# US 4,395,406 A · 5-Halopyrimid-2-ones

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- Number: US 4,395,406 A
- Document ID: US4395406A
- Status: Granted
- Kind: A
- Application number: 06/166,600
- Filed: 1980-07-07
- Granted: 1983-07-26
- Earliest claimed: 1975-10-16
- Assignees: Nyegaard & Co. A/S
- Inventors: Mikkel J. Gacek; Reidar Oftebro; Soren Laland; Kjell Undheim
- Web page: https://patentgrep.com/patent/US4395406A

## CPC

- C07D 239/36: as doubly bound oxygen atom or as unsubstituted hydroxy radical
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- C07D 239/56: One oxygen atom and one sulfur atom
- C07H 19/06: Pyrimidine radicals
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)

## Abstract

Novel derivatives of pyrimid-2-one having interesting pharmacological properties are described. The compounds of the invention have been found to be of use in the control of, and in particular in the inhibition of the metaphase of malignant tumours and leukaemias. Processes for the preparation of the novel compounds and pharmaceutical compositions containing them are also described.

## Claims

### Claim 1

A compound of the formula: ##STR16## wherein X represents a fluorine, chlorine or bromine atom; R.sup.1 and R.sup.2, which may be the same or different, each represent hydrogen or a group Alk or SAlk; and R.sup.3 represents a group Alk; Alk being an alkyl, alkenyl or alkynyl group having up to 4 carbon atoms, which group may carry one or more halogen atoms or oxo groups or optionally substituted hydroxy, mercapto, carboxyl, carboxamido or amino groups, wherein the optional substituent is a C.sub.1-4 alkyl, alkenyl, or alkynyl group, with the proviso that R.sup.3 is other than a methyl or ethyl group; or salts thereof.

### Claim 2 (depends on 1)

A compound as claimed in claim 1 in which one of R.sup.1 and R.sup.2 is Alk and the other is hydrogen.

### Claim 3 (depends on 1)

A compound as claimed in claim 1 wherein Alk is an esterified carboxymethyl, allyl, 3-chloroallyl, propargyl or 3-chloropropargyl group.

### Claim 4 (depends on 1)

A compound as claimed in claim 1 which is
1-Propargyl-5-bromopyrimid-2-one,
1-Propargyl-5-chloropyrimid-2-one,
1-(3-chloroallyl)-5-bromopyrimid-2-one,
1-Propargyl-5-fluoropyrimid-2-one,
1-(3-Chloroallyl)-5-chloropyrimid-2-one,
1-Propargyl-4-propargylthio-5-fluoropyrimid-2-one,
1-Allyl-5-chloropyrimid-2-one,
1-Allyl-5-bromopyrimid-2-one,
1-(2-Chloroethyl)-5-bromopyrimid-2-one,
1-(2-Chloroethyl)-5-chloropyrimid-2-one,
1-Propargyl-4-methylthio-5-fluoropyrimid-2-one,
Ethyl ester of 1-carboxymethyl-5-chloropyrimid-2-one,
Ethyl ester of 1-carboxymethyl-5-fluoropyrimid-2-one,
1-Allyl-5-fluoropyrimid-2-one,
1-(2-Hydroxyethyl)-5-chloropyrimid-2-one,
1-(2-Hydroxyethyl)-5-fluoropyrimid-2-one,
1-(2-Hydroxy-3-chloropropyl)-5-bromopyrimid-2-one,
1-(2-Hydroxy-3-chloropropyl)-5-chloropyrimid-2-one,
1-Propyl-5-fluoropyrimid-2-one,
1-(2-Hydroxyethyl)-5-bromopyrimid-2-one,
1-(2,3-Dihydroxypropyl)-5-chloropyrimid-2-one,
1-(2-Hydroxy-3,3,3-trichloropropyl)-5-bromopyrimid-2-one,
1-(2-Dimethylaminoethyl)-5-chloropyrimid-2-one, or
1-Carboxymethyl-5-fluoropyrimid-2-one.

### Claim 5 (depends on 4)

The compound of claim 4 which is 1-propargyl-5-chloropyrimid-2-one.

### Claim 6 (depends on 1)

A compound as claimed in claim 1 wherein Alk is an alkenyl or alkynyl group having up to 4 carbon atoms, which group may carry one or more halogen atoms or oxo groups or optionally substituted hydroxy, mercapto, carboxyl, carboxyamido or amino groups, wherein the optional substituent is a C.sub.1-4 alkyl, alkenyl or alkynyl group; or salts thereof.

### Claim 7 (depends on 1)

A pharmaceutical composition for the inhibition of the metaphase in the growth of malignant tumors and leukaemia, comprising in association with a pharmaceutical carrier or excipient, at least one compound as claimed in claim 1.

### Claim 8 (depends on 7)

A composition as claimed in claim 7 in dosage unit form, each dosage unit containing 100 mg to 1 g of said compound.

### Claim 9 (depends on 8)

A composition as claimed in claim 8 also containing cytosine arabinoside.