ES2274725B1 - INDENO DERIVATIVES, ITS PREPARATION AND ITS USE AS MEDICATIONS. - Google Patents

Abstract

Indeno derivatives, its preparation and its use as medicines. The present invention refers to new indene derivatives of general formula (I), as well as to its preparation process, its application as medicaments and pharmaceutical compositions comprising them. (I) The new compounds of formula I show affinity for 5-HT6 receptors and are therefore effective for the treatment of diseases mediated by these receptors.

Description

Indeno derivatives, their preparation and their use as medicines.

Field of the Invention

The present invention refers to new indene derivatives of general formula (I), as well as their preparation procedure, to its application choir medications and to pharmaceutical compositions that comprise them.

one

The new compounds of formula I show affinity for 5-HT6 receptors so they are effective for the treatment of diseases mediated by these receptors.

Background of the invention

The 5-HT serotonin receptor superfamily includes 7 classes (5-HT_ {1} -5-HT_ {7}) covering 14 subclasses [D. Hoyer, et al., Neuropharmacology , 1997 , 36 , 419]. The 5-HT6 receptor is the last serotonin receptor identified by molecular cloning in both rat [FJ Monsma, et al., Mol. Pharmacol ., 1993 , 43 , 320; M. Ruat, et al., Biochem. Biophys Res. Commun ., 1993 , 193 , 268], as in humans [R. Kohen, et al., J. Neurochem ., 1996 , 66 , 47]. Compounds with affinity for 5-HT 6 receptors are suitable for the treatment of various disorders of the central nervous system and the gastrointestinal tract, such as irritable bowel syndrome. Compounds with affinity for 5-HT 6 receptors are also suitable for the treatment of anxiety depression and cognitive memory disorders [M. Yoshioka, et al., Ann. NY Acad. Sci ., 1998 , 861 , 244; A. Bourson, et al., Br. J. Pharmacol ., 1998 , 125 , 1562; DC Rogers, et al., Br. J. Pharmacol. Suppl ., 1999 , 127 , 22P; A. Bourson, et al., J. Pharmacol Exp. Ther ., 1995 , 274 , 173; AJ Sleight, et al., Behav. Brain Res ., 1996 , 73 , 245; TA Branchek, et al., Annu. Rev. Pharmacol. Toxicol ., 2000 , 40 , 319; C. Routledge, et al., Br. J. Pharmacol ., 2000 , 130 , 1606]. It has been shown that typical and atypical antipsychotic drugs to treat schizophrenia have a high affinity for 5-HT 6 receptors [BL Roth, et al., J. Pharmacol. Exp. Ther ., 1994 , 268 , 1403; CE Glatt, et al., Mol. Med ., 1995 , 1 , 398; FJ Mosma, et al., Mol. Pharmacol ., 1993 , 43 , 320; T. Shinkai, et al., Am. J. Med. Genet ., 1999 , 88 , 120]. Compounds with affinity for 5-HT6 receptors are also suitable for treating childhood hyperkinesia (DA / DH; Attention Deficit / Hyperactivity Disorder) [WD Hirst, et al., Br. J. Pharmacol ., 2000 , 130 , 1597; C. Gérard, et al., Brain Research , 1997 , 746 , 207; MR Pranzatelli, Drugs of Today , 1997 , 33 , 379]. It has also been shown that 5-HT6 receptors also play a role in food intake [ Neuropharmacology , 2001 , 41 , 210-219]. Eating disorders, particularly obesity, are a serious and growing threat to public health in all age groups, as they increase the risk of developing other more serious and life-threatening diseases such as diabetes or coronary heart disease

There are several patent documents that are refer to compounds with affinity for receptors of the 5-HT superfamily. WO 96/23783, WO 96/02537, WO 96/11929 and WO 97/08167, describe compounds heterocyclic receptor antagonists 5-HT2b / 2c.

On the other hand, there are other documents of patent described indeno derivatives with activity therapy. US Patents 5092827, US 6025394, US 5958982 US 5965619, US 6028116, US 2001/0006965 and US 2001/0020020 describe Indene derivatives suitable for treating psoriasis, acne, sarcoidosis, precancerous lesions and neoplasms as well as diabetic retinopathy and macular degeneration. The effect Therapeutic of these compounds seems to come from their action cGMP specific phosphodiester inhibitor (cGMP PDE) such and as described in US 6177471.

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Surprisingly, the authors of this invention have observed that indene compounds derived from general formula (I) show an affinity for receptors 5-HT6 between good or excellent. These compounds therefore become especially suitable as pharmacologically active agents in medications for prophylaxis and / or treatment of disorders or diseases related to 5-HT6 receptors.

Object of the invention

First, the present invention has as its object an indene derived from general formula I:

2

The compounds of general formula I have shown high affinity for 5HT6 receptors, so they assume a good therapeutic alternative for the treatment of disorders mediated by said receptors.

Another object of the present invention are the procedures for the preparation of indene derived from general formula I. As will be seen later, in the present application describes the procedures for obtaining the compounds (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ik) and (In), particular embodiments of the compounds of formula general I. Specifically, to obtain the compounds (Ia) and (Ib) more than one possible procedure is described.

Another additional object of the present invention are the intermediates of general formula (II):

3

for obtaining the compounds of formula (I)

Likewise, the object of the present invention is the use of the indene derivatives of general formula (I) in the development of a medication for the treatment of disorders or diseases mediated by 5HT6 receptors. Between the 5HT6 receptor-mediated diseases or disorders, for which are indene derivatives derived from general formula I are disorders or diseases related to food intake, preferably those related to appetite regulation, maintenance, increase or reduction of body weight, obesity, bulimia, anorexia, cachexia or type II diabetes, or irritable bowel / bowel syndrome; central nervous system disorders; anxiety; attacks of panic; depression; bipolar disorders; cognitive disorders; memory disorders; senile dementia; psychosis; schizophrenia; neurodegenerative disorders preferably selected from Alzheimer's disease, Parkinson's disease, Huntington's disease and multiple sclerosis; or disorders of hyperactivity preferably attention deficit / disorder hyperactivity, or for the improvement of cognitive ability.

A final object of the present invention is a pharmaceutical composition comprising an indene derived from general formula I and at least one pharmaceutically additive acceptable. Pharmaceutical compositions according to the invention can be adapted to be administered by any route of administration either oral or parenteral such as pulmonary, nasal, rectal, and intravenous. Therefore, the formulation of according to the invention can be adapted for the application topical or systemic, especially dermal, subcutaneous application, intramuscular, intrarticular, intraperitoneal, pulmonary, buccal, sublingual, nasal, percutaneous, vaginal, oral or parenteral.

Detailed description of the invention

A first aspect of the invention makes reference to an indene derived from general formula I:

4

where

n is 0, 1, 2, 3 or 4

R 1 represents a saturated or unsaturated cycloaliphatic radical, optionally at least monosubstituted, optionally at least with a heteroatom selected from N, O and S as a member of the ring that may be condensed with an optionally at least monosubstituted mono or polycyclic ring system ; a radical -NR 8 R 9; a radical
-CONR 8 R 9; -COOH; or -OH

where

R 8 and R 9 represent, independently of one another, an atom of hydrogen; or a linear C 1-5 aliphatic radical or branched, saturated or unsaturated, which may be substituted with 1, 2, 3 substituents independently selected from F, Cl, Br, -OH, -NH2, -SH, -O-CH3, -O-C 2 H 5, -NO 2, -CN, -NH-CH 3 and -S-CH 3;

or

R 8 and R 9 together with the nitrogen form a ring 3 to 9 membered heterocyclic saturated, unsaturated or aromatic, which may be substituted with 1, 2 or 3 substituents selected independently between C_ {1-5} -alkyl, -O-C_ {1-5} -alkyl, -S-C_ {1-5} -alkyl, oxo (= O), thioxo (= S), -C (= O) -OH, -C (= O) -O-C_ {1-5} -alkyl, -OR- C (= O) -C_ {1-5} -alkyl, F, Cl, Br, I, -CN, -CF 3, -OCF 3, -SCF 3, -OH, -SH, -NH2, -NH (C_ {1-5} -alkyl), -N (C 1-5 -alkyl) 2, -NO2, -CHO, -CF2H, -CFH2, -C (= O) -NH2, -C (= O) -NH (C_ {1-5} -alkyl), -C (= O) -N (C_ {1-5} - alkyl) 2, -S (= O) 2 -C_ 1-5 -alkyl, -S (= O) 2 -phenyl and which may contain 1, 2 or 3 additional heteroatoms independently selected from N, O and S as ring members

R 2, R 3, R 4 and R 5 represent, independently of each other, a hydrogen atom; -NO2; -NH2; -SH; -OH;
-CN; -C (= O) -H; -C (= O) -R 10; -OR 11; -SR 12; -SOR 13, -S (= O) 2 -R 13, -S (= O) 2 -N (R 14) R 15, - N (R 16) - S (= O) 2 -R 17; -NH-R 18; -NR 19 R 20; -N (R 21) - CO-R 22; F; Cl, Br; I; a linear or branched, saturated or unsaturated C 1 -C 6 aliphatic radical, which may be substituted by 1, 2 or 3 substituents independently selected from F, Cl, Br, -OH, -NH 2, - SH, -O-CH 3, -O-C 2 H 5, -NO 2, -CN, -NH-CH 3 and -S-CH 3; or a 5-14 membered aryl or heteroaryl radical, which may be substituted with 1, 2 or 3 substituents independently selected from -CF 3, C 1-5, alkyl, -O-C 1-5 -alkyl, -S-C_ {1-5} -alkyl, -C (= O) -OH, -C (= O) -O-C_ {1-5} -alkyl, -OC (= O) -C_ {1-5} -alkyl, F, Cl, Br, I, -CN, -OCF 3, -SCF 3, -OH, -SH, -NH 2, -NH (C 1- { 5} -alkyl), -N (C 1-5 -alkyl) 2, -NH-C (= O) -C_ {1-5} -alkyl, -N (C_ 1-5) -alkyl) -C (= O) -C_ {1-5} -alkyl, -NO_ {2}, -CHO, -CF2H, -CFH_2, -C (= O) -NH_ { 2}, -C (= O) -NH (C_1-5 -alkyl), -C (= O) -N (C_1-5 -alkyl) 2, -S (= O ) 2 -C 1-5 -alkyl, -S (= O) 2 -phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, phenoxy, benzyloxy and benzyl and which may be attached through of a C 1 -C 6 linear or branched alkylene group and wherein the heteroaryl radical contains 1, 2 or 3 heteroatoms independently selected from N, O and S as ring members;

with the proviso that at least one of the substituents R 2, R 3, R 4 and R 5 represent a radical -NO_ {2}, -SOR_ {13}, -S (= O) 2 -R 13, -S (= O) 2 -N (R 14) R 15, -N (R 16) - S (= O) 2 -R 17, -N (R 21) - CO-R 22;

A represents:

5

which means respectively type compounds (Ix) and (Iy):

6

R 6 and R '6, identical or different, represent a hydrogen atom; NO2; -NH2; -SH; -OH; -CN; -C (= O) -R 10; -OR 11; -SR 12; F; Cl, Br; I; a linear or branched C 1 -C 10 aliphatic radical, saturated or unsaturated, which may be substituted by 1, 2 or 3 substituents independently selected from F, Cl, Br, -OH, -SH, -O-CH_ {3}, -O-C2H5, -NO2, -CN and -S-CH3; or a 5-14 membered aryl or heteroaryl radical, which may be substituted by 1, 2 or 3 substituents independently selected from -CF 3, C 1-5, alkyl, -O-C 1-5 -alkyl, -S-C_ {1-5} -alkyl, -C (= O) -OH, -C (= O) -O-C_ {1-5} -alkyl, -OC (= O) -C_ {15} -alkyl, F, Cl, Br, I, -CN, -OCF3, -SCF3, -OH, -SH, -NH2, -NH (C_ {1-5} -alkyl), -N (C 1-5 -alkyl) 2,
-NH-C (= O) -C_ {1-5} -alkyl, -N (C_ {1-5} -alkyl) -C (= O) -C_ {1-5} -alkyl, -NO_ {2 }, -CHO, -CF2H, -CFH2, -C (= O) -NH2, -C (= O) -NH
(C_ {1-5} -alkyl), -C (= O) -N (C_ {1-5} -alkyl) 2, -S (= O) 2 -C_ {1-5 -alkyl, -S (= O) 2 -phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, phenoxy, benzyloxy and benzyl and which may be linked through a C 1 -C 6 group alkylene, C 2 -C 6 alkenylene or C 1 -C 6 linear or branched ilidene and where the heteroaryl radical contains 1, 2 or 3 heteroatoms independently selected from N, O and S as members of the ring;

R 7 represents a hydrogen atom; a C 1 -C 6 linear aliphatic radical or branched that may be substituted by 1, 2 or 3 substituents independently selected from F, Cl, Br, -OH, -SH, -O-CH 3, -O-C 2 H 5, -NO 2, -CN and -S-CH 3;

R 10 to R 22 represent, independently of one another, a hydrogen atom; a linear or branched, saturated or unsaturated C 1 -C 5 aliphatic radical, which may be substituted with 1, 2 or 3 substituents independently selected from F, Cl, Br, -OH, -NH 2, - SH, -O-CH 3, -O-C 2 H 5, -NO 2, -CN, -NH-CH 3 and -S-CH 3; a saturated or unsaturated 3 to 8 membered cycloaliphatic radical, which may be substituted with 1, 2 or 3 substituents independently selected from C 1-5, alkyl, -O-C 1-5, alkyl, -S- C_ {1-5} -alkyl, oxo (= O), thioxo (= S), -C (= O) -OH, -C (= O) -O-C_ {1-5} -alkyl, -OC (= O) -C_ {1-5} -alkyl, F, Cl, Br, I, -CN, -CF_ {3}, -OCF_ {3}, -SCF_3, -OH, -SH, - NH 2, -NH (C 1-5 -alkyl), -N (C 1-5 -alkyl) 2,
-NO_ {2}, -CHO, -CF_2H, -CFH_2, -C (= O) -NH_ {2}, -C (= O) -NH (C_ {1-5} - alkyl), -C (= O) -N (C 1-5 -alkyl) 2, -S (= O) 2 -C_15 -alkyl,
-S (= O) 2 -phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, phenoxy benzyloxy and benzyl and which may optionally contain 1, 2 or 3 heteroatoms independently selected from N, O and S as ring members and which may be linked through a linear or branched C 1 -C 6 alkylene group; or a 5-14 membered aryl or heteroaryl radical that may be substituted with 1, 2 or 3 substituents independently selected from
-CF 3, C 1-5, alkyl, -S-C 1-5, alkyl, -C (= O) -OH, -C (= O) -O-C_ {1 -5} -alkyl, -OC (= O) -C_ {1-5} -alkyl, F, Cl, Br, I, -CN, -OCF_3, -SCF3, -OH, -SH , -NH 2, -NH (C 1-5, alkyl), -N (C 1-5, alkyl) 2, -NH-C (= O) -C 1- 5} -alkyl, -N (C_ {1-5} -alkyl) -C (= O) -C_ {1-5} -alkyl, -NO_ {2}, -CHO, -CF2H, - CFH2, -C (= O) -NH2, -C (= O) -NH (C_ {1-5} -alkyl), -C (= O) -N (C_ {1-5 -alkyl) 2, -S (= O) 2 -C 1-5 -alkyl, -S (= O) 2 -phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, phenoxy, benzyloxy and benzyl and which can be linked through a linear C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 2 -C 6 alkynylene group or branched and wherein the heteroaryl radical contains 1, 2 or 3 heteroatoms independently selected from N, O and S as ring members;

preferably on the condition that when R 1 is -COOH; R2, R3, R4 or R5 are not -SOR 13, -S (= O) 2 -R 13 or -S (= O) 2 -N (R 14) R 15 and A does not represent C = C (R6) R_ {6} 'given the situation joint in which R6 or R6 'are one H and the other a phenyl replaced by -S (= O) 2 -C_ 1-5 -alkyl, -NH2, -O-C_ {1-5} -alkyl, F, Cl, Br, CN, -C (= O) -OH or -C (= O) -O-C_ {1-5} -alkyl,  or the situation in which both R_ {6} and R_ {6} 'represent -OR 11, and / or

preferably on the condition that when R 1 is -OH; R2, R3, R4 or R5 are not -S (= O) 2 -R 13 or -S (= O) 2 -N (R 14) R 15, I

preferably on the condition that when R 1 is -CONR 8 R 9; R 2, R 3, R 4 or R 5 other than -SOR 13, -S (= O) 2 -R 13 or -S (= O) 2 -N (R 14) R 15 and A does not represent C = C (R6) R_ {6} 'given the situation joint in which R6 or R6 'are one H and the other a phenyl replaced by -S (= O) 2 -C_ 1-5 -alkyl, -NH2, -O-C_ {1-5} -alkyl, F, Cl, Br, I, CN, -C (= O) -OH or -C (= O) -O-C_ {1-5} -alkyl,  an arite or a heteroaryl, and / or

preferably on the condition that when R 1 is -NR 8 R 9; R2, R3, R4 or R5 no  be -SOR 13 or -S (= O) 2 -R 13 and A do not represent C = C (R6) R_ {6} 'given the joint situation where R6 or R6 'is one H and the other a phenyl substituted by -S (= O) 2 -C_ 1-5 -alkyl,  -NH2, -O-C_ {1-5} -alkyl, F, Cl, Br, CN, -C (= O) -OH or -C (= O) -O-C_ {1-5} -alkyl

or a pharmaceutically acceptable salt, a isomer, a prodrug or a solvate thereof,

optionally, in the form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and / or diasteromers, in any mixing ratio or a physiologically acceptable salt of same or the corresponding solvate thereof.

The term "salt" should be understood as any form of an active compound used in accordance with the invention in which said compound is in phonic form or is charged and is coupled with a counter-ion (a cation or an anion) or is in solution. This definition also includes the quaternary ammonium salts as well as molecule complexes active with other molecules and ions, particularly those complexes formed via ionic interactions. The definition includes, particularly, the physiologically acceptable salts term this which should be understood as equivalent to "sales pharmacologically acceptable. "

The term "physiologically salts acceptable "means in the context of this invention any salt that is physiologically tolerated (usually meaning that It is not toxic, especially as a result of counter-ion) if used properly for a treatment, especially applied or used in humans and / or mammals

These physiologically acceptable salts can be formed with cations or bases and, in the context of this invention, they are understood as salts formed by at least one compound used according to the invention - usually an acid (deprotonated) - as an anion and at least one cation, preferably inorganic, physiologically tolerated - especially if it is used in humans and / or mammals. They are particularly preferred salts with alkali metals and alkaline earth and also those formed with ammonium cations (NH4 +). Salts formed with (mono) or are preferred (di) sodium, (mono) or (di) potassium, magnesium or calcium.

These physiologically acceptable salts may also be formed with anions or acids and, in the context of this invention, are understood as salts formed by at least one compound used in accordance with the invention.
- normally protonated, for example in nitrogen - as a cation and at least one physiologically tolerated anion - especially if it is used in humans and / or mammals. This definition particularly includes, in the context of this invention, a salt formed with a physiologically tolerated acid, that is, salts of a specific active compound with organic or inorganic acids that are physiologically tolerated - especially if used in humans and / or mammals Examples of this type of salts are those formed with: hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid, formic acid, acetic acid, oxalic acid, succinic acid, malic acid, tartaric acid, mandelic acid, fumaric acid, lactic acid or citric acid.

The term "solvate" according to this invention should be understood as any form of the active compound according to the invention in which said compound has attached via another non-covalent bond another molecule (usually a solvent polar) especially including hydrates and alcoholates, for example methanolate.

In a particular and preferred embodiment of the invention R 1 represents:

7

8

where the dotted line represents an optional chemical bond and R '1 represents an atom of hydrogen, a C 1-5 aliphatic radical, or a group protector such as benzyl

In another preferred embodiment of the invention R 1 represents a radical -NR 8 R 9; and R 8 and R 9 independently or jointly represent a hydrogen atom or a C 1-5 aliphatic radical.

In another preferred embodiment of the invention R 1 represents a radical -NR 8 R 9; and R 8 and R 9 together with nitrogen they form a heterocyclic ring of 3 to 9 members saturated, unsaturated or aromatic that optionally contains 1, 2 or 3 additional heteroatoms independently selected from N, O and S.

Another preferred embodiment of the invention defines those compounds of formula I in which R1 represents a radical -CONR 8 R 9; and R 8 and R 9 independently or jointly represent an atom of hydrogen or a C 1-5 aliphatic radical.

It is also a preferred embodiment the compounds of formula I in which R 1 represents a radical -CONR 8 R 9; and R 8 and R 9 together with the nitrogen forms a 3 to 9 member heterocyclic ring saturated, unsaturated or aromatic that optionally contains 1, 2 or 3 additional heteroatoms independently selected from N, O and S.

On the other hand, indens are also preferred derivatives of general formula I where at least one of R 2, R 3, R 4 or R 5 represents a radical -SOR 13.

Another preferred embodiment is one in which at least one of R 2, R 3, R 4 or R 5 represents a radical
-S (= O) 2 -R 13.

Also preferred is the embodiment in which the minus one of R 2, R 3, R 4 or R 5 represents a radical -S (= O) 2 -N (R 14) R 15.

It is also considered a preferred embodiment. that in which at least one of R 2, R 3, R 4 or R 5 represents a radical -N (R 16) - S (= O) 2 -R 17.

A further preferred embodiment is that in which at least one of R 2, R 3, R 4 or R 5 represents a radical -N (R 21) - CO-R 22.

With respect to other substituents such as R 6 and R '6, an indene derived from general formula I is preferred where R 6 and R '6, identical or different, represent a hydrogen atom, a C 1-5 aliphatic radical or an aryl or heteroaryl radical of 5 to 14 members optionally substituted by a phenyl that can be linked through a C 1 -C 6 alkylene or a C_ {1} -C_ {6} ilidene.

Finally, those compounds are preferred of general formula I where R 10 to R 22 represent a aryl or heteroaryl radical containing 1, 2 or 3 heteroatoms independently selected from N, O and S and that may be replaced by a Cl.

Among all the compounds described in the general formula I are especially preferred any of the selected from:

[1] (2-Methyl-6-nitro-3 H -inden-1-yl) acetic acid

[2] [2-methyl-6- (naphthalene-2-sulfonylamino) -3 H -inden-1-yl] acetic acid

[3] [3 ( Z ) -benzylidene-2-methyl-6- (naphthalen-2-sulfonylamino) -3 H -inden-1-yl] acetic acid

[4] [2-Methyl-4- (naphthalene-2-sulfonylamino) -3 H -inden-1-yl] acetic acid

[5] [6- (naphthalene-2-sulfonylamino) -3 H -inden-1-yl] acetic acid

[6] [6- (5-Chloro-3-methylbenzo [ b ] thiophene-2-sulfonylamino) -2-methyl-3H-inden-1-yl] acetic acid

[7] [2-methyl-6- (naphthalen-1-ylsulfamoyl) -3 H -inden-1-yl] acetic acid

[8] N, N -Dimethyl-2- (2-methyl-6-nitro-3 H -inden-1-yl) acetamide

[9] 2- (2-Methyl-6-nitro-3 H -inden-1-yl) -1-pyrrolidin-1-iletanone

[10] 2- [3 ( Z ) -Benciliden-2-methyl-6- (naphthalen-2-sulfonylamino) -3 H -inden-1-yl] - N, N -dimethyl acetamide

[11] N, N -Dimethyl-2- [2-methyl-6- (naphthalen-2-sulfonylamino) -3 H -inden-1-yl] acetamide

[12] N - [2-Methyl-3- (2-oxo-2-pyrrolidin-1-ylethyl) -1 H -inden-5-yl] naphthalene-2-sulfonamide

[13] N - [2-Methyl-1- (2-oxo-2-pyrrolidin-1-ylethyl) -3 H -inden-4-yl] naphthalene-2-sulfonamide

[14] N - [3- (2-Oxo-2-pyrrolidin-1-ylethyl) -1 H -inden-5-yl] naphthalene-2-sulfonamide

[15] N - [2-Methyl-3- (2-oxo-2-pyrrolidin-1-ylethyl) -1 H -inden-5-yl] -5-chloro-3-methylbenzo [ b ] thiophene-2- sulfonamide

[16] N, N -Dimethyl-2- [2-methyl-6- (naphthalen-1-ylsulfamoyl) -3 H -inden-1-yl] acetamide

[17] Dimethyl- [2- (2-methyl-6-nitro-3 H -inden-1-yl) ethyl] amine

[18] 3- (2-Dimethylaminoethyl) -2-methyl-1 H -inden-5-ylamine

[19] N - [3- (2-Dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] -ó-chloroimidazo [2,1- b ] thiazol-5-sulfonamide

[20] N - [3- (2-Dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] -5-chloro-3-methylbenzo [ b ] thiophene-2-sulfonamide

[21] N - {4- [3- (2-Dimethylaminoethyl) -2-methyl-1 H -inden-5-ylsulfamoyl] phenyl} acetamide

[22] N - [3- (2-Dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] benzo [1,2,5] thiadiazol-4-sulfonamide

[23] N -Ethyl- N - [3- (2-dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] -5-chloro-3-methylbenzo [ b ] thiophene-2-sulfonamide

[24] 4-Amino- N - [3- (2-dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] benzenesulfonamide

[25] N - [3- (2-Pyrrolidin-1-ylethyl) -2-methyl-1 H -inden-5-yl] -2- (4-benzyloxyphenyl) acetamide

[26] 2-Methyl-3- (2-pyrrolidin-1-ylethyl) -1 H -inden-5-ylamine

[27] (2- {6 - [(5-Chloro-3-methylbenzo [ b ] thiophene-2-sulfonyl) ethylamino] -2-methyl-3 H -inden-1-yl} ethyl) ethyldimethylammonium iodide

[28] 1- [2- (2-Methyl-6-nitro-3 H -inden-1-yl) ethyl] pyrrolidine

[29] N - [3- (2-Pyrrolidin-1-ylethyl) -2-methyl-1 H -inden-5-yl] -6-chloroimidazo [2,1- b ] thiazol-5-sulfonamide

[30] N - {4- [3- (2-Pyrrolidin-1-ylethyl) -2-methyl-1 H -inden-5-ylsulfamoyl] phenyl} acetamide

[31] N - [3- (2-Pyrrolidin-1-ylethyl) -2-methyl-1 H -inden-5-yl] -benzo [1,2,5] thiadiazol-4-sulfonamide

[32] 4-Amino- N - [3- (2-pyrrolidin-1-ylethyl) -2-methyl-1 H -inden-5-yl] benzenesulfonamide

[33] N - [1 ( Z ) -Benciliden-3- (2-dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] naphthalene-2-sulfonamide

[34] N - [3- (2-Dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] naphthalen-2-sulfonamide

[35] N - [2-Methyl-3- (2-pyrrolidin-1-ylethyl) -1 H -inden-5-yl] naphthalene-2-sulfonamide

[36] N - [2-Methyl-1- (2-pyrrolidin-1-ylethyl) -3 H -inden-4-yl] naphthalene-2-sulfonamide

[37] N - [3- (2-Pyrrolidin-1-ylethyl) -1 H -inden-5-yl] naphthalene-2-sulfonamide

[38] N - [2-Methyl-3- (2-pyrrolidin-1-ylethyl) -1 H -inden-5-yl] -5-chloro-3-methylbenzo [ b ] thiophene-2-sulfonamide

[39] N - (Naftalen-1-yl) -3- (2-dimethylaminoethyl) -2-methyl-1 H -indene-5-sulfonamide

[40] N - [3- (2-Hydroxyethyl) -2-methyl-1 H -inden-5-yl] naphthalene-2-sulfonamide.

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A particular embodiment of the invention is that in which the indeno derivatives of the invention represent a compound with the general formula (Ia):

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9

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where R2, R3, R4, R 5, R 7, A, and n has the meanings above described.

It is also a particular embodiment that in which the indeno derivatives of the invention are represented by the general formula (Ib):

       \ vskip1.000000 \ baselineskip
    

10

       \ vskip1.000000 \ baselineskip
    

where R2, R3, R4, R 5, R 7, R 8, R 9, A and n have the meanings previously noted.

In addition, it also represents an embodiment Particular indene derivatives of general formula (Ic):

       \ vskip1.000000 \ baselineskip
    

eleven

       \ vskip1.000000 \ baselineskip
    

where R2, R3, R4, R 5, R 7, R 8, R 9, A and n have the meanings previously noted.

       \ newpage
    

Another particular embodiment of the invention are Compounds with the general formula (Id):

       \ vskip1.000000 \ baselineskip
    

12

       \ vskip1.000000 \ baselineskip
    

where the amino group can occupy any position within the benzene ring and the other positions thereof can be substituted according to the above described for the formula I preferably hydrogen, -OR 11, -SR 11, F, Cl, Br, I or a C 1-4 alkyl radical, and where R 1, R 7, R 11, A and n have the meanings above
noted.

Another particular embodiment is one in which The compounds of the invention have the general formula (Ie):

       \ vskip1.000000 \ baselineskip
    

13

       \ vskip1.000000 \ baselineskip
    

where -NHSO_ {R} {13} can occupy any position of the benzene ring and the other positions thereof can be substituted according to the above described for formula I, preferably hydrogen, -OR_ {11}, -SR_ {11 }, F, Cl, Br, I or a C 1-4 alkyl radical, and where R 1, R 7, R 11, R 13, A and n have the meanings above
noted.

Another particular embodiment of the invention are the indene derived from the general formula (If):

       \ vskip1.000000 \ baselineskip
    

14

       \ vskip1.000000 \ baselineskip
    

where -N (R 16) SO 2 R 13 may occupy any position of the benzene ring and the other positions thereof may be substituted in accordance with the above described for formula I, preferably hydrogen, -OR_ { 11}, -SR 11, F, Cl, Br, I or a C 1-4 alkyl radical, and where R 1, R 7, R 13, R 11, R_ {16}, A and n have the meanings above
noted.

       \ newpage
    

Another particular embodiment is the indene derivatives that have the general formula general formula (Ig):

       \ vskip1.000000 \ baselineskip
    

fifteen

       \ vskip1.000000 \ baselineskip
    

where R2, R3, R4, R_ {5}, R_ {7}, A have the meanings indicated above and n = 1, 2, 3, Four.

Another particular embodiment of the invention are the compounds of general formula (Ih):

       \ vskip1.000000 \ baselineskip
    

16

       \ vskip1.000000 \ baselineskip
    

where R2, R3, R4, R 5, R 6, R 6, R 7 and n have the meanings previously noted.

Another particular embodiment of the invention are Compounds of general formula (In):

       \ vskip1.000000 \ baselineskip
    

17

       \ vskip1.000000 \ baselineskip
    

where R2, R3, R4, R 5, R 6, R 6, R 7 and n have the meanings previously noted.

       \ newpage
    

Finally it is also a particular embodiment of the invention the compounds of the general formula (Ik):

18

where R2, R3, R4, R 5, R 7 and n have the meanings above noted.

In another different aspect, the invention makes reference to the procedures for obtaining the indene derivatives of general formula I. Several procedures have been developed to prepare the indene derivatives of the invention. Then Each of them will be explained.

Method TO

First, a procedure is described for the preparation of indene derivatives of the general formula (Ia).

19

where R2, R3, R4, R 5, R 7, A and n have the meaning indicated above that for the particular case where n = 1 comprises the following stages:

to)

put on in in a suitable reaction medium an indanone of general formula II:

twenty

where R2 R 3, R 4, R 5, R 7 and A have the meaning above, with an alkyl carboxylate to obtain an intermediate alcohol

b)

do react the resulting intermediate alcohol in a solution of a acid, preferably H 2 SO 4.

In the first stage, you work at temperatures very low near -80ºC in a reaction medium that preferably comprises LHMDS and THF. In addition, this first stage It is preferable to carry it out under argon. In these conditions are reacted to the indanone of formula II with a alkyl carboxylate. An alcohol is obtained from this reaction intermediate that is dried and filtered and that is subsequently undergoing the second stage comprising a treatment of alcohol with an acid, preferably H 2 SO 4, at a adequate temperature and time. The reaction mixture is extracted with an organic acid and after filtration and drying a precipitate that can be identified as an acid of formula general (Ia).

Before proceeding with step a of method A, the indanones of general formula II may be nitrated at positions R2 to R5 as described in DL Musso, FR Cochran, JL Kelley, EW McLean , JL Selph, GC Rigdon, GF Orr, RG Davis, BR Cooper, VL Styles, JB Thompson, and WR Hall, J. Med. Chem ., 2003 , 46 , 399-408.

Method B

This procedure also allows to obtain indenylalkylcarboxylic acids and consists of three stages main, although the first one is common to method A. Thus thus, a procedure for the preparation of indene is described derivatives of general formula (Ia):

twenty-one

that for the particular case in which n = 1 includes the following stages:

to)

put on in in a suitable reaction medium an indanone of general formula II:

22

where R2, R 3, R 4, R 5, R 7 and A have the meaning above, with an alkyl carboxylate to obtain intermediate alcohol

b)

add TFA drop by drop over alcohol resulting intermediate in an appropriate medium

C)

do react the resulting mixture with sodium metal dissolved in methanol bringing the mixture to reflux temperature.

As mentioned, the stage until the Obtaining intermediate alcohol is common to that of method A. obtained intermediate alcohol is dissolved in an appropriate solution as for example, CH 2 Cl 2 and on it the TFA is added drop by drop at a temperature slightly below 0 ° C and preferably in agitation This mixture is evaporated and resuspended in a medium. suitable as for example dry methanol. About this solution is add a sufficient amount of sodium metal dissolved in it medium in which the previous mixture is resuspended. Mix resulting is brought to reflux temperature and reacted for a suitable time. The product of this reaction mixture it is dried and filtered and a solid is obtained which can be identified as an acid of general formula (Ia).

As in method A, the indanones of general formula II can be nitrated at positions R 2 to R 5 as described in DL Musso, FR Cochran, JL Kelley, EW McLean, JL Selph, GC Rigdon, GF Orr, RG Davis, BR Cooper, VL Styles, JB Thompson, and WR Hall, J. Med. Chem ., 2003 , 46 , 399-408.

On the other hand, the compounds of formula (Ia) where n is different from 1 can be prepared via acids carboxylic, according to the methodology described in:

?

H. Ochiai, T. Nishihara, Y. Tamaru, and Z. Yoshida. Titanium (IV) -Mediated Aldol-Type Condensation of Zinc Esters and Zinc Ketones with Carbonyl Electrophiles. J. Org. Chem ., 1988 , 53 , 1343-1344.

?

DAH Taylor. 1,2,3,4-Tetrahydro-8-methylfluoren-1-one. Journal of the Chemical Society, Abstracts , 1960 , 2805-2806.

?

GR Clemo, LH Groves, L. Munday, and GA Swan. Indene series. I. A synthesis of 1,2,3,8-tetrahydro-1-ketocyclopent [a] indene. Journal of the Chemical Society, Abstracts , 1951 , 863-867.

?

M. Finze, SE Reybuck, and RM Waymouth. Propylene Polymerization with 1,2'-Bridged Bis (indennyl) zirconium Dichlorides. Macromolecules , 2003 , 36 , 9325-9334.

Also, the compounds of formula (I) where n is different from 1 according to the described methodology in:

?

R. Perrone, F. Berardi, NA Colabufo, V. Tortorella, F. Fiorentini, V. Olgiati, E. Vanotti, and S. Govoni. Mixed 5-HT, AID-2 Activity of a New Model of Arylpiperazines: I -Aryl-4- [3- (1, 2-dihydronaphtalen-4-yl) -n-propyl] piperazines. 1. Synthesis and Structure-Activity Relationships. J. Med. Chem ., 1994 , 37 , 99-104.

?

K. Fukatsu, O. Uchikawa, M. Kawada, T. Yamano, M. Yamashita, K. Kato, K. Hirai, S. Hinuma, M. Miyamoto, and S. Ohkawa. Synthesis of a Novel Series of Benzocycloalkene Derivatives as Melatonin Receptors Agonists. J. Med. Chem ., 2002 , 45 , 4212-4221.

Method C

In this section, a procedure is described for the preparation of indene derivatives of the general formula (Ib):

2. 3

where R2, R3, R4, R 5, R 7, R 8, R 9 and A have the meaning above and n = 0, 1, 2, 3 or Four.

which comprises contacting a means of suitable reaction, an acid of general formula (Ia):

24

with a sufficient amount of SOCl 2 at reflux temperature and add on the residue obtained and redissolved an amine of formula NR 8 R 9.

       \ newpage
    

The reaction between the compound of formula general (Ia) and the SOCl_ {2} must be carried out in a medium suitable, such as CH 2 Cl 2, and at a temperature of Reflux. The residue obtained after removing excess SOCl2 under reduced pressure it is dissolved again in an appropriate medium (by example CH 2 Cl 2) and mixed with the amine of formula NR 8 R 9 at a temperature close to 0 ° C. The mixture is left react for the necessary time at room temperature and preferably under stirring.

The product obtained after purification in silica gel column chromatography is characterized as a compound of general formula (Ib).

Method D

Method D provides, just like the method C, a procedure to obtain an indenylamide. Specifically, a procedure for the preparation of indene is described derivatives of general formula (Ib):

       \ vskip1.000000 \ baselineskip
    

25

       \ vskip1.000000 \ baselineskip
    

where R2, R3, R4, R 5, R 7, R 8, R 9 and A have the meaning above and n = 0, 1, 2, 3 or 4

which comprises contacting a means of suitable reaction an acid of general formula (Ia):

       \ vskip1.000000 \ baselineskip
    

26

       \ vskip1.000000 \ baselineskip
    

with CDI in agitation and add to the reaction mixture an amine of formula NR 8 R 9.

The preferred reaction medium for carrying The reaction between the compound (Ia) and the CDI comprises THF. This reaction in addition to favoring in agitation is also seen favored when carried out in an argon atmosphere. For another side, the second stage in which the amine of formula is added NR 8 R 9 to the reaction mixture is also carried preferably carried out under stirring. Both reactions lead to preferably run at room temperature for a while suitable.

As in the case of method C, after purification on silica gel column compounds are obtained which identify as compounds of general formula (Ib).

       \ newpage
    

Method AND

In this section, a procedure is described for the preparation of an indene derived from the general formula (Ic):

27

where R2, R3, R4, R 5, R 7, R 8, R 9 and A have the meaning above and n = 0, 1, 2, 3 or 4

which comprises contacting a means of Suitable reaction a compound of general formula (Ib):

28

with a solution of AIH_ {3} -DMEA.

The reaction is carried out in a medium of reaction preferably comprising THF, at near temperatures at 0 ° C and under argon for an appropriate time. He residue purified by silica gel column chromatography allows to identify an indenylamine of general formula (Ic).

Method F

Method F represents a procedure for Preparation of an indene derived from general formula (Id):

29

where the amino group can occupy any position within the benzene ring and the others positions thereof may be substituted according to previously described for formula I preferably hydrogen, -OR_ {11}, -SR_ {11}, F, Cl, Br, I or an alkyl radical C 1-4 and where R 1, R 7, R 11 A they have the meanings indicated above and n = 0, 1, 2, 3 or 4, comprising contacting in a suitable medium, a compound of general formula (Im):

30

where the nitro group can occupy any position within the benzene ring and the others positions thereof may be substituted according to previously described for formula I preferably hydrogen, -OR_ {11}, -SR_ {11}, F, Cl, Br, I or an alkyl radical C 1-4, and where R 1, R 7, R 11 and A they have the meanings indicated above and n = 0, 1, 2, 3 or 4,

with a suspension of Zn powder with acid acetic.

The reaction is carried out at temperature ambient for a suitable time preferably under stirring. A wash with an appropriate basic aqueous solution confirms that the product obtained is an indenylamine of general formula (Id).

Method G

Method G represents a procedure for Preparation of an indene derived from general formula (Ie):

       \ vskip1.000000 \ baselineskip
    

31

       \ vskip1.000000 \ baselineskip
    

where -NHSO_ {2} R_ {13} can occupy any position of the benzene ring and the others positions thereof may be substituted according to described above for formula I, preferably hydrogen, -OR_ {11}, -SR_ {11}, F, Cl, Br, I or a radical C 1-4 alkyl, and where R 1, R 7, R 11, R 13, A have the meanings above indicated n = 0, 1, 2, 3 or 4, which includes contacting a suitable medium, an indenylamine of general formula (Id):

       \ vskip1.000000 \ baselineskip
    

32

       \ vskip1.000000 \ baselineskip
    

where the amino group can occupy any position within the benzene ring and the others positions thereof may be substituted according to previously described for formula I preferably hydrogen, -OR_ {11}, -SR_ {11}, F, Cl, Br, I or an alkyl radical C 1-4, and where R 1, R 7, R 11, A they have the meanings indicated above and n = 0, 1, 2, 3 or 4, with a solution of R 13 SO 2 Cl at temperature ambient.

The indenylamine of formula (Id) is made react dissolved in an appropriate medium preferably pyridine dry with R 13 SO 2 Cl also dissolved at temperature atmosphere and argon atmosphere for a suitable time. The silica gel column purification confirms that the product obtained is a compound of general formula (Ie).

       \ newpage
    

Method H

Method H represents a procedure for Preparation of an indene derived from the general formula (If):

33

where -N (R_ {16}) SO_ {2} R_ {13} can occupy any position of the benzene ring and the other positions thereof may be substituted in accordance with the above described for formula I, preferably hydrogen, -OR 11, -SR 11, F, Cl, Br, I or an alkyl radical C 1-4, and where R 1, R 7, R 13, R 11, R 16, A have the meanings above indicated and n = 0, 1, 2, 3 or 4, which includes contacting a  suitable medium, an indenylsulfonamide of the general formula (Ie):

3. 4

where -NHSO_ {2} R_ {13} can occupy any position of the benzene ring and the others positions thereof may be substituted according to described above for formula I, preferably hydrogen, -OR_ {11}, -SR_ {11}, F, Cl, Br, I or a radical C 1-4 alkyl, and where R 1, R 7, R 11, R 13, A have the meanings above indicated n = 0, 1, 2, 3 or 4, with a reaction medium comprising K 2 CO 3 and an appropriate alkyl halide at temperature ambient.

The indenylsulfonamide of formula (Ie) is made react dissolved in an appropriate medium, such as acetonitrile, with K2CO3 and an alkyl halide appropriate 1 to 5 linear or branched carbons also dissolved at room temperature and under argon for a while suitable. The silica gel column purification confirms that The product obtained is a compound of general formula (If).

Method I

Method I represents a procedure for Preparation of an indene derived from general formula (Ig):

35

where R2, R3, R4, R 5, R 7 and A have the meaning indicated above and n = 1, 2, 3 or 4 which comprises contacting a means of suitable reaction, an indenilic acid of the general formula (Ia):

36

where R2, R3, R4, R 5, R 7 and A have the meaning indicated above and n = 0, 1, 2, 3 or 4 with a solution of LiAlH4 -AlCl3.

The reaction is carried out in a medium of reaction preferably comprising THF, at near temperatures at 0 ° C and under argon for an appropriate time. He residue purified by silica gel column chromatography allows to identify an alcohol of general formula (Ig).

Method J

Method J represents a procedure for Preparation of an indene derived from general formula (Ih):

37

where R2, R3, R4, R_ {5}, R_ {6}, R_ {6 '}, and R_ {7} have the meaning above and n = 0, 1, 2, 3 or Four.

which comprises contacting a means of suitable reaction, an indenilic acid of general formula (Ik):

38

where R2, R3, R4, R_ {5} and R_ {7} have the meaning indicated above and n = 0, 1, 2, 3 or Four.

with a reaction medium comprising NaH and a appropriate aldehyde at reflux temperature.

The acid of general formula (Ik) is made react dissolved in an appropriate medium with NaH and an aldehyde appropriate also dissolved at the reflux temperature and in Argon atmosphere for a suitable time. Acidification and silica gel column purification of the reaction mixture confirm that the product obtained is an acid of general formula (Ih)

Another fundamental aspect of the invention are the intermediates for obtaining the compounds of formula I, of general formula (II):

39

where R2, R3, R4, R 5, R 7 and A have the meaning above indicated.

They are particular realizations of these intermediates of formula (II) the following compounds:

[41] 2-Methyl-6-nitroindan-1-one

[42] 2-Methyl-4-nitroindan-1-one

[43] 6-Amino-2-methylindan-1-one

[44] N - (2-Methyl-3-oxoindan-5-yl) naphthalene-2-sulfonamide

[Four. Five] 4-Amino-2-methylindan-1-one

[46] N - (2-Methyl-1-oxoindan-4-yl) naphthalene-2-sulfonamide

[47] 6-Nitroindan-1 -one

[48] 4-Nitroindan-1-one

[49] 6-Aminoindan-1-one

[50] N - (3-Oxoindan-5-yl) naphthalene-2-sulfonamide

[51] N - (2-Methyl-3-oxoindan-5-yl) -5-chloro-3-methylbenzo [ b ] thiophene-2-sulfonamide

[52] Chloride 2-methyl-3-oxoindan-5-sulfonyl

[53] N - (Naftalen-1-yl) -2-methyl-3-oxoindane-5-sulfonamide.

Another additional aspect of the invention is refers to the therapeutic use of the compounds of general formula I. As mentioned at the beginning the indene derivatives of formula general I have an important affinity to the receptors 5-HT_ {6} and can behave like agonists, antagonists, inverse agonists, partial antagonists or partial agonists thereof. For this reason they are made suitable for the treatment and prophylaxis of disorders or receptor-mediated diseases 5-HT6. In this sense, the indene derived from general formula I are especially suitable for use in the prophylaxis and / or treatment of disorders or diseases related to food intake, preferably for appetite regulation, for maintenance, increase or reduction of body weight, for prophylaxis and / or treatment of obesity, bulimia, anorexia, cachexia or type II diabetes, or for the prophylaxis and / or treatment of irritable bowel / intestine; central nervous system disorders; anxiety; panic attacks; depression; bipolar disorders; cognitive disorders; memory disorders; senile dementia; psychosis; schizophrenia; neurodegenerative disorders preferably selected from Alzheimer's disease, the Parkinson's disease, Huntington's disease and multiple sclerosis; or hyperactivity disorders preferably attention deficit / hyperactivity disorder, or for improvement of cognitive ability.

Another fundamental aspect of the invention is a pharmaceutical composition comprising some compound of formula general I and at least one additive and / or auxiliary material pharmaceutically acceptable.

The auxiliary and / or additive material can be select between carriers, excipients, support materials, lubricants, fillers, solvents, diluents, dyes, flavor conditioners such as sugars, antioxidants and / or binders. In the case of a suppository, this may involve waxes or esters of fatty acids or preservatives, emulsifiers and / or carriers for parenteral application. The selection of these auxiliary and / or additive materials and of the quantities to be used depend on how the pharmaceutical composition

Pharmaceutical compositions according to the invention can be adapted to be administered by any route of administration, either orally or parenterally, for example, pulmonary, nasal, rectal and / or intravenous. Therefore, the formulation according to the invention can be adapted for the application topical or systemic, especially for dermal application, subcutaneous, intramuscular, intrarticular, intraperitoneal, Pulmonary, oral, sublingual, nasal, percutaneous, vaginal, oral or parenteral

For oral applications, the preparations in the form of tablets, chewing gum, capsules, granules, drops or syrups.

For parenteral applications, the solutions, suspensions, reconstitutable dry preparations or in spray.

The compounds of the invention as deposits in dissolved form or in a patch, optionally with agents that promote dermal penetration, are examples of ways of percutaneous application.

Dermal applications include ointments, gels, creams, lotions, suspensions or emulsions.

The preferred form of rectal application is through suppositories.

Optionally, the compositions according to the invention may be slow release in applications Above mentioned, especially for oral applications, rectal and percutaneous.

The amount of active ingredient to be administered to the patient varies depending on the weight of the patient, the type of application, indication and severity of the disease. Normally, in humans 1 to 500 mg are applied daily of the active compound in one or several doses.

A series of illustrative examples of the invention:

Example 1 Synthesis of (2-methyl-6-nitro-3 H -inden-1-yl) acetic acid (compound 1) by method A

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40

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To the sufficient amount of cooled anhydrous THF at -78 ° C 1.1-2.1 equivalents of a 1M LHMDS solution in THF, under argon. Later, 1.05 equivalents of dry AcOEt was added and stirred at -78 ° C for 30 minutes Finally, a solution of 1 was added equivalent of the 2-methyl-6-nitroindan-1-one in sufficient amount of anhydrous THF and kept 1-2 hours at -78 ° C. The reaction mixture is acidified with 1N HCl, the temperature was allowed to rise gradually until reaching 20 ° C and extracted with AcOEt. Extracts organic, after being dried with anhydrous Na2SO4 and filtered, evaporated to dryness; obtaining a residue that identified by 1 H NMR as the intermediate alcohol.

On a solution of H2SO4 50% (1: 1), cooled to -5 ° C, the above alcohol was added and heated to 60 ° C for 2-5 hours. The evolution of the reaction 1 H NMR of aliquots of the reaction mixture was followed. TO the reaction mixture was added H2O and extracted with AcOEt. The organic extracts, after being dried with Na 2 SO 4 anhydrous and filtered, evaporated to dryness. The residue obtained triturated with dry CH2Cl2 and the precipitate was filtered formed, obtaining a solid that was identified as the acid indenylacetic

Example 2 Synthesis of [2-methyl-6- (naphthalene-2-sulfonylamino) -3 H -inden-1-yl] acetic acid (compound 2) by method B

41

To a sufficient amount of anhydrous THF cooled to -78 ° C 1.1-2.1 equivalents were added of a solution of 1M LHMDS in THF, under argon. Subsequently, 1.05 equivalents of dry AcOEt was added and stirred at -78 ° C for 30 minutes. Finally, a solution of 1 equivalent of the N- (2-methyl-3-oxoinda-5il) naphthalene-2-sulfonamide in the sufficient amount of THE anhydrous and remained 1-2 hours at -78 ° C.

The reaction mixture was acidified with 1N HCl, the temperature was allowed to rise gradually until reaching 20 ° C and extracted with AcOEt. Organic extracts, after being dried with anhydrous and filtered Na2SO4, they were evaporated to dryness; obtaining a residue that was identified by 1 H NMR as the intermediate alcohol

To a solution of the above alcohol in Dry CH 2 Cl 2 cooled to -10 ° C and under an argon atmosphere added, drop by drop, 7 equivalents of TFA and stirred thereto temperature for 30 minutes. The resulting mixture was evaporated at dryness.

On the sufficient amount of dry methanol, Slowly added 4 equivalents of sodium metal. One time dissolved all the sodium, the solution was transferred to a suspension of the above residue in dry methanol. The resulting mixture is heated under argon at reflux temperature for 18 hours. The course of the reaction was followed by layer chromatography. thin silica gel (hexane: AcOEt: AcOH 50: 45: 5).

To the reaction mixture was added EtOH and evaporated to dryness. To the resulting residue, a solution of 5% Na 2 CO 3 was added and washed with AcOEt. The aqueous solution was acidified with 5N HCl and extracted with AcOEt. The organic extracts, after being dried with anhydrous Na2SO4 and filtered, were evaporated to dryness to obtain a solid that was identified as the acid [2-methyl-6- (naphthalene-2-sulfonylamino) -3 H -inden-1-yl] acetic.

Example 3 Synthesis of N, N- Dimethyl-2- [2-methyl-6- (naphthalen-2-sulfonylamino) -3 H -inden-1-yl] acetamide (compound 11) by method C

42

On a solution of 1 equivalent of compound obtained in the previous example in dry CH2Cl2 Sufficient amount of SOCl2 was added. Then the reaction mixture was heated at reflux temperature for 2 hours. Once the reaction mixture was cooled, the excess was evaporated of SOCl2 under reduced pressure.

The obtained residue was dissolved in CH 2 Cl 2 dry, cooled to 0 ° C, 2.25 equivalents was added of the amine N, N-dimethylamine and stirred at room temperature, under argon, for 18 hours. He course of the reaction was followed by thin layer chromatography of silica gel (AcOEt).

H 2 O was added to the reaction mixture, acidified with 5N HCl and extracted with AcOEt. The organic extracts, after being dried with anhydrous Na2SO4 and filtered, evaporated to dryness. The obtained residue was purified by silica gel column chromatography (CH2Cl2: MeOH, mixtures of increasing polarity), to provide a compound that was identified as N, N -Dimethyl-2- [2- methyl-6- (naphthalen-2-sulfonylamino) -3 H -inden-1-yl] acetamide.

Example 4 Synthesis of N, N- Dimethyl-2- [2-methyl-6- (naphthalen-2-sulfonylamino) -3 H -inden-1-yl] acetamide (compound 11) by method D

43

To a solution of 1 equivalent of the compound obtained in example 2 in anhydrous THF was added, in small portions, 2 equivalents of CDI and stirred at room temperature under argon for 2 hours. Subsequently, to the mix reaction was added 2 equivalents of the amine N, N-dimethylamine and kept under stirring at same temperature for 18 hours. The course of the reaction is followed by silica gel thin layer chromatography (CH 2 Cl 2: MeOH 9: 1).

The reaction mixture was evaporated to dryness. The obtained residue was dissolved in AcOEt and washed with 1N HCl. The organic extract, after being dried with anhydrous Na2SO4 and filtered, was evaporated to dryness. The obtained residue was purified by silica gel column chromatography (CH2Cl2: MeOH, mixtures of increasing polarity), to provide a compound that was identified as N, N -Dimethyl-2- [2- methyl-6- (naphthalen-2-sulfonylamino) -3 H -inden-1-yl] acetamide.

Example 5 Synthesis of N - [3- (2-Dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] naphthalen-2-sulfonamide (compound 34) by method E

44

About sufficient amount of anhydrous THF cooled to 0 ° C 1.1-2.5 equivalents of a solution of 0.5M AIH3 -DMEA in toluene. Subsequently, a solution of 1 equivalent of compound obtained in examples 3 or 4 in anhydrous THF cooled to 0 ° C After the addition was finished, the mixture was kept the same temperature and under argon for 30 minutes. The course of the reaction was followed by thin layer chromatography of SiO2 (CH 2 Cl 2 / NH 3 gas: MeOH 99: 1).

Water and 10% H 2 SO 4 were added slowly to the reaction mixture and the temperature was allowed to gradually rise to 20 ° C. It was made alkaline with 20% NH 3 and extracted with AcOEt. The organic extracts, after being dried with anhydrous Na2SO4 and filtered, evaporated to dryness. The obtained residue was purified by silica gel column chromatography (CH2Cl2 / NH3 gas: MeOH, mixtures of increasing polarity), providing a compound that was identified as the N - [3- (2-Dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] naphthalen-2-sulfonamide.

Example 6 Synthesis of 3- (2-dimethylaminoethyl) -2-methyl-1 H -inden-5-ylamine (compound 18) by method F

Four. Five

On a solution of 1 equivalent of N, N-dimethyl- [2- (2-methyl-6-nitro-3 H -inden-1-yl) ethyl] amine in glacial AcOH, 10 equivalents of Zn were added. The resulting suspension was stirred at room temperature for 3 hours. The course of the reaction was followed by silica gel thin layer chromatography (CH2Cl2 / NH3 gas: MeOH 4: 1). The reaction mixture was filtered through Celite® and the filtered liquids evaporated to dryness. The obtained residue was dissolved in CH2Cl2 and washed with 10% NaHCO3. The organic extract, after being dried with anhydrous Na2SO4 and filtered, was evaporated to dryness. The obtained residue was purified by silica gel column chromatography (CH 2 Cl 2 / NH 3 gas: MeOH, mixtures of increasing polarity), obtaining a brown solid that was identified as 3- (2 -dimethylaminoethyl) -2-methyl-1 H -inden-5-ylamine.

Example 7 Synthesis of compounds 19, 20, 21 and 22 (Method G)

46

To a solution of 1 equivalent of 3- (2-dimethylaminoethyl) -2-methyl-1 H -inden-5-ylamine in dry pyridine was added a solution of 1.1-1.5 equivalents of the 6-chloroimidazo chloride [ 2,1- b ] thiazol-5-sulfonyl in dry pyridine. The resulting mixture was stirred at room temperature under argon for 2-18 hours. The course of the reaction was followed by silica gel thin layer chromatography (CH2Cl2 / NH3 gas: MeOH 4: 1).

The reaction mixture was evaporated to dryness. The obtained residue was dissolved in CH2Cl2 and washed with a saturated solution of Na2CO3 (3x100 ml). The organic extract, after being dried with anhydrous Na2SO4 and filtered, was evaporated to dryness. The obtained residue was purified by silica gel column chromatography (CH 2 Cl 2 / NH 3 gas: MeOH, mixtures of increasing polarity), obtaining a solid that was identified as the N - [3- (2-Dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] -6-chloroimidazo [2,1- b ] thiazol-5-sulfonamide.

Compounds No. 20, 21 and 22 are obtained according to the same method from chloride 5-chloro-3-methylbenzo [b] thiophene-2-sulfonyl, of 4-acetylaminobenzenesulfonyl chloride and chloride 2,1,3-benzothiadiazol-4-sulfonyl  respectively.

Example 8 Synthesis of N -ethyl- N - [3- (2-dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] -5-chloro-3-methylbenzo [ b ] thiophene-2-sulfonamide (compound 23) by method H

47

To a solution of 1 equivalent of N - [3- (2-dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] -5-chloro-3-methylbenzo [ b ] thio-
Pheno-2-sulfonamide in dry acetonitrile was added 6 equivalents of potassium carbonate. The resulting mixture was stirred at room temperature under argon for 1 hour. Subsequently, 1.05 equivalents of ethyl iodide was added and stirring was maintained for 17 hours at room temperature. The course of the reaction was followed by silica gel thin layer chromatography (CH2Cl2 / NH3 gas: MeOH 9: 1).

The reaction mixture was filtered and the resulting solution evaporated to dryness to provide a residue that was purified by silica gel column chromatography (CH2Cl2 / NH3 gas: MeOH, polarity mixtures increasing), obtaining N- ethyl- N - [3- (2-dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] -5-chloro-3-methylbenzo [ b ] thiophene-2-sulfonamide.

Example 9 Synthesis of N - [3- (2-Hydroxyethyl) -2-methyl-1 H -inden-5-yl] naphthalene-2-sulfonamide (compound 40) by method I

48

On a suspension of 3.6 equivalents of LiAlH 4 in anhydrous THF cooled to 0 ° C, 1.2 equivalents of AlCl 3 was added. The temperature was allowed to rise gradually to 20 ° C and stirring was maintained under an argon atmosphere for 1 hour. Subsequently, the resulting suspension was cooled to 0 ° C and a solution of 1 equivalent of [2-methyl-6- (naphthalene-2-sulfonylamino) -3 H -inden-1-yl] acetic acid was added dropwise THF anhydrous. After the addition, stirring was maintained at 0 ° C for 2 hours. The course of the reaction was followed by silica gel column chromatography (CH 2 Cl 2: AcOH 95: 5).

To the reaction mixture was added 37% HCl and water and extracted with CH2Cl2. The organic extracts were washed with a saturated NaCl solution and, after being dried with anhydrous Na2SO4 and filtered, evaporated to dryness. A residue was obtained which was purified by silica gel column chromatography (CH 2 Cl 2: AcOH 95: 5), yielding N - [3- (2-hydroxyethyl) -2-methyl-1 H - inden-5-yl] naphthalene-2-sulfonamide.

Example 10 Synthesis of N - (naphthalen-1-yl) -3- (2-dimethylaminoethyl) -2-methyl-1 H -indene-5-sulfonamide (compound 39) by methods B, C and E

49

On a solution of 1 equivalent of 6-aminoindan-1-one in CH 3 CN cooled to -10 ° C, glacial AcOH, 37% HCl and a solution of 1.2 equivalents of NaNO2 in H2O. The resulting mixture was stirred at the same temperature for 30 minutes SO 2 was bubbled into the reaction mixture for about 20 minutes. Next, a solution of 1.25 was added equivalents of CuCl 2 • 2H 2 O of H 2 O, keeping the temperature at -10 ° C. The temperature of the reaction mixture gradually until reaching 20 ° C and stirred for 16 hours. To the resulting solution was added H2O, was basified with Na2CO3 and extracted with CH 2 Cl 2. The organic extract, after being dried with Anhydrous and filtered Na2SO4 was evaporated to dryness; obtaining an oil that was identified as the chloride of 2-methyl-3-oxoindan-5-sulfonyl

To a solution of 1.1 equivalents of 1-naphthylamine in dry CH2Cl2 and dry pyridine was added, under argon, a solution of 1 equivalent of the above sulfonyl chloride in CH2Cl_ { 2} dry. The reaction mixture was stirred at room temperature for 18 hours. The course of the reaction was followed by silica gel thin layer chromatography (AcOEt: hexane 1: 1). To the reaction mixture was added CH2Cl2 and washed with 2.5N HCl. The organic extract, after being dried with anhydrous Na2SO4 and filtered, was evaporated to dryness. The obtained residue was purified by silica gel column chromatography (CH 2 Cl 2: MeOH, mixtures of increasing polarity), obtaining a compound that was identified by NMR as the N - (naphthalen-1-yl) -2-methyl-3-oxoindane-5-sulfonamide.

To the sufficient amount of anhydrous THF cooled to -78 ° C, 2.1 equivalents of a solution of 1M LHMDS in THF was added under argon. Subsequently, 1.05 equivalents of dry AcOEt was added and stirred at the same temperature for 30 minutes. Finally, an equivalent solution 1 of the above indanone in anhydrous THF was added and stirring was maintained for 1 hour at -78 ° C. The reaction mixture was acidified with 1N HCl, the temperature was allowed to rise gradually to 20 ° C and extracted with AcOEt. The organic extracts, after being dried with anhydrous Na2SO4 and filtered, evaporated to dryness. To a solution of the resulting residue in dry CH 2 Cl 2 cooled to -10 ° C and under argon was added 7 equivalents of TFA and stirred at the same temperature for 30 minutes. The resulting mixture was evaporated to dryness. On the sufficient amount of dry methanol 4 equivalents of sodium metal were added. Once all the sodium had dissolved, the solution was transferred to a suspension of the above residue in dry methanol. The resulting mixture was heated under argon at reflux temperature for 18 hours. The course of the reaction was followed by silica gel thin layer chromatography (hexane: AcOEt: AcOH 50: 45: 5). To the reaction mixture was added EtOH and evaporated to dryness. To the resulting residue was added 5% Na 2 CO 3 and washed with AcOEt. The aqueous solution was acidified with 5N HCl and extracted with AcOEt. The organic extracts, after being dried with anhydrous Na2SO4 and filtered, were evaporated to dryness to obtain a compound that was identified as the acid [2-methyl-6- (naphthalen-1-ylsulfamoyl) -3 H- inden-1-yl] acetic.

A sufficient amount of SOCl2 was added to a solution of 1 equivalent of the above acid in dry CH2Cl2. Then, the reaction mixture was heated at reflux temperature for 2 hours. After cooling the reaction mixture, the excess SOCl2 was evaporated under reduced pressure. On a solution cooled to 0 ° C of the residue obtained in dry CH 2 Cl 2, 2.5 equivalents of HNMe 2 was added and stirred at room temperature, under argon, for 18 hours. The course of the reaction was followed by silica gel thin layer chromatography (CH 2 Cl 2: MeOH 9: 1). H 2 O was added to the reaction mixture, acidified with 5N HCl and extracted with AcOEt. The organic extracts, after being dried with anhydrous Na2SO4 and filtered, evaporated to dryness. The residue obtained was purified by silica gel column chromatography (CH 2 Cl 2: MeOH, mixtures of increasing polarity), to provide a solid that was identified as the N, N- dimethyl-2- [2] amide. -methyl-6- (naphthalen-1-ylsulfamoyl) -3 H -inden-1-yl] acetamide.

On the sufficient amount of anhydrous THF cooled to 0 ° C, 2 equivalents of a 0.5M AlH 3 -DMEA solution in toluene was added. Next, a solution, previously cooled to 0 ° C, of 1 equivalent of the above amide in anhydrous THF was added. Stirring was maintained under argon at 0 ° C for 30 minutes. The course of the reaction was followed by silica gel thin layer chromatography (CH2Cl2 / NH3 gas: MeOH 95: 5). Water and 10% H 2 SO 4 were added to the reaction mixture and the temperature was allowed to gradually rise to 20 ° C. It was made alkaline with 20% NH 3 and extracted with AcOEt. The organic extracts, after being dried with anhydrous Na2SO4 and filtered, evaporated to dryness. The residue obtained was purified by silica gel column chromatography (CH2Cl2 / NH3 gas: MeOH, mixtures of increasing polarity), yielding N- (naphthalen-1-yl) -3- (2-dimethylaminoethyl) -2-methyl-1 H -indene-5-sulfonamide.

Example 11 Synthesis of [3 ( Z ) -benzylidene-2-methyl-6- (naphthalen-2-sulfonylamino) -3 H -inden-1-yl] acetic acid (compound 3) by method J

fifty

On a suspension of 6 equivalents of NaH in anhydrous THF cooled to 0 ° C, a solution of 1 equivalent of [2-methyl-6- (naphthalene-2-sulfonylamino) -3 H -inden-1 acid was added under argon -yl] acetic acid in anhydrous THF and stirred at room temperature for one hour. Subsequently, a solution of 5 equivalents of benzaldehyde in anhydrous THF was added. After the addition, the resulting mixture was heated at reflux temperature for 5 hours. The course of the reaction was followed by silica gel thin layer chromatography (hexane: AcOEt: AcOH 50: 45: 5).

EtOH was added to the reaction mixture and evaporated to dryness. To the resulting residue was added a saturated NaCl solution and washed with CH2Cl2. The aqueous solution was acidified with 5N HCl and extracted with CH2Cl2. The organic extracts, after being dried with anhydrous Na2SO4 and filtered, evaporated to dryness; obtaining a residue that was purified by silica gel column chromatography (hexane: AcOEt 1: 1 and AcOEt). A solid was obtained which was identified as [3 ( Z ) -benzylidene-2-methyl-6- (naphthalene-2-sulfonylamino) -3 H -inden-1-yl] acetic acid.

The melting point, as well as the data of spectroscopy of any of the compounds of general formula I prepared according to the examples are shown in the following table:

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51

52

53

54

55

56

57

58

59

60

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Also, the following table shows some of the intermediates of general formula (II) used of in accordance with the procedures described here to obtain the compounds of general formula (I), together with their data physicochemical:

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61

62

63

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5-HT6 receptor binding assay

HEK-293 cell membranes expressing the 5HT6 recombinant human receptor were supplied by Receptor Biology. In these membranes the concentration of receptor is 2.18 pmol / mg protein and the concentration of protein is 9.17 mg / ml. The experimental protocol follows the method of BL Roth et al [BL Roth, SC Craigo, MS Choudhary, A. Uluer, FJ Monsma, Y. Shen, HY Meltzer, DR Sibley: Binding of Typical and Atypical Antipsychotic Agents to 5-Hydroxytryptamine- 6 and Hydroxytriptamine-7 Receptors. The Journal of Pharmacology and Experimental Therapeutics , 1994 , 268 , 1403] with slight modifications. The commercial membrane is diluted (dilution 1:40) with the binding buffer: 50 mM Tris-HCl, 10 mM MgCl2 0.5 mM EDTA (pH 7.4). The radioligand used is [3 H] -LSD at a concentration of 2.7 nM, the final volume being 200 µl. Incubation is initiated by the addition of 100 µl of the membrane suspension, (2222.9 µg membrane protein), and is prolonged for 60 minutes at a temperature of 37 ° C. The incubation is terminated by rapid filtration in a Harvester Brandel Cell through Schleicher & Schuell GF 3362 brand fiberglass filters pretreated with a 0.5% polyethylenimine solution. The filters are washed three times with three milliliters of 50 mM Tris-HCl buffer pH 7.4. The filters are transferred to vials and 5 ml of Ecoscint H liquid scintillation cocktail is added to each vial. The vials are allowed to equilibrate for several hours before being counted in a Wallac Winspectral 1414 scintillation counter. The non-specific binding is determined in the presence of 100 µM serotonin. The tests are carried out in triplicate. Inhibition constants (Ki, nM) are calculated by nonlinear regression analysis using the EBDA / LIGAND program [Munson and Rodbard, Analytical Biochemistry , 1980 , 107 , 220]. Binding results for some of the compounds object of the present invention are indicated in the following Table.

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Example % Inhibition % Inhibition % Inhibition K, (nM) 10-6 M 10-7 M 10-8 M 19 97 - - - - 4.8 twenty - - 42 13 - - 29 82 53 32 63 26 33 - - - - 216.5 3. 4 100 71 18 50.6 35 92 - - - - 62.9 36 72 - - - - 157.5 37 92 - - - - 46.3 38 100 - - - - 20.2 39 - - 51 25 - - 40 Four. Five 16 8 - -

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Pharmaceutical formulation

The daily dosage in human medicine is between 1 milligram and 500 milligrams of product that It can be administered in one or several doses. The compositions are prepared under forms compatible with the route of administration used, such as tablets, dragees, capsules, suppositories, solutions or suspensions. These compositions are prepared by known methods and comprise from 1 to 60% in weight of the active substance (compound of general formula I) and 40 a 99% by weight of appropriate pharmaceutical vehicle and compatible with the active substance and the physical form of the composition used. TO example title is presented the formula of a tablet that It contains a product of the invention.

Formula example by compressed: Example 19 5 mg Lactose 60 mg Crystalline cellulose 25 mg Povidone K 90 5 mg Pregelatinized starch 3 mg Colloidal Silica Dioxide one mg Magnesium stearate one mg Total weight per tablet 100 mg

Claims (57)

1. An indene derived from general formula I:

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64

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where n is 0, 1, 2, 3 or 4 R 1 represents a saturated or unsaturated cycloaliphatic radical, optionally at least monosubstituted, optionally at least with a heteroatom selected from N, O and S as a member of the ring that may be condensed with an optionally at least monosubstituted mono or polycyclic ring system ; a radical -NR 8 R 9; a radical
-CONR 8 R 9; -COOH; or -OH

where

R 8 and R 9 represent, independently of one another, an atom of hydrogen; or a linear C 1-5 aliphatic radical or branched, saturated or unsaturated, which may be substituted with 1, 2, 3 substituents independently selected from F, Cl, Br, -OH, -NH2, -SH, -O-CH3, -O-C 2 H 5, -NO 2, -CN, -NH-CH 3 and -S-CH 3;

or

R 8 and R 9 together with the nitrogen form a ring 3 to 9-membered saturated, unsaturated or aromatic heterocyclic, which may be substituted with 1, 2 or 3 substituents selected independently between C_ {1-5} -alkyl, -O-C_ {1-5} -alkyl, -S-C_ {1-5} -alkyl, oxo (= O), thioxo (= S), -C (= O) -OH, -C (= O) -O-C_ {1-5} -alkyl, -O-C (= O) -C_ {1-5} -alkyl, F, Cl, Br, I, -CN, -CF 3, -OCF 3, -SCF 3, -OH, -SH, -NH2, -NH (C_ {1-5} -alkyl), -N (C 1-5 -alkyl) 2, -NO2, -CHO, -CF2H, -CFH2, -C (= O) -NH2, -C (= O) -NH (C_ {1-5} -alkyl), -C (= O) -N (C_ {1-5} -al- quil) 2, -S (= O) 2 -C_ 1-5 -alkyl, -S (= O) 2 -phenyl and which may contain 1, 2 or 3 additional heteroatoms independently selected between N, O and S as ring members

R 2, R 3, R 4 and R 5 represent, independently of each other, a hydrogen atom; -NO2; -NH2; -SH; -OH;
-CN; -C (= O) -H; -C (= O) -R 10; -OR 11; -SR 12; -SOR 13, -S (= O) 2 -R 13, -S (= O) 2 -N (R 14) R 15, - N (R 16) - S (= O) 2 -R 17; -NH-R 18; -NR 19 R 20; -N (R 21) - CO-R 22; F; Cl, Br; I; a linear or branched, saturated or unsaturated C 1 -C 6 aliphatic radical, which may be substituted by 1, 2 or 3 substituents independently selected from F, Cl, Br, -OH, -NH 2, - SH, -O-CH 3, -O-C 2 H 5, -NO 2, -CN, -NH-CH 3 and -S-CH 3; or a 5-14 membered aryl or heteroaryl radical, which may be substituted with 1, 2 or 3 substituents independently selected from -CF 3, C 1-5, alkyl, -O-C 1-5 -alkyl, -S-C_ {1-5} -alkyl, -C (= O) -OH, -C (= O) -O-C_ {1-5} -alkyl, -OC (= O) -C_ {1-5} -alkyl, F, Cl, Br, I, -CN, -OCF 3, -SCF 3, -OH, -SH, -NH 2, -NH (C 1- { 5} -alkyl), -N (C 1-5 -alkyl) 2, -NH-C (= O) -C_ {1-5} -alkyl, -N (C_ 1-5) -alkyl) -C (= O) -C_ {1-5} -alkyl, -NO_ {2}, -CHO, -CF2H, -CFH_2, -C (= O) -NH_ { 2}, -C (= O) -NH (C_1-5 -alkyl), -C (= O) -N (C_1-5 -alkyl) 2, -S (= O ) 2 -C 1-5 -alkyl, -S (= O) 2 -phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, phenoxy, benzyloxy and benzyl and which may be attached through of a C 1 -C 6 linear or branched alkylene group and wherein the heteroaryl radical contains 1, 2 or 3 heteroatoms independently selected from N, O and S as ring members; with the proviso that at least one of the substituents R 2, R 3, R 4 and R 5 represent a radical -NO 2, -SOR 13, -S (= O) 2 -R 13, -S (= O) 2 -N (R 14) R 15, -N (R 16) - S (= O) 2 -R 17, -N (R 21) - CO-R 22;

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A represents: 65 which means respectively type compounds (Ix) and (Iy): 66 R 6 and R '6, identical or different, represent a hydrogen atom; NO2; -NH2; -SH; -OH; -CN; -C (= O) -R 10; -OR 11; -SR 12; F; Cl, Br; I; a linear or branched C 1 -C 10 aliphatic radical, saturated or unsaturated, which may be substituted by 1, 2 or 3 substituents independently selected from F, Cl, Br, -OH, -SH, -O-CH_ {3}, -O-C2H5, -NO2, -CN and -S-CH3; or a 5-14 membered aryl or heteroaryl radical, which may be substituted by 1, 2 or 3 substituents independently selected from -CF 3, C 1-5, alkyl, -O-C 1-5 -alkyl, -S-C_ {1-5} -alkyl, -C (= O) -OH, -C (= O) -O-C_ {1-5} -alkyl, -OC (= O) -C_ {1-5} -alkyl, F, Cl, Br, I, -CN, -OCF 3, -SCF 3, -OH, -SH, -NH 2, -NH (C 1- { 5} -alkyl), -N (C_ {1-5} -
alkyl) 2, -NH-C (= O) -C_ {1-5} -alkyl, -N (C_ {1-5} -alkyl) -C (= O) -C_ {1-5} -alkyl, -NO_ {2}, -CHO, -CF_2H, -CFH_2, -C (= O) -NH_2, -C (= O) -NH (C_ {1- { 5-alkyl), -C (= O) -N (C 1-5 -alkyl) 2, -S (= O) 2 -C 1-5 -alkyl, - S (= O) 2 -phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, phenoxy, benzyloxy and benzyl and which may be linked through a C 1 -C 6 alkylene group, C_ { 2} -C 6 alkenylene or C 1 -C 6 ylidene linear or branched and where the heteroaryl radical contains 1, 2 or 3 heteroatoms independently selected from N, O and S as ring members; R 7 represents a hydrogen atom; a C 1 -C 6 linear aliphatic radical or branched that may be substituted by 1, 2 or 3 substituents independently selected from F, Cl, Br, -OH, -SH, -O-CH 3, -O-C 2 H 5, -NO 2, -CN and -S-CH 3; R 10 to R 22 represent, independently of one another, a hydrogen atom; a linear or branched, saturated or unsaturated C 1 -C 5 aliphatic radical, which may be substituted with 1, 2 or 3 substituents independently selected from F, Cl, Br, -OH, -NH 2, - SH, -O-CH 3, -O-C 2 H 5, -NO 2, -CN, -NH-CH 3 and -S-CH 3; a saturated or unsaturated 3 to 8 membered cycloaliphatic radical, which may be substituted with 1, 2 or 3 substituents independently selected from C 1-5, alkyl, -O-C 1-5, alkyl, -S- C_ {1-5} -alkyl, oxo (= O), thioxo (= S), -C (= O) -OH, -C (= O) -O-C_ {1-5} -alkyl, -OC (= O) -C_ {1-5} -alkyl, F, Cl, Br, I, -CN, -CF_ {3}, -OCF_ {3}, -SCF_3, -OH, -SH, - NH 2, -NH (C 1-5 -alkyl), -N (C 1-5 -alkyl) 2,
-NO_ {2}, -CHO, -CF_2H, -CFH_2, -C (= O) -NH_ {2}, -C (= O) -NH (C_ {1-5} - alkyl), -C (= O) -N (C 1-5 -alkyl) 2, -S (= O) 2 -C_ {1-5} -alkyl, -S (= O) 2 -phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, phenoxy, benzyloxy and benzyl and which may optionally contain 1, 2 or 3 heteroatoms independently selected from N, O and S as ring members and which may be linked through a linear or branched C 1 -C 6 alkylene group; or a 5 to 14 membered arito or heteroaryl radical that may be substituted with 1, 2 or 3 substituents independently selected from -CF 3, C 1-5, alkyl, -O-C 1-5 alkyl, -S-C_ 1-5 -alkyl, -C (= O) -OH, -C (= O) -O-C_ {1-5} -alkyl, -OC (= O) -C_ { 1-5} -alkyl, F, Cl, Br, I, -CN, -OCF 3, -SCF 3, -OH, -SH, -NH 2, -NH (C_ {1-5 -alkyl), -N (C 1-5 -alkyl) 2, -NH-C (= O) -C_ {1-5} -alkyl, -N (C_ {1-5} - alkyl) -C (= O) -C_ {1-5} -alkyl, -NO2, -CHO, -CF2H, -CFH2, -C (= O) -NH_ {2 }, -C (= O) -NH (C_ {1-5} -alkyl), -C (= O) -N (C_ {1-5} -alkyl) 2, -S (= O) 2 -C 1-5 -alkyl, -S (= O) 2 -phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, phenoxy, benzyloxy and benzyl and which may be linked through a C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 2 -C 6 alkynylene group linear and branched and wherein the heteroaryl radical contains 1, 2 or 3 heteroatoms independently selected from N, O and S as ring members; with the proviso that when R1 is -COOH; R2, R3, R4 or R5 are not -SOR13 -S (= O) 2 -R 13 or -S (= O) 2 -N (R 14) R 15 and A does not represent C = C (R6) R_ {6} 'given the situation joint in which R6 or R6 'are one H and the other a phenyl replaced by -S (= O) 2 -C_ 1-5 -alkyl,  -NH2, -O-C_ {1-5} -alkyl, F, Cl, Br, CN, -C (= O) -OH or -C (= O) -O-C_ {1-5} -alkyl, or the situation in which both R6 and R_ {6} 'represent -OR 11, and with the proviso that when R * {1} is -OH; R2, R3, R4 or R5 are not -S (= O) 2 -R 13 or -S (= O) 2 -N (R 14) R 15, Y with the proviso that when R1 is -CONR 8 R 9; R2, R3, R4 or R5 are not -SOR 13, -S (= O) 2 -R 13 or -S (= O) 2 -N (R 14) R 15 and A does not represent C = C (R6) R_ {6} 'given the situation joint in which R6 or R6 'are one H and the other a phenyl replaced by -S (= O) 2 -C_ 1-5 -alkyl,  -NH2, -O-C_ {1-5} -alkyl, F, Cl, Br, I, CN, -C (= O) -OH or -C (= O) -O-C_ {1-5} -alkyl, an aryl or a heteroaryl, and with the proviso that when R1 is -NR 8 R 9; R2, R3, R4 or R5 are not -SOR 13 or -S (= O) 2 -R 13 and A no represent C = C (R6) R_ {6} 'giving the joint situation in that R6 or R6 'are one H and the other a phenyl substituted by -S (= O) 2 -C_ 1-5 -alkyl, -NH2, -O-C_ {1-5} -alkyl,  F, Cl, Br, CN, -C (= O) -OH or -C (= O) -O-C_ {1-5} -alkyl or a pharmaceutically acceptable salt, a isomer, a prodrug or a solvate thereof, optionally in the form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and / or diasteromers, in any mixing ratio or a physiologically acceptable salt of same or the corresponding solvate thereof. 2. An indene derived from general formula I: 67 where n is 0, 1, 2, 3 or 4 R 1 represents a saturated or unsaturated cycloaliphatic radical, optionally at least monosubstituted, optionally at least with a heteroatom selected from N, O and S as a member of the ring that may be condensed with an optionally at least monosubstituted mono or polycyclic ring system ; a radical -NR 8 R 9; a radical
-CONR 8 R 9; -COOH; or -OH

where

R 8 and R 9 represent, independently of one another, an atom of hydrogen; or a linear C 1-5 aliphatic radical or branched, saturated or unsaturated, which may be substituted with 1, 2, 3 substituents independently selected from F, Cl, Br, -OH, -NH2, -SH, -O-CH3, -O-C 2 H 5, -NO 2, -CN, -NH-CH 3 and -S-CH 3;

or

R 8 and R 9 together with the nitrogen form a ring 3 to 9-membered saturated, unsaturated or aromatic heterocyclic, which may be substituted with 1, 2 or 3 substituents selected independently between C_ {1-5} -alkyl, alkyl, -S-C_ {1-5} -alkyl, oxo (= O), thioxo (= S), -C (= O) -OH, -C (= O) -O-C_ {1-5} -alkyl, -OR- C (= O) -C_ {1-5} -alkyl, F, Cl, Br, I, -CN, -CF 3, -OCF 3, -SCF 3, -OH, -SH, -NH2, -NH (C- {1-5} -alkyl), -N (C 1-5 -alkyl) 2, -NO2, -CHO, -CF2H, -CFH2, -C (= O) -NH_ {2}, -C (= O) - NH (C 1-5) alkyl, -C (= O) -N (C 1-5 -alkyl) 2, -S (= O) 2 -C_ 1-5 -alkyl, -S (= O) 2 -phenyl and which may contain 1, 2 or 3 additional heteroatoms independently selected between N, O and S as ring members

R 2, R 3, R 4 and R 5 represent, independently of each other, a hydrogen atom; -NO2; -NH2; -SH; -OH;
-CN; -C (= O) -H; -C (= O) -R 10; -OR 11; -SR 12; -SOR 13, -S (= O) 2 -R 13, -S (= O) 2 -N (R 14) R 15, - N (R 16) - S (= O) 2 -R 17; -NH-R 18; -NR 19 R 20; -N (R 21) - CO-R 22; F; Cl, Br; I; a linear or branched, saturated or unsaturated C 1 -C 6 aliphatic radical, which may be substituted by 1, 2 or 3 substituents independently selected from F, Cl, Br, -OH, -NH 2, - SH, -O-CH 3, -O-C 2 H 5, -NO 2, -CN, -NH-CH 3 and -S-CH 3; or a 5-14 membered aryl or heteroaryl radical, which may be substituted with 1, 2 or 3 substituents independently selected from -CF 3, C 1-5, alkyl, -O-C 1-5 -alkyl, -S-C_ {1-5} -alkyl, -C (= O) -OH, -C (= O) -O-C_ {1-5} -alkyl, -OC (= O) -C_ {1-5} -alkyl, F, Cl, Br, I, -CN, -OCF 3, -SCF 3, -OH, -SH, -NH 2, -NH (C 1- { 5} -alkyl), -N (C 1-5 -alkyl) 2, -NH-C (= O) -C_ {1-5} -alkyl, -N (C_ 1-5) -alkyl) -C (= O) -C_ {1-5} -alkyl, -NO_ {2}, -CHO, -CF2H, -CFH_2, -C (= O) -NH_ { 2}, -C (= O) -NH (C_1-5 -alkyl), -C (= O) -N (C_1-5 -alkyl) 2, -S (= O ) 2 -C 1-5 -alkyl, -S (= O) 2 -phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, phenoxy, benzyloxy and benzyl and which may be attached through of a C 1 -C 6 linear or branched alkylene group and wherein the heteroaryl radical contains 1, 2 or 3 heteroatoms independently selected from N, O and S as ring members; with the proviso that at least one of the substituents R 2, R 3, R 4 and R 5 represent a radical -SOR 13, -S (= O) 2 -R 13, -S (= O) 2 -N (R 14) R 15, -N (R 16) - S (= O) 2 -R 17, -N (R 21) - CO-R 22 A represents: 68 which means respectively type compounds (Ix) and (Iy): 69 R 6 and R '6, identical or different, represent a hydrogen atom; NO2; -NH2; -SH; -OH; -CN; -C (= O) -R 10; -OR 11; -SR 12; F; Cl, Br; I; a linear or branched C 1 -C 10 aliphatic radical, saturated or unsaturated, which may be substituted by 1, 2 or 3 substituents independently selected from F, Cl, Br, -OH, -SH, -O-CH_ {3}, -O-C2H5, -NO2, -CN and -S-CH3; or a 5-14 membered aryl or heteroaryl radical, which may be substituted by 1, 2 or 3 substituents independently selected from -CF 3, C 1-5, alkyl, -O-C 1-5 -alkyl, -S-C_ {1-5} -alkyl, -C (= O) -OH, -C (= O) -O-C_ {1-5} -alkyl, -OC (= O) -C_ {1-5} -alkyl, F, Cl, Br, I, -CN, -OCF 3, -SCF 3, -OH, -SH, -NH 2, -NH (C 1- { 5-alkyl), -N (C 1-5 -alkyl) 2,
-NH-C (= O) -C_ {1-5} -alkyl, -N (C_ {1-5} -alkyl) -C (= O) -C_ {1-5} -alkyl, -NO_ {2 }, -CHO, -CF2H, -CFH2, -C (= O) -NH2, -C (= O) -NH
(C_ {1-5} -alkyl), -C (= O) -N (C_ {1-5} -alkyl) 2, -S (= O) 2 -C_ {1-5 -alkyl, -S (= O) 2 -phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, phenoxy, benzyloxy and benzyl and which may be linked through a C 1 -C 6 group alkylene, C 2 -C 6 alkenylene or C 1 -C 6 linear or branched ilidene and where the heteroaryl radical contains 1, 2 or 3 heteroatoms independently selected from N, O and S as members of the ring; R 7 represents a hydrogen atom; a C 1 -C 6 linear or aliphatic radical branched that may be substituted by 1, 2 or 3 substituents independently selected from F, Cl, Br, -OH, -SH, -O-CH 3, -O-C 2 H 5, -NO 2, -CN and -S-CH 3; R 10 to R 22 represent, independently of one another, a hydrogen atom; a linear or branched, saturated or unsaturated C1-05 aliphatic radical, which may be substituted with 1, 2 or 3 substituents independently selected from F, Cl, Br, -OH, -NH2, -SH, -O-CH_ {3}, -O-C2H5, -NO2, -CN, -NH-CH3 and -S-CH3; a saturated or unsaturated 3 to 8 membered cycloaliphatic radical, which may be substituted with 1, 2 or 3 substituents independently selected from C 1-5 -alkyl, -O-C 1-5 -alkyl, 5-alkyl , oxo (= O), thioxo (= S), -C (= O) -OH, -C (= O) -O-C_ {1-5} -alkyl, -OC (= O) -C_ {1 -5} -alkyl, F, Cl, Br, I, -CN, -CF 3, -OCF 3, -SCF 3, -OH, -SH, -NH 2, -NH ( C 1-5 alkyl, -N (C 1-5 alkyl) 2,
-NO_ {2}, -CHO, -CF_2H, -CFH_2, -C (= O) -NH_ {2}, -C (= O) -NH (C_ {1-5} - alkyl), -C (= O) -N (C 1-5 -alkyl) 2, -S (= O) 2 -C_15 -alkyl,
-S (= O) 2 -phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, phenoxy, benzyloxy and benzyl and which may optionally contain 1, 2 or 3 heteroatoms independently selected from N, O and S as members of the ring and which may be linked through a linear or branched C 1 -C 6 alkylene group; or a 5 to 14-membered aryl or heteroaryl radical that may be substituted with 1, 2 or 3 substituents independently selected from -CF 3, C 1-5, alkyl, -O-C 1-5 alkyl, -S-C_ 1-5 -alkyl, -C (= O) -OH, -C (= O) -O-C_ {1-5} -alkyl, -OC (= O) -C_ { 1-5} -alkyl, F, Cl, Br, I, -CN,
-OCF 3, -SCF 3, -OH, -SH, -NH 2, -NH (C 1-5, alkyl), -N (C 1-5, alkyl) {2}, -NH-C (= O) -C_ {1-5} -alkyl, -N (C_ {1-5} -alkyl) -C (= O) -C_ {1-5} -alkyl, -NO_ {2}, -CHO, -CF_2H, -CFH_2, -C (= O) -NH_ {2}, -C (= O) -NH (C_ {1-5} - alkyl), -C (= O) -N (C 1-5 -alkyl) 2, -S (= O) 2 -C_ {1-5} -alkyl, -S (= O) 2 -phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, phenoxy, benzyloxy and benzyl and which may be linked through a C 1 -C 6 alkylene, C 2 - group C 6 alkenylene or C 2 -C 6 linear or branched alkynylene and where the heteroaryl radical contains 1, 2 or 3 heteroatoms independently selected from N, O and S as ring members; with the proviso that when R1 is -COOH; R2, R3, R4 or R5 are not -SOR13, -S (= O) 2 -R 13 or -S (= O) 2 -N (R 14) R 15 and A does not represent C = C (R6) R_ {6} 'given the situation joint in which R6 or R6 'are one H and the other a phenyl substituted by alkyl, -NH2, -O-C_ {1-5} -alkyl, F, Cl, Br, CN, -C (= O) -OH or -C (= O) -O-C_ {1-5} -alkyl, or the situation in which both R6 and R_ {6} 'represent -OR 11, and with the proviso that when R1 is -OH; R2, R3, R4 or R5 are not -S (= O) 2 -R 13 or -S (= O) 2 -N (R 14) R 15, Y with the proviso that when R1 is -CONR 8 R 9; R2, R3, R4 or R5 are not -SOR 13, -S (= O) 2 -R 13 or -S (= O) 2 -N (R 14) R 15 and A does not represent C = C (R6) R_ {6} 'given the situation joint in which R6 or R6 'are one H and the other a phenyl replaced by -S (= O) 2 -C_ 1-5 -alkyl, -NH2, -O-C_ {1-5} -alkyl, F, Cl, Br, I, CN, -C (= O) -OH or -C (= O) -O-C_ {1-5} -alkyl, an aryl or a heteroaryl, and with the proviso that when R1 is -NR 8 R 9; R2, R3, R4 or R5 are not -SOR 13 or -S (= O) 2 -R 13 and A no represent C = C (R6) R_ {6} 'giving the joint situation in that R6 or R6 'are one H and the other a phenyl substituted by -S (= O) 2 -C_ 1-5 -alkyl, -NH2, -O-C_ {1-5} -alkyl,  F, Cl, Br, CN, -C (= O) -OH or -C (= O) -O-C_ {1-5} -alkyl or a pharmaceutically acceptable salt, a isomer, a prodrug or a solvate thereof, optionally in the form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and / or diasteromers, in any mixing ratio or a physiologically acceptable salt of same or the corresponding solvate thereof. 3. An indene derived from the general formula (I): 70 where n is 0, 1, 2, 3 or 4 R 1 represents a saturated or unsaturated cycloaliphatic radical, optionally at least monosubstituted, optionally at least with a heteroatom selected from N, O and S as a member of the ring that may be condensed with an optionally at least monosubstituted mono or polycyclic ring system ; a radical -NR 8 R 9; a radical
-CONR 8 R 9; -COOH; or -OH

where

R 8 and R 9 represent, independently of one another, an atom of hydrogen; or a linear C 1-5 aliphatic radical or branched, saturated or unsaturated, which may be substituted with 1, 2, 3 substituents independently selected from F, Cl, Br, -OH, -NH2, -SH, -O-CH3, -O-C 2 H 5, -NO 2, -CN, -NH-CH 3 and -S-CH 3;

or

R 8 and R 9 together with the nitrogen form a ring 3 to 9 membered heterocyclic saturated, unsaturated or aromatic, which may be substituted with 1, 2 or 3 substituents selected independently between C_ {1-5} -alkyl, -O-C_ {1-5} - alkyl, -S-C_ {1-5} -alkyl, oxo (= O), thioxo (= S), -C (= O) -OH, -C (= O) -O-C_ {1-5} -alkyl, -OR- C (= O) -C_ {1-5} -alkyl, F, Cl, Br, I, -CN, -CF 3, -OCF 3, -SCF 3, -OH, -SH, -NH2, -NH (C_ {1-5} -alkyl), -N (C 1-5 -alkyl) 2, -NO2, -CHO, -CF2H, -CFH2, -C (= O) -NH_ {2}, -C (= O) - NH (C 1-5) alkyl, -C (= O) -N (C 1-5 -alkyl) 2, -S (= O) 2 -C_ 1-5 -alkyl, -S (= O) 2 -phenyl and which may contain 1, 2 or 3 additional heteroatoms independently selected between N, O and S as ring members

R 2, R 3, R 4 and R 5 represent, independently of each other, a hydrogen atom; -NO2; -NH2; -SH; -OH;
-CN; -C (= O) -H; -C (= O) -R 10; -OR 11; -SR 12; -SOR 13, -S (= O) 2 -R 13, -S (= O) 2 -N (R 14) R 15, - N (R 16) - S (= O) 2 -R 17; -NH-R 16; -NR 19 R 20; -N (R 21) - CO-R 22; F; Cl, Br; I; a linear or branched, saturated or unsaturated C 1 -C 6 aliphatic radical, which may be substituted by 1, 2 or 3 substituents independently selected from F, Cl, Br, -OH, -NH 2, - SH, -O-CH 3, -O-C 2 H 5, -NO 2, -CN, -NH-CH 3 and -S-CH 3; or a 5-14 membered aryl or heteroaryl radical, which may be substituted with 1, 2 or 3 substituents independently selected from -CF 3, C 1-5, alkyl, -O-C 1-5 -alkyl, -S-C_ {1-5} -alkyl, -C (= O) -OH, -C (= O) -O-C_ {1-5} -alkyl, -OC (= O) -C_ {1-5} -alkyl, F, Cl, Br, I, -CN, -OCF3, -SCF3, -OH, -SH, -NH2,
-NH (C_ 1-5 -alkyl), -N (C_ {1-5} -alkyl) 2, -NH-C (= O) -C_ {1-5} -alkyl, -N (C_ {1-5} -alkyl) -C (= O) -C_ {1-5} -alkyl, -NO2, -CHO, -CF2H,
-CFH_ {2}, -C (= O) -NH_ {2}, -C (= O) -NH (C_ {1-5} -alkyl), -C (= O) -N (C_ {1-} 5-alkyl) 2, -S (= O) 2 -C 1-5 -alkyl, -S (= O) 2 -phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl , phenyl, phenoxy, benzyloxy and benzyl and which may be linked through a linear or branched C 1 -C 6 alkylene group and where the heteroaryl radical contains 1, 2 or 3 heteroatoms independently selected from N, O and S as members of the ring; with the proviso that at least one of the substituents R 2, R 3, R 4 and R 5 represent a radical –NO_ {2} A represents: 71 which means respectively type compounds (Ix) and (Iy): 72 R 6 and R '6, identical or different, represent a hydrogen atom; NO2; -NH2; -SH; -OH; -CN; -C (= O) -R 10; -OR 11; -SR 12; F; Cl, Br; I; a linear or branched C 1 -C 10 aliphatic radical, saturated or unsaturated, which may be substituted by 1, 2 or 3 substituents independently selected from F, Cl, Br, -OH, -SH, -O-CH_ {3}, -O-C2H5, -NO2, -CN and -S-CH3; or a 5-14 membered aryl or heteroaryl radical, which may be substituted by 1, 2 or 3 substituents independently selected from -CF 3, C 1-5, alkyl, -O-C 1-5 -alkyl, -S-C_ {1-5} -alkyl, -C (= O) -OH, -C (= O) -O-C_ {1-5} -alkyl, -OC (= O) -C_ {1-5} -alkyl, F, Cl, Br, I, -CN, -OCF 3, -SCF 3, -OH, -SH, -NH 2, -NH (C 1- { 5-alkyl), -N (C 1-5 -alkyl) 2,
-NH-C (= O) -C_ {1-5} -alkyl, -N (C_ {1-5} -alkyl) -C (= O) -C_ {1-5} -alkyl, -NO_ {2 }, -CHO, -CF2H, -CFH2, -C (= O) -NH2, -C (= O) -NH
(C_ {1-5} -alkyl), -C (= O) -N (C_ {1-5} -alkyl) 2, -S (= O) 2 -C_ {1-5 -alkyl, -S (= O) 2 -phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, phenoxy, benzyloxy and benzyl and which may be linked through a C 1 -C 6 group alkylene, C 2 -C 6 alkenylene or C 1 -C 6 linear or branched ilidene and where the heteroaryl radical contains 1, 2 or 3 heteroatoms independently selected from N, O and S as members of the ring; R 7 represents a hydrogen atom; a C 1 -C 6 linear aliphatic radical or branched that may be substituted by 1, 2 or 3 substituents independently selected from F, Cl, Br, -OH, -SH, -O-CH 3, -O-C 2 H 5, -NO 2, -CN and -S-CH 3; R 10 to R 22 represent, independently of each other, a hydrogen atom; a radical linear or branched C 1 -C 5 aliphatic, saturated or unsaturated, which may be substituted with 1, 2 or 3 substituents independently selected from F, Cl, Br, -OH,  -NH 2, -SH, -O-CH 3, -O-C 2 H 5, -NO 2, -CN, -NH-CH 3 and -S-CH 3; a cycloaliphatic radical of 3 to 8 members saturated or unsaturated, which may be substituted with 1, 2 or 3 substituents independently selected from C_ {1-5} -alkyl, -O-C_ {1-5} -alkyl, 5-alkyl, oxo (= O), thioxo (= S), -C (= O) -OH, -C (= O) -O-C_ {1-5} -alkyl, -O-C (= O) -C_ {1-5} -alkyl, F, Cl, Br, I, -CN, -CF 3, -OCF 3, -SCF 3, -OH, -SH, -NH2, -NH (C_ {1-5} -alkyl), -N (C 1-5 -alkyl) 2,  -NO2, -CHO, -CF2H, -CFH2, -C (= O) -NH2, -C (= O) -NH (C_ {1-5} -alkyl), -C (= O) -N (C 1-5 -alkyl) 2, -S (= O) 2 -C_ 1-5 -alkyl, -S (= O) 2 -phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, phenoxy, benzyloxy and benzyl and that optionally it can contain 1, 2 or 3 heteroatoms independently selected from N, O and S as members of the ring and that can be linked through a group C 1 -C 6 linear or branched alkylene; or a 5 to 14 membered arito or heteroaryl radical that may be substituted with 1, 2 or 3 substituents independently selected from -CF_ {3}, C_ {1-5} -alkyl, alkyl, -S-C_ {1-5} -alkyl, -C (= O) -OH, -C (= O) -O-C_ {1-5} -alkyl, -O-C (= O) -C_ {1-5} -alkyl, F, Cl, Br, I, -CN, -OCF 3, -SCF 3, -OH, -SH, -NH 2, -NH (C_ {1-5} -alkyl), -N (C 1-5 -alkyl) 2, -NH-C (= O) -C_ {1-5} -alkyl, -N (C_ {1-5} -alkyl) -C (= O) -C_ {1-5} -alkyl, -NO2, -CHO, -CF2H, -CFH2, -C (= O) -NH2, -C (= O) -NH (C_ {1-5} -alkyl), -C (= O) -N (C 1-5 -alkyl) 2, -S (= O) 2 -C_ 1-5 -alkyl, -S (= O) 2 -phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, phenoxy, benzyloxy and benzyl and that can be united through a group C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C_ {2} -C_ {6} linear or branched alkynylene and where the heteroaryl radical contains 1, 2 or 3 heteroatoms independently selected from N, O and S as members of the ring; with the proviso that when R1 is -COOH; R2, R3, R4 or R5 are not -SOR13, -S (= O) 2 -R 13 or -S (= O) 2 -N (R 14) R 15 and A does not represent C = C (R6) R_ {6} 'given the situation joint in which R6 or R6 'are one H and the other a phenyl replaced by -S (= O) 2 -C_ 1-5 -alkyl,  -NH2, -O-C_ {1-5} -alkyl, F, Cl, Br, CN, -C (= O) -OH or -C (= O) -O-C_ {1-5} -alkyl, or the situation in which both R6 and R_ {6} 'represent -OR 11, and with the proviso that when R1 is -OH; R2, R3, R4 or R5 are not -S (= O) 2 -R 13 or -S (= O) 2 -N (R 14) R 15, Y with the proviso that when R1 is -CONR 8 R 9; R2, R3, R4 or R5 are not -SOR 13, -S (= O) 2 -R 13 or -S (= O) 2 -N (R 14) R 15 and A does not represent C = C (R6) R_ {6} 'given the situation joint in which R6 or R6 'are one H and the other a phenyl replaced by -S (= O) 2 -C_ 1-5 -alkyl,  -NH2, -O-C_ {1-5} -alkyl, F, Cl, Br, I, CN, -C (= O) -OH or -C (= O) -O-C_ {1-5} -alkyl, an aryl or a heteroaryl, and with the proviso that when R1 is -NR 8 R 9; R2, R3, R4 or R5 are not -SOR 13 or -S (= O) 2 -R 13 and A no represent C = C (R6) R_ {6} 'giving the joint situation in that R6 or R6 'are one H and the other a phenyl substituted by -S (= O) 2 -C_ 1-5 -alkyl, -NH2, -O-C_ {1-5} -alkyl,  F, Cl, Br, CN, -C (= O) -OH or -C (= O) -O-C_ {1-5} -alkyl or a pharmaceutically acceptable salt, a isomer, a prodrug or a solvate thereof, optionally in the form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and / or diasteromers, in any mixing ratio or a physiologically acceptable salt of same or the corresponding solvate thereof. 4. An indene derived from general formula I of according to any one of claims 1 to 3 wherein R 1 represents a radical -NR 8 R 9; and R 8 and R 9 together with nitrogen they form a heterocyclic ring of 3 to 9 members saturated, unsaturated or aromatic that optionally contains 1, 2 or 3 additional heteroatoms independently selected from N, O and S. 5. An indene derived from general formula I of according to any of claims 1 to 3 wherein R 1 represents a radical -NR 8 R 9; and R 8 and R 9 independently or jointly represent a hydrogen atom or a C 1-5 aliphatic radical. 6. An indene derived from general formula I of according to any one of claims 1 to 3 wherein R 1 It represents: 73 74 where the dotted line represents an optional chemical bond and R '1 represents an atom of hydrogen, an aliphatic radical C_ {1-5}. 7. An indene derived from general formula I of according to any one of claims 1 to 3 wherein R 1 represents a radical -CONR 8 R 9; and R 8 and R 9 independently or jointly represent a hydrogen atom or a C 1-5 aliphatic radical. 8. An indene derived from general formula I of according to any one of claims 1 to 3 wherein R 1 represents a radical -CONR 8 R 9; and R 8 and R 9 together with nitrogen they form a heterocyclic ring of 3 to 9 members saturated, unsaturated or aromatic that optionally contains 1, 2 or 3 additional heteroatoms independently selected from N, O and S. 9. An indene derived from general formula I of according to claims 1 or 2 wherein at least one of R 2, R 3, R 4 and R 5 represents a radical -SOR 13. 10. An indene derived from general formula I of according to claims 1 or 2 wherein at least one of R 2, R 3, R 4 and R 5 represents a radical -S (= O) 2 -R 13. 11. An indene derived from general formula I of according to claims 1 or 2 wherein at least one of R 2, R 3, R 4 and R 5 represents a radical -S (= O) 2 -N (R 14) R 15. 12. An indene derived from general formula I of according to claims 1 or 2 wherein at least one of R 2, R 3, R 4 and R 5 represents a radical -N (R 16) - S (= O) 2 -R 17. 13. An indene derived from general formula I of according to claims 1 or 2 wherein at least one of R 2, R 3, R 4 and R 5 represents a radical -N (R 21) - CO-R 22. 14. An indene derived from general formula I of according to any one of claims 1 to 3 wherein R 6 and R '6, identical or different, represent an atom of hydrogen or a 5-14 membered aryl or heteroaryl radical optionally substituted by a phenyl that may be attached to through a C 1 -C 6 alkylene or a C_ {1} -C_ {6} ilidene. 15. An indene derived from general formula I of according to any one of claims 1 to 3 wherein R 10 to R 22 represent an aryl or heteroaryl radical containing 1, 2 or 3 heteroatoms independently selected from N, O and S and that may be substituted by a Chlorine. 16. An indene derived from general formula I according to claims 1 to 2 wherein preferably
n = 0, 1, 2, 3 or 4; Y R 1 represents a radical -COOH, -OH, -NR 8 R 9 or -CONR 8 R 9 where R 8 and R 9 represent so independent or joint a hydrogen atom or a radical aliphatic C_ {1-5}, or R 8 and R 9 together with the nitrogen forms a 3 to 9 member heterocyclic ring saturated, unsaturated or aromatic that optionally contains 1, 2 or 3  additional heteroatoms independently selected from N, O and S; or R 1 represents one of the following groups: 75

         \ vskip1.000000 \ baselineskip
      

76 where the dotted line represents an optional chemical bond and R '1 represents an atom of hydrogen, a C 1-5 aliphatic radical; Y where at least one of R 2, R 3, R 4 and R 5 represents a radical -NO 2; and / or -NH2; and / or -SOR 13; and / or -S (= O) 2 -R 13; I -S (= O) 2 -N (R 14) R 15; I -N (R 16) - S (= O) 2 -R 17; and / or -N (R 21) - CO-R 22; and the others are selected from hydrogen, -OR_ {11}, -SR_ {11}, F, Cl, Br, I or a C 1-4 alkyl radical; and where A represents: 77 which means respectively type compounds (Ix) and (Iy): 78 and where R 6 and R '6, identical or different, they represent a hydrogen atom or a 5 to 14-membered aryl or heteroaryl radical optionally substituted by a phenyl that can be linked through a C 1 -C 6 alkylene or a C 1 -C 6 ilidene; Y where R 11, R 13, R 14, R 15, R 16, R 17, R 21 and R 22 represent, independently of each other, a hydrogen atom, a radical C 1-5 aliphatic, an aryl or heteroaryl radical containing 1, 2 or 3 independently selected heteroatoms between N, O and S and that can be substituted by a Chlorine. 17. An indene derived from general formula I of according to claim 1 selected from: [1] (2-Methyl-6-nitro-3 H -inden-1-yl) acetic acid [2] [2-methyl-6- (naphthalene-2-sulfonylamino) -3 H -inden-1-yl] acetic acid [3] [3 ( Z ) -benzylidene-2-methyl-6- (naphthalen-2-sulfonylamino) -3 H -inden-1-yl] acetic acid [4] [2-Methyl-4- (naphthalene-2-sulfonylamino) -3 H -inden-1-yl] acetic acid [5] [6- (naphthalene-2-sulfonylamino) -3 H -inden-1-yl] acetic acid [6] [6- (5-Chloro-3-methylbenzo [ b ] thiophene-2-sulfonylamino) -2-methyl-3 H -inden-1-yl] acetic acid [7] [2-methyl-6- (naphthalen-1-ylsulfamoyl) -3 H -inden-1-yl] acetic acid [8] N, N -Dimethyl-2- (2-methyl-6-nitro-3 H -inden-1-yl) acetamide [9] 2- (2-Methyl-6-nitro-3 H -inden-1-yl) -1-pyrrolidin-1-iletanone [10] 2- [3 ( Z ) -Benzyliden-2-methyl-6- (naphthalen-2-sulfonylamino) -3 H -inden-1-yl] - N, N- dimethylacetamide [11] N, N -Dimethyl-2- [2-methyl-6- (naphthalen-2-sulfonylamino) -3 H -inden-1-yl] acetamide [12] N - [2-Methyl-3- (2-oxo-2-pyrrolidin-1-ylethyl) -1 H -inden-5-yl] naphthalene-2-sulfonamide [13] N - [2-Methyl-1- (2-oxo-2-pyrrolidin-1-ylethyl) -3 H -inden-4-yl] naphthalene-2-sulfonamide [14] N - [3- (2-Oxo-2-pyrrolidin-1-ylethyl) -1 H -inden-5-yl] naphthalene-2-sulfonamide [15] N - [2-Methyl-3- (2-oxo-2-pyrrolidin-1-ylethyl) -1 H -inden-5-yl] -5-chloro-3-methylbenzo [ b ] thiophene-2- sulfonamide [16] N, N -Dimethyl-2- [2-methyl-6- (naphthalen-1-ylsulfamoyl) -3 H -inden-1-yl] acetamide [17] Dimethyl- [2- (2-methyl-6-nitro-3 H -inden-1-yl) ethyl] amine [18] 3- (2-Dimethylaminoethyl) -2-methyl-1 H -inden-5-ylamine [19] N - [3- (2-Dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] -6-chloroimidazo [2,1- b ] thiazol-5-sulfonamide [20] N - [3- (2-Dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] -5-chloro-3-methylbenzo [ b ] thiophene-2-sulfonamide [21] N - {4- [3- (2-Dimethylaminoethyl) -2-methyl-1 H -inden-5-ylsulfamoyl] phenyl} acetamide [22] N - [3- (2-Dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] benzo [1,2,5] thiadiazol-4-sulfonamide [23] N -Ethyl- N - [3- (2-dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] -5-chloro-3-methylbenzo [ b ] thiophene-2-sulfonamide [24] 4-Amino- N - [3- (2-dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] benzenesulfonamide [25] N - [3- (2-Pyrrolidin-1-ylethyl) -2-methyl-1 H -inden-5-yl] -2- (4-benzyloxyphenyl) acetamide [26] 2-Methyl-3- (2-pyrrolidin-1-ylethyl) -1 H -inden-5-ylamine [27] (2- {6 - [(5-Chloro-3-methylbenzo [ b ] thiophene-2-sulfonyl) ethylamino] -2-methyl-3 H -inden-1-yl} ethyl) ethyldimethylammonium iodide [28] 1- [2- (2-Methyl-6-nitro-3 H -inden-1-yl) ethyl] pyrrolidine [29] N - [3- (2-Pyrrolidin-1-ylethyl) -2-methyl-1 H -inden-5-yl] -6-chloroimidazo [2,1- b ] thiazol-5-sulfonamide [30] N - {4- [3- (2-Pyrrolidin-1-ylethyl) -2-methyl-1 H -inden-5-ylsulfamoyl] phenyl} acetamide [31] N - [3- (2-Pyrrolidin-1-ylethyl) -2-methyl-1 H -inden-5-yl] -benzo [1,2,5] thiadiazol-4-sulfonamide [32] 4-Amino- N - [3- (2-pyrrolidin-1-ylethyl) -2-methyl-1 H -inden-5-yl] benzenesulfonamide [33] N - [1 (Z) -Benciliden-3- (2-dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] naphthalene-2-sulfonamide [34] N - [3- (2-Dimethylaminoethyl) -2-methyl-1 H -inden-5-yl] naphthalen-2-sulfonamide [35] N - [2-Methyl-3- (2-pyrrolidin-1-ylethyl) -1 H -inden-5-yl] naphthalene-2-sulfonamide [36] N - [2-Methyl-1- (2-pyrrolidin-1-ylethyl) -3 H -inden-4-yl] naphthalene-2-sulfonamide [37] N - [3- (2-Pyrrolidin-1-ylethyl) -1 H -inden-5-yl] naphthalene-2-sulfonamide [38] N - [2-Methyl-3- (2-pyrrolidin-1-ylethyl) -1 H -inden-5-yl] -5-chloro-3-methylbenzo [ b ] thiophene-2-sulfonamide [39] N - (Naftalen-1-yl) -3- (2-dimethylaminoethyl) -2-methyl-1H-indene-5-sulfonamide [40] N - [3- (2-Hydroxyethyl) -2-methyl-1 H -inden-5-yl] naphthalene-2-sulfonamide. 18. An indene derived according to any of claims 1 to 3 having the general formula (Ia): 79 where R2, R3, R4, R 5, R 7, A, have the meanings indicated above and n = 0, 1, 2, 3 or Four. 19. An indene derived according to any of claims 1 to 3 having the general formula (Ib):

         \ vskip1.000000 \ baselineskip
      

80

         \ vskip1.000000 \ baselineskip
      

where R2, R3, R4, R 5, R 7, R 8, R 9, A have the meanings previously indicated and n = 0, 1, 2, 3 or Four. 20. An indene derived according to any of claims 1 to 3 having the formula (Ic):

         \ vskip1.000000 \ baselineskip
      

81

         \ vskip1.000000 \ baselineskip
      

where R2, R3, R4, R 5, R 7, R 8, R 9, A have the meanings previously indicated and n = 0, 1, 2, 3 or Four. 21. An indene derived according to any of claims 1 to 3 having the general formula (Id):

         \ vskip1.000000 \ baselineskip
      

82

         \ vskip1.000000 \ baselineskip
      

where the amino group can occupy any position within the benzene ring and the others positions thereof may be substituted in accordance with the claim 1, preferably hydrogen, -OR 11, -SR 11, F, Cl, Br, I or a C 1-4 alkyl radical, and where R_ {1}, R_ {7}, R_ {11} and A have the meanings previously indicated and n = 0, 1, 2, 3 or Four.

         \ newpage
      

22. An indene derived in accordance with the claims 1 or 2 having the general formula (Ie):

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83

         \ vskip1.000000 \ baselineskip
      

where -NHSO_ {2} R_ {13} can occupy any position of the benzene ring and the others positions thereof may be substituted in accordance with the claim 1, preferably hydrogen, -OR 11, -SR 11, F, Cl, Br, I or an alkyl radical C_ {1-4}, and where R 1, R 7, R 11, R_ {13}, A have the meanings indicated above and n = 0, 1, 2, 3 or Four. 23. An indene derived in accordance with the claims 1 or 2 having the general formula (If):

         \ vskip1.000000 \ baselineskip
      

84

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where -N (R_ {16}) SO_ {2} R_ {13} can occupy any position of the benzene ring and the other positions thereof may be substituted according to claim 1, preferably hydrogen, -OR 11, -SR 11, F, Cl, Br, I or a C 1-4 alkyl radical, and where R 1, R 7, R 13, R 11, R 16, A have the meanings previously indicated and n = 0, 1, 2, 3 or Four. 24. An indene derived according to any of claims 1 to 3 having the general formula formula general (Ig):

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85

         \ vskip1.000000 \ baselineskip
      

where R2, R3, R4, R_ {5}, R_ {7} and A have the meanings indicated above and n = 0, 1, 2, 3 or Four.

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25. An indene derived according to any of claims 1 to 3 having the general formula (Ih):

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86

         \ vskip1.000000 \ baselineskip
      

where R2, R3, R4, R 5, R 6, R 6, R 7 have the meanings previously indicated and n = 0, 1, 2, 3 or Four. 26. An indene derived according to any of claims 1 to 3 having the general formula (In):

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87

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where R2, R3, R4, R 5, R 6, R 6, R 7 have the meanings previously indicated and n = 0, 1, 2, 3 or Four. 27. An indene derived according to anyone of claims 1 to 3 having the general formula (Ik):

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88

         \ vskip1.000000 \ baselineskip
      

where R2, R3, R4, R_ {5}, R_ {7} have the meanings indicated above and n = 0, 1, 2, 3 or Four.

         \ newpage
      

28. Procedure for the preparation of indene derivatives of general formula (Ia):

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89

         \ vskip1.000000 \ baselineskip
      

where R2, R3, R4, R_ {5}, R_ {7} and A have the meaning indicated above and n = 0, 1, 2, 3 or 4, comprising the following stages:

to)

put on in in a suitable reaction medium an indanone of general formula II:

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90

         \ vskip1.000000 \ baselineskip
      

where R2 R 3, R 4, R 5, R 7 and A have the meaning above indicated with an alkyl carboxylate to obtain an intermediate alcohol

b)

do react the resulting intermediate alcohol in a solution of a acid, preferably H 2 SO 4.

29. Procedure in accordance with the claim 28 wherein the reaction medium where it is carried to carry out the reaction between the compound of formula II and the carboxylate alkyl comprises LHMDS and THF. 30. Procedure for the preparation of indene derivatives of general formula (Ia):

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91

         \ vskip1.000000 \ baselineskip
      

where R2, R3, R4, R_ {5}, R_ {7}, A have the meaning indicated above and n = 0, 1, 2, 3 or 4

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which comprises the following stages:

to)

put on in in a suitable reaction medium an indanone of general formula II:

92

where R2 R 3, R 4, R 5, R 7 and A have the meaning above indicated with an alkyl carboxylate to obtain an intermediate alcohol

b)

add drop by drop on alcohol resulting intermediate, TFA in an appropriate medium

C)

do react the resulting mixture with sodium metal dissolved in methanol bringing the mixture to reflux temperature.

31. Procedure in accordance with the claim 30 wherein the reaction medium where it is carried to carry out the reaction between the compound of formula II and carboxylate of alkyl comprises LHMDS and THF. 32. Procedure in accordance with the claim 30 wherein the medium in which the intermediate alcohol and the TFA is added dropwise comprises CH 2 Cl 2. 33. Procedure for the preparation of indene derivatives of general formula (Ib): 93 which comprises contacting a suitable reaction medium an indenylcarboxylic acid of General Formula (Ia): 94 with a sufficient amount of SOCl 2 at reflux temperature and add on the residue obtained and redissolved an amine of formula NR 8 R 9 where R 2, R 3, R 4, R 5, R 7, R 8, R 9 and A they have the meaning indicated above and n = 0, 1, 2, 3 or Four. 34. Procedure in accordance with the claim 33 wherein the reaction medium comprises CH 2 Cl 2. 35. Procedure for the preparation of indene derivatives of general formula (Ib): 95 which comprises contacting a suitable reaction medium an indenilic acid of formula general (Ia): 96 with CDI in agitation and add to the reaction mixture an amine of formula NR 8 R 9 where R 2, R 3, R 4, R 5, R 7, R 8, R 9 and A they have the meaning indicated above and n = 0, 1, 2, 3 or Four. 36. Procedure in accordance with the claim 35 wherein the reaction medium comprises THF. 37. Procedure for the preparation of a Indene derived from general formula (Ic): 97 which comprises contacting a suitable reaction medium an indenylamide of the general formula (Ib): 98 with a solution of AIH3-DMEA where R2, R3, R4, R5, R 7, R 8, R 9 and A have the meaning above indicated and n = 0, 1, 2, 3 or Four. 38. Procedure in accordance with the claim 37 wherein the reaction medium comprises THF. 39. Procedure for the preparation of a indene derived from general formula (Id): 99 according to claim 21 wherein the amino group can occupy any position within the benzene ring and the other positions thereof can be substituted according to claim 1, preferably hydrogen,
-OR_ {11}, -SR_ {11}, F, Cl, Br, I or an aliphatic radical C_ {1-6} and where R_ {1}, R_ {7}, R_ {11} and A have the meaning noted above and n = 0, 1, 2, 3 or 4 comprising contacting in a suitable medium, a compound of general formula (Im): 100 where the nitro group can occupy any position within the benzene ring and the others positions thereof may be substituted in accordance with the claim 1, preferably hydrogen, -OR 11, -SR 11, F, Cl, Br, I or a C 1-6 aliphatic radical, and where R_ {1}, R_ {7}, R_ {11}, A have the meaning above and n = 0, 1, 2, 3 or 4 with a suspension of Zn powder with acid acetic. 40. Procedure for the preparation of a indene derived from general formula (Ie):

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101 according to claim 22 wherein the radical -NHSO_ {2} (R_ {13}) can occupy any position within the benzene ring and the other positions of the they may be substituted according to claim 1, preferably hydrogen, -OR 11, -SR 11, F, Cl, Br, I or an aliphatic radical C_ {1-6} which comprises contacting a medium suitable an indenyl amine of the general formula Id: 102 according to claim 21 wherein the radical –NH_ {2} can occupy any position within the ring benzene and the other positions thereof may be substituted according to claim 1, preferably hydrogen, -OR_ {11}, -SR_ {11}, F, Cl, Br, I or an aliphatic radical C 1-6, with a solution of R 13 SO 2 Cl a room temperature and where where R 1, R 7, R 11, R_ {13} A have the meaning indicated above and n = 0, 1, 2, 3 or Four. 41. Procedure in accordance with the claim 40 wherein the reaction medium comprises pyridine dry 42. Procedure for preparing the Preparation of an indene derived from the general formula (If): 103 according to claim 23 wherein the radical -N (R 16) SO 2 (R 13) can occupy any position within the benzene ring and the others positions thereof may be substituted in accordance with the claim 1, preferably hydrogen, -OR 11, -SR 11,  F, Cl, Br, I or an aliphatic radical C_ {1-6}, which comprises contacting a medium suitable, an indenylsulfonamide of general formula (Ie): 104 according to claim 22, wherein the radical -NHSO_ {R} {13} can occupy any position of the benzene ring and the other positions thereof may be substituted according to claim 1, preferably hydrogen, -OR_ {11}, -SR_ {11}, F, Cl, Br, I or a radical C 1-6 aliphatic, with a reaction medium that it comprises K 2 CO 3 and an alkyl halide of 1 to 5 carbons, linear or branched at room temperature where R1, R_ {7}, R_ {11}, R_ {13}, R_ {16}, A have the meaning above and n = 0, 1, 2, 3 or Four. 43. A process according to claim 42 characterized in that it is carried out in a medium with acetonitrile. 44. A process according to claim 42 characterized in that the alkyl halide is ethyl iodide.

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45. A procedure for the preparation of a Indene derived from general formula (Ig): 105 where R2, R3, R4, R_ {5}, R_ {7} and A have the meaning indicated above and n = 1, 2, 3 or 4, which comprises contacting a means of suitable reaction, an indenilic acid of general formula (Ia): 106 with a solution of LiAlH 4 -AlCl 3 where R 2, R 3, R 4, R 5, R 7 and A have the meaning above indicated and n = 0, 1, 2, 3 or Four. 46. A method according to claim 45 characterized in that the reaction medium comprises THF. 47. A procedure for the preparation of a Indene derived from general formula (Ih): 107 which comprises contacting a suitable reaction medium, an indenylcarboxylic acid of General Formula (Ik): 108

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with a reaction medium that comprises NaH and an appropriate aldehyde at reflux temperature of the solvent where R 2, R 3, R 4, R 5, R 6, R_ {6 '}, R_ {7} and A have the meaning indicated above and n = 0, 1, 2, 3 or Four. 48. A method according to claim 47 characterized in that the reaction medium comprises THF. 49. A process according to claim 47 characterized in that the appropriate aldehyde is benzaldehyde. 50. An indanone of general formula (II):

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109

         \ vskip1.000000 \ baselineskip
      

R 2, R 3, R 4, R 5, R_ {6}, R_ {7} and A have the same meanings indicated previously. 51. An indanone of general formula (II) of according to claim 50 selected from: [41] 2-Methyl-6-nitroindan-1-one [42] 2-Methyl-4-nitroindan-1-one [43] 6-Amino-2-methylindan-1-one [44] N - (2-Methyl-3-oxoindan-5-yl) naphthalene-2-sulfonamide [Four. Five] 4-Amino-2-methylindan-1-one [46] N - (2-Methyl-1-oxoindan-4-yl) naphthalene-2-sulfonamide [47] 6-Nitroindan-1-one [48] 4-Nitroindan-1-one [49] 6-Aminoindan-1-one [50] N - (3-Oxoindan-5-yl) naphthalene-2-sulfonamide [51] N - (2-Methyl-3-oxoindan-5-yl) -5-chloro-3-methylbenzo [ b ] thiophene-2-sulfonamide [52] Chloride 2-methyl-3-oxoindan-5-sulfonyl [53] N - (Naftalen-1-yl) -2-methyl-3-oxoindane-5-sulfonamide. 52. An indene derived from general formula I of according to any of claims 1 to 27 for use as a medicine 53. An indene derived in accordance with the claim 52 for use in the treatment of disorders or 5HT6 receptor mediated diseases. 54. An indene derived in accordance with the claim 53 for use in the prophylaxis and / or treatment of disorders or diseases related to intake food, preferably for appetite regulation, for  maintenance, increase or reduction of body weight, for prophylaxis and / or treatment of obesity, bulimia, anorexia, cachexia or type II diabetes, or for prophylaxis and / or treatment of irritable bowel / bowel syndrome; disorders of the central nervous system; anxiety; panic attacks; depression; bipolar disorders; cognitive disorders; disorders of memory; senile dementia; psychosis; schizophrenia; disorders neurodegenerative preferably selected from the Alzheimer's disease, Parkinson's disease, disease of Huntington and multiple sclerosis; or disorders of hyperactivity preferably attention deficit / disorder hyperactivity, or for the improvement of cognitive ability. 55. Use of an indene derived from the general formula I according to any one of claims 1 to 3 in the development of a medication for the treatment of disorders or diseases mediated by 5HT6 receptors. 56. Use of a derivative indene in accordance with the claim 55 in the preparation of a medicament for the prophylaxis and / or treatment of disorders or diseases related to food intake, preferably for appetite regulation, for maintenance, increase or reduction of body weight, for prophylaxis and / or treatment of obesity, bulimia, anorexia, cachexia or type II diabetes, or for the prophylaxis and / or treatment of irritable bowel / intestine; central nervous system disorders; anxiety; panic attacks; depression; bipolar disorders; cognitive disorders; memory disorders; senile dementia; psychosis; schizophrenia; neurodegenerative disorders preferably selected from Alzheimer's disease, the Parkinson's disease, Huntington's disease and multiple sclerosis; or hyperactivity disorders preferably attention deficit / hyperactivity disorder, or for improvement of cognitive ability. 57. Pharmaceutical composition comprising a compound of general formula I according to any of the claims 1 to 27 and at least one pharmaceutically additive acceptable.