Quaternary amine compounds with isopropylmethylphenol ester moieties as antivirals, antibacterials and antimycotics
Disclosed are compounds having the following formula (I):Formula (I) wherein R is an alkylene chain having between 8 and 20 carbon atoms, and A is one or more anions having a total charge of −2, or R is a quaternary amine having the following formula (Ia):Formula (Ia) wherein R a and R b are each an alkylene chain having between 8 and 20 carbon atoms, and A is one or more anions having a total charge of −3; R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently selected from C 1-10 alkyl and H; E has the following Formula (Ib), wherein the ester oxygen is bonded to the aromatic ring of each E at the same position, the position being position 2 or 3; and wherein R E is H or a halide.
1 . A compound having the following formula:
wherein R is an alkylene chain having between 8 and 20 carbon atoms, and A is one or more anions having a total charge of −2,
or R is an amine having the following formula:
wherein R a and R b are each an alkylene chain having between 8 and 20 carbon atoms, and A is one or more anions having a total charge of −3;
R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently selected from C 1-10 alkyl and H;
E has the following formula
wherein the ester oxygen is bonded to the aromatic ring of each E at the same position, the position being position 2 or 3; and wherein RE is H or a halide.
2 . A compound according to claim 1 , having the following formula:
3 . A compound according to claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each methyl.
4 . A compound according to claim 1 , having the following formulae:
5 . A compound having the following formula:
wherein R is an alkylene chain having between 8 and 20 carbon atoms, and A is one or more anions having a total charge of −2,
or R is an amine having the following formula:
wherein R a and R b are each an alkylene chain having between 8 and 20 carbon atoms, and A is one or more anions having a total charge of −3;
R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently selected from C 1-10 alkyl and H;
E has the following formula
wherein the ester oxygen is bonded to the aromatic ring of each E at the same position, the position being 2 or 3;
wherein RE is H or a halide and wherein X is 2, 3, 4 or 6.
6 . A compound according to claim 5 having the following formula:
7 . A compound according to claim 1, 2, 5 or 6 , wherein R is a saturated linear alkylene chain having between 8 and 16 carbon atoms.
8 . A compound according to claim 1, 2, 5 or 6 , wherein R a and R b are each a saturated linear alkylene chain having between 8 and 16 carbon atoms.
9 . A compound according to claim 1, 2, 5 or 6 , wherein the one or more anions are selected from chloride anions and bromide anions.
10 . A compound according to claim 5 or 6 having the following formula:
wherein X is 3 or 6.
11 . A pharmaceutical composition comprising the compound of any of claim 1, 2, or 3-6 .
12 . A compound according to any one of claim 1, 2, or 3-6 for use as a medicament.
13 . A compound according to any one of claim 1, 2, or 3-6 for use in the treatment of fungal infections and/or bacterial infections.
14 . A compound according to any one of claim 1, 2, or 3-6 for use in the treatment of Herpes virus and/or Human Papilloma virus.
15 . A process for producing the compound according to claim 1 comprising:
i) reacting a compound having the formula (XV)
wherein the alcohol group is bonded to the benzene ring in position 2 or 3, and RE is H or a halide, with R 7 CH 2 COCl to form a compound having the formula (XVI):
wherein R 7 is chlorine or bromine, E is
wherein the ester oxygen is bonded to the aromatic ring of E at position 2 or 3, and wherein RE is H or a halide; and
ii) reacting 1 molar equivalents of the compound having the formula (XVII)
with 2 molar equivalent of the compound having formula (XVI) to form a compound having the formula
wherein R is an alkylene chain having between 8 and 20 carbon atoms, and A is one or more anions having a total charge of −2;
or R is an amine having the following formula:
wherein R a and R b are each an alkylene chain having between 8 and 20 carbon atoms, and A is one or more anions having a total charge of −3;
E has the following formula
wherein the ester oxygen is bonded to the aromatic ring of each E at the same position, the position being position 2 or 3 and wherein RE is H or a halide;
R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently selected from C 1-10 alkyl and H.
16 . The process according to claim 15 , wherein the reactions of step II is carried out in acetonitrile as solvent.
17 . A process for the production of a compound according to claim 5 comprising reacting the compound having formula (I)
with bromine to form a compound having formula (VIII)
wherein R is an alkylene chain having between 8 and 20 carbon atoms, and A is one or more anions having a total charge of −2,
or R is an amine having the following formula:
wherein R a and R b are each an alkylene chain having between 8 and 20 carbon atoms, and A is one or more anions having a total charge of −3;
R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently selected from C 1-10 alkyl and H;
E has the following formula
wherein the ester oxygen is bonded to the aromatic ring of each E at the same position, the position being 2 or 3;
wherein RE is H or a halide; and wherein X is 2, 3, 4 or 6.
18 . A compound according to claim 1, 2, 5 or 6 , wherein R is a saturated linear alkylene chain having 10 carbon atoms.
19 . A compound according to claim 1, 2, 5 or 6 , wherein R a and R b are each a saturated linear alkylene chain having 10 carbon atoms.