SUBSTITUTED 1-(ALKOXY-IMINOALKYL)IMIDAZOLE DERIVATIVES

Abstract: 1-(Alkoxy-iminoalkyl)imidazole derivatives of formula (I), wherein R is hydrogen or C1-C4 alkyl; A is C1-C4 alkylene optionally substituted by phenyl optionally substituted by halogen or trifluoromethyl; R is (a) hydrogen or a C1-C10 hydrocarbon radical; (b) an aryl or aryl-C1-C4 alkyl group wherein the said aryl is optionally substituted either by halogen, trihalo-methyl, C1-C4 alkyl, C2-C3 alkenyl, C2-C6 alkynyl, C1-C4 alkoxy, C1-C4 alkylthio or C1-C4 alkylsulfonyl or by C5-C8 alkyl, C4-C8 alkenyl, C5-C8 alkoxy, C5-C8 alkylthio or phenyl optionally substituted by halogen, trihalomethyl or C1-C4 alkyl; or (c) a C5-C8 cycloalkyl or C5-C8 cycloalkyl-C1-C4 alkyl group, wherein the said cycloalkyl is optionally substituted by C1-C4 alkyl; T is a C1-C6 hydrocarbon chain or phenylene; X is a bond, -O-CH2-, -C(R' R'')-, Si(R' R'')-, vinylene or isopropenylene, each R' and R'' being hydrogen, fluorine or C1-C4 alkyl; and R2 is -OR3 or -N(R3R4), each R3 and R4 being hydrogen, C1-C6 alkyl, phenyl or benzyl; and the pharmaceutically acceptable salts thereof; are useful in the treatment of a disease state related to enhancement of thromboxane A2 (TxA2) synthesis.

Description: SUBSTITUTED l-(ALKOXY-IMINOALKYL)I IDAZOLE DERIVATIVES The present invention relates to new l-(alkoxy-iminoalkyl) imidazole derivatives, to a process for their preparation, to pharmaceutical compositions containing them and to their use as therapeutic agents. The present invention provides novel compounds having the general formula (I) wherein R is hydrogen or C -C alkyl; A is a C -C alkylene chain unsubstituted or substituted by a phenyl ring unsubstituted or substituted by one or two substituents chosen independently from halogen and trifluoro methyl; R 1 is a) hydrogen or a straight or branched, saturated or un- saturated C -C hydrocarbon radical; b) an aryl or aryl- C -C alkyl group, wherein the aryl group or the aryl moi¬ ety is unsubstituted or substituted either by one to four substituents independently chosen from halogen, trihalo- methyl, C.-C. alkyl, C -C_ alkenyl, C -C alkynyl, C -C 1 4 d > <_ b 1 4 alkoxy, C -C alkylthio and C -C alkylsulfonyl or by a substituent chosen from C -C alkyl, C 4~ C R a l ken yl • C 5~ C 8 alkoχ y' c 5 ~c 8 alk y lthio an <3 phenyl, in which TE SHEET the phenyl ring is unsubstituted or substituted by a substituent chosen from halogen, trihalomethyl and C -C alkyl; or (c) a C 5 -C 8 cycloalkyl or C 5 -C 8 cyclo- alkyl-C -C alkyl group, wherein the cycloalkyl group or moiety is unsubstituted or substituted by one to three C -C alkyl groups; T is a straight or branched, saturated or unsaturated C 1 -C 8 hydrocarbon chain, or a phenylene radical; X is a bond or a divalent group consisting of -0-CH -, -C(R' R")-, -Si(R' R")-, vinylene or isopropenylene.wherein each of R 1 and R" being the same or different is hydrogen, fluorine or C -C alkyl; R ^ is an -0R_ or -N(R_R.) group, wherein each of R and R independently is hydrogen, alkyl, phenyl or benzyl; and the pharmaceutically acceptable salts thereof. The invention also includes within its scope all the possible isomers, stereoisomers and their mixtures and the metabolites and the metabolic precursors or bioprecursors of the compound of formula (I). in particular the compounds of formula (I) exhibit either E o Z isomerism about the oximic double bond. Both the single E and Z isomers of the compounds of formula (I) and their mixtu are also included within the scope of the present invention. The alkylene chain A may be, independently, a straight or bra ed chain, unsubstituted or substituted, as defined above. Typically -CH 2 -, -CH 2 -CH 2 -,-CH^CH^CH^ ^CH-CH ,. , ~CH-CH -Ph,-CH -CH(Ph)-,^CH-CH -CH -Ph, ^CH-CH(CH.)-CH.Ph, . d. ά ^ 3 2 CH 2 -CH(CH 2 Ph)- and -CH-CH 2 -CH(CH 3 )-Ph, wherein Ph represents phenyl ring as defined above. ITUTE SHEET When R is a C -C hydrocarbon radical as defined above unde a), it is preferably a C -C alkyl or C -C alkenyl radical, 1 8 2 9 for example C -C alkenyl, in particular pentyl , hexyl and 2 8 heptyl or propenyl and butenyl , respectively. When R_ , and/or R„ is a C -C_ alkyl group it is, e.g., methyl, 3 4 l b ethyl, propyl, isopropyl, butyl or tert.butyl, more preferabl methyl or ethyl. When R is an aryl or arylalkyl group as defined abυv<_ under b), the aryl group or the aryl moiety may be an aromatic or heteroaromatic group, for example phenyl, pyridyl, thienyl an naphthyl, in particular phenyl, pyridyl and thienyl. According to the definition of R as an aryl or arylalkyl group given hereabove, a pyridyl group is preferably a 2- or 3-pyridyl group; a thienyl group is preferably a 2-thienyl group and a naphthyl group is preferably a 1- or 2-naphthyl group. Accordingly, an arylalkyl group, as defined above, is prefer¬ ably a phenyl-, thienyl- or pyridyl-C -C alkyl group, in particular a benzyl, thienylmethyl or pyridylmethyl group. When R is a cycloalkyl or cycloalkyl-alkyl group as defined above under c), the cycloalkyl group or the cycloalkyl moiety is preferably a cyclohexyl or cycloheptyl group. Accordingly, a cycloalkyl-alkyl group, as defined above, is preferably a cyclohexyl- or cycloheptyl-C -C alkyl group, in particular cyclohexylmethyl or cycloheptylmethyl . When T is a hydrocarbon chain it is preferably an alkylene or alkenylene,radical , for example a C -C alkylene chain, in parti¬ cular -CH 2 -, -CH 2 -CH 2 - or -CH_.-CH_.-CH_-, -CH_-CH.-CH_ . -CH- or a C -C alkenylene chain, in particular -CH=CH-, -CH -CH=CH- or -CH=CH-CH 2 -. When T is a phenylene radical, it is e.g. a 1,2-, 1,3- or 1, 4-phenylene , in particular a 1, 3-phenylene radical. The alkyl, alkoxy, alkylsulfonyl and alkylthio groups may be brancned or straight chain groups. A C -C alkyl group is e.g. methyl, ethyl, propyl ,isopropyl , butyl or tert.butyl, more preferably methyl or butyl. A C -C alkoxy group is e.g. methoxy, ethoxy, propoxy, iso- propoxy, butoxy or tert.butoxy, preferably methoxy, ethoxy or propoxy. A C -C alkylthio group is e.g. methylthio, ethylthio, propylthio or butylthio, in particular methylthio or ethyl¬ thio. A C -C alkyl group is preferably hexyl or heptyl. 5 8 A C __-C alkenyl group is preferably ethenyl. A C -C alkenyl group is preferably butenyl or hexenyl. A C -C_ alkynyl group is preferably a C.-C. alkynyl group in 2 b 2 4 particular ethynyl. A C -C alkoxy group is preferably pentyloxy or hexyloxy. 5 8 A C -C. alkylthio group is preferably pentylthio or hexylthio. b 8 A halogen atom is suitably bromine, chlorine or fluorine, preferably it is bromine or fluorine. A C -C alkylsulfonyl group is preferably a methyl- or ethyl- sulfonyl, in particular methylsulfonyl, group. A trihalomethyl group is e.g. trichloromethyl or trifluoro- methyl, in particular trifluoromethyl. Pharmaceutically acceptable salts- of the compounds of the invention include acid addition salts, with inorganic, e.g. nitric, hydrochloric, hydrobromic, sulphuric, perchloric and phosphoric acids, an organic, e.g. acetic, propionic, glycolic, lactic, oxalic, malonic, malic, maleic, tartaric, citric, benzoic, cinnamic, mandelic and salicylic acids, and salts with inorganic, e.g. alkali metal, especially sodium or potassium, bases or alkaline-earth metal, especially calcium or magnesium, bases, or with organic bases, e.g. alkylamines, preferably triethyl-amine. As stated above the present invention also includes within its scope pharmaceutically acceptable bio-precursors (other¬ wise known as pro-drugs) of the compounds of formula (I), i.e. compounds which have a different formula to formula (I) above but which nevertheless upon administration to a human being are converted directly or indirectly in vivo into a compound of formula (I) . Preferred compounds of the invention are the compounds of formu (I) , wherein, R is hydrogen or methyl; A is a C -C alkylene chain optionally substituted by phenyl, in its turn optionally substituted by one or two substituents independently chosen from halogen and trifluoromethyl; R is a) C -C alkyl or C -C alkenyl; b) a phenyl, naphthyl, 1 1 O — o thienyl or pyridyl group unsubstituted or substituted either by one or two substituents independently chosen from halogen, trihalomethyl, C -C alkyl, C -C alkoxv, C -C alkylsulfonyl and C1-C4. alkylthio, or by a substituent chosen from C5-C8_. alkyl, C -C_ alkenyl, C -C. alkoxy, C -C_ alkylthio and phenyl, 4 8 5 8 5 8 in which the phenyl ring is unsubstituted r> r substituted by a substituent chosen from halogen, trihalomethyl and C 1 ~ C alkyl; or (c) a cyclohexyl or cycloheptyl group unsubstituted or substituted by one or two C 1-C4. alkyl groups; T is a C 1-C_5 alkylene or C2-C5 alkenylene group ; or a phenylene group; X is a bond or a -0-CH - group; R is an -OR or -NHR group, wherein R is hydrogen or C -C alkyl; and the pharmaceutically acceptable salts thereof. More preferred compounds of the invention are the compounds of formula (I), wherein, - -— * R is hydrogen; A is -CH -, -CH(CH )-, -CH -CH - or -CH(CH Ph)- in which Ph means phenyl optionally substituted by a halogen atom; R is a) C -C alkyl; b) a phenyl, pyridyl or thienyl ring, unsubstituted or substituted by halogen, C -C alkyl, C -C alkoxy or trifluoromethyl; or c) a cyclohexyl or cycloheptyl ring; T is a C -C alkylene or phenylene group; X is a bond or a -0-CH - group; R is an -OR group wherein R is hydrogen or C -C alkyl; c. 1 and the pharmaceutically acceptable salts thereof. Examples of specific compounds according to the present invention are the following compounds, either as Z or E-isomers or Z, E-mixtures of said isomers; SUBSTITUTE SHEET 1) 5-[l-phenyl-2-(imidazol-l-yl)ethylidene]aminoxypent- anoic acid; 2) 5-[l-phenyl-2-{imidazol-l-yl)ethylidene]aminoxype- ntanamide; 5 3) ethyl 4-Cl-phenyl-2-(imidazol-l-yl)ethylidenej aminoxybutanoate; 4) 4-[1-phenyl-2-(imidazol-l-yl)ethylideneJaminoxybu- tanoic acid; 5) methyl 3-[l-phenyl-2-(imidazol-l-yl)ethylideneJami- 10 noxypropanoate; 6) ethyl 5-[l-(3-trifluoromethylphenyl)-2-(imidazol -1-yl)ethylidene]aminoxypentanoate; 7) 5-t1-(3-trifluoromethylphenyl)-2-(imidazol-l-yl)e- thylidene]aminoxypentanoic acid; 1.5 8) 5-[l-(3-bromophenyl)-2-(imidazol-l-yl)ethylidene] aminoxypentanoic acid; 9) 4-[1-(3-trifluoromethylphenyl)-2-(imidazol-l-yl)e- thylidene]aminoxybutanoic acid; 10) 5-[l-(3-(n-butyl)phenyl)-2-(imidazol-l-yl)ethyl- 20 ider«]aninoxypentanoic acid; 11) 5-t1-(2-m3thoxyphenyl)-2-(imidazol-l-yl)ethylidene] aminoxypentanoic acid; 12) ethyl 3-oxa-5-[l-phenyl-2-(imidazol-l-yl)ethylidene] aminoxypentanoate; 25 13) 3-oxa-5-[l-ρhenyl-2-(imidazol-l-yl)ethylidene]ami- noxypentanoic acid; 14) 3-oxa-5-[1-(3-trifluoromethylphenyl)-2-(imidazol- l-yl)ethylidene]aminoxypentanoic acid; 15) tert-butyl 5- [l-phenyl-2-(imidazol-l-yl)-2-methyl- 30 ethylidene]aminoxypentanoate; SUBSTITUTE SHEET 16) 5-tl-phenyl-2-(imidazol-l-yl)-2-methylethylidene]- aminoxypentanoic acid; 17) 3-[l-phenyl-2-(imidazol-l-yl)ethylidene " ] aminoxymethylbenzoic acid; 18 ) 4-[l-phenyl-3-(imidazol-l-yl)propylidene]aminoxy- butanoic acid; 19) 5-t1-(n-hexyl)-2-(imidazol-l-yl)ethylidene]aminoxy¬ pentanoic acid; 20) ethyl 5-[l-cyclohexyl-2-(imidazol-l-yl)ethylidene] aminoxypentanoate; 21) tert-butyl 5-[l-cyclohexyl-2-(imidazol-l-yl)ethyli¬ dene]aminoxypentanoate; 22) 5-[1-cyclohexyl-2-(imidazol-l-yl)ethylidene]amino¬ xypentanoic acid; 23) ethyl 4-tl-cyclohexyl-2-(imidazol-l-yl)ethylidene] aminoxybutanoate; 24) 4-[1-cyclohexyl-2-(imidazol-l-yl)ethylidene] aminoxybutanoic acid; 25) 5-[l-cyclohexyl-2-(imidazol-l-yl)ethylidene] aminoxypentanamide; 26) 3-oxa-5-[1-cyclohexyl-2-(imidazol-l-yl)ethylidene] aminoxypentanoic acid; 27) 5-[l-(3,3-dimethylcyclohexyl)-2-(iιnidazol-l-yl) ethylidene] aminoxypentanoic acid; 28) 5-[l-cyclopentyl-2-(imidazol-l-yl)ethylidene] aminoxypentanoic acid; 29) 5-[l-(2-thienyl)-2-{imidazol-l-yl)ethylidene] aminoxypentanoic acid; 30) ethyl 5-[l-(3-pyridyl)-2-(imidazol-l-yl) ethylidene] aminoxypentanoate; 31) 5-[l-(3-pγridyl)-2-(imidazol-l-γl)ethylidene3 aminoxypentanoic acid; 32) 4-[1-(3-ρyridyl)-2-(iraidazol-1-yl)ethylidene] aminoxybutanoic acid; SUBSTITUTE SHEET 33) 5- _l-(3-n-butyloxyphenyl)-2-( imidazol-l-yl )ethylidene.1 aminoxypentanoic acid; 34) ethyl 5- [l-(3-n-butyloxyphenyl )-2-(imidazol-l-yl) ethylidene]aminoxypentanoate; 5 35) 6-[l-cyclohexyl-2-(imidazol-l-yl)ethylideneJaminoxyhexan acid; 36) 3-oxa-6- Cl-cyclohexyl-2-( imidazol-l-yl)ethylidenej aminoxyhexanoic acid; 37) 5-Cl-cycloheptyl-2-(imidazol-l-yl )ethylidenelaminoxy- ^ pen anoic acid; 38) 6- Hl-cycloheptyl-2-(imidazol-l-yl)ethylidene_aminoxyhexa acid; 39) 5- tl-n-hep y1-2-(imidazol-l-yl)ethylidene.aminoxypentano acid; -> 40) 5- [l-phenyl-2-(imidazol-l-yl )-2-benzylelhylidene_. aminoxypentanoic acid; 41) 5- 1.1-cyclohexyl-2-(imidazol-l-yl )-2-benzyle hylideneJ aminoxypentanoic acid; 42) ethyl 5-{j.-phenyl-2-imidazol-l-yl )-2-benzylethylideneJ ^ aminoxypentanoate; 43) ethyl 5- (_l-cyclohexyl-2-(imidazol-l-yl )-2-benzyl- ethylidenejaminoxypentanoate ; 44) 6- [l-phenyl-2-(imidazol-l-yl)-2-benzylethylidene] aminoxyhexanoic acid; 5 45) 6- [l-cyclohexyl-2-(imidazol-l-yl )-2-benzylethylidene] aminoxyhexanoic acid; SUBSTITUTE SHEE" 46) 5- l-(4-fluorophenyl)-2-(imidazol-l-yl)-2-(4-fluorobenzyl ethylidenej aminoxypentanoic acid; 47) 5-fl-cyclohexy1-2-(imidazol-l-yl)-2-(4-fluorobenzyl) ethylidene]aminoxypentanoic acid; and 48) 3-oxa-5-(_l-phenyl-2-(imidazol-l-yl)-2-benzylethylidene aminoxypentanoic acid; and the pharmaceutically acceptable salts thereof. SUBSTITUTE SHEET SUBSTITUTE SHEET SUBSTITUTE - 13 - In the above table Ph means phenyl; Me means methyl; Et means ethyl; and Bu means butyl. The compounds of the invention and the salts thereof can be obtained by a process comprising: a) reacting an oxime of formula (II) or a salt thereof wherein R.AandR. are as defined above, with a compound of for¬ mula (III) Y-CH -T-X-COR (III) wherein T, X and R are as defined above and Y is a leaving group; or b) reacting an oxime of formula (II) as defined above or a salt thereof with a lactone of formula (IV) wherein T and X are as defined above, thus obtaining a compound of formula (I) in which R is -OH; or SUBSTITUTE SHEET c) reacting a compound of formula (V) wherein R,A andR are as defined above, with a compound of formula (VI) H ) 2_N-0-CH2_-T-X-COR_ (VI 2 wherein T, X and R are as defined above; or d) reacting a compound of formula (V), as defined above, with a compound of formula (VII) wherein T, X and R are as defined above and each of Q and Q' is independently hydrogen, lower alkyl or phenyl; or e) reacting a compound of formula (VIII) or a salt thereof / ",~Y * - * C=N-0-CH -T-OH (VIII) >" wherein SUBSTITUTE SHEET R,R A and T are as defined above, with a compound of for¬ mula (IX) Y-CH 2 -C0R (IX) wherein Y and R are as defined above, thus obtaining a compound of formula (I) wherein X is a -0-CH - group; and if desired, converting a compound of formula (I) into another compound of formula (I), and/or, if desired converting a compound of formula (I) into a salt thereof, and/or, if desired, con- verting a salt of a compound of formula (I) into a free com¬ pound, and/or, if desired, separating a mixture of isomers of a compound of formula (I) into the single isomers, and/ or, if desired, altering by isomerization on the oxime double bond the ratio of E- and Z-isomers of a compound of formula (I) in a mixture thereof so as to obtain a differ¬ ent ratio of such isomers, and/or, if desired, converting by isomerization on the oxime double bond a pure E-isomer of a compound of formula (I) either into a pure Z-isomer thereof or into a mixture of E- and Z-isomers thereof; and/ or if desired converting by isomerization on the oxime double bond a pure Z-isomer of a compound of formula (I) either into a pure E-isomer or into a mixture of E- and Z- isomers thereof. SUBSTITUTE A salt of a compound of formula (II) is for example an alkali metal salt, in particular a sodium or lithium salt. A salt of a compound of formula (II) may be obtained according to known methods, for example a compound of formula (II) can be reacted with an alkali metal hydride, preferably NaH, in an inert organic solvent, e.g. dimethylformamide. The leaving group Y in a compound of formula (III) is for example an halo group, in particular a chloro or bromo group, or a residue of an active ester group, in particular mesyl or tosyl. The reaction of a compound of formula (II) , or a salt thereof, with a compound of formula (III) can be carried out according to known methods, for example in the presence of an inert reaction organic solvent e.g. dimethylformamide, dimethylsulfoxide, tert. butanol or benzene, and by addition of an appropriate basic agent e.g. an alkali metal carbonate, in particular sodium carbonate, or sodium hydride or potassium tert. butylate, at a temperature ranging from about 0 β C to reflux temperature. SUBSTITUTE SHEET The reaction of a compound of formula (II) or a salt thereof, as defined above, with acompound offormula (IV) may be performed according to known methods. For example such reaction can be carried out by following the same reaction conditions described as to the reaction of a compound of formula (II), or a salt thereof, with a compound of formula (III). The reaction of a carbonyl compound of formula (V) with an aminooxi derivative of formula (VI) can be carried out for example, by dissolving the carbonyl compound in a reaction inert solvent e.g. water, a lower alkanol in particular ethanol, dioxane, tetrahydrofuran, an aromatic hydrocarbon in particular benzene, toluene or xylene, or mixtures of such solvents, and by adding an appropriate basic agent, for example an alkali metal hydroxide in particular sodium or potassium hydroxide, a carbonate or hydrogen carbonate in particular the sodium and potassium ones, or an organic basic agent e.g. a tertiary amine or pyridine. When one or both of Q and Q' in a compound of formula (VII) is lower alkyl, it is for example C--C. alkyl in particular methyl or ethyl. Also the reaction of a compound of formula (V) with a compound of formula (VII) can be carried out according to known methods. For example such reaction can be performed in an inert reaction solvent e.g. acetonitrile or acetic acid, and if required in the presence of a mineral acid e.g. sulphuric or SUBSTITUTE H hydrochloric acid, at temperatures ranging from room temperature to reflux temperature. A salt of a compound of formula (VIII) is for example an alkali metal salt, in particular a sodium or lithium salt. The leaving group Y in a compound of formula (IX) is for example a halo group, in particular a chloro or bromo group, or a residue of an active ester group, in particular mesyl or tosyl. The reaction of a compound of formula (VIII), or a sale thereof, witn a compound of formula lIX) can be carried out by following the same reaction conditions described above as to the reaction of a compound of formula (II), or a salt thereof, with a compound of formula (ITT^. The conversion of a compound of formula (I) into another compound of formula (I) can be carried out by methods known in themselves. For example, a compound of formula (I) containing an esterified carboxy group can be converted into the corresponding free carboxylic acid by known methods. In particular a compound of formula (I) in which R, is an OR 3 group wherein R 3 , being as defined above, is other than hydrogen can be converted by acidic or alkaline hydrolysis into the respective free carboxylic acid. The reaction is preferably carried out at temperatures ranging from about -5°C to about 50°C. A compound of formula (I) containing a free carboxy group, such as a compound of formula (I) in which R 2 is hydroxy, can be converted into a corresponding esterified carboxy derivative, e.g. a compound of formula (I) in which R 2 is an -OR 3 group, wherein R 3 , being as defined above, is other than hydrogen. Such esterification reaction can be carried out according to known methods, preferably via an intermediate reactive derivative of the carboxylic acid, which may be isolated or not, by reaction with the appropriate alcohol of formula R_0H, in which R being as defined above is other than hydrogen. The reaction can be carried out in customary solvent e.g. benzene or toluene, or in the presence of an excess of the alcohol itself of formula R 3 0H. The temperature reaction may range from about 10 β C to about 50 β C. Intermediate reactive derivatives of the carboxylic acid may be for example acidic halides, e.g. the chloride, mixed anhydrides e.g. ethoxycarbonyl or tert. butyloxy anhydrides, or a suitable reactive intermediate obtained in situ e.g. by reaction with a diimide e.g., dicyclohexylcarbodiimide, or carbonyl diimidazole. A compound of formula (I) wherein , is hydroxy, i.e. containing a free carboxy group, can be converted into a corresponding compound of formula (I) wherein R- is a -NR 3 R. group, in which R 3 and R. are as defined above, according to known methods; preferably via an inter¬ mediate reactive derivative thereof, which can be isolate or not. Intermediate reactive derivatives may be active esters e.g. NO--phenyl esters, or N-hydroxysuccinimide esters, acid halides, preferably chloride, mixed anhydrides e.g. ethoxycarbonyl or tert-butylcarbonyl anhydrides, or the reactive intermediates obtained in situ by reaction of the acid with dicyclohexylcarbodiimide or carbonyldiimidazole. For example, a reactive intermediate as defined above, which can be obtained following conventional WSQTS, as those usually employed in the synthesis of peptides, is reacted with aπnonia or an appropriate anine in a customary solvent or with an excess of the a ine itself t temperatures ranging from about -10 β C to about 50 β C. The optional salification of a compound of formula (I) as well as the conversion of a salt into the free compound and the separation of a mixture of isomers into the single isomers may be carried out by conventional methods. SUBSTITUTE For example the separation of a mixture of geometric isomers, e.g. Z- nd E-isomers, may be carried out by fractional crystallization from a suitable solvent or by chromatography, either column chromatography or high pressure liquid chromatography. The optional isomerization on the oxime double bond in a compound of formula (I), which is an equilibrium reaction, can be performed according to known methods; preferably in the presence of a mineral acid e . g. hydrochloric acid and/or by heating. The oxi es of formula (II) can be obtained according to know methods. For example a*) by reaction of a compound of formula (V), as defined above, with hydroxylamine or an acid addition salt thereof, e.g. the sodium or potas- slum salt, or b') by reaction of an oxime of formula (X) ,C-N-0H (X) "l wherein Y, A and R 1 are as defined above, with imidazole, C -C 4 alkyl imidazole or a salt thereo f , e.g. following for example the procedure in Arzneim.Forsch./D Res. , J29(II) , 1510-13, (1979). In view of the oxime double bond, also an oxime of formula (II) may be obtained either as pure Z or E isomer or as a mixture thereof. Also an oxime of formula (II), if desired, can be submitted to the same iso erizations on the oxime double bond described above as to a compound of formula (I) , according to known methods. Similarly, a mixture of Z and E isomers of an oxime of formula (II) can be separated into the single isomers by following customary methods. The compounds of formula (III), (IV) and (V) are either known compounds or can be obtained by known methods from known compounds. Also the compounds of formula(VI) are either known compounds or can be obtained from known compounds by following known methods, e.g. those described in Tetrahedron (1967), 22, 4441, or in general described in Organic Functional Group Preparation, by S.R.Sandier and W.Karo, Vol. Ill, chapter X, Academic Press, (1972). The compounds of formula (VII) can be obtained by reaction of a known compound of formula (XI) ^ C=0 (XI) Q wherein Q and Q' are as defined above, with a compound of formula (VI) as defined above, by following the same reaction procedures described above under process c). Alternatively a compound of formula (VII) can be obtained from a compound of formula (XI), via the corresponding oxime of formula (XII) ^TC=N-0H (XII) wherein Q and Q' are as defined above, by reaction either with a compound either of formula (III) or of formula (IV) by following the same reaction conditions described above under processes a) and b) . The compounds of formula (VIII) can be obtained from known compounds by following procedures similar to those described under processes a),b),c) and ) above. When in the compounds of the invention and in the intermediate products thereof groups are present which need to be protected during the reactions reported above, the groups can be protected in conventional way before the reaction takes place and then deprotected after its end, according to well known methods. PHARMACOLOGY We have found that the compounds of formula (I), and the pharmaceutically acceptable salts thereof are selective inhibitors of thromboxane A (TxA ) synthesis and are therefore useful in the treatment of diseases related in particular to an enhancement of TxA synthesis in mam¬ mals, including humans. The compounds of formula (I) were for example tested for their ability to inhibit TxA Synthase activity (as re ¬ flected by TxB generated in whole blood during clotting or in isolated glomeruli) in vitro in the rat. BSTITUTE SHEET The in vitro experiments were carried out as follows: The effect of the compounds on TxA synthesis was evaluat¬ ed in serum and in glomeruli isolated from kidney cortex of reduced renal mass rats (RRM). Ablation of > 70 % of re- nal mass in the rat results in hypertension, proteinuria and glomerular sclerosis of the remnant kidney. Rats with a remnant kidney have increased excretion of thromboxane in the urine when compared with normal rats (Purkerson et al. , Proc. Natl. Acad. Sci. USA 8_2, 193, 1985). Blood was withdrawn from the abdominal aorta of the animals under light ether anesthesia. The blood was immediately di¬ vided in portions of 0.5 ml and distributed in glass tubes each containing a concentration of the test compounds or of the reference compounds, i.e. Dazoxiben, which is thrombox- ane synthase inhibitor (Randall et al. - Thromb. Res. 23, 145, 1981) and Acetylsalicylic acid (ASA), which is cyclo- oxygenase inhibitor. Samples were then allowed to clot for 1 h at 37°C, centrifuged at 3000 rpm for 10 min, serum collected and stored at -20 β C until assayed. TxB 2 levels were determined by RIA according to previously described procedures [Patrono et al. -Thromb.Res♦17,3/4, 317,1980] using highly specific antibody. The isolation of glomeruli was performed as previously described [Patrignani et al. , -J.Pharm.Exp.Ther.228, 2,472,1984]. SUBSTITUTE SHEET The isolated glomeruli of 4 rats were pooled, suspended in modified Krebs buffer (pH 7.3) and divided into portions of 1 ml each containing a concentration of rhe test compounds or of the reference compounds. The T A, synthesis was induced by incubating the glomeruli under shaking at 37 β C &r 1 h. At that time the incubation was stopped by centrifugation at +4 β C, the supernatant collected and stored at -20 β C until assayed by RIA. The compounds of the invention showed remarkable activity in the above tests. In particular for example, the compounds of the invention (Z)-5-[l-cyclohexyl~2-(imidazol-l-yl)-ethylidene]amino- xypentanoic acid (internal code FCE 26398),(+) (Z)- -5-[l-phenyl-2-(imidazol-l-yl)-2-benzylethylidene]aminox pentanoic acid (FCE 27108) and (+) (E)-5-Cl-phenyl-2- -(imidazol-l-yl)-2-benzylethylidene_aminoxypentanoic aci (FCE 27109),were found to exhibit a marked inhibitory activity on TxA synthesis significantly more potent tha that of reference compounds Dazoxiben and ASA. These results are summarized in Table 1. SUBSTITUTE SHEET Table 1 - In vitro effects on TxB_ production in whole blood and glomeruli of RRM rats. [Data are expressed as IC (M) and limits for p=0.95]. 50 Wherein n is the number of replications. The compounds of the invention, being able to inhibit selectively the formation of TxA , can be- used as vase- dilatory and antiaggregant agents, for example in all the cases of thrombosis, peripheral vasculopathies and coronary artery disease. In fact inhibition of TxA production reduces the probaoility of thrombi formation and of vasoconstriction with consequent ischemic events and leaving unaltered (or increasing) PGI„ production, improves vasodilation, tissue blood supplies and protects the vessel wall . Moreover the compounds of the invention were tested for TxA antagonism in a binding assay in washed human platelets, using as radiolabelled ligand /_^H/-S 29,548. The experiments were carried out as follows: Blood from healthy volunteers of both sexes who had no taken any medication for at least 10 days is collected into one-tenth volume of acid citrate dextrose containing indomethacin (28 ι ) . Platelet rich plasma (PRP), obtained by centrifugation of the blood at 200xg for 20 min, is washed twice (lOOOxg for 10 min). The platelets are then resuspended in Tyrode-Hepes buffer (pH 7«4) to a final g concentration of 5-10x10 " cells/ml and incubated for 0-60 min at 25° with / H7-S_ ) 29,548 (5 nM) . For displacement experiments various concentrations (10-9-10~4M) of competing ligands were added and incubated for 30 min at 25°C. SUBSTITUTESHEET Non-specific binding was determined in the presence of 50 ,uM U46619 and was approximately 5% of total binding of JH/-S 29,548. After the incubation, 4 ml of ice-cold TRIS-HCL buffer (10 mM, pH 7 -4) was added to each tube and the reaction mixture was immediately filtered by suction through a Whatman GF/C glass filter disc which was washed 2 times with ice-cold TRIS-HC1 (4 ml) and counted for radioactivity by a Packard-β- counter. The binding data were analysed by computerized non-linear curve fitting using the Ligand program and expressed as IC _ In Table II, as an example, the result obtained with the compound of the invention (+_) (E)-5- i /l-phenyl-2-imidazol-l-yl)- 2-benzylethylidene/aminoxypentanoic acid (code number FCE 27109) in the binding test is compared to that obtained with the reference standard compound Sulotroban (BM 13177) /DE-A-2,809,372/- This result shows that the compound of the invention FCE 27109 besides being active as TxA synthase inhibitor, has also a good affinity for the receptor better than that showed by the known compound Sulotroban (BM 13177), which on the other hand is devoid of TxA synthase inhibitory activity. SUBSTITUTE SHEET Table II - H SQ 29,548 binding displacement (washed human platelets) .IC ^ (M) . -6 BM 13177 7-3 x 10 -7 FCE 27109 1.9 x 10 Being the compounds of the present invention both TxA synthase inhibitors and PGA (TxA )antagonists in the platelets on the basis of the state of the art, as reported e.g. in J. Clin. Invest. _8θ_, 1435 (1987) and in Adm. Prostaglandins, Tromboxanes, Leukotrienes Res. Vol. jL_7_ (1987) p. 49, these compounds result particularly suitable for the treatment of a disease state in which an enhancement of TxA synthesis exerts a pathogenic effect, for instance in those mentioned above. T Another use of the compounds of the invention is for the treatment of migraine. As is known, for example, in the case of migraine it has been demonstrated a diffused vasoconstriction induced by platelet TxA. overproduction [J. Clin. Pathol. (1971), 24, 250; J. Headache (1977) 17, 101J. A platelet overproduction of TxA, and MDA ( alondialdehyde) in diabetes mellitus has been demonstrated and correlated with microcirculatory defects in the illness (Metabolism (1979) 2_8, 394; Eu. J. Clin. Invest. (1979) , 223; Thrombosis Haemost. (1979), 42, 983; J. Lab. Clin. Ned. (1981) 9_7, 67]. Therefore, the compounds of the invention can be used in the treatment of diabetes, in particular, diabetic microangiopathy. Moreover, the compounds of the invention can be used as anti-inflammatory agents. As is known, for example, fluid obtained from carrageenin-induced granuloma converts arachidonic acid into TxA. in vitro and TxA 2 levels are increased in the synovial fluid of rheumatoid arthritis patients and in the fluid of carrageenin-induced inflammation in rats [Prostaglands (1977), 1_3, 17; Scand. J. Rheum. (1977), 6 , 151]. Recently it has been also demonstrated that an overproduction of TxA, is involved in the pathogenesis of hypertension and that a specific inhibitor of TxA. production may be employed in hypertension (Eu. J. Pharmacol. (1981), 7_£» 247]. In fact the compounds of the invention can be used as hypotensive agents. For example an increased TxA. synthesis and decreased prostacyclin synthesis are reported in pregnancy-induced hypertension (Am. J. Obβtet:Gynecol. (1987), 157, 325; Hypertension (1988), 11, 550]. Treatment with thromboxane synthase inhibitors is therefore useful in this pathology. Furthermore it has been shown a role of TxA, in the pathogenesis of ulcerative disorders of the stomach in accordance with its powerful gastric vaβoconstrictory activity, so that also in this field a TxA, inhibitor is useful (Nature (1981), 202, 472]. In fact the compounds of the invention are indicated for the treatment of peptic ulcers. The compounds of the invention can be also antitu oral agents. It is known, for example, that a selective inhibition of TxA, synthesis has been demonstrated to reduce the number of lung etastases and to slow down tumor growth (Nature (1982), 295, 188]. In view of the correlation between TxA, synthesis and calcium transport, recently showed by some authors, specific TxA. synthetase inhibitors, such as the compounds of the invention, can also find use in the treatment of osteoporosis, e.g. post-menopausal osteoporosis {Prostaglandins (1981), 2J., 401]. Moreover the compounds of the invention are indicated for the treatment of angina pectoris and heart failure. In SUBSTITUTE SHEET this respect, it is known, for example, that high levels of TxB, have been found in patients with Prinzmetal's angina [Prostaglandins and Med. (1979), 2 , 243] and in patients with recurrent angina attacks (Sixth Intern. Congress on Thrombosis, Monte Carlo October, 1980 Abs N* 140]. The platelet antiaggregatory activity of the compounds of the invention was evaluated in vitro and in vivo, for example, according to the modified methods of Born [Born G.V.R., Nature 1_94_, 927 (1962)] and Silver (Silver M.J., Science JL83, 1085 (1974)]. The compounds of this invention were found in vitro to have inhibitory activity on platelet aggregation induced by collagen or AOF (adenosine-5'-diphosphate) in platelet rich plasma of guinea pig [Ounkin Hantley Iva: POH (SPF) Ivanovas GmBH, Germany]. Therefore the compounds of the invention may be useful in preventing or reducing platelet loss during extracorporeal circulation; for example during coronary artery bypass and graft procedures or during kidney dialaysis. It has been moreover shown that circulatory shock, for example endotoxic and haemorragic shock, is associated with increased TxA, synthesis so that the compounds of the invention can be useful in these pathologies. Moreover, the compounds of the present invention can also be useful for the treatment of bronchial hyperreactivity in the therapy of asthma. SUBSTITUTE SHEET 91/13062 - 34 - A role for TxA, in asthma can be inferred on the basis of its bronchoconβtrictory activity in experimental animal models (Br. J. Pharmacol. (1984), 82 ( 3 ) 565]. An inhibitory activity of bronchospasm induced by Platelet Activating Factor (PAF) in rats is also reported, e.g. for the TxA, synthetase inhibitors described in GB-B-2205494. The compounds of the present invention can also find use in the treatment of nephropathies e.g. forms of glomerulonephritis, diabetic nephropathy or nephropathies secondary to systemic lupus erithematous (SLE), and in the prevention and/or treatment of Cyclosporin A- induced nephrosis. Accordingly the compounds of this invention can also be used for preventing and/or treating toxemia during pregnancy, typically preeclampsia, eclampsia and preeclamptic (ecla ptic, ecla ptogenic) toxemia. Recently a positive correlation between enhanced intrarenal synthesis of TxA, and the progression of chronic glomerular disease has been demonstrated in different animal models of immune and non-immune renal damage and in humans _J. Clin. Invest. (1985) J_5, 94, J. Clin. Invest. (1985), J_6, 1011]. Accordingly, the TxA, synthase inhibitors recently described e.g. in GB-B-2205240 were found to be active in reducing proteinuria and creatinine serum levels in the doxorubicin induced nephrosis in rats and in reducing proteinuria and increasing the glomerular filtration rate (GFR) in the spontaneous focal glomureuloscleroβiβ in the Milan Normotensive Strain (MNS) rats. The compounds of the invention may be also used to inhibit the renal and cardiac transplant rejection. In fact after transplantation increased urinary TxB, excretion or whole blood TxA, synthesis have been reported both in man and rats [Lancet (1981), ii, 431; Transplantation (1987) 4_3, 346]. Another use of the compounds of the present invention is in the treatment of hyperlipidae ia, namely hypercholesterolaemia and hypertriglyceridaemia secondary to nephrotic syndrome. Hyperlipidaemia is a common feature of nephrotic syndrome in man [New Engl. J. Med. (1983) 312 (24) 1544] and in addition elevated triglycerides and cholesterol levels are reported in animal models such as doxorubicin induced nephrotic syndrome [Expt. Mol. Pathology (1983), 1' 282); elevated urinary albumin excretion has been suggested as the pathogenetic mechanisms [Kidney International (1987), 32, 813]. Also TxA, synthase inhibitors recently described in GB-B-2205240, e.g. proved to be active in reducing cholesterol and triglycerides in aged Milan Normotβniβve Strain rats and in reducing triglycerides in doxorubicin treated rats. HEET It has also been shown that in cholesterol fed rabbit, an animal model of diet induced atherosclerosis, arachidonic acid metabolism is an important factor in early lesion development. In particular a shift in metabolism from TxA, to PGE, may suppress lesion development (i.e. atheromatous plaque) in hypercholesterolemia. The compounds of invention can be therefore used in this pathology. The compounds of the invention can also be used in association with thrombolytic agents (e.g. tPA, Streptokinase, pro-Urokinase) in order to reduce the dose of the latter required in thrombolytic therapy, and to lower the incidence of reocclusion and possibly haemorrage. A further application of the compounds of the invention is the prevention and/or treatment of restenosis after percutaneous transluminal angiopla The toxicity of the compounds of the invention is negligible, therefore they can be safely used in therapy. Mice and rats which had been deprived of food for nine hours were treated orally with single administrations of increasing doses of compounds of the invention, then housed and normally fed. The oriβntativβ acute toxicity (LD. f ) was assessed on the seventh day after the treatment. In view of their high activity and low toxicity, the compounds of the invention can be safely used in medicine. The therapeutic regimen for the different clinical syndromes must be adapted to the type of pathology, taking into account, as usual, also the route of administration, the form in uhich the compound is administered and the age, weight and conditions of the subject involved. The oral route is employed, in general, for all condi¬ tions requiring such compounds. Preference is given to intravenous injection or infusion for the treatment of acute pathological states. Tor maintenance regimens the oral or parenteral , e.g. int.ramυsru1ar, route is preferred. The dosage level suitable for oral administration to adult humans of the compounds of the invention e.g. (E) (_+) 5- Ϊ-phenyl-2-(imidazol-l-yl)-2-benzy3ethylidene7 aminoxypentanoic acid may range from about 50 mg to about 500 mg per dose, 1 to 3 times a day. Of course, these dosage regimens may be adjusted to pro- vide the optimal therapeutic response. The nature of the pharmaceutical compositions contai¬ ning the compounds of this invention in association with pharmaceuticaJ ly acceptable carriers or diluents will, of course, depend upon the desired route of administration. The compositions may be formulated in the conventional manner with the usual ingredients, for example, the com¬ pounds of the invention may be administered in the form ot aqueous or oily solutions, or suspensions tablets, pills, gelatine capsules, syrups, drops or suppositories. Thus, for oral administration, the pharmaceutical compositions containing the compounds of this invention are preferably tablets, pills or gelatine capsules which contain the active substance together with diluents, such as lactose, dextrose, sucrose, mannitol, sorbitol, cellulose; lubricants, for instance silica, talc, stearic acid, magnesium or calcium stearate, and/or polyethylene glycols; or they may also contain binders, such as starches, gelatine, methylcellulose, carboxymethylcellulose, gum- arabic, tragacanth, polyvinylpirrolidone; disaggregating agents, such as starches, alginic acid, alginates, sodium starch glycolate; effervescing mixtures; dyestuffs; sweeteners; wetting agents, such as lecithin, polysorbates, laurylsulphates; and in general, non-toxic and pharmacologically inactive substances used in pharmaceutical formulations. Said pharmaceutical preparations may be manufactured in known manner, for example by means of mixing, granulating, tabletting, sugar-coating, or film- coating processes. The liquid dispersions for oral administration may be e.g. syrups, emulsions and suspensions. The syrups may contain as carrier, for example, saccharose or saccharose with glycerine and/or mannitol and/or sorbitol. The suspensions and the emulsions may contain as carrier, for example, a natural gum, agar, sodium alginate, pectin, methylcellulose, carboxymethylcellulose, or polyvinyl alcohol. The suspensions or solutions for intramuscular injections may contain together with the active compound a pharmaceutically acceptable carrier, e.g. sterile water, olive oil, ethyl oleate, glycols, e.g. propylene glycol, and if desired, a suitable amount of lidocaine hydrochloride. The solutions for intravenous injection or infusion may contain as carrier, for example, sterile water or preferably they may be in the form of sterile aqueous isotonic saline solutions. The suppositories may contain together with the active compound a pharmaceutically acceptable carrier e.g. cocoa-butter, polyethylene glycol, a polyoxyethylene sorbitan fatty acid ester surfactant or lecithin. The following examples illustrate but do not limit the present invention. SUBSTITUTE SHEET Example 1 To a stirred mixture of 5 g (0.025 moles) of (Z)-l-phenyl- 2-(imidazol-l-yl)ethanone oxime and 20 ml of dimethylform- amide, 0.9 g (0.03 moles) of sodium hydride dispersion 80 % are added portionwise at room temperature. Upon completion, stirring is continued till hydrogen evolution stODS. Then 4.74 ml (0.03moles) of ethyl 5-bromopentanoate are added dropwise at room temperature and stirring is continued for 6 hours. The reaction mixture is evaporated under vacuum, diluted with water and extracted with chloroform. The organ¬ ic phase dried over CaCl is evaporated to dryness. The re¬ sidue is purified by column chromatography over silica gel (eluant: chloroform / methanol = 97/3). The pure fractions are collected and evaporated, yielding 4.41 g (53 %) of ethyl (Z)-5-Cl-phenyl-2-(imidazol-l-yl)ethylidene!aminoxypentanoate. N R (CDC1 ): 1.15 (3H,t, -C00CH CH ) 1.6-1.9 (4H,m, -0CH 2 CH 2 CH 2 CH 2 -) 2.35 (2H,m, -CH C00-) 4.13 (2H,q, -C00CH 2 CH..) 4.27 (2H,m, -0CH 2 CH 2 CH 2 CH 2 -) 5.16- (2H,s, -CH 2 -N=) 6.89 (1H, dd, CH at 5 position of imi¬ dazole ring) 6.98 (lH.dd, CH at 4 position of imida¬ zole ring) 7.25-7.70 (6H,m, -N=CH-N- + phenyl ring) TUTE SHEET starting from By the same procedure , /either an (E) or (Z) oxime of formula (II) or a mix¬ ture thereo , the following compounds can be prepared: ethyl ( Z ) -4- £l- phenyl-2- ( imidazol-l-yl ) e thylidene3 aminoxy- butanoate : Microanalysis: Found: C 64.03; H 6.80; N 13.01 Calculated for c l7 H 2 ι N 3°3 : C 6 - 74 »' H 6.71; N 13.32 NMR ( CDC1 ) 1 . . 24 (3H, t, -C00CH CH ) 2 2., .0077 (2H, m, -OCHgCH CH -) 2 , . 40 (2H, t, -OCH 2 CH 2 CH C00-) 4 , , 12 (2H, q, -COOCH CH ) 4. , 30 (2H, t, -DCH 2 CH 2 CH 2 -) 5. 15 (2H, s, -CH 2 -N=) 6 6..8 888 (1H, bs, CH at 5 position of imi¬ dazole ring) 6.98 (1H, bs, CH at 4 position of imi¬ dazole ring) 7.30-7.60 (6H, m, -N=CH-N- + phenyl ring) methyl (Z)-3-D--phenyl-2-(imidazol-l-yl ) ethylideneDaminoxy- propanoate: Microanalysis: Found: C 61.81; H 6.05; N 14.35 Calculated for C, _H_ -.N_0 : C 62. 71 ; H 5. 96 ; N 14. 62 1 5 1 / NMR (CDC1 ) 2.80 (2H, t, -CH COOCH ) 3.70 (3H, s, -C00CH 3 ) 4.54 (2H, t, -0CH 2 CH 2 -) 5.14 (2H, s, -CH 2 -N=) 6.88 (IH, t, CH at 5 position of imi¬ dazole ring) 6.98 (IH, t, CH at 4 position of imi¬ dazole ring) 7.30-7.60 (6H, m, -N=CH-N- + phenyl ring) ethyl (Z)-5- _1-(3-trifluoromethylphenyl)-2-(imidazol-l-yl) ethylidene_]aminoxypentanoate: NMR (CDC1 ) 1. ,26 (3H, t, -COOCH CH ) 1. ,6-1.9 (4H, m, -OCH 2 CH 2 CH 2 CH 2 -) 2. ,38 (2H, m, -CH C00-) 4. ,15 (2H, q, -COOCH CH ) 4. .34 (2H, m, -0CH 2 CH 2 CH 2 CH 2 -) 5. .24 (2H, s, -CH 2 -N= ) 6. .91 (IH, bs, CH at 5 position of imi¬ dazole ring) 7.04 (IH, bs, CH at 4 position of imi¬ dazole ring) 7.40-7.80 (4H, m, phenyl ring) 7.87 (IH, bs, -N-CH-N- ) ethyl (Z)-5-/_l- (3-n-butyloxyphenyl )-2-(imidazol-l- l ) ethylidene/aminoxypentanoate: Microanalysis: Found: C 65-32; H 7-86; N 9-93 Calculated for C-.H-.N-O.-C 65-81 ; H 7-78; N 10.47 22 31 3 4 NMR (CDC1 ) 0 0 .95 (3H, t, CH_-CH_-CH 2 -) 1 -23 (3H, t, -C00-CH 2 -CH ) 1 .4-1 .8 (8H, m, -0-CH -CH -CH--CH -C00-+ CH 3 -CH 2 -CH 2 -CH 2 -0-) 2, • 34 (2H, m, -CH -C00-) 3- , 8-4. .3 (6H, m, -C00-CH -CH +-0CH -CH - 5. .12 (2H, s, -CH 2 -N=) 6. 8-7. ■ 5 (7H, m, phenyl ring + imidazole ring) SUBSTITUTE SHEET ethyl (Z)-5- l-(3-pyridyl)-2-(imidazol-l-yl)ethylidene/ aminoxypentanoate: Microanalysis: Found: C 60.18; H 6.84; N 16.64 Calculated for C 17 H 2 2 N 4 0 C 6l - 8 °" H 6.71; N 16.96 NMR (CDC1 ) 1.22 (3H 3 t, -C00CH 2 -CH 3 ) 1-75 (4H, π, -0CH 2 -CH 2 -CH 2 -CH 2 -) 2.35 (2H, m, -CH -C00-) 4.10 (2H, q, -COOCH_-CH ) 4.29 (2H, m, -0CH_-CH 2 -CH_-CH 2 -) 5-17 (2H, s, -CH 2 -N=) 6.8-7.8 (5H, m, CH at 4 and 5 positions of pyridinering + imidazole ring) 8.57 (IH, ddj C_H at 6 position of pyridine ring) 8.78 (IH, dd, CH at 2 position of pyridine ring) TUTE SHEET and analogously: ethyl (Z)-3-oxa-5-[l-phenyl-2-(imidazol-l-yl)ethylidenejaminoxy¬ pentanoate; tert-butyl(+)(E)-5-El-phenyl-2-(imidazol-l-yl)-2-me hy1ethyl- idenejaminoxypentanoate; ethyl (E)-5-[l-cyclohexyl-2-(imidazol-l-yl)ethylidene " ]aminoxy¬ pentanoate; and tert-butyl (E)-5- l-cyclohexy1-2-(imidazol-l-yl)ethylidene] aminoxypentanoate. Example 2 By proceeding according to the method described in Example 1 and starting from the appropriate oxime of formula (II) as a mixture of Z- and E-isomers, after separation by column chro¬ matography over silica gel of the crude reaction mixture, using as eluant chloroform and methanol in different ratios, the following compounds can be obtained either as (Z) or (E) isomer: tert-butyl(±) (E)-5-[l-phenyl-2-(imidazol-l-yl)-2-methylethyl ¬ idene] minoxypentanoate: NMR (CDC1 ): 1.42 OH, s, -C(CH 3 ) 3 ) 1.60 (4H, m, -0CH 2 CH 2 CH 2 CH 2 -) 1.68 (3H, d, -CH(CH 3 )N- ) 2.19 (2H, t, -CH 2 C00-) 4.07 (2H, t, -0CH_CH 2 CH 2 CH 2 -) 5.12 (IH, q, -CH(CH )N-) 6.80-7.20 (7H, m, CH at 4 and 5 positions of imidazole ring + phenyl ring) 7.42 (IH, bs, -NsCH-N- ) tert-butyl(^)(Z)-5-C -phenyl-2-(imidazol-l-yl)-2-methylethyl- idene_jaminoxypentanoate: NMR ( CDC1 ) 1 . , 44 (9H, s, -C(CH 3 ) 3 ) 1 . , 60 (4H, , -OCH 2 CH 2 CH 2 CH 2 -) 1 -.. , 7.3 (3H, d, -CH(CH,)N- ) o 2. , 28 (2H, t, -CH COO- ) 4. , 23 (2H, t, -0CH 2 CH 2 CH 2 CH 2 -) 5. , 97 (IH, q, -CH(CH 3 )N- ) 6. . 80- -7. 20 (7H, m, CH at 4 and 5 positions of imidazole ring + phenyl ring) 7.52 (IH, bs, -N=CH-N- ) ethyl (E)-5- l-cyclohexyl-2-(imidazol-l-yl)ethylidene!aminoxy¬ pentanoate: NMR (CDC1 3 ): 1 - 1.7 (18H, m, protons of cyclohexyl ring + -CO-O-CH CH + -0-CH 2 -CH 2 -CH 2 -CH 2 -) 2.3 (2H, m, -CH 2 -C0 2 CH 2 CH 3 ) 4.1 (4H, , -0-CH_ -CH 2 -CH - + -C0-0-CH 2 -CH ) 4.58 (2H, s, -CH 2 N= ) 6.9 (IH, bs, CH at 5 position of imi¬ dazole ring) 7> (IH, bs, C_H at 4 position of imi¬ dazole ring) 7.6 (IH, bs, -N=CH-N) ethyl (Z)-5- l-cyclohexyl-2-(imidazol-l-yl)ethylidene]]aminoxy- pentanoate: Microanalysis: Found: C 63.25; H 8.74; N 12.17 Calculated for C 1Q H -0_: C 64.45; H 8.71; N 12.53 18 29 —> — NMR (CDC1 ): 1.24 (3H, t, -C0-0-CH 2 -CH 3 ) 1.0-1.4 (6H, m, CH at 3, 4, 5 positionsof cyclohexyl ring) 1.5-1.8 (8H, , CH at 2, 6 positiors of cyclohexyl ring + -0-CH -CH -CH -CH - 2.0 (IH, m, CH at 1 position of cyclo¬ hexyl ring) 2.32 (2H, m, -CH_ 2 -C0 2 CH 2 CH 3 ) 4.12 (4H, m, -0-CH 2 -CH 2 -CH 2 - + -C0-0-CH CH 3 ) 4.74 (2H, s, -CH 2 -N= ) 6.90 (IH, bs, CH at 5 position of imi¬ dazole ring) 7.05 (IH, bs, CH at 4 position of imi¬ dazole ring) 7.54 (IH, bs, -N=CH-N-) SUBSTITUTE SHEET tert-butyl (E)-5-[l-cyclohexyl-2-(imidazol-l-yl)-ethylidene] aminoxyp ntanoate: NMR (CDC1 ): 1. 15 ( 6H , m, -CH at 3 , 4 , 5 positiore of cyclohexyl ) 1.45 ( 9H, s , -C(CH 3 ) 3 ) 1.7 (9H, - , CH at 1 position of cyclohexyl ring + CH- at 2, 6 positiore of cyclohexyl ring + -0-CH 2 -CH 2 -CH 2 -CH 2 - ) 2.25 (2H, m, -CH 2 -C0 2 -C(CH 3 ) 3 ) 4.05 (2H, , -0-CH 2 -CH -CH - ) 4.55 (2H, s, -CH 2 -N= ) 6.9 (IH, bs, CH at 5 position of imidazole ring) 7.05 (IH, bs, CH at 4 position of imidazole ring) 7.5 (IH, bs, -N»CH-N ) tert-butyl ( Z ) -5- l-cyclohexyl-2- ( imidazol-l-yl ) -ethylidene aminoxypentanoate : NMR (CDC1 ) : 1.2 (6H, m, -CH at 3, 4, 5 positionsof cycl hexyl ring) 1.4 (9H, s, -C(CH 3 ) 3 ) 1.7 (9H, m, CH at 1 position of cyclohexyl ring + CH 2 at 2, 6 positiore of cyclohexy ring + -0-CH 2 -CH 2 -CH 2 -CH 2 -) SUBSTITUTE SHEET - 49 - 2.25 (2H, m, -CH 2 -C0 2 -C(CH 3 ) 3 ) 4.1 (2H, , -0-CH 2 -CH 2 -CH 2 -) 4.74 (2H, s, -CH 2 -N= ) 6.9 (IH, bs, CH at 5 position of imidazole ring) 7.05 (IH, bs, CH at 4 position of imidazole ring) 7.5 (IH, bs, -N=CH-N) ethyl ( Z ) -4- [l-cyclohexyl-2- ( imidazol-l-yl ) ethylidene! aminoxy- butanoate: NMR (CDC1 ) 1 .24 (3H, t, -C0-0-CH 2 CH ) 1. .1-1.4 (6H, m, C_H at 3, 4, 5 positiore of cyclo¬ hexyl ring) 1, .55-1.8 (4H, , CH at 2, 6 positiore of cyclohexyl ring) 1. ,95 (IH, m, CH at 1 position of cyclohexyl ring 2. ,1 (2H, m, -CH -CH -CO- ) 2. ,4 (2H, m, -CH 2 -CH 2 -C0- ) 4. 15 (4H, m, -0-CH 2 -CH 2 -CH 2 - + -CO-O-CH^CH.,) 4. 75 (2H, s, -CH 2 -N= ) 6. 90 (IH, bs, CH at 5 position of imidazole ring) 7.05 (IH, bs, CH at 4 position of imidazole ring) 7.48 (IH, bs, -N=CH-N-) EET /13062 - 50 - Example 3 To a stirred solution of 3.8 g (0.01$ moles) of ethyl (Z)- 5-[l-phenyl-2-(imidazol-l-yl)-ethylidene3aminoxypentanoate in 20 ml of ethanol, 35 ml of aqueous sodium hydroxyde IN are added at room temperature. Stirring is continued for 2 hours, and ethanol is removed under vacuum without heating. The aqueous solution is acidified with aceti acid till pH 6 with external cooling. The precipitated pro¬ duct is filtered, washed with ether and filtered again, yiel ing 2.63 g (75 %) of (Z)-5-ri-phenyl-2-(imidazol-l-yl)-ethyl idenejaminoxypentanoic acid. .p. 89-90°C Microanalysis: Found: C 63.14; H 6.35; N 13.74 Calculated for c 1 6 H ι 9 N 3 0 3 : c 63 - 77 ϊ H 6.35; N 13.94 NMR (DMSO): 1.4-1.8 (4H, m,-0CH CH CH CH -) 2.25 (2H, m, -CH COOH ) 4.23 (2H, m, -OCH CH CH CH -) SUBSTITUTE SHEET - 51 - 5. 30 ( 2H, s , -CH -N= ) 6.80 (IH, bs, CH at 5 position of imidazole ring) 7.00 (IH, bs, CH at 4 position of imidazole ring) 7.2-7.7 (6H, m, -N=CH-N- + phenyl ring) By the same procedures the following compounds can be prepared: (Z)-4-fl-phenyl-2-(imidazol-l-yl)-e hylidenelaminoxybutanoic acid: m.p. 108-109°C Microanalysis: Found: C 62.23; H 5.98; N 14.42 Calculated for Cl,_bH1,_/N.0_: C 62.71; H 5.96; N 14.62 NMR (CDC1-): 2.41 (2H, t, -CH g C00H) 4.34 (2H, t, -0CH 2 CH 2 CH 2 -) 5.11 (2H, s, -CH 2 -N= ) 6.83 (IH, bs, CH at 5 position of imidazole ring) 6.96 (IH, bs, CH at 4 position of imidazole ring) 7.30-7.55 (5H, , phenyl ring) 7.65 (IH, bs, -N=CH-N- ) 10.50 (IH, bs, -C00H ) SUBSTITUTE SHEET (Z)-3- l-phenyl-2-(imidazol-l-yl)ethylidene] minoxymethylben- zoic acid m.p. 140-142°C Microanalysis: Found: C 66.51; H 5.10; N 12.00 Calculated for C 19 H 17 N 3 0 3 : c 68.04; H 5.10; N 12.52 NMR (DMS0): 5.38 (4H, s, -CH -N= + -OCH - ) 6.78 (IH, dd, CH at 5 position of imidazole ring) 6.97 (IH, dd, CH at 4 position of imidazole ring) 7.25-8.10 (10H, m, -N=CH-N + phenyl rings) (Z)-5-fjL-(3-trifluoromethylphenyl)-2-(imidazol-l-yl)-ethyl- idenejaminoxypentanoic acid: m.p. 124-6°C MicrQanalysis: Found: C 55.24; H 4.92; N 11.20 Calculated for C ι 7 H 18 F 3 N 3 0 3 : c 55.28; H 4.91; N 11.38 NMR (CDC1 ): 1.6-1.9 (4H, m, -OCH CH CH CH - ) 2.37 (2H, m, -CH COO- ) 4.32 (2H, m,' -OCH CH CH CH -) 6.87 (IH, s, CH at 5 position of imidazole ring) 7.02 (IH, s, CH at 4 position of imidazole ring) 7.40-7.75 (4H, m, phenyl ring) 7.86 (IH, s, -N=CH-N- ) (Z)-5-[l-cyclohexyl-2-(imidazol-l-yl)ethylidene]aminoxypen¬ tanoic acid: m.p. 80-82°C Microanalysis: Found: C 62.26; H 7.85; N 13.46 Calculated for Cl_o.H25 ό.0 ό_ . : C 62.5; H 8.2; N 13.67 NMR (CDC1 ) 1.0-1.4 (6H, m, CH of 3, 4, 5 positions-of cyclo¬ hexyl ring) 1 . 55-1 . , 85 (8H, m, CH of 2, 6 positionsof cyclohexyl ring + -0-CH 2 -CH 2 -CH 2 -CH 2 -) 2 05 (IH, m, CH at l position of cyclohexyl rin 2 . 35 (2H, , -CH -C00H) 4 . . 10 (2H, m, -0-CH 2 -CH -CH -) 4 . , 72 (2H, s, -CH -N=) 6 . 91 (IH, bs, CH at 5 position of imidazole rin 7 . 05 (IH, bs,-CH at 4 position of imidazole rin 7 . 66 (IH, bs, -N=CH-N-) SUBSTITUTE SHEET (E)-5-Cl-cyclohexy1-2-(imidazol-l-yl)e hylidene_] aminoxy- pentanoic acid: m.p. 117-119°C Microanalysis: Found: C 62.14; H 13.34; N 8.01 Calculated for C, _H ol _N_,0_ : C 62.5; H 8.2; N 13.67 16 25 3 NMR (CDC1 ): 1.0-1.4 (6H, m, CH at 3, 4, 5 positionyof cyclo¬ hexyl ring) 1.5-1.8 (8H, m, CH at 2,6 positions-of cyclohexyl ring + -0-CH 2 -CH 2 - H 2 -CH 2 -) 2.40 (2H, m, -CH -C00H) 2.97 (IH, m, CH at 1 position of cyclohexyl ri 4.08 (2H, m, -0-CH -CH -CH -) 4.56 (2H, s, -CH -N«) 6.94 (IH, bs, CH at 5 position of imidazole ri 7.07 (IH, bs, CH at 4 position of imidazole ri 7.68 (IH, bs, -N=CH-N-) (Z ) -4-fi-cyclohexyl-2-(imidazol-l-yl)ethylidene!aminoxybutano acid: m.p. 120-122°C Microanalysis: Found: C 60.74; H 8.28; N 13.83 Calculated for: C, _H _0 : C 61.41; H 7.90; N 14.3 15 23 3 3 BSTITUTE SHEET NMR (CDC1 ) 1.1-1.4 (6H, m, CH at 3, 4, 5 positions of cyclo¬ hexyl ring) 1.6-1.8 (4H, m, CH 2 at 2, 6 positionyof cyclohexyl ring) 1 .95- ■ 2. ,15 (3H, m, CH at 1 position of cyclohexyl ring + -0-CH 2 -CH 2 -CH 2 -) 2 .39 (2H, t, -CH -C00H) 4, .17 (2H, t, -0-CH 2 -CH 2 -CH -) 4. ,65 (2H, s, -CH -N-) 6. ,85 (IH, bs, CH at 5 position of imidazole ring 7. 02 (IH, bs, CH at 4 position of imidazole ring 7. 50 (IH, bs, -N-CH-N-) (Z)-6-Cl-phenyl-2-(imidazol-l-yl)ethylidene]aminoxyhexanoic aci m.p. 109-110°C Microanalysis: Found: C 64.42; H 6.72; N 13.10 Calculated for C 17 H 21 N 3 0 3 : C 6 - 74 ; H 5 - 71 ; N 13.31 NMR (DMSO): 1.3-1.8 (6H, m, -0-CH 2 -CH 2 -CH 2 -CH 2 -CH 2 -) 2.22 (2H,t, -CH 2 -C00-) 4.22 (2H,t, -0-CH 2 -CH 2 -CH 2 -) 5.30 (2H,s , -CH 2 -N=) 6.8-7.7 (8H, m, phenyl ring + imidazole ring) SUBSTITUTE SHEET and analogously: (Z)-5-Tl-(3-bromophenyl)-2-(imidazol-l-yl)ethylidenejaminoxy¬ pentanoic acid; (Z)-4-Cl-(3-tri luoromethylphenyl)-2-(imidazol-l-yl)ethylidene] aminoxybutanoic acid; (Z)-5-Cl-(3-(n-butyl)phenyl)-2-(imidazol-l-yl)ethylidene]aminoxy pentanoic acid; (Z)-5-0--(2-methoxyphenyl)-2-(imidazol-l-yl)ethylidene!aminoxy¬ pentanoic acid; (Z)-3-oxa-5-D--phenyl-2-(imidazol-l-yl)ethylidene]aminoxypentano acid; (Z)-3-oxa-5-Cl-(3-trifluoromethylphenyl)-2-(imidazol-l-ylEthyl¬ idene!aminoxypentanoic acid; (Z)-5-/_l-(3-n-butyloxyphenyl)-2-(imidazol-l-yl)ethylidene/aminoxy pentanoic acid: m.p. 104-105°C Microanalysis: Found: C 64.28; H 7.28; N 11.10 Calculated for C H N 0 : C 64.32; H 7.24; N 11.25 NMR ( CDC1 ) : 0. 95 (3H, t, CH 3 -CH 2 -CH 2 -. 1. 35-1. 9 (8H, m, CH 3 -CH 2 -CH 2 -CH 2 -0- + -0-CH -CH 2 -CH -CH -COO-) 2. 35 (2H, m, -CH -C00-) 3. 93 (2H,t,-0-CH 2 -CH 2 -CH 2 -CH 3 ) SUBSTITUTE SHEET 4. 25 ( 2H , m , -0-CH 2 -CH 2 -CH 2 -CH 2 -C00- ) 5. 13 ( 2H , s , -CH _-N= ) 6.75-7.7 (7H, m, phenyl ring + imidazole ring) (Z)-5—/_l-(3-pyridyl)-2-(imidazol-l-yl)ethylidene/aminoxy- pentanoic acid: m.p. 65-70°C Microanalysis: Found: C 58.90; H 6.01; N 17.93 Calculated for C.lb_Hl 1 o D N4.0_ : C 59.59; H 6.00; N 18.53 NMR (CDC1 ): 1.6-1.9 (4H, m, -0-CH 2 -CH 2 -CH 2 -CH 2 ") 2.35 (2H, m, -CH -C00-) 4.30 (2H, m, -0CH 2 -CH 2 -CH 2 -CH_-) 5.20 (2H, S, -CH -N=) 6.85-7.90 (5H, m, CH at 4 and 5 positions of pyridine ring + imidazole ring) 8.58 (IH, dd, CH at 6 position of pyridine ring) 8.81 (IH, d, CH at 2 position of pyridine ring) SUBSTITUTE SHEET (Z)-4-/_l-(3-pyridyl)-2-(imidazol-l-yl)ethylidene/aminoxy¬ butanoic acid: Microanalysis: Found: C 57.41; H 5.54; N 18.92 Calculated for C i 4 H 16 N 4 0 3 : c 61-30; H 5.82; N 20.43 NMR ( CDC1 ) 2. , 11 (2H, m, -0-CH -CH -CH -COO-) 2. , 43 (2H, m, -CH 2 -C00-) 4. , 37 (2H, m, -0-CH 2 -CH 2 -CH 2 -) 55.. , 1133 (2H, S, -CH -N=) 6. , 8-7 . 8 (5H, m, CH at 4 and 5 positions of pyridine ring + imidazole ring) 8.55 (IH, dd, CH at 6 position of pyridine ring) 8.76 (IH, d, CH at 2 position of pyridine rin (E) -A-/_l-cyclohexyl-2-(imidazol-l-yl)ethylidene/aminoxy¬ butanoic acid: m.p. 126-129°C Microanalysis Found: C 61,22; H 7.73; N 13.93 Calculated for C,l_bH__N ό0 ό o : C 61.41; H 7.90; N 14.3 NMR (CDClg) 0.9-1.75 (10H, m, CH at 2, 3, 4, 5, 6 position of cyclohexyl ring) 2.0 (2H, m, -0-CH -CH -CH -) SUBSTITUTE SHEET 2 , . 40 (2H, m, -CH 2 -C00H) 2 . , 95 (IH, m, CH at 1 position of cyclohexyl ring) 4. 10 (2H, m, -0-CH 2 -CH 2 -CH 2 -) 4. 55 (2H, s, -CH 2 -N=) 6. 93 (IH, bs, CH at 5 position of imidazole ring) 7.06 ' (IH, bs, CH aft 4 position of imidazole ring) 7.68 (IH, bs, -N=CH-N-) (Z)-6-/_l-cyclohexyl-2-(imidazol-l-yl)ethylidene/aminoxy¬ hexanoic acid: m.p. 107-108°C Microanalysis : Found: C 63.08; H 8.57; N 8.01 Calculated for C <1 _H._N-,0_ : C 63.53; H 8.47; N 13.07 17 27 3 3 NMR (CDC1 ) 1.1-1.85 (16H, , CH at 2,3,4,5,6 position of cyclohexyl ring + -O-CHg-CHg-CHg-CHg-) 2.05 (IH, m, CH at 1 position of cyclohexyl ring) 2.33 (2H, m, -CH -C00H) 4.07 (2H, m, -0-CH_ 2 -CH 2 -CH 2 -) 4.69 (2H, s, -CH 2 -N=) 6.88 (IH, bs, CH at 5 position of imidazole ring) SUBSTITUTE SHEET 7.02 (IH, bs, CH at 4 position of imidazole ring) 7.63 (IH, bs, -N=CH-N-) (E)-5-/_l-n-hexyl-2-(imidazol-l-yl)ethylidene/aminoxy- pentanoic acid: m.p. 82-85°C Microanalysis: Found: C 61.81; H 8.54; N 13.28 Calculated for C. c H__N 0 : C 62.11; H 8.79; N 13.58 lb d I NMR (CDC1 ): 0.87 (3H, m, CH -CH -CH -) . __ 1.05-1.58 (8H, m, CH -(CH ) -) 1.58-1.94 (4H, m, -0-CH 2 ~CH 2 -CH 2 -CH -) 1.94-2.60 (4H, m, -CH -C00-+-CH -CH -C=N-) 4.11 (2H, m, -0-CH -CHg-CH -CH ) 4.57 (2H, s, -CH 2 -N=) 6.94 (IH, bs, CH at 5 position of imidazole ring) 7.09 (IH, bs, CH at 4 position of imidazole ring) 7.66 (IH, bs, -N=CH-N-) S UBSTITUTE SHEET (Z)-5-/_l-n-hexyl-2-(imidazol-l-yl)ethylidene/aminoxy¬ pentanoic acid: Microanalysis: Found: C 61.94; H 8.79; N 13.36 Calculated for C„ _H__N„0_ : C62.ll ; H 8.79; N 13.58 lo d I 3 3 NMR 1 :CDCI 3 ) 0.87 (3H, m, CH 3 -CH 2 -CH 2 ) 1.02- -1.60 (8H, m, CH 3 -(CH 2 ) 4 -) 1.60- -1.88 (4H, m, -0-CH 2 -CJH 2 -CH 2 -CH 2 - 1 1..8888-- -22..2244 (2H, m, -CH 2 -CH_ 2 -C=N-) 2.39 (2H, m, -CH -C00-) 4.14 (2H, m, -0-CH 2 -CH 2 -CH 2 -CH 2 -) 4.81 (2H, s, -CH 2 -N=) 6.92 (IH, bs, CH at 5 position of imidazole ring) 7.10 (IH, bs, CH at 4 position of imidazole ring) 7.65 (IH, bs, -N=CH-N-) SUBSTITUTE SHEET 4- [l-phenyl-3- ( imidazol-l-yl )propylidene] aminoxybutanoic acid ; 3-oxa-5-/_l-cyclohexyl-2- ( imidazol-l-yl ) ethylidene/ aminoxy¬ pentanoic acid ; 5- /_1- ( 3 , 3-dimethylcyclohexyl ) -2- ( imidazol-l-yl ) ethyl idene aminoxypentanoic acid ; 5-/_l-cyclopentyl-2- ( imidazol-l-yl ) ethylidene/ aminoxypentanoic acid ; (Z)-5-/_l-(2-thienyl)-2-(imidazol-1 -yl)ethylidene_/aminoxy¬ pentanoic acid; 3-oxa-6-/_l-cyclohexyl-2-(imidazol-l-yl)ethylidene/aminoxyhexano acid; 5-/_l-cycloheptyl-2-(imidazol-l-yl)ethylidene/aminoxypentanoic acid; 6-/_l-cycloheptyl-2-(imidazol-l-yl)ethylidene aminoxyhexanoic acid; and 5-/_l-n-hep yl-2-(imidazol-l-yl)ethylidene/aminoxypentanoic acid Example 4 Trifluoroacetic acid (1.3 ml) is added dropwise at -10°C to 0.23 g (0.643 mmoles) of tert-butyl (E)-5-/_l-phenyl-2-(imidazol l-yl)ethylidene/aminoxypentanoate. The mixture is stirred at -10°C for 1 hour and 30 minutes. A cooled saturated sodium hydrogencarbonate solution is added to the reaction mixture at 0°C till pH=7 and the mixture is extracted with ethyl acetate. The aqueous phase is cooled, acidified with acetic acid and extracted twice with ethyl acetate. The organic phase is dried and evaporated. The residue is taken up twice wi UBSTITUTE SHEET toluene and evaporated under vacuum without heating, yielding 0.11 g (57%) of (E)-5-0--phenyl-2-(imidazol-l-yl)ethylidene aminoxypentanoic acid. Microanalysis: Found: C 59.12; H 5.93; N 12.23 Calculated for C, H ft N_0_: C 63.77; H 6.35; N 13.94 16 19 3 3 NMR (CDC1 ): 1.75 (4H, m, -OCH CH CH CH -) 2—2—2 2 2.39 (2H, m, -CH COOH) 4.12 (2H, m, -0CH 2 CH 2 CH 2 CH 2 -) 4.92 (2H, s, -CH -N= ) 6.87 (IH, bs, CH at 5 position of imidazole r 7.02 (IH, bs, CH at 4 position of imidazole r 7.2-7.5 (5H, m, phenyl ring) 7.72 (IH, bs, -N=CH-N-) By the same procedure the following compoundscan be prepared: ( +_)(E)-5-Cl-pnenyl-2-(imidazol-l-yl)-2-methylethy1idene!amino pentanoic acid: Microanalysis: Found: C 64.20; H 6.56; N 12.72 Calculated for C ι 7 H 2 ι N 3°3 : C 64.74; H 6.71; N 13.32 NMR(CDC1 ): 1.5-1.8 (7H, m, -CH(CH )N-+-0CH CH CH CH ) 2.35 (2H, , -CH C00-) 4.10 (2H, m -OCH CH CH CH -) SUBSTITUTE S 5 . 24 ( IH, q , -CH( CH ) N- ) 6.9-7.5 (7H, m, CH at 4 and 5 positions of imi- dazole ring + phenyl ring) 8.01 (IH, bs, -NtCH-N-) (+)(Z)-5-Tl-phenyl-2-(imidazol-l-yl)-2-methylethylidene!aminox pentanoic acid; NMR(CDC1 ): 1.6-1.9 (7H, m, -CH(CH )N-+-0CH CH CH CH -) £. . ._. 2.40 (2H, m, -CH^COO-) 4.25 (2H, m, -0CH_ 2 CH 2 CH 2 CH -) 5.98 (IH, q, -CH(CH 3 )N-) 6.8-7.4 (7H, m, CH at 4 and 5 positions of imidazole ring + phenyl ring) 7.82 (IH, bs, -N=CH-N-) and analogously: (E)-4-Q-phenyl-2-(imidazol-l-yl)ethylidene!aminoxybutanoic acid; (E)-5-0.-(3-trifluoromethylphenyl)-2-(imidazol-l-yl)ethyliden aminoxypentanoic acid; (E)-5- -(3-bromophenyl)-2-(imidazol-l-yl)ethylidene!aminoxy¬ pentanoic acid; (E)-4-0--(3-trifluoromethylphenyl)-2-(imidazol-l-yl)ethyliden aminoxybutanoic acid; (E)-5-Cl-(3-(n-butyl)phenyl)-2-(imidazol-l-yl)ethylidene]amin pentanoic acid; (E)-5-[l-(2-methoxyphenyl)-2-(imidazol-l-yl)ethylidene]aminox pentanoic acid; TE SHEET (E)-3-oxa-5-[l-phenyl-2-(imidazol-l-yl)ethylidene]aminoxypenta acid; (E)-3-oxa-5- l-(3-trifluoromethylphenyl)-2-(imidazol-l-ylEthyl idene!aminoxypentanoic acid; (E)-3-[l-phenyl-2-(imidazol-l-yl)ethylidene]aminoxymethylbenzoi acid; (E)-5-(ϊ-6-thieπyl)-2-(imidazol-l-yl)ethylidene]aminoxypentanoic acid; (E)-5- l-(3-pyridyl)-2-(imidazol-l-yl)ethylidene]aminoxypentano acid; and (E)-4-[l-(3-pyridyl)-2-(imidazol-l-yl)ethylidene] minoxybutanoi acid. Example 5 To a stirred mixture of 0.50 g (0.0025 moles) of (Z)-l-phenyl-2 (imidazol-l-yl)ethanone oxime and 2 ml of dimethylformamide,0.1 (0.0034 moles) of sodium hydride dispersion 55% are added porti wise at room temperature. Upon completion, stirring is continu ed till hydrogen evolution stops; then 0.42 g (0.0049 mole of tf-butyrolactone are added and the mixture is heated at 80°C for 4 hours. The reaction mixture is evaporated under vacuum, diluted with water and acidified with acetic acid till pH 6,with external cooling. The precipitated product is filtered, washed with ether and filtered again, yielding 0.40 g (56%) of (Z)-4-jL- phenyl-2-(imidazol-l-yl)ethylidene! minoxybutanoic acid. SUBSTITUTE SHEET m . p . 108-109 ° C Microanalysis: Found: C 62.23; H 5.98: N 14.42 Calculated for CloHX /N 0v_>: C 62.71; H 5.96: N 14.62 NMR (CDC1 ): 2.11 (2H, m, -0CH 2 CH 2 CH 2 - ) 2.41 (2H, t, -CH COOH) 4.34 (2H, t, -OCH CH CH -) 5.11 (2H, s, -CH -N= ) 6.83 (IH, bs, CH at 5 position of imidazole ring) 6.96 (IH, bs, CH at 4 position of imidazole ring) 7.30-7.55 (5H, m, phenyl ring) 7.65 (IH, bs, -N=CH-N- ) 10.50 (IH, bs, -C00H ) By proceeding analogously the following compounds can be obtained: 4-Ll-(3-trifluoromethylphenyl)-2-(imidazol-l-yl)ethylidene! aminoxybutanoic acid: 4-El-phenyl-3-(imidazol-l-yl)propylidene]aminoxybutanoic acid: 4-lTl-cyclohexyl-2-(imidazol-l-yl)ethylidene] minoxybutanoic aci and 4- D.-( 3-pyridyl )-2-( imidazol-l-yl )ethylidene3-aminoxybutanoic ac Example 6 To a solution of 400 mg (1.19 mmoles) of ethyl (E)-5-ϋl- cyclohexyl-2-(imidazol-l-yl)ethylidene] aminoxypentanoate in 5 ml of 1,4-dioxane, 9- ml of an aqueous ammonium hydroxide solution 30% are added. After stirring for 48 hours at room temperature the reaction mixture is diluted with water, extracted twice with ethyl acetate, dried and evaporated. The residue is purified by column chromatography over silica gel (eluant: methylene chloride/methanol=95/5) . The pure fractions are collected and evaporated, yielding 140 mg (60%) of (E) -5-C_-cyclohexyl-2-(imidazol-l-yl) ethylidenejaminoxypentanamide. NMR (CDC1 ): 1.0-1.4 (6H, m, CH at 3, 4, 5 positions of cyclo¬ hexyl ring) 1.5-1.8 (8H, m, CH at 2, 6 positionsof cyclohexyl ring + -0-CH 2 -CH 2 -CH 2 -CH 2 -) 2.25 (2H, m,-CH CO- ) 2.93 (IH, m, CH at 1 position of cyclohexyl rin 4.07 (2H, m, -0-CH -CH -CH - ) 4.57 (2H, s, -CH 2 -N= ) 4.70 (IH, bs, CONH) 5.70 (IH, bs, CONH) 6.93 (IH, bs, CH at 5 position of imidazole rin 7.06 (IH, bs, CH at 4 position of imidazole ring 7.63 (IH, bs, -N=CH-N-) SUBSTITUTE SH By proceeding analogously the following compound can be prepared: (Z)-5-l/_l-(3-pyridyl)-2-(imidazol-l-yl)ethylidene/aminoxy¬ pentanamide: m.p. 102-107°C Microanalysis: Found: C 58.69; H 6.35; N 21.93 Calculated for 15 H 19 N 5 0 2 : c 59.80; H 6.36; N 23.24 NMR (CDC1 ) i. ,6-1. ,9 (4H, m, -0-CH 2 -CH 2 -CH 2 -CH 2 -) 2. ,20 (2H, m, -CH 2 -C0NH 2 ) 4. ,3 (2H, m, -0-CH 2 -CH 2 -CH 2 -CH 2 ) 5. ,17 (2H, s, -CH -N=) 5. ,55 (IH, bs, -CO-NH ) 5. ,90 (IH, bs, -CO-NH Ώ.,) 6. ,8-7. ,9 (5H, m, CH at 4 and 5 positions of pyridinering + imidazole ring) 8.59 (IH, dd, CH at 6 position of pyridine ring) 8.82 (IH, d, CH at 2 position of pyridine ring) and similarly: 5-/l-phenyl-2-(imidazol-l-yl)e hylidene/aminoxypentanamide. Example 7 To a stirred mixture of 1.5 g (0.005 moles) of (+)(E+Z)-1- phenyl-2-(imidazol-l-yl)-2-benzylethanone oxime and 10 ml of dimethylformamide , 0.26 g (0.006 moles) of sodium hydride dispersion 55 % are added portionwise at room temperature. Upon completion, stirring is continued till hydrogen evolu¬ tion stops. Then 0.79 ml (0.005 moles) of ethyl 5-bromopen- tanoate are added at room temperature and stirring is con¬ tinued for 6 hours. The reaction mixture is diluted with water and extracted twice with ethyl acetate. The organic phase is washed with water and with saturated sodium chloride solution, dried over anhydrous Na SO and evaporated to dryness. The residue is purified by column chromatography over silica gel (eluant: dichloromethane/methanol = 190/10) yielding 1.25 g (60 % ) of ethyl (+) (E+Z)-5-[l-phenyl-2-(imidazol-l-yl )-2- benzylethylidene] aminoxypentanoate. Microanalysis: Found: C 70.31; H 6.92; N 9.54. Calculated for C._H_ n N_0.: C 71.58; H 6.97; N 10.02. 2b 29 3 3 NMR (CDC1 ): 5.07 (IH, dd, CH-N=, E isomer) 6.03 (IH, t, CH-N=, Z isomer) Analogously the following compound can be prepared: ethyl (+) (E+Z)-5-[l-cyclohexyl-2-(imidazol-l-yl)-2-benzyl- ethylidene]aminoxypentanoate. Example 8 To a stirred solution of 1 g (0.0024 moles) of ethyl (+_)(E+Z)- 5- Cl-phenyl-2-(imidazol)-1-yl)-2-benzylethylidene]aminoxypen¬ tanoate in 20 ml of ethanol, 10 ml of aqueous sodium hydroxide IN are added at room temperature. Stirring is continued for 30' at 60°C and then ethanol is removed under vacuum. The aqueous solution is acidified with acetic acid till pH 6 with external cooling and extracted three times with ethyl acetate. The organic phase is washed with water, with saturated sodium chloride solution, dried over anhydrous Na SO and evaporated to dryness. The residue is purified by column chromatography over silica gel (eluant: chloroform/methanol = 180/20) yield¬ ing 0.235 g of (+) (E)-5-[l-phenyl-2-(imidazol-l-yl)-2-benzyl- ethylidene]aminoxypentanoic acid and 0.427 g of the correspond ing "Z" isomer. ( (E)-5-Cl-pnenyl-2-(imidazol-l-yl)-2-benzylethylidene]amin¬ oxypentanoic acid; Microanalysis: Found: C 69.13; H 6.58; N 10.33. Calculated for C o H _N_0 : C 70.57; H 6.44; N 10.73. do do 3 3 NMR (CDC1 ) : 1.7 (4H,m,-0-CH -CH -CH -CH -COO-) 2.35 (2H,m,-CH 2 -C00-) 3.25 (lH,dd,Ph-CH -) 3.49 (lH,dd,Ph-CH -) 4.15 (2H,m,-0-CH -CH -CH -CHg-COO-) 5.09 ( IH,dd,-CH-N=) 6.8-7.5 (13H,m,2 phenyl rings + imidazole ring) ( ■ _) (Z)-5-[jL-phenyl-2-(imidazol-l-yl)-2-benzylethylidene]amin¬ oxypentanoic acid: Microanalysis: Found: C 68.21; H 6.68; N 9.94. Calculated for C H N 0 : C 70.57; H 6.44; N 10.73. NMR ( CDC1 3 ) 1 , . 7 (4H,m,-0-CH 2 -CH 2 -CH 2 -CH 2 -C00-) 2 , . 35 (2H,m,-CH -C00-) 3. , 35 (lH,dd, Ph-CH -) 3 3.. ,4499 (IH.dd, Ph-CH -) a 4. , 2 (2H,m,-0-CH 2 -CH 2 -CH 2 -CH 2 -C00-) 6 . 00 (lH,dd,-CH-N=) 6 . 8-7 . 7 (13H,m, 2 phenyl rings + imidazole ring) By the same procedure, starting from either an (E) or (Z) ester, prepared according to the method described in Example 1, or a mixture thereof, the following compounds can be pre¬ pared: (+)(Z)-5-El-cyclohexyl-2-(imidazol-l-yl)-2-benzylethylidene] aminoxypentanoic acid: NMR (CDC1 ): 0.53-2.15 (14H,m,-0CH -CH 2 CH_ 2 CH 2 -C00- + CH at 2,3,4,5 and 6 positions of cyclohexyl ring) 2.15-2.60 (3H,m,-CH COO- + CH at 1 position of cyclohexyl ring) 2.76-3.60 (2H,m,Ph-CH -) SUBSTITUTE SHEET 4.10 (2H,m,-0-CH 2 -CH 2 ) 5.62 (lH,dd,-CH-N=) 6.67-7.42 (7H,m,phenyl ring + CH at 4 and 5 positions of imidazole ring) 7.73 (lH,bs,-N=CH-N-) ; (+_) (E ) -5- £l-cyclohexyl-2- ( imidazol-l-yl )-2-benzyl ethyl idene] aminoxypentanoic acid: NMR (CDC1 ) : 0.37-2.16 (14H,m,-0CH CH CH -CH -COO- + CH at 2,3,4,5 and 6 positions of cyclohexyl ring) 2.41 (2H,m,-CH-C00-) 2.61-3.63 (3H,m,Ph-CH + CH at 1 position of cyclohexyl ring) 4.19 (2H,m,-0-CH -CH -) 4.87 (lH,dd,-CH-N=) 6.52-7.40 (7H,m,phenyl ring + CH at 4 and 5 positions of imidazole ring) 7.58 (lH,bs,-N=CH-N-) ; (_+) (Z)-6-Cl-phenyl-2-(imidazol-l-yl)-2-benzylethylidene] amin¬ oxyhexanoic acid: Microanalysis: Found: C 70.11; H 6.83; N 9.99. Calculated for C H N 0 : C 71.09; H 6.71; N 10.36. NMR (CDC1 ): 1.3-1.7 (6H,m,-0-CH -CH -CH -CH -CH -) 2.35 (2H,m,-CH -C00-) 3.33 (IH, dd,Ph-CH -) —A " 3.49 (IH, dd, Ph-CH -) 4.2 (2H,m,-OCH 2 CH 2 CH 2 CH 2 CH 2 -) 5.97 (lH,t,-CH-N=) 6.8-7.8 (13H,m,2 phenyl rings + imidazole ring); 5 (_ + )(E)-6-[l-phenyl-2-(imidazol-l-yl)-2-benzylethylidene]amin¬ oxyhexanoic acid: Microanalysis: Found: C 70.32; H 6.63; N 10.15 Calculated for C H N 0 :C 71.09; H 6.71; N 10.36 10 NMR (CDC1 ): 1.2-1.8 (6H,m,-OCH 2 -CH_ 2 CH 2 -CH 2 -CH 2 -) 2.3 (2H,m,-CH C00-) 3.27 (lH,dd,PhCH A -) 3.51 (IH,dd,Ph-CH -) ' 15 4.1 (2H,m,-0CH 2 CH 2 CH 2 CH 2 CH 2 -) 5.10 (lH,dd,-CH-N=) 6.8-7.6 (13H,m,2 phenyl rings + imidazole ring); (+)(Z)-6-El-cyclohexyl-2-(imidazol-l-yl)-2-benzyle hylidene] aminoxyhexanoic acid; 20 ( (E)-6-D.-cyclohexyl-2-(imidazol-l-yl)-2-benzylethylidene] aminoxyhexanoic acid; (+)(Z)-5-Cl-(4-fluorophenyl)-2-(imidaz<_l-l-yl)-2-(4-fluoro- benzyDethylidene] minoxypentanoic acid; (±)(E)-5-[l-(4-fluorophenyl)-2-(imidazol-l-yl)-2-(4-fluoro- 2 * 5 benzyl)ethylidene]aminoxypentanoic acid; (+)(Z)-5-Cl-cyclohexyl-2-(imidazol-l-yl)-2-(4-fluorobenzyl) ethylideneI aminoxypentanoic acid; ( + ) ( E ) -5-£l-cyclohexyl-2- ( imidazol-l-yl ) -2-(4-fluorobenzyl) ethylidene]aminoxypentanoic acid; SUBSTITUTE SHEET ( + ) (Z)-3-oxa-5- D.-pheny1-2-( imidazol-1-yl)-2-benzyle hylidene aminoxypentanoic acid; and ( + )(E)-3-oxa-5-[l-phenyl-2-(imidazol-l-yl)-2-benzylethylidene aminoxypentanoic acid. Example 9 To a stirred solution of 1 g (0.005 moles) of (Z)-5-/_l-phenyl-2-(imidazol)-1-yl)ethylidene/aminoxypentanoi acid in 10 ml of methanol, 820 mg (0.015 moles) of a sodium methoxide solution in methanol are added. The reaction mixture is evaporated and the precipitate product is filtere off and dried yielding 970 mg (60%) of sodium (Z)-5-/_l-pheny 2-(imidazol-l-yl)ethylidene/aminoxypentanoate. Example 10 Tablets, each weighing 150 mg and containing 50 mg of the 5 active substance can be manufactured as follows: Composition (for 10,000 tablets) (Z)-5-/_l-cyclohexyl-2-(imidazol-l-yl)ethylidene aminoxy¬ pentanoic acid 500 g Lactose 710 g o Corn starch 237.5 g Talc powder 37.5 g Magnesium stearate 15 g (Z)-5-/_l-cyclohexyl-2-(imidazol-l-yl)ethylidene/aminoxy- pentanoic acid, lactose and a half of the corn starch are 5 mixed: the mixture is then forced through a sieve of 0.5 mm openings. Corn starch (18 mg) is suspended in warm water (180 ml). The resulting paste is used to granulate the powde The granules are dried, comminuted on a sieve of sieve size 1.4 mm, then the remaining quantity of starch, talc and 0 magnesium are added, carefully mixed, and processed into tablets using punches of 8 mm diameter. Example 11. Tablets, each weighing 150 mg and containing 50 mg of the active substance can be manufactured as follows: Composition (for 10,000 tablets) _+5-(E)-ft.-phenyl-2-(imidazol-l-yl)-2-benzyl- ethylidene]aminoxypentanoic acid 500 g Lactose 710 g Corn starch 237.5 g Talc powder 37.5 g Magnesium stearate 15 g _+5-(E)-D.-phenyl-2-(imidazol-l-yl)-2-benzyl-ethylidene]amin¬ oxypentanoic acid, lactose and a half of the corn starch are mixed: the mixture is then forced through a sieve of 0.5 mm openings. Corn starch (18 mg) is suspended in warm water (180 ml). The resulting paste is used to granulate the pow¬ der. The granules are dried, comminuted on a sieve of sieve size 1.4 mm, then the remaining quantity of starch, talc and magnesium are added, carefully mixed, and processed into tab¬ lets using punches of 8 mm diameter. SUBSTITUTE SHEET

Claims: CLAIMS 1. A compound of general formula (I) wherein R is hydrogen or C 1 -C alkyl; A is a Cι-C 4 alkylene chain unsubstituted or substituted by a phenyl ring unsubstituted or substituted by one or two substituents chosen independently from halogen and trifluoromethyl; R_ is a) hydrogen or a straight or branched, saturated or unsaturated C^C ] ^ hydrocarbon radical; b) an aryl or aryl- C1-C4 alkyl group, wherein the aryl group or the aryl moiety is unsubstituted or substituted either by one to four substituents independently chosen from halogen, trihalomethyl, C1-C4 alkyl, C 2 -C 3 alkenyl, C 2 -C 6 alkynyl, C1-C4 alkoxy, C 1 -C 4 alkylthio and C1-C4 alkylsulfonyl or by a substituent chosen from C5~C 8 alkyl, C4-C8 alkenyl, C5-C 8 alkoxy, C5-C 8 alkylthio and phenyl, in which the phenyl ring is unsubstituted or substituted by a substituent chosen from halogen, trihalomethyl and C -C4 alkyl; or (c) a C 5 -C 8 cycloalkyl or C5-C8 cycloalkyl-C 1 -C 4 alkyl group, wherein the cycloalkyl group or moiety is unsubstituted or substituted by one to three C1-C4 alkyl groups; T is a straight or branched, saturated or unsaturated C -Cg hydrocarbon chain, or a phenylene radical; X is a bond or a divalent group consisting of -0-CH -, -C(R' R")-, -Si(R' R")-, vinylene or isopropenylene, wherein each of R' and R" being the same or different is hydrogen, fluorine or ^-04 alkyl; R 2 is an -OR3 or -N(R 3 R 4 ) group, wherein each of R 3 and R 4 independently is hydrogen, 0 -0 alkyl, phenyl or benzyl; and the pharmaceutically acceptable salts thereof. 2. A compound of formula (I), according to claim 1, wherein R is hydrogen or methyl; A is a C1-C4 alkylene chain optionally substituted by phenyl, in its turn optionally substituted by one or two substituents independently chosen from halogen and trifluoromethyl; R l is a) Ci^-Cg alkyl or C 2 -C 8 alkenyl; b) a phenyl, naphthyl, thienyl or pyridyl group unsubstituted or substituted either by one or two substituents independently chosen from halogen, trihalomethyl, C;L-C4 alkyl, C;L-C4 alkoxy, ^-04 alkylsulfonyl and C1-C4 alkylthio, or by a substituent chosen from C 5 -C 8 alkyl, C4-C 3 alkenyl, C 5 -C 8 alkoxy, C5~C 8 alkylthio and phenyl, in which the phenyl ring is unsubstituted or substituted by a substituent chosen from halogen, trihalomethyl and C;L-C4 alkyl; or (c) a cyclohexyl or cycloheptyl group unsubstituted or substituted by one or two C!-C 4 alkyl groups; T is a C1-C5 alkylene or C 2 -C5 alkenylene group; or a phenylene group; X is a bond or a -0-CH 2 - group; R 2 is an -0R 3 or -NHR 3 group, wherein R 3 is hydrogen or C_- C 4 alkyl; and the pharmaceutically acceptable salts thereof. 3. A compound of formula (I), according to claim 1, wherein R is hydrogen; A is -CH -, -CH(CH )-, -CH -CH - or -CH(CH 2 Ph)- in which Ph means phenyl optionally substituted by a halogen atom; R1, is a) C5-C7_ alkyl; b) a phenyl, pyridyl or thienyl ring, unsubstituted or substituted by halogen, C -C alkyl, C -C alkoxy or trifluoromethyl; or c) a cyclohexyl or cycloheptyl ring; T is a C_-C alkylene or phenylene group; X is a bond or a -0-CH - group; R is an -OR group wherein R is hydrogen or C -C alkyl; and the pharmaceutically acceptable salts thereof. 4. A compound selected from the group consisting of the following, either as Z- or E-isomers or Z,E-mixtures of said isomers: 5-[l-phenyl-2-(imidazol-l-yl)ethylidene]aminoxypent¬ anoic acid; 5-[l-phenyl-2-(imidazol-l-yl)ethylidene]aminoxype- ntanamide; ethyl 4-Cl-phenyl-2-(imidazol-l-yl)ethylidene] aminoxybutanoate; 4-[l-phenyl-2-(imidazol-l-yl)ethylidene]aminoxybu¬ tanoic acid; methyl 3-[l-phenyl-2-(imidazol-l-yl)ethylidene]ami- noxypropanoate; ethyl 5-[1-(3-trifluoromethylphenyl)-2-(imidazol -1-yl)ethylidene] minoxypentanoate; 5-[1-(3-trifluoromethylphenyl)-2-(imidazol-l-yl)e- thylidene]aminoxypentanoic acid; 5-t1-(3-bromophenyl)-2-(imidazol-l-yl)ethylidene] aminoxypentanoic acid; 4-t1-(3-trifluoromethylphenyl)-2-(imidazol-l-yl)e- thylidene]aminoxybutanoic acid; 5- [l- ( 3-(n-butyl )phenyl) -2- ( imidazol-l-yl )ethyl- idene] aminoxypentanoic acid; 5- [ 1- ( 2-m3thoxyphenyl ) -2- ( imidazol-l-yl ) ethylidene] aminoxypentanoic acid; ethyl 3-oxa-5- [ l-phenyl-2-( imidazol-l-yl ) ethylidene ] aminoxypentanoate ; 3-oxa-5-[ l-phenyl-2- ( imidazol-l-yl ) ethylidene] ami¬ noxypentanoic acid; 3- oxa-5- [ 1- ( 3-trif luoromethylphenyl ) -2- ( imidazol- 1-yl ) ethylidene ] aminoxypentanoic acid; tert-butyl 5- [l-phenyl-2- ( imidazol-l-yl ) -2-methyl- e thylidene] aminoxypentanoate ; 5- [ l-phenyl-2- ( imidazol-l-yl ) - 2 -methyle thylidene ] - aminoxypentanoic acid; 3- [ l-phenyl-2- ( imidazol-l-yl ) ethylidene] aminoxymethylbenzoic acid ; 4- ( l-phenyl-3- ( imidazol-l-yl )propy lidene ] aminoxy¬ butanoic acid; 5- [ 1- ( n-hexyl ) -2- ( imidazol-l-yl ) ethylidene ]aminoxy- pentanoic acid; ethyl 5-[l-cyclohexyl-2-(imidazol-l-yl)ethylidene] aminoxypentanoate; tert-butyl 5-[1-cyclohexyl-2-(imidazol-l-yl)ethyli¬ dene]aminoxypentanoate; 5 ~[l-cyclohexyl-2-(imidazol-l-yl)ethylidene] mino¬ xypentanoic acid; ethyl 4- [l-cyclohexyl-2-(imidazol-l-yl)ethylidene] aminoxybutanoate; 4-[l-cyclohexyl-2-(imidazol-l-yl)ethylidene] aminoxybutanoic acid; 5-[l-cyclohexyl-2-(imidazol-l-yl)ethylidene] aminoxypentanamide; 3-oxa-5-[1-cyclohexyl-2-(imidazol-l-yl)ethylidene] aminoxypentanoic acid; 5-[1-(3,3-dimethylcyclohexyl)-2-(imidazol-l-yl) ethylidene] aminoxypentanoic acid; 5-[1-cyclopentyl-2-(imidazol-l-yl)ethylidene] aminoxypentanoic acid; SUBSTITUTE SHEET 5- [l-(2-thienyl)-2-( imidazol-l-yl ) ethylidene ] aminoxypentanoic acid; ethyl 5- [l-( 3 -pyridyl) -2- (imidazol-l-yl) ethylidene] aminoxypentanoate ; 5-[l-(3-pyridyl)-2-(iraidazol-l-yl)ethylidene aminoxypentanoic acid; 4- [ 1- ( 3-pyridyl ) -2- ( imidazol-l-yl ) ethylidene ] aminoxybutanoic acid; 5- |_l-( 3-n-butyloxyphenyl )-2-( imidazol-l-yl )ethylidene . 1 aminoxypentanoic acid; ethyl 5- [i-(3-n-butyloxyphenyl )-2-( imidazol-l-yl ) ethylidene] aminoxypen anoate ; 6- [i-cyclohexyl-2-( imidazol-l-yl )ethylideneJaminoxyhexanoic acid; 3-oxa-6- ϋl-cyclohexyl-2-( imidazol-l-yl )e thylidene] aminoxyhexanoic acid; 5-Cl-cyclohepLyl-2-( imidazol-l-yl )ethylidene] aminoxy¬ pentanoic acid; 6- [l-cycloheptyl-2-( imidazol-l-yl )ethylidene_ aminoxyhexanoic acid; 5- [l-n-heptyl-2-( imidazol-l-yl )ethylidene_ aminoxypentanoic acid; 5-[l-phenyl-2-(imidazol-l-yl)-2-benzyle hylidenel aminoxypen anoic acid; 5- |_l-cyclohexyl-2-( imidazol-l-yl )-2-benzyle hylidene] aminoxypentanoic acid; ethyl 5- | .-phenyl-2-imidazol-l-yl )-2-benzylethylidene] aminoxypentanoate; e hyl 5-( .-cyclohexyl-2-(imidazol-l-yl )-2-benzyl- ethy1idenejaminoxypentanoate; 6- £l-phenyl-2-(imidazol-l-yl)-2-benzylethylidene] aminoxyhexanoic acid; 6- .-cyclohexyl-2-( imidazol-l-yl )-2-benzylethylidene] aminoxyhexanoic acid; SUBSTITUTE SHEET 5- ri-(4-fluorophenyl ) -2- ( imidazol-l-yl )-2- ( 4- f luorobenzyl ) ethylidenej aminoxypentanoic acid; 5- l-cyclohexyl-2-(imidazol-l-yl )-2-( -f luorobenzyl ) ethylidene] aminoxypentanoic acid; and 3-oxa-5- [ " l -phenyl- 2- ( imidazol-l-yl )-2-benzylethylidene aminoxypentanoic acid; and the pharmaceutically acceptable salts thereof. 5. A process for the preparation of a compound of formula (I), or a salt thereof, according to claim 1, the process comprising : a) reacting an oxime of formula (II) or a salt thereof wherein claim 1 R, A andR. are as defined in/ , with a compound of for- mula (III) Y-CH -T-X-C0R„ 2 2 (III) wherein claim 1 T, X and R are as defined in/ and Y is a leaving group; or SUBSTITUTE SHEET b) reacting an oxime of formula (II) as defined in 1 or a salt thereof with a lactone of formula (IV)- wherein claim 1 T and X are as defined in/ , thus obtaining a compound of formula (I) in which R is -OH; or c) reacting a compound of formula (V) wherein claim 1 R,A andR are as defined in/ , with a compound of formula (VI) H N-O-CH -T-X-COR (VI) wherein T, X and R are as defined in claim 1; or d) reacting a compound of formula (V), as defined in claim 1, with a compound of formula (VII) wherein - 83 - in claim 1 , T, X and R_ are as defined / and each of 0 and 0' is independently hydrogen, lower alkyl or phenyl; or e) reacting a compound of formula (VIII) or a salt thereof wherein clai-3 1 R.R., A and T are as defined in/ , with a compound of for¬ mula (IX) Y-CH 2 -C0R (IX) wherein claim 1 Y and R are as defined in/ , thus obtaining a compound of formula (I) wherein X is a -0-CH - group; and if desired, converting a compound of formula (I) into another compound of formula (I), and/or, if desired converting a compound of formula (I) into a salt thereof, and/or, if desired, con- verting a salt of a compound of formula (I) into a free com¬ pound, and/or, if desired, separating a mixture of isomers of a compound of formula (I) into the single isomers, and/ or, if desired, altering by isomerization on the oxime double bond the ratio of E- and Z-isomers of a compound of formula (I) in a mixture thereof so as to obtain a differ¬ ent ratio of such isomers, and/or, if desired, converting by isomerization on the oxime double bond a pure E-isomer of a compound of formula (I) either into a pure Z-isomer thereof or into a mixture of E- and Z-isomers thereof; and/ or if desired converting by isomerization on the oxime double bond a pure Z-isomer of a compound of formula (I) either into a pure E- somer or into a mixture of E- and Z- isomers thereof. 6. A pharmaceutical composition containing a suitable carrier and/or diluent and, as an active principle, a com¬ pound of formula (I) according to claim 1, or a pharmaceutical¬ ly acceptable salt thereof. 7. A compound of formula (I) or salt thereof, according to claim 1, for use in the treatment of a disease related to an enhancement of thomboxane A synthesis. 8. A compound of formula (I) or a salt thereof, according to claim 1, for use in the treatment of nephropathies. 9. A compound of formula (I) or a salt thereof, according to claim 1, for use in the prevention and/or treatment of cyclo- sporin A-induced nephrosis. 10. A compound of formula (I) or a salt thereof, according to claim 1, for use in the treatment of hyperlipidaemia secondary to nephrotic syndrome. SUBSTITUTE SHEET

Inventors: COZZI PAOLO, FERTI CORRADO, MENICHINCHERI MARIA, ROSSI ARSENIA, SALVATI PATRICIA, COZZI, PAOLO, FERTI, CORRADO, MENICHINCHERI, MARIA, ROSSI, ARSENIA, SALVATI, PATRICIA
Applicants: ERBA CARLO SPA, FARMITALIA CARLO ERBA S.R.L.
Application year: 1991
Main classification: A61K31
IPC codes: A61K31, A61P3, A61P13, A61P15, A61P43, C07D233, C07D521, C07F7