# US 5,344,830 A · N,N-diacylpiperazine tachykinin antagonists

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- Number: US 5,344,830 A
- Document ID: US5344830A
- Status: Granted
- Kind: A
- Application number: 07/988,514
- Filed: 1992-12-10
- Granted: 1994-09-06
- Earliest claimed: 1992-12-10
- Assignees: Merck & Co., Inc.
- Inventors: Sander G. Mills; Richard J. Budhu; Conrad P. Dorn; William J. Greenlee; Malcolm MacCoss; Mu T. Wu
- Web page: https://patentgrep.com/patent/US5344830A

## CPC

- C07D 241/04: having no double bonds between ring members or between ring members and non-ring members
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Diacylpiperazines of general structure ##STR1## are tachykinin receptor antagonists useful in the treatment of inflammatory diseases, pain or migraine, and asthma, and calcium channel blockers useful in the treatment of cardiovascular conditions such as angina, hypertension or ischemia.

## Claims

### Claim 1

A compound which is selected from the group consisting of:
1) 4-(N,N-di-n-pentylcarbamoyl)-1-(N,N -diphenyl-carbamoyl)-N-[3-(4-morpholinyl)propyl]-2-piperazinecarboxamide;
2) 4-(N,N-di-n-pentylcarbamoyl)-1-(N,N-diphenyl-carbamoyl)-N-[2-(4-morpholiny l)ethyl]-2-piperazinecarboxamide;
3) 4-(N,N-di-n-pentylcarbamoyl)-1-(N,N-diphenyl-carbamoyl)-N-[2-(1-piperidiny l)ethyl]-2-piperazinecarboxamide;
4) 4-(N,N-di-n-pentylcarbamoyl)-1-(N,N-diphenyl-carbamoyl)-N-[2-(acetamido)et hyl]-2-piperazinecarboxamide;
5) 4-(N,N-di-n-pentylcarbamoyl)-1-(N,N-diphenyl-carbamoyl)-N-[2-(N'-benzyl-N' -methylamino)-ethyl]-N-methyl-2-piperazinecarboxamide;
6) 4-(N,N-di-n-pentylcarbamoyl)-1-(N,N-diphenyl-carbamoyl)-N-[3-(benzyloxycar bonyl)propyl]-N-methyl-2-piperazinecarboxamide;
7) 4-(N,N-di-n-pentylcarbamoyl)-1-(N,N-diphenyl-carbamoyl)-N-[2-[(N'-(3,5-dim ethylphenyl)-methyl-(N'-methyl)amino]ethyl]-N-methyl-2-piperazinecarboxamid e;
8) 4-(N,N-di-n-pentylcarbamoyl)-1-(N,N-diphenyl-carbamoyl)-N-[2-[(N'-[3,5-di- (trifluoro-methyl)phenyl]methyl)-(N'-methyl)amino]ethyl]-N-methyl-2-piperaz inecarboxamide;
9) 4-(N,N-di-n-pentylcarbamoyl)-1-(N,N-diphenyl-carbamoyl)-N-[2-[(N'-(2-metho xyphenyl)-methyl)-(N'-methyl) amino]ethyl]-N-methyl-2-piperazinecarboxamide;
10) 4-(N,N-di-n-pentylcarbamoyl)-1-(N,N-diphenyl-carbamoyl)-N-[2-(N'-[(1,1-dim ethyl)ethoxy-carbonyl]-(N'-methyl)aminoethyl]-N-methyl-2-piperazinecarboxam ide;
11) (S)-2-(2-(N-(2-methoxybenzyl)amino)ethylaminocarbonyl)-4-(N,N-di-n-pentylc arbamoyl)-1-(N,N-diphenylcarbamoyl)-piperazine;
12) 2-(2-(N-methyl-N-(2-methoxybenzyl)amino)-ethylamino-carbonyl)-4-(N,N-di-n- pentylcarbamoyl)-1-(N,N-diphenylcarbamoyl)piperazine;
13) (S)-2-(2-(1-piperidinyl)ethylaminocarbonyl)-1-[N-(3-chlorophenyl)-N-phenyl carbamoyl]-4-(N,N-di-n-pentylcarbamoyl)piperazine;
14) (S)-2-(2-(1-piperidinyl)ethylaminocarbonyl)-4-(N,N-di-n-pentylcarbamoyl)-1 -(N,N-diphenyl-carbamoyl)piperazine;
15) (S)-2-(2-(N,N-bis(2-methoxybenzyl)amino)-ethylamino-carbonyl)-1-(N,N-diphe nylcarbamoyl)-4-(N,N-di-n-pentylcarbamoyl)piperazine;
16) (S)-4-(N,N-di-n-pentylcarbamoyl)-1-(N,N-diphenyl-carbamoyl)-2-(2-(4-morpho linyl)ethylaminocarbonyl)-piperazine;
17) (S)-2-(2-(N-benzyl-N-methylamino)-N-(methyl)ethylaminocarbonyl)-4-(N,N-di- n-pentylcarbamoyl)-1-(N,N-diphenylcarbamoyl)piperazine;
18) (S)-1-(N-(3-chlorophenyl)-N-phenylcarbamoyl)-2-(2-(N-methyl-N(2-methoxyben zyl)amino)-ethylaminocarbonyl)-4-(N,N-di-n-pentylcarbamoyl)piperazine;
19(S)-1-(N-(3,5-dimethylphenyl)-N-phenylcarbamoyl)-2-(2-(N-methyl-N-(2-meth oxybenzyl)-amino)ethylaminocarbonyl)-4-(N,N-di-n-pentyl-carbamoyl)piperazin e;
20) (S)-1-(N-(3,5-dichlorophenyl)-N-phenylcarbamoyl)-2-(2-(N-methyl-N-(2-metho xybenzyl)-amino)ethylaminocarbonyl)-4-(N,N-di-n-pentyl-carbamoyl)piperazine
21) (S)-4-(N,N-di-n-pentylcarbamoyl)-1-(N,N-diphenyl-carbamoyl)-2-(2-N-(benzyl oxycarbonylmethyl)amino)-ethylaminocarbonyl)piperazine;
22) (S)-4-(N,N-di-n-pentylcarbamoyl)-1-(N,N-diphenyl-carbamoyl)-2-(2-N-(benzyl oxycarbonylmethyl)-N-methylamino)ethylaminocarbonyl)piperazine;
or a pharmaceutically acceptable salt thereof.

### Claim 2

A compound which is selected from the group consisting of:
1) 2-[2-((N-[2-(N'-benzyl -N'-methyl)aminoethyl])-N -methyl)aminoethyl]-4-(N,N-di-n-pentyl-carbamoyl)-1-(N,N-diphenylcarbamoyl )-piperazine;
2) 2-[2-(N,N-dibenzylamino)ethyl]-4-(N,N-di-n-pentyl-carbamoyl)-1-(N,N-diphen ylcarbamoyl)-piperazine;
3) 2-[2-(N -[2-phenylethyl]amino)ethyl]-4-(N,N -di-n-pentylcarbamoyl)-1-(N,N-diphenyl-carbamoyl)piperazine;
4) 2-[2-(N-benzylamino)ethyl]-4-(N,N-di-n-pentylcarbamoyl)-1-(N,N-diphenylcar bamoyl)-piperazine;
5) 2-[2-(N -[4-phenylbutyl]amino)ethyl]-4-(N,N-di-n-pentylcarbamoyl)-1-(N,N-diphenyl- carbamoyl)piperazine;
6) 4-(N,N-di-n-pentylcarbamoyl)-1-(N,N-diphenyl-carbamoyl)-2-(2-(3-phenylprop ylamino)ethyl)-piperazine;
7) 4-(N,N-di-n-pentylcarbamoyl)-1-(N,N-diphenyl-carbamoyl)-2-(2-(2-(2-methoxy phenyl)ethylamino)ethyl)piperazine;
8) 2-(2-(2-(3,5-di-methylphenyl)ethylamino)ethyl)-4-(N,N -di-n-pentylcarbamoyl)-1-(N,N-di-phenylcarbamoyl)piperazine;
or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of the compound of claim 1.

### Claim 4 (depends on 2)

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of the compound of claim 2.