NZ264122A

NZ264122A - Substituted 1-benzenesulphonyl dihydroindolones; medicaments

Info

Publication number: NZ264122A
Application number: NZ264122A
Authority: NZ
Inventors: Malta Alain Di; Loic Foulon; Georges Garcia; Dino Nisato; Richard Roux; Claudine Serradeil-Legal; Gerard Valette; Jean Wagnon
Original assignee: Sanofi Sa
Priority date: 1993-07-30
Filing date: 1994-07-28
Publication date: 1996-07-26
Also published as: RU2141476C1; JPH07247269A; CA2129215A1; EP0636608A1; AU684791B2; HU9402232D0; TW375609B; AU6878994A; KR950003271A; FR2708605A1; IL110482A; ZA945656B; FI943570A0; CN1107467A; FI943570A; NO301824B1; IL110482A0; NO942834D0; RU94027576A; NO942834L

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number £641 ££ 9 ft A 1 o 0 Complete Specification Filed:2. $..7.^./..^.... Class: (6) !{<■&.C.PJM.C mftplja cj7fik\3}n^co3Dknh%).Ml?Mll!.% pSblteSfifDate: .2. S..J.UJL..1996 | P.O. Journal No: NO 1itfi LJ "li j j M.Z. PATKfJT GFFfCS 2.8 JUL 1994 i™J?3S£!i:SEL Patents Form No. Our Refs JB203501 NEW ZEALAND PATENTS ACT 1953 COMPLETE SPECIFICATION 1—BENZENESUIiFONYL—1, 3—DIHYDROINDOL—2—ONE DERIVATIVES, THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS IN IiHICH THEY ARE PRESENT We, SANOFI, a French company 32-34 Rue Marbeuf, 75008 Paris, France hereby declare the invention, for which we pray that a patent may be granted to us and the method by which it is to be performed, to be particularly described in and by the following statement s PT0598996 - 1 - (followed by page la) 264122 The present Invention relates to 1-benzenesulfonyl-1,3-dihydroindol-2-one derivatives, to their preparation and to the pharmaceutical compositions in which they are present. International patent application WO 91/01306 describes 2-oxoindole derivatives which are useful for the treatment of senile dementia. These compounds have the formula R"9 (^R"3 riV> x I corh4 in which - R''i is a hydrogen, a halogen, an alkyl or an alkoxy; - Rm2 is hydrogen or a lower alkyl; - R''3 is an alkyl, a cycloalkylmethyl, a benzodioxanylmethyl or an optionally substituted benzyl; and - R' '4 is a 1-propylbutyl, a pyridyl or an optionally substituted phenyl. Several patent applications have recently described families of compounds of non-peptide structure which are active on the vasopressin and/or ocytocin receptors. There may be mentioned European patent applications EP 382 185, EP 444 945, EP 514 667, EP 469 984 and EP 526 348, international patent applications WO 91/05 549 and WO 93/15 051, patent application JP 04/321 669 and, more particularly, patent application JP 03/127 732. This last patent application describes indole-3-propionic acid derivatives of the formula (followed by page 2) i C J 5 in which - R'''i is hydrogen, an alkyl, an alkenyl, a phenylalkyl, a tetrahydrofuryl, an alkoxycarbonyl, an alkoxycarbonylalkyl, a carboxyalkyl or an alkanoyl; - R'''2 is hydrogen, a hydroxyl, an alkoxy, an alkyl, a 10 phenylalkyl, a phenylalkoxy or a halogen; - R' ' '3 is a hydrogen, an alkoxy, a free or substituted amino group or an amino acid residue; - R'''4 is hydrogen, an alkyl or a phenylalkyl; and R' '' 5 is a benzoyl, a phenyl, an alkyl, a 15 phenylalkenylcarbonyl, a thienylcarbonyl, a phenylsulfonyl, a pyridylcarbonyl or an imidazolylcarbonyl, it being possible for the phenyl and alkyl groups of the substituent R'''5 to be substituted. These compounds are vasopressin antagonists. 20 Patent US 4 803 217 claims hapalindolinones obtained by fermentation which are vasopressin antagonists. These compounds have the following formula: in which R is H or CI. £* -Q Novel 1-benzenesulfonyl-l,3-dihydroindol-2-one derivatives have now been found which also have an affinity for the vasopressin and ocytocin receptors. Vasopressin is a hormone known for its 5 antidiuretic effect and its effect in the regulation of arterial pressure. It stimulates several types of receptors, namely Vi (Via, V]_b) and V2. These receptors are localized in the liver, vessels (coronary, renal, cerebral), platelets, kidney, uterus, adrenal glands, 10 central nervous system and pituitary gland. Ocytocin has a peptide structure similar to that of vasopressin. The ocytocin receptors are also found on the smooth muscle of the uterus, as well as on myoepithelial cells of the mammary gland, in the central nervous system and in the 15 kidney. The localization of the different receptors is described in: S. JARS et al., Vasopressin and ocytocin receptors: an overview, in Progress in Endocrinology? H. IMURA and K. SHIZURNE ed., Experta Medica, Amsterdam, 1988, 1183-1188, and in the following articles: Presse 20 M6dicale, 1987, lfi. (10), 481-485; J. Lab. Clin. Med., 1989, H4. (6), 617-632; and Pharmacol. Rev., 1991, 43. (1), 73-108. Vasopressin thus exerts cardiovascular, hepatic, antidiuretic and aggregating effects and effects on the central and peripheral nervous system and in the 25 uterine domain. Ocytocin is involved in parturition, lactation and sexual behavior. The compounds according to the present invention make it possible selectively either to mimic the effects of the hormone (in the case of agonists) or to inhibit 30 them (in the case of antagonists). Vasopressin receptor antagonists can affect the regulation of the central and peripheral circulation, especially the coronary, renal and gastric circulation, as well as the regulation of hydration and the release of adrenocorticotrophic hormone 35 (ACTH). Vasopressin agonists can advantageously replace vasopressin or its analogs in the treatment of diabetes 4 & U a ]i insipidus; they can also be used in the treatment of enuresis and in the regulation of hemostasis: treatment of hemophilia and von Wille brand's syndrome, antidote to platelet aggregating agents, F.A. LASZLO, Pharmacol. 5 Rev., 1991, 43, 73-108; and Drug Investigation, 1990, 2. (Suppl. 5), 1-47. The hormones themselves, namely vasopressin and ocytocin, and some of their peptide or non-peptide analogs are used in therapeutics and have been found to be effective. Several reviews and numerous 10 literature articles may be mentioned: Vasopressin, P. GROSS et al. ed., John Libbey Eurotext, 1993, in particular 243-257 and 549-562; F.A. LASZLO and F.A. LASZLO Jr., Clinical perspectives for vasopressin antagonists, Drug News Perspect., 1993, 6 (8); W.G. 15 NORTH, J. Clin. Endocrinol., 1991, 23., 1316-1320; J.J. LE6ROS et al., Prog. Neuro-Pharmacol. Biol. Psychiat., 1988, 12., 571-586; K.E. ANDERSSON et al., Drugs Today, 1988, 24 (7), 509- 528; D.L. STUMP et al., Drugs, 1990, 39. 38-53; S. CALTABIANO et al., Drugs Future, 1988, 13. 20 25-30; Y. MURA et al., Clin. Nephrol., 1993, 4Q, 60-61; and FASEB J., 1994, & (5), A 587 : 3398. Thus the compounds according to the invention are useful especially in the treatment of complaints of the central and peripheral nervous system, the cardiovascular 25 system, the renal domain and the gastric domain and in disorders of sexual behavior, in man and animals. The present invention relates to compounds of the formula 30 (I) in which Rl and R2 are each independently a hydrogen; a 5 hydroxyl; an w-halogeno-Ci-Cy-alkoxy; a halogen; a C^-Cy-alkyl; a trifluoromethyl; a C^-Cy-alkoxy; a polyhalogeno-Ci-Cy-alkoxy; an co-hydroxy-C2-C7-alkoxy; an oj-methoxyalkoxy in which the alkyl is C2-C7; an 01-amino-C2_C7-alkoxy which is free or substituted by one or 10 two Ci-C7-alkyls; a C3-C7-cycloalkoxy; a cycloalkylmethoxy in which the cycloalkyl is C3-C7; a phenoxy; a benzyloxy; a Ci-C7-alkylthio; a phenylthio; a nitro; an amino which is free or substituted by one or two Ci-C7~alkyls; a cyano; a (Ci-Cg)alkylcarbonyl; a 15 formyl; a (C^-Cg)alkylcarbonyloxy; a formyloxy; a C1-C7-alkylsulfonamido; a phenylsulfonamido; a benzylsulfonamide; a Ci-C7-alkylamido; a C1-C7-alkoxycarbonylamino; a ureido which is unsubstituted or substituted by a phenyl, a benzyl or one or two C1-C7-20 alkyls; or a thioureido which is unsubstituted or substituted by a phenyl, a benzyl or one or two C1-C7-alkyls; - R3 and R4 are each independently a Ci-C7-alkyl; a C3-C7-cycloalkyl; a phenyl; a benzyl; a cycloalkylmethyl in 25 which the cycloalkyl is C3-C7? or an o)-hydroxy-C2- C7-alkyl in which the hydroxyl is free or substituted by a group selected from Ci-C4-alkyl groups, (C1-C5)-alkoxyalkyl groups in which the alkyl is C1-C4, &*» u""3jJ 1 2 c phenylalkoxyalkyl groups In which the alkoxy is C1-C2 and the alkyl is C1-C4, and tetrahydrofuranyl and tetrahydropyranyl groups; or 5 - R3 and R4 together form a group -(CH2)pX(CH2)q~; or - R3 and R4, together with the carbon to which they are bonded, form an optionally fused, saturated or unsaturated C3~C12 hydrocarbon ring which is 10 unsubstituted or substituted by one or more Ci-Cy-alkyl groups, by an oxo group, by a C3-C5-spirocycloalkyl or by one or two hydroxyls which are free or substituted by a group selected from C1-C4-alkyl groups, (C^-C5)alkoxyalkyl groups in which the alkyl is C1-C4 , to- 15 hydroxyalkyl groups in which the alkyl is C1-C4, triphenylmethoxyalkyl groups in which the alkyl is C1-C4, phenylalkoxyalkyl groups in which the alkoxy is C1-C2 and the alkyl is C1-C4, and tetrahydrofuranyl, tetrahydropyranyl, formyl and (C1-C7)aIky1carbony1 20 groups; - R5 and Rg are each independently a hydrogen; a halogen; a C1-C7-alkyl; a trifluoromethyl; a cyano; a nitro; an amino which is free or substituted by one or two C1-C7-alkyls; a hydroxyamino; a hydroxyl; a carboxyl; a 25 guanidino which is unsubstituted or monosubstituted or disubstituted by a Ci-C7-'alkyl, a phenyl or a benzyl; a group -OR7; a group -SR7; a (C]_-C6 )alkylcarbonyl; a formyl; a Ci-C7-alkoxycarbonyl; a phenoxycarbonyl; a benzyloxycarbonyl; a carbamoyl substituted by groups R' 5 30 and R''g; a thiocarbamoyl which is free or substituted by one or two Ci-C7~alkyls; a sulfamoyl; an alkylsulfamoyl or dialkylsulfamoyl in which the alkyl is C1-C7; a group -S02R'7; an alkylsulfonamido in which the alkyl is C1-C7; a phenylsulfonamido; a benzylsulfonamido; a group -COR'7; 35 a group -NRgRg; or a group -CO-NH-CRiqr'io~cor12? if appropriate, the phenyl group forming part of the 9 o substituent R5 and/or Rg can be unsubstituted or monosubstituted or polysubstituted by a Ci-Cy-alkyl, a trifluoromethyl, a Ci-Cy-alkoxy, a halogen, a sulfamoyl, an alkylsulfamoyl in which the alkyl is C1-C7, a 5 carboxyl, an alkoxycarbonyl in which the alkyl is C1-C7, a (C1-C5)alkylcarbonyloxy or an imidazolyl; - R'g and R''5 are each independently hydrogen; a C1-C7-alkyl which is unsubstituted or substituted by one or more halogens or R'''5; a C3~C7-cycloalkyl which is 10 unsubstituted or substituted by a (Ci-C4)alkyl; a phenyl; a pyridyl; a methylpyridyl; a piperidin-4-yl; a methylpiperidin-4-yl; or a pyrrolidin-l-yl; or R'g and R''6, with the nitrogen atom to which they are bonded, form a pyrrolidino group substituted by a hydroxymethyl 15 or by a carbamoyl which is free or substituted by one or two Cj-Cy-alkyls; - R'''g is a hydroxyl; a Ci-C7-alkoxy; an amino which is free or substituted by one or two Ci~C7-alkyls; a carbamoyl which is free or substituted by one or two C^- 7.0 C7~alkyls or in which the two substituents, together with the nitrogen atom to which they are bonded, form a pyrrolidino, a piperidino or a perhydroazepino; a cyano; a carboxyl which is free or esterified by a Ci-C7-alkyl or a benzyl; a phenyl; a C3-C7-cycloalkyl; an adamantyl; 25 or a heterocyclic radical selected from pyridyl, methylpyridyl, furanyl, tetrahydrofuranyl, thienyl, methylthienyl, pyrrolidine, piperidino and perhydroazepino groups; - R7 is a Ci-C7~alkyl; a phenyl; a benzyl; a C3-C7-30 cycloalkyl; a C2-C7~alkenyl; an o>~halogeno-C2-C7- alkyl; a polyhalogeno-Ci-C7-alkyl; an to-hydroxy-C2- C7~alkyl; a (Ci-C6 Jalkylcarbonyl; a formyl; an «- carboxy-Ci-C7~ alkyl which is free or esterified by a Ci-C7-alkyl or a benzyl; an <i)-amino-C2-C7-alkyl in which the amino group 35 is free, substituted by one or two Ci-C7~alkyls or in the form of an ammonium ion; or an c)-carbamoyl-Ci-C7-alkyl n P ■" , ... * 6 ] £ ? which is free or substituted by one or two C^-Cy-alkyls; - R'7 is a piperazin-l-yl group which is unsubstituted or substituted in the 4-position by a group R''^; a piperidino group which is unsubstituted or substituted in 5 the 4-position by a group R''^; an azetidin-l-yl group which is unsubstituted or substituted in the 3-position by a group R'''7; or a pyrrolidino group which is unsubstituted or substituted by a group R''''7; - R' ' 7 is a Ci-C7-alkyl; a phenyl; a benzyl; a (Ci-Cg) 10 alkylcarbonyl; or a formyl; - R'''7 is R''7; or an amino which is free or carries a protecting group; - R'','y is R'''7? or a carboxyl group which is free or esterified by a Ci-C7~alkyl; 15 - Rg and Rg are each independently a hydrogen? a C1-C7-alkyl; a benzyl; or a phenyl; Rg can also be a C3-C8-alkene; a (Ci-Cg)alkylcarbonyl; a formyl; a (C1-C5)-alkylthiocarbonyl; a cycloalkylcarbonyl in which the cycloalkyl is C3-C7; a cycloalkylthiocarbonyl in which 20 the cycloalkyl is C3-C7; an <0-amino (C2-Cg )-alkylcarbonyl; an co-hydroxyCCi-Cg) alkylcarbonyl; an co-benzyloxy(Ci-Cg)alkylcarbonyl; a phenoxycarbonyl; a phenoxythiocarbonyl; a thienocarbonyl; a pyridylcarbonyl; a methylpyridylcarbonyl; a Ci-Cy-alkoxycarbonyl; a 25 benzoyl; a phenacetyl; a group -CO-CRiqR'10" NR11R'11' a group -CRiqr' 10cor12; a STrouP -(CH2 )tco Ri2? a group -CO(CH2)-t,COR12' a carbamoyl which is unsubstituted or substituted by R14 and R'i4; a thiocarbamoyl which is unsubstituted or substituted by R14 and R,i4? or a 30 heterocyclic radical selected from pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyridyl and thiazolyl groups; or - Rg and Rg, together with the nitrogen atom to which 35 they are bonded, form hydantoin; N-methylhydantoin; or a heterocycle selected from pyrrol-1-yl, A3- pyrrolin-l-yl, pyrrolidin-l-yl and isoindolin-2-yl in which the benzene ring can be unsubstituted or substituted by a halogen, a Ci-C7-alkyl, a trifluoromethyl or a methoxy; - Rig and R'io are each independently hydrogen; a C^- C7-5 alkyl; or a benzyl; or Riq an(* Rll0' together with the carbon atom to which they are bonded, form a C3- C7-cycloalkyl; - R^i and R'n are each independently hydrogen; or a C^-Cy-alkyl; 10 - r12 is a hydroxyl; a C1-C7-alkoxy; or an amino which is unsubstituted or substituted by one or two C1-C7- alkyls; - R13 is hydrogen; a C]_-C7-alkyl; a phenyl; a benzyl; a (Ci-Cg)alkylcarbonyl; a formyl; a Ci~C7-alkoxycarbonyl; or a carbamoyl which is unsubstituted or substituted by 15 one or 2 Ci-C7~alkyls; - R14 and R'i4 are each independently a C1-C7-alkyl which is unsubstituted or substituted by R15; a phenyl which is unsubstituted or substituted by R'is; a C3-C7-cycloalkyl; or an adamantyl; 20 or - R14 and R'i4, together with the nitrogen atom to which they are bonded, form a heterocycle selected from morpholine, thiomorpholine, piperazine, azetidine, pyrrolidine, piperidine and perhydroazepine, said 25 heterocycle being unsubstituted or substituted by one or more methyl groups, by a phenyl or by an amino group which is free or carries a protecting group; - R15 is a phenyl; a pyridyl; a hydroxyl; a C1-C7-alkoxy; an amino which is free or substituted by one or 30 two Ci-C7~alkyls; or a carboxyl which is free or esterified by a Ci-C7~alkyl; - R'is is a hydroxyl; or an amino which is free or substituted by one or two Ci-C7-alkyls; - m is 1 or, if Rg is a halogen, a Ci~C7-alkyl or a C^-35 C7-alkoxy, m can also be 2, 3 or 4, or else (Rg)m can be m substituents having different meanings selected from 10 g.0 i. 1 2 2 halogen, Ci-Cy-alkyl and Ci-C7~alkoxy; - p and q are each an integer, wherein their sum vary from 3 to 6; - t is an integer from 2 to 5; 5 - t' is an integer from 0 to 3; - X is oxygen; a group S(0)n; a group NR13; or a group N(0)Ri3; and - n is 0, 1 or 2; with the limitation that if 10 - and R2 are as defined above with the exception of the ureido group substituted by a benzyl group, or the thioureldo group which Is unsubstituted or substituted by a phenyl, a benzyl or one or two C^- C4~alkyls; - R3 and R4 are each independently a C^-Cg-alkyl; a C3-15 C7-cycloalkyl; a phenyl; a benzyl; or a cycloalkyl methyl in which the cycloalkyl is C3-C7; or - R3 and R4 together form a group -(CH2)pX(CH2)q- in which X is oxygen, sulfur or a group NR13; 20 or - R3 and R4, together with the carbon to which they are bonded, form an optionally fused, saturated or unsaturated C3-C10 hydrocarbon ring which is unsubstituted or substituted by one or more Ci~C7-alkyl 25 groups or by a C3-C5-spirocycloalkyl; - R5 and Rg are other than a hydrogen; a halogen; a C^-C7-alkyl; a trifluoromethyl; a cyano; a nitro; an amino which is free or substituted by one or two C7-alkyls; a hydroxyamino; a hydroxyl; a carboxyl; a group -OR7; a 30 group -SR7; a (C^-Cg)alkylcarbonyl; a formyl; a C1-C7-alkoxycarbonyl; a phenoxycarbonyl; a benzyloxycarbonyl; a carbamoyl substituted by groups R'g and R''g? a thiocarbamoyl which is free or substituted by one or two Ci-C7-alkyls; a sulfamoyl; an alkylsulfamoyl 35 dialkylsulfamoyl in which the alkyl is C1-C7; a gr< S02R'7; an alkylsulfonamido in which the alkyl is a group -COR'7; a group -NRgRg; or a group -CO-NH-CH(Riq)~C0R12' it being possible, if appropriate, for the phenyl group forming part of the substituent R5 and/or Rg to be unsubstituted or monosubstituted or polysubstituted by a Ci-C7~alJcyl, a trif luoromethyl, a methoxy, a halogen, a sulfamoyl, an alkylsulfamoyl in which the alkyl is C^-Cy, a carboxyl, an alkoxycarbonyl in which the alkyl is C1-C7, a Ci-Cg-alkylcarbonyloxy, a formyloxy or an imidazolyl; in which groups R5 and/or Rg: - R'g and R''g are each independently hydrogen; a C1-C7-alkyl which is unsubstituted or substituted by R1 "g; a phenyl; a pyridyl; a methylpyridyl; a piperidin-4- yl; or a methylpiperidin-4-yl; - R'''6 is a hydroxyl; a cyano; a carboxyl which is free or esterified by a C1-C7-alkyl or a benzyl; a phenyl; a pyridyl; a methylpyridyl; or an amino which is free or substituted by one or two -C7-alkyls; - R7 is a Ci-C7-alkyl; a phenyl; a benzyl; a C3-C7-cycloalkyl; a C2-C4~alkenyl; an co-halogeno-C2-C7~ alkyl; a polyhalogeno-Cj.-C7-alkyl; a (Ci-Cg)alkylcabonyl; a formyl; an o)-carboxy-Ci-C7-alkyl which is free or esterified by a Ci-C4~alkyl or a benzyl; or an Q)-amino-C2-C7-alkyl in which the amino group is free, substituted by one or two C1-C4-alkyls or in the form of an ammonium ion; - R'7 is a piperazin-l-yl group which is unsubstituted or substituted in the 4-position by a group R''7; a piperidino group which is unsubstituted or substituted in the 4-position by a group R''^; an azetidin- 1-yl group which is unsubstituted or substituted in the 3-position by a group R'1'7; - R''7 is a Ci-C4-alkyl'; a phenyl; a benzyl; or a (Ci-C3)alkylcarbonyl; - R'''7 is R''7; or an amino which is free or carries a protecting group; 12 Z6 A 1 - Rg and Rg are each independently a hydrogen; a C1-C7-alkyl; a phenyl; or a benzyl; Rg can also be a (Cj.-Cg)alkylcarbonyl; a formyl; a cycloalkylcarbonyl in which the cycloalkyl is C3-C7; a cycloalkylthiocarbonyl in 5 which the cycloalkyl Is C3-C7; an a>-amino(C2-C3) alkylcarbonyl; an co-hydroxy (C1-C3) alkylcarbonyl; an 0)-benzyloxy(Ci~C3) alkylcarbonyl; a phenoxycarbonyl; a thienocarbonyl; a pyridylcarbonyl; a methyl-pyridylcarbonyl; a Ci-C4~alkoxycarbonyl; a benzoyl; a 10 group -CO-CH(Rio)-NRiiR'n; a group -CH(Riq)C02Rh; a group -(CH2)t',cor12' a group -C0(CH2)t•«COR12? or a carbamoyl which is unsubstituted or substituted by a phenyl or one or two Ci-C4~alkyls; - t'1 is an integer which can vary from 1 to 3; 15 - Rig is hydrogen; a Ci~C4-alkyl; or a benzyl; - R11 and R'n are each independently hydrogen; or a C^-C4~alkyl; - Ri2 is a hydroxyl; a Ci~C4-alkoxy; or an amino which is unsubstituted or substituted by one or two C1-C4- alkyls; 20 and - R13 is hydrogen; a Ci-C4~alkyl; a phenyl; a benzyl? a (C1-C3)alkylcarbonyl; a formyl; a Ci-C4~alkoxycarbonyl; or a carbamoyl which is unsubstituted or substituted by one or 2 Cq-C^alkyls; provided that when one of R3 and R4 is methyl or ethyl, the other being methyl; m = 1 and one of R5 and R5 is hydrogen, the other is different from p-methyl; If a compound according to the invention has one or more asymmetric carbons, the invention includes all the optical isomers of this compound. If a compound according to the invention exhibits 30 conformational isomerism of the axial-equatorial type, the invention includes all the conformational isomers of this compound. The salts of the compounds of formula ( according to the present invention include those 35 mineral or organic acids which permit a su separation or crystallization of the compounds of ffcrmula (I), such as picric acid, oxalic acid or an optically active acid, for example a mandelic acid or a camphosulfonic acid, and mineral or organic acids which form physiologically acceptable salts such as the 5 hydrochloride, hydrobromide, sulfate, hydrogensulfate, dihydrogenphosphate, maleate, fumarate or naphthalene-2-sulfonate. The salts of the compounds of formula (I) also include the salts with organic or mineral bases, for 10 example the salts of alkali metals or alkaline earth metals, such as the sodium, potassium and calcium salts, the sodium and potassium salts being preferred, or with an amine such as trometamol, or else the salts of arginine, lysine or any physiologically acceptable amine. 15 According to the present invention, halogen is understood as meaning an atom selected from fluorine, chlorine, bromine and iodine, preferably fluorine or chlorine. Amlne-protecting group is understood as meaning a group such as, for example, a Ci-C4-alkyl, such 20 as methyl or tert-butyl,; benzhydryl; trityl; benzoyl; a C1-C4-alkylcarbonyl, such as tert-butoxycarbonyl, benzyloxycarbonyl; benzyl or substituted benzyl such as p-nitrobenzyl, p-chlorobenzyl or p-methoxybenzyl. According to the present invention, C1-C4-, Ci~ 25 C3-, C1-C5-, Ci-Cg-, C1-C7-, C2-C5- or C2-C7-alkyl Is understood as meaning a linear or branched alkyl. According to the present invention, optionally fused, saturated or unsaturated C3-C12 hydrocarbon ring is understood as meaning various hydrocarbon rings of 30 monocyclic, bicyclic or tricyclic structure, for example a cyclobutane, a cyclopentane, a cyclohexane, a cycloheptane, a cyclooctane, an indane, a hexahydro indane, an adamantane, a norbornane, a norbornene, a dihydrophenalene, a tricyclo[5.2.1.0^6]decane, a tri-35 cyclo[5.2.l.O^f®]dec-8-ene, a bicyclo[2.2.1]heptane or a bicyclo[3.3.1]nonane. According to the present invention, if R3 and R4, together with the carbon to which they are bonded, form an optionally fused, saturated or unsaturated C3- C12 hydrocarbon ring substituted by a hydroxyl, the preferred groups for substituting said hydroxyl are the methyl, ethyl, methoxymethyl, methoxyethyl, phenylmethoxymethyl, tetrahydrofuranyl and tetrahydropyranyl groups. The compounds of formula (I) in which R^ is in the 5-position of the indol-2-one and R2 is hydrogen are preferred compounds. The compounds of formula (I) in which Rj is a chlorine or fluorine atom or an ethoxy group in the 5-position of the indol-2-one and R2 is hydrogen are preferred compounds. The compounds of formula (I) in which R3 and R4, together with the carbon to which they are bonded, form a C3-C12 hydrocarbon ring are preferred compounds; particularly preferred compounds are those in which R3 and R4, together with the carbon to which they are bonded, form a cycloheptane, an adamantane, a tricyclo-[5.2.1.02'6]dec-8-ene, a tricyclo[5.2. l.O^, 6]aecane/ a bicyclo[2.2.1]heptane, a bicyclo[3.3.1]nonane or a cyclohexane which is unsubstituted or substituted by a C3~C5-spirocycloalkyl or by one or two Ci-Cy-alkyl groups. More particularly preferred compounds are those in which R3 and R4, together with the carbon to which they are bonded, form a cyclohexane substituted by a group selected from methoxy, ethoxy and 2-methoxy-ethoxy. The compounds of formula (I) in which the substituents R5 and Rg are in the 2,4-position of the phenyl ring are preferred compounds. The compounds of formula (I) in which R5 is an orthomethoxy group and Rg in the para-position is a group selected from: - (piperidin-1-y1)carboxamido, ? R L i . Un 2 6 4 i 9 - (2-cyanoprop-2-yl)carbonyl, - pyrrolidin-l-yl, - 3,3-diethylguanidino and - N',N'-diethylthioureido 5 are preferred compounds. The following abbreviations are used in the description and In the Examples: DCM: dichloromethane ether: ethyl ether 10 iso ether: isopropyl ether Boc: tert-butoxycarbonyl Me, MeO: methyl, methoxy Et, EtO: ethyl, ethoxy Pr, iPr, nPr: propyl, isopropyl, n-propyl 15 Bu, iBu, tBu: butyl, isobutyl, tert-butyl Ph: phenyl Bz: benzyl Ts: tosyl Ac: acetyl 20 AcOEt: ethyl acetate AcOH: acetic acid HCl: hydrochloric acid MeOH: methanol EtOH: ethanol 25 DMF: dimethyl formamide THF: tetrahydrofuran DMSO: dimethyl sulfoxide DIPEA: diisopropylethylamine NaOH: sodium hydroxide 30 NaHC03: sodium hydrogencarbonate TEA: triethylamine TFA: trifluoroacetic acid TMEDA: tetramethylethylenediamine Lawesson's reagent: 2,4-bis(4-methoxyphenyl)-l,3-35 dithia-2,4-diphosphetane 2,4-disulfide M.p.: melting point 2 6 4 i i saline solution: saturated aqueous sodium chloride solution TLC: thin layer chromatography HPLC: high pressure liquid chromatography 5 aqueous hydrochloric acid: dilute hydrochloric acid, about 1 N RT: room temperature B.p.: boiling point NMR: nuclear magnetic resonance 10 s: singlet bs: broad singlet d: doublet t: triplet q? quadruplet 15 m: unresolved signals mt: multiplet The present invention further relates to a process for the preparation of the compounds according to the invention, and their salts, which comprises: 20 1/ reacting a benzenesulfonyl halide of the formula Hal-S02 '\R ) m (RVl)ra 25 in which Hal is a halogen atom, preferably chlorine, and R'5 and Ryi are respectively either R5 and R5 as defined above for (I), or precursor groups of R5 and R0, with a l,3-dihydroindol-2-one disubstituted in the 3-position of the formula 30 17 £. U J R*3 R'i^^n R*4 o (n) in which R'i, R,2» R,3 an<* R*4 are respectively either Rj_, R2, R3 and R4 as defined for (I), or precursor groups 5 of Rj, R2, R3 and R4; and 2/ either, if R'i - Rlt R'2 - R2, R,3 - R3' R,4 - R4* r,5 ™ r5 RVI " r6' isolating the resulting compound of formula (I); 3/ or, if any one of the groups R'i, R'2* R'3* R,4, R,5 10 and/or Ryj is respectively a precursor group of Rj_, R2, R3, R4, R5 and/or R5, subjecting the compound obtained, hereafter called the compound of formula (I*), to a subsequent treatment In order to prepare the compound of formula (I) by converting any one of the groups R'i, R'2/ IS R'3, R'4, R's and/or RVI to R1# R2, R3, R4, R5 and/ or Rg respectively; and 4/ if desired, converting the resulting compound of formula (I) to one of its salts. The reaction of step 1/ is carried out in an 20 anhydrous solvent such as DMF or THF, in the presence of a metal hydride such as, for example, sodium hydride, or in the presence of an alcoholate such as potassium tert-butylate. The l,3-dihydroindol-2-ones (II) are known or can 25 be prepared by known methods using different procedures. Compounds (II) in which R'i and/or R'2 are a halogen and R'3 and R*4, together with the carbon to which they are bonded, form a spirocyclobutane, a spirocyclohexane or a spirocycloheptane are known, for 30 example from D.W. Robertson et al., J. Med. Chem., 1987, SflL (5), 824-829. Also, 5-chloro-3-spirocyclo- pentaneindol-2-one is described in patent US 3 947 451. 1Q ■e' . - •< ' ^ AO ,-t» To prepare the compounds (II) In the case where R'3 and R'4 together are a hydrocarbon group, it is possible to use the Brunner reaction described by R.F. Moore and S.G.P. Plant in J. Chem. Soc., 1951, 3475-3478, which leads to the preparation of compounds (II) in which CR'3R'4 is a cyclopentane or a cyclohexane. This reaction is carried out by cyclizing a phenylhydrazlde derivative of the formula 10 R'i NH-NH-C-CH 0 (IV) 15 in which R'i, R'2/ R'3 and R,4 are as defined above for (II), for example by heating in quinoline in the presence of calcium oxide. According to the same authors, the phenylhydrazlde derivative (IV) is obtained by reacting a hydrazine derivative of the formula 20 R' R1' -NH-NH' (v) 25 in which R'i and R*2 are as defined above for (II), with an acid halide of the formula / Hal-C—CH II \ O r; K (vi) in which R'3 and R'4 are as defined above for (II). 19 In one particular embodiment, if R'3 and R'4, together with the carbon to which they are bonded, form a polycondensed hydrocarbon ring, for example a norbornane or a norbornene, the reaction is carried out by the 5 method described by J. Wolff et al.. Tetrahedron, 1986, 42 (15), 4267-4272: First of all, a lithium salt of the compound (IV) is prepared by reaction with a lithium reagent such as n-butyllithium, in an inert solvent such as THF, at low temperature, and then the cyclization is 10 effected by heating in a solvent such as naphthalene or prehnitene (1,2,3,4-tetramethylbenzene). The compounds (II) in which R'i ■ R'2 - H and CR'3R'4 is adamantane are described in I. Fleming et al., J. Chem. Soc., Perkin Trans. I, 1991, 3., 617-626. The 15 compounds (II) in which R'3 and R'4, together with the carbon atom to which they are bonded, form an adamantane and R'2. and R'2 are other than hydrogen can be prepared by the method described above. The hydrazine derivatives (V) are known or are 20 prepared by known methods. The same applies to the acid halldes (VI). A l,3-dihydroindol-2-one disubstituted in the 3-posltion (II) can also be prepared from a 1,3-dihydroindol-2-one of the formula 25 R,i^N| J=o (VII) in which R'i and R'2 are as defined above for (II), by using various processes. 30 For example, the method described by A.S. Kende and J.C. Hodges in Synth. Commun., 1982, 12 (1), 1-10, involves the addition of an alkylating agent in an appropriate solvent. Thus, to prepare a compound (II) in 20 ■- i .1' * % which R'3 = R'4, the reaction is carried out in THF at -75 *C, in the presence of TMEDA, by the addition of an alkyllithium such as butyllithium, followed by reaction with a halide of the formula R'3Hal; if R'3 and R'4 are 5 different, the alkylation reaction can be performed in 2 steps with 2 different alkyl halides of the formulae R*3Hal and R^Hal. To prepare a compound (II) in which R'3 and R'4 together form a group of the formula -(CH2)n~ , where n varies from 3 to 12, the reagent used is a 10 compound of the formula Z(CH2 )nz^ in which Z is an electrophilic group such as a halogen, preferably bromine or iodine, a tosyloxy group or a mesyloxy group. In one variant of this process, the reaction can also be carried out by the addition of an alkali metal alcoholate, such 15 as potassium tert- butylate, onto a compound of formula (VII), in THF at -40*C, followed by the addition of a compound of the formula Z-(CH2)nz as defined above. The compounds (II) in which R'3 and R'4, together with the carbon to which they are bonded, form a C4-C8 20 hydrocarbon ring substituted by one or more Cj- C7-alkyl groups or by a C3-C5-spirocycloalkyl are prepared in the same way. The compounds of formula (II) in which R'3 and R'4 are each independently an alkyl or a phenyl are 25 known. For example, patent DE 3 300 522 describes 5-alkoxy-3,3-dimethylindol-2-ones. If R'3 and R'4 together form a group -(CH2)pX-(CH2)q-, in which p, q and X are as defined above for (I), a l,3-dihydroindol-2-one disubstituted in the 3-30 position of formula (II) can be prepared from a 1,3-dihydroindol-2-one unsubstituted in the 3-position (VII) by reaction with a compound of the formula Z-(CH2)p-X-(CH2)q-Z (VIII) 35 in which Z is as defined above and X, p and q are as 21 defined above for (I). The reaction is carried out in the presence of an alcoholate, for example potassium tert-butylate, in an anhydrous solvent such as, for example, THF. 5 If X is a nitrogen atom substituted by a (Cj- Cg)alkylcarbonyl, a formyl, a Ci-C7-alkoxycarbonyl or a Ci-Cy-alkylcarbamoyl, the substitution on X can be effected either on the l,3-dihydroindol-2-one derivative (II) or on the final compound (I) starting from a 10 compound in which the nitrogen atom (X = NH) is unsubstituted. Thus, if X is a nitrogen atom substituted by a Ci-Cy-alkoxycarbonyl, the first step is to prepare a compound (II) or (I) in which X is NH, which is then 15 reacted with the appropriate chloroformate to give the desired compound (II) or (I). In the same way, a C^- C7-alkyl isocyanate is reacted with a compound (II) or (I) in which X « NH to give a derivative (II) or a compound (I) in which X is a nitrogen atom substituted by an 20 alkylcarbamoyl. An acid chloride or an anhydride is reacted with a compound (II) or a compound (I) in which X = NH in order to prepare a compound of formula (II) or (I) in which X is a nitrogen atom substituted by a (C^-Cg)alkylcarbonyl. 25 Formic acid in the presence of acetic anhydride is reacted with a compound (II) or (I) in which X ■ NH in order to prepare a compound of formula (II) or (I) in which X is a nitrogen atom substituted by a formyl. If X is a sulfur atom or a nitrogen atom 30 substituted by R3.3, it is also possible firstly to prepare a compound of the formula 22 (CH2)pZ (CH2)qZ (n)' in which R'i, R'2, z, P and q are as defined above, and to perform a nucleophilic substitution with a hydrogen 5 sulfide salt or an amine of the formula H2NR13, in a solvent such as an alcohol, an ether, DMF or a mixture thereof, at a temperature between 5*C and the reflux temperature. The l,3-dihydroindol-2-ones of formula (II') are 10 obtained from the corresponding ddols, either as such or protected, for example by a tetrahydropyran-2- yl group. The reaction can be carried out with dibromotriphenylphosphorane according to J. Chem. Soc., Chem. Commun., 1989, 1619. 15 The compounds (II) in which R'3 and R'4, together with the carbon to which they are bonded, form a pyrrolidine, N-alkylpyrrolidine, piperidine or N-alkylpiperidine ring are described by M.J. Kornet in J. Med. Chem., 1976, 12. (7), 892-899. 20 In particular, horsfiline of the formula H 25 is an alkaloid described in A. Jossang et al., J. Org. Chem., 1991, (23), 6527-6530. To prepare a compound of formula (II) in which R' 3 and R' 4, together with the carbon to which they are 23 * *- bonded, form a tricyclo[5.2.1.02»^]decane or a tricyclo[5.2.1.02'dec-8-ene, a compound (VII') or, respectively, a compound (VII'1) of the formulae z-ch2 z-ch2 (vny (vn)" in which Z is as defined above, is reacted with a compound of formula (VII). Compounds (VII') and (VII'') substituted by one or more Ci-Cy-alkyl groups are used to 10 prepare compounds (II) in which said carbocycles are substituted. A compound of formula (II) in which R'3 and R'4, together with the carbon to which they are bonded, form a tricyclo[5.2.1.02'6]decane can also be prepared by the 15 catalytic hydrogenation of a compound of formula (ii) in which R'3 and R'4, together with the carbon to which they are bonded, form a tricyclo[5.2.1.02'®]dec- 8-ene, for example in the presence of palladium-on- charcoal or Raney® nickel. 20 a compound of formula (i) in which R3 and R4, together with the carbon to which they are bonded, form a tricyclo[5.2.1.02'®]decane can also be prepared by the catalytic hydrogenation of a compound of formula (i) in which R3 and R4, together with the carbon to which they 25 are bonded, form a tricyclo[5.2.1.02'^]dec- 8-ene, for example in the presence of palladium-on- charcoal or Raney® nickel. To prepare a compound (II) in which R'3 and R' 4, together with the carbon to which they are bonded, form 30 an indane or a hexahydroindane, a compound (VIII') or, respectively, a compound (VIII'') of the formulae 24 z-ch2 z-ch2 - (viiiy (vm)" In which Z is defined as indicated above for (VIII), is reacted with a compound (VII). Compounds (VIII') and 5 (VIII'') substituted by one or more C^-Cy-allcyl groups are used to prepare compounds (II) in which the indane or hexahydroindane is substituted. The method of A.S. Kende and J.C. Hodges described above or its variant described above can be 10 used to prepare compounds of formula (II) in which the substituents R'3 and R'4, together with the carbon to which they are bonded, form an optionally fused, saturated or unsaturated C3-C12 hydrocarbon ring substituted by one or more C1-C7-alkyl groups or by a 15 group selected from an oxo group protected under acetal form, a C3-C5-spirocycloalkyl, or one or two hydroxyls substituted by a Ci-C4~alkyl, a (C1-C5)alkoxyalkyl in which the alkyl is C1-C4, a triphenylmethoxyalkyl in which the alkyl is C1-C4, a phenylalkoxyalkyl in which 20 the alkoxy is Ci~C2 and the alkyl is C1-C4, a tetrahydrofuranyl or a tetrahydropyranyl. To obtain the compounds of formula (I) in which R3 and R4, together with the carbon to which they are bonded, form an optionally fused, saturated or unsaturated C3-C3.2 25 hydrocarbon ring substituted by one or two hydroxyls, the corresponding compounds of formula (I) in which the hydroxyl group or groups are substituted by a (C^-CsJalkoxyalkyl in which the alkyl is C1-C4, a tetrahydrofuranyl or a tetrahydropyranyl are deprotected. 30 This deprotection is effected in an acid medium, for example in the presence of a mineral or organic acid, in an alcohol or ether solvent such as THF, at a temperature between 15*C and the reflux temperature; the deprotection 25 ti c. can be carried out: for example in the presence of hydrochloric acid or pyridlnium toluenesulfonate in an alcohol. To obtain the compounds of formula (I) in which 5 R3 and R4, together with the carbon to which they are bonded, form an optionally fused, saturated or unsaturated C3-C12 hydrocarbon ring substituted by one or two o)-hydroxy(Ci-C4) alkoxy groups, the corresponding com pounds of formula (I) in which R3 and R4, together 10 with the carbon to which they are bonded, form an optionally fused, saturated or unsaturated C3-C12 hydrocarbon ring substituted by one or two (C^-C5)alkoxy(Ci~C4)alkoxy groups are deprotected. This deprotection is effected in an acid medium, for example 15 trifluoroacetic acid, in a solvent such as DCM. Compounds of formula (I) in which R3 and R4, together with the carbon to which they are bonded, form an optionally fused, saturated or unsaturated C3-C12 hydrocarbon ring substituted by one or two (C1-C4)-alkoxy 20 groups or one or two (C1-C5)alkoxy(C1-C4)alkoxy groups can also be prepared by alkylating compounds of formula (I) in which R3 and R4, together with the carbon to which they are bonded, form an optionally fused, saturated or unsaturated C3-C12 hydrocarbon ring substituted by one or 25 two hydroxyls. This alkylation is carried out more particularly with powerful alkylating reagents such as alkyl trifluoromethanesulfonates, in solvents such as DCM or carbon tetrachloride, In the presence of a base such as 2,6-di-tert-butylpyridine, by the method described in 30 Carbohydrate Research, 1975, 4A, C5-C7. The alkyl trifluoromethanesulfonates can be obtained from the alkyl iodides by reaction with a trlfluoromethanesulfonic acid salt such as the silver salt (Chemical Reviews, 1977, 77). 35 Compounds of formula (I) in which R3 and R4, together with the carbon to which they are bonded, form m p ~ , * ' 9 9 •'.re J ■ ; 1 ' /*w an optionally fused, saturated or unsaturated C3-CJ2 hydrocarbon ring substituted by one or two formyloxy groups or one or two (C2.-C7 )alkylcarbonyloxy groups can be prepared by reacting dimethyl sulfate in the presence 5 of cesium carbonate or, respectively, by reacting an acid halide or an anhydride with a compound of formula (I) in which R3 and R4, together with the carbon to which they are bonded, form an optionally fused, saturated or unsaturated C3-C12 hydrocarbon ring substituted by one or 10 two hydroxyls. A compound of formula (I) in which R3 and R4, together with the carbon to which they are bonded, form a tricyclo[5.2.1.02'®]decane-8,9-diol can also be obtained from a compound of formula (1) in which R3 and R4, 15 together with the carbon to which they are bonded, form a tricyclo[5.2.1.02'®]dec-8-ene, which is reacted with metachloroperbenzoic acid at room temperature, in a solvent such as DCM, to give an intermediate compound of formula (I) in which R3 and R4, together with the carbon 20 to which they are bonded, form a tricyclo-[5.2.1.02'6]decan-8,9-epoxy; the intermediate epoxide derivative is then hydrolyzed by refluxing in water in the presence of sulfuric acid or in a basic medium. The compounds of formula (II) in which R'3 and 25 R'4, together with the carbon to which they are bonded, form either an optionally fused, saturated or unsaturated C3-C12 hydrocarbon ring substituted by an oxo group, or a group -(CH2 )p-X-(CH2 )q- in which X is a group SO, SO2 or N(0)Ri3, are prepared by known oxidation reactions 30 starting from the corresponding compounds of formula (II) in which R'3 and R*4, together with the carbon atom to which they are bonded, respectively form either an optionally fused, saturated or unsaturated C3-C12 hydrocarbon ring substituted by a hydroxyl, or a group -(CH2 )p-X-(CH2 )q- in which X is a sulfur atom or a group NRi3. 35 27 ?'■ O o 5 tL. & For example, the oxidation of secondary alcohols to ketones can be carried out in the presence of chromium oxide complexes such as pyridinium chlorochromate, in an inert solvent such as methylene chloride, or with 5 oxidizing agents such as DMSO, by the methods described in Tetrahedron, 1978, 2Ar 1651. The oxidation of the compounds (II) containing a sulfur or nitrogen atom (X » S, NR13) can be effected in the presence of hydrogen peroxide or peracids such as 10 peracetic or metachloroperbenzoic acid, in inert solvents such as ketones or acetic acid, at temperatures between 0*C and 50'C. If R'3 and R'4 are each a phenyl, the process described in Helv. Chim. Acta, 1946, 25L, 415-432, can be 15 used to prepare a compound (II). The 1,3-dihydroindol-2-one derivatives (VII) are known or are prepared by known methods. An example which may be cited is J.V. RajanBabu in J. Org. Chem., 1986, 51, 1704-1712. 20 The compounds of formula (II) which carry certain substituents R'i and R'2 on their benzene moiety are used as precursors for the preparation of compounds of formula (II) which carry other substituents R' 1 and R'2« For example, the compounds (IX) in which R'i and/or R'2 11 H 25 can be nitrated with the conventional reagents; they can also be acylated by reaction with an acid chloride of the formula RC0C1, in which R is a Ci-Cy-alkyl, in the presence of a Lewis acid such as aluminum chloride, in order to prepare a compound (II) in which R'^ and/or R'2 30 —COR. The compound (II) in which R'i is an amino group is prepared by the catalytic hydrogenation of a compound (II) in which R'i is a nitro group and R'2 is hydrogen. The benzenesulfonyl halides (III) are prepared by known methods. Thus, for example, 4-dimethylamino-35 benzenesulfonyl chloride is prepared according to C.N. Sukenlk et al., J. Amer. Chem. Soc., 1977, £2., 851-858. 28 More generally, the benzenesulfonyl halides (XII) In which the substituent R' 5 is a dimethyl amino group are known or are prepared by known methods; p-benzyloxy-benzenesulfonyl chloride is prepared according to European patent application EP 229 566. The alkoxybenzenesulfonyl chloride is prepared from the sodium alkoxybenzenesulfonate, which is itself prepared by reacting an alkyl halide with sodium hydroxybenzenesulfonate. 2,4-Dimethoxybenzenesulfonyl chloride is prepared according to J. Am. Chem. Soc., 1952, 2A, 2008. The halogenoalkoxybenzenesulfonyl chlorides can be prepared according to patent US 2 540 057. The benzenesulfonyl halides of the formula so2ci OAlk YR (iny V in which - Alk is a Ci-C7~alkyl; Y is O or S; and - Ry is a Ci--C7-alkyl, a C3-C7-cycloalkyl, a C2-C7-alkenyl, an co-halogeno-Ci-C7-alkyl, a polyhalogeno- C]_-C7-alkyl, a benzyl, a (Ci-Cg)alkylcarbonyl, a formyl or an (i)-carboxy-Ci-C7-alkyl esterified by a Ci-C4-alkyl or a benzyl, are prepared according to D. Hofmann et al. in Liebigs Ann. Chem., 1982, 287-297. Benzene compounds carrying the substituents YRy and OAlk in the 1- and 3-positions are reacted with 29 &K V 5 L» trlmethylsilyl chlorosulfonate in a solvent such as DCM, at RT. The method of R. Passerlni et al. in Gazz. Chim. Ital., 1960, 30., 1277-89, is then applied and this Is followed by neutralization, for example with alkali metal carbonate, and then by reaction with a halide such as POCI3 to give the desired benzenesulfonyl halide. The benzenesulfonyl halides (III) in which the substituent R'5 is an alkoxycarbonyl, a phenoxycarbonyl, a benzyloxycarbonyl, an alkylthio, a phenylthio, a benzylthio or a group -SR7, R7 being as defined for (I), are prepared according to Col. Czechoslov. Chem. Commun., 1984, 49. 1184, from an aniline derivative substituted by the same grouping R's, said aniline derivative itself being obtained from the corresponding nitro derivative. The nitrobenzoic acid derivatives are known; the corresponding alkyl and phenyl esters are obtained by subjecting this acid to an appropriate esterification reaction. The benzenedisulfonyl dihalides (III, R5 -SC>2Hal) are known or are prepared by known methods. For example, 2,4-dimethoxybenzene-l,5-disulfonyl dichloride is described in R.J.W. Cremlyn, J. Chem. Soc. C, 1969, 1344. The halogenoalkoxybenzenesulfonyl chlorides (III, R' 5 » co-halogenoalkoxy) are used to prepare compounds according to the invention in which the substituent R5 is an (o-aminoalkoxy which is unsubstituted or substituted by one or two alkyls, according to the following equation: -O-Alk1 -Hal + NHAA' -» -O-Alk'-NAA' in which Alk' is a C2~C7-alkyl and A and A' are independently hydrogen or a C1-C7-alkyl. For certain meanings of the substituents Ri, R2, R5 and/or Rg, the compounds (I) according to the 30 64122 invention can be prepared from a precursor of formula (I* ) substituted by a group R' i, R' 2 / R' 5 and/or Ryj, called a precursor group of Rj., R2, R5 and/or Rg, by using methods known to those skilled in the art. 5 The description which follows relates to the preparation of the compounds of formula (I) carrying substituents Ri and/or R5; the same methods apply to the preparation of the compounds in which the substituents R2 and/or Rg have the meanings indicated for and R5. 10 The compounds (I) in which R^ and/or R5 are a hydroxyl can be obtained by the catalytic hydrogenation of a compound of formula (I1) in which R'i and/or R'5 are a benzyloxy, for example in the presence of palladium-on-charcoal. These compounds can also be prepared from IS analogous compounds of formula (I') in which R' 1 and/or R' 5 are an amino group by using the method described in J. Org. Chem., 1977, 42, 2053. The compounds of formula (I) in which R^ and/or R5 are a Ci-C7~alkoxy can be prepared directly by the 20 process according to the invention starting from the correctly substituted compounds of formulae (II) and (III). The compounds (I') in which R'j and/or R'5 are a hydroxyl can also be used to prepare compounds (I) in 25 which Ri and/or R5 are a Ci-C7-alkoxy by reaction with a Ci~C7-alkyl halide in the presence of a base such as a metal hydride or an alkali metal or alkaline earth metal carbonate like K2CO3 or Cs2C03, in a solvent such as THF or DMF. Likewise, the compounds of formula (I) in which 30 Ri and/or R5 are an to-aminoalkoxy are prepared by reacting an ui-chloroalkylamine with the compounds in which R'i and/or R*5 » OH; similarly, the compounds in which Ri and/or R5 are an to-hydroxyalkoxy are prepared by reaction with a chloroalkyl alcohol; in the particular 35 case of the preparation of a compound (I) in which R^ and/or R5 = -0(CH2)20H, it is also possible to react ethylene carbonate with a compound (I' ) in which R' ^ and/or R's * OH. The compounds of formula (I) in which and/or R5 are a (C^-Cg)alkylcarbonyloxy are obtained by reacting 5 an acid halide or an anhydride with a compound (I') in which R11 and/or R'5 are a hydroxyl. The compounds of formula (I) in which R^ and/or R5 are a formyloxy are obtained for example by reacting formic acid in the presence of dicyclohexylcarbodiimide 10 with a compound (I') in which R'i and/or R'5 are a hydroxyl (J. HUANG et al, J. Chem. Res.(S), 1991, 292-293). The compounds of formula (I) in which R5 is a group -OR7, R7 being an co-carbamoyl-Ci-C7-alkyl which is 15 free or substituted by one or two Ci-C7~alkyls, can be prepared from a compound (I' ) in which R'5 is a group -ORy, Ry being an ti)-carboxy-Ci-C7-alkyl esterified by a Ci-Cy-alkyl. This preparation is carried out by reaction with a correctly chosen amine in a manner conventional to 20 those skilled in the art. To prepare compounds of formula (1) in which and/or R5 are a (Ci-C7)monoalkylamino, a compound of formula (I' ) in which R' ^ and/or R' 5 are an amino group is reacted with an aldehyde or ketone in an acid medium, 25 in the presence of a reducing agent such as sodium cyanoborohydride; the compounds (I) in which R^ and/or R5 are a dialkylamino are prepared by an identical reaction. The compounds of formula (I) in which R5 is an amino group substituted by a benzyl, which is Itself 30 optionally substituted, or by a C3-Cg-alkene can be prepared by reacting a benzyl chloride or a C3~Cg-chloroalkene with a compound of formula (I') in which R'5 is an amino or alkylamino group. The compounds of formula (1) in which R5 is a A3-35 pyrrolin-l-yl group are prepared by reacting cis- 1,4-dichlorobut-2-ene with the compounds of formula (I * ) in 32 264 1 2 which R'5 is an amino group, in -the presence of a base puch as triethylamine, under an inert atmosphere. The compounds of formula (I) in which R5 is a pyrrolidin-l-yl group are then prepared by hydrogenation. The reaction 5 of cis-1,4-dichlorobut-2-ene with the compounds (I1) in which R' 5 is an amino group can also be carried out in air, in the presence of a base such as sodium carbonate, under which conditions It results in the formation of a mixture of a compound of formula (I) in which R5 is a A3-10 pyrrolin-l-yl and a compound of formula (I) in which R5 is a pyrrol-l-yl group, which can be separated by chromatography. The compounds of formula (I) in which R5 is an isoindolin-2-yl group are prepared by reacting a, a' -IS dibromo-o-xylene with the compounds of formula (I') in which R'5 is an amino group, in the presence of a base such as triethylamine, and in a solvent such as dimethylformamide, under reflux. The compounds of formula (I) in which R5 is a 1-20 methyl-2,4-dioxoimidazolin-3-yl group (NRgRg ■«. N-methylhydantoin) are prepared in two steps: Sarcosine is reacted with a compound of formula (I') in which R'5 is a phenoxycarboxamido, in the presence of a base such as triethylamine, to give a compound of formula (I') in 25 which R'5 is an N' -carboxymethyl-N' -methylureido; the previously obtained product then cyclizes on heating at 100'C under vacuum. The compounds of formula (I) in which R5 is a 2,4-dioxoimidazolin-3-yl group (NRgRg -hydantoin) are prepared in the same manner by reacting 30 glycine with a compound of formula (I') as defined above. If R'i and/or R'5 are an amino, it is also possible to perform a nitrosation, for example in the presence of nitrous acid or sodium nitrite, in order to prepare a compound (I') in which R'i and/or R'5 are a 35 diazonium 3alt; reactions known to those skilled in the art then afford the compounds (I) according to the 33 ft n- 0 Or* invention in which and/or R5 are a cyano, a halogeno or a Ci-C7-thioalkyl. Finally, compounds (I) in which R]_ and/or R5 are a group of the formula RCONH-, ROCONH-, RNHCONH- or RSO2NH-, in which R is a Cx-Cy-alkyl, a 5 phenyl or a benzyl, can be prepared by conventional reactions starting from compounds (I' ) in which R'1 and/or R'5 » NH2* The compounds of formula (I) in which R5 is a C^-C7-alkoxycarbonyl can be prepared directly by the process 10 according to the invention. Using methods known to those skilled in the art, they make it possible to obtain the compounds of formula (I) in which R5 is a carboxyl group. The compounds of formula (!') in which R'5 is a benzyloxycarbonyl can also be used to obtain the 15 compounds (I) in which R5 is a carboxyl by catalytic hydrogenation. Reaction with a thionyl halide gives the compounds of formula (I') in which R'5 is a halogenocarbonyl. Such compounds are used to prepare compounds of formula (I) in which R5 is a carbamoyl 20 substituted by R'g and R''g by reaction with a compound HNR' gR' ' 5. The compounds of formula (I' ) in which the substituent R'5 is a phenoxycarbonyl can also be used to obtain the compounds (I) in which R5 is a phenylcarbamoyl or a Ci-C7-alkylcarbamoyl by reaction with an aniline or 25 a C2.-C7-alkylamine. An aniline substituted on the phenyl or an alkylaralne substituted on the alkyl can be used to obtain compounds of formula (I) in which R5 Is a phenylcarbamoyl substituted on the phenyl or, respectively, an alkylcarbamoyl substituted on the alkyl 30 by Rg". In the same way, the compounds of formula (I) In which r5 is a group -conthcrior' iocor12 are prepared from compounds of formula (I') in which R'5 is either a group -coc1 or a phenoxycarbonyl group by reaction with 35 h2ncr10r,10cor12. The compounds of formula (I) in which R5 is a 34 0 e~ Vy-j ) group -COR'7 are prepared from corresponding compounds (I') in which R'5 is a phenoxycarbonyl by reaction with R'7H. A compound (I') in which R'5 is a nitro group 5 makes it possible to obtain a compound (I) in which R5 is an amino group by catalytic hydrogenation, for example in the presence of platinum oxide, Raney® nickel or palladium-on-charcoal, or by chemical reduc tion, for example in the presence of tin or iron in an acid medium; 10 other compounds in which the amino group is substituted can then be prepared using reactions well known to those skilled in the art. For example, if it is desired to obtain a compound (I) according to the invention in which R5 is a 15 group -NRgRg, Rg being an optionally substituted benzoyl, benzoyl chloride in which the phenyl carries the appropriate substituent is reacted with a compound (I* ) in which R'g is an amino group, in the presence of an amine such as triethylamine. For example, 4-chloro-20 sulfonylbenzoyl chloride can be reacted in order to prepare a compound (I') in which R'5 is a 4-chloro-sulfonylbenzamido group, after which a compound (1) in which the substituent R5 is a 4-sulfamoylbenzantido group or a 4-alkylsulfamoylbenzamido group is obtained by 25 reaction with ammonia or a Ci-C4-alkylamine respectively. In the same way, the acid chloride RuR' uNCRiqR' iqCOCI is reacted with a compound of formula (I') in which R'5 is a group -NHRq in order to prepare a compound of formula (I) in which R5 is an -NRg substituted by -30 COCRxoR'ioNRllR'll' If it is desired to prepare a compound (I) In which R5 is a group -NRgRg, Rg being a (Ci-Cg)alkyl-carbonyl, the appropriate anhydride or the appropriate acid chloride is reacted with a compound (I') in which 35 R'5 is an amino group, in the presence of an amine such as triethylamine. To prepare a compound (I) in which R5 35 t 0 is a group -NRgRg, Rg being a formyl, formic acid is reacted with a compound (I') in which R'5 is an amino group, in the presence of acetic anhydride and of an amine such as triethylamine. 5 In another preparatory example, a compound (I) in which R5 is an alkylsulfonamido group is obtained by reacting an alkylsulfonyl halide with a compound (I') in which R'5 is an amino group. The compounds of formula (I') in which R'5 is an 10 amino group are also useful for the preparation of compounds in which this amino group is substituted by a group -(CH2)-t~c0Ri2* In "this case, a compound of the formula Hal-(CH2)^-COOAlk, in which Hal is a halogen, for example bromine, and Alk is a C^-Cy-alkyl, is reacted IS with (I') in the presence of cuprous chloride; if required, the resulting ester is converted to the acid or an amide. A compound (I) in which R5 ■ -NHCO-(CH2)t'C02H' where t' - 2 or 3, can be prepared by reacting an anhydride, such as succinic anhydride or glutaric 20 anhydride, with a compound (I') in which R'5 is an amino. If required, the resulting acid is converted to an ester or an amide. A compound (I) in which R5 - -NHC0C02Et or -NHC0CH2C02Et can be prepared by reacting ethyloxalyl 25 chloride, or, respectively, ethylmalonylchloride, with a compound (I') in which R'^ is an amino. In the same way, the compounds of formula (I) in which R5 is an amino group substituted by a group CRiqr'10cor12 are prepared by reacting a compound of the 30 formula Hal-CRioR'10C0R12 with the corresponding compounds (I') in which the substituent R'5 is an amino. A compound (I) in which R5 is an amino group substituted by a Ci-Cy-alkoxycarbonyl or a phenoxycarbonyl is prepared by reacting a C1-C7-alkyl or 35 phenyl chloroformate with a compound (I' ) in which the substituent R'5 is an amino. 36 Likewise, a compound of formula (1) in which R5 is a phenoxythlocarbonylamino is obtained by reacting a phenoxythiocarbonyl chloride with a compound of formula (I') in which R'5 is an amino group. 5 A compound of formula (I) in which R5 is a ureldo or a thioureido Is prepared by reacting ammonia with a compound of formula (I1) in which R'5 is an amino group substituted by a phenoxycarbonyl or a phenoxythiocarbonyl; such a compound of formula (IV) is 10 reacted with a correctly substituted aniline or a correctly substituted Ci-Cy-monoalkylamine or -dialkyl-amine in order to prepare a compound of formula (I) in which R5 is a correctly substituted N'-phenylureido or a correctly substituted N'-alkylureido or N',N'-di-15 alkylureido in which the alkyl is C1-C7. It is also possible to prepare a compound (I) in which R5 is a ureido (-NHCONR14R' 14) or a thioureido (-NHCSNRi4R'14) by reacting a compound NHRj^R'j^ with a compound (I') in which R'5 is a phenoxycarbonylamino or, 20 respectively, phenoxythlocarbonylamino group. A further possibility is to prepare a compound (I) in which R5 is a ureido (-NHCONRi4R'i4) or a thioureido by reacting a carbamoyl chloride (CICONR^R*14) or, respectively, a thiocarbamoyl chloride 25 with a compound of formula (I' ) in which R'5 is an amino group. It is also possible to prepare a compound (1) in which R5 is a thioureido by reacting Lawesson's reagent with a compound (I') in which R'5 is the corresponding 30 ureido. The compounds (I) in which R5 is a guanidino group which is unsubstituted or monosubstituted or disubstituted by a Ci-Cy-alkyl, a phenyl or a benzyl can be prepared from the compounds (I' ) in which R' 5 is a 35 phenoxyamido group by reaction with cyanamide or a derivative thereof correctly substituted on the nitrogen. A compound (I) in which R5 is a carbamoyl which is unsubstituted or substituted by one or 2 C^-Cy-alkyl groups is prepared by reacting an appropriate amine with a compound (I1) in which the substituent R'5 is an amino, 5 in the presence of phosgene. It is also possible to prepare a compound (I) in which R5 is an amino group substituted by an alkylcarbamoyl or a phenylcarbamoyl by reacting an alkyl or phenyl isocyanate with a compound (I' ) in which the 10 substituent R'5 is an amino. Furthermore, a compound (I) in which R5 is a sulfamoyl group which is unsubstituted or substituted by a Ci-Cy-alkyI is prepared by reacting ammonia or a C1-C7-alkylamine with a compound (!') in which R'5 is a 15 halogenosulfonyl group. The affinity of the compounds according to the invention for the vasopressin receptors was determined in vitro using the method described in C.J. Lynch et al., J. Biol. Chem., 1985, 260 (5), 2844-2851. This method 20 consists in studying the displacement of tritiated vasopressin bound to the Vi sites of rat liver membranes. The concentrations of the compounds according to the invention which cause a 50% inhibition of the binding of tritiated vasopressin (IC50) are low, ranging down to 10" 25 7 M. The affinity of the compounds (I) according to the invention for the V2 receptors was measured on a bovine kidney membrane preparation by a method adapted from P. Crause et al., Molecular and Cellular 30 Endocrinology, 1982, 2fl, 529-541, and F.L. Stassen et al., J. Pharmacol. Exp. Ther., 1982, 223 r 50-54. The com pounds according to the invention inhibit the binding of tritiated arginine vasopressin to the receptors of the membrane preparation. The IC50 values of the compounds 35 according to the invention are low, ranging down to 10""^ M. 38 The antagonistic activity of the compounds according to the invention towards the V2 receptors was demonstrated by the adenylate cyclase activity assay performed by a method adapted from M. Laburthe et al., 5 Molecular Pharmacol., 1986, 22., 23-27. A bovine kidney membrane preparation is used and each product is incubated for 10 minutes at 37 *C, either by itself or in the presence of AVP (arglnine vasopressin) at a concentration of 3.10"® M. The cyclic AMP (cyclic 10 adenosine monophosphate) produced is measured by radioimmunoassay. The concentration which causes a 50% inhibition (IC50) of the stimulation of adenylate cyclase induced by 3.10~® M AVP is determined. The IC50 values determined are of the order of 10"7 M, ranging down to 15 10"8 M. The agonistic or antagonistic activity of the compounds according to the invention, administered orally, towards the vasopressin receptors is evaluated in hyperhydrated rats (OFA, Sprague-Dawley strain) treated 20 with vasopressin. The antagonistic activity of the compounds according to the invention was also evaluated in normally hydrated rats (OFA strain or Sprague-Dawley strain) by the technique described in Br. J. Pharmacol., 1992, 105r 787-791. The diuretic effect was observed for 25 some of the compounds at a dose of 10 mg/kg. Likewise, the affinity of the compounds (I) according to the invention for the ocytocin receptors was determined in vitro by the displacement of a radioiodinated ocytocin analog bound to the receptors of 30 a gestating rat mammary gland membrane preparation by a technique similar to that described by J. Eland et al. in Eur. J. Pharmacol., 1987, 147r 197-207. The IC50 values of the compounds according to the invention reach 10"® M. The compounds according to the invention are 35 active after administration by different routes, especially orally. 39 No signs of toxicity are observed with these compounds at the pharmacologically active doses. Thus the compounds according to the invention can be used in the treatment or prevention of various 5 vasopressin-dependent or ocytocin-dependent complaints, cardiovascular complaints such as hypertension, pulmonary hypertension, cardiac insufficiency, myocardial infarction or coronary vasospasm, in particular in smokers, unstable angina and PTCA (percutaneous 10 transluminal coronary angioplasty), cardiac ischemia, hemostatic disorders, especially hemophilia, and von Willebrand's syndrome, complaints of the central nervous system, for example migraine, cerebral vasospasm, cerebral hemorrhage, cerebral edemas, depression, 15 anxiety, psychotic states and memory disorders, complaints of the renal system, such as edemas, renal vasospasm, necrosis of the renal cortex, hyponatremia, hypokalemia and Schwartz Bartter's syndrome, complaints of the gastric system, such as gastric vasospasm, 20 hepatocirrhosis, ulcers, the pathology of vomiting, for example nausea, including nausea due to chemotherapy, travel sickness or else the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), diabetes insipidus and enuresis. The compounds according to the 25 invention can also be used in the treatment of disorders of sexual behavior; in women, the compounds according to the Invention can be used for treating dysmenorrhea or premature labor. The compounds according to the invention can also be used in the treatment of small cell lung 30 cancer, hyponatremic encephalopathy, Raynaud's disease, pulmonary syndrome and glaucoma and in postoperative treatments, especially after abdominal surgery. The present invention further relates to pharmaceutical compositions containing an effective dose 35 of a compound according to the invention, or a pharmaceutical^ acceptable salt, and suitable 40 <r% r: £ V) excipients. Said excipients are chosen according to the pharmaceutical form and the desired mode of administration. 5 in the pharmaceutical compositions of the present invention for oral, sublingual, subcutaneous, intramuscular, intravenous, topical, intratracheal, intranasal, transdermal or rectal administration, the active principles of formula (I) above, or their salts 10 where appropriate, can be administered to animals and humans in unit forms of administration, mixed with conventional pharmaceutical carriers, for the prophylaxis or treatment of the above disorders or diseases. The appropriate unit forms of administration include forms IS for oral administration, such as tablets, gelatin capsules, powders, granules and solutions or suspensions to be taken orally, forms for sublingual, buccal, intratracheal or intranasal administration, forms for subcutaneous, intramuscular or intravenous administration 20 and forms for rectal administration. For topical application, the compounds according to the invention can be used in creams, ointments or lotions. To obtain the desired prophylactic or therapeutic effect, the dose of active principle can vary between 25 0.01 and 50 mg per kg of body weight and per day. Each unit dose can contain from 0.5 to 1000 mg, preferably from 1 to 500 mg, of active ingredients in combination with a pharmaceutical carrier. This unit dose can be administered 1 to 5 times a day so as to 30 administer a daily dosage of 0.5 to 5000 mg, preferably 1 to 2500 mg. If a solid composition is prepared in the form of tablets, the main active ingredient is mixed with a pharmaceutical vehicle such as gelatin, starch, lactose, 35 magnesium stearate, talc, gum arable or the like. The tablets can be coated with sucrose, a cellulose 41 2 6 % 1 derivative or other appropriate substances, or else they can be treated so as to have a sustained or delayed activity and so as to release a predetermined amount of active principle continuously. 5 A preparation in the form of gelatin capsules is obtained by mixing the active ingredient with a diluent and pouring the resulting mixture into soft or hard gelatin capsules. A preparation in the form of a syrup or elixir or 10 for administration in the form of drops can contain the active ingredient together with a sweetener, which is preferably calorie-free, methylparaben and propylparaben as antiseptics, a flavoring and an appropriate color. The water-dispersible powders or granules can 15 contain the active ingredient mixed with dispersants or wetting agents, or suspension agents such as polyvinylpyrrolidone, as well as with sweeteners or taste correctors. Rectal administration is effected using 20 suppositories, which are prepared with binders melting at the rectal temperature, for example cocoa butter or polyethylene glycols. Parenteral administration is effected using aqueous suspensions, isotonic saline solutions or sterile 25 and injectable solutions which contain pharmacologically compatible dispersants and/or wetting agents, for example propylene glycol or butylene glycol. The active principle can also be formulated as microcapsules, if appropriate with one or more carriers 30 or additives. In addition to the products of formula (I) above or one of the pharmaceutically acceptable salts, the compositions of the present invention can contain other active principles which may be useful in the treatment of 35 the disorders or diseases indicated above. Thus the present invention further relates to 42 ^ P. C. v ** pharmaceutical compositions in which several active principles are present in association, one of them being a compound according to the invention. Thus, according to the present invention, it is 5 possible to prepare pharmaceutical compositions in which a compound according to the invention is present in association with a compound which acts on the renin-angiotensin system, such as a converting enzyme inhibitor, an angiotensin II antagonist or a renin 10 inhibitor. A compound according to the invention can also be associated for example with a peripheral vasodilator, a calcium inhibitor, a beta-blocker, an alpha-1- blocker or a diuretic. Such compositions will be useful in particular in the treatment of hypertension 15 or heart failure. It is also possible to associate two compounds according to the Invention, namely a specific Vj. receptor antagonist with a specific V2 receptor antagonist, or else a specific receptor antagonist with a specific 20 ocytocin antagonist. These associations will make it possible to reinforce the therapeutic activities of the compounds according to the invention. 25 Preparation of the 1.3-dlhvdrolndol-2-ones Preparation 1: 1,3-Dihydro-4,6-dimethyl-3-spirocyclohexane-indol-2-one 30 This compound is prepared according to Moore and Plant in J. Chem. Soc., 1951, 3475. A mixture containing 15 ml of guinoline and 10 g of calcium oxide is refluxed under an inert atmosphere and 5 g of the 3,5-dimethylphenylhydrazide of 35 cyclohexanecarboxylic acid (IV, R'i, R'2 " CH3, CR^R^ » cyclohexane) are added over 30 minutes. The reaction medium Is cooled and then poured Into an Ice/hydrochlorlc acid mixture. Extraction is carried out with ethyl acetate and the extract is washed with normal hydrochloric acid and with water until the washings are neutral, and then dried and concentrated under vacuum to give a brown solid. Trituration in iso ether gives the expected compound. M.p. - 223*C. The l,3-dihydroindol-2-one derivatives described in Table 1 below are obtained by following the same procedure and varying the starting hydrazide. These compounds are purified by chromatography on a silica column using DCM as the eluent or by chromatography on an alumina column using DCM or iso ether as the eluent. TABLE 1 Ri f"K' -=o N H R'l R'2 CR'3R'4 M.p. *C Cl-5 H cyclobutane 191 CI-5 H cyclopentane 189 Cl-5 H cyclohexane 186 H H cyclohexane 123-124 CH3-5 H cyclohexane 164 CH3O-5 H cyclohexane 226 Cl-6 H cyclohexane 168 CF3O-5 H cyclohexane 164 CfiHsO-5 H cyclohexane 160 44 y ife» Preparation 2; The 1,3-dihydro-3-spirocyclohexaneindol-2-one described in Table 1 above can also be obtained by alkylation of the indol-2-one using the process according 5 to A.S. Kende and J.C. Hodges or a variant described below. A solution of 30 g of 1,3-dihydroindol-2-one in 900 ml of THF is kept at -40* C under a nitrogen atmosphere and 101 g of potassium tert-butylate are 10 added. The temperature is allowed to rise to 0*C over 1 hour, the mixture is then cooled to -60 *C and a solution of 52 g of 1,5-dibromopentane in 50 ml of THF is added dropwise. After 30 minutes at -60*C, the temperature is allowed to rise to RT, 30 ml of water are then added and is the solvent is evaporated off under reduced pressure. The residue is taken up with 500 ml of DCM and 200 ml of water, the insoluble material is then filtered off and the organic phase is separated off, washed with 100 ml of water, dried over magnesium sulfate and evaporated under 20 vacuum. The residue is chromatographed on silica using a cyclohexane/ether mixture as the eluent to give the expected compound, which is recrystalllzed from heptane, m - 34 g. M.p. - 123-124*C. A similar procedure can be applied starting from 25 other 1,3-dihydroindol-2-ones and other alkylating agents. By way of example, among the starting compounds of formula (VII), 5-chloro-l,3-dihydroindol-2-one is described by Wright in J. Am. Chem. Soc., 1956, 23, 221, 30 and by RajanBabu in J. Org. Chem., 1986, SI, 1704. 4-Chloro-l,3-dihydroindol-2-one can be prepared from 2-chloro-6-nitrotoluene by the method described in J. Am. Chem. Soc., 1956, 23, 221. 1,3-Dihydro-5-methoxyindol-2-one is prepared from 35 4-methoxyaniline by the method described in J. Am. Chem. Soc., 1974, 5512. In the same way, various 1,3- 45 dihydroindol-2-ones are prepared from the appropriate aniline derivative. Preparation 3: 5-Ethoxy-l,3-dihydroindol-2-one 5 A - 3-Methylthio-5-ethoxy-l,3-dihydroindol-2- one 23.6 g of ethyl methylthioacetate in 60 ml of DCM are added to a solution, cooled to about -70*C, of 12.5 g of chlorine in 400 ml of DCM. After stirring for 5 10 minutes at the same temperature, a solution of 4-ethoxyaniline (48.3 g) in 120 ml of DCM is added. The mixture is stirred for one hour at about -70*C, 39.3 ml of triethylamine are added and the resulting mixture is allowed to warm up to room temperature. 200 ml of water 15 are added and the organic phase is decanted, dried over magnesium sulfate and evaporated under reduced pressure. The residue is taken up with 500 ml of isopropanol and 20 ml of concentrated hydrochloric acid. The mixture is stirred for about 16 hours at room temperature and 20 filtered and the precipitate is separated off. The filtrate is concentrated under reduced pressure to give the expected product. B - 5-Ethoxy-l,3-dihydroindol-2-one The above solid, in 1500 ml of isopropanol, is 25 dethiomethylated in the presence of 100 g of Raney® nickel (80 to 100 m2 per g), under reflux, for 3 hours, under a nitrogen atmosphere. The mixture is filtered on talc, the material on the filter is rinsed with 1000 ml of Isopropanol and the filtrate is concentrated under 30 reduced pressure. 16 g of the expected product are isolated after recrystallization from toluene. M.p. -156*C. The following are isolated in the same manner starting from the corresponding anilines: 35 5-benzyloxy-l,3-dihydroindol-2-one m.p. = 152#C 46 5-n-propyl-l,3-dihydroindol-2-one m.p. - 136*C 5-ethyl-l,3-dihydroindol-2-one m.p. - 152*C 5-(2,2,2-trifluoroethoxy)-l,3-dihydroindol-2-one m.p. ■ 145*C 5-trifluoromethyl-l,3-dihydroindol-2-one m.p. » 193*C 5-fluoro-l,3-dihydroindol-2-one m.p. » 143*C The compounds of formula (II) described below are obtained by following the technique described in Preparation 2 and varying the starting 1,3-dihydro-indol-2-one derivative and the alkylating reagent. TABLE 2 (n) R'l R'2 CR'3R'4 M.p.'C alkylating reagent 5-C1 H cyclohexane 186-189 Br(CH2)5Br 5-C1 H cycloheptane 202 Br(CH2)6Br 5-C1 H 4,4-dimethyl 180 TSO(CH2>2C(CH3)2- cyclohexane -(CH2)20Ts 5-a H hexahydroindane-2 223 cis~l ,2-diiodomethyl- cyclohexane 5-OCH3 H 4,4-dimethyl 202 TsO(CH2>2qCH3)2- cyclohexane -(CH^-OTs TABLE 2 (continuation) R'l R'2 CR'3R'4 m.p. *C alkylating reagent 5-Cl h indane-2 228 a.a'-dibromomethyl orthoxyl&ne 5-c1 h CCCH3)2 160 ch3I 5-Cl h qch2ch3)2 156 ch3ch2i 5-Cl h C(nPr)2 158 nPrl 5-Cl h C(iBu)2 164 iBuI 5-Cl h N-methyl 260 C1(CH2)2N(CH3)- piperidinc-4 -(CH^Cl 5-Cl h tctrahydropyran-4 223 I(CH2)20(CH2)2l 4-a h cyclohexane 215 brcch^br 5-OBz h cyclohexane 162 btfch^br h h qch2c6h5)2 206 C6H5CH2Br 5-a h C(n-pentyl)2 142 CH3(CH2)4Br BrCH2 CH2Br 5-Cl h 2,3-dihydro - phenalene-2 5-OBz H 4,4-dimethyl 154 TSO(CH2)2V"XCH3)2- cyclohexane -(CH^OTs 5-a H 4-spirocyclopentane 202 (CH2)2OTs (CH2)2OTs 5-nPr H cyclohexane 151 Br(CH2)5Br 5-OEt H N-tBu (CH2)2Br piperidine-4 tBu-N (CH2)2Br TABLE 2 (continuation) R'l R'2 CR'3R'4 M.p. *C alkylating reagent 5-Cl H N-Bz piperidinc-4 165 (CH2)2Br Bz-N (CH2)2Br 5-Cl H N-phenyl piperidine-4 188 (CH2)2C1 c6h5-* ^(CH2)2Q 5-Cl H *09 300 ^ XH^OSOoCHa cc ^^^^Vn>CH20S02CH3 5-OEt 5-OEt 5-OEt 5-OEt 5-Et 5- OCH2CF3 H 5-CF3 5-F H H H H H H H H H 4,4-dicthyl cyclohexane cyclohexane 4,4-dimethyl cyclohexane cycloheptane 4,4-dimethyl cyclohexane 4,4-dimethyl cyclohexane 4,4-dimethyl cyclohexane 4,4-dimethyl cyclohexane 4,4-dimethyl cyclohexane 132 163 178 139 160 164 169 211 171 TsO(CH2)2qC2H5)2 -(CH2)20Ts Bi(CH2)5Br TsCXCH2)2C(CH3)2--(CH2)20TS BrCCH2)6Br TSO(CH2)2C(CH3)2--(CH2)20TS idem idem idem idem TABLE 2 (continuation) Preparation 4: 1,3-Dihydro-3-spiroadamantaneindol-2-one This compound is prepared according to I. Fleming et al., Tetrahedron Letters, 1982, 2053-2056, starting from 2-bromoaniline and adamantan-2-one. Preparation 5; 5-Chloro-l,3-dihydro-3,3-diphenylindol-2-one This compound is prepared by the method described in Helv. Chim. Acta, 1946, 23., 415-431, by the reaction of benzene witn 5-chloroisatin in the presence of aluminum chloride. M.p. » 281*C. Preparation 6: 5 1,3-Dihydro-5-nitro-3-spirocyclohexaneindol-2- one This compound is prepared by the method described in J. Am. Chem. Soc., 1945, fiZ, 499, by the nitration of l,3-dihydro-3-spirocyclohexaneindol-2-one. M.p. « 192*C. 10 1,3-Dihydro-5-nitro-3-spiroadamantaneindol-2- one is prepared in the same manner starting from 1,3-dihydro-3-spiroadamantaneindol-2-one. M.p. > 260*C. 1,3-Dihydro-5-nitro-3-spiro(4,4-dimethylcyclo-hexane)indol-2-one is also prepared. M.p. - 195*C. 15 Preparation 7; 5-Amino-l,3-dihydro-3-spirocyclohexaneindol-2- one This compound is prepared by the method described in J. Chem. Soc., 1951, 3475, by the reduction of 1,3-20 dihydro-5-nitro-3-spirocyclohexaneindol-2-one, prepared above. M.p. - 176'C. 5-Amino-l,3-dihydro-3-spiroadamantaneindol-2- one is prepared in the same manner. M.p.c - 245*C. 25 Preparation fl: 5-Fluoro-l,3-dihydro-3-spirocyclohexaneindol-2- one A - 5-Diazonium-l,3-dihydro-3-spirocyclohexane-indol-2-one tetrafluoroborate 30 A solution containing 4 g of 5-amino-l,3-dihydro- 3-spirocyclohexaneindol-2-one in 9.2 ml of 6 N hydrochloric acid is cooled to 0*C and 2.27 g of sodium nitrite in 2.6 ml of water are added, followed by 2.54 g of sodium tetrafluoroborate in 9 ml of water. After 35 stirring for 5 minutes, the precipitate is filtered off and washed with a 5% solution of tetrafluoroborate, with X L-J& 51 3 ml of methanol cooled to about 0*C and then with 5 ml of ether. The salt obtained is dried under vacuum at RT in the presence of phosphorus pentoxide. B - 5-Fluoro-l,3-dihydro-3-spirocyclohexane-5 indol-2-one 1 g of the compound obtained in step A is placed in 5 ml of xylene and heated at about 115*C for 2 hours. The mixture is cooled to RT, the precipitate is filtered off and rinsed with toluene and 0.1 g of active charcoal 10 is added to the filtrate. After filtration, the solvent is evaporated off under reduced pressure to give 0.45 g of the expected compound, which is recrystallized from pentane. M.p. » 114*C. Preparation 9; 15 5-Cyano-l,3-dihydro-3-spirocyclohexaneindol-2- one 4.78 g of potassium cyanide and 4.95 g of cuprous cyanide are dissolved at RT in 40 ml of DMSO. The solution Is cooled to about 15*C and 4.15 g of the 20 diazonium salt obtained in step A of the previous preparation are added. After stirring for 30 minutes at RT, 100 ml of water and 100 ml of ether are added and the organic phase is then separated off, dried over magnesium sulfate and 25 evaporated under reduced pressure. The residue is chromatographed on silica using a cyclohexane/ether mixture as the eluent to give the expected compound, which is recrystallized from heptane. m - 1.4 g. M.p. - 216*C. 30 Preparation 1Q: 5-Chloro-l,3-dihydro-3-spiroadamantaneindol-2- one 1 g of the p-chlorophenylhydrazide of adamantane-35 2-carboxylic acid is dissolved in THF and 2.5 ml of a solution of n-butyllithium (1.6 M in hexane) are added at 52 p- 4 i 9 n -40*C. After stirring for 5 minutes, the mixture is concentrated under vacuum, the temperature being kept below 30*C. 30 ml of 1,2,3,4-tetramethylbenzene are added and the mixture is refluxed for 1 hour. It is 5 concentrated under reduced pressure, the residue is taken up with normal hydrochloric acid, extraction is carried out with ether and the extract is washed, dried and concentrated under vacuum. The oil obtained is chromatographed on a silica column using DCM as the 10 eluent to give 0.3 g of the expected product in the form of a wax, which is crystallized from iso ether. M.p. ■ 249'C. Preparation 11: 5-Chloro-3-cyclohexyl-l,3-dihydro-3-methyl-15 indol-2-one The method described in Synth. Commun., 1982, 12 (1), 1-10, is used to prepare 5-chloro-3-cyclohexyl- 1,3-dihydrolndol-2-one as an intermediate, and the expected compound is then obtained by reaction with methyl iodide. 20 Preparation 12i 5-Acetyl-l,3-dihydro-3-spirocyclohexaneindol-2- one 2.56 g of acetyl chloride and then 8.25 g of anhydrous aluminum chloride are added to a solution, 25 cooled to 5*C, of 4 g of l,3-dihydro-3-spirocyclo-hexaneindol-2-one in 35 ml of 1,2-dichloroethane. The mixture is refluxed for 2 hours, the solvent is evaporated off under reduced pressure and the medium is hydrolyzed with 50 g of ice and extracted with ethyl 30 acetate. The organic phase is washed with water, dried over magnesium sulfate and then evaporated under reduced pressure. The residue is chromatographed on a silica column using a mixture of heptane and ethyl ether as the 35 eluent to give 3.6 g of the expected product. M.p. » 192*C. 53 V Preparation 13: 5-Chloro-l,3-dihydro-3-spiro(tetrahydrothio-pyran-4-yl)indol-2-one A - 5-Chloro-l,3-dihydro-3,3-di(2-bromoethyl)-5 indol-2-one 7.66 g of bromine are added slowly to a mixture, cooled to about 0*C, of 12.4 g of triphenyl-phosphine in 70 ml of DCM, and 4.58 g of 5-chloro-l,3- dihydro-3,3-di[2-(tetrahydropyran-2-yloxy)ethyl]indol- 2-one, 10 described in Table 2, are then added. After 16 hours at RT, 60 ml of water are added and the organic phase is separated off, washed with 60 ml of water and then dried over magnesium sulfate and evaporated under vacuum. The residue is chromatographed on a silica column using DCM IS as the eluent to give 3.12 g of the expected product. M.p. - 215*C. B - 5-Chloro-l,3-dihydro-3-spiro(tetrahydro-thiopyran-4-yl)indol-2-one Under an inert atmosphere, 3 g of the product 20 prepared in step A are added to 3.2 ml of DMF and 2 g of sodium sulfide monohydrate and the mixture Is heated for 2 hours at 50*C. It is cooled to RT, 6 ml of water are added and the mixture is extracted with DCM. The organic phase is washed with water, dried over magnesium sulfate 25 and evaporated under reduced pressure. The oily residue obtained is purified by chromatography on silica using DCM as the eluent to give 2.02 g of the expected compound. NMR spectrum at 200 MHz in CDCI3: 30 8.12 ppm : s : 1H 7.2 ppm : m : 2H 6.8 ppm : d : 1H 3.25 ppm : m : 2H 2.65 ppm : m : 2H 35 2 ppm : m : 4H 54 Preparation 14: 5-Ethoxy-l,3-dihydro-3-spiro[4-(methoxymethoxy) -cyclohexane]indol-2-one A - 3-(Methoxymethoxy)pentane-l,5-diol 5 270 ml of a 1 M solution of lithium aluminum hydride in THF, diluted in 540 ml of anhydrous THF, is cooled to 0*C and a solution of 63 g of diethyl 3-(methoxymethoxy)glutarate (prepared according to J.L. Gras in Synthesis, 1985, 74) in 400 ml of THF is added. 10 The mixture is stirred for 16 hours at RT and then cooled to 0*C and 9 ml of water, 30 ml of a 15% solution of NaOH and 9 ml of water are added successively. The mineral salts are filtered off and the filtrate is evaporated under vacuum to give 24 g of the expected product after is distillation under reduced pressure. B.p. - 125*C under 1.2 Pa. B - 3-(Methoxymethoxy)-l,5-ditosyloxypentane A solution of 46 g of p-toluenesulfonyl chloride and 38 ml of triethylamine in 80 ml of THF is cooled to 20 0*C, a solution of 18 g of the compound obtained in the previous step in 100 ml of THF is added and the mixture is stirred for 16 hours at RT. 150 ml of water are added to the reaction mixture, the solvent is evaporated off under vacuum, the residue is extracted with AcOEt and the 25 latter is evaporated off under vacuum. The oil obtained is taken up with 250 ml of ether and 200 ml of 2 N NaOH and the mixture is stirred for 16 hours at RT. After decantatlon, the organic phase is dried over magnesium sulfate and the solvent is evaporated off under vacuum to 30 give 45 g of the expected product after crystallization from cyclohexane. M.p. < 50 *C. C - 5-Ethoxy-l,3-dihydro-3-spiro[4-(methoxymethoxy ) cyclohexane] indol-2-one This compound is prepared by the procedure 35 described In Preparation 2 starting from 5-ethoxy-l,3-dihydrolndol-2-one and the compound obtained in the previous step. The expected product is obtained in the form of a mixture of isomers. M.p. = 98*C. Preparation 15: 5-Ethoxy-l,3-dihydro-3-spiro[4-tricyclo-5 [5.2.1.02/6]decane]indol-2-one A mixture of 3 g of 5-ethoxy-l,3-dihydro-3-spiro[4-tricyclo[5.2.1.02» 6]dec-8-ene]indol-2-one, described in Table 2, and 1.5 g of 10% palladiura-on-charcoal in 160 ml of MeOH is hydrogenated for 16 hours 10 at 40*C under a pressure of 20 bar. The catalyst is filtered off on C61ite® and washed with MeOH and the filtrate is evaporated under vacuum to give 2.95 g of the expected product. M.p. « 236*C. Preparations 16 and 17: 15 5-Ethoxy-l,3-dihydro-3-spiro(4-methoxycyclo- hexane)indol-2-one, the less polar isomer and the more polar isomer A - 3-Methoxypentane-l,5-diol 25 ml of methyl trifluoromethylsulfonate are 20 added to a solution of 30 g of diethyl 3-hydroxy-glutarate and 33 ml of 2,6-di-tert-butylpyridine in 500 ml of DCM and the mixture is refluxed for 6 hours. After cooling, 500 ml of a 0.5 N solution of HC1 are added, the organic phase is decanted and dried over magnesium 25 sulfate and the solvent is evaporated off under vacuum. The residue obtained is taken up with 200 ml of anhydrous THF, the mixture is filtered and the filtrate is then cooled to -5*C. 160 ml of a 1 M solution of lithium aluminum hydride in THF are then added slowly and the 30 mixture is stirred for 16 hours, the temperature being allowed to rise to RT. The reaction mixture is cooled to 0*C and 5.5 ml of water, 18 ml of a 15% solution of NaOH and 5.5 ml of water are added successively. The mineral salts are filtered off and the filtrate is evaporated 35 under vacuum to give the expected product after distillation under reduced pressure. B.p. » 104*C under 56 i r tf 1.5 Pa. B - 3-Methoxy-l,5-ditosyloxypentane A solution of 31 g of p-toluenesulfonyl chloride and 26 ml of triethylamine in 120 ml of THF is cooled to S 0*C, 10 g of the compound obtained in the previous step are added and the mixture is stirred for 24 hours at RT. 120 ml of water are added to the reac tion mixture, the solvent is evaporated off under vacuum, the residue is extracted with AcOEt and dried over magnesium sulfate and 10 the solvent is evaporated off under vacuum. The oil obtained is taken up with 200 ml of ether and 200 ml of 2 N NaOH and the mixture is stirred for 16 hours at RT. After decantation, the organic phase is dried over magnesium sulfate and the solvent is evaporated off under 15 vacuum to give 26 g of the expected product after crystallization from cyclohexane. M.p. - 58*C. C - 5-Ethoxy-l,3-dihydro-3-spiro(4-methoxy-cyclohexane)indol-2-one, the less polar isomer and the more polar isomer 20 These compounds are prepared by the procedure described in Preparation 2 starting from 11.85 g of 5-ethoxy-l,3-dihydroindol-2-one, 34 g of potassium tert-butylate and 26 g of the compound obtained in the previous step. They are chromatographed on silica using 25 a cyclohexane/AcOEt mixture (80/20; v/v) as the eluent. The two isomers are separated into - the less polar Isomer: compound of Preparation 16, m.p. - 173*C; - the more polar isomer: compound of Preparation 30 17, m.p. - 186*C. In addition, the benzenesulfonyl chlorides described in the Table below were prepared using the procedure 35 described in the general section. ci I so2 YRV Y RV M.p.'C S ch3 85 O CH2BZ 95 O CH2CC>2Et 89 O (CH,hBr 106-108 Starting from the various 1,3-dihydroindol-2-ones described above and appropriate benzenesulfonyl chlorides, the compounds according to the invention were prepared using the procedures reported in the Examples below. EXAMPLES 1 and 2 5-Ethoxy-l,3-dihydro-l-[2-methoxy-4-(pyrrol-l-yl)benzenesulfonyl]-3-spirocyclohexaneindol-2-one and 5-ethoxy-l,3-dihydro-l-[2-methoxy-4-(A3-pyrrolin-l-yl) benzenesulfonyl]-3-spirocyclohexaneindol-2-one A) 5-Ethoxy-l,3-dihydro-l-(2-methoxy-4-nitrobenzenesul-f ony1)-3-spirocyclohexaneindol-2-one A solution of 15 g of 5-ethoxy-l,3-dihydro-3-spirocyclohexaneindol-2-one in 150 ml of THF is cooled in an ice bath to a temperature between 10*C and 15*C. 2.4 g of sodium hydride as a 60% dispersion in oil are added over 2 hours and 18 g of 2-methoxy-4-nitroben-zenesulfonyl chloride are then introduced in portions over 30 minutes. After stirring for 18 hours at RT, the suspension obtained is poured into an iced solution of sodium chloride and then extracted with AcOEt. The organic phase is dried over sodium sulfate and evaporated 5 to dryness and the residue is then crystallized from 200 ml of hot iso ether to give 23 g of the expected product. M.p. - 160*C. This compound is also obtained by following the procedure described below. 10 A') 5-Ethoxy-l,3-dihydro-l-(2-methoxy-4-nitrobenzene- sulfonyl)-3-spirocyclohexaneindol-2-one A solution of 15 g of 5-ethoxy-l,3-dihydro-3-spirocyclohexaneindol-2-one in 300 ml of THF is cooled to about -50 'C and 7.2 g of potassium tert-butylate are IS added. The mixture is stirred, the temperature being allowed to rise to about 0*C, and then cooled to -50*C and a solution of 16.2 g of 2-methoxy-4-nitrobenzenesulfonyl chloride in THF is added. The mixture is stirred for 1 hour at RT, 100 ml of water are 20 added and the solvent is evaporated off under vacuum. The aqueous phase is extracted with DCM and dried over magnesium sulfate and the solvent is evaporated off under vacuum to give the expected product after crystallization from hot iso ether. 25 The following nitro derivatives are prepared by the latter procedure starting from the appropriate 1,3-dihydroindol-2-ones: no2 r1 cr3r4 M.p.'CorNMR cl-EtO-F-CF3 cl-EtO-Cl-cl- EtO- EtO- EtO- 4,4-dimethylcyclohcxane 4,4-dimethylcyclohexanc 4,4-dimcthylcyclohexanc 4,4-dimcthylcyclohcxane cycloheptane cycloheptane tetrahydropyran-4 tetrahydrothiopyran-4 169 110 137 137 125 212 116 88 140 nmr* *NMR spectrum at 200 MHz in DMSO 1.3 ppm : "t : 3H 1.3-1.5 ppm : nrt : 6H 2.2 ppm : mt : 4H 3.7 ppm : s : 3H 4.0 ppm : q : 2H 7.0 ppm : mt : 2H 5 7.6 ppm : d : 1H 7.9 ppm : mt : 2H 8.2 ppm : d : 1H B) l-(4-Amino-2-methoxybenzenesulfonyl)-5-ethoxy-l,3-dihydro-3-spirocyclohexaneindol-2-one 10 A suspension containing 20 g of the compound obtained in the previous step, 20 g of iron powder, 70 ml of water and 70 ml of 96* alcohol is brought to the reflux point; a solution of 7 ml of concentrated hydrochloric acid in 35 ml of water is added over 30 15 minutes. After 4 hours under reflux, 15 ml of sodium hydroxide solution are added and the mixture is then extracted with DCM. The organic phase is filtered on CfeliteR and then dried over sodium sulfate. The residue is crystallized from 100 ml of a hot iso ether/AcOEt 20 mixture (80/20; v/v) to give 15.8 g of the expected product. M.p. - 177*C. This compound is also obtained by following the procedure described below. B') l-(4-Amino-2-methoxybenzenesulfGnyl)-5-ethoxy-l,3-25 dihydro-3-spirocyclohexaneindol-2-one A solution of 0.5 g of the compound obtained in step A) in 10 ml of EtOH is cooled to about 5*C and 0.8 ml of concentrated HCl and 0.4 g of tin powder are added. The mixture is heated at 40 *C for 45 minutes and the 30 solvent is evaporated off under vacuum. The residue is neutralized by the addition of NaOH, extracted with AcOEt, dried over magnesium sulfate and filtered on C61iteR and the filtrate is evaporated under vacuum. The residue is chromatographed on silica using a DCM/MeOH 35 mixture (99/1; v/v) as the eluent to give the expected product. The following anilines are also prepared by the latter procedure: NHo r1 cr3r4 M.p.'C Cl-EtO- F-CF3-cl-EtO-cl-cl- EtO- EtO- EtO- 4,4-dimethylcyclohcxane 4,4-dimethylcyclohexane 4,4-dimcthylcyclohexane 4,4-dimcthylcyclohcxane cycloheptane cycloheptane tetrahy dropy ran - 4 tetrahydrothiopyran-4 222 230 130 184 128 220 229 241 232 189 62 ^ r /■ n B' ' ) The compound obtained in step B) above can also be prepared from the corresponding nitro derivative by hydrogenation in the presence of 10% palladium-on-charcoal for 2 hours at 50*C under a pressure of 1 bar. 5 C) 5-Ethoxy-l,3-dihydro-l-[2-methoxy-4-(pyrrol-l-yl)-benzenesulfonyl]-3-spirocyclohexaneindol-2-one and 5-ethoxy-1,3-dihydro-l-[2-methoxy-4-(D3-pyrrolin-l-yl)-benzenesulfonyl]-3-spirocyclohexaneindol-2-one A mixture containing 500 mg of the compound 10 prepared in step B), 10 ml of DMF, 0.3 g of sodium carbonate and 300 mg of cis-1,4-dichlorobut-2-ene is refluxed for 4 hours. The reaction mixture is poured into a water/ice mixture and then extracted with AcOEt and washed with water; the solvent is evaporated off and IS the residue obtained is then chromatographed on silica using a DCM/heptane mixture (95/5; v/v) and then pure DCM as the eluent. 70 mg of the less polar product (compound of Example 1), m.p. - 174*C, are collected, followed by 60 mg of the more polar product (compound of Example 2), 20 m.p. - 170*C. The compounds described in the Tables of steps A) and B) above can be used to prepare compounds according to the invention which are analogous to that obtained in step C). 25 example 3 5-Ethoxy-l,3-dihydro-l-[2-methoxy-4-(pyrroli-din-l-yl)benzenesulfonyl]-3-spirocyclohexaneindol-2-one 450 mg of the compound obtained in Example 2 are placed in 25 ml of 95* EtOH and 25 ml of AcOEt, in the 30 presence of 150 mg of 5% palladium-on-charcoal, and are hydrogenated for 4 hours at 35 *C under a pressure of 40 bar. The catalyst is filtered off and the filtrate is evaporated to dryness. The expected pro duct crystallizes from iso ether, m = 110 mg. M.p. = 185*C. t 63 EXAMPLE 4 5-Ethoxy-l,3-dihydro-l-[4-(isoindolin-2-yl)-2-methoxybenzenesulfonyl]-3-spirocyclohexanGindol-2-one A mixture containing 500 mg oi: the compound 5 prepared in Example 1 step B), 10 ml of DMF, 0.5 ml of TEA and 310 mg of a,a'-dibromoorthoxylene is refluxed for 2 hours. The reaction medium is poured into a water/ice mixture, extracted with AcOEt, dried over sodium sulfate and evaporated to dryness. The residue is 10 chromatographed on silica using DCM and then DCM/ AcOEt (95/5; v/v) as the eluent to give the expected product, which is crystallized from iso ether, m ■ 170 mg. M.p. « 190*C. EXAMPLE 5 15 5-Ethoxy-l,3-dihydro-l-[2-methoxy-4-((3-methyl- thien-2-yl)carboxamido)benzenesulfonyl]-3-spirocyclo-hexaneindol-2-one A mixture containing 500 mg of the compound prepared in Example 1 step B), 10 ml of DCM, 2 ml of 20 pyridine and 250 mg of 3-methylthiophene-2-carboxylic acid chloride Is stirred for 3 hours at RT. The medium is washed with 1 N hydrochloric acid and then with water. It is dried over sodium sulfate and then evaporated to dryness. The residue is chromatographed on silica using 25 DCM as the eluent. The expected product recrystallizes from iso ether, m » 0.21 g. M.p. « 174*C. EXAMPLE 6 1-[4-(N-Benzylcarbamoyl)-2-methoxybenzenesul-fonyl]-5-ethoxy-l,3-dihydro-3-spirocyclohexaneindol-2-30 one A) Benzyl 3-methoxy-4-[(5-ethoxy-2,3-dihydro-2-oxo-3-spirocyclohexaneindol-l-yl)sulfonyl]benzoate 1.4 g of sodium hydride are added in small portions to a solution of 11.8 g of 5-ethoxy-l,3-35 dihydro-3-spirocyclohexaneindol-2-one in 100 ml of THF. After stirring for 30 minutes at RT, 17 g of benzyl 4- chlorosulfonyl-3-methoxybenzoate are added and stirring Is maintained at RT for 1 hour. The reaction medium is poured into 400 ml of a water/alcohol mixture (50/50; v/v). The precipitate formed is filtered off, dried and then recrystallized from alcohol. m - 22.65 g. M.p. - 135*C. B) 3-Methoxy-4-[(5-ethoxy-2,3-dihydro-2-oxo-3-spiro-eyclohexaneindol-l-yl)sulfonyl]benzoic acid 2.5 g of 10% palladium-on-charcoal in oil are added to a solution of 22.65 g of the benzyl ester prepared in the previous step in 600 ml of AcOEt and the mixture is then hydrogenated for 2 hours at 40 *C under atmospheric pressure. The insoluble material is filtered off and the medium is then concentrated. The expected product crystallizes from pentane. m - 18.3 g. M.p. * 181*C. C) 3-Methoxy-4-[(5-ethoxy-2,3-dihydro-2-oxo-3-spiro-cyclohexaneindol-l-yl)sulfonyl]benzoyl chloride A solution of 2.3 g of the above acid in 20 ml of thionyl chloride is refluxed for 3 hours. The reaction medium is concentrated to dryness and the product is used in the crude form, as a solution in DCM, in the next step. D) 1-[4-(N-Benzylcarbamoyl)-2-methoxybenzenesulfonyl]-5-ethoxy-l,3-dihydro-3-spirocyclohexaneindol-2-one A mixture containing 500 mg of the compound prepared in the previous step and 200 mg of benzylamine in 20 ml of DCM and 0.5 ml of TEA is stirred at RT for 30 minutes. It is washed with a 1 N solution of HCl, dried over sodium sulfate and concentrated. The expected product crystallizes from iso ether. m «= 440 mg. M.p. « 196*C. The compound of Example 6 does not belong to the compounds of formula (I) according to the invention, but the intermediate obtained in step C) is used to prepare the compound of Example 8. The procedure described in Example 6 step D) is also used, together with the appropriate amines, to prepare the compounds of Examples 44-54. EXAMPLE 7 5 l-[4-(2-Carbamoylpyrrolidin-l-ylcarbonyl)-2- methoxybenzenesulfonyl]-5-chloro-l,3-dihydro-3-spiro-cyclohexaneindol-2-one A) Phenyl 4-[(5-chloro-2,3-dihydro-2-oxo-3-spirocyclo-hexaneindol-l-yl)sulfonyl]-3-methoxybenzoate 10 A mixture containing 1 g of 5-chloro-l,3-di- hydro-3-spirocyclohexaneindol-2-one, 50 ml of THF and 115 mg of sodium hydride is stirred for 30 minutes at RT under nitrogen. 1.5 g of 2-methoxy-4-phenoxycarbo-nylbenzenesulfonyl chloride are introduced and stirring IS is maintained for 20 hours at RT. The reaction medium is concentrated under vacuum and the residue is taken up with 30 ml of water and extracted with AcOEt. The organic phase is washed, dried and concentrated under vacuum. The product obtained is purified by 20 chromatography on silica using an iso ether/hexane mixture (40/60; v/v) as the eluent to give 1.4 g of the expected compound. M.p. - 165'C. B) 1-£4-(2-Carbamoylpyrrolidin-l-ylcarbonyl)-2-methoxy-benzenesulfonyl]-5-chloro-l,3-dihydro-3-spirocyclo- 25 hexaneindol-2-one A mixture containing 300 mg of the compound prepared in the previous step, 500 mg of (L)-prolinamide hydrochloride, 1 ml of TEA and 20 ml of prehnitene is refluxed for 1 hour. After cooling, the reaction medium 30 is taken up with AcOEt, washed with a IN solution of HCl and with water and then dried over sodium sulfate and concentrated. The residue is chromatographed on silica using a DCM/MeOH mixture (98/2; v/v) as the eluent to give 0.09 g of the expected product. M.p. = 142*C. 35 EXAMPLE 8 5-Ethoxy-l,3-dihydro-l-[2-methoxy-4-(2-methoxy- t 66 2 A carbonylpyrrolidin-l-ylcarbonyl)benzenesulfonyl]-3-spirocyclohexaneindol-2-one 500 mg of the hydrochloride of the methyl ester of (L)-proline, 0.5 ml of TEA and 20 ml of DCM are added 5 to 500 mg of 3-methoxy-4-[(5-ethoxy-2,3-dihydro-- 2-oxo-3-spirocyclohexaneindol-l-yl)sulfonyl]benzoyl chloride, prepared In Example 6 step C). After stirring for one hour at RT, the mixture is washed with 1 N HCl, dried and concentrated. The residue Is chromatographed on silica 10 using a DCM/MeOH mixture (98/2; v/v) as the eluent to give 300 mg of the expected product, which is characterized by its NMR spectrum. NMR at 200 MHz in DMSO (2.5 ppm): 1.25 ppm : t : 3H 15 1.3-2.35 ppm : m : 14H 3.1-3-7 ppm : m : 8H 3.8 ppm : q : 2H 4.35 ppm ; mt : 3H 6.7-8 ppm : m : 6H 20 EXAMPLE 9 1-[4-(N'-Cyclopentylureido)-2-methoxybenzene-sulfonyl]-5-ethoxy-l,3-dihydro-3-spirocyclohexaneindol-2-one A) 5-Ethoxy-l,3-dihydro-l-(2-methoxy-4-phenoxycarbox-25 amidobenzenesulfonyl)-3-spirocyclohexaneindol-2-one A mixture containing 2 g of l-(4-amino-2-methoxybenzenesulfonyl)-5-ethoxy-l,3-dihydro-3-spiro-cyclohexaneindol-2-one (prepared in Example 1 step B)), 3.6 ml of phenyl chloroformate and 120 ml of ether is 30 cooled to a temperature below 5*C. 960 mg of sodium hydroxide in 16 ml of water are added and the temperature is allowed to rise for 24 hours, with stirring. The precipitate is filtered off and washed with water and then with ether. The residue is chromatographed on 35 silica using DCM as the eluent to give the expected product. M.p. - 181*C. B) l-[4-(N'-Cyclopentylureido)-2-methoxybenzenesulfo-nyl]-5-ethoxy-l,3-dihydro-3-spirocyclohexaneindol-2-one 2 g of the compound prepared In the previous step are dissolved in 40 ml of 100* EtOH and 30 ml of DCM. 2 5 ml of cyclopentylamine are added and the mixture is stirred for 18 hours at RT. The alcohol is evaporated off under vacuum and the residue is then chromatographed on silica using a DCM/AcOEt mixture (95/5; v/v) as the eluent to give 1.8 g of the expected product, which 10 crystallizes from iso ether. M.p. - 195*C. EXAMPLE 10 5-Chloro-l,3-dihydro-l-[4-(N',N'-diethyl-ureido)-2-methoxybenzenesulfonyl]-3-spiro-(tetrahydro-thiopyran-15 4-yl-l-oxide)indol-2-one This is prepared in the same manner as in Example 9 (steps A) and B)). A) 5-Chloro-l,3-dihydro-l-[4-(N",N'-diethylureido)-2-methoxybenzenesulfonyl]-3-spiro(tetrahydrothiopyran-4- 20 yl)indol-2-one, m.p. - 214*C, from 5-chloro-l,3-dihydro-l- [4-amino-2-methoxybenzenesulfonyl]-3-spiro-(tetrahydrothiopyran-4-yl)indol-2-one, m.p. « 229*C B) 5-Chloro-l,3-dihydro-l-[4-(N',N'-diethylureido)-2-methoxybenzenesulfonyl]-3-spiro(tetrahydrothiopyran-4-yl- 25 l-oxide)indol-2-one A mixture of 0.45 g of the compound prepared in step A) and 0.2 g of sodium perlodate in 3 ml of methanol and 2 ml of water is stirred for 24 hours at RT. The precipitate is filtered off and the methanol is 30 evaporated off from the filtrate under reduced pressure. The residue is extracted with DCM and dried over magnesium sulfate and the solvent is evaporated off. The residue is chromatographed on a silica column using a DCM/methanol mixture (98/2; v/v) as the eluent and 0.4 g 35 of the expected product is isolated. M.p. - 217*C. 68 ft & EXAMPLE 11 5-Chloro-l,3-dihydro-l-[4-(N',N'-diethylureido)-2-methoxybenzenesulfonyl]-3-spiro(tetrahydrothiopyran-4-yl-1,1-dioxyde)indol-2-one 5 A mixture of 0.45 g of the compound of Example 10 and 0.5 g of metachloroperbenzolc acid in 10 ml of DCM is stirred at RT for 4 hours. 12 ml of a saturated aqueous solution of sodium bicarbonate are then added and the organic phase Is decanted, washed with water, dried and 10 evaporated under reduced pressure. The residue is recrystallized from a mixture of cyclohexane and ethyl acetate (7/3? v/v) to give 0.35 g of the expected product. M.p. ■ 211*C. EXAMPLE 12 15 l-[4-(N'-Cyclopentylthioureido)-2-methoxy benzenesulf onyl] -5-ethoxy-l,3-dihydro-3-spirocyclo-hexaneindol-2-one The compound obtained in Example 9 is placed in 50 ml of toluene in the presence of 1.5 g of Lawesson's 20 reagent. The mixture is refluxed for 24 hours. The toluene is driven off and the residue is then chromato graphed on silica using pure DCM and then a DCM/AcOEt mixture (ranging up to 90/10; v/v) as the eluent to give the expected product, which crystallizes from iso ether. 25 M.p. - 197'C. EXAMPLE 13 1-[4-(3-(N-Boc-amino)azetidin-l-ylcarboxamido)-5-methoxybenzenesulfonyl] -2-ethoxy-l, 3-dihydro->3-spiro-cyclohexaneindol-2-one 30 A) l-Benzhydryl-3-(N-Boc-amino)azetidine A mixture containing 5 g of 3-amino-l-benzhy-drylazetidine and 5 g of (Boc)20 in 130 ml of dioxane and 4 ml of TEA is stirred at RT for 2 hours. The dioxane is evaporated off and the residue is taken up with AcOEt and 35 washed with water. It is dried over sodium sulfate and then evaporated to dryness. The expected product 69 264 crystallizes from iso ether, m = 6 g. B) 3-(N-Boc-amino)azetidine hydrochloride A mixture containing 6 g of the compound prepared in the previous step, 300 ml of 95' EtOH, 700 mg of 5 palladium hydroxide and 3 ml of concentrated HCl is prepared. It is hydrogenated for 2 hours at 35-40*C under a pressure of 2 bar. The catalyst is filtered off and the filtrate is evaporated to dryness. The expected product crystallizes from iso ether 10 m = 3.4 g. C) 1-[4-(3-(N-Boc-amino)azetidin-1-ylcarboxamido)-5-methoxybenzenesulfonyl]-2-ethoxy-l,3-dihydro-3-spiro cyclohexaneindol-2-one A mixture containing 500 mg of the compound 15 prepared in Example 9 step A), 20 ml of 100* alcohol, 15 ml of DCM, 250 mg of the compound prepared in step B) and 0.5 ml of TEA is stirred for 24 hours at RT. The solvents are evaporated off and the residue is then chromatographed on a silica column using a DCM/AcOEt 20 mixture (95/5; v/v) as the eluent. The expected product crystallizes from iso ether. m - 200 mg. M.p. » 156*C. EXAMPLE 14 l-[4-(N'-Carboxymethyl-N'-methylureido)-2-25 methoxybenzenesulfonyl]-5-ethoxy-l,3-dihydro-3-spiro-cyclohexaneindol - 2-one A mixture containing 500 mg of the compound prepared in Example 9 step A), 20 ml of 100* EtOH, 15 ml of DCM, 1.5 g of sarcosine and 2 ml of triethylamine is 30 prepared. After stirring for 24 hours at RT, the solvents are evaporated off, the residue is then taken up with hot AcOEt and the insoluble material is filtered off. The filtrate is evaporated to dryness and the residue is then chromatographed on silica using pure DCM 35 and then a DCM/MeOH mixture (85/15; v/v) as the eluent to give the expected product, which is characterized by its 70 ^ <" L u NMR spectrum at 200 MHz in DMSO (2.5 ppm): 1.3 ppm : t : 3H 1.4-2.1 ppm : m : 10H 2.95 ppm : s : 3H 5 3.5 ppm : s : 3H 3.9 ppm : s : 2H 4 ppm : q : 2H 6.7-7.9 ppm r m : 6H 9.45 ppm : bs : 1H 10 EXAMPLE 15 5-Ethoxy-1,3-dihydro-1-[2-methoxy-4-(1-methyl-2,4-dioxoimidazolin-3-yl)benzenesulfonyl]-3-spirocyclo-hexaneindol-2-one On heating at 100*C for 24 hours under vacuum, is the product obtained in the previous Example is cyclized to give 230 mg of the expected product. M.p. - 200*C. EXAMPLE 16 l-[4-(N',N'-Diethylthioureido)-2-methoxybenzene 20 sulfonyl]-5-ethoxy-l,3-dihydro-3-spirocyclohexaneindol-2-one A) 5-Ethoxy-l,3-dihydro-l-(2-methoxy-4-phenoxythio-carboxamidobenzenesulfonyl)-3-spirocyclohexaneindol-2-one 25 A mixture containing 500 mg of the compound obtained in Example 9 step A), 900 mg of phenoxythiocarbonyl chloride, 30 ml of ether, 8 ml of water, 120 mg of sodium hydroxide and 20 ml of DCM is prepared. After stirring for 24 hours at RT, the 30 solvents are evaporated off and the residue is then chromatographed on silica using DCM as the eluent. The expected product crystallizes from iso ether. m » 140 mg. M.p. « 157*C. B) l-[4-(N',N'-Diethylthioureido)-2-methoxybenzene- 35 sulfonyl]-5-ethoxy-l,3-dihydro-3-spirocyclohexaneindol-2-one 71 264 A mixture containing 140 mg of the compound prepared in step A), 20 ml of 100* EtOH, 5 ml of DCM and 1 ml of diethylamine is stirred at RT for 18 hours. The solvents are evaporated off and the residue is then 5 chromatographed on a silica column using pure DCM and then a DCM/AcOEt mixture (up to 90/10; v/v) as the eluent. The expected product crystallizes from iso ether. m * 105 mg. M.p. ■ 167*C. EXAMPLE 17 10 5-Ethoxy-l,3-dihydro-l-(2-methoxy-4-guanidino- benzenesulfonyl)-3-spirocyclohexaneindol-2-one A mixture containing 500 mg of the compound prepared in Example 1 step B), 125 mg of cyanamide, 7 ml of AcOEt, 1 ml of EtOH and 0.2 ml of a 20% solution of 15 hydrochloric acid in EtOH is refluxed for 1 hour. The solvents are evaporated off and the residue is then chromatographed on a silica column using DCM and then MeOH as the eluent. The product isolated solidifies in ether. A 2 N solution of NaHC03 is added and the base 20 formed is then extracted with AcOEt; the extract is evaporated to dryness and the expected product solidifies in iso ether, m - 0.055 g. M.p. =■ 235*C. EXAMPLE 18 5-Ethoxy-l,3-dihydro-l-[2-methoxy-4-(N-methyl-25 carbamoylmethoxy)benzenesulfonyl]-3-spirocyclohexane-indol-2-one A) Potassium 2-methoxy-4-(ethoxycarbonylmethoxy)phenyl-sulfonate 10 g of ethyl (3-methoxyphenoxy)acetate and 30 ml 30 of DCM are mixed at 0*C and 7.5 ml of trimethyl-silylsulfonyl chloride in 30 ml of DCM are added over 20 minutes. The temperature is allowed to rise to RT, with stirring, 30 g of ice are added after 2 hours and the mixture is stirred again. After decantation, the aqueous 35 phase is washed with ether, and potassium carbonate is added in a sufficient amount to bring the pH to 7. The 72 L. v white precipitate which forms is filtered off and then washed with acetone and ether to give 3.1 g of the expected product, which is characterized by its NMR spectrum. 5 B) 2-Methoxy-4-(ethoxycarbonylmethoxy)phenylsulfonyl chloride 3.1 g of the compound obtained in the previous step in 30 ml of phosphorus oxychloride are refluxed for 3 hours. The medium is concentrated under vacuum and 10 then taken up with ice. It is extracted with ethyl acetate, washed with water, with N sodium hydroxide and then with water again, dried over sodium sulfate and concentrated under vacuum. The expected product crystallizes from iso ether, m - 2.5 g. M.p. = 89*C. 15 C) Ethyl 3-methoxy-4-[(5-ethoxy-2,3-dihydro-2-oxo-3-spirocyclohexaneindol-l-yl)sulfonyl]phenoxyacetate A mixture containing 0.5 g of 5-ethoxy-l,3-dihydro-3-spirocyclohexaneindol-2-one, 5 ml of THF and 60 mg of sodium hydride is prepared. After stirring for 15 20 minutes at 15*C, 0.66 g of the compound prepared in the previous step is added. Stirring is maintained for 15 minutes and the medium is then concentrated under vacuum. It is extracted with ether and washed with water and the expected product is then crystallized from iso ether. 25 m ■ 0.85 g. M.p. - 160*C. D) 5-Ethoxy-l,3-dihydro-l-[2-methoxy-4-(N-methyl-carbamoylmethoxy)benzenesulfonyl]-3-spirocyclohexane-indol-2-one A mixture containing 0.5 g of the compound 30 prepared in the previous step, 15 ml of a 33% solution of methylamine in MeOH and 15 ml of EtOH is stirred for 4 days at RT. It is concentrated under vacuum and the residue is then chromatographed on silica. The column is washed with DCM and then eluted with AcOEt to give the 35 expected product, m «= 0.1 g. M.p. » 192-195*C. 73 264 EXAMPLE 19 5-Ethoxy-1,3-dihydro-l-[2-methoxy-4-(N-methyl-N-(2-methylallyl)amino)benzenesulfonyl]-3-spirocyclo-hexanelndol-2-one 5 A) 5-Ethoxy-l,3-dihydro-l-[2-methoxy-4-(N-methylamino)-benzenesulfonyl]-3-splrocyclohexaneindol-2-one 2 g of the compound prepared in Example 1 step B), cooled in an ice bath to 10*C, are dissolved in 6 ml of a 37% aqueous solution of formaldehyde and 40 ml of 10 acetonitrile. 1.7 g of 85% pure sodium cyanoboro-hydride and then 0.5 ml of acetic acid are added and the mixture is stirred at RT for 24 hours. The acetonitrile is evaporated off and the residue is taken up with water and AcOEt, The organic phase is decanted, dried and then 15 chromatographed twice in succession on silica using a DCM/heptane mixture (85/15; v/v), then pure DCM and finally a DCM/AcOEt mixture (98/2; v/v) as the eluent to give the expected compound, m => 0.36 g. M.p. » 157*C. B) 5-Ethoxy-l,3-dihydro-l-[2-methoxy-4-(N-methyl-N-(2-20 methylallyl)amino)benzenesulfonyl]-3-spirocyclohexane-indol-2-one A mixture containing 500 mg of the compound obtained in the previous step, 10 ml of DMF, 0.5 ml of diethylamine and 0.5 ml of 3-chloro-2-methylpropene is 25 refluxed for 10 hours. The reaction medium is poured into a water/ice mixture and then extracted with AcOEt, washed with water and chromatographed on silica using DCM as the eluent. The expected compound crystallizes from pentane. m = 190 mg. M.p. ■ 118'C. 30 74 26 4 1 v The compounds (I) according to the invention described in Table 3 below were prepared by following the procedures described in the previous Examples. TABLE 3 Example R1 CR3R4 R6 M.p'C 20 (a) Cl- cyclohexane N — 179 21 (a) EtO- 4,4-dimethyl cyclohexane N — 167 22 (b) Cl- cyclohexane EtOCOCH2NHCONH- 167 75 n ft /« -s v '/ £ u s- -- TABLE 3 (continua-tion) Example R1 CR3R4 R6 M.p *C 23 (b) Cl- cyclohexane < V-N-CONH- Me 139 24 (c) EtO- cyclohexane N-CONH-Me 150 25 (c) EtO- cyclohexane / \ Me-N N-CONH- \ / 197 26 EtO- cyclohexane MeONCONH- | 177 (c) Me 27 EtO- cyclohexane MeNH(CH2)2NCONH- 170 (c) Me hydrochloride 28 EtO- cyclohexane HONCONH- | monohydrate 185 (c) Me 29 EtO- cyclohexane HOCH9CH,NCONH- Mf I 128 CO Me 30 (c) EtO- cyclohexane \ N-CONH- / 139 31 (c) EtO- cyclohexane / \ ( N-CONH- 210 TABLE 3 (continuation) Example R1 cr3r4 r6 M.p.'C 32 (c) EtO- cyclohexane O ^N-CONH - \ / 190 33 (c) EtO- cyclohexane / \ S N-CONH- \ / 212 34 (c) EtO- cyclohexane / N-CONH- 179 35 (c) EtO- cyclohexane / \ Me —< N-CONH- \ / 146 36 EtO- cyclohexane Me 198 (c) \ N-CONH- 37 (c) EtO- cyclohexane Me McN(CH2)2NCONH Me Et 208 hydrochloride monohydrate 38 (c) EtO- cyclohexane / ^ Ph-^ N-CONH- 195 39 EtO- cyclohexane MeN(CH2)2NCONH- 200 (c) Mc Me fumaratc 77 26 4 1 2 ^ TABLE 3 (continuation) Example R1 cr3r4 r6 M.p'C 40 (c) EtO- cyclohexane < =N WCH2)2NC0NH 159 Me 41 (d) Cl- 4,4-dimethyl-cyclohexane S II Et2NCNH- 179 42 (d) EtO- 4,4-dimethyl-cyclohexane S II Et2NCNH- 146 44 (c) EtO- cyclohexane 0 ch2nhco- 189 45 (e) EtO- cyclohexane CF3CH2NHCO- 210 46 (e) EtO- cyclohexane nhco- 196 47 (e) EtO- cyclohexane < V-NHCO- 155 48 (e) EtO- cyclohexane \ N-NHCO- / 204 » 6 4 1 TABLE 3 (continuation) Example R1 cr3r4 R« M.p.'C 49 EtO- cyclohexane 143 (e) * ^-ch2nhco- 50 EtO- cyclohexane EtO(CH2)2NHCO- 166 (e) 51 EtO- cyclohexane h2ncoch2nhco- 245 (e) 52 EtO- cyclohexane Et2n-coch2nhco- 161 (e) 53 EtO- cyclohexane (Et2N-COCH2)2NCO- 141 (c) 54 EtO- cyclohexane nc-c(MC)2NHCO- 198 (e) 55 EtO- cyclohexane Et2NC(NH)NH- 137 (f) hydrochloride hemihydrate 56 (g) cl- (CH2)2oJ^ J \ / 0 (CH2)2O_1^OJ ch30- 136 79 §4 1 2 2 TABLE 3 (continuation) Example R1 CR3R4 r6 M.p.'C 57(1) 00 Eto- \ / \ c VoCHo 1 2 OCH3 Et2NCONH- 88 58(1) 00 EtO- \ / \ C /—OH / v_y EtoNCONH- 130 (a) This compound is prepared by the procedure 5 described in EXAMPLE 2 step C), the reaction being carried out under an inert atmosphere using triethylamine as the base. (b) This compound is prepared by the procedures described in EXAMPLE 9 step A) and then step B) using 10 the appropriate amino derivatives or nitrogen heterocycles. (c) This compound is prepared by the procedure described in EXAMPLE 9 step B) using the appropriate amino derivatives or nitrogen heterocycles. 15 (d) This compound is prepared by the procedures described in EXAMPLE 16 step A) and then step B). (e) This compound is prepared by the procedure described in EXAMPLE 6 step D) using the appropriate amines. 20 (f) This compound is prepared by the procedure described in EXAMPLE 17 using N,N-diethylcyanamide. (g) This compound is prepared by the procedure described in EXAMPLE 1 step A) using 2,4-dimethoxy-benzenesulfonyl chloride and the appropriate indol-2- 25 one. (h) This compound is prepared by the procedure described in EXAMPLE 68 starting from the compound obtained in EXAMPLE 57 (mixture of isomers). (1) mixture of isomers 5 * EXAMPLE 59 5-Ethoxy-l-[4-(N', N'-diethylureido)-2-methoxybenzenesulf onyl]-1,3-dihydro-3-spiro(4-oxocyclohexane)-indol-2-one 0.25 hydrate 10 a mixture of 0.3 g of the compound obtained in EXAMPLE 68, 0.3 g of pyridinium chlorochromate and 1.5 ml of DCM is stirred for 16 hours at RT. 10 ml of water are added to the reaction mixture, the DCM is evaporated off under vacuum, the residue is extracted 15 with AcOEt and dried over magnesium sulfate and the solvent is concentrated under vacuum. The residue is chromatographed on silica using a DCM/MeOH mixture (98/2; v/v) as the eluent to give 0.26 g of the expected product. M.p. - 100*C. 20 EXAMPLE 60 5-Fluoro-1,3-dihydro-1-[2-methoxy-4-(D3-pyrrol in- 1-yl )benzenesulfonyl]-3-spiro(4,4-dimethylcyclo-hexane)indol-2-one This compound is prepared by the procedure 25 described in EXAMPLE 2 step C), the reaction being carried out under an inert atmosphere using triethylamine as the base. EXAMPLE 61 5-Chloro-3,3-dihydroxyethyl-l,3-dihydro-l-(2,4-30 dimethoxybenzenesulfonyl)indol-2-one This compound is prepared by the method described in J. Org. Chem., 1977, 42, 3772. 0.037 g of pyridinium toluenesulfonate in 12 ml of ethanol is added to 0.92 g of the compound of Example 56 described 35 in Table 3 above, and the mixture is heated at about 55*C for 3 hours. The solvent is evaporated off under 81 I 4 i ti reduced pressure and the residue is chromatographed on a silica column using DCM as the eluent. The expected product is Isolated and crystallized from a hot cyclohexane/ethyl acetate mixture (50/50; v/v). M.p. -5 166*C. EXAMPLES 62 and 63 5-Ethoxy-l,3-dihydro-l-(2-methoxy-4-nitroben-zenesulfonyl)-3-spiro[4-(methoxymethoxy)cyclohexane]-indol-2-one, the less polar Isomer and the more polar 10 isomer These compounds are prepared by the procedure described in EXAMPLE 1 step A') starting from 5-ethoxy-1,3-dihydro-3-spiro[4-(methoxymethoxy)cyclohexane]-indol-2-one. They are chromatographed on silica using a 15 cyclohexane/AcOEt mixture (95/5; v/v) as the eluent. The two Isomers are separated into - the less polar isomer: compound of EXAMPLE 62, m.p. - 127*C; - the more polar isomer: compound of EXAMPLE 20 63, m.p. - 118*C. EXAMPLES 64 and 65 ^ 1-(4-Amino-2-methoxybenzenesulfonyl)-5-ethoxy-1,3-dihydro-3-spiro[4-(methoxymethoxy)cyclohexane]-indol-2-one, the less polar Isomer and the more polar 25 isomer These compounds are prepared by the procedure described in EXAMPLE 1 step B1 ' ) starting from the mixture of compounds obtained in EXAMPLES 62 and 63 before chromatography. They are chromatographed on 30 silica using a cyclohexane/AcOEt mixture (95/5; v/v) as the eluent. The two isomers are separated into - the less polar isomer: compound of EXAMPLE 64, m.p. » 103'C; - the more polar isomer: compound of EXAMPLE 35 65, m.p. - lll'C. 82 tkm EXAMPLE 66 5-Ethoxy-l-[4-(N' ,N* -diethylureido)-2-methoxy-benzenesulfonyl] -1,3-dihydro-3-spi.ro [4-(methoxymethoxy )-cyclohexane]indol-2-one, the less polar Isomer 5 This compound is prepared by the procedure described in EXAMPLE 9 step A) and then step B) starting from the compound obtained in EXAMPLE 64 and using diethylamine in the 2nd step. The expected product is obtained after recrystallization from a 10 cyclohexane/ AcOEt mixture. M.p. - *60*C. EXAMPLE 67 5-Ethoxy-l-[4-(N',N'-diethylureido)-2-methoxybenzenesulf onyl]-1,3-dihydro-3-spiro[4-(methoxymethoxy) cyclohexane] indol-2-one, the more polar isomer 15 This compound is prepared by the procedure described in EXAMPLE 9 step A) and then step B) starting from the compound obtained in EXAMPLE 65 and using diethylamine in the 2nd step. The expected product is obtained after recrystallization from a 20 cyclohexane/ AcOEt mixture. M.p. « 137*C. EXAMPLE 68 5-Ethoxy-l-[4-(N',N'-diethylureido)-2-methoxy-benzenesulfonyl]-1,3-dihydro-3-spiro(4-hydroxycyclo-hexane)indol-2-one monohydrate, the less polar isomer 25 A solution of 2.2 g of the compound obtained in EXAMPLE 66 in 6 ml of MeOH and 1.2 ml of concentrated HCl is heated at 50*C for 30 minutes. 10 ml of water are added to the reaction mixture, extraction is carried out with AcOEt, the extract is dried over 30 magnesium sulfate and the solvent is evaporated off under vacuum. The residue is chromatographed on silica using a DCM/MeOH mixture (90/10; v/v) as the eluent to give 1.9 g of the expected product after recrystallization from a cyclohexane/AcOEt mixture. 35 M.p. - 138'C. t 26 4 1 '£> 2. EXAMPLE 69 5-Ethoxy-l -[4-.(N', N1 -diethylureido)-2-methoxy-benzenesulfonyl]-1,3-dihydro-3-spiro(4-hydroxycyclo-hexane)lndol-2-one monohydrate, the more polar isomer S This compound is prepared by the procedure described in EXAMPLE 68 starting from the compound obtained in EXAMPLE 67. The expected product is obtained after recrystallization from a cyclohexane/AcOEt mix ture. M.p. « 144*C. 10 EXAMPLE 70 5-Ethoxy-l,3-dihydro-l-(2-methoxy-4-nitroben-zenesulfonyl)-3-spiro(4-methoxycyclohexane)indol-2-one, the more polar Isomer This compound is prepared by the procedure 15 described in EXAMPLE 1 step A' ) starting froir the more polar isomer of 5-ethoxy-l,3-dihydro-3-spiro(4-methoxycyclohexane )indol-2-one (compound of Preparation 17). The expected product is obtained. M.p. - 141*C. EXAMPLE 71 20 l-(4-Amino-2-methoxybenzenesulfonyl)-5-ethoxy- 1,3-dihydro-3-spiro(4-methoxycyclohexane)indol-2-one, the more polar Isomer This compound is prepared by the procedure described in EXAMPLE 1 step B'') starting from the 25 compound obtained in EXAMPLE 70. M.p. - 199"C. EXAMPLE 72 5-Ethoxy-l-[4-(N',N'-diethylureido)-2-methoxybenzenesulf onyl]-1,3-dihydro-3-spiro(4-methoxycyclohexane )indol-2-one, the less polar isomer 30 A) 5-Ethoxy-l,3-dihydro-l-(2-raethoxy-4-nitrobrmzene- sulfonyl)-3-spiro(4-methoxycyclohexane)indol-2-one, the less polar isomer This compound is prepared by the procedure described in EXAMPLE 1 step A' ) starting from the 35 compound obtained in Preparation 16 (the less polar isomer). 84 •fl C ton ^ B) 1- (4-Amino-2-methoxybenzenesulf onyl) -5-ethoxy-l, 3-dihydro-3-spiro(4-methoxycyclohexane)indol-2-one, the less polar Isomer This compound Is prepared by the procedure 5 described in EXAMPLE 1 step B' ') starting from the compound obtained in the previous step. C) 5-Ethoxy-l-[4-(N',N'-diethylureido)-2-methoxyben-zenesulfonyl]-1,3-dihydro-3-spiro(4-methoxycyclo-hexane)indol-2-one, the less polar isomer 10 This compound is prepared by the procedure described in EXAMPLE 9 step A) and then step B) starting from the compound obtained in the previous step and using diethylamine. M.p. - 118*C. EXAMPLE 73 15 5-Ethoxy-l-[4-(N',N'-diethylureido)-2-methoxy benzenesulf onyl]-1,3-dihydro-3-spiro(4-methoxycyclohexane) indol -2 -one, the more polar isomer This compound is prepared by the procedure described in EXAMPLE 9 step A) and then step B) 20 starting from the compound obtained in EXAMPLE 71 and using diethylamine in the 2nd step. The expected product is obtained after recrystallization from a cyclohexane/ AcOEt mixture. M.p. » 164*C. EXAMPLE 74 25 5-Ethoxy-l,3-dihydro-l-(2-methoxy-4-nitroben- zenesulfonyl)-3-spiro(4-hydroxycyclohexane)indol-2-one, the more polar Isomer A mixture of 2.2 g of the compound obtained in EXAMPLE 63 and 1.2 ml of concentrated HCl in 6 ml of 30 MeOH is heated at 50*C for 1 hour. 10 ml of water are adtf«jd to the reaction mixture and the precipitate formed is filtered off, washed with water and dried under vacuum at 50 *C to give 1.3 g of the expected product. M.p. = 135*C. 35 EXAMPLE 75 5-Ethoxy-l-[4-(N',N'-diethylureido)-2-methoxy- 85 €u&> benzenesulfonyl]-1,3-dihydro-3-spiro(4-ethoxycyclohexane )lndol-2-one A) 5-Ethoxy-l,3-dihydro-l-(2-methoxy-4-nitrobenzene sulfonyl)-3-sp±ro(4-ethoxycyclohexane)indol-2-one 5 A solution of 0.25 g of 5-ethoxy-l,3-dihydro- l-(2-methoxy-4-nltrobenzenesulfonyl)-3-spiro(4-hydroxy-cyclohexane)indol-2-one (prepared by the procedure described In EXAMPLE 74 starting from the mixture of Isomers obtained in EXAMPLES 62 and 63 before 10 chromatography), 0.6 ml of 2,6-di-tert-butylpyridine and 0.37 ml of ethyl tr If luoromethanesul f onate in DCM is stirred for 6 hours at 40*C. 5 ml of 5 N HCl are added to the reaction mixture, extraction is carried out with AcOEt, the organic phase is washed three times 15 with 0.5 N HCl and with a saturated solution of NaCl and dried over magnesium sulfate and the solvent is evaporated off under vacuum to give 0.5 g of the expected product in the form of an oil, which is used as such in the next step. 20 B) 1-(4-Amino-2-snethoxybenzenesulf onyl)-5-ethoxy-l, 3-dihydro-3-spiro(4-ethoxycyclohexane)indol-2-one This compound is prepared by the procedure described in EXAMPLE 1 step B' ) by chemical reduction of the compound obtained in the previous step. It is 25 chromatographed on silica using a DCM/MeOH mixture (99/1; v/v) as the eluent to give the expected product. M.p. - 110*C. C) 5-Ethoxy-1,3-dihydro-1-(2-methoxy-4-phenoxycarbox-amidobenzenesulfonyl)-3-spiro(4-ethoxycyclohexane)- 30 indol-2-one This compound is prepared by the procedure described in EXAMPLE 9 step A) starting from the compound obtained in the previous step. This gives the expected product, which is used as such in the next 35 step. D) 5-Ethoxy-l-[4-(N',N'-diethylureido)-2-methoxy- t 86 U benzenesulfonyl]-1,3-dihydro-3-spiro(4-ethoxycyclohexane )indol-2-one This compound Is prepared by the procedure described In EXAMPLE 9 step B) starting from the 5 compound obtained In the previous step and diethylamine. The expected product is obtained. M.p. - 121*C. EXAMPLE 76 5-Ethoxy-l-[4-(N',N'-diethylureido)-2-methoxy-10 benzenesulfonyl] -1,3-dihydro-3-spiro[4-(2-methoxyeth-oxy)cyclohexane]indol-2-one A) 5-Ethoxy-l,3-dihydro-l-(2-methoxy-4-nitrobenzene-sulfonyl)-3-spiro[4-(2-methoxyethoxy)cyclohexane]-indol-2-one 15 A mixture of 0.2 g of 5-ethoxy-l,3-dihydro- 1- (2-methoxy-4-nitroben«enesulfonyl)-3-spiro(4-hydroxy-cyclohexane)indol-2-one, 2 g of l-iodo-2-methoxyethane, 0.9 ml of 2,6-di-tert-butylpjridine and 2.15 g of silver trifluoromethanesulfonate in 17 ml of CCI4 and 8 20 ml of DCM is stirred for 24 hours at RT. 100 ml of 0.1 N HCl are added to the reaction mixture, the solvents are evaporated off under vacuum, the residue is extracted with AcOEt and dried over magnesium sulfate and the solvent is evaporated off under vacuum. 25 The residue is chromatographed on silica using cyclohexane as the eluent to give 0.36 g of the expected product, which is used as such in the next step. B) l-(4-Amino-2-methoxybenzenesulfonyl)-5-ethoxy-l,3-30 dihydro-3-spiro[4-(2-methoxyethoxy)cyclohexane]indol-2- one This compound is prepared by the procedure described in EXAMPLE 1 step B' ) by reduction of the compound obtained in the previous step. The expected 35 product is obtained. M.p. = 118*C. C) 5-Ethoxy-l,3-dihydro-l-(2-methoxy-4-phenoxycarbox- t -T> £*"•> l r\ ■■ j 'J- 87 / n s v ^ amidobenzenesulfonyl)-3-spiro[4-(2-methoxyethoxy)-cyclohexane]indol-2-one This compound is prepared by the procedure described in EXAMPLE 9 step A) starting from the 5 compound obtained in the previous step. This gives the expected product, which is used as such in the next step. D) 5-Ethoxy-l-[4-(N*,N'-diethylureido)-2-methoxy-benzenesulfonyl]-1,3-dihydro-3-spiro[4-(2-methoxy-10 ethoxy)cyclohexane]indol-2-one This compound is prepared by the procedure described in EXAMPLE 9 step B) starting from the compound obtained In the previous step and diethylamine. The expected product is obtained. 15 M.p. - 98*C. EXAMPLE 77 5-Ethoxy-l-[4-(N*,N'-diethylureido)-2-methoxy-benzenesulfonyl]-1,3-dihydro-3-spiro(4-n-propoxycyclo-hexane)indol-2-one 20 This compound is prepared by the procedures described in EXAMPLE 76 step A) starting from 5-ethoxy-1,3-dihydro-l-(2-methoxy-4-nitrobenzenesulfonyl)-3-spiro(4-hydroxycyclohexane)indol-2-one and 1-iodopro-pane in benzene, and then steps B), C) and D). The 25 expected product is obtained. M.p. - 115*C. EXAMPLE 78 5-Ethoxy-l-[4-(N',N'-diethylureido)-2-methoxybenzenesulf onyl] -1,3-dihydro-3-spiro(4-isopropoxycyclo-hexane)indol-2-one hemihydrate 30 This compound is prepared by the procedures described in example 76 step a) starting from 5-ethoxy-l ,3-dihydro-l-(2-methoxy-4-nitrobenzenesulfonyl)-3-spiro(4-hydroxycyfclohexane)indol-2-one and 2-iodopro-pane in benzene, and then steps B), C) and D). The 35 expected product is obtained. M.p. = 130*C. EXAMPLE 79 5-Ethoxy-l-[4-(N', N'-diethylureido)-2-methoxybenzenesulfonyl] -1,3-dihydro-3-spiro[4-(2-tert-butoxy-ethoxy)cyclohexane]indol-2-one 5 This compound is prepared by the procedures described in EXAMPLE 76 step A) star-ting from 5-ethoxy-l, 3-dihydro-l-(2-methoxy-4-nitrobenzenesulf onyl )-3-spiro(4-hydroxycyclohexane)indol-2-one and l-iodo-2-tert-butoxyethane, and then steps B), C) and D). The 10 expected product is obtained. M.p. » 103*C. EXAMPLE 80 5-Ethoxy-l-[4-(N',N'-diethylureido)-2-methoxy-benzenesulfonyl]-1,3-dihydro-3-spiro[4-(2-hydroxy-ethoxy)cyclohexane]indol-2-one 15 A mixture of 0.35 g of the compound obtained in EXAMPLE 79 and 4 ml of trifluoroacetic acid in 15 ml of DCM is stirred for 2 hours at RT. 40 ml of a saturated solution of NaHC03 are added, the mixture is decanted, the organic phase is washed with water and dried over 20 magnesium sulfate and the solvent is evaporated off under vacuum. The residue is chromatographed on silica using a DCM/MeOH mixture (90/10; v/v) as the eluent to give the expected product. M.p. » 109*C. EXAMPLE 81 25 5-Ethoxy-l-[4-(N',N'-diethylureido)-2-methoxy- benzenesulfonyl]-1,3-dihydro-3-spiro(4-formyloxycyclo-hexane)indol-2-one, the more polar isomer A mixture of 0.25 g of the compound obtained in EXAMPLE 69, 0.18 g of cesium carbonate, 0.45 ml of 30 dimethyl sulfate and 12 ml of DMF is heated at 40*C for 12 hours. 10 ml of water are added, the reaction mix ture is extracted with AcOEt, the organic phase is washed with water and dried over magnesium sulfate and the solvent is evaporated off under vacuum. The 35 residue is chromatographed on silica using DCM as the eluent to give 0.2 g of the expected product after recrystallization from a cyclohexane/AcOEt mixture. M.p. - 155*C. EXAMPLE 82 5-Ethoxy-l-[4-(N',N'-diethylureido)-2-methoxy-5 benzenesulfonyl]-1,3-dihydro-3-spiro(4-acetoxycyclo-hexane)indol-2-one, the more polar isomer A mixture of 3 g of the compound obtained in EXAMPLE 69, 0.75 g of 4-dimethylaminopyridine, 3 ml of acetic anhydride and 5 ml of DCM is heated at 40'C for 10 5 hours. Water is added to the reaction mixture, ex traction is carried out with DCM, the extract is washed with water and dried over magnesium sulfate and the solvent is evaporated off under vacuum. The residue is chromatographed on silica using a DCM/cyclohexane 15 mixture as the eluent to give the expected product after recrystallization from iso ether. M.p. - 140*C. EXAMPLE 83 5-Ethoxy-l,3-dihydro-l-(2,4-dimethoxybenzene- sulfonyl)-3-spiro(8,9-dihydroxytricyclo[5.2.1.0^f6]» 20 decan-4-yl)indol-2-one A) 5-Ethoxy-1,3-dihydro-l-(2,4-dimethoxybenzenesulfonyl )-3-spiro(8,9-epoxytricyclo[5.2.1.0^, 6 ]decan-4-yl)indol-2-one A mixture of 0.3 g of 5-ethoxy-l,3-dihydro- 1-25 (2,4-dimethoxybenzenesulfonyl)-3-spiro(tricyclo- [5.2.1.o2f6]dec-8-en-4-yl)indol-2-one and 0.2 g of metachloroperbenzolc acid in 20 ml of DCM is stirred for 3 hours at RT. .15 ml of a saturated solution of NaHC03 are added, the mixture is decanted, extraction 30 is carried out with DCM, the extract is dried over mag nesium sulfate and the solvent is evaporated off under vacuum. The residue is chromatographed on silica using DCM as the eluent to give 0.25 g of the expected product after recrystallization from an acetone/DCM 35 mixture. M.p. = 263*C. B) 5-Ethoxy-l,3-dihydro-l-(2,4-dimethoxybenzenesul- </div>

Claims

<div class="application article clearfix printTableText" id="claims"> 90 fonyl)-3-spiro(8,9-dihydroxytricyclo[5.2.1.02'6]decan-4-yl)indol-2-one A mixture of 0.2 g of the compound obtained in the previous step, 20 ml of water, 2 ml of concentrated 5 sulfuric acid and 20 ml of THF is refluxed for 8 hours. The reaction mixture is neutralized by the addition of a saturated solution of NaHC03, the solvent is evaporated off under vacuum, the residue is extracted with DCM and dried over magnesium sulfate and the 10 solvent is evaporated off under vacuum. The residue is chromatographed on silica using a DCM/MeOH mixture (99/1; v/v) as the eluent to give 0.17 g of the expected product. M.p. = 150*C. 15 20 25 30 WHAT ttWE CLAIM IS:- A compound of the formula Ri l2 -R/ so' 7tr5 x(r«) m 00 In which - Ri and R2 are each Independently a hydrogen; a hydroxyl; an co-halogeno-Ci~C7-alkoxy; a halogen; a C\-C7~alkyl; a trifluoromethyl; a Ci-C7-alkoxy; a polyhalogeno-Ci-C7~alkoxy; an co-hydroxy-C2-C7-alkoxy; an to-methoxyalkoxy in which the alkyl is C2-C7; an co-amino-C2-C7-alkoxy which is free or substituted by one or two Ci-C7~alkyls; a C3-C7-cycloalkoxy; a cycloalkylmethoxy in which the cycloalkyl is C3-C7; a phenoxy; a benzyloxy; a C1-C7-alkylthio; a phenylthio; a nitro; an amino which is free or substituted by one or two Ci-C7~alkyls; a cyano; a (C^-Cg)alkylcarbonyl; a formyl; a (C^-Cg)alkylcarbonyloxy; a formyloxy; a C\-Cy-alkylsulfonamido; a phenylsulfonamido; a benzylsulfonamido; a Ci-C7-alkylamido; a C^- C7-alkoxycarbonylamino; a ureido which is unsubstituted or substituted by a phenyl, a benzyl or one or two C1-C7-alkyls; or a thioureido which is unsubstituted or substituted by a phenyl, a benzyl or one or two C1-C7-alkyls; - R3 and R4 are each independently a C1-C7-alkyl; a C3-C7-cycloalkyl; a phenyl; a benzyl; a cycloalkylmethyl 92 in which the cycloalkyl is C3-C7; or an a>-hydroxy-C2_ C7~alkyl in which the hydroxyl is free or substituted by a group selected from Ji-C4-alkyl groups, (C1-C5) alkoxyalkyl groups in which the alkyl is C1-C4, phenylalkoxyalkyl groups in which the alkoxy is C1-C2 and the alkyl is C1-C4, and tetrahydrofuranyl and tetrahydropyranyl groups; or - R3 and R4 together form a group -(CH2)pX(CH2)q-; or - R3 and R4, together with the carbon to which they are bonded, form an optionally fused, saturated or unsaturated C3-C12 hydrocarbon ring which is unsubstituted or substituted by one or more Ci-Cy-alkyl groups, by an oxo group, by a C3-C5-spirocycloalkyl or by one or two hydroxyls which are free or substituted by a group selected from Ci~C4-alkyl groups, (C^-C5)alkoxyalkyl groups in which the alkyl is C^- C4, o)~ hydroxyalkyl groups in which the alkyl is C^- C4, triphenylmethoxyalkyl groups in which the alkyl is Cj-C4, phenylalkoxyalkyl groups in which the alkoxy is C^-C2 and the alkyl is C1-C4, and tetrahydrofuranyl, tetrahydropyranyl, formyl and (C^-Cy)alkylcarbonyl groups; - R5 and Rg are each independently a hydrogen; a halogen; a Ci-C7~alkyl; a trifluoromethyl; a cyano; a nitro; an amino which is free or substituted by one or two Ci-Cy-alkyls; a hydroxyamino; a hydroxyl; a carboxyl; a guanidino which is unsubstituted or mono substituted or disubstituted by a Ci-C7-alkyl, a phenyl or a benzyl; a group --OR7; a group -SR7; a (Ci~ Cg)alkylcarbonyl; a formyl; a Ci-C7~alkoxycarbonyl; a phenoxycarbonyl; a benzyloxycarbonyl; a carbamoyl substituted by groups R'6 and R''g; a thiocarbamoyl which is free or substituted by one or two C1-C7-alkyls; a sulfamoyl; an alkylsulfamoyl or % 93 9 R * a *j / i £ tCaa dialkylsulfamoyl in which the alkyl is C1-C7; a group -S02R'7; an alkylsulfonamido in which the alkyl is C^-C7; a phenylsulfonamido; a benzylsulfonamido; a group -COR'7; a group -NRgRg; or a group -CO-NH- CRio^'lO" 5 COR12? if appropriate, the phenyl group forming part of the substituent R5 and/or Rg can be unsubstituted or monosubstituted or polysubstituted by a Ci-C7-alkyl, a trifluoromethyl, a Ci-C7~alkoxy, a halogen, a sulfamoyl, an alkylsulfamoyl in which the alkyl is Ci~ 10 C7, a carboxyl, an alkoxycarbonyl in which the alkyl is C1-C7, a (Ci-Cg)alkylcarbonyloxy or an imidazolyl; - R'g and R''6 are each independently hydrogen; a C^-C7- alkyl which is unsubstituted or substituted by one or more halogens or Rn,g; a C3-C7-cycloalkyl which is 15 unsubstituted or substituted by a (C1-C4)alkyl; a phenyl; a pyridyl; a methylpyridyl; a piperidin-4-yl; a methylpiperidin-4-yl; or a pyrrolidin-l-yl; or R'g and R''6/ with the nitrogen atom to which they are bonded, form a pyrrolidino group substituted by a hydroxymethyl 20 or by a carbamoyl which is free or substituted by one or two Ci~C7-alkyls; - R' ''g is a hydroxyl; a Ci-C7~alkoxy; an amino which is free or substituted by one or two Cj-Cy-alkyls; a carbamoyl which is free or substituted by one or two 25 -C7-alkyls or in which the two substituents, together with the nitrogen atom to which they are bonded, form a pyrrolidino, a piperidino or a perhydroazepino; a cyano; a carboxyl which is free or esterified by a C^-C7~alkyl or a benzyl; a phenyl; a C3-C7-cycloalkyl; an 30 adamantyl; or a heterocyclic radical selected from pyridyl, methylpyridyl, furanyl, tetrahydrofuranyl, thienyl, methylthienyl, pyrrolidino, piperidino and perhydroazepino groups; - R7 is a Ci-C7~alkyl; a phenyl; a benzyl; a C3-C7-35 cycloalkyl; a C2-C7-alkenyl; an o>-halogeno-C2-C7- alkyl; a polyhalogeno-Ci-C7-alkyl; an co-hydroxy-C2- C7- 94 »■ ; v alkyl; a (Cj_-Cg) alkylcarbonyl; a formyl; an to- carboxy-Ci-C7-alkyl which is free or esterified by a C^-Cy alkyl or a benzyl; an co-amino-C2-C7-alkyl in which the amino group is free, substituted by one or two C1-C7-5 alkyls or in the form of an ammonium ion; or an (o-carbamoyl-Ci-c7-alkyl which is free or substituted by one or two Ci-C7-alkyls; - R'7 is a piperazin-l-yl group which is unsubstituted or substituted in the 4-position by a group R''7; a 10 piperidino group which is unsubstituted or substituted in the 4-position by a group R1 ' 17; an azetidin- 1-yl group which is unsubstituted or substituted in the 3-position by a group R'''7; or a pyrrolidino group which is unsubstituted or substituted by a group R'''17 ? 15 - R''7 is a C'i-c7-alkyl; a phenyl; a benzyl; a (Ci-Cg)-alkylcarbonyl; or a formyl; - R'''7 is R''7; or an amino which is free or carries a protecting group; - R' ' ''7 is R''17; or a carboxyl group which is free or 20 esterified by a Ci-C7~alkyl; - Rg and Rg are each independently a hydrogen; a C1-C7-alkyl; a benzyl; or a phenyl; Rg can also be a C3-C8-alkene; a (C^-Cg)alkylcarbonyl; a formyl; a (C^-Cg) alkylthiocarbonyl; a cycloalkylcarbonyl in which the 25 cycloalkyl is c3-c7; a cycloalkylthiocarbonyl in which the cycloalkyl is c3-c7; an a)-amino(c2-Cg) alkylcarbonyl; an G)-hydroxy(Ci-Cg) alkylcarbonyl; an 00-benzyloxy(Ci~Cg)alkylcarbonyl; a phenoxycarbonyl; a phenoxythiocarbonyl; a thienocarbonyl; a 30 pyridylcarbonyl; a methylpyridylcarbonyl; a C1-C7-alkoxycarbonyl; a benzoyl; a phenacetyl; a group -CO- CRioR'10- NRiiR'n? a group -criqR'iocor12? a group -(CH2)*tC0 R12? a group -C0(CH2)t'C0Ri2/ a carbamoyl which is unsubstituted or substituted by R14 and R'i4; 35 a thiocarbamoyl which is unsubstituted or substituted by R14 and R'14; or a heterocyclic radical selected 95 n & 4 o 0 u s a. £ from pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyridyl and thiazolyl groups; or 5 - Rg and Rg, together with the nitrogen atom to which they are bonded, form hydantoin; N-methylhydantoin; or a heterocycle selected from pyrrol-l-yl, A3- pyrrolin-1-yl, pyrrolidin-l-yl and isoindolin-2-yl in which the benzene ring can be unsubstituted or substituted by a 10 halogen, a Ci-Cy-alkyl, a trifluoro methyl or a methoxy; - Rio and R'io are each independently hydrogen; a c^-C7-alkyl; or a benzyl; or an<5 R,10' together with the carbon atom to which they are bonded, form a C3- 15 C7-cycloalkyl; - Rn and R'n are each independently hydrogen; or a Ci-C7-alkyl; - R12 is a hydroxyl; a C^-C7~alkoxy; or an amino which is unsubstituted or substituted by one or two C1-C7- 20 alkyls; - R13 is hydrogen; a Ci-C7-alkyl; a phenyl; a benzyl; a (C1-C5)alkylcarbonyl; a formyl; a Ci~C7-alkoxycarbonyl; or a carbamoyl which is unsubstituted or substituted by one or 2 Ci-C7~alkyls; 25 - R14 and R*i4 are each independently a C1-C7-alkyl which is unsubstituted or substituted by R15; a phenyl which is unsubstituted or substituted by R'is; a C3-C7-cycloalkyl; or an adamantyl; or 30 - r^4 and R'i4, together with the nitrogen atom to which they are bonded, form a heterocycle selected from morpholine, thiomorpholine, piperazine, azetidine, pyrrolidine, piperidine and perhydroazepine, said heterocycle being unsubstituted or substituted by one 35 or more methyl groups, by a phenyl or by an amino group which is free or carries a protecting group; 96 f**- 0 ^ - R15 is a phenyl; a pyridyl; a hydroxyl? a C1-C7-alkoxy; an amino which is free or substituted by one or two C^-Cy-allcyls; or a carboxyl which is free or esterified by a Ci-C7~alkyl; 5 - R'15 is a hydroxyl; or an amino which is free or substituted by one or two Ci-C7-alkyls; - m is 1 or, if Rg is a halogen, a Ci-C7~alkyl or a C^-C7-alkoxy, m can also be 2, 3 or 4, or else (Rg)m can be m substituents having different meanings selected 10 from halogen, Ci-C7-alkyl and Ci-C7~alkoxy; - p and q are each an integer, it being possible for their sum to vary from 3 to 6; - t is an integer which can vary from 2 to 5; - t' is an integer which can vary from 0 to 3; 15 - X is oxygen; a group S(0)n; a group NR13; or a group N(0)Ri3; and - n is 0, 1 or 2; with the limitation that if - R^ and R2 are as defined above with the exception of 20 the ureido group substituted by a benzyl group, or the thioureido group which is unsubstituted or substituted by a phenyl, a benzyl or one or two C^- C4~alkyls; - R3 and R4 are each independently a Ci-Cg-alkyl; a C3-C7-cycloalkyl; a phenyl; a benzyl; or a cycloalkyl- 25 methyl in which the cycloalkyl is C3-C7; or - R3 and R4 together form a group -(CH2)pX(CH2>q- in which X is oxygen, sulfur or a group NR13; or 30 - R3 and R4, together with the carbon to which they are bonded, form an optionally fused, saturated or unsaturated C3-C10 hydrocarbon ring which is unsubstituted or substituted by one or more Ci-C7-alkyl groups or by a C3-C5-spirocycloalkyl; 35 - R5 and Rg are other than a hydrogen; a halogen; a Cj-C7~alkyl; a trifluoromethyl; a cyano; a nitro; an amino 26 4122- - R^5 is a phenyl; a pyridyl; a hydroxyl; a C1-C7-alkoxy; an amino which is free or substituted by one or two Ci-C7~alkyls; or a carboxyl which is free or esterified by a Ci-C7-alkyl; 5 - R'is is a hydroxyl; or an amino which is free or substituted by one or two Ci-C7-alkyls; - m is 1 or, if Rg is a halogen, a Ci-C7-alkyl or a Ci~ C7-alkoxy, in can also be 2, 3 or 4, or else (Rg)m can be m substituents having different meanings selected 10 from halogen, Ci~C7-alkyl and Ci-C7-alkoxy; - p and q are each an integer, wherein their sum vary from 3 to 6; - t is an integer from 2 to 5; - t' is an integer from 0 to 3; 15 - X is oxygen; a group S(0)n; a group NR13; or a group N(0)Ri3; and - n is 0, 1 or 2; with the limitation that if - Ri and R2 are as defined above with the exception of 20 the ureido group substituted by a benzyl group, or the thioureido group which is unsubstituted or substituted by a phenyl, a benzyl or one or two Ci- Chalky Is; - R3 and R4 are each independently a C^-Cg-alkyl; a C3-C7-cycloalkyl; a phenyl; a benzyl; or a cycloalkyl- 25 methyl in which the cycloalkyl is C3-C7; or - R3 and R4 together form a group - (CH2 )pX( CH2 )q- in which X is oxygen, sulfur or a group NR13; or 30 - R3 and R4, together with the carbon to which they are bonded, form an optionally fused, saturated or unsaturated C3-C10 hydrocarbon ring which is unsubstituted or substituted by one or more Ci-C7~alkyl groups or by a C3-C5-spirocycloalkyl; 35 - R5 and Rg are other than a hydrogen; a halogen; C7~alkyl; a trifluoromethyl; a cyano; a nitro; an 97 r which is free or substituted by one or two C]_- C7-alkyls; a hydroxyamino; a hydroxyl; a carboxyl; a group -OR7; a group -SR7; a (Ci~Cg)alkylcarbonyl; a formyl; a Ci-C7-alkoxycarb°nyl; a phenoxycarbonyl; a 5 benzyloxycarbonyl; a carbamoyl substituted by groups R'g and R''g; a thiocarbamoyl which is free or substituted by one or two Ci-C7~alkyls; a sulfamoyl; an alkyl sulfamoyl or dialkylsulfamoyl in which the alkyl is C1-C7; a group -S02R'7; an alkylsulfonamido in which 10 the alkyl is C1-C7; a group -COR17; a group -NRgRg; or a group -C0-NH-CH(Riq)-C0Ri2» it being possible, if appropriate, for the phenyl group forming part of the substituent R5 and/or Rg to be unsubstituted or monosubstituted or polysubstituted by a Ci-C7~alkyl, a 15 trifluoromethyl, a methoxy, a halogen, a sulfamoyl, an alkylsulfamoyl in which the alkyl is Ci~C7/ a carboxyl, an alkoxycarbonyl in which the alkyl is C1-C7, a Ci-Cg-alkylcarbonyloxy; a formyloxy or an imidazolyl; in which groups R5 and/or Rg: 20 - R'g and R''g are each independently hydrogen; a C^-C7- alkyl which is unsubstituted or substituted by R'''g; a phenyl; a pyridyl; a methylpyridyl; a piperidin-4- yl; or a methylpiperidin-4-yl; - RV'g is a hydroxyl; a cyano; a carboxyl which is 25 free or esterified by a Ci-C7~alkyl or a benzyl; a phenyl; a pyridyl; a methylpyridyl; or an amino which is free or substituted by one or two Ci-C7~alkyls; - R7 is a Ci-C7~alkyl; a phenyl; a benzyl; a C3-C7-cycloalkyl; a C2-C4-alkenyl; an oo-halogeno-C2-C7- 30 alkyl; a polyhalogeno-Ci-C7-alkyl; a (Ci~Cg)alkylcar bonyl; a formyl; an co-carboxy-Ci-C7-alkyl which is free or esterified by a Ci-C4~alkyl or a benzyl; or an co-amino-C2-C7-alkyl in which the amino group is free, substituted by one or two Ci-C4~alkyls or in the form 35 of an ammonium ion; 98 26 41*2. - R*7 is a piperazin-l-yl group which is unsubstituted or substituted in the 4-position by a group R' '7; a piperidino group which is unsubstituted or substituted in the 4-position by a group R'''7; an azetidin- 1-yl 5 group which is unsubstituted or substituted in the 3-position by a group R'''7; - R' '7 is a Ci-C4~alkyl; a phenyl; a benzyl; or a (C^-C3)alkylcarbonyl; - R'' '7 is R''7; or an amino which is free or carries a 10 protecting group; - Rg and Rg are each independently a hydrogen; a C1-C7-alkyl; a phenyl; or a benzyl; Rg can also be a (C^-Cg)alkylcarbonyl; a formyl; a cycloalkylcarbonyl in which the cycloalkyl is C3-C7; a cycloalkylthiocarbo 15 nyl in which the cycloalkyl is C3-C7; an o>-amino(C2-C3) alky lcarbonyl; an ti)-hydroxy (C^-C3) alky lcarbonyl; an co-benzyloxy(C1-C3)alkylcarbonyl; a phenoxycarbonyl; a thienocarbonyl; a pyridylcarbonyl; a methyl pyridylcarbonyl; a Ci~C4-alkoxycarbonyl; a benzoyl; a 20 group -CO-CH(Rio)-NRnR'n; a group -CH(Riq)C02Rh; a group -(CK2)t•1COR12' a group -CO(CH2)t'1 COR12' or a carbamoyl which is unsubstituted or substituted by a phenyl or one or two Ci-C4~alkyls; - t'' is an integer which can vary from 1 to 3; 25 - R^o is hydrogen; a Ci-C4~alkyl; or a benzyl; - R11 and R'ii are each independently hydrogen; or a Ci-C4-alkyl; - R12 is a hydroxyl; a C1-C4-alkoxy; or an amino which is unsubstituted or substituted by one or two C1-C4- 30 alkyls; and - R13 is hydrogen; a Ci-C4~alkyl; a phenyl; a benzyl; a (C1-C3)alkylcarbonyl; a formyl; a -C4~alkoxycarbonyl; or a carbamoyl which is unsubstituted or substituted by one or 2 C-i-C^-alkyls; provided that when one of R3 and R4 is methyl or ethyl, the other being methyl; m = 1 and one of R5 is hydrogen, the other is different from p-methyl; and its salts when appropriate. J*- J 99 26412?
2. A compound of formula (I) according to claim 1 wherein Is a chlorine or fluorine atom or an ethoxy group in the 5-position of the 1,3-dihydroindol-2-one derivative and Rj is hydrogen. 5
3. A compound of formula (1) according to claim 1 or 2 wherein R3 and R4, together with the carbon to which they are bonded, form a C3-C12 hydrocarbon ring.
4. A compound of formula (I) according to claim 3 wherein R3 and R4, together with the carbon to which 10 they are bonded, form a cycloheptane, an adamantane, a tricyclo[5.2.1.0^/6]dec-8-ene, a tricyclo[5.2.1.0^*6] decane, a bicyclo[2.2.1]heptane, a bicyclo[3.3.l]nonane or a cyclohexane which is unsubstituted or substituted by a C3-C5-spirocycloalkyl or by one or two Ci-C7-alkyl 15 groups.
5. A compound of formula (I) according to claim 1 or 2 wherein R3 and R4, together with the carbon to which they are bonded, form a cyclohexane substituted by a group selected from methoxy, ethoxy and 2-methoxy- 20 ethoxy.
6. A compound of formula (I) according to any one of claims 1 to 5 wherein R5 is an orthomethoxy group and Rg in the para-position is a group selected from: - (piperidin-l-yl)carboxamido, 25 - (2-cyanoprop-2-yl)carbonyl, - pyrrolidin-l-yl, - 3,3-diethylguanidino and - N',N'-diethylthioureido.
7. A process for the preparation of a compound of 30 formula (I) according to claim 1, and its salts, which comprises: 1/ reacting a benzenesulfonyl halide of the formula Hal-S02 (RVI>m (tII) 100 261 W"1 in which Hal is a halogen atom, m as defined in claim 1, and R' 5 and Rvi are respectively either R5 and Rg as defined for (I) in claim 1, or precursor groups of R5 and Rg, with a l,3-dihydroindol-2-one disubstituted in the 3-position of the formula 10 (n) 1, R'2/ r,3 and R'4 are respectively either Rl, R2, R3 and R4 as defined for (I) in claim 1, or precursor groups of Rj_, R2, R3 and R4; and 15 2/ either, if R'x - Rlf R'2 - R2/ R'3 - R3> R,4 - R4, r,5 " r5 an<* RVI " r6' isolating the resulting compound of formula (I); 3/ or, if any one of the groups R'i, R'2' R,3» R,4/ R,5 and/or is respectively a precursor group of R^, R2, 20 R0, R4, Rg and/or Rg, subjecting the compound obtained in step 1/ to a subsequent treatment in order to prepare the compound of formula (X) by converting any one of the groups R'i, R'2» R,3^ R,4> R,5 and/or Ryj to Rl» R2» r3* r4» r5 and/or Rg respectively; and 25 4/ if desired, converting the resulting compound of formula (I) to one of its salts.
8. A process as claimed in claim 7 in which benzenesulfonyl halide of the formula III is as defined in step 1 and wherein Hal is chlorine.
9. A pharmaceutical composition in which a compound according to any one of claims 1 to 6 is present as the active principle. 30
10. A pharmaceutical composition in which a pound according to any one of claims 1 to 6 is in association with knovher active principle. *.6 412?
11. A pharmaceutical composition in which two compounds according to any one of claims 1 to 6 are present, one being a specific Vi receptor antagonist and the other being a specific V2 receptor antagonist.
12. A pharmaceutical composition in which two compounds according to any one of claims 1 to 6 are present, one being a specific V]_ receptor antagonist and the other being a specific ocytocin antagonist.
13. A compound of formula (I) according to claim 1, substantially as described with reference to any one of the Examples.
14. A compound of formula (I) according to any one of claims 1-6, substantially as herein described.
15. A process according to claim 7 or claim 8> substantially as described with reference to any one of the Examples.
16. A process according to claim 7 or claim 8, substantially as herein described.
17. A pharmaceutical composition according to any one of claims 9-12, substantially as herein described. ( / By its attorneys ^ BALDWIN SON and CAREY </div>