# US 4,400,395 A · Allylsulfoxide enzyme inhibitors

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

- Number: US 4,400,395 A
- Document ID: US4400395A
- Status: Granted
- Kind: A
- Application number: 06/349,809
- Filed: 1982-02-18
- Granted: 1983-08-23
- Earliest claimed: 1979-08-15
- Assignees: Merck & Co., Inc.
- Inventors: Raymond A. Firestone
- Web page: https://patentgrep.com/patent/US4400395A

## CPC

- A61K 31/18: Sulfonamides (compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

Organic sulfoxides having a latent allyl group bound to the sulfur are enzyme inhibitors of the suicide or K.sub.cat type.

## Claims

### Claim 1

A compound of structural formula: ##STR61## or a pharmaceutically acceptable salt thereof wherein X is hydrogen, fluoro, chloro, bromo, iodo, C.sub.2-4 alkanoyloxy, toluenesulfonyloxy, benzenesulfonyloxy, C.sub.1-3 alkanesulfonyloxy, p-nitrobenzoyloxy, or ##STR62## Y is hydrogen or ##STR63## and Z is fluoro, chloro, bromo, iodo, C.sub.2-4 alkanoyloxy, toluenesulfonyloxy, benzenesulfonyloxy, C.sub.1-3 alkanesulfonyloxy, p-nitrobenzoyloxy, or ##STR64## or Y and Z taken together form .dbd.CH.sub.2 ; with the proviso that one and only one of X, Y and Z is a sulfoxide, and one and only one of X and Z is halo; wherein
R is
(1) phenyl,
(2) nitrophenyl,
(3) cyanophenyl,
(4) C.sub.1-3 alkylsulfonylphenyl,
(5) C.sub.1-3 alkoxycarbonylphenyl,
(6) di(trifluoromethyl)phenyl,
(7) o-C.sub.1-3 alkylphenyl, or
(8) o,o-di(C.sub.1-3 alkyl)phenyl; and
R.sup.1 is
(1) 3,4-dihydroxyphenyl, or
(2) 4-hydroxyphenyl.

### Claim 2 (depends on 1)

The compound of claim 1 which is
2-fluoromethyl-3-(p-nitrophenylsulfinyl)dopa;
2-([1-fluoro-2-p-nitrophenylsulfinyl]ethyl)dopa;
2-fluoromethyl-3-p-nitrophenylsulfinyltyrosine;
2-([1-fluoro-2-p-nitrophenylsulfinyl]ethyl)tyrosine;
or a pharmaceutically acceptable salt thereof.

### Claim 3

A pharmaceutical enzyme inhibiting composition comprising a pharmaceutical carrier and an effective enzyme inhibiting amount of a compound of structural formula: ##STR65## or a pharmaceutically acceptable salt thereof wherein X is hydrogen, fluoro, chloro, bromo, iodo, C.sub.2-4 alkanoyloxy, toluenesulfonyloxy, benzenesulfonyloxy, C.sub.1-3 alkanesulfonyloxy, p-nitrobenzoyloxy, or ##STR66## Y is hydrogen or ##STR67## and Z is fluoro, chloro, bromo, iodo, C.sub.2-4 alkanoyloxy, toluenesulfonyloxy, benzenesulfonyloxy, C.sub.1-3 alkanesulfonyloxy, p-nitrobenzoyloxy, or ##STR68## or Y and Z taken together form .dbd.CH.sub.2 ; with the proviso that one and only one of X, Y and Z is a sulfoxide, and one and only one of X and Z is halo; wherein
R is
(1) phenyl,
(2) nitrophenyl,
(3) cyanophenyl,
(4) C.sub.1-3 alkylsulfonylphenyl,
(5) C.sub.1-3 alkoxycarbonylphenyl,
(6) di(trifluoromethyl)phenyl,
(7) o-C.sub.1-3 alkylphenyl, or
(8) o,o-di(C.sub.1-3 alkyl)phenyl; and
R.sup.1 is
(1) 3,4-dihydroxyphenyl, or
(2) 4-hydroxyphenyl.

### Claim 4 (depends on 3)

The pharmaceutical composition of claim 3 wherein the compound is
2-fluoromethyl-3-(p-nitrophenylsulfinyl)dopa;
2-([1-fluoro-2-p-nitrophenylsulfinyl]ethyl)dopa;
2-fluoromethyl-3-p-nitrophenylsulfinyltyrosine;
2-([1-fluoro-2-p-nitrophenylsulfinyl]ethyl)tyrosine;
or a pharmaceutically acceptable salt thereof.

### Claim 5

A method of inhibiting enzymes in a patient in need of such treatment which comprises the administration of an enzyme inhibitory amount of a compound of structural formula: ##STR69## or a pharmaceutically acceptable salt thereof wherein X is hydrogen, fluoro, chloro, bromo, iodo, C.sub.2-4 alkanoyloxy, toluenesulfonyloxy, benzenesulfonyloxy, C.sub.1-3 alkanesulfonyloxy, p-nitrobenzoyloxy, or ##STR70## Y is hydrogen or ##STR71## and Z is fluoro, chloro, bromo, iodo, C.sub.2-4 alkanoyloxy, toluenesulfonyloxy, benzenesulfonyloxy, C.sub.1-3 alkanesulfonyloxy, p-nitrobenzoyloxy, or ##STR72## or Y and Z taken together form .dbd.CH.sub.2 ; with the proviso that one and only one of X, Y and Z is a sulfoxide, and one and only one of X and Z is halo; wherein
R is
(1) phenyl,
(2) nitrophenyl,
(3) cyanophenyl,
(4) C.sub.1-3 alkylsulfonylphenyl,
(5) C.sub.1-3 alkoxycarbonylphenyl,
(6) di(trifluoromethyl)phenyl,
(7) o-C.sub.1-3 alkylphenyl, or
(8) o,o-di(C.sub.1-3 alkyl)phenyl; and
R.sup.1 is
(1) 3,4-dihydroxyphenyl, or
(2) 4-hydroxyphenyl.

### Claim 6 (depends on 5)

The method of claim 5 wherein the compound is
2-fluoromethyl-3-(p-nitrophenylsulfinyl)dopa;
2-([1-fluoro-2-p-nitrophenylsulfinyl]ethyl)dopa;
2-fluoromethyl-3-p-nitrophenylsulfinyltyrosine;
2-([1-fluoro-2-p-nitrophenylsulfinyl]ethyl)tyrosine;
or a pharmaceutically acceptable salt thereof.