NZ208118A - Diphenylazomethine derivatives containing an esterfied chain and pharmaceutical compositions - Google Patents

Abstract

1. Claims (for the contracting states : BE, CH, DE, FR, GB, IT, LI, LU, NL, SE) Diphenylazomethines containing an esterified chain and corresponding to the formula (I) see diagramm : EP0125975,P15,F1 in which X1 , X2 and X3 independently of one another each represent a hydrogen or halogen atom or a (C1-6 )alkyl radical, R represents a straight-chain or branched (C1-6 )alkyl radical, n represents an integer from 1 to 10 and R' represents a straight-chain or branched (C1-6 )alkyl radical, a (C3-6 )cycloalkyl(C1-4 )alkyl radical, a (C3-7 )cycloalkyl radical, a (C2-6 )alkenyl radical, a (C3-6 )alkynyl radical, a (C1-4 )alkoxy(C1-4 )alkyl radical, a hydroxy-(C1-4 )alkyl radical, a (C1-4 )alkoxy-[(C1-4 )alkoxy]m -(C1-4 )alkyl radical, in which m is an integer from 1 to 3, a (C1-4 )alkoxycarbonyl(C1-4 )alkyl radical, a tetrahydrofurylmethyl radical, a phenyl-(C1-4 )alkyl radical which can carry a halogen atom, or a (C1-4 )alkoxy radical. 1. Claim (for the contracting state AT) Process for the preparation of diphenylazomethines containing an esterified chain and corresponding to the formula (1) see diagramm : EP0125975,P17,F1 in which X1 , X2 and X3 independently of one another each represent a hydrogen or halogen atom or a (C1-6 )alkyl radical, R represents a straight-chain or branched (C1-6 )alkyl radical, n represents an integer from 1 to 10 and R' represents a straight-chain or branched (C1-6 )alkyl radical, a (C3-6 )cycloalkyl (C1-4 )alkyl radical, a (C3-7 )cycloalkyl radical, a (C2-6 )alkenyl radical, a (C3-6 )alkynyl radical, a (C1-4 )alkoxy-(C1-4 )alkyl radical, a hydroxy-(C1-4 )alkyl radical, a (C1-4 )alkoxy[(C1-4 )alkoxy]m -(C1-4 )alkyl radical, in which m is an integer from 1 to 3, a (C1-4 )alkoxy-carbonyl-(C1-4 )alkyl radical, a tetrahydrofurylmethyl radical, a phenyl-(C1-4 )alkyl radical which can carry a halogen atom, or a (C1-4 )alkoxy radical, process characterised in that either a benzophenone (II) see diagramm : EP0125975,P17,F2 is reacted with the hydrochloride of an ester of an omega-amino-alkanoic acid (III) H2 N-(CH2 )n -COOR', HCl or an acid (IV) see diagramm : EP0125975,P17,F3 is reacted with an alcohol R'OH (V) in the presence of carbonyldiimidazole, or an alkali metal salt of an acid (VI) see diagramm : EP0125975,P18,F1 is reacted with a compound R'Y (VII), in which Y represents a halogen atom or a labil group, such as mesyl or tosyl, the radicals X1 , X2 , X3 , n, R and R' having the meanings given above.

Description

New Zealand Paient Spedficaiion for Paient Number £08118 208O8 /% Priority Date(s): Ji- ^ ?? Complete Specification Filed: (?. Class: c.?.7. ^W/4.. (\&(&./&.

C.?M4?jJ.'A Publication Date: .2 3 JAN 1987 P.O. Journal, No: .......

HO DRAWINGS NEW ZEALAND PATENTS ACT, 1953 No.: Date: COMPLETE SPECIFICATION DIPENYLAZOMETHINES CONTAINING AN ESTERIFIED CHAIN, THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM o K/We SYNTHELABO, a French Body Corporate of 58, rue de la Glaciere, 75621 Paris, France, hereby declare the invention for which K / we pray that a patent may be granted to mX/us, and the method by which it is to be performed, to be particularly described in and by the following statement: - (Followed by page DESCRIPTION DIPHENYLAZOMETHINBS CONTAINING AN ESTERIFIED CHAIN, THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM The present invention relates to diphenylazomethines containing an esterified chain, their preparation and their use in therapy.

The diphenylazomethine compounds according to the invention are of the formula in which X^, X2 and X^r which may be the same or different, each represent a hydrogen or halogen atom or a (C^_g) alkyl group, R represents a straight-chain or branched (C^_g) alkyl group, n represents an integer from 1 to 10 and R' represents a straight-chain or branched (Ct_g) alkyl group, a (C^_g) cycloalkyl alkyl group, a (C^_^) cycloalkyl group, a (C2_g) alkenyl group, a (C^_g) alkynyl group, a alkoxy-(C^_^) alkyl group, a hydroxy-(C^_^)alkyl group, a (Cj__^J alkoxy-[(Cj_^) alkoxy] (C2_4 ) alkyl group, in which m is an integer from 1 to 3, a alkoxy-carbonyl-(C^_^) alkyl group, a tetrahydrofurylmethyl group or a phenyl-(C^) alkyl group which can carry a halogen atom or a (_4) alko^y^i^^^ R (I) X 3 group 208118 n o Preferred compounds according to the invention are those of the formula R C=N- X3 in which X^, X£ and X^> which may be the same or different, 10 each represent a hydrogen atom, a chlorine atom or a methyl, ethyl or propyl group, n represents 3, 4 or 5, R represents a methyl, ethyl, n-propyl or isobutyl group and R' represents a straight-chain or branched (C^_g) alkyl group or a cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl, 15 allyl, hydroxyethyl, (ci_4) alkoxy-ethyl, ethoxycarbonylmethyl, tetrahydrofuryl-methyl, (methoxy-2-ethoxy)-2-ethyl, [(methoxy-2-ethoxy)-2-ethoxy]-2-ethyl, cyclohexyl, cyclopentyl, benzyl, propargyl, methoxy-benzyl or iso-penten-2-yl group; in particular compounds in which X^, 20 X2 and X.^, which may be the same or different, each represent a hydrogen atom, a chlorine atom or a methyl group, n is 3, 4 or 5, R represents a methyl, ethyl or n-propyl group and R' represents a methyl, ethyl, propyl, allyl or ethoxyethyl group; and more particularly compounds which correspond to 25 the formula 208118 =N-(CH2)n-cO0R' X. in which the symbols have the meanings given above; of these Latter compounds/ the compounds of choice are those for which X ^ is a chlorine atom, X2 is a chlorine atom or a methyl group and X^ is a hydrogen atom.

According to the invention, the compounds may be prepared by any one of the following three methods: method A D + method B H-N-(CHJ -COOR' , H CI (hi) -> (I; l| ^II> 3 carbonyldi imidazole 'CH2)n-C00H + R'OH (IV) (v) : I) 208118 - 4 — » (I) M = alkali metal Y = halogen or a labile group, such as mesyl or tosy I.

According to method A, a ketone (II) is reacted with the hydrochloride of an ester of an w-amino-alkanoic acid (III) in a solvent, such as an alco~ hoi (methanol or ethanol), at a temperature from 60 to 100°C.

According to method B, an acid (IV), described in NZ Patent Specif ications Nos 202519 and 206409, is reacted with an alcohol R'OH (V) in the presence of carbonyldiimidazole in a solvent, such as tetrahydrofuran, at a temperature from 60 to 140°C.

According to method C , an alkali metal salt of the acid (VI), described in NZ Patent Specifications Nos • 202519 and 206409, is reacted with a compound R'Y (VII) in a solvent, such as anhydrous dimethyl sulphoxide, in the presence of a base, such as triethy I amine, at a temperature from 50 to 150°C. 208118 v./' The hydrochlorides of esters of w-amino-a Ikanoic acids (III) can be prepared from the w-amino-aIkanoic acid by reaction with the corresponding alcohol R'OH in the presence of SOC^.

The alcohols R'OH (V) and the compounds R'Y (VII) ^ are described in the Literature.

The Examples which follow iLlustrate the invention.

The structures of the compounds were confirmed by 10 microanalyses and IR( UV and NMR spectra.

E xamp Le 1. Ethyl 4-£C(5-ch10ro-2-hydroxy-3-n-propylphenyl)-(4-chlorophenyl)-methyleneDaminoj-butanoate (X1 = 5-Cl, X2 = 4-Cl, X3 = H, n = 3, R = n-C3H?/ R' = C2H5) 1. A suspension of 206 g (2 moles) of 4-aminobu- tanoic acid and 1/200 cm' of ethanol is brought to 50-60°C in an oil bath/ while stirring. 252 ml of SOC 12 are added in the course of 1 hour, while bringing up and maintaining the mixture at the reflux temperature for 3 20 hours.

The mixture is evaporated to dryness and the residue is washed twice with 500 cm' of ether each time.

After purification of the solution of the residue in ethanol with the aid of vegetable charcoal and washing 25 with ether, white hygroscopic crystals are obtained. Melting point = 72°C. 2. A mixture of 6 g (0.0194 mole) of (5-chloro- 2031 1 ® D 2-hydroxy-3-n-propy lphenyl)-(4-ch lorophenyD-methanone, 4.06 g (0.0242 mole) of the hydrochloride of ethyl 4-arii nobutanoate and 4.06 g (0.0483 mole) of sodium bicarbonate in 600 ml of ethanol is evaporated to dryness. The 5 reaction mixture is stirred under reduced pressure at 100°C for 15 minutes.

The mixture is then evaporated 3 times with 500 ml of ethanol each time. The residue is taken up in 300 ml of CH2ci2 and 200 ml of water, the reaction 10 mixture is decanted and the organic phase is separated off and dried over MgSO^. It is evaporated to dryness. The residue is purified over a silica column, the mixture being eluted with 2.5 litres of C H 2 C 12 .

The fractions are dried over MgSO^, filtered 15 and evaporated to dryness. The residue is crystallised from 50 ml of ether. The crystals are filtered off, drained and dried in a desiccator in the presence of p2o5.

Melting point = 57-58°C.

Examp le 2. Ethyl 5-(5-ch10ro-2-hydroxy-3-methy I - ' phenyl)-(4-chlorophenyl) methyleneDamino^-pentanoate.

CX1 = 5-Cl, X2 = 4-Cl, x3 = H, n = 4, R = CH3, r' = c2h5: g (0.0533 mole) of (5 - v. h I o ro-2-h y d r oxy-3-25 methy1pheny I)-(4-ch Ioropheny I)-methanone, 2.96 g (0.0547 mole) of sodium methylate and 6.25 g (0.0533 mole) of 5-aminopentanoic acid are introduced into a 1 litre flask. \ 1 208118 400 ml of toluene and 100 ml of methanol are added, the mixture is heated progressively and the azeotrope formed is distilled off, and the mixture is then heated at the reflux temperature of toluene, using a Dean-Stark appara-5 tus, for 6 hours.

The mixture is evaporated to dryness, the residue is triturated in ether and the solid is filtered off. The solid is introduced into water and acidified to pH 4 with citric acid. The solid is filtered off, dissolved 10 in chloroform, dried over magnesium sulphate and evaporated. The compound is recrysta 11ised from a mixture of cyclohexane/benzene. The solid is dissolved again in methylene chloride and the solution is passed over a silica column, elution being carried out with methylene 15 chloride and with a mixture of methylene chloride/ethyl acetate 80/20. After evaporation, a solid is obtained, and is dried.

Melting point = 110-111°C. g (0.0131 mole) Of 5-(5-ch loro-2-hydroxy-3-20 methylphenyl)-(4-chlorophenyl)-methylene3aminojpentanoi c acid, obtained above, are dissolved in 100 ml of tetrahy-drofuran. 3.5 g (0.0215 mole) of carbonyldiimidazole are then added and the reaction mixture is stirred at room temperature for one hour. A further 3.5 g (0.0215 25 mole) of carbonyIdiimidazo I e is added and stirring is continued for one hour. The mixture is evaporated to • dryness and the residue is taken up in 200 ml of ether 208118 and 200 ml of water; the reaction mixture is decanted, the organic phase is separated off and dried over M g S 0 ^ , the MgSO^ is filtered off and the filtrate is evaporated to dryness.

After addition of 30 ml of hexane to the residue, the product crystallises.

After filtration and recrystaLlisation, the crystals are dried.

Melting point = 73-74°C.

ExampIe 3. CyclohexyLmethyL 4-(5-chloro-2-hy- droxy-3-methylphenyl)-(4-chlorophenyl) methylene]aminoj> -butanoate.

CX-, =5-C I, X2=4-Cl, X3=H, n=3, R = CH3, R' = ^ CH_-] 2.5 ml of cyclohexyLmethyL bromide (d=1.27, that 15 is to say 0.018 mole) and 2 drops of triethylamine are added to 5.8 g (0.015 mole) of the sodium salt of 4-£[(5-chloro-2-hydroxy-3-methylphenyl)-(4-chlorophenyl) met h y-leneUaminoj-butanoic acid in 100 ml of anhydrous dimethyl sulphoxide; the reaction mixture is heated at 100°C 20 for 4 hours, while stirring. The dimethyl sulphoxide is then evaporated off in vacuo and the residue is partitioned between 100 ml of ether and 100 ml of water. The mixture is decanted, the ethereal phase is dried over MgSO^ and filtered and the filtrate is evapora-25 ted to dryness. An oil is obtained, which crystallises in 40 ml of pentane. The crystals are filtered off, washed with 10 ml of pentane, drained and dried in a n <>081 18 desiccator, whilst being heated at 40 , in the presence of P2^5 ■ Melting point = 53-54°c. 1 2 3 4 6 7 8 9 11 12 13 14 16 Table 208118 C=N-(CH-) -COOR' £ n X1 X2 X3 R R' n lelting Point (°C) or nD -C1 4-Cl H <*3 3 n2°=l- 5889 -C1 3-CH3 H <*3 <*3 3 m-P»64-65 -C1 4-Cl h n-C3H7 ch3 3 n21D5=l-5820 -C1 h h ^3 3 m-p*=73-74 -CH3 4-Cl H ^3 3 "•P =6 3-64 -C1 4-Cl H <2*5 3 m.p ^52-53 -C1 4-CH3 H (gh3)2-ch-ffl2- ®3 3 n22' 5=1-5669 -C1 4-C2h5 H C w 2"5 ffi3 3 n2*«l-5756 -C1 4-Cl H C,3 3 m-p-=—82—83 -C1 4-Cl h ^3 c2h5 1 »-P«=108-109 -C1 4-Cl H nc4h9 3 m-p >=53-54 -C1 4-CH3 » <*3 ch3 3 n2p=l-5884 -C1 4-Cl H ffl3 ®3 2 "•p-72-73 -C1 4-Cl h n-C3H? C2H5 3 ™>.p -=57-58 -C1 4-Cl h <*3 3 22- 5 Hp =1-6064 -C1 3-CH3 H <*3 C2H5 3 n2p=l•5300 -C1 4-Cl H ch3 C2H5 4 ™-P =73-74 I- ' " -V I i. • , n Table (continuation 1) Compound X1 X2 X3 R R' n Melting point (°C) or 18 -Cl 4-Cl H ®3 CT3 1 ■ • P- =133-134 19 -Cl 4-Cl H <*3 tC^Lj 3 m. p. -=54-56 21 -Cl 5-Cl 4-Cl 4-Cl E H ®3 CH2-CH=CH2 m3 3 4 m. p. =57-58 ■-P- =61-62 22 -CH3 4-Cl H : ®3 ^5 3 m. P. =52-53 23 -Cl 4-Cl H QI3 m3 m. p. =39-40 24 -Cl 5-Cl 4-Cl 4-Cl H H . ^3 m3 C2H5 0^2 2 3 m. P.=55—56 m.p. =53—54 26 -Cl 4-Cl H nC3H7 ffi3 2 m-p.-59_70 27 -Cl 4-Cl H rC^n c2h5 2 m.p. =71-72 28 -Cl 4-Cl H • ^3 nCjHn 3 n21D5=l. 5669 29 -Cl 4-Cl H. <=3 C2H5 »-p- =34-35 -Cl 4-CH3 H (CH3) 2-C-:-C-:2 <7*5 3 n2*=l-5609 31 -Cl 4-C2h5 H C2H5 C2H5 3 n2J=l- 5669 32 33 -Cl 5-Cl 4-Cl 4-Cl H H CT3 <*3 O^O^CH CH2CH2OCH2CH3 3 3 ».P. =74-75 «. p. =35-36 34 -Cl 5-Cl 4-Cl 4-Cl H H ^3 CH2CH2OCH3 al2ai2OC4Hg 3 3 ».p. =34-35 n2J 5=15643 36 -Cl 4-CH3 H ®3 C2H5 3 n.P- -57-58 37 38 -Cl 5-Cl 4-Cl 4-Cl H H <*3 <*3 m2-OOOC2H5 3 3 22 n £=1-5700 n.p. =77-78 39 40 -Cl 5-Cl 4-Cl 4-Cl H <*3 ®3 Eai2)2-°3-2CH3 X) 3 3 »-p- =30-21 n.D. =76-77 ?08118 Table (continuation 2) Compound X1 X2 X3 b r' n Melting point (°C) or nD 41 -Cl 4-CH3 2-CH3 ch3 c2h5 3 n20"5=1-5743 42 -Cl 4-Cl h ch3 ca*l2) 3 "B1" 15575 43 -Cl 4-Cl h ch3 -Cl 3 m-p-85 95-96 44 -Cl 4-CH3 h nC3H? ^3 3 n21' 5=1- 5774 45 -Cl 4-Cl h nC3H? ch3 4 64-65 46 -Cl 4-Cl h nC3H? C2H5 4 n.p.s 41-42 47 -Cl 4-Cl h nc3h? CH3 m.p.ss 40-41 48 -^3 4-ch3 2-CH3 ch3 ch3 3 n23= 1-5710 49 -Cl 4-Cl h nc3h? c2h5 n23= 1-5663 d 50 -Cl 4-Cl h ch3 ra2-0 3 m.p.= 101-102 51 -Cl 4-CH3 2-CH3 ch3 ch3 3 23 = 1-5770 52 -Cl 4-Cl h ch3 ch2-0 3 n.p.= 102-103 53 -Cl 4-Cl h ch3 -CH2C=CH 3 ™.d.= 70-71 54 -CH3 4-nC3H7 H C2H5 CBj 3 n2l= 1-5610 55 -Cl 4-Cl h ch3 i-cjh? 3 n2l= 1-5751 56 -CH3 4-Cl 2-CH3 ch3 ch3 3 n22"5=1-5810 57 -Cl 4-Cl H ch3 -CH ^ ^2*5 3 n2l = 1 -5725 Table (continuation 3) 1 Comp ound X1 *3 R R' n Melting point t°C) or nn 58 -Cl 4-Cl H ^3 (CH^CH^O) 3CH3 3 23 n 3=1-5559 59 -Cl 4-Cl H ffi3 3 m-p«58-59 60 -Cl 4-Cl H <*3 uCHj ®3 7 1 • p <=39—40 61 -Cl 4-Cl H "3 6 "3—38-39 62 -Cl 4-Cl H ®3 OL-CHsC^3 3 n2J=J- 5751 63 -Cl 4-Cl H ffi3 1C4H9 3 n-P.=84-85 64 -Cl 4-Cl H <*3 ®3 8 »-p -=37-38 65 -Cl 4-CL H ch3 GH3 9 "•p-=54-55 66 -Cl 4-Cl H nC^Lj CH2Oi2OC^s 3 n2p=l - 5663 67 -Cl 4-Cl H ^3 a3 m.Pe39_40 68 -Cl 4-Cl H nC3H7 (CH2)2OCH3 4 n*D 5=1- 5654 69 -Cl 4-Cl H nC3H? (CH^20-C2H5 4 24 5 n p' =1. 5620 70 -Cl 4-Cl H nCjB, CH2-CH=CH2 4 -36 71 -Cl 4-Cl H nCjH, (CH2)2OC2H5 n2®'5=l-5554 72 -Cl 4-CH3 H nCjB, <*3 4 73-74 73 -Cl 4-Cl H nC3H? (CH2)2OCH3 n2p 5=1-5634 74 -Cl 4-CH3 H nC3H7 C2H5 4 62-63 \ 8 \ 18 Table (continuation O Compound *1 *2 x3 r r' n Melting point (°C) or nQ 75 -Cl 4-Cl h nC3H? iC^ 4 55-56 76 -Cl 4-CH3 h C2H5 3 n^4=l-5635 77 -Cl 4-Cl h ®3 (CH2)2OC2H5 n^°=l- 5558 78 -Cl 4-Cl h <*3 ch(ch3)ch2och3 3 55-56 79 -Cl 4-CH3 h nc3h7 ®3 31-32 80 -Cl 4-Cl h ch3 (CH2)2OC2H5 4 n£6=l. 5600 81 -Cl 4-Cl h CH3 (CH2)3OC2H5 3 n^8=l-5650 82 -Cl 4-Cl h <*3 (CH2)2CH(OCH3)-CH3 3 n^8=l•5653 83 -Cl 4-CH3 h nC3H? (ch2)2oc2h5 4 n^3=l•5042 84 -Cl 4-Cl h CT3 CH2COCH3 3 78-2 85 -Cl 4-ch3 h ra3 <*3 4 70-71 86 -Cl 4-CH3 h <*3 ^3 . . 40-41 87 -Cl 4-C2h5 h c2«5 <*3 n^3=l.5693 88 -Cl 4"C2H5 h C2H5 <*3 4 23 n£ =1.5722 89 -Cl 4-Cl h C2H5 m3 4 70-71 90 -Cl 4-Cl h C2H5 ffi3 n^XL.5799 2'CffrV The compounds according to the invention have been subjected to pharmacological tests demonstrating their activity on the central nervous system.

The acute toxicity was determined on mice by oral administration. The LDjq (50% lethal dose) which causes the death of 50% of the animals is greater than 1,000 mg/kg.

The anticonvulsive activity of the compounds was demonstrated by antagonism of the mortality induced by bicuculline in mice.

Bicuculline is a relatively selective blocker of post-synaptic GABA-ergic receptors and its convulsive and lethal effects are antagonised by compounds which increase the level of cerebral GABA or have a GABA-mimetic activity.

The 50% active dose (ADjg), that is to say the dose which protects 50% of the animals from the effect of bicuculline, of the substances studied was evaluated.

The AD50 on oral administration of the compounds according to the invention varies from 10 to 200 mg/kg.

The compounds according to the invention are active as anticonvulsants and also have antidepressive, anxiolytic, analgesic, antiinflammatory, antiulcerous and antidyskinetic properties. They can be used in human and veterinary therapy, inter alia for the treatment of various diseases of the central nervous system, for example for the treatment of depression, psychoses and certain 2081 18 neurological diseases, such as epilepsy, spasticity and dyskinesia.

The invention accordingly relates to all pharmaceutical compositions containing the compounds (I) as a c-5 tive principles, together with any excipients suitable for their administration, in particular oral (tablets, coated tablets, gelatin capsules, capsules, cachets and solutions or suspensions for oral use) or parenteral administration.

The daily posology may be from 100 to 4,000 mg. ,/ ?' •• ■ ■ 2081X8 17

Claims (9)

WHAT WE CLAIM IS:

1. A diphenylazomethine containing an esterified chain and corresponding to the formula (I) in which XX2 and X3, which may be the same or different, each represent a hydrogen or halogen atom or a (C1_g) alkyl group, R represents a straight-chain or branched (C1_g) alkyl group, n represents an integer from 1 to 10 and R' represents a straight-chain or branched (Cj.g) alkyl group, a (C3_g) cycloalkyl—(C1-4) alkyl group, a cycloalkyl group, a (C2_6) alkenyl group, a (C3_6) alkynyl group, a

2. A compound according to claim 1, wherein X^, X2 and X^, which may be the same or different, each represent a hydrogen atom, a chlorine atom or a methyl, ethyl or propyl group, n represents 3, 4 or 5, R represents a methyl, ethyl, n-propyl or isobutyl group and R1 represents a straight-chain or branched (C^_g) alkyl group or a cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl, allyl, hydroxyethyl, {C^_4) alkoxy-ethyl, ethoxycarbonylmethyl, tetrahydrofuryl-methyl, (methoxy-2-ethoxy)-2-ethyl, [ (methoxy-2-ethoxy)-2-ethoxy]-2-ethyl, cyclohexyl, cyclopentyl, benzyl, propargyl, methoxy-benzyl or iso-penten-2-yl group.

3. A compound according to claim 2, in which X^, X2 and which may be the same or different, each represent a hydrogen atom, a chlorine atom or a methyl group, n is 3, 4 or 5, R represents a methyl, ethyl or n-propyl group and R' represents a methyl, ethyl, propyl, allyl or ethoxyethyl group.

4. A compound according to claim 3, corresponding to the formula R A J -V I o 08^ 18 - 19 - in which the various symbols are as defined in claim 3.

5. A compound according to claim 4, in which is a chlorine atom, X2 is a chlorine atom or a methyl group, X^ is a hydrogen atom, and n, R and R' are as defined in claim 3.

6. A diphenylazomethine according to claim 1 substantially as described with reference to any one of Examples 1 to 90 in the Table.

7. A process for the preparation of a diphenylazomethine as claimed in any one of claims 1 to 6, wherein (i) a benzophenone of the formula (II) R (II) 'W is reacted with the hydrochloride of an ester of anO-amino- alkanoic acid of the formula (III) H2N-(CH2)n-C00R',HC1 (III); or (ii) an acid of the formula (IV) R =N-(CH,) -C00H 4 n (IV) 20^\ IS 20 is reacted with an alcohol R'OH (V) in the presence of carbonyldiimidazole; or (iii) an alkali metal salt of an acid (VI) in which M represents an alkali metal is reacted with a compound R'Y (VII ), in which Y represents a halogen atom or a labile group, the symbols X^, *3 > n' R an<* Rl being as defined in any one of claims 1 to 5.

8. A process according to claim 7 substantially as described with reference to Example 1, 2 or 3.

9. A pharmaceutical composition which comprises as active ingredient at least one compound as claimed in any one of claims 1 to 6, together with a pharmaceutical^ acceptable excipient. r (vi) Jl/JjJULuiLsrYl^)