# US 4,396,772 A · Phosphinylalkanoyl amino acids

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 4,396,772 A
- Document ID: US4396772A
- Status: Granted
- Kind: A
- Application number: 06/323,859
- Filed: 1981-11-23
- Granted: 1983-08-02
- Earliest claimed: 1981-11-23
- Assignees: F. R. Squibb & Sons, Inc.
- Inventors: Edward W. Petrillo, Jr.
- Web page: https://patentgrep.com/patent/US4396772A

## CPC

- C07F 9/3211: {Esters of acyclic saturated acids which can have further substituents on alkyl}
- A61P 9/12: Antihypertensives
- C07F 9/301: {Acyclic saturated acids which can have further substituents on alkyl}
- C07F 9/5728: {condensed with carbocyclic rings or carbocyclic ring systems}
- C07F 9/6506: having the nitrogen atoms in positions 1 and 3
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Angiotensin converting enzyme activity is inhibited by compounds having the formula ##STR1## and salts thereof wherein R.sub.1 is alkyl, aryl, arylalkyl, cycloalkyl, or cycloalkyl(alkyl); R.sub.2 and R.sub.4 each is independently hydrogen, alkyl, arylalkyl or ##STR2## wherein X is hydrogen, alkyl, or phenyl and Y is hydrogen, alkyl, phenyl or alkoxy, or together X and Y are --(CH.sub.2).sub.2 --, --(CH.sub.2).sub.3 --, --CH.dbd.CH--or ##STR3## R.sub.3 is hydrogen or alkyl; ##STR4## is a residue of an amino acid selected from the group consisting of glycine, alanine, valine, norvaline, leucine, N-methylleucine, norleucine, isoleucine, phenylalanine, tyrosine, serine, threonine, cysteine, methionine, aspartic acid, glutamic acid, arginine, lysine, asparagine, glutamine, histidine, or tryptophane; and n is 0 or 1.

## Claims

### Claim 1

A compound having the formula ##STR18## or a salt thereof, wherein R.sub.1 is alkyl, aryl, arylalkyl, cycloalkyl, or cycloalkyl(alkyl);
R.sub.2 and R.sub.4 each is independently hydrogen, alkyl, arylalkyl or ##STR19## wherein X is hydrogen, alkyl, or phenyl and Y is hydrogen, alkyl, phenyl or alkoxy, or together X and Y are --(CH.sub.2)--.sub.2, --(CH.sub.2).sub.3 --, --CH.dbd.CH-- or ##STR20## R.sub.3 is hydrogen or alkyl; ##STR21## is a residue of an amino acid selected from the group consisting of glycine, alanine, valine, norvaline, leucine, N-methylleucine, norleucine, isoleucine, phenylalanine, tyrosine, serine, threonine, cysteine, methionine, aspartic acid, glutamic acid, arginine, lysine, asparagine, glutamine, histidine, or tryptophane; and
n is 0 or 1;
wherein the amino acid residue ##STR22## is linked to the adjacent carbonyl group by an amide bond.

### Claim 2 (depends on 1)

A compound in accordance with claim 1 wherein n is 1.

### Claim 3 (depends on 1)

A compound in accordance with claim 1 wherein R.sub.2 and R.sub.4 each is hydrogen.

### Claim 4 (depends on 1)

A compound in accordance with claim 1 wherein one of R.sub.2 and R.sub.4 is hydrogen and the other is ##STR23##

### Claim 5 (depends on 1)

The compound in accordance with claim 1 N-[[ethoxy(4-phenylbutyl)phosphinyl]acetyl]-L-tyrosine, methyl ester.

### Claim 6 (depends on 1)

The compound in accordance with claim 1 N-[[hydroxy(4-phenylbutyl)phosphinyl]acetyl]-L-tyrosine, methyl ester.

### Claim 7 (depends on 1)

The compound in accordance with claim 1 N-[[hydroxy(4-phenylbutyl)phosphinyl]acetyl]-L-tyrosine.

### Claim 8 (depends on 1)

The compound in accordance with claim 1 N.sup.2 -[[ethoxy(4-phenylbutyl)phosphinyl]acetyl]-L-arginine.

### Claim 9 (depends on 1)

The compound in accordance with claim 1 N.sup.2 -[[hydroxy(4-phenylbutyl)phosphinyl]acetyl]-L-arginine.

### Claim 10 (depends on 1)

The compound in accordance with claim 1 N-[[(2-phenylethyl)(phenylmethoxy)phosphinyl]-acetyl]-L-tryptophan, phenylmethyl ester.

### Claim 11 (depends on 1)

The compound in accordance with claim 1 N-[[hydroxy(2-phenylethyl)phosphinyl]acetyl]-L-tryptophan, ammonia salt.