# US 2014/0194470 A1 · Derivatives of 2-pyridin-2-yl-pyrazol-3(2h)-one, preparation and therapeutic use thereof

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- Number: US 2014/0194470 A1
- Document ID: US20140194470A1
- Status: Published application
- Kind: A1
- Application number: 14/200,698
- Filed: 2014-03-07
- Published: 2014-07-10
- Earliest claimed: 2011-06-29
- Assignees: Sanofi
- Inventors: Jean-Michel Altenburger; Valerie Fossey; Stephane Illiano; Geraldine Manette
- Web page: https://patentgrep.com/patent/US20140194470A1

## CPC

- C07D 401/14: containing three or more hetero rings
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 7/06: Antianaemics
- 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 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 13/12: of the kidneys
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 27/02: Ophthalmic agents
- A61P 27/06: Antiglaucoma agents or miotics
- A61P 31/12: Antivirals
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- C07D 471/04: Ortho-condensed systems
- C07D 491/052: the oxygen-containing ring being six-membered
- C07D 495/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention relates to compounds corresponding to formula (I), in the form of the base or of an acid-addition salt: in which n is equal to 0, 1, 2, 3 or 4; m is equal to 0, 1 or 2; o is equal to 0 or 1; X represents a group —CH2, —CH(R′)—, —NH(R′)— or a heteroatom chosen from O and S, it being understood that R′ represents a group —(C1-C5)alkyl, —(C1-C5)alkoxy, —CH2-aryl, —C(O)R5 or —COOR5; R1 represents an oxo group, —COOR5, —W—OH or —W—NR5R6; R2 represents an H atom or a group chosen from the groups (i) —(C1-C5)alkyl, (ii) —(C1-C5)alkoxy, (iii) —COOR5, (iv) —NR5R6, (v) —C(O)—NR5R6, (vi) —SO2—NR3R4, (vii) heteroaryl optionally substituted with a group —(C1-C5)alkyl, (viii) —W-aryl, (ix) —W-heteroaryl, (x) —O—W-aryl, (xi) —O—W-heteroaryl and (xii) —O—W—NR5R6; it being understood that R3 and R4, (i) which may be identical or different, represent, independently of each other, an H atom, a group —(C1-C5)alkyl, —(C3-C6)cycloalkyl, aryl, heteroaryl, —CH2-heteroaryl, —(C1-C5)alkyl-NR5R6, —W—OH or —W—NR5R6; or (ii) form, together with the nitrogen atom that bears them, a heterocycloalkyl group optionally substituted with one or more groups chosen from the groups —(C1-C5)alkyl and —CH2-aryl; W is a group —(C1-C5)alkylene, optionally substituted with one or more hydroxyl groups; R5 and R6, which may be identical or different, represent, independently of each other, a hydrogen atom or a group chosen from the groups —(C1-C5)alkyl and the groups —(C3-C6)cycloalkyl, and also the process for preparing them and the therapeutic uses thereof.

## Claims

### Claim 1

A compound of formula (I):
wherein:
n is equal to 0, 1, 2, 3 or 4;
m is equal to 0, 1 or 2;
o is equal to 0 or 1;
X represents —CH2, —CH(R′)—, —N(R′)—, an oxygen atom or a sulfur atom, provided that when X is a sulfur atom, m+n do not equal 2; it being understood that R′ represents —(C1-C5)alkyl, —(C1-C5)alkoxy, —CH2-aryl, —C(O)R5 or —COOR5 with R5 as defined below;
R1 represents oxo, —COOR5, —W—OH or —W—NR5R6, with W, R5 and R6 as defined below;
R2 represents hydrogen or a group chosen from (i) groups —(C1-C5)alkyl, (ii) groups —(C1-C5)alkoxy, (iii) groups —COOR5, (iv) groups —NR5R6, (v) groups —C(O)—NR5R6, (vi) groups —SO2—NR3R4, (vii) heteroaryl groups optionally substituted with a group —(C1-C5)alkyl, (viii) groups —W-aryl, (ix) groups —W-heteroaryl, (x) groups —O—W-aryl, (xi) groups —O—W-heteroaryl and (xii) groups —O—W—NR5R6, with W, R3, R4, R5 and R6 as defined below;
R3 and R4,
(i) which may be identical or different, represent, independently of each other, hydrogen, —(C1-C5)alkyl, —(C3-C6)cycloalkyl, aryl, heteroaryl, —CH2-heteroaryl, —(C1-C5)alkyl-NR5R6, —W—OH or —W—NR5R6; or
(ii) form, together with the nitrogen atom that bears them, a heterocycloalkyl group optionally substituted with one or more groups chosen from —(C1-C5)alkyl and —CH2-aryl;
W is —(C1-C5)alkylene, optionally substituted with one or more hydroxyl groups; and
R5 and R6, which may be identical or different, represent, independently of each other, hydrogen, —(C1-C5)alkyl or —(C3-C6)cycloalkyl;
in the form of the base or of an acid-addition salt.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein:
R2 represents hydrogen, —(C1-C5)alkyl, —(C1-C5)alkoxy, —COOR5, —NR5R6, —C(O)—NR5R6 or —SO2—NR3R4;
R3 and R4
(i) represent, independently of each other, hydrogen, —(C1-C5)alkyl, —(C3-C6)cycloalkyl, aryl, heteroaryl, —CH2-heteroaryl or —(C1-C5)alkyl-NR5R6; or
(ii) form, together with the nitrogen atom that bears them, a heterocycloalkyl group optionally substituted with —(C1-C5)alkyl or aryl; and
R5 and R6 represent, independently of each other, hydrogen or —(C1-C5)alkyl;
in the form of the base or of an acid-addition salt.

### Claim 3 (depends on 1)

The compound according to claim 1, wherein:
o is equal to 0;
R1 represents oxo, —CH2-aryl, —C(O)R5- or —COOR5;
R3 and R4
(i) represent, independently of each other, hydrogen, —(C1-C5)alkyl, —(C3-C6)cycloalkyl, aryl, heteroaryl, —CH2-heteroaryl or —(C1-C5)alkyl-NR5R6; or
(ii) form, together with the nitrogen atom that bears them, a heterocycloalkyl group optionally substituted with one or more group(s) —(C1-C5)alkyl or aryl, advantageously, the said heterocycloalkyl group representing a piperidyl group or a hexamethyleneimino group and the said aryl group representing a phenyl group;
R5 represents —(C1-C5)alkyl or —(C3-C6)cycloalkyl; and
R6 represents hydrogen or (C1-C5)alkyl;
in the form of the base or of an acid-addition salt.

### Claim 4 (depends on 3)

The compound according to claim 3, wherein R1 represents benzyl; and R3 and R4 represent, independently of each other, phenyl, pyridyl or furyl, or R3 and R4 form, together with the nitrogen atom that bears them, piperidyl or hexamethyleneimino, wherein the piperidyl or hexamethyleneimino is optionally substituted with one or more —(C1-C5)alkyl or phenyl; in the form of the base or of an acid-addition salt.

### Claim 5 (depends on 1)

The compound according to claim 1, wherein:
n is equal to 1, 2, 3 or 4;
R1 represents oxo, COOR5, —W—OH or —W—NR5R6;
R2 represents —SO2—NR3R4;
R3 and R4
(i) represent, independently of each other, hydrogen, —(C1-C5)alkyl, —(C3-C6)cycloalkyl, aryl, heteroaryl or —CH2-heteroaryl, or
(ii) form, together with the nitrogen atom that bears them, a heterocycloalkyl group; and
R5 and R6 represent —(C1-C5)alkyl;
in the form of the base or of an acid-addition salt.

### Claim 6 (depends on 1)

The compound according to claim 1, wherein:
n is equal to 1, 2, 3 or 4;
R1 represents oxo;
R2 represents hydrogen, —(C1-C5)alkyl, —(C1-C5)alkoxy, —COOR5, —NR5R6 or —C(O)—NR5R6; and
R5 and R6 represent, independently of each other, hydrogen, —(C1-C5)alkyl or —(C3-C5)cycloalkyl;
in the form of the base or of an acid-addition salt.

### Claim 7 (depends on 1)

The compound according to claim 1, wherein R2 represents hydrogen, —(C1-C5)alkyl, —(C1-C5)alkoxy, —COOR5, —NR5R6, —C(O)—NR5R6, heteroaryl substituted with —(C1-C5)alkyl, —O—W-aryl or —O—W-heteroaryl; in the form of the base or of an acid-addition salt.

### Claim 8 (depends on 1)

The compound according to claim 1, wherein R2 represents —SO2—NR3R4; in the form of the base or of an acid-addition salt.

### Claim 9 (depends on 1)

The compound according to claim 1, wherein R2 is a substituent on the atom in the beta position of pyridine; in the form of the base or of an acid-addition salt.

### Claim 10 (depends on 1)

The compound according to claim 1, wherein R2 is a substituent on the atom in the gamma position of pyridine; in the form of the base or of an acid-addition salt.

### Claim 11

A compound selected from the group consisting of:
2-[5-(piperidin-1-ylsulfonyl)pyridin-2-yl]-1,2,4,5,6,7-hexahydro-3H-indazol-3-one;
6-methyl-2-[5-(piperidin-1-ylsulfonyl)pyridin-2-yl]-1,2,4,5,6,7-hexahydro-3H-indazol-3-one;
2-[5-(piperidin-1-ylsulfonyl)pyridin-2-yl]-1,4,5,6,7,8-hexahydrocyclohepta[c]pyrazol-3(2H)-one;
N-ethyl-6-(3-oxo-1,3,4,5,6,7-hexahydro-2H-indazol-2-yl)-N-phenylpyridine-3-sulfonamide;
6-(5-benzyl-3-oxo-1,3,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)-N-ethyl-N-phenylpyridine-3-sulfonamide;
(±)-2-(5-{[(3R,5S)-3,5-dimethylpiperidin-1-yl]sulfonyl}pyridin-2-yl)-1,2,4,5,6,7-hexahydro-3H-indazol-3-one;
2-(pyridin-2-yl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3(2H)-one;
(±)-5-benzyl-2-(5-{[(3R,5S)-3,5-dimethylpiperidin-1-yl]sulfonyl}pyridin-2-yl)-1,2,4,5,6,7-hexahydro-3H-pyrazolo[4,3-c]pyridin-3-one;
(±)-2-(5-{[(3R,5S)-3,5-dimethylpiperidin-1-yl]sulfonyl}pyridin-2-yl)-6-methyl-1,2,4,5,6,7-hexahydro-3H-indazol-3-one;
6-(5-benzyl-3-oxo-1,3,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)-N,N-diethylpyridine-3-sulfonamide;
N-ethyl-6-(3-oxo-1,3,4,5,6,7,8,9-octahydro-2H-cycloocta[c]pyrazol-2-yl)-N-phenylpyridine-3-sulfonamide;
6-(5-benzyl-3-oxo-1,3,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)-N,N-di(propan-2-yl)pyridine-3-sulfonamide;
6-methoxy-2-(pyridin-2-yl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3(2H)-one;
N-ethyl-6-(3-oxo-1,4,6,7-tetrahydropyrano[4,3-c]pyrazol-2(3H)-yl)-N-phenylpyridine-3-sulfonamide;
sodium 4-benzyl-2-{5-[ethyl(phenyl)sulfamoyl]pyridin-2-yl}-5-oxo-4,5,6,7-tetrahydro-2,1-pyrazolo[4,3-b]pyridin-3-olate;
tert-butyl 2-{5-[ethyl(phenyl)sulfamoyl]pyridin-2-yl}-3-oxo-1,2,3,4,6,7-hexahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylate;
6-(5-acetyl-3-oxo-1,3,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)-N-ethyl-N-phenylpyridine-3-sulfonamide;
methyl 2-{5-[ethyl(phenyl)sulfamoyl]pyridin-2-yl}-3-oxo-1,2,3,4,6,7-hexahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylate;
sodium 2-{5-[ethyl(phenyl)sulfamoyl]pyridin-2-yl}-6-methoxy-2,4,5,6-tetrahydroeyclopenta[c]pyrazol-3-olate;
N-ethyl-6-(3-oxo-3,4,5,6-tetrahydrocyclopenta[c]pyrazol-2(1H)-yl)-N-phenylpyridine-3-sulfonamide;
N-cyclopentyl-N-ethyl-6-(3-oxo-3,4,5,6-tetrahydrocyclopenta[c]pyrazol-2(1H)-yl)pyridine-3-sulfonamide; and
2,2-dimethylpropyl 6-[5-(methylsulfonyl)-3-oxo-1,3,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridin-2-yl]pyridine-3-carboxylate; or
in the form of the base or of an acid-addition salt.

### Claim 12 (depends on 1)

A process for preparing the compound according to claim 1, comprising reacting a compound of formula (IVa) or (IVb) or both:
wherein X, R1, R2, n, m and are as defined in claim 1, and z represents an alkyl group, with an organic base.

### Claim 13

(canceled)

### Claim 14 (depends on 1)

A pharmaceutical composition, comprising the compound according to claim 1, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

### Claim at position 15

15-20. (canceled)