# US 4,395,401 A · Renally active dipeptides

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- Number: US 4,395,401 A
- Document ID: US4395401A
- Status: Granted
- Kind: A
- Application number: 06/300,546
- Filed: 1981-09-09
- Granted: 1983-07-26
- Earliest claimed: 1981-09-09
- Assignees: SmithKline Beckman Corporation
- Inventors: Francis R. Pfeiffer
- Web page: https://patentgrep.com/patent/US4395401A

## CPC

- C07K 5/06165: {and Pro-amino acid; Derivatives thereof}
- A61P 9/12: Antihypertensives
- A61P 13/02: of urine or of the urinary tract, e.g. urine acidifiers
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- C07K 5/0823: {and Pro-amino acid; Derivatives thereof}
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A group of prolyl-.alpha.-lower alkylphenylalanine dipeptides have been found to improve kidney function especially on cumulative administration. A species is N-4-(4'-hydroxyphenyl)-butyryl-L-propyl-D,L-.alpha.-methyl-3,4-dimethoxyph enylalanyl-L-arginine.

## Claims

### Claim 1

A chemical compound of the structural formula: ##STR6## in which: R is ##STR7## or --NH--(CH.sub.2).sub.3 --NH.sub.2 ; R.sup.1, R.sup.2 or R.sup.3 are each hydrogen, hydroxy or methoxy; and
R.sup.4 is lower alkyl of 1-3 carbons; or pharmaceutically acceptable acid addition salts thereof.

### Claim 2 (depends on 1)

A compound of claim 1 in which R.sup.4 is methyl.

### Claim 3 (depends on 1)

A compound of claim 1 in which at least one of R.sup.1, R.sup.2 or R.sup.3 is hydroxy or methoxy.

### Claim 4 (depends on 1)

A compound of claim 1 in which R is --NH(CH.sub.2).sub.3 --NH.sub.2.

### Claim 5 (depends on 1)

The compound of claim 1 being N-4-(4'-hydroxyphenylbutyryl)-L-prolyl-D,L-.alpha.-methyl-3,4-dimethoxyphe nylalanyl-L-arginine or a pharmaceutically acceptable acid addition salt thereof.

### Claim 6 (depends on 1)

The compound of claim 1 being N-4-(4'-hydroxyphenylbutyryl-L-prolyl-D,L-.alpha.-methylphenylalanine-3-am inopropylamide or a pharmaceutically acceptable acid addition salt thereof.

### Claim 7 (depends on 1)

The compound of claim 1 being N-4-(4'-hydroxyphenylbutyryl)-L-prolyl-D,L-.alpha.-methyltyrosyl-L-arginin e or a pharmaceutically acceptable acid addition salt thereof.

### Claim 8 (depends on 1)

The compound of claim 1 being N-4(4'-hydroxyphenylbutyryl)-L-prolyl-D,L-.alpha.-methyl-3,4-dimethoxyphen ylalanine-3-quanidinopropylamide or a pharmaceutically acceptable salt thereof.

### Claim 9

A chemical compound of the structural formula: ##STR8## in which: R.sup.1, R.sup.2 and R.sup.3 are each hydrogen, hydroxy or methoxy; and
R.sup.4 is lower alkyl of 1-3 carbons.

### Claim 10 (depends on 1, 2, 3, 4, 5, 6, 7, 8)

A pharmaceutical composition capable of improving kidney function comprising a nontoxic, pharmaceutically effective therefor quantity of a compound of claims 1, 2, 3, 4, 5, 6, 7 or 8 combined with a pharmaceutical carrier adapted for oral, anal or injectable administration.

### Claim 11 (depends on 1, 2, 3, 4, 5, 6, 7, 8)

A method of improving kidney function in a patient in need thereof comprising administering orally, anally or parenterally to a said patient a nontoxic quantity of a compound of claims 1, 2, 3, 4, 5, 6, 7 or 8 which is effective therefor.