Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-07-14
2001-10-09
Berch, Mark L (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C546S099000
Reexamination Certificate
active
06300340
ABSTRACT:
BACKGROUND OF THE INVENTION
Compounds derived from bisimides have already been described in the literature. This is more particularly the case for the compounds described in patents EP 506 008, DE 4034687, WO 9500490 or DE 4232739.
DETAILED DESCRIPTION OF THE INVENTION
The compounds of the present invention have entirely original structures compared with those described in the prior art. They are either symmtrical or dissymmetrical compounds which have never been described previously. Moreover, the power of their pharmacological activities makes them particularly advantageous as new drugs that are useful in the treatment of cancers and in particular solid tumors.
More specifically, the present invention relates to the compounds of formula (I)
in which:
m, and n, which may be identical or different, represent 0 or 1,
X and Y, which may be identical or different, represent a hydrogen or halogen atom or a linear or branched (C
1
-C
6
) alkyl, linear or branched (C
1
-C
6
) trihaloalkyl, linear or branched (C
1
-C
6
) alkoxy, hydroxyl, cyano, nitro, amino, alkylamino or dialkylamino group,
Z represent a linear or branched C
4
to C
2
alkylene chain in which one or more —CH
2
— groups are optionally replaced by any one of the following atoms or groups: —NR— (in which R represents a hydrogen atom or a linear or branched (C
1
-C
6
) alkyl group), —O—, —S—, —SO—, —SO
2
—, or —CONH—, or by a substituted or unsubstituted heterocylcic group,
A forms, with two adjacent carbon atoms of the phenyl ring:
a substituted or unsubstituted phenyl ring,
a substituted or unsubstituted naphthyl ring,
a substituted or unsubstituted tetrahydronaphthyl ring or substituted or unsubstituted 1,4-dioxo-1,2,3,4-tetrahydronaphthyl ring,
or a substituted or unsubstituted heterocycle,
represents any one of the following groups:
in which:
m
1
and n
1
, which may be identical or different, represent 0 or 1,
X
1
and Y
1
, which may be identical or different, represent a hydrogen or halogen atom or a linear or branched (C
1
-C
6
) alkyl, linear or branched (C
1
-C
6
) trihaloalkyl, linear or branched (C
1
-C
6
) alkoxy, hydroxyl, cyano, nitro, amino, alkylamino or dialkylamino group,
A
1
forms, with two adjacent carbon atoms of the phenyl ring:
a substituted or unsubstituted phenyl ring,
a substituted or unsubstituted naphthyl ring,
a substituted or unsubstituted tetrahydronaphthyl ring or substituted or unsubstituted 1,4-dioxo-1,2,3,4-tetrahydronaphthyl ring, or
a substituted or unsubstituted heterocycle,
in which X
2
, and Y
2
, which may be identical or different, represent a hydrogen or halogen atom or a linear or branched (C
1
-C
6
) alkyl, linear or branched (C
1
-C
6
) trihaloalkyl, linear or branched (C
1
-C
6
) alkoxy, hydroxyl, cyano, nitro, amino, alkylamino or dialkylamino group,
their isomers and their addition salts with a pharmaceutically acceptable acid or base.
Among the pharmaceutically acceptable acids which may be mentioned, without any limitation being implied, are hydrochloric acid, hydrobromic acid, sulfuric acid, phosphonic acid, acetic acid, trifluoracetic acid, lactic acid, pyruvic acid, malonic acid, succinic acid, glutaric acid, fumaric acid, tartaric acid, maleic acid, citric acid, ascorbic acid, oxalic acid, methanesulfonic acid, camphoric acid, etc.
Among the pharmaceutically acceptable bases which may be mentioned, without any limitation being implied, are sodium hydroxide, potassium hydroxide, triethylamine, tert-butylamine, etc.
The terms substituted or unsubstituted phenyl group, substituted or unsubstituted naphthyl group and substituted or unsubstituted tetrahydronaphthyl group are understood to refer to a phenyl, naphthyl or tetrahydronaphthyl group which is optionally substituted with one or more halogen atoms or linear or branched (C
1
-C
6
) alkyl, linear or branched (C
1
-C
6
) trihaloalkyl, linear or branched (C
1
-C
6
) alkoxy, hydroxyl, nitro or cyano groups or amino groups (optionally substituted with one or more linear or branched (C
1
-C
6
) alkyl groups).
The term substituted or unsubstituted heterocycle is understood to refer to a mono- or bicyclic, saturated or unsaturated 5- to 16-membered group containing 1, 2 or 3 hetero atoms chosen from oxygen, nitrogen and sulfur, it being understood that the heterocycle may optionally be substituted with one or more halogen atoms or linear or branched (C
1
-C
6
) alkyl, linear or branched (C
1
-C
6
) alkoxy, hydroxyl, trihalomethyl, nitro or cyano groups or amino groups (optionally substituted with one or more linear or branched (C
1
-C
6
) alkyl groups).
The preferred compounds according to the invention are those in which:
A forms, with two adjacent carbon atoms of the phenyl ring:
a substituted or unsubstituted naphthyl ring,
or a substituted or unsubstituted heterocycle preferably chosen from substituted or unsubstituted indole, substituted or unsubstituted benzo[b]thiophene and substituted or unsubstituted benzo[b]furan rings.
The preferred consitutents are those for which Z represents a C
4
to C
12
alkylene chain in which 1, 2 or 3 —CH
2
— groups are replaced by 1, 2 or 3 —NR— groups (in which R represents a linear or branched (C
1
-C
6
) alkyl group).
The invention also covers the process for the preparation of the compounds of formula (I), which process uses, as starting material, an anhydride of formula (II):
in which A, X, Y, m and n are as defined in formula (I),
which is reacted with an excess of a diamine of formula (III):
H
5
H
2
N—Z—NH
2
(III)
in which Z is as defined in formula (I),
in order to lead, after separation:
either to the compound of formula (I/a), a specific case of the compounds of formula (I):
in which A, X, Y, Z, m and n have the same meaning as in formula (I),
or to the compound of formula (IV):
in which A, X, Y, Z, m and n have the same meaning as in formula (I),
which is reacted:
either with the anhydride of formula (II/a):
in which A
1
, X
1
, Y
1
, m
1
and n
1
are as defined in formula (I), in order to lead to the compound of formula (I/b), a specific case of the compounds of formula (I):
in which A, X, Y, m, n, Z, A
1
, X
1
, Y
1
, m
1
, and n
1
have the same meaning as in formula (I),
or with the anhydride of formula (V)
in which X
2
and Y
2
are as defined in formula (I),
in order to lead to the compound of formula (I/c), a specific case of the compounds of formula (I):
in which A, X, Y, X
2
, Y
2
, Z, mn and n have the same meaning as in formula (I),
which compound of formula (I/a), (I/b) or (I/c), may undergo, if so desired, standard reactions for the transformation of substituents on aromatic rings, which is purified, where appropriate, according to a standard purification technique, the isomers of which are optionally separated according to a standard separation technique and which is converted, if so desired, into its addition salts with a pharmaceutically acceptable acid or base.
The anhydrides of formula (II) or (V) are either commercial compounds or are obtained according to known procedures.
The invention also covers pharmaceutical compositions containing, as active principle, at least one compound of formula (I) with one or more inert, non-toxic, suitable excipients. Among the pharmaceutical compositions according to the invention which may be mentioned more particularly are those which are suitable for oral, parenteral (intravenous or subcutaneous) or nasal administration, simple or sugar-coated tablets, sublingual tablets, gelatin capsules, lozenges, suppositories, creams, ointments, dermal gels, injectable preparations, drinkable suspensions, etc.
The appropriate dosage may be adapted according to the nature and severity of the complaint, the route of administration and the age and weight of the patient. This dosage ranges from 0.1 to 400 mg per day in one or more dosage intakes.
REFERENCES:
patent: 3873567 (1975-03-01), Cyba et al.
Atassi Ghanem
Hautefaye Patrick
Kraus-Berthier Laurence
Lavielle Gilbert
Leonce Stephane
Adir et Compagnie
Berch Mark L
Habte Kahsay
Sage G. Patrick
The Firm of Hueschen and Sage
LandOfFree
Bisimide compounds does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Bisimide compounds, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Bisimide compounds will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2607971