# US 4,393,060 A · Isocyanuric acid derivatives, method of preparation, therapeutic compositions with a cytostatic action and therapeutic method

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- Number: US 4,393,060 A
- Document ID: US4393060A
- Status: Granted
- Kind: A
- Application number: 06/194,908
- Filed: 1980-10-07
- Granted: 1983-07-12
- Earliest claimed: 1979-10-08
- Assignees: Henkel Kommanditgesellschaft auf Aktien
- Inventors: Herbert Fischer; Manfred Budnowski; Ulrich Zeidler
- Web page: https://patentgrep.com/patent/US4393060A

## CPC

- A61K 31/335: having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K 31/53: having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495})
- A61K 31/535: having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- C07D 251/30: Only oxygen atoms
- C07D 251/32: Cyanuric acid; Isocyanuric acid
- C07D 251/34: Cyanuric or isocyanuric esters
- C07D 303/36: with hydrocarbon radicals, substituted by nitrogen atoms (nitro, nitroso radicals C07D303/08)
- C07D 405/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 405/14: containing three or more hetero rings
- C07D 407/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 413/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 413/08: linked by a carbon chain containing alicyclic rings
- C07D 417/14: containing three or more hetero rings
- 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)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

N-substituted-diglycidyl-isocyanurates having the formula: ##STR1## wherein R represents a hydrocarbon-containing radical selected from the group consisting of alkyl, aryl, aralkyl, alkaryl and cycloalkyl, optionally containing: (a) heterocycles except epoxides, and unsaturation, and (b) substituents selected from the group consisting of halogen, hydroxyl, amino, N-substituted amino, mercapto, alkylmercapto, arylmercapto, alkylsulfoxy, arylsulfoxy, alkoxy, aryloxy and acyloxy, and R.sub.1 represents a member selected from the group consisting of hydrogen and alkyl having from 1 to 4 carbon atoms, as well as the method for preparing said N-substituted-diglycidyl-isocyanurates, therapeutic compositions with cytostatic action comprising said N-substituted-diglycidyl-isocyanurates, and a method of treatment of malignant neoplasias in warm-blooded animals by administering a therapeutically effective amount of said N-substituted-diglycidyl-isocyanurate.

## Claims

### Claim 1

A cytostatic composition consisting essentially of a cytostatically effective amount of at least one N-substituted-diglycidyl-isocyanurate having the formula: ##STR14## wherein R has from 1 to 15 carbon atoms, which R is a hydrocarbon-containing radical selected from the group consisting of alkyl, aryl, aralkyl, alkaryl, cycloalkyl, and unsaturated derivatives thereof, which R may be further substituted by: heterocycles selected from the group consisting of piperidine, hexamethylenimine, morpholine, benzthiazol-2-ylthio and benzimidazol-2-ylthio, and further substituents on said R selected from the group consisting of halogen, hydroxyl, amino, N-substituted amino having the formula:
--NHR.sub.2 and --NR.sub.2 R.sub.3
wherein R.sub.2 and R.sub.3 together have a total of no more than 8 carbon atoms and are members selected from the group consisting of alkyl and alkyl substituted by hydroxy, halogen and alkoxy, mercapto, alkylmercapto, alkylmercapto substituted by hydroxy, halogen and alkoxy, arylmercapto, alkylsulfoxyl, arylsulfoxyl, alkoxy, aryloxy and alkanoyloxy and aroyloxy, and R.sub.1 represents a member selected from the group consisting of hydrogen and alkyl having from 1 to 4 carbon atoms, and a pharmaceutically acceptable carrier therefor.

### Claim 2 (depends on 1)

The therapeutic composition of claim 1 wherein R has from 1 to 12 carbon atoms.

### Claim 3 (depends on 1)

The therapeutic composition of claim 1 wherein R has from 1 to 8 carbon atoms.

### Claim 4 (depends on 1)

The therapeutic composition of claim 1 wherein R has the formula: ##STR15## where Y is O, N, S or SO.sub.2 ; X is H, hydroxyl, halogen, lower alkyl, lower alkylol, hydrocarbon aryl and lower alkanoyl; n is an integer of the valence of Y minus 1, and R.sub.1 has the above-assigned values.

### Claim 5 (depends on 4)

The therapeutic composition of claim 4 wherein R.sub.1 is H.

### Claim 6 (depends on 1, 3)

The therapeutic composition of claim 1 or 3 wherein R is selected from the group consisting of dihydroxyalkyl, halohydroxyalkyl, N-alkylaminohydroxyalkyl, N-dialkylaminohydroxyalkyl, alkoxyhydroxyalkyl, alkylmercaptohydroxyalkyl, alkylsulfoxyhydroxyalkyl and alkanoyloxyhydroxyalkyl.

### Claim 7 (depends on 6)

The therapeutic composition of claim 6 wherein R is selected from the group consisting of dihydroxypropyl, halo-hydroxypropyl, N-alkylamino-hydroxypropyl, N-dialkylamino-hydroxypropyl, alkoxyhydroxypropyl, alkylmercaptohydroxypropyl, alkylsulfoxyhydroxypropyl and alkanoyloxyhydroxypropyl where the hydroxy is in the position selected from the group consisting of the 2 position and the 3 position and the remaining substituent is in the other of the 2 position or the 3 position.

### Claim 8

A cytostatic method in warm-blooded animals comprising administering a cytostatically effective amount of at least one N-substituted-diglycidyl-isocyanurate having the formula: ##STR16## wherein R has from 1 to 15 carbon atoms, which R is a hydrogen-containing radical selected from the group consisting of alkyl, aryl, aralkyl, alkaryl, cycloalkyl, and unsaturated derivatives thereof, which R may be further substituted by: heterocycles selected from the group consisting of piperidine, hexamethylenimine, morpholine, benzthiazol-2-ylthio and benzimidazol-2-ylthio, and further substituents on said R selected from the group consisting of halogen, hydroxyl, amino, N-substituted amino having the formula:
--NHR.sub.2 and --NR.sub.2 R.sub.3
wherein R.sub.2 and R.sub.3 together have a total of no more than 8 carbon atoms and are members selected from the group consisting of alkyl and alkyl substituted by hydroxy, halogen and alkoxy, mercapto, alkylmercapto, alkylmercapto substituted by hydroxy, halogen and alkoxy, arylmercapto, alkylsulfoxyl, arylsulfoxyl, alkoxy, aryloxy and alkanoyloxy and aroyloxy, and R.sub.1 represents a member selected from the group consisting of hydrogen and alkyl having from 1 to 4 carbon atom, to a warm-blooded animal.

### Claim 9

N-substituted-diglycidyl-isocyanurates selected from the group consisting of:
diglycidyl-(2-hydroxy-3-diethylaminopropyl)isocyanurate,
diglycidyl-(2-hydroxy-3-N-morpholinopropyl)isocyanurate,
diglycidyl-(2-hydroxy-3-(2-hydroxyethylthio)-propyl)isocyanurate,
diglycidyl-(propionyloxy-hydroxy-propyl)isocyanurate,
diglycidyl-(2-hydroxy-3-propoxypropyl)isocyanurate,
diglycidyl-2-hydroxypropyl isocyanurate,
diglycidyl-2-hydroxy-3-(2',3'-dihydroxypropylthio)-propyl isocyanurate,
diglycidyl-2-hydroxy-3-n-octylthiopropyl isocyanurate,
diglycidyl-2-hydroxy-3-(benzthiazole-2'-ylthio)-propyl isocyanurate, and
diglycidyl-2-hydroxy-3-(benzimidazol-2'-ylthio)-propyl isocyanurate.

### Claim 10 (depends on 1)

The cytostatic composition of claim 1 wherein the N-substituted-diglycidyl-isocyanurate is present in an amount of 0.05 to 5% by weight.