Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2002-06-13
2003-09-30
Tsang, Cecilia (Department: 1626)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C548S420000
Reexamination Certificate
active
06627650
ABSTRACT:
DESCRIPTION OF THE PRIOR ART
The compounds of the present invention are new.
BACKGROUND OF THE INVENTION
Anti-cancer therapeutic requirements call for the constant development of new anti-tumour agents with the aim of obtaining medicaments that are simultaneously more active and better tolerated.
In addition to the fact that the compounds of the invention are new, they exhibit anti-tumour properties that are of special interest.
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates more specifically to the compounds of formula (I):
wherein:
R represents:
a hydrogen atom,
a linear or branched (C
1
-C
6
)alkyl group optionally substituted by a carboxy group, by a linear or branched (C
1
-C
6
)alkoxycarbonyl group or by a NR
10
R
11
group (wherein R
10
and R
11
, which may be identical or different, each represents a linear or branched (C
1
-C
6
)alkyl group or together, with the nitrogen carrying them, form a nitrogen-containing heterocycle),
or a linear or branched (C
1
-C
6
)alkenyl group,
R
1
to R
8
, which may be identical or different, each represents:
a hydrogen atom,
a linear or branched (C
1
-C
6
)alkyl group optionally substituted by an aryl, carboxy or linear or branched (C
1
-C
6
)alkoxycarbonyl group,
a hydroxy group,
a linear or branched (C
1
-C
6
)acyloxy group,
a group of formula NR
12
R
13
, wherein R
12
and R
13
, which may be identical or different, each represents a hydrogen atom or a linear or branched (C
1
-C
6
)alkyl group optionally substituted by a group of formula NR
14
R
15
, wherein R
14
and R
15
, which may be identical or different, each represents a linear or branched (C
1
-C
6
)-alkyl group or together, with the nitrogen atom carrying them, form a nitrogen-containing heterocycle,
a carboxy group,
a linear or branched (C
1
-C
6
)alkoxy group optionally substituted by an aryl group or by a group of formula NR
14
R
15
, wherein R
14
and R
15
, which may be identical or different, each represents a linear or branched (C
1
-C
6
)alkyl group or together, with the nitrogen atom carrying them, form a nitrogen-containing heterocycle,
a linear or branched (C
1
-C
6
)alkenyloxy group,
or one of the groups R
1
to R
8
forms, with another of the groups R
1
to R
8
that is adjacent, a (C
1
-C
2
)alkylenedioxy group,
X represents an oxygen atom or an NR
16
group, wherein R
16
represents a hydrogen atom or a linear or branched (C
1
-C
6
)alkyl group, an aryl group or an aryl-(C
1
-C
6
)alkyl group in which the alkyl moiety may be linear or branched,
R
9
represents a hydrogen atom or an aryl, heteroaryl, or linear or branched (C
1
-C
6
)alkyl group, wherein the alkyl group optionally contains one or more unsaturations and is optionally substituted by one or more identical or different groups selected from aryl, heteroaryl, (C
3
-C
8
)cycloalkyl, cyano and NR
17
R
18
(wherein R
17
and R
18
, which may be identical or different, each represents a linear or branched (C
1
-C
6
)alkyl group or together, with the nitrogen atom carrying them, form a nitrogen-containing heterocycle),
to isomers thereof, and also to addition salts thereof with a pharmaceutically acceptable acid or base.
Isomers are to be understood as optical isomers and geometrical isomers of the C=N X R
9
double bond.
Among the pharmaceutically acceptable acids there may be mentioned, without implying any limitation, hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, acetic acid, trifluoroacetic acid, lactic acid, pyruvic acid, malonic acid, succinic acid, glutaric acid, fumaric acid, tartaric acid, maleic acid, citric acid, ascorbic acid, oxalic acid, methanesulphonic acid, benzenesulphonic acid, camphoric acid, etc.
Among the pharmaceutically acceptable bases there may be mentioned, without implying any limitation, sodium hydroxide, potassium hydroxide, triethylamine, tert-butylamine, etc.
An aryl group is to be understood as phenyl, biphenylyl or naphthyl, each of those groups optionally being substituted by one or more identical or different groups selected from halogen, linear or branched (C
1
-C
6
)alkyl (optionally substituted by one or more halogen atoms), linear or branched (C
1
-C
6
)alkenyl (optionally substituted by a phenyl group), linear or branched (C
1
-C
6
)alkoxy (optionally substituted by a phenyl group), phenoxy, nitro, cyano, amino (optionally substituted by one or two linear or branched (C
1
-C
6
)alkyl groups) and (C
1
-C
2
)alkylenedioxy.
A heteroaryl group is to be understood as an aromatic mono- or bi-cyclic group having from 5 to 12 ring members containing one, two or three hetero atoms selected from oxygen, nitrogen and sulphur, wherein the heteroaryl may optionally be substituted by one or more identical or different groups selected from halogen, linear or branched (C
1
-C
6
)-alkyl, hydroxy, linear or branched (C
1
-C
6
)alkoxy, linear or branched (C
1
-C
6
)polyhaloalkyl, and amino (optionally substituted by one or more linear or branched (C
1
-C
6
)alkyl groups). Amongst the heteroaryl groups the following groups may be mentioned without implying any limitation: thienyl, pyridyl, furyl, pyrrolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, quinolyl, isoquinolyl, pyrimidinyl, thiadiazolyl.
Preferred heteroaryl groups are thienyl, pyridyl, furyl and thiadiazolyl groups.
A nitrogen-containing heterocycle is to be understood as a saturated monocyclic group having from 5 to 7 ring members containing one, two or three hetero atoms, one of those hetero atoms being a nitrogen atom, and the additional hetero atom or atoms optionally present being selected from the atoms oxygen, nitrogen and sulphur. Preferred nitrogen-containing heterocycles are the groups pyrrolidinyl, piperidyl, morpholinyl and piperazinyl.
Preferred compounds of formula (I) are those wherein X represents an oxygen atom.
Preferred compounds of formula (I) are those wherein R
1
to R6 and R
8
, which may be identical or different, each represents a hydrogen atom, a hydroxy group or a linear or branched (C
1
-C
6
)alkoxy group.
Preferred compounds of formula (I) are those wherein R
7
represents a 2-dimethylaminoethoxy group or a 2-(1-pyrrolidinyl)-ethoxy group.
Amongst the preferred compounds of formula (I), the following, more especially, may be mentioned:
(10Z)-8-(2-dimethylaminoethoxy)-2,3-dimethoxyindeno[1,2-b]indole-10(5H)-one O-(1-phenyl-2-propynyl)oxime, isomers thereof, and addition salts thereof with a pharmaceutically acceptable acid,
(10Z)-8-(2-dimethylaminoethoxy)-2,3-dimethoxyindeno[1,2-b]indole-10(5H)-one O-(2-propynyl)oxime, isomers thereof, and addition salts thereof with a pharmaceutically acceptable acid,
(10Z)-8-(2-dimethylaminoethoxy)-2,3-dimethoxyindeno[1,2-b]indole-10(5H)-one O-(1-methyl-2-propynyl)oxime, isomers thereof, and addition salts thereof with a pharmaceutically acceptable acid,
(10Z)-8-(2-dimethylaminoethoxy)-2,3-dimethoxyindeno[1,2-b]indole-10(5H)-one O-[1-(3-furyl)-2-propynyl]oxime, isomers thereof, and addition salts thereof with a pharmaceutically acceptable acid,
(10Z)-8-(2-(1-pyrrolidinyl)ethoxy)-2,3-dimethoxyindeno[1,2-b]indole-10(5H)-one O-[1-(3-furyl)-2-propynyl]oxime, isomers thereof, and addition salts thereof with a pharmaceutically acceptable acid,
and (10Z)-8-(2-dimethylaminoethoxy)-2,3-dimethoxyindeno[1,2-b]indole-10(5H)-one O-((1S)-1-methyl-2-propynyl)oxime, isomers thereof, and addition salts thereof with a pharmaceutically acceptable acid.
The invention extends also to a process for the preparation of compounds of formula (I) which is characterised in that a compound of formula (II): a
wherein R
1
, R
2
, R
3
and R
4
are as defined for formula (I), is reacted
with N-bromosuccinimide to yield a compound of formula (III):
wherein R
1
, R
2
, R
3
and R
4
are as defined hereinbefore,
which is reacted with triphenylphosphine to yield a compound of formula (IV):
wherein R
1
, R
2
, R
3
and R
4
are as defined hereinbefore,
which is reacted with a compound of formula (V):
wherein R
1
, R
6
, R
7
and R
8
are as def
Atassi Ghanem
Boussard Marie-Françoise
Guilbaut Nicolas
Hickman John
Kraus-Berthier Laurence
Les Laboratoires Servier
Sackey Ebenezer
The Firm of Hueschen and Sage
Tsang Cecilia
LandOfFree
Indenoindolone 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 Indenoindolone compounds, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Indenoindolone compounds will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3049146