# US 7,745,630 B2 · Triazolyl piperidine arginine vasopressin receptor modulators

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- Number: US 7,745,630 B2
- Document ID: US7745630B2
- Status: Granted
- Kind: B2
- Application number: 11/009,768
- Filed: 2004-12-10
- Published: 2005-07-14
- Granted: 2010-06-29
- Earliest claimed: 2003-12-22
- Inventors: Justin Stephen Bryans; Patrick Stephen Johnson; Lee Richard Roberts; Thomas Ryckmans
- Web page: https://patentgrep.com/patent/US7745630B2

## CPC

- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- 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 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 15/06: Antiabortive agents; Labour repressants
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C07D 249/08: 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D 249/14: Nitrogen atoms
- C07D 401/14: containing three or more hetero rings
- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- C07D 405/14: containing three or more hetero rings
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- C07D 413/14: containing three or more hetero rings
- C07D 471/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Compounds of formula (I), or pharmaceutically acceptable derivatives thereof, wherein: Z, O, A, V, Y and Y′ are as defined herein; are useful for treating dysmenorreah.

## Claims

### Claim 1

A compound of formula (I),
or a pharmaceutically acceptable salt thereof, wherein:
X is —[CH2]a—R or —[CH2]a—O—[CH2]b—R;
a is 1;
b is a number selected from 0 to 4;
R is H, CF3 or Het;
Het is imidazolyl or triazolyl;
Y is one to three substituents independently selected from H, halo, CN, C1-6 alkyl, C1-6 alkoxy, wherein said C1-6 alkyl is unbranched and is optionally substituted on its terminal carbon atom with one to three fluoro or one pyrrolidinyl and wherein said C1-6 alkoxy is unbranched and is optionally substituted on its terminal carbon atom with one to three fluoro;
V is a direct bond;
Ring A is a piperidine ring, wherein said piperidine ring is optionally substituted with one to three groups selected from C1-6 alkyl, phenyl or hydroxy;
Q is a direct bond;
Z is selected from the group consisting of phenyl, pyridyl, quinolinyl, isoquinolinyl, naphthyl, benzoimidazolyl, benzotriazolyl, oxadiazolyl, indazolyl and indolyl, each optionally substituted with one to three groups selected from W;
W independently at each occurrence is halo, hydroxy, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylSO2, C1-6 alkylSO, C1-6 alkylS, C3-6 cycloalkoxy, C3-6 cycloalkyl, phenyl, phenoxy, pyridinyl, pyrimidinyl, benzyl, benzyloxy or H2NSO2, wherein said C1-6 alkyl or said C1-6 alkoxy are each unbranched and are each optionally substituted on the terminal carbon atom with one to three fluoro.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein X is —[CH2]a—R or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 2)

The compound according to claim 2, wherein R is Het, or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

The compound according to claim 1, wherein Y is halo, or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 4)

The compound according to claim 4, wherein Y is chloro, or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 5)

The compound according to claim 5, wherein Y is 4-chloro, or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 1)

The compound according to claim 1, wherein Z is phenyl optionally substituted with one to three groups independently selected from W, or a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 1)

The compound according to claim 1, wherein Z is substituted with halo, or a pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 1)

The compound according to claim 1 selected from
(3-Chloro-phenyl)-{4-[4-(4-chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-methanone;
(4-Chloro-phenyl)-{4-[4-(4-chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-methanone;
(5-Chloro-2-fluoro-phenyl)-{4-[4-(4-chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-methanone;
{4-[4-(4-Chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-(3,5-difluoro-phenyl)-methanone;
{4-[4-(4-Chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-(3-fluoro-phenyl)-methanone;
{4-[4-(4-Chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-(2,3-difluoro-phenyl)-methanone;
(3-Chloro-2-fluoro-phenyl)-{4-[4-(4-chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-methanone;
(3-Chloro-4-fluoro-phenyl)-{4-[4-(4-chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-methanone;
{4-[4-(4-Chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-(4-trifluoromethyl-phenyl)-methanone;
{4-[4-(4-Chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-(3-trifluoromethyl-phenyl)-methanone;
{4-[4-(4-Chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-(2-trifluoromethyl-phenyl)-methanone;
(3-Chloro-5-fluoro-phenyl)-{4-[4-(4-chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-methanone;
{4-[4-(4-Chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-(4-difluoromethyl-phenyl)-methanone;
{4-[4-(4-Chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-(1H-indazol-3-yl)-methanone;
or a pharmaceutically acceptable salt thereof.

### Claim 10

{4-[4-(4-Chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-(3,5-difluoro-phenyl)-methanone, or a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 1)

A method of treating cardiovascular disease, primary dysmenorrhea, secondary dysmenorrhea, premature labor or Raynaud's disease comprising administering a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, according to claim 1.

### Claim 12 (depends on 11)

The method according to claim 11, wherein primary dysmenorrhea or secondary dysmenorrhea is treated.

### Claim 13 (depends on 1)

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

### Claim 14 (depends on 13)

The pharmaceutical composition according to claim 13 wherein the compound is {4-[4-(4-Chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-(3,5-difluoro-phenyl)-methanone, or a pharmaceutically acceptable salt thereof.

### Claim 15 (depends on 11)

The method according to claim 11 wherein the compound is {4-[4-(4-Chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-(3,5-difluoro-phenyl)-methanone, or a pharmaceutically acceptable salt thereof.