Halogenated benzamide derivatives
View Patent ↗A halogenated benzamide derivative characterized by greater specificity for viral pathogens and less disruptive to beneficial gut microflora, according to formula (III): in which R 1 is a halogen atom, and R 2 -R 6 are independently hydrogen, hydroxyl, C 1 -C 4 alkyl, —C 1 -C 4 alkoxy, acyloxy, nitro, halogen, —C(O)R 7 where R7 is —C1-C4 alkyl, or, aromatic including salts and hydrates of these compounds.
1. A compound according to formula (III):
in which R 1 is a halogen atom, and R 2 -R 6 are independently hydrogen, hydroxyl, C 1 -C 4 alkoxy, acyloxy, —C(O)R 7 where R 7 is —C 1 -C 4 alkyl, or, aromatic including salts and hydrates of these compounds, wherein at least one of R 2 -R 6 is other than hydrogen.
2. A compound as in claim 1 , wherein at least one of R 2 -R 6 is hydroxyl.
3. A compound as in claim 2 , wherein said at least one hydroxyl is in the ortho position.
4. A compound as in claim 2 , wherein the remainder of R 2 -R 6 are hydrogen.
5. A compound as in claim 1 , wherein at least two of R 2 -R 6 are other than hydrogen.
6. A compound as in claim 1 , wherein one of R 2 -R 6 is hydroxyl, and the remainder of R 2 -R 6 are independently hydrogen, —C 1 -C 4 alkoxy, acyloxy (preferably acetoxy or propionoxy) —C(O)R 7 where R 7 is —C 1 -C 4 alkyl, or, aromatic, including salts and hydrates of these compounds.
7. A compound as in claim 1 , wherein one of R 2 -R 6 is hydroxyl, and at least one of R 2 -R 6 is —C 1 -C 4 alkoxy, acyloxy, —C(O)R 7 where R 7 is -C 1 -C 4 alkyl, or aromatic, including salts and hydrates of these compounds.
8. A compound as in claim 1 , wherein said acyloxy is acetoxy or propionoxy, and wherein said aromatic is phenyl or benzyl, which may be further substituted.
9. A compound as in claim 1 , wherein R 1 is Br or Cl.
10. A compound as in claim 1 , wherein R 2 -R 6 include no more than one acyloxy.
11. A compound as in claim 1 , wherein two adjacent R 2 -R 6 together form a benzyl ring.
12. A compound as in claim 1 , wherein one of R 2 -R 6 is hydroxyl, and the remainder of R 2 -R 6 are independently hydrogen, —C 1 -C 4 alkoxy, acyloxy, or —C(O)R 7 where R 7 is —C 1 -C 4 alkyl, including salts and hydrates of these compounds.
13. A compound as in claim 1 , selected from the group consisting of
2-(acetolyloxy)-N-(5-bromo-2-thiazolyl)benzamide (RM4820);
2-(acetolyloxy)-5-methoxy-N-(5-bromo-2-thiazolyl)benzamide (RM4821); and
2-(acetolyloxy)-5-methoxy-N-(5-bromo-2-thia2olyl)benzamide (RM4822).
14. A compound according to (III):
wherein: R 1 is halogen, R 2 is OR 8 in which R 8 is —C(O)R 10 , in which R 10 is —C 1 -C 4 alkyl, R 3 is -C 1 -C 4 alkyl or —C 1 -C 4 alkoxy, and R 4 -R 6 are independently hydrogen, hydroxyl, C 1 -C 4 alkyl, —C 1 -C 4 alkoxy, acyloxy, halogen, —C(O)R 7 where R 7 is —C 1 -C 4 alkyl, or, aromatic including salts and hydrates of these compounds.
15. A compound as in claim 14 , wherein R 1 is Cl or Br.
16. A compound as in claim 14 , wherein R 8 is —C(O)R 10 , in which R 10 is methyl, ethyl, propyl or butyl, including isomers thereof.
17. A compound as in claim 14 , wherein R 9 is methyl or methoxy.
18. A compound as in claim 14 , selected from the group consisting of:
2-(acetolyloxy)-3-methyl-N-(5-bromo-2-thiazolyl)benzamide (RM4803);
2-(acetolyloxy)-3-methyl-N-(5-chloro-2-thiazolyl)benzamide (RM4804); and
2-(acetolyloxy)-3-methoxy-N-(5-bromo-2-thiazolyl)benzamide (RM4806).
19. A pharmaceutical composition comprising as active agent a compound according to formula (III): in which R 1 is a halogen atom, and R 2 -R 6 are independently hydrogen, hydroxyl, —C 1 -C 4 alkoxy, acyloxy, —C(O)R 7 where R 7 is —C 1 -C 4 alkyl, or, aromatic including salts and hydrates of these compounds, wherein at least one of R 2 -R 6 is other than hydrogen.