US2004266844A1PendingUtilityA1
Antimicrobial and radioprotective compounds
Priority: Jun 18, 2001Filed: Jun 14, 2002Published: Dec 30, 2004
Est. expiryJun 18, 2021(expired)· nominal 20-yr term from priority
A61P 43/00A61P 39/00A61P 31/04A61P 33/02A61P 31/06A61P 31/00A61P 27/02A61P 31/12A61P 31/02A61P 33/06A61P 31/10A61P 31/08A61P 1/00A61P 15/02A61P 11/00C07D 317/46C07D 317/52C07D 235/06A61K 31/357C07D 263/56C07D 235/08A61K 31/4184A61K 31/36Y02A50/30
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Claims
Abstract
The present invention relates to a method of treatment and/or prophylaxis of a microbial infection, comprising administering an effective amount of a compound of formula I as defined herein, or pharmaceutically acceptable salts or derivatives, pro-drugs, tautomers and/or isomers thereof. The invention also relates to a method for protecting a subject from radiation damage, a method of cancer radiotherapy and use as an antimicrobial or radioprotective agent of the compound of formula I. Some of the compounds of formula I are novel and are also described in the present invention, together with pharmaceutical or veterinary compositions containing them.
Claims
exact text as granted — not AI-modified1 . A method of treatment and/or prophylaxis of a microbial infection, comprising the step of administering an effective amount of a compound of formula I:
in which
X and Y are either the same or different and selected from a heteroatom;
is a double or single bond depending on the heteroatoms X and Y;
R 1 to R 5 are either the same or different and selected from hydrogen or a non-deleterious substituent; and
R 6 and R 7 are either the same or different and selected from hydrogen and a non-deleterious substituent or one of R 6 and R 7 are absent when there is a double bond present,
or pharmaceutically acceptable salts or derivatives, pro-drugs, tautomers and/or isomers thereof.
2 . A method according to claim 1 , in which the microbial infection is a bacterial infection, fungal infection, yeast infection, protozoal infection or viral infection.
3 . A method according to claim 1 , in which the microbial infection is caused by a Gram Positive bacterium.
4 . A method according to claim 1 , in which the microbial infection is caused by Staphylococcus aureus, Enterococcus fecalis, Klebsiella pneumonia, Salmonella typhimurium or pseudotuberculosis, Acinetobacteria, Pseudomonas aeruginosa, Clostridium perfringens, Clostridium difficile, Campylobacter jejuni or Bacteroides fragilis.
5 . A method according to claim 1 , in which the microbial infection is a fungal or yeast infection caused by Trichophyton interdigitale, Aspergillus fumigatus or Candida albicans.
6 . A method according to claim 1 , in which the microbial infection is a protozoal infection caused by Plasmodium falciparum or Trichomonas vaginalis.
7 . A method according to claim 1 , in which the microbial infection is a bacterial or fungal wound infection, mucosal infection, enteric infection, septic condition, pneumonia, trachoma, ornithosis, trichomoniasis or salmonellosis.
8 . A method according to claim 1 , in which X and Y are either the same or different and selected from O and N.
9 . A method according to claim 8 , in which X and Y are both O.
10 . A method according to claim 1 , in which R 1 and R 2 are either the same or different and selected from hydrogen, hydroxy, halogen or optionally substituted C 1-6 alkyl.
11 . A method according to claim 1 , in which R 3 to R 5 are either the same or different and selected from hydrogen, hydroxy, halogen, nitro, C 1-6 alkoxy or optionally substituted C 1-6 alkyl.
12 . A method according to claim 10 , in which the halogen is chlorine or bromine.
13 . A method according to claim 1 , in which the compound of the formula I is in the form of the E isomer.
14 . A method according to claim 1 , in which X, Y, , R 6 and R 7 are as defined in claim 1; R 1 and R 2 are either the same or different and selected from hydrogen, hydroxy, Cl, Br and C 1-4 alkyl; and R 3 to R 5 are either the same or different and selected from hydrogen, hydroxy, Cl, Br, nitro, C 1-4 alkoxy or C 1-4 alkyl.
15 . A method according to claim 2 , in which X and Y are O, R 1 is methyl and R 2 and R 3 are hydrogen (3,4-methylenedioxy-β-methyl-β-nitrostyrene)
X and Y are O and R 1 to R 3 are hydrogen (3,4-methylenedioxy-β-nitrostyrene)
X is N, Y is NH, R 1 is methyl and R 2 and R 3 are hydrogen (benzimidazole-5-β-nitropropylene)
X is N, Y is NH, R 1 is hydrogen, R 2 is methyl and R 3 is absent (2-methyl benzimidazole-5-β-nitroethylene)
X is O, Y is N, R 1 and R 2 are hydrogen and R 3 is absent (benzoxazole-5-β-nitroethylene)
X is N, Y is O, R 1 and R 2 are methyl and R 3 is absent (2-methyl benzoxazole-5-β-nitropropylene)
16 . A method according to claim 1 , in which the microbial infection is caused by a Gram Negative bacterium.
17 . A method according to claim 11 , in which the halogen is chlorine or bromine.
18 . A method for protecting a subject from radiation damage which comprises administering an effective amount of the compound of formula I as defined in claim 1 to a subject in need thereof.
19 . A method according to claim 18 , in which the radiation is ionising radiation.
20 . A method of cancer radiotherapy which comprises administering to a subject in need of such therapy an effective amount of the compound of formula I as defined in claim 1 and subjecting the locus of a tumour in the subject to a radiation source.
21 . A process according to claim 24 which is performed in the presence of a catalyst.
22 . A compound of formula Ia:
in which
X, Y, and R 1 to R 7 are as defined in formula I above, with the provisos that:
(i) when both X and Y are O and R 2 to R7 are hydrogen, then R 1 is not hydrogen, C 1-4 alkyl, CO 2 Et,
or CH 2 CO 2 R 8 in which R 8 is C 1-12 alkyl or phenyl optionally substituted by one or more halogen;
(ii) when both X and Y are O, then R 1 to R 7 are not hydrogen;
(iii) when R 2 , R 6 and R 7 are hydrogen, one of R 3 , R 4 or R 5 is methyl and X and Y are O, then R 1 is not methyl;
(iv) when R 2 , R 3 , R 5 , R 6 and R 7 are hydrogen, R 4 is OCH 3 and X and Y are O, then R 1 is not H, CH 3 or CH 2 CH 3 ;
(v) when R 1 to R 5 are H and X and Y are O, then at least one of R 6 and R 7 is not methyl;
(vi) when R 2 , R 4 , R 5 , R 6 and R 7 are H, R 3 is OCH 3 and X and Y are O, then R 1 is not CH 3 ; and
(vii) when R 1 , R 2 , R 3 , R 5 , R 6 and R 7 are H and X and Y are O, then R 4 is not OCH 3 .
23 . A process for the preparation of the compound of formula Ia defined in claim 22 which comprises condensing a compound of formula II:
in which X, Y, , R 3 to R7 are as defined in formula Ia in claim 22 with a compound of formula III:
R 1 R 2 CHNO 2 III
in which R 1 and R 2 are as defined in formula Ia in claim 22 .
24 . A process for the preparation of the compound of formula Ia defined in claim 22 which comprises reacting a compound of formula IV:
in which X, Y, , R 1 to R 7 are as defined in formula Ia in claim 22 with C(NO 3 ) 4 .
25 . A process according to claim 23 which is performed in the presence of a catalyst.
26 . A compound according to claim 22 together with a pharmaceutically or veterinarily acceptable carrier.
27 . A compound according to claim 26 in which the pharmaceutically or veterinarily acceptable carrier is a topical, oral or parenteral carrier composition.
28 . A compound according to claim 26 in which the pharmaceutically or veterinarily acceptable carrier is an organic solvent.
29 . A compound according to claim 28 in which the organic solvent is acetone, benzene, acetonitrile, DMSO or an alcohol.
30 . A method according to claim 1 , in which the method of treatment and/or prophylaxis occurs in vivo.
31 . A method according to claim 1 , in which the microbial infection is caused by a resistant microbial species.Join the waitlist — get patent alerts
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