# US 5,703,240 A · Piperidine derivatives

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- Number: US 5,703,240 A
- Document ID: US5703240A
- Status: Granted
- Kind: A
- Application number: 08/612,843
- Filed: 1996-03-21
- Granted: 1997-12-30
- Earliest claimed: 1993-09-22
- Assignees: Glaxo Group Limited
- Inventors: Duncan Robert Armour; Brian Evans; David Middlemiss; Alan Naylor; Neil Anthony Pegg; Maria Victoria Vinader; Gerard Martin Paul Giblin; Tania Hubbard; Michael Menteith Hann; Xiao-Qing Lewell; Stephen Paul Watson
- Web page: https://patentgrep.com/patent/US5703240A

## CPC

- C07D 401/12: linked by a chain containing hetero atoms as chain links
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/08: for nausea, cinetosis or vertigo; Antiemetics
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to piperidine derivatives of formula (I) ##STR1## wherein R.sup.1 is a C.sub.1-4 alkoxy group; R.sup.2 is ##STR2## R.sup.3 is a hydrogen or halogen atom; R.sup.4 and R.sup.5 may each independently represent a hydrogen or halogen atom, or a C.sub.1-4 alkyl, C.sub.1-4 alkoxy or trifluoromethyl group; R.sup.6 is a hydrogen atom, a C.sub.1-4 alkyl, (CH.sub.2).sub.m cyclopropyl, --S(O).sub.n C.sub.1-4 alkyl, phenyl, NR.sup.7 R.sup.8, CH.sub.2 C(O)CF.sub.3 or trifluoromethyl group; R.sup.7 and R.sup.8 may each independently represent a hydrogen atom, or a C.sub.1-4 alkyl or acyl group; x represents zero or 1; n represents zero, 1 or 2; m represents zero or 1; and pharmaceutically acceptable salts and solvates thereof; to processes for their preparation; and their use in the treatment of conditions mediated by tachykinins.

## Claims

### Claim 1

A compound of formula (I) ##STR32## wherein R.sup.1 is a C.sub.1-4 alkoxy group; R.sup.2 is ##STR33## R.sup.3 is a hydrogen or halogen atom; R.sup.4 and R.sup.5 may each independently represent a hydrogen or halogen atom, or a C.sub.1-4 alkyl, C.sub.1-4 alkoxy or trifluoromethyl group;
R.sup.6 is a hydrogen atom, a C.sub.1-4 alkyl, (CH.sub.2).sub.m cyclopropyl, --S(O).sub.n C.sub.1-4 alkyl, phenyl,
NR.sup.7 R.sup.8, CH.sub.2 C(O)CF.sub.3 or trifluoromethyl group;
R.sup.7 and R.sup.8 may each independently represent a hydrogen atom, or a C.sub.1-4 alkyl or acyl group;
x represents zero or 1;
n represents zero, 1 or 2;
m represents zero or 1;
or a pharmaceutically acceptable salt or solvate thereof.

### Claim 2 (depends on 1)

A compound according to claim 1 wherein R.sup.1 is a C.sub.1-4 alkoxy group, R.sup.2 is ##STR34## where R.sup.6 is a hydrogen atom, a C.sub.1-4 alkyl, cyclopropyl or trifluoromethyl group, x is zero and R.sup.3, R.sup.4 and R.sup.5 are each hydrogen atoms.

### Claim 3 (depends on 1)

A compound according to claim 1 wherein R.sup.1 is a methoxy group.

### Claim 4 (depends on 1)

A compound according to claim 1 wherein R.sup.2 is ##STR35##

### Claim 5 (depends on 1)

A compound according to claim 1 wherein R.sup.3 is hydrogen.

### Claim 6 (depends on 1)

A compound according to claim 1 wherein R.sup.4 and R.sup.5 are each hydrogen atoms.

### Claim 7 (depends on 1)

A compound according to claim 1 wherein R.sup.6 is hydrogen, a C.sub.1-4 alkyl or trifluoromethyl group.

### Claim 8 (depends on 1)

A compound according to claim 1 wherein x is zero.

### Claim 9

The compound which is (2-Methoxy-5-tetrazol-1-yl-benzyl)-(2S-phenyl-piperidin-3S-yl)-amine or a pharmaceutically acceptable salt or solvate thereof.

### Claim 10

The compound which is ›2-Methoxy-5-(5-trifluoromethyl-tetrazol-1-yl)-benzyl!-(2S-phenyl-piperidi n-3S-yl)-amine or a pharmaceutically acceptable salt or solvate thereof.

### Claim 11 (depends on 9)

A compound according to claim 9 in the form of its dihydrochloride salt.

### Claim 12 (depends on 1)

A compound according to claim 1 for use in therapy.

### Claim 13 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof, together with a pharmaceutically acceptable carrier.

### Claim 14 (depends on 1)

A method for the treatment of a condition mediated by tachykinins, including substance P and other neurokinins, in a mammal comprising administration of an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof.

### Claim 15 (depends on 1)

A process for preparing a compound of formula (I) as defined in claim 1, or a pharmaceutically acceptable salt or solvate thereof which comprises:
(A) reacting a compound of formula (II) ##STR36## with a compound of formula (III) ##STR37## followed by reduction: or (B), a process for preparing a compound of formula (I) where R.sup.2 is a group (A) as defined hereinbefore, x is zero and R.sup.6 is --NH.sub.2 which comprises reacting a compound of formula (XXIII) ##STR38## with ammonium chloride and sodium azide: or (C) reducing a compound of formula (XXIV) ##STR39##

### Claim 16 (depends on 10)

A compound according to claim 10 in the form of its dihydrochloride salt.

### Claim 17 (depends on 1)

A pharmaceutical composition comprising a compound of formula (I) as defined in claim 1 in combination with a 5HT.sub.3 antagonist.

### Claim 18 (depends on 17)

A pharmaceutical composition according to claim 17 wherein the 5HT.sub.3 antagonist is selected from ondansetron, granisetron or metoclopramide.

### Claim 19 (depends on 14)

A method of treatment according to claim 14 wherein the condition is emesis.

### Claim 20 (depends on 14)

A method of treatment according to claim 14 wherein the condition is pain.