl)methyl)morpholin-2-yl)isobenzofuran-1(3H)-one;
(R)-4-(4-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-pyrazol-1-yl)benzonitrile;
(R)-4-methyl-5-(4-((1-(6-methylpyrazin-2-yl)-1H-pyrazol-4-yl)methyl)morpholin-2-yl)isobenzofuran-1(3H)-one;
(R)-5-(4-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-3-(4-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-pyrazol-1-yl)benzonitrile;
(R)-4-methyl-5-(4-((1-(pyridin-4-yl)-1H-pyrazol-4-yl)methyl)morpholin-2-yl)isobenzofuran-1(3H)-one;
(R)-4-methyl-5-(4-((1-(4-(methylsulfonyl)phenyl)-1H-pyrazol-4-yl)methyl)morpholin-2-yl)isobenzofuran-1(3H)-one;
(R)-2-methyl-4-(4-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-pyrazol-1-yl)benzonitrile;
(R)-3-methyl-4-(4-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-pyrazol-1-yl)benzonitrile;
(R)-5-(4-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-pyrazol-1-yl)picolinonitrile;
(R)-2-methoxy-4-(4-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-pyrazol-1-yl)benzonitrile;
(R)-4-methyl-5-(4-((1-(pyrazolo[1,5-a]pyrimidin-5-yl)-1H-pyrazol-4-yl)methyl)morpholin-2-yl)isobenzofuran-1(3H)-one;
(R)-3-methoxy-4-(4-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-pyrazol-1-yl)benzonitrile;
(R)-4-methyl-6-(3-methyl-4-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-4-methyl-6-(3-((2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(S)-4-methyl-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-5-(5-methoxy-4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)-3-methylbenzo[d]oxazol-2(3H)-one;
(R)-7-fluoro-3-methyl-5-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-l-yl)methyl)-1H-pyrazol-1-yl)benzo[d]oxazol-2(3H)-one;
(R)-7-methoxy-3-methyl-5-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)benzo[d]oxazol-2(3H)-one;
(R)-3,7-dimethyl-5-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)benzo[d]oxazol-2(3H)-one;
(R)-3-methyl-5-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)benzo[d]oxazol-2(3H)-one;
(R)-4-methoxy-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-3-methyl-5-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)benzo[d]oxazol-2(3H)-one;
(R)-6-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1,3,4-oxadiazol-2-yl)nicotinonitrile;
(R)-4-methoxy-5′-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-[2,2′-bipyridine]-5-carbonitrile;
(R)-1-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyridin-2-yl)-1H-pyrazole-4-carbonitrile;
(R)-1-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyridin-2-yl)-1H-imidazole-4-carbonitrile;
(R)-4-methyl-5-(4-((6-(4-methyl-1H-imidazol-1-yl)pyridin-3-yl)methyl)piperazin-2-yl)isobenzofuran-1(3H)-one;
(R)-4-methyl-5-(4-((6-(3-methyl-1H-1,2,4-triazol-1-yl)pyridin-3-yl)methyl)piperazin-2-yl)isobenzofuran-1(3H)-one;
(R)-6-(4-((4-acetyl-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile;
(R)-4-methyl-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-4-(methylsulfonyl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-4-methyl-6-(4-((4-methyl-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-3-methyl-5-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-5-oxopiperazin-l-yl)methyl)-1H-pyrazol-1-yl)benzo[d]oxazol-2(3H)-one;
(R)-3-methyl-5-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-5-oxopiperazin-l-yl)methyl)-1H-1,2,3-triazol-1-yl)benzo[d]oxazol-2(3H)-one;
(R)-1-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-5-oxopiperazin-1-yl)methyl)pyridine-2-yl)-1H-1,2,4-triazole-3-carbonitrile;
(R)-4-methoxy-5′-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-5-oxopiperazin-1-yl)methyl)-[2,2′-bipyridine]-5-carbonitrile;
(R)-6-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-4-((6-(3-methyl-1H-1,2,4-triazol-1-yl)pyridin-3-yl)methyl)piperazin-2-one;
(R)-6-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-4-((6-(4-methyl-1H-imidazol-1-yl)pyridin-3-yl)methyl)piperazin-2-one;
(R)-4-methyl-6-(4-((4-methyl-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-5-oxopiperazin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-4-methoxy-6-(4-((5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-2-oxooxazolidin-3-yl)methyl)-1H-imidazol-1-yl)nicotinonitrile;
(R)-6-(5-methoxy-4-((5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-2-oxooxazolidin-3-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile;
(R)-3-methyl-5-(4-((5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-2-oxooxazolidin-3-yl)methyl)-1H-pyrazol-1-yl)benzo[d]oxazol-2(3H)-one;
6-(4-(((3R,5R)-3-(hydroxymethyl)-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile;
6-(4-((3,3-dimethyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2H-1,2,3-triazol-2-yl)-4-methylnicotinonitrile;
4-methyl-6-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2H-1,2,3-triazol-2-yl)nicotinonitrile;
6-(4-(((3R,4R)-4-hydroxy-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)-4-methylnicotinonitrile;
2,4-dimethyl-6-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2H-1,2,3-triazol-2-yl)nicotinonitrile;
4-methoxy-2-methyl-6-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)nicotinonitrile;
6-(4-((3-(hydroxymethyl)-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile, (Enantiomer-III);
6-(4-((3-(hydroxymethyl)-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)-4-methylnicotinonitrile, (Enantiomer-III);
6-(4-((3-(hydroxymethyl)-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methoxynicotinonitrile, (Enantiomer-III);
6-(4-((3-(hydroxymethyl-d2)-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile, (Enantiomer-I);
1-(5-(((3R,5R)-3-(hydroxymethyl)-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyridin-2-yl)-3-methyl-1H-pyrazole-4-carbonitrile;
6-(4-(((3R,4R)-4-hydroxy-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-1H-pyrazol-1-yl)-2,4-dimethylnicotinonitrile;
2-methoxy-6-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
5-((2R,6S)-4-((2-(4,5-dimethyl-1H-imidazol-1-yl)pyrimidin-5-yl)methyl)-6-methylpiperazin-2-yl)-4-methylisobenzofuran-1(3H)-one;
4,6-dimethyl-2-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-imidazol-1-yl)pyrimidine-5-carbonitrile;
4-methyl-2-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)pyrimidine-5-carbonitrile;
4-methoxy-6-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-imidazol-1-yl)nicotinonitrile;
4-methyl-6-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-imidazol-1-yl)nicotinonitrile;
4-methoxy-2-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)pyrimidine-5-carbonitrile;
4-methyl-2-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2H-1,2,3-triazol-2-yl)pyrimidine-5-carbonitrile;
2-methoxy-4-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-imidazol-1-yl)benzonitrile;
4-methyl-5-((2R,6S)-6-methyl-4-((1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)methyl)piperazin-2-yl)isobenzofuran-1(3H)-one;
4-methoxy-2-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-imidazol-1-yl)pyrimidine-5-carbonitrile;
2-(4-(((3R,5R)-3-(hydroxymethyl)-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2H-1,2,3-triazol-2-yl)-4-methylpyrimidine-5-carbonitrile;
4-methyl-6-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
4-methyl-6-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)nicotinonitrile;
4-methoxy-6-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2H-1,2,3-triazol-2-yl)nicotinonitrile;
3-methyl-1-(5-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyrimidin-2-yl)-1H-pyrazole-4-carbonitrile;
5-(4-(((3R,5R)-3-(hydroxymethyl)-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2H-1,2,3-triazol-2-yl)-3-methylbenzo[d]oxazol-2(3H)-one;
6-(4-(((3R,4R)-4-hydroxy-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile;
6-(4-(((3R,4R)-4-hydroxy-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-2H-1,2,3-triazol-2-yl)-4-methoxynicotinonitrile;
6-(4-(((3R,4R)-4-hydroxy-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methoxynicotinonitrile;
4,4-methyl-6-(5-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)thiazol-2-yl)nicotinonitrile;
6-(4-((4-hydroxy-4-methyl-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile;
4-methyl-6-(4-((2-methyl-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
6-(4-((4-hydroxy-3,3-dimethyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile;
4-methyl-6-(5-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2-oxooxazol-3(2H)-yl)nicotinonitrile;
(R)-4-methyl-6-(4-((4-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-2-oxoimidazolidin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-4-methyl-6-(4-((4-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-1,1-dioxido-1,2,5-thiadiazolidin-2-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
2-methyl-6-(5-(((3 S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyridin-2-yl)pyridazin-3 (2H)-one;
4-methyl-6-(4-(1-((R)-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)ethyl)-2H-1,2,3-triazol-2-yl)nicotinonitrile (Dia-I:Ena-I);
4-methyl-6-(4-(1-((R)-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)ethyl)-2H-1,2,3-triazol-2-yl)nicotinonitrile (Dia-II:Ena-I);
4-methyl-6-(3-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-1,2,4-triazol-1-yl)nicotinonitrile;
6-(4-((2-(hydroxymethyl)-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile (Dia-I:Ena-I);
6-(4-((2-(hydroxymethyl)-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile (Dia-I:Ena-II);
6-(5-(((3R,4R)-4-hydroxy-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)thiazol-2-yl)-4-methylnicotinonitrile;
5-((2R,6S)-4-((1-(2-methoxypyridin-4-yl)-1H-imidazol-4-yl)methyl)-6-methylpiperazin-2-yl)-4-methylisobenzofuran-1(3H)-one;
5-((2R,6S)-4-((1-(2-(difluoromethyl)pyridin-4-yl)-1H-pyrazol-4-yl)methyl)-6-methylpiperazin-2-yl)-4-methylisobenzofuran-1(3H)-one;
4-methyl-5-((2R,6S)-6-methyl-4-((1-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazol-4-yl)methyl)piperazin-2-yl)isobenzofuran-1(3H)-one;
1-(difluoromethyl)-4-(4-(((3 S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)pyridin-2(1H)-one;
1-(5-(((3R,5R)-3-(hydroxymethyl)-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyridin-2-yl)-3-methyl-1H-pyrazole-4-carbonitrile;
1-(difluoromethyl)-4-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-imidazol-1-yl)pyridin-2(1H)-one;
6-(4-(((3R,4R)-4-hydroxy-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)oxazol-2-yl)-4-methylnicotinonitrile;
4-methyl-6-(5-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)oxazol-2-yl)nicotinonitrile;
5-((2R,6S)-4-((1-(6-(difluoromethyl)pyridin-3-yl)-1H-imidazol-4-yl)methyl)-6-methylpiperazin-2-yl)-4-methylisobenzofuran-1(3H)-one;
(R)-3,4-dimethyl-5-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)benzo[d]oxazol-2(3H)-one;
(R)-1-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyridin-2-yl)-1H-pyrazole-3-carbonitrile;
(R)-4-ethoxy-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-1-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyridin-2-yl)-1H-pyrazole-4-carboxamide;
(R)-5-(4-((2-(2,4-dimethyl-1H-imidazol-1-yl)pyrimidin-5-yl)methyl)piperazin-2-yl)-4-methylisobenzofuran-1(3H)-one;
(R)-4-isopropoxy-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-4-methyl-5-(4-((4-methyl-6-(4-methyl-1H-imidazol-1-yl)pyridin-3-yl)methyl)piperazin-2-yl)isobenzofuran-1(3H)-one;
(R)-4-methyl-5-(4-((2-methyl-6-(4-methyl-1H-imidazol-1-yl)pyridin-3-yl)methyl)piperazin-2-yl)isobenzofuran-1(3H)-one;
(R)-4,6′-dimethoxy-5′-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-[2,2′-bipyridine]-5-carbonitrile;
(R)-5-(4-((5-fluoro-6-(4-methyl-1H-imidazol-1-yl)pyridin-3-yl)methyl)piperazin-2-yl)-4-methylisobenzofuran-1(3H)-one;
(R)-4-methyl-6-(3-methyl-4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-4-methyl-6-(5-methyl-4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-4-methyl-5-(4-((6-(4-methyl-1H-imidazol-1-yl)-4-(trifluoromethyl)pyridin-3-yl)methyl)piperazin-2-yl)isobenzofuran-1(3H)-one;
(R)-5-(4-((2-(4,5-dimethyl-1H-imidazol-1-yl)pyrimidin-5-yl)methyl)piperazin-2-yl)-4-methylisobenzofuran-1(3H)-one;
(R)-5-(4-((4-methoxy-6-(4-methyl-1H-imidazol-1-yl)pyridin-3-yl)methyl)piperazin-2-yl)-4-methylisobenzofuran-1(3H)-one;
(R)-5-(4-((2-(5-(difluoromethyl)-4-methyl-1H-imidazol-1-yl)pyrimidin-5-yl)methyl)piperazin-2-yl)-4-methylisobenzofuran-1(3H)-one;
4,6-dimethyl-2-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2H-1,2,3-triazol-2-yl)pyrimidine-5-carbonitrile;
3-(3-methyl-5-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)phenyl)oxazolidin-2-one;
(R)-4-methyl-5-(4-((6-(4-methyl-1H-imidazol-1-yl)pyridazin-3-yl)methyl)piperazin-2-yl)isobenzofuran-1(3H)-one;
4-methoxy-6-(3-(((R)-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyrrolidin-1-yl)nicotinonitrile (Diastereomer-I);
4-methoxy-6-(3-(((R)-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyrrolidin-1-yl)nicotinonitrile (Diastereomer-II);
4-methyl-6-(3-(((R)-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyrrolidin-1-yl)nicotinonitrile (Diastereomer-I);
4-methyl-6-(3-(((R)-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyrrolidin-1-yl)nicotinonitrile (Diastereomer-II);
4-methyl-6-(4-(((R)-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2-oxopyrrolidin-1-yl)nicotinonitrile (Diastereomer-II);
4-methoxy-6-(4-(((R)-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2-oxopyrrolidin-1-yl)nicotinonitrile (Diastereomer-I);
4-methyl-6-(5-(((R)-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2-oxooxazolidin-3-yl)nicotinonitrile (Diastereomer-II);
4-methyl-5-((2R,6S)-6-methyl-4-((1-(5-(methyl sulfonyl)pyridin-2-yl)-1H-pyrazol-4-yl)methyl)piperazin-2-yl)isobenzofuran-1(3H)-one;
4-(4-(((3R,4R)-4-hydroxy-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-1H-imidazol-1-yl)-2-methoxybenzonitrile;
6-(4-(((3R,4R)-4-hydroxy-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-1H-imidazol-1-yl)-4-methylnicotinonitrile;
4-methyl-2-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-imidazol-1-yl)pyrimidine-5-carbonitrile;
4-methyl-5-((2R,6S)-6-methyl-4-((6′-(methylsulfonyl)-[2,3′-bipyridin]-5-yl)methyl)piperazin-2-yl)isobenzofuran-1(3H)-one;
4-methoxy-2-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2H-1,2,3-triazol-2-yl)pyrimidine-5-carbonitrile;
4-methoxy-2-(2-methyl-4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-imidazol-1-yl)pyrimidine-5-carbonitrile;
(R)-4-methoxy-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2H-1,2,3-triazol-2-yl)nicotinonitrile;
(R)-4-methyl-6-(4-methyl-5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2H-1,2,3-triazol-2-yl)nicotinonitrile;
4-methoxy-6-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2-oxopyrrolidin-1-yl)nicotinonitrile (Diastereomer-I);
6-(4-(((3R,4R)-4-hydroxy-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazol-1-yl)-4-methoxynicotinonitrile;
6-(3-isopropyl-4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)-4-methoxynicotinonitrile;
3-methyl-4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1-(2-methylpyrimidin-4-yl)-1,3-dihydro-2H-imidazol-2-one;
3-(5-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-[2,4′-bipyridin]-2′-yl)oxazolidin-2-one;
6-(4-((3,3-dimethyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-5-methyl-2H-1,2,3-triazol-2-yl)-4-methylnicotinonitrile (Enantiomer-I);
4-methyl-6-(5-methyl-4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)nicotinonitrile;
(R)-4-methyl-5-(4-((1-(1-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-4-yl)methyl)morpholin-2-yl)isobenzofuran-1(3H)-one;
4-methyl-5-((2R,6S)-6-methyl-4-((1-(p-tolyl)-1H-imidazol-4-yl)methyl)piperazin-2-yl)isobenzofuran-1(3H)-one;
4-methyl-5-((2R,6S)-6-methyl-4-((1-(3-methylpyridin-4-yl)-1H-imidazol-4-yl)methyl)piperazin-2-yl)isobenzofuran-1(3H)-one;
4-methyl-5-((2R,6S)-6-methyl-4-((1-(6-methylpyridin-3-yl)-1H-imidazol-4-yl)methyl)piperazin-2-yl)isobenzofuran-1(3H)-one;
5-((2R,6S)-4-((1-(2,6-dimethylpyridin-4-yl)-1H-imidazol-4-yl)methyl)-6-methylpiperazin-2-yl)-4-methylisobenzofuran-1(3H)-one;
5-((2R,6S)-4-((1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-1H-imidazol-4-yl)methyl)-6-methylpiperazin-2-yl)-4-methylisobenzofuran-1(3H)-one;
(R)-4-methyl-6-(2-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyrimidin-5-yl)nicotinonitrile;
(R)-2,4-dimethyl-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2H-1,2,3-triazol-2-yl)nicotinonitrile;
(R)-3-(2-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)pyridin-4-yl)oxazolidin-2-one;
(R)-2,4-dimethyl-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)nicotinonitrile;
(R)-4-methoxy-2-methyl-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)nicotinonitrile;
(R)-4-methoxy-2-methyl-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2H-1,2,3-triazol-2-yl)nicotinonitrile;
(R)-2-methoxy-4-methyl-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)nicotinonitrile;
6-(4-((3,3-dimethyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2H-1,2,3-triazol-2-yl)-4-methoxynicotinonitrile (Enantiomer-I);
4-methyl-6-(5-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1,3,4-oxadiazol-2-yl)nicotinonitrile;
4-methoxy-6-(4-(2-((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)ethyl)-1H-pyrazol-1-yl)nicotinonitrile;
6-(5-(((3R,4R)-4-hydroxy-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)isoxazol-3-yl)-4-methylnicotinonitrile;
5-((2R,6S)-4-((1-(4-methoxy-1,3,5-triazin-2-yl)-1H-pyrazol-4-yl)methyl)-6-methylpiperazin-2-yl)-4-methylisobenzofuran-1(3H)-one;
6-(4-(((3R,5R)-3-(hydroxymethyl)-4-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile;
6-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)-4-(trifluoromethyl)nicotinonitrile;
4-methyl-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile (Enantiomer-I);
(R)-2-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)isonicotinonitrile;
6-(4-((3-hydroxy-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile (Enantiomer-IV);
6-(4-((3-methoxy-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile (Enantiomer-II);
(R)-5-(4-((2-(3,5-dimethyl-4H-1,2,4-triazol-4-yl)pyrimidin-5-yl)methyl)piperazin-2-yl)-4-methylisobenzofuran-1(3H)-one;
3-methyl-2-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)isonicotinonitrile;
6-(4-(((3-fluoro-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)-4-methylnicotinonitrile (Enantiomer-I);
6-(4-((3-(1-hydroxyethyl)-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methoxynicotinonitrile (Enantiomer-I);
6-(4-((3-(difluoromethyl)-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile (Enantiomer-I);
4-methyl-5-((2R,6S)-6-methyl-4-((1-(5-methylpyrazin-2-yl)-1H-pyrazol-4-yl)methyl)piperazin-2-yl)isobenzofuran-1(3H)-one;
5-((2R,6S)-4-((1-(6-methoxypyrimidin-4-yl)-1H-pyrazol-4-yl)methyl)-6-methylpiperazin-2-yl)-4-methylisobenzofuran-1(3H)-one;
5-((2R,6S)-4-((1-(2-methoxypyrimidin-5-yl)-1H-pyrazol-4-yl)methyl)-6-methylpiperazin-2-yl)-4-methylisobenzofuran-1(3H)-one;
4-methyl-5-((2R,6S)-6-methyl-4-((1-(2-methylpyrimidin-5-yl)-1H-pyrazol-4-yl)methyl)piperazin-2-yl)isobenzofuran-1(3H)-one;
4-methyl-6-(3-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)isoxazol-5-yl)nicotinonitrile;
6-(4-((3-hydroxy-4-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)pyrrolidin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile (Diastereomer-I: Enantiomer-I);
6-(4-((3-fluoro-4-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)pyrrolidin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile (Diastereomer-I: Enantiomer-II);
6-(4-((3-(2-hydroxypropan-2-yl)-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile (Enantiomer-I);
4-methyl-6-(5-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)isoxazol-3-yl)nicotinonitrile;
(R)-4-methyl-5-(4-((2-(4-methyl-1H-imidazol-1-yl)pyrimidin-5-yl)methyl)piperazin-2-yl)isobenzofuran-1(3H)-one;
(R)-1-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyrimidin-2-yl)-1H-imidazole-4-carbonitrile;
(R)-1-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyrimidin-2-yl)-1H-1,2,4-triazole-3-carbonitrile;
(R)-3-cyclopropyl-1-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyrimidin-2-yl)-1H-pyrazole-4-carbonitrile;
(R)-3-(difluoromethoxy)-1-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyridin-2-yl)-1H-pyrazole-4-carbonitrile;
(R)-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)-4-morpholinonicotinonitrile;
(R)-3-methyl-1-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyrimidin-2-yl)-1H-pyrazole-4-carbonitrile;
(R)-4-methyl-5-(4-((6-(4-methyl-1H-1,2,3-triazol-1-yl)pyridin-3-yl)methyl)piperazin-2-yl)isobenzofuran-1(3H)-one;
(R)-3-methoxy-1-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyridin-2-yl)-1H-pyrazole-4-carbonitrile;
(R)-4-methyl-5-(4-((2-(4-methyl-1H-imidazol-1-yl)pyrimidin-5-yl)methyl)morpholin-2-yl)isobenzofuran-1(3H)-one;
(R)-1-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyridin-2-yl)-1H-1,2,3-triazole-4-carbonitrile;
(R)-3-ethyl-1-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyridin-2-yl)-1H-pyrazole-4-carbonitrile;
(R)-3-methoxy-1-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyrimidin-2-yl)-1H-pyrazole-4-carbonitrile;
(R)-3-ethyl-1-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyrimidin-2-yl)-1H-pyrazole-4-carbonitrile;
(R)-3-(difluoromethyl)-1-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyrimidin-2-yl)-1H-pyrazole-4-carbonitrile;
(R)-4-methyl-2-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)pyrimidine-5-carbonitrile;
(R)-2-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)-5-(pyrrolidin-1-yl)isonicotinonitrile;
4-methyl-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-4-oxopiperidin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
(R)-6-(3-(difluoromethyl)-4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-l-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile;
(R)-5-(4-((2-(1H-1,2,4-triazol-1-yl)pyrimidin-5-yl)methyl)piperazin-2-yl)-4-methylisobenzofuran-1(3H)-one;
(R)-5-(4-((6-(4 (difluoromethyl)-1H-imidazol-1-yl)pyridin-3-yl)methyl)piperazin-2-yl)-4-methylisobenzofuran-1(3H)-one;
(R)-4-methyl-5-(4-((2-(4-(trifluoromethyl)-1H-imidazol-1-yl)pyrimidin-5-yl)methyl)piperazin-2-yl)isobenzofuran-1(3H)-one;
(R)-6-(3-cyclopropyl-4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile;
1′-methyl-5-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-[2,3′-bipyridin]-6′(1′H)-one;
(R)-4-methyl-6-(4-((3-(1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile;
4-methyl-6-(4-(((6R)-2-methyl-6-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-pyrazol-1-yl)nicotinonitrile (Diastereomer-I);
(R)-3-methyl-1-(6-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyridin-3-yl)-1H-pyrazole-4-carbonitrile;
(R)-4-methyl-1-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyridin-2-yl)-1H-pyrazole-3-carbonitrile;
(R)-4-methyl-1-(5-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyrimidin-2-yl)-1H-pyrazole-3-carbonitrile;
4-methyl-6-(4-((2-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinonitrile (Enantiomer-II);
6-(3-(difluoromethyl)-4-(((3R,4R)-4-hydroxy-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile;
6-(4-(((3S,5R)-4-hydroxy-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2H-1,2,3-triazol-2-yl)-4-methylnicotinonitrile;
4′-methyl-4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2-oxo-2H-[1,2′-bipyridine]-5′-carbonitrile;
N-(1-((1-(5-cyano-4-methylpyridin-2-yl)-1H-pyrazol-4-yl)methyl)-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-4-yl)acetamide (Diastereomer-II Enantiomer-I);
3-(6-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)pyridin-2-yl)oxazolidin-2-one;
6-(4-(((3R,4R)-4-hydroxy-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazol-1-yl)-4-methylnicotinonitrile;
3-(2-methyl-6-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)pyridin-4-yl)oxazolidin-2-one;
N-methyl-N-(6-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazol-1-yl)pyridin-2-yl)methanesulfonamide;
5-((2R,6S)-4-((1-(4-(1,1-dioxidoisothiazolidin-2-yl)-6-methylpyridin-2-yl)-1H-pyrazol-4-yl)methyl)-6-methylpiperazin-2-yl)-4-methylisobenzofuran-1(3H)-one;
1-(2-methoxypyridin-4-yl)-4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)pyrrolidin-2-one (Diastereomer-I);
(R)-4-methoxy-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)nicotinonitrile;
6-(4-((2,2-dimethyl-6-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)morpholino)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile (Enantiomer-II);
N-(1-((1-(5-cyano-4-methylpyridin-2-yl)-1H-pyrazol-4-yl)methyl)-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-3-yl)acetamide (Enantiomer-I);
1-((1-(5-cyano-4-methylpyridin-2-yl)-1H-pyrazol-4-yl)methyl)-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-4-yl methylcarbamate (Enantiomer-I);
4-methyl-6-(3-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1,2,4-oxadiazol-5-yl)nicotinonitrile;
(R)-1-(5-cyano-4-methoxypyridin-2-yl)-N-methyl-4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazole-3-carboxamide;
6-(4-((3-(hydroxymethyl)-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-1H-pyrazol-1-yl)-4-methylnicotinonitrile (Diastereomer-II: Enantiomer-II);
(R)-1-(5-cyano-4-methoxypyridin-2-yl)-4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-pyrazole-3-carboxamide;
(R)-4-(methoxy-d3)-6-(4-((3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)nicotinonitrile;
(R)-4-methyl-5-(4-((6-(3-methyl-1,2,4-oxadiazol-5-yl)pyridin-3-yl)methyl)piperazin-2-yl)isobenzofuran-1(3H)-one;
2-methyl-4-(5-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2H-tetrazol-2-yl)benzonitrile;
3-methyl-4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1-(2-methylpyridin-4-yl)-1,3-dihydro-2H-imidazol-2-one;
6-(5-((3,3-dimethyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1,3,4-oxadiazol-2-yl)-4-methylnicotinonitrile (Enantiomer-I);
6-(5-((3,3-dimethyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)isoxazol-3-yl)-4-methylnicotinonitrile (Enantiomer-I);
4-methoxy-6-(5-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)isoxazol-3-yl)nicotinonitrile;
1-(difluoromethyl)-4-(4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2H-1,2,3-triazol-2-yl)pyridin-2(1H)-one;
5-((2R,6S)-4-((1-(2-(difluoromethyl)pyrimidin-4-yl)-1H-imidazol-4-yl)methyl)-6-methylpiperazin-2-yl)-4-methylisobenzofuran-1(3H)-one;
4-(5-(((3R,4R)-4-hydroxy-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperidin-1-yl)methyl)-2H-tetrazol-2-yl)-2-methoxybenzonitrile;
6-(5-((3-(difluoromethyl)-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1,3,4-oxadiazol-2-yl)-4-methylnicotinonitrile (Enantiomer-I);
4-methoxy-6-(3-methyl-4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-2-oxoimidazolidin-1-yl)nicotinonitrile (Diastereomer-I);
1-(2-methoxypyridin-4-yl)-3-methyl-4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1,3-dihydro-2H-imidazol-2-one;
1-(2-(difluoromethyl)pyridin-4-yl)-3-methyl-4-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)piperazin-1-yl)methyl)-1,3-dihydro-2H-imidazol-2-one; and
4-methoxy-6-(5-(((3S,5R)-3-methyl-5-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl-3,3-d2)piperazin-1-yl)methyl)isoxazol-3-yl)nicotinonitrile.

### Claim 11 (depends on 1)

A pharmaceutical composition comprising one or more compounds according to claim 1, or a salt thereof; and a pharmaceutically acceptable carrier or diluent.

### Claim 12 (depends on 1)

A pharmaceutical composition, which comprises a pharmaceutically acceptable carrier and a compound as defined in claim 1, or pharmaceutically acceptable salt, alone or in combination with another therapeutic agent.

### Claim 13 (depends on 1)

A method for the treatment of a cardiovascular disease, which comprises administering to a patient having said disease a therapeutically affective amount of a compound of claim 1, or pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 13)

The method of claim 13, wherein the cardiovascular disease is selected from hypertension, coronary heart disease, stroke, heart failure, systolic heart failure, diastolic heart failure, diabetic heart failure, acute-decompensated heart failure, post-operative volume overload, idiopathic edema, pulmonary hypertension, pulmonary arterial hypertension, cardiac insufficiency, nephrotic syndrome, and acute kidney insufficiency.

### Claim 15 (depends on 1)

A method for promoting diuresis or natriuresis, which comprises administering to a patient in need thereof a therapeutically affective amount of a compound of claim 1, or pharmaceutically acceptable salt thereof.

### Claim 16 (depends on 5)

A compound of claim 5, or salt thereof, wherein:
R2 is phenyl, pyridinyl, indolyl, indazolyl, benzo[d]oxazol-2(3H)-onyl, pyrazolo[4,3-b]pyridinyl, pyridin-2(1H)-onyl, pyrazolyl, pyrimidinyl, imidazolyl, pyrazolyl, triazolyl, oxadiazolyl, thiadiazolyl, [1,2,4]triazolo[1,5-a]pyridinyl, imidazo[1,2-b]pyridazinyl, pyrazinyl, pyrazolo[1,5-a]pyrimidinyl, thiophenyl, [1,2,4]triazolo[4,3-b]pyridazinyl, pyrazolo[1,5-a]pyrimidinyl, or benzo[d]oxazol-2(3H)-only, each being substituted with 0-3 R2a; and
R2a is OH, ═O, CN, halo, C1-4alkyl, C1-4 fluoroalkyl, C1-4 alkoxy, or C1-4 fluoroalkoxy.

### Claim 17 (depends on 16)

A compound of claim 16, or salt thereof, wherein:
R1 is
R1a is independently H or —CH3.

### Claim 18 (depends on 17)

The compound according to claim 17, or salt thereof, wherein:
Ring B is pyridinyl, triazolyl, thiazolyl, oxadiazolyl, imidazolyl, or pyrrazolyl; and
R2 is phenyl, pyridinyl, pyrimidinyl, benzo[d]oxazol-2(3H)-onyl, imidazolyl, pyrazolyl, triazolyl, or oxadiazolyl, each being substituted with 0-3 Rea.

### Claim 19 (depends on 18)

The compound according to claim 18, or salt thereof, wherein:
V is —O—, —NR4—, or —CR5R5—;
Y is —C(R6)2—C(R6)2— or —C(R6)2—;
L1 is —C(R)2—; wherein R is independently hydrogen, F, OH, C1-3 alkyl, C1-3 hydroxyalkyl, C1-3 alkoxyalkyl, or C1-3 fluoroalkyl; and
R6 is independently H, C1-3-alkyl, C1-3-fluoroalkyl, or C3-6-cycloalkyl.

### Claim 20

A compound, wherein the compound is
or salt thereof.

### Claim 21

A compound, wherein the compound is

### Claim 22 (depends on 20)

A pharmaceutical composition comprising one or more compounds according to claim 20, or a salt thereof; and a pharmaceutically acceptable carrier or diluent.

### Claim 23 (depends on 20)

A pharmaceutical composition, which comprises a pharmaceutically acceptable carrier and a compound as defined in claim 20, or pharmaceutically acceptable salt, alone or in combination with another therapeutic agent.

### Claim 24 (depends on 20)

A method for the treatment of a cardiovascular disease, which comprises administering to a patient having said disease a therapeutically affective amount of a compound of claim 20, or pharmaceutically acceptable salt thereof.

### Claim 25 (depends on 24)

The method of claim 24, wherein the cardiovascular disease is selected from hypertension, coronary heart disease, stroke, heart failure, systolic heart failure, diastolic heart failure, diabetic heart failure, acute-decompensated heart failure, post-operative volume overload, idiopathic edema, pulmonary hypertension, pulmonary arterial hypertension, cardiac insufficiency, nephrotic syndrome, and acute kidney insufficiency.

### Claim 26 (depends on 20)

A method for promoting diuresis or natriuresis, which comprises administering to a patient in need thereof a therapeutically affective amount of a compound of claim 20, or pharmaceutically acceptable salt thereof.

### Claim 27

A compound, wherein the compound is
or salt thereof.

### Claim 28

A compound, wherein the compound is

### Claim 29 (depends on 27)

A pharmaceutical composition comprising one or more compounds according to claim 27, or a salt thereof; and a pharmaceutically acceptable carrier or diluent.

### Claim 30 (depends on 27)

A pharmaceutical composition, which comprises a pharmaceutically acceptable carrier and a compound as defined in claim 27, or pharmaceutically acceptable salt, alone or in combination with another therapeutic agent.

### Claim 31 (depends on 27)

A method for the treatment of a cardiovascular disease, which comprises administering to a patient having said disease a therapeutically affective amount of a compound of claim 27, or pharmaceutically acceptable salt thereof.

### Claim 32 (depends on 31)

The method of claim 31, wherein the cardiovascular disease is selected from hypertension, coronary heart disease, stroke, heart failure, systolic heart failure, diastolic heart failure, diabetic heart failure, acute-decompensated heart failure, post-operative volume overload, idiopathic edema, pulmonary hypertension, pulmonary arterial hypertension, cardiac insufficiency, nephrotic syndrome, and acute kidney insufficiency.

### Claim 33 (depends on 27)

A method for promoting diuresis or natriuresis, which comprises administering to a patient in need thereof a therapeutically affective amount of a compound of claim 27, or pharmaceutically acceptable salt thereof.

### Claim 34

A compound, wherein the compound is
or salt thereof.

### Claim 35

A compound, wherein the compound is

### Claim 36 (depends on 34)

A pharmaceutical composition comprising one or more compounds according to claim 34, or a salt thereof and a pharmaceutically acceptable carrier or diluent.

### Claim 37 (depends on 34)

A pharmaceutical composition, which comprises a pharmaceutically acceptable carrier and a compound as defined in claim 34, or pharmaceutically acceptable salt, alone or in combination with another therapeutic agent.

### Claim 38 (depends on 34)

A method for the treatment of a cardiovascular disease, which comprises administering to a patient having said disease a therapeutically affective amount of a compound of claim 34, or pharmaceutically acceptable salt thereof.

### Claim 39 (depends on 38)

The method of claim 38, wherein the cardiovascular disease is selected from hypertension, coronary heart disease, stroke, heart failure, systolic heart failure, diastolic heart failure, diabetic heart failure, acute-decompensated heart failure, post-operative volume overload, idiopathic edema, pulmonary hypertension, pulmonary arterial hypertension, cardiac insufficiency, nephrotic syndrome, and acute kidney insufficiency.

### Claim 40 (depends on 34)

A method for promoting diuresis or natriuresis, which comprises administering to a patient in need thereof a therapeutically affective amount of a compound of claim 34, or pharmaceutically acceptable salt thereof.

### Claim 41

A compound, wherein the compound is
or salt thereof.

### Claim 42

A compound, wherein the compound is

### Claim 43 (depends on 41)

A pharmaceutical composition comprising one or more compounds according to claim 41, or a salt thereof; and a pharmaceutically acceptable carrier or diluent.

### Claim 44 (depends on 41)

A pharmaceutical composition, which comprises a pharmaceutically acceptable carrier and a compound as defined in claim 41, or pharmaceutically acceptable salt, alone or in combination with another therapeutic agent.

### Claim 45 (depends on 41)

A method for the treatment of a cardiovascular disease, which comprises administering to a patient having said disease a therapeutically affective amount of a compound of claim 41, or pharmaceutically acceptable salt thereof.

### Claim 46 (depends on 45)

The method of claim 45, wherein the cardiovascular disease is selected from hypertension, coronary heart disease, stroke, heart failure, systolic heart failure, diastolic heart failure, diabetic heart failure, acute-decompensated heart failure, post-operative volume overload, idiopathic edema, pulmonary hypertension, pulmonary arterial hypertension, cardiac insufficiency, nephrotic syndrome, and acute kidney insufficiency.

### Claim 47 (depends on 41)

A method for promoting diuresis or natriuresis, which comprises administering to a patient in need thereof a therapeutically affective amount of a compound of claim 41, or pharmaceutically acceptable salt thereof.

### Claim 48

A compound, wherein the compound is
or salt thereof.

### Claim 49

A compound, wherein the compound is

### Claim 50 (depends on 48)

A pharmaceutical composition comprising one or more compounds according to claim 48, or a salt thereof; and a pharmaceutically acceptable carrier or diluent.

### Claim 51 (depends on 48)

A pharmaceutical composition, which comprises a pharmaceutically acceptable carrier and a compound as defined in claim 48, or pharmaceutically acceptable salt, alone or in combination with another therapeutic agent.

### Claim 52 (depends on 48)

A method for the treatment of a cardiovascular disease, which comprises administering to a patient having said disease a therapeutically affective amount of a compound of claim 48, or pharmaceutically acceptable salt thereof.

### Claim 53 (depends on 52)

The method of claim 52, wherein the cardiovascular disease is selected from hypertension, coronary heart disease, stroke, heart failure, systolic heart failure, diastolic heart failure, diabetic heart failure, acute-decompensated heart failure, post-operative volume overload, idiopathic edema, pulmonary hypertension, pulmonary arterial hypertension, cardiac insufficiency, nephrotic syndrome, and acute kidney insufficiency.

### Claim 54 (depends on 48)

A method for promoting diuresis or natriuresis, which comprises administering to a patient in need thereof a therapeutically affective amount of a compound of claim 48, or pharmaceutically acceptable salt thereof.

### Claim 55

A compound, wherein the compound is
or salt thereof.

### Claim 56

A compound, wherein the compound is

### Claim 57 (depends on 55)

A pharmaceutical composition comprising one or more compounds according to claim 55, or a salt thereof; and a pharmaceutically acceptable carrier or diluent.

### Claim 58 (depends on 55)

A pharmaceutical composition, which comprises a pharmaceutically acceptable carrier and a compound as defined in claim 55, or pharmaceutically acceptable salt, alone or in combination with another therapeutic agent.

### Claim 59 (depends on 55)

A method for the treatment of a cardiovascular disease, which comprises administering to a patient having said disease a therapeutically affective amount of a compound of claim 55, or pharmaceutically acceptable salt thereof.

### Claim 60 (depends on 59)

The method of claim 59, wherein the cardiovascular disease is selected from hypertension, coronary heart disease, stroke, heart failure, systolic heart failure, diastolic heart failure, diabetic heart failure, acute-decompensated heart failure, post-operative volume overload, idiopathic edema, pulmonary hypertension, pulmonary arterial hypertension, cardiac insufficiency, nephrotic syndrome, and acute kidney insufficiency.

### Claim 61 (depends on 55)

A method for promoting diuresis or natriuresis, which comprises administering to a patient in need thereof a therapeutically affective amount of a compound of claim 55, or pharmaceutically acceptable salt thereof.