Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-05-14
1998-10-20
Raymond, Richard L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
5483054, A61K 31415, C07D23518
Patent
active
058246983
DESCRIPTION:
BRIEF SUMMARY
CROSS REFERENCE TO RELATED APPLICATION
This application is an application under 35 U.S.C. .sctn. 371 of International Application No. PCT/CH95/00255 which designated the United States.
The invention is concerned with dibenzimidazole derivatives. In particular, it is concerned with 2,2'-bis-substituted 6,6'-dibenzimidazoles of the general formula ##STR2## wherein R.sup.1 and R.sup.2 can be the same or different and signify C.sub.6 H.sub.4 R.sup.3 --, C.sub.6 H.sub.3 (OH)R.sup.4 -- or heterocyclyl, pharmaceutically usable salts of compounds of general formula I.
These compounds are novel with the exception of
The compounds of formula I and their pharmaceutically usable salts exhibit a very good antibacterial activity, primarily against gram-positive pathogens such as Staphylococcus and Enterococcus faecalis. Further, they also exhibit a good activity against Helicobacter pylori.
They are therefore suitable for the prophylaxis and treatment of illnesses which are caused by such pathogens.
Symmetrical bis-benzimidazoles have been described in the literature as starting materials for the preparation of polybenzimidazoles (J. Org. therapeutically active substances, especially for the prevention or treatment of bacterial diseases, is novel.
Objects of the present invention are compounds of general formula I and pharmaceutically usable salts thereof for use as therapeutically active substances, especially as active substances against bacterial pathogens; medicaments containing one or more compounds of general formula I defined in claim 1 or pharmaceutically usable salts thereof; the use of these compounds in the control or prevention of illnesses which are caused by bacterial pathogens and for the production of medicaments for the mentioned indications; as well as the novel compounds of formula II, their pharmaceutically usable salts as well as the manufacture of these novel compounds and salts.
The term "lower alkyl" used in the present description conveniently denotes those with up to 7, preferably up to 4, C atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl and the like.
Halogen signifies chlorine, bromine, fluorine or iodine.
The term "lower alkoxy" denotes a lower alkyl residue bonded via an oxygen atom.
In accordance with the present description the term "heterocyclyl" signifies a 5- or 6-membered unsaturated ring with at least one hetero atom such as O, S or N, for example furyl, pyranyl, thienyl, pyrrolyl or pyridyl.
Especially preferred for use as therapeutically active substances are those compounds of formula I in which R.sup.1 and R.sup.2 are the same or different and signify C.sub.6 H.sub.4 R.sup.3 -- or C.sub.6 H.sub.3 (OH)R.sup.4 --, R.sup.3 and R.sup.4 have the significance given above and wherein a substituent preferably occupies a 4-position or optionally a 3-position on the phenyl ring.
It has been found that the antibacterial activity is especially high when the substituent R.sup.3 or R.sup.4 or the hydroxy group in C.sub.6 H.sub.3 (OH)R.sup.4 -- for R.sup.1 or R.sup.2 is situated in the 4-position.
Thus, compounds in which a hydroxy group is situated in the 4-position on the phenyl ring are particularly preferred. The following compounds are particularly preferred for use as therapeutically active substances: ; ol; ol;
The symmetrically substituted compounds of formula I in which R.sup.1 and R.sup.2 have the same significance can be manufactured in accordance with the invention by reacting the compound of the formula ##STR3## with an excess of a reactive compound which yields the residue R.sup.1 or R.sup.2.
The unsymmetrically substituted compounds of formula I in which R.sup.1 and R.sup.2 do not have the same significance can be manufactured in accordance with the invention by reacting the compound of formula II simultaneously with two different reactive compounds which yield the residues R.sup.1 and R.sup.2.
A further possibility for the manufacture of symmetrical or unsymmetrical compounds of formula I comprises reacting a compound of the formula ##STR4#
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Hasler Walter
Ji Yu-Hua
Leupin Werner
Hoffman-La Roche Inc.
Johnston George W.
Kass Alan P.
Raymond Richard L.
Tramaloni Dennis P.
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