# US 2013/0158002 A1 · Positive allosteric modulators of mglur2

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- Number: US 2013/0158002 A1
- Document ID: US20130158002A1
- Status: Published application
- Kind: A1
- Application number: 13/581,819
- Filed: 2011-02-28
- Published: 2013-06-20
- Earliest claimed: 2010-03-04
- Assignees: Merck Sharp & Dohme Corp.
- Inventors: Mark E. Layton; Michael J. Kelly; Timothy J. Hartingh
- Web page: https://patentgrep.com/patent/US20130158002A1

## CPC

- C07D 285/14: condensed with carbocyclic rings or ring systems
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 417/04: directly linked by a ring-member-to-ring-member bond
- C07D 417/10: linked by a carbon chain containing aromatic rings
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 417/14: containing three or more hetero rings
- C07D 471/10: Spiro-condensed systems
- C07D 491/107: with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D 491/113: with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
- C07D 498/04: Ortho-condensed systems
- C07D 513/04: Ortho-condensed systems
- C07D 519/00: Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention is directed to 5-substituted 1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide and 1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2,-dioxide derivatives which are potentiators of metabotropic glutamate receptors, particularly the mGluR2 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.

## Claims

### Claim 1

A compound according to Formula I
wherein:
X is selected from C and N;
Y is C1-6alkyl;
R1 is selected from the group consisting of:
(1) C2-8alkyl,
(2) C2-8alkenyl,
(3) C2-8alkynyl,
(4) C3-6cycloalkyl-(CH2)p—, wherein p is 1, 2, 3 or 4, and
(5) benzyl,
wherein groups (1) to (5) above are optionally substituted with 1 to 3 R2 groups;
each R2 is independently selected from the group consisting of: halo, OH, C1-4alkyl, C1-4alkoxy, CF3, —OCF3 and —CN;
ring A is selected from aryl and heteroaryl, wherein said aryl and heteroaryl are optionally substituted with one or more R3 groups up to the maximum number of substitutable positions;
each R3 is independently selected from the group consisting of:
(1) halo,
(2) C1-8alkyl,
(3) C2-6alkenyl,
(4) C2-6alkynyl,
(5) C3-6cycloalkyl,
(6) C1-6alkoxy,
(7) C3-6cycloalkoxy,
(8) —CN,
(9) —OH,
(10) —C(O)—O—C1-4alkyl,
(11) —C(O)—C1-4alkyl,
(12) —N(R)2,
(13) —C(O)—N(R)2,
(14) —S(O)k—C1-4alkyl, wherein k is 0, 1 or 2,
(15) -aryl,
(16) -heteroaryl,
(17) -heterocycle,
(18) —C(O)-aryl,
(19) —N(R)-aryl,
(20) benzyl,
(21) benzyloxy,
(22) aryl-O—,
(23) heteroaryl-O—,
(24) heterocycle-O—
(23) —CO2H,
(24) —SH,
(25) —SO2N(R)R,
(26) —N(R)C(O)N(R)R,
(27) —N(R)C(O)C1-4alkyl,
(28) —N(R)SO2N(R)R,
(29) —B(OH)2,
(30) heteroaryl-CH2—,
(31) heterocycle-CH2—,
(32) aryl-C(O)—N(R)—CH2—,
(33) heteroaryl-C(O)—N(R)—CH2—,
(34) heterocycle-C(O)—N(R)—CH2—,
(35) aryl-C(O)—N(R)—CH2—,
(36) heteroaryl-CH2—C(O)—N(R)—CH2—,
(37) heterocycle-CH2—C(O)—N(R)—CH2—, and
(38) C1-6alkyl-C(O)—N(R)—CH2—,
wherein groups (2) to (7), (10), (11), (14) to (24), (27) and (30) to (38) above are optionally substituted from one up to the maximum number of substitutable positions with one or more substituents independently selected from the group consisting of: OH, CN, halo, —N(R)2, —C(O)—N(R)2, —CH2—N(R)2, —C(O)—CH2—N(R)2, carboxy, —C(O)—O—C1-4alkyl, —C(O)—C(R)2—C(O)—O—C1-4alkyl, —CH2—C3-6cycloalkyl, C1-4alkoxy, C1-4alkylamino, acetyl, acetylamino, methylsulfonyl, methylsulfonylamino, phenyl, heterocycle, heteroaryl, heteroaryl-C(O)—, C1-4alkyl and C1-4alkyl-C(O)—, said C1-4alkyl, C1-4alkyl-C(O)—, heteroaryl and heteroaryl-C(O)-optionally substituted with 1 to 3 halogen atoms and hydroxyl, and heteroaryl and heteroaryl-C(O)— additionally optionally substituted with methyl, and each R is independently selected from the group consisting of: H and C1-4alkyl;
aryl at each occurrence is independently selected from the group consisting of: phenyl, naphthyl, anthryl and phenanthryl;
heteroaryl at each occurrence independently means a 5- or 6-membered monocyclic aromatic or 9- or 10-membered bicyclic aromatic, wherein at least one atom in the aromatic is selected from N(R), O and S, the sulfur optionally oxidized to sulfone or sulfoxide, and the remaining atoms are selected from C, N(R), O and S, the sulfur optionally oxidized to sulfone or sulfoxide;
heterocycle at each occurrence independently means a 5- or 6-membered monocyclic non-aromatic ring or 9- or 10-membered bi- or spiro-cyclic non- or partially-aromatic ring, each optionally substituted with 1 to 2 oxo groups, wherein at least one atom is selected from N(R), O and S, the sulfur optionally oxidized to sulfone or sulfoxide, and the remaining atoms are selected from C, N(R), O and S, the sulfur optionally oxidized to sulfone or sulfoxide;
and pharmaceutically acceptable salts thereof.

### Claim 2 (depends on 1)

A compound according to claim 1 wherein each R3 is independently selected from the group consisting of:
(1) halo,
(2) C1-8alkyl,
(3) C2-6alkenyl,
(4) C2-6alkynyl,
(5) C3-6cycloalkyl,
(6) C1-6alkoxy,
(7) C3-6cycloalkoxy,
(8) —CN,
(9) —OH,
(10) —C(O)—O—C1-4alkyl,
(11) —C(O)—C1-4alkyl,
(12) —N(R)2,
(13) —C(O)—N(R)2,
(14) —S(O)k—C1-4alkyl, wherein k is 0, 1 or 2,
(15) -aryl,
(16) -heteroaryl,
(17) -heterocycle,
(18) —C(O)-aryl,
(19) —N(R)-aryl,
(20) benzyl,
(21) benzyloxy,
(22) aryl-O—,
(23) heteroaryl-O—,
(24) heterocycle-O—
(23) —CO2H,
(24) —SH,
(25) —SO2N(R)R,
(26) —N(R)C(O)N(R)R,
(27) —N(R)C(O)C1-4alkyl,
(28) —N(R)SO2N(R)R,
(29) —B(OH)2,
(30) heteroaryl-CH2—,
(31) heterocycle-CH2—,
(32) aryl-C(O)—N(R)—CH2—,
(33) heteroaryl-C(O)—N(R)—CH2—,
(34) heterocycle-C(O)—N(R)—CH2—, and
(35) aryl-C(O)—N(R)—CH2—,
wherein groups (2) to (7), (10), (11), (14) to (24), (27) and (30) to (35) above are optionally substituted from one up to the maximum number of substitutable positions with one or more substituents independently selected from the group consisting of: OH, CN, halo, —N(R)2, —C(O)—N(R)2, —CH2—N(R)2, carboxy, —C(O)—O—C1-4alkyl, C1-4alkoxy, C1-4alkylamino, acetyl, acetylamino, methylsulfonyl, methylsulfonylamino, phenyl, heterocycle, heteroaryl, heteroaryl-C(O)—, C1-4alkyl and C1-4alkyl-C(O)—, said C1-4alkyl, C1-4alkyl-C(O)— and heteroaryl optionally substituted with 1 to 3 halogen atoms and hydroxy, and each R is independently selected from the group consisting of: H and C1-4alkyl.

### Claim 3 (depends on 2)

The compound according to claim 2 wherein X is C.

### Claim 4 (depends on 2)

The compound according to claim 2 wherein X is N.

### Claim 5 (depends on 2)

The compound according to claim 2 wherein Y is methyl.

### Claim 6 (depends on 2)

The compound according to claim 2 wherein R1 is selected from the group consisting of: cyclopropylmethyl, 2,2-difluorocyclopropylmethyl, cyclobutylmethyl, 2,2-dimethylpropyl and benzyl, optionally substituted with methoxy or —OCF3.

### Claim 7 (depends on 2)

The compound according to claim 2 of Formula Ia
and pharmaceutically acceptable salts thereof.

### Claim 8 (depends on 7)

The compound according to claim 7 wherein R3 is selected from the group consisting of: (1) —CN, (2) halo, (3) —CF3, (4) 1,1-dioxidothiomorpholin-4-yl, (5) morpholin-4-ylmethyl, (6) —C(O)—O—C1-4 alkyl, (7) C1-6alkoxy, (8) C1-6alkyl, optionally substituted with hydroxy, (9) piperazinyl, optionally substituted with —C(O)—O—C1-4alkyl or isoxazolylcarbonyl, and (10) piperidinyl, optionally substituted with —C(O)—O—C1-4alkyl or isoxazolylcarbonyl.

### Claim 9 (depends on 2)

The compound according to claim 2 of Formula Ib
and pharmaceutically acceptable salts thereof.

### Claim 10 (depends on 9)

The compound according to claim 9 wherein R3 is selected from the group consisting of: (1) —CN, (2) halo, (3) —CF3, (4) 1,1-dioxidothiomorpholin-4-yl, (5) morpholin-4-ylmethyl, (6) —C(O)—O—C1-4alkyl, (7) C1-6alkoxy, (8) C1-6alkyl, optionally substituted with hydroxy, (9) piperazinyl, optionally substituted with —C(O)—O—C1-4alkyl or isoxazolylcarbonyl, and (10) piperidinyl, optionally substituted with —C(O)—O—C1-4alkyl or isoxazolylcarbonyl.

### Claim 11 (depends on 2)

The compound according to claim 2 of Formula Ic
and pharmaceutically acceptable salts thereof, wherein
ring B is heteroaryl,
R3 is CN, halo or C1-4alkyl, optionally substituted with 1-5 halo atoms, and
each R4 is independently selected from the group consisting of: —CN, halo, —N(R)2, C1-4alkoxy, —C(O)—O—C1-4alkyl, and C1-4alkyl, optionally substituted with hydroxy.

### Claim 12 (depends on 2)

The compound according to claim 2 of Formula Id
and pharmaceutically acceptable salts thereof, wherein
ring C is heterocycle,
R3 is CN, halo or C1-4alkyl, optionally substituted with 1-5 halo atoms, and
each R5 is independently selected from the group consisting of: OH, acetyl, methylsulfonyl, acetylamino, —C(O)—O—C1-4alkyl and C1-4alkyl, optionally substituted with 1-3 halo atoms or hydroxy.

### Claim 13 (depends on 2)

The compound according to claim 2 of Formula Ie
and pharmaceutically acceptable salts thereof, wherein
R3 is CN, halo or C1-4alkyl, optionally substituted with 1-5 halo atoms, and
R6 is independently selected from the group consisting of: pyrimidinyl, pyridyl, methylsulfonyl, acetyl, 2-hydroxypropanoyl and 2-hydroxyethanoyl.

### Claim 14 (depends on 2)

The compound according to claim 2 of Formula If
and pharmaceutically acceptable salts thereof, wherein
R3 is CN, halo or C1-4alkyl, optionally substituted with 1-5 halo atoms, and
R7 is selected from the group consisting of: pyrimidinyl, pyridyl, methylsulfonyl, acetyl, 2-hydroxypropanoyl and 2-hydroxyethanoyl.

### Claim 15 (depends on 2)

The compound according to claim 2 of Formula Ig
and pharmaceutically acceptable salts thereof, wherein
n is 0 or 1,
R3 is CN, halo or C1-4alkyl, optionally substituted with 1-5 halo atoms, and
R8 is selected from the group consisting of: acetylamino, methylsulfonyl, methylsulfonylamino, pyrimidinyl, pyridyl, 2-oxo-1-pyrrolidinyl, —C(O)—N(R)2 and C1-4alkyl, said C1-4alkyl optionally substituted with 1-3 halo atoms or hydroxy, and said pyridyl optionally substituted with fluoro.

### Claim 16 (depends on 2)

The compound according to claim 2 of Formula Ih
and pharmaceutically acceptable salts thereof, wherein
R3 is CN, halo or C1-4alkyl, optionally substituted with 1-5 halo atoms, and
R9 is pyridyl and R10 is hydroxy or R9 and R10 and joined together with the atom to which they are attached to form 5-oxo-imidazolidine, oxetane or azetidine, said azetidine optionally substituted with —C(O)—O—C1-4alkyl.

### Claim 17 (depends on 2)

The compound according to claim 2 of Formula Ij
and pharmaceutically acceptable salts thereof, wherein
ring D is heteroaryl,
R3 is CN, halo or C1-4alkyl, optionally substituted with 1-5 halo atoms, and
each R11 is independently selected from the group consisting of: —CN, halo, —N(R)2, C1-4alkoxy, —C(O)—O—C1-4alkyl, and C1-4alkyl, optionally substituted with hydroxy.

### Claim 18 (depends on 2)

The compound according to claim 2 of Formula Ik
and pharmaceutically acceptable salts thereof, wherein
ring E is heteroaryl,
R3 is CN, halo or C1-4alkyl, optionally substituted with 1-5 halo atoms, and
each R12 is independently selected from the group consisting of: —CN, halo, —N(R)2, C1-4alkoxy, —C(O)—O—C1-4alkyl, and C1-4alkyl, optionally substituted with hydroxy.

### Claim 19 (depends on 2)

A compound according to claim 2 selected from the following group:
2-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzonitrile;
2-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]-6-fluorobenzonitrile;
1-(cyclopropylmethyl)-3-methyl-5-(2-methylphenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
1-(cyclopropylmethyl)-5-(2-ethylphenyl)-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
2-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]-5-fluorobenzonitrile;
4-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzonitrile;
1-(cyclopropylmethyl)-3-methyl-5-phenyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
1-(cyclopropylmethyl)-5-(2-fluorophenyl)-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzonitrile;
2-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]-3-fluorobenzonitrile;
2-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]-3,6-difluorobenzonitrile;
1-(cyclopropylmethyl)-3-methyl-5-[2-(trifluoromethyl)phenyl]-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]-4-fluorobenzonitrile;
3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]-2-fluorobenzonitrile;
1-(cyclopropylmethyl)-3-methyl-5-[3-(trifluoromethyl)phenyl]-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
1-(cyclopropylmethyl)-5-[4-(1,1-dioxidothiomorpholin-4-yl)phenyl]-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
1-(cyclopropylmethyl)-5-[3-(1,1-dioxidothiomorpholin-4-yl)phenyl]-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
2-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]pyridine-3-carbonitrile;
4-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]pyridine-3-carbonitrile;
4-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]pyridine-2-carbonitrile;
1-(cyclopropylmethyl)-3-methyl-5-(4-methylpyridin-3-yl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]pyridine-2-carbonitrile;
5-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]pyridine-2-carbonitrile;
1-(cyclopropylmethyl)-5-(2-fluoropyridin-3-yl)-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
1-(cyclopropylmethyl)-3-methyl-5-(5-methylpyridin-3-yl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]pyridine-4-carbonitrile;
1-(cyclopropylmethyl)-3-methyl-5-[3-(morpholin-4-ylmethyl)phenyl]-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
2-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]-4-(morpholin-4-ylmethyl)benzonitrile;
2-{2-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]phenyl}propan-2-ol;
2-{3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]phenyl}propan-2-ol;
2-{4-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]phenyl}propan-2-ol;
1-(cyclopropylmethyl)-3-methyl-5-(3-methylpyridin-2-yl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}benzonitrile;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-(hydroxymethyl)benzonitrile;
ethyl 3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-2-fluorobenzoate;
1-[(2,2-difluorocyclopropyl)methyl]-5-[3-(1,1-dioxidothiomorpholin-4-yl)phenyl]-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-methoxybenzonitrile;
2-[1-(2,2-dimethylpropyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzonitrile;
2-[1-(3-hydroxypropyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzonitrile;
2-[1-(cyclobutylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzonitrile;
1-(cyclobutylmethyl)-5-[3-(1,1-dioxidothiomorpholin-4-yl)phenyl]-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
2-[1-(4-methoxybenzyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzonitrile;
2-{3-methyl-2,2-dioxido-1-[4-(trifluoromethoxy)benzyl]-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}benzonitrile;
5-[3-(1,1-dioxidothiomorpholin-4-yl)phenyl]-3-methyl-1-[4-(trifluoromethoxy)benzyl]-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
6-(4-cyano-3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}phenoxy)pyridine-2-carbonitrile;
4-(4-cyano-3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}phenoxy)pyridine-2-carbonitrile;
4-[(3-chloropyrazin-2-yl)oxy]-2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}benzonitrile;
2-(4-cyano-3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}phenoxy)-1,3-thiazole-4-carbonitrile;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-(pyrazin-2-yloxy)benzonitrile;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-{[6-(hydroxymethyl)pyrazin-2-yl]oxy}benzonitrile;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-[(6-methylpyrazin-2-yl)oxy]benzonitrile;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-[(3-methylpyrazin-2-yl)oxy]benzonitrile;
methyl 2-(4-cyano-3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}phenoxy)pyrimidine-5-carboxylate;
4-[(2-chloropyrimidin-4-yl)oxy]-2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}benzonitrile;
4-amino-2-(4-cyano-3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}phenoxy)pyrimidine-5-carbonitrile;
methyl 5-(4-cyano-3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}phenoxy)pyrazine-2-carboxylate;
3-(4-cyano-3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}phenoxy)pyrazine-2-carbonitrile;
6-(4-cyano-3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}phenoxy)pyrazine-2-carbonitrile;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-{[4-(methylamino)pyrimidin-2-yl]oxy}benzonitrile;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-[(2-methoxypyrimidin-4-yl)oxy]benzonitrile;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-{[2-(methylamino)pyrimidin-4-yl]oxy}benzonitrile;
4-{4-cyano-3-[1-(2,2-dimethylpropyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]phenoxy}pyridine-2-carbonitrile;
4-{4-cyano-3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]phenoxy}pyridine-2-carbonitrile;
4-(4-cyano-3-{3-methyl-2,2-dioxido-1-[4-(trifluoromethoxy)benzyl]-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}phenoxy)pyridine-2-carbonitrile;
4-(cyanomethoxy)-2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}benzonitrile;
2-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-methylphenyl)propan-2-ol;
2-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-methylphenyl)propan-2-ol;
2-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-2-fluorophenyl)propan-2-ol;
2-{3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]-4-methylphenyl}propan-2-ol;
2-{3-[1-(2,2-dimethylpropyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]-4-methylphenyl}propan-2-ol;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-[(3-hydroxy-6,7-dihydroisoxazolo[4,5-c]pyridin-5(4H)-yl)methyl]benzonitrile;
4-[(4-acetylpiperazin-1-yl)methyl]-2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}benzonitrile;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-{[4-(methylsulfonyl)piperazin-1-yl]methyl}benzonitrile;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-[(1,1-dioxidothiomorpholin-4-yl)methyl]benzonitrile;
5-{5-[(4-acetylpiperazin-1-yl)methyl]-2-fluorophenyl}-1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-5-(2-fluoro-5-{[4-(methylsulfonyl)piperazin-1-yl]methyl}phenyl)-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-5-(2-fluoro-5-{[4-(2,2,2-trifluoroethyl)piperazin-1-yl]methyl}phenyl)-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
5-{3-[(4-acetylpiperazin-1-yl)methyl]-2-fluorophenyl}-1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-5-(2-fluoro-3-{[4-(methylsulfonyl)piperazin-1-yl]methyl}phenyl)-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-5-(2-fluoro-3-{[4-(2,2,2-trifluoroethyl)piperazin-1-yl]methyl}phenyl)-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
2-cyano-N-{3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzyl}benzamide;
2-{3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzyl}-1H-isoindole-1,3(2H)-dione;
N-{3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzyl}benzamide;
3-cyano-N-{3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzyl}benzamide;
N-{3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzyl}isoxazole-3-carboxamide;
2-({3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzyl}amino)nicotinonitrile;
4-({3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzyl}amino)pyridine-2-carbonitrile;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(6-{[4-(methylsulfonyl)piperazin-1-yl]methyl}pyridin-2-yl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
5-{6-[(4-acetylpiperazin-1-yl)methyl]pyridin-2-yl}-1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
5-{6-[(4-acetylpiperazin-1-yl)methyl]pyridin-3-yl}-1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(6-{[4-(methylsulfonyl)piperazin-1-yl]methyl}pyridin-3-yl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
5-{5-[(4-acetylpiperazin-1-yl)methyl]pyridin-3-yl}-1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(5-{[4-(methylsulfonyl)piperazin-1-yl]methyl}pyridin-3-yl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
5-{2-[(4-acetylpiperazin-1-yl)methyl]pyridin-4-yl}-1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(2-{[4-(methylsulfonyl)piperazin-1-yl]methyl}pyridin-4-yl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
5-{4-[(4-acetylpiperazin-1-yl)methyl]pyridin-2-yl}-1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(3-methyl-6-{[4-(methylsulfonyl)piperazin-1-yl]methyl}pyridin-2-yl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
1-{4-[(6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-5-methylpyridin-2-yl)methyl]piperazin-1-yl}ethanone;
2-(6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-5-methylpyridin-2-yl)propan-2-ol;
2-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl]benzonitrile;
1-(cyclopropylmethyl)-5-[3-(1,1-dioxidothiomorpholin-4-yl)phenyl]-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}benzonitrile;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(2-methylphenyl)-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-[2-(trifluoromethyl)phenyl]-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-5-[3-(1,1-dioxidothiomorpholin-4-yl)phenyl]-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
tert-butyl 4-(4-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}phenyl)piperazine-1-carboxylate;
tert-butyl 4-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}phenyl)piperazine-1-carboxylate;
(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}phenyl)methanol;
(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-fluorophenyl)methanol;
(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-2-fluorophenyl)methanol;
2-[1-(2,2-dimethylpropyl)-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl]benzonitrile;
1-(2,2-dimethylpropyl)-5-[3-(1,1-dioxidothiomorpholin-4-yl)phenyl]-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-{3-[1-(methylsulfonyl)piperidin-4-yl]phenyl}-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-{4-[4-(methylsulfonyl)piperazin-1-yl]phenyl}-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-{3-[4-(methylsulfonyl)piperazin-1-yl]phenyl}-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-5-{4-[4-(isoxazol-3-ylcarbonyl)piperazin-1-yl]phenyl}-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[4-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}phenyl)piperazin-1-yl]ethanone;
4-(4-cyano-3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}phenoxy)pyridine-2-carbonitrile;
4-{4-cyano-3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl]phenoxy}pyridine-2-carbonitrile;
4-{4-cyano-3-[1-(2,2-dimethylpropyl)-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl]phenoxy}pyridine-2-carbonitrile;
2-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-2-fluorophenyl)propan-2-ol;
2-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylphenyl)propan-2-ol;
2-{3-[1-(cyclopropyl methyl)-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl]-4-methyl phenyl}propan-2-ol;
2-{3-[1-(2,2-dimethyl propyl)-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl]-4-methyl phenyl}propan-2-ol;
1-[4-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)piperazin-1-yl]ethanone;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(2-methyl-5-{[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]methyl}phenyl)-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(2-methyl-5-{[4-(methylsulfonyl)piperazin-1-yl]methyl}phenyl)-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-5-{5-[(1,1-dioxidothiomorpholin-4-yl)methyl]-2-methylphenyl}-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(2-methyl-5-{[4-(methylsulfonyl)piperidin-1-yl]methyl}phenyl)-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(2-methyl-5-{[4-(methylsulfonyl)piperazin-1-yl]methyl}phenyl)-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
N-[1-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)piperidin-4-yl]acetamide;
tert-butyl (3aR,6aS)-5-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(2-methyl-5-{[4-(pyrimidin-2-yl)piperazin-1-yl]methyl}phenyl)-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(2-methyl-5-{[4-(pyridin-2-yl)piperazin-1-yl]methyl}phenyl)-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(2-methyl-5-{[4-(pyrazin-2-yl)piperazin-1-yl]methyl}phenyl)-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(2-methyl-5-{[4-(pyridin-4-yl)piperazin-1-yl]methyl}phenyl)-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)piperidine-4-carboxamide;
1-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)-N-methylpiperidine-4-carboxamide;
2-[1-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)piperidin-4-yl]propan-2-ol;
1-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)-4-(pyridin-3-yl)piperidin-4-ol;
1-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)-4-(pyridin-2-yl)piperidin-4-ol;
N-[1-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)piperidin-4-yl]methanesulfonamide;
tert-butyl 7-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)-2,7-diazaspiro[3.5]nonane-2-carboxylate;
tert-butyl 7-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)-1,7-diazaspiro[3.5]nonane-1-carboxylate;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(2-methyl-5-{[4-(pyrimidin-2-yl)piperidin-1-yl]methyl}phenyl)-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
8-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)-1,3,8-triazaspiro[4.5]decan-4-one
1-[(2,2-difluorocyclopropyl)methyl]-5-(5-{[4-(6-fluoropyridin-2-yl)piperidin-1-yl]methyl}-2-methylphenyl)-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-[2-methyl-5-(2-oxa-7-azaspiro[3.5]non-7-ylmethyl)phenyl]-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[1-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)piperidin-4-yl]pyrrolidin-2-one;
1-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)-4-[(dimethylamino)methyl]piperidin-4-ol;
[1-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)piperidin-4-yl]methanol;
[3-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)-3-azabicyclo[3.1.0]hex-6-yl]methanol;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(2-methyl-5-{[4-(pyridin-4-yl)piperidin-1-yl]methyl}phenyl)-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(2-methyl-5-{[4-(pyridin-2-yl)piperidin-1-yl]methyl}phenyl)-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)piperidine-3-carboxamide;
[1-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)piperidin-3-yl]methanol;
7-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)-2,7-diazaspiro[4.5]decan-1-one;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(2-methyl-5-{[3-(methylsulfonyl)pyrrolidin-1-yl]methyl}phenyl)-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
[1-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)pyrrolidin-3-yl]methanol;
1-[4-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}benzyl)piperazin-1-yl]ethanone;
1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(3-{[4-(methylsulfonyl)piperazin-1-yl]methyl}phenyl)-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[4-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-fluorobenzyl)piperazin-1-yl]ethanone;
1-[(2,2-difluorocyclopropyl)methyl]-5-(2-fluoro-5-{[4-(methylsulfonyl)piperazin-1-yl]methyl}phenyl)-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[4-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-2-fluorobenzyl)piperazin-1-yl]ethanone;
1-[(2,2-difluorocyclopropyl)methyl]-5-(2-fluoro-3-{[4-(methylsulfonyl)piperazin-1-yl]methyl}phenyl)-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-5-{3-[(1,1-dioxidothiomorpholin-4-yl)methyl]-2-fluorophenyl}-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
1-[(2,2-difluorocyclopropyl)methyl]-5-(2-fluoro-3-{[4-(methylsulfonyl)piperidin-1-yl]methyl}phenyl)-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide;
(2R)-1-[4-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)piperazin-1-yl]-2-hydroxypropan-1-one;
(2S)-1-[4-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)piperazin-1-yl]-2-hydroxypropan-1-one;
1-[4-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)piperazin-1-yl]-2-hydroxyethanone;
and pharmaceutically acceptable salts of any of the foregoing compounds.

### Claim 20 (depends on 1)

A compound according to claim 1 selected from the following group:
N-{3-[1-(cyclopropylmethyl)-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl]benzyl}benzamide;
1-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)-3-methylimidazolidine-2,4-dione;
N-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)-2-(1H-1,2,4-triazol-1-yl)acetamide;
(2R)-1-[4-(4-chloro-3-{1-(2R)—N-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)-2-hydroxypropanamide;
1-[4-(4-chloro-3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl]benzyl)piperazin-1-yl}ethanone;
(2R)-1-[4-(4-chloro-3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}benzyl)piperazin-1-yl]-2-hydroxypropan-1-one;
2-[4-(6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-5-methylpyridin-2-yl)piperazin-1-yl]-2-oxoethanol;
3-cyano-6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-2-[4-(isoxazol-3-ylcarbonyl)piperazin-1-yl]pyridinium chloride;
3-cyano-2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-6-[4-(isoxazol-3-ylcarbonyl)piperazin-1-yl]pyridinium chloride;
tert-butyl 4-(5-cyano-6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}pyridin-2-yl)piperazine-1-carboxylate;
tert-butyl 4-(3-cyano-6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}pyridin-2-yl)piperazine-1-carboxylate;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-6-(1,1-dioxidothiomorpholin-4-yl)-3-methylpyridinium chloride;
6-{4-[(acetyloxy)acetyl]piperazin-1-yl}-2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-3-methylpyridinium trifluoroacetate;
4-(5-cyano-6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}pyridin-2-yl)piperazin-1-ium chloride;
6-chloro-2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}nicotinonitrile;
2-chloro-6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}nicotinonitrile;
(2R)-1-[4-(6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-5-methylpyridin-2-yl)piperazin-1-yl]-1-oxopropan-2-ol;
(2S)-1-[4-(6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-5-methylpyridin-2-yl)piperazin-1-yl]-1-oxopropan-2-ol;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-6-[4-(methylsulfonyl)piperazin-1-yl]nicotinonitrile;
1-(6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-5-methylpyridin-2-yl)piperidin-4-one;
8-(6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-5-methylpyridin-2-yl)-1,4-dioxa-8-azaspiro[4.5]decane;
8-(6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-3-methylpyridin-2-yl)-1,4-dioxa-8-azaspiro[4.5]decane;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-3-methyl-6-morpholin-4-ylpyridinium chloride;
6-{4-[2-(acetyloxy)-2-methylpropanoyl]piperazin-1-yl}-2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-3-methylpyridinium trifluoroacetate;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-6-{4-[(dimethylammonio)acetyl]piperazin-1-yl}-3-methylpyridinium dichloride;
1-[4-(6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-5-methylpyridin-2-yl)piperazin-1-yl]-2-methyl-1-oxopropan-2-ol;
1-(6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-5-methylpyridin-2-yl)piperidin-4-ol;
4-(6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-5-methylpyridin-2-yl)-1-(2,2,2-trifluoroethyl)piperazin-1-ium chloride;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-6-(4-methoxypiperidin-1-yl)-3-methylpyridinium chloride;
1-(cyclopropylmethyl)-4-(6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-5-methylpyridinium-2-yl)piperazin-1-ium dichloride;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-3-methyl-6-[4-(methylsulfonyl)piperazin-1-yl]pyridinium chloride;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-3-methyl-6-{4-[(1-methyl-1H-imidazol-3-ium-2-yl)carbonyl]piperazin-1-yl}pyridinium dichloride;
2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-6-[4-(isoxazol-3-ylcarbonyl)piperazin-1-yl]-3-methylpyridinium chloride;
1-[(2,2-difluorocyclopropyl)methyl]-5-(6-fluoro-3-methylpyridin-2-yl)-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;
and pharmaceutically acceptable salts of any of the foregoing compounds.

### Claim 21 (depends on 1)

The compound according to claim 1 wherein R1 is 2,2-difluorocyclopropyl.

### Claim 22 (depends on 1)

A compound according to claim 1 of Formula Il
and pharmaceutically acceptable salts thereof, wherein:
one of the R3 groups shown in Formula Il is selected from H, CN or methyl; the other R3 group is H;
R13 is selected from the group consisting of: —C(O)—CH2—N(R)2, —C(O)—O—C1-4alkyl, —C(O)—C(R)2—C(O)—O—C1-4alkyl, —CH2—C3-6cycloalkyl, C1-4alkoxy, methylsulfonyl, heteroaryl-C(O)—, C1-4 alkyl and C1-4alkyl-C(O)—, said C1-4 alkyl, C1-4 alkyl-C(O)— and heteroaryl-C(O)— optionally substituted with 1 to 3 halogen atoms and hydroxy and heteroaryl-C(O)— additionally optionally substituted with methyl, and each R is independently selected from the group consisting of: H and C1-4alkyl.

### Claim 23 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1 in combination with a pharmaceutically acceptable carrier.

### Claim 24 (depends on 1)

A method for treating a neurological or psychiatric disorder associated with glutamate dysfunction in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound according to claim 1.

### Claim 25 (depends on 24)

The method according to claim 24 wherein the neurological or psychiatric disorder associated with glutamate dysfunction is schizophrenia.