CONDENSED PYRAZOLE COMPOUNDS

Abstract: Use of a compound which is a condensed pyrazole derivative of formula (I) wherein W is -CONH-, -SO2- or -CO-; X is -O- or -NR4- in which R4 is hydrogen, C1-C6 alkyl, benzyl, pyridyl, tetrahydropyranyl or a phenyl ring, the phenyl ring being unsubstituted or substituted by one or two substituents which are the same or different and are chosen independently from halogen, trifluoromethyl, C1-C6 alkyl, C1-C6 alkoxy, nitro, amino, hydroxy, formylamino, C2-C6 alkanoylamino and C1-C6 alkoxy-carbonyl; each of R, R1, and R2, which are the same or different, is independently hydrogen, halogen, hydroxy, trifluoromethyl, nitro, amino, phenyl, benzyl, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkanoylamino, formylamino or C1-C6 alkoxy-carbonyl; and R3 is hydrogen, or R2 and R3 taken together form a C2-C6 alkylene, -CH=CH-CH= or -O-(CH2)n- chain in which n is 1, 2 or 3; m is zero or an integer of 1 to 6; and Q is C1-C14 alkyl, a phenyl ring or an unsaturated pentatomic heteromonocyclic ring containing two or three heteroatoms which are the same or different and are chosen independently from oxygen, sulphur and nitrogen, wherein the phenyl ring and the heteromonocyclic ring are unsubstituted or substituted by one or two substitutents which are the same or different and are chosen independently from halogen, hydroxy, trifluoromethyl, nitro, amino, phenyl, benzyl, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkanoylamino, formylamino and C1-C6 alkoxy-carbonyl; or a pharmaceutically acceptable salt thereof; in the manufacture of a medicament for use as a kynurenine-3-hydroxylase inhibitor.

Description: CONDENSED PYRAZOLE COMPOUNDS The present invention relates to condensed pyrazole compounds, to a process for their preparation, to pharmaceutical compositions containing them and their use in therapy. The compounds of the invention act as inhibitors of kynurenine-3-hydroxylase (KYN- OH), an enzyme which forms part of the metabolic pathway of kynurenine. It is well known that through the kynurenine pathway, triptophan metabolism gives rise to the formation of 3-hydroxy-kynurenine (3-OH-KYN) and quinolinic acid (QULN), on the one side, and kynurenic acid (KYNA), on the other side, as shown in Figure 1. (The legend to Figure 1 is to be found on the last page of the experimental part of the specification). KYNA is endowed with neuroprotective properties (J. Neurosci. 1990, 10, 2965-2973), whereas QUIN is a relatively potent neurotoxin which has been implicated in the pathogenesis of a variety of neurological disorders including Huntington's disease and epilepsy (Life Sci. 1984, 35, 19-32; Nature, 1986, 321 , 168-171 ; Science, 1983, 219, 316- 318). Increased concentrations of QUIN have also been indicated as responsible for neurological disorders accompanying many infections and inflammatory diseases including Acquired Immunodeficiency Syndrome (AIDS) (Ann. Neurol. 1991, 29, 202- 209). One of the main strategies aimed at altering the KYNA/QUIN balance blocking 3- OH-KYN and QUIN's production and increasing KYNA production, entails inhibition of the key enzyme of the kynurenine (KYN) pathway, among which KYN-OH is of primary importance. Consequently, there is a need in therapy of compounds able of inhibiting this enzyme. The compounds of the present invention fulfill such a need. EP-B-0278603 and EP-B-0347773 describe condensed pyrazole compounds active as immunomodulating agents. A selected class of compounds falling within the general formula of such documents have been found to be also active as inhibitors of KYN-OH. Accordingly the present invention provides the use of a compound which is a condensed pyrazole derivative of formula (I) wherein W is -CONH-, -S0 2 - or -CO-; X is -O- or -NR 4 - in which R 4 is hydrogen, C,-C 6 alkyl, benzyl, pyridyl, tetrahydropyranyl or a phenyl ring, the phenyl ring being unsubstituted or substituted by one or two substituents which are the same or different and are chosen independently from halogen, trifluoromethyl, C,-C 6 alkyl, C,-C 6 alkoxy, nitro, amino, hydroxy, formylamino, C 2 -C 6 alkanoylamino and C,-C 6 alkoxy-carbonyl; each of R, R„ and R 2 , which are the same or different, is independently hydrogen, halogen, hydroxy, trifluoromethyl, nitro, amino, phenyl, benzyl, C,-C 6 alkyl, C,-C 6 alkoxy, C 2 -C 6 alkanoylamino, formylamino or C,-C 6 alkoxy-carbonyl; and R 3 is hydrogen; or R 2 and R 3 taken together form a C 2 -C 6 alkylene, -CH=CH-CH= or -O-(CH 2 ) n - chain in which n is 1, 2 or 3; m is zero or an integer of 1 to 6; Q is C,-C H alkyl, a phenyl ring or an unsaturated pentatomic heteromonocyclic ring containing two or three heteroatoms which are the same or different and are chosen independently from oxygen, sulphur and nitrogen, wherein the phenyl ring and the heteromonocyclic ring are unsubstituted or substituted by one or two substituents which are the same or different and are chosen independently from halogen, hydroxy, trifluoromethyl, nitro, amino, phenyl, benzyl, C,-C 6 alkyl, C,-C 6 alkoxy, C 2 -C 6 alkanoylamino, formylamino and C,-C 6 alkoxy-carbonyl; or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use as kynurenine-3- hydroxylase inhibitor. As will be apparent, in the compounds of formula (I) and in the other compounds of the invention herein disclosed the -CO-CH(CN)-W- chain can also be represented by a tautomeric structure, namely the following enol structure -C(OH)=C(CN)-W-. It is clear that, when in the compounds of the invention R 2 and R 3 taken together form an -O-(CH 2 ) n - chain, the oxygen atom is directly linked to the condensed phenyl ring. The present invention includes within its scope all the possible isomers, stereoisomers, optical isomers and their mixtures and the metabolites and the metabolic precursors (or bioprecursors) of the compounds of formula (I). Examples of pharmaceutically acceptable salts of the compounds of the invention are either those with inorganic bases, such as sodium, potassium, calcium and aluminium hydroxides, or with organic bases such as lysine, triethylamine, triethanolamine, dibenzylamine, methylbenzylamine, di-(2-ethyl-hexyl)-amine, piperidine, N- ethylpiperidine, N,N-diethylaminoethylamine, N-ethylmorpholine, β-phenethylamine, N- benzyl-β-phenethylamine, N-benzyl-N,N-dimethylamine and the other acceptable organic amines, as well as the salts with inorganic, e.g. hydrochloric, hydrobromic and sulphuric acids and with organic acids, e.g. citric, tartaric, maleic, malic, fumaric, methanesulfonic and ethanesulfonic acids. Preferred salts of the compounds of formula (I) are the sodium and the potassium salts thereof. As stated above, the present invention also includes within its scope pharmaceutically acceptable bioprecursors (otherwise known as pro-drugs) of the compounds of formula (I), i.e. compounds which have a different to formula (I) but which nevertheless upon administration to a human being are converted directly or indirectly in vivo into a compound of formula (I). The alkyl, alkoxy, alkanoylamino and alkoxy-carbonyl groups may be branched or straight chain groups. A C 2 -C 6 alkylene, -(CH 2 ) m -, -(CH 2 ) n - chain or C,-C I4 alkyl may be a branched or straight chain. A C,-C l4 alkyl group is preferably a C,-C 6 alkyl group. A C,-C 6 alkyl group is preferably a C r C 4 alkyl group. Representative examples of C,-C 4 alkyl groups include methyl, ethyl, n- and iso-propyl, n-, iso-, sec-, and tert-butyl. A C,-C 6 alkoxy group is preferably a C,-C 4 alkoxy group. Representative examples of C,- C 4 alkoxy groups include methoxy, and ethoxy. A C 2 -C 6 alkanoylamino group is preferably an acetylamino or propionylamino group. A C,-C 6 alkoxy-carbonyl group is preferably a C,-C 4 alkoxy-carbonyl group typically a C,-C 2 one. When Q is a heteromonocyclic ring as defined above it is preferably chosen from oxazole, isoxazole, thiazole, pyrazole, imidazole, 1,2,3-triazole, 1 ,2,4-triazole, 1,2,4-oxadiazole and 1,3,4-thiadiazole. A halogen is fluorine, bromine, chlorine or iodine, in particular chlorine, bromine or fluorine. Preferred compounds for use in the invention are those wherein, in formula (I), W is as defined above; X is O or NR 4 , wherein R 4 is hydrogen, C r C 4 alkyl, benzyl, pyridyl, tetrahydropyranyl or phenyl, the phenyl ring being unsubstituted or substituted by one or two substituents which are the same or different and are chosen independently from halogen, trifluoromethyl, C,-C 4 alkyl, C,-C 4 alkoxy, nitro, amino, hydroxy, formylamino, C 2 -C 4 alkanoylamino and C,-C 4 alkoxy-carbonyl; each of R, R, and R 2 , which are the same or different, is independently hydrogen, halogen, hydroxy, trifluoromethyl, amino, C,-C 4 alkyl, C,-C 4 alkoxy, C 2 -C 4 alkanoylamino, or C,- C 4 alkoxy-carbonyl; and R 3 is hydrogen; or R 2 and R 3 taken together form a C 2 -C 4 alkylene, -CH=CH-CH= or -O-(CH 2 )„- group in which n is 1 or 2; m is zero or 1 ; Q is C,-C 4 alkyl or a phenyl, oxazole, isoxazole, thiazole, pyrazole, imidazole, 1,2,3- triazole, 1,2,4-triazole, 1,2,4-oxadiazole or 1,3,4-thiadiazole ring unsubstituted or substituted by one or two substituents, which are the same or different and are selected independently from halogen, hydroxy, trifluoromethyl, nitro, amino, C,-C 4 alkyl, C,-C 4 alkoxy, C 2 -C 4 alkanoylamino and C,-C 4 alkoxy-carbonyl; and the pharmaceutically acceptable salt thereof. Examples of preferred compounds for use in the invention are the following: 2-Cyano-N-phenyl-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2-c]pyrazol-9-yl)- 3-oxo-propanamide; 2-Cyano-N-(4-methoxy-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2- c]pyrazol-9-yl)-3-oxo-propanamide; 2-Cyano-N-(4-fluoro-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2- c]pyrazol-9-yl)-3-oxo-propanamide; 2-Cyano-N-(3-nitro-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2- c]pyrazol-9-yl)-3-oxo-propanamide; 2-Cyano-N-(3-trifluoromethyl-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH- acenaphtho[l,2-c]pyrazol-9-yl)-3-oxo-propanamide; 2-Cyano-N-(3-methyl-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2- c]pyrazol-9-yl)-3-oxo-propanamide; 2-Cyano-N-(3-chloro-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2- c]pyrazol-9-yl)-3-oxo-propanamide; 3-(6-Chloro-7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2-c]pyrazol-9-yl)-2-cyano-3- oxo-N-phenyl-propanamide; 3-(6-Methoxy-7-methyl-2,3,7,9b-tetrahydro-l H-acenaphtho[l,2-c]pyrazol-9-yl)-2-cyano- 3-oxo-N-phenyl-propanamide; 2-Cyano-3-(l-methyl-l ,4-dihydro-indeno[l ,2-c]pyrazol-3-yl)-N-phenyl-3-oxo- propanamide; 2-Cyano-3-(l -phenyl- l ,4-dihydro-indeno[l,2-c]pyrazol-3-yl)-N-phenyl-3-oxo- propanamide; 2-Cyano-3-(l-methyl-l,4-dihydro-indeno[l ,2-c]pyrazol-3-yl)-N-(4-methoxy-phenyl)-3- oxo-propanamide ; 2-Cyano-3-(7-fluoro-l-methyl-l,4-dihydro-indeno[l ,2-c]pyrazol-3-yl)-N-phenyl-3-oxo- propanamide; 2-Benzenesulfonyl-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l ,2-c]pyrazol-9-yl)- 3-oxo-propanenitrile; 2-Benzoyl-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l ,2-c]pyrazol-9-yl)-3-oxo- propanenitrile; 2-Cyano-N-phenyl-3-( 1 ,2,3, 9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)- 3-oxo-propanamide; 2-Benzenesulfonyl-3 -( 1 -methyl- 1 ,4-dihydro-indeno [ 1 ,2-c]pyrazol-3 -y l)-3 -oxo- propanenitrile; 2-Benzoyl-3-(l-methyl-l,4-dihydro-indeno[l,2-c]pyrazol-3-yl)-3-oxo-propanenitrile; 2-Cyano-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-N-phenyl-3-oxo-propanamide; 2-Benzenesulfonyl-3-(8H-3-oxa-2-aza-cyclopenta[a]inden- 1 -yl)-3-oxo-propanenitrile; 2-Benzoyl-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-3-oxo-propanenitrile; 2-Benzoyl-3-(l,2,3,9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)-3-oxo- propanenitrile; 2-Benzenesulfonyl-3-(l,2,3,9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)- 3-oxo-propanenitrile; 2-Cyano-3-(7-methyl-l,2,7,9b-tetrahydro-3-oxa-7,8-diaza-cyclopenta[a]acenaphthylen-9- yl)-N-phenyl-3-oxo-propanamide; 2-Cyano-3-(6-methoxy-7-methyl- 1 ,2,7,9b-tetrahydro-3-oxa-7,8-diaza- cyclopenta[a]acenaphthylen-9-yl)-N-phenyl-3-oxo-propanamide; 2-Benzoyl-3-(7-methyl- 1 ,2,7,9b-tetrahydro-3-oxa-7,8-diaza-cyclopenta[a]acenaphthylen- 9-yl)-3-oxo-propanenitrile; 2-Benzenesulfonyl-3-(7-methyl-l,2,7,9b-tetrahydro-3-oxa-7,8-diaza- cyclopenta[a]acenaphthylen-9-yl)-3-oxo-propanenitrile; 2-Cyano-3-(7-methyl-7H-acenaphtho[l,2-c]pyrazol-9-yl)-3-oxo-N-phenyl-propanamide; 2-Cyano-3-(7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)-3-oxo-N-phenyl-propanamide; 2-Benzoyl-3-(7-methyl-7H-acenaphtho[l,2-c]pyrazol-9-yl)-3-oxo-propanenitrile; 2-Benzenesulfonyl-3-(7-methyl-7H-acenaphtho[l,2-c]pyrazol-9-yl)-3-oxo-propanenitrile; 2-Cyano-N-benzyl-3-(7-methyl-2,3,7,9b-tetrahydro-l H-acenaphtho[l,2-c]pyrazol-9-yl)-3- oxo-propanamide; 2-Cyano-N-butyl-3-(7-methyl-2,3,7,9b-tetrahydro-l H-acenaphtho[l,2-c]pyrazol-9-yl)-3- oxo-propanamide; 2-Cyano-3-( 1 -methyl- 1 ,4-dihydro-indeno[ 1 ,2-c]pyrazol-3-yl)-N-benzyl-3-oxo- propanamide; 2-Cyano-3-(l -methyl- l,4-dihydro-indeno[l,2-c]pyrazol-3-yl)-N-butyl-3-oxo- propanamide; and the pharmaceutically acceptable salts thereof. The present invention further provides a novel compound which is a condensed pyrazole derivative of formula (IA) wherein W is -CONH-, -SO 2 - or -CO-; X is -O- , or -NR 4 - in which R 4 is hydrogen, C,-C 6 alkyl, benzyl, pyridyl, tetrahydropyranyl or a phenyl ring, the phenyl ring being unsubstituted or substituted by one or two substituents, which are the same or different and are chosen independently from halogen, trifluoromethyl, C,-C 6 alkyl, C,-C 6 alkoxy, nitro, amino, hydroxy, formylamino, C 2 -C 6 alkanoylamino and C,-C 6 alkoxy-carbonyl; each of R, R„ and R 2 , which are the same or different, is independently hydrogen, halogen, hydroxy, trifluoromethyl, nitro, amino, phenyl, benzyl, C,-C 6 alkyl, C,-C 6 alkoxy, C 2 -C 6 alkanoylamino, formylamino or C,-C 6 alkoxy-carbonyl; and R 3 is hydrogen; or R 2 and R 3 taken together form a C 2 -C 6 alkylene, -CH=CH-CH= or -O-(CH 2 ) n - chain in which n is 1, 2 or 3; m is zero or an integer of 1 to 6; Q is C,-C, 4 alkyl, a phenyl ring or an unsaturated pentatomic heteromono-cyclic ring containing two or three heteroatoms which are the same or different and are chosen from independently oxygen, sulphur and nitrogen, wherein the phenyl ring and the heteromonocyclic ring are unsubstituted or substituted by one or two substituents, which are the same or different and are chosen independently from halogen, hydroxy, trifluoromethyl, nitro, amino, phenyl, benzyl, C,-C 6 alkyl, C,-C 6 alkoxy, C 2 -C 6 alkanoylamino, formylamino and C,-C 6 alkoxy-carbonyl; or a pharmaceutically acceptable salt thereof; and wherein, when at the same time X is -NR 4 in which R 4 is C,- C 6 alkyl, pyridyl or a phenyl ring unsubstituted or substituted by one or two substituents, which are the same or different and are chosen from halogen, C,-C 6 alkyl, C,-C 6 alkoxy, nitro, amino. formylamino, C 2 -C 6 alkanoylamino, C,-C 6 alkoxy-carbonyl and trifluoromethyl; R and R, are hydrogen, hydroxy, halogen, trifluoromethyl, nitro, amino, C,-C 6 alkyl, C,-C 6 alkoxy, C 2 -C 6 alkanoylamino, formylamino or C,-C 6 alkoxy-carbonyl; R 2 and R 3 are hydrogen; m is zero or an integer of 1 to 6 and Q is C,-C 14 alkyl or a phenyl ring optionally substituted by one or two substituents which are the same or different and are chosen from halogen, hydroxy, trifluoromethyl, nitro, amino, C,-C 6 alkyl, C,-C 6 alkoxy, C 2 -C 6 alkanoylamino, formylamino and C,-C 6 alkoxy-carbonyl; then W is other than -CONH-; and wherein when at the same time X is -NR 4 -, in which R 4 is C,-C 6 alkyl, benzyl, pyridyl or a phenyl ring optionally substituted by one or two substituents which are the same or different and are chosen from halogen, C,-C 6 alkyl, C,-C 6 alkoxy, nitro, amino, formylamino, C 2 -C 6 alkanoylamino or trifluoromethyl; R and R, are hydrogen, halogen, hydroxy, nitro, amino, C,-C 6 alkyl, C,-C 6 alkoxy, formylamino and C 2 -C 6 alkanoylamino; R 2 and R 3 taken together form a C 2 -C 6 alkylene chain, a -CH=CH- CH= or -0-(CH 2 ) n - chain as defined above; m is zero or an integer of 1 to 6 and Q is C,- C 14 alkyl, or m is zero, 1 or 2 and Q is a phenyl ring optionally substituted by one or two substituents which are the same or different and are chosen from halogen, hydroxy, trifluoromethyl, nitro, amino, C,-C 6 alkyl, C,-C 6 alkoxy, C 2 -C 6 alkanoylamino and formylamino; then W is other than -CONH-. The preferred features exemplified above as to a compound of formula (I) apply also to a compound of formula (I A) . Preferred compounds of the invention are those wherein, in formula (IA) and subject to the above provisos, W is -CONH-, -SO 2 - or -CO-; X is O or NR 4 , wherein R 4 represents hydrogen, C,-C 4 alkyl, benzyl, pyridyl, tetrahydropyranyl or phenyl, the phenyl being unsubstituted or substituted by one or two substituents which are the same or different and are chosen independently from halogen, trifluoromethyl, C r C 4 alkyl, C,-C 4 alkoxy, nitro, amino, hydroxy, formylamino, C 2 -C 4 alkanoylamino and C,-C 4 alkoxy-carbonyl; each of R, R, and R 2 , which are the same or different, is independently hydrogen, halogen, hydroxy, trifluoromethyl, amino, C,-C 4 alkyl, C,-C 4 alkoxy, C 2 -C 4 alkanoylamino or C,-C 4 alkoxy carbonyl; and R 3 is hydrogen; or R 2 and R 3 taken together form a C 2 -C 4 alkylene, -CH=CH-CH= or -O-(CH 2 ) n - group in which n is 1 or 2; m is zero or 1 ; Q is C,-C 4 alkyl or a phenyl, oxazole, isoxazole, thiazole, pyrazole, imidazole, 1,2,3- triazole, 1,2,4-triazole, 1,2,4-oxadiazole or 1,3,4-thiadiazole ring unsubstituted or substituted by one or two substituents which are the same or different and are selected from halogen, hydroxy, trifluoromethyl, nitro, amino, C,-C 4 alkyl, C,-C 4 alkoxy, C 2 -C 4 alkanoylamino and C,-C 4 alkoxy-carbonyl. A preferred class of compounds are those wherein, in formula (IA), X is NR 4 in which R 4 is as defined above, W is -CONH-, Q is a heteromonocyclic ring, containing two or three heteroatoms chosen from oxygen and nitrogen, optionally substituted by one or two substituents which are the same or different and are independently chosen from halogen, hydroxy, trifluoromethyl, nitro, amino, phenyl, benzyl, C,-C 6 alkyl, C,-C 6 alkoxy, C 2 -C 6 alkanoylamino, formylamino and C,-C 6 alkoxy-carbonyl; and m, R, R,, R 2 and R 3 are as defined above A preferred class of compounds of the invention are those wherein, in formula (IA), W is -S0 2 - or -CO-, X is -O- or -NR 4 - in which R 4 is as defined above, and m, R, R,, R 2 , R 3 and Q are as defined above; and the pharmaceutically acceptable salts thereof. Examples of preferred compounds of the invention are the following condensed pyrazole derivatives of formula (IA): 2-Benzenesulfonyl-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2-c]pyrazol-9-yl)- 3-oxo-propanenitrile; 2-Benzoyl-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2-c]pyrazol-9-yl)-3-oxo- propanenitrile; 2-Cyano-N-phenyl-3-( 1,2,3, 9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)- 3-oxo-propanamide; 2-Benzenesulfonyl-3-( 1 -methyl- 1 ,4-dihydro-indeno[ 1 ,2-c]pyrazol-3-yl)-3-oxo- propanenitrile; 2-Benzoyl-3-(l -methyl- 1 ,4-dihydro-indeno[ 1 ,2-c]pyrazol-3-yl)-3-oxo-propanenitrile; 2-Cyano-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-N-phenyl-3-oxo-propanamide; 2-Benzenesulfonyl-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-3-oxo-propanenitrile; 2-Benzoyl-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-3-oxo-propanenitrile; 2-Benzoyl-3-(l,2,3,9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)-3-oxo- propanenitrile; 2-Benzenesulfonyl-3-(l,2,3,9b-tetralιydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)- 3-oxo-propanenitrile; 2-Benzoyl-3-(7-methyl- 1 ,2,7,9b-tetrahydro-3-oxa-7,8-diaza-cyclopenta[a]acenaphthylen- 9-yl)-3-oxo-propanenitrile; 2-Benzenesulfonyl-3-(7-methyl-l,2,7,9b-tetrahydro-3-oxa-7,8-diaza- cyc)openta[a]acenaphthylen-9-yl)-3-oxo-propanenitrile; 2-Cyano-3-(7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)-3-oxo-N-phenyl-propanamide; 2-Benzoyl-3-(7-methyl-7H-acenaphtho[l,2-c]pyrazol-9-yl)-3-oxo-propanenitrile; 2-Benzenesulfonyl-3-(7-methyl-7H-acenaphtho[l,2-c]pyrazol-9-yl)-3-oxo-propanenitrile; 2-Cyano-N-benzy 1-3 -(1 ,2,3, 9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)- 3-oxo-propanamide; 2-Cyano-N-butyl-3-( 1 ,2,3, 9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)-3- oxo-propanamide; 2-Cyano-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-N-benzyl-3-oxo-propanamide; 2-Cyano-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-N-butyl-3-oxo-propanamide; and the pharmaceutically acceptable salts thereof. The present invention further provides the following compounds and the pharmaceutically acceptable salts thereof, which fall within the scope of EP-B-0278603 and EP-B-0347773, cited above, but are not specifically mentioned therein: 2-Cyano-3-(l -methyl- l ,4-dihydro-indeno[l,2-c]pyrazol-3-yl)-N-(4-methoxy-phenyl)-3- oxo-propanamide; 2-Cyano-3-(7-fluoro-l -methyl- l,4-dihydro-indeno[l ,2-c]pyrazol-3-yl)-N-phenyl-3-oxo- propanamide; 2-Cyano-3-( 1 -methyl- 1 ,4-dihydro-indeno[ 1 ,2-c]pyrazol-3-y l)-N-benzyl-3-oxo- propanamide; 2-Cyano-3-(l-methyl-l ,4-dihydro-indeno[l ,2-c]pyrazol-3-yl)-N-butyl-3-oxo- propanamide; which therefore are new chemical entities. A pharmaceutically acceptable salt of a compound of formula (IA) or of a new chemical entity, cited above, is for instance a pharmaceutically acceptable salt as defined as to a compound of formula (I). The present invention also provides a compound which is a condensed pyrazole derivative of formula (IA), or a novel chemical entity as defined above, or a pharmaceutically acceptable salt thereof, for use in a method of treatment of the human or animal body by therapy. In particular the compound thus defined is for use as a kynurenine-3- hydroxylase enzyme inhibitor. The condensed pyrazole derivatives of formula (I) and (IA), the above new chemical entities and the pharmaceutically acceptable salts of the said derivatives and chemical entities are defined as "compounds of the invention". The present invention also provides a method of treating a mammal, including a human, in need of a kynurenine-3 -hydroxy lase inhibitor; such method comprising administering thereto a therapeutically effective amount of a compound of the invention, as defined above. The compounds of the invention can be obtained by an analogy process as disclosed for instance in EP-B-0278603 and in EP-B-0347773. In particular a novel condensed pyrazole derivative of formula (IA) or a pharmaceutically acceptable salt thereof can be obtained by a process comprising: a) reacting a compound of formula (II) wherein R, R,, R 2 , and R 3 are as defined above and X is O or NR 4 wherein R 4 is as defined above except hydrogen and Z is a derivative of a carboxy group, with a compound of formula (III) CN-CH 2 -W-(CH 2 ) m -Q (III) wherein m, Q and W are as defined above, thus obtaining a compound of formula (IA) in which X being NR 4 , R 4 is as defined above except hydrogen; or b) reacting a compound of formula (IV) wherein R, R,, R 2 , and R 3 are as defined above and X is O or NR 4 wherein R 4 is as defined above except hydrogen, with a compound of formula (V) or (VI) Z-(CH 2 ) m -Q (V) OCN-(CH 2 ) m -Q (VI) wherein Q, m and Z are as defined above, so obtaining a compound of formula (IA) wherein W is a -CO- or a -CONH- group respectively and X being NR 4 , R 4 is as defined above except hydrogen; or c) hydrolysing a compound of formula (I A) in which X is NR 4 wherein R 4 is tetrahydropyranyl, to obtain a compound of formula (IA) in which R 4 is hydrogen; and if desired, converting a compound of formula (IA) into another compound of formula (IA), and/or, if desired, converting a compound of formula (IA) into a salt thereof, and/or, if desired converting a salt of a compound of formula (IA) into a free compound of formula (IA), and if desired, separating a mixture of isomers of a compound of formula (IA) into the single isomers. A compound of formula (I A) may be converted into another compound of formula(IA) by known methods. For example, in a compound of formula (IA) a nitro group may be converted into an amino group by treatment, for example, with stannous chloride in concentrated hydrochloric acid using, an organic cosolvent such as dioxane, tetrahydofuran at a temperature varying between room temperature and about 100 °C. Furthermore, for example, an amino group may be converted into a formylamino or a C 2 - C 4 alkanoylamino group, for example by reacting with formic acid or with a suitable C 2 - C 4 alkanoyl anhydride without any solvent or in a organic solvent such as dioxane, dimethylformamide, tetrahydofuran, usually in the presence of a base such as triethylamine, at a temperature varying between 0 °C and about 100 °C. When Z is a derivative of a carboxy group it is for example a reactive derivative thereof, i.e., a halocarbonyl group, preferably a chlorocarbonyl group, or a C,-C 7 alkoxy-carbonyl, preferably a C,-C 3 alkoxy-carbonyl group. The reaction between a compound of formula (II) wherein Z is a reactive derivative of a carboxy group and a compound of formula (III) can be carried out, for example, in the presence of a strong base such as sodium hydride, potassium t-butoxide, in a inert solvent such as 1 ,2-dimethoxyethane, dioxane, dimethylformamide, at a temperature ranging from about 0 °C to 100 °C. The reaction between a compound of formula (IV) and a compound of formula (V) or (VI) can be carried out, for example, in the presence of a base such as triethylamine, in a inert solvent such as toluene, dioxane, tetrahydofuran, dimethylformamide, dichloromethane at a temperature varying between 0 °C and about 100 °C. The above process c) can be carried out according to well known methods in the art. For example, the hydrolysis can be performed in a aqueous solution of a halohydric acid, typically HC1, in a suitable solvent, e.g. dioxane or tetrahydrofuran at a temperature varying from room temperature to about 40 °C. The intermediate compounds (II) and (VI) are either novel or known compounds or can be obtained by known methods from known compounds. For instance the compounds of formula (II) wherein X is O, R 2 and R 3 taken together form a -CH=CH-CH= chain, Z is methoxy- or ethoxy-carbonyl and R and R, are hydrogen as described in J. Chem. Soc. (C), 2375-81 (1971). The remaining compounds of formula (II) wherein R, R,, R 2 , R 3 and Z are as defined above and X is O are new and are a further object of this invention. They may be obtained, for example, by reacting a compound of formula (VII) (VII) wherein R, R,, R 2 , and R 3 are as defined above and R 5 is C,-C 6 alkyl, preferably C,-C 2 alkyl with hydroxylamine hydrochloride. This reaction may be carried out, for example, in acetic acid at a temperature varying between room temperature and 70 °C. The compounds of formula (IV) wherein R, R, , R 2 , and R 3 are as defined above and X is O are new and are a further object of this invention. They may be obtained, for example, reacting a compound of formula (II) wherein R, R,, R 2 , R 3 and Z are as defined above and X is O with acetonitrile in dioxane in the presence of NaH at 60 °C following the procedure described in EP-B- 0278603 and in EP-B-0347773. The compounds of formula (II) wherein R, R„ R 2 , and R 3 are as defined above, X is NR 4 wherein R 4 is as defined above except hydrogen and Z is a reactive derivative of a carboxy group are described in EP-B-0278603 and in EP-B-0347773. The compounds of formula (IV) wherein R, R„ R 2 , and R 3 are as defined above and X is NR 4 wherein R 4 is as defined above except hydrogen are described in EP-B-0278603 and in EP-B-0347773. The compounds of formula (VII) are described in EP-B-0278603 and in EP-B-0347773. The compounds of formula (III), (V), (VI) are commercially available or may be prepared by well known procedures. When in the compounds of the invention and the intermediate thereof groups are present which may interfere with the reaction they may be protected before the reaction takes place and then deprotected at the end of the reaction. The protection and deprotection steps involve conventional techniques well known in synthetic organic chemistry. For instance, hydroxy, amino and/or carboxy groups may be protected and then deprotected according to the common techniques known from the peptide chemistry. Pharmacology The compounds of the invention are active as kynurenine-3-hydroxylase enzyme inhibitors and therefore are useful in the prevention and/or treatment of neuropathological processes, related to a deranged production of quinolinic acid and/or 3- hydroxykynurenine due to excessive activation of neuro-transmission mediated by excitatory amino acid receptors and/or oxidative stress. Examples of such neuropathological processes are neurodegenerative pathologies including, e.g. Huntington's chorea, Alzheimer's disease, Parkinson's disease, olivoponto cerebellar atrophy, non-Alzheimer's dementias, including the dementia like syndrome caused by Acquired Immunodeficiency Syndrome (AIDS), multi-infarctual dementia, cerebral amyotrophic lateral sclerosis, cerebral ischemia, cerebral hypoxia, spinal and head trauma, and epilepsy. A human or animal in need of a kynurenine-3-hydroxylase enzyme inhibitor can thus be treated by a method which comprises the administration thereto of a therapeutically effective amount of a compound of the invention or a salt thereof. The condition of the human or animal can thereby be improved. The efficacy of the compounds of the invention in the inhibition of the enzyme kynurenine-3-hydroxylase was evaluated e.g., in rat liver mitochondrial extract following the method reported below, according to the procedure described in "Analytical Biochem. (1992), 205, 257-262", with minor modifications. The assay for kynurenine 3-hydroxylase is based on the enzymatic synthesis of tritiated water during the hydroxylation reaction. Radiolabeled water was quantified following selective adsorption of the isotopic substrate and its metabolite with activated charcoal. Rat liver mitochondrial extract was used as enzymatic preparation for this assay. The assay for kynurenine 3-hydroxylase activity was carried out at 37°C for a time of 30 min. The reaction mixture of a total volume of 100 μl was constituted of 44 μg of suspended extract, 100 mM Tris/Cl " buffer pH 8.1 , 10 mM EDTA, 100 mM KC1, 0.8 mM NADPH, 0.025 mM L-Kynurenine, 0.5 μCi L-(3,5- 3 H)Kynurenine (10 Ci/mmol) and 10 μl of different concentration of inhibitor solutions. After the incubation, the reaction was terminated by the addition of 1 ml of 7.5% (W/v) activated charcoal, vortexed and centrifuged for 7 min.. A 500 μl aliquot of supernatant was counted by scintillation, spectroscopy in 5 ml of liquid scintillation. The obtained results, which have been reported in the following Table 1, demonstrate the efficacy of representative compounds of the invention: 2-Cyano-3-hydroxy-N-phenyl-3-(7-methyl-2,3 ,7,9b-tetrahydro- 1 H-acenaphtho[l ,2- c]pyrazol-9-yl)-acrylamide, sodium salt hydrate (internal code PNU 155154A); 2-Cyano-N-(4-methoxy-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l ,2- c]pyrazol-9-yl)-3-oxo-propanamide (internal code PNU 151567); 2-Cyano-N-(4-fluoro-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro- 1 H-acenaphtho[ 1 ,2- c]pyrazol-9-yl)-3-oxo-propanamide (internal code PNU 152632); 2-Cyano-N-(3-nitro-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2- c]pyrazol-9-yl)-3-oxo-propanamide (internal code PNU 152633); 2-Cyano-N-(3-trifluoromethyl-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH- acenaphtho[l,2-c]pyrazol-9-yl)-3-oxo-propanamide (internal code PNU 154442); 2-Cyano-N-(3-methyl-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro- 1 H-acenaphtho[ 1 ,2- c]pyrazol-9-yl)-3-oxo-propanamide (internal code PNU 151527); 2-Cyano-N-(3-chloro-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro- 1 H-acenaphtho[ 1 ,2- c]pyrazol-9-yl)-3-oxo-propanamide (internal code PNU 151275); 2-Cyano-N-butyl-3-(7-methyl-2,3,7,9b-tetrahydro-l H-acenaphtho[l ,2-c]pyrazol-9-yl)-3- oxo-propanamide (internal code PNU 153510); 3-(6-Methoxy-7-methyl-2,3 ,7,9b-tetrahydro- 1 H-acenaphtho[ 1 ,2-c]pyrazol-9-yl)-2-cyano- 3-oxo-N-phenyl-propanamide (internal code PNU 165938); 3-(6-Chloro-7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l ,2-c]pyrazol-9-yl)-2-cyano-3- oxo-N-phenyl-propanamide (internal code PNU 152729); 2-Cyano-3-(6-methoxy-7-methyl-l,2,7,9b-tetrahydro-3-oxa-7,8-diaza- cyclopenta[a]acenaphthylen-9-yl)-N-phenyl-3-oxo-propanamide (internal code PNU 152732); 2-Cyano-3-hydroxy-3-(l -methyl- l ,4-dihydro-indeno[l ,2-c]pyrazol-3-yl)-N-phenyl- acrylamide, sodium salt (internal code PNU 168755 A); 2-Cyano-3-(l -phenyl- l,4-dihydro-indeno[l,2-c]pyrazol-3-yl)-N-phenyl-3- oxo-propanamide (internal code PNU 152215); 2-Benzenesulfonyl-3-hydroxy-3-(7-methyl-2,3,7,9b-tetrahydro-l H-acenaphtho[l,2- c]pyrazol-9-yl)-acrylonitrile, sodium salt dihydrate (internal code PNU 190179A); 2-Cyano-N-benzyl-3-(7-methyl-2,3,7,9b-tetrahydro- 1 H-acenaphtho[ 1 ,2-c]pyrazol-9-yl)-3- oxo-propanamide (internal code PNU 151712); Table 1 The dosage level, suitable for administration to a mammal, e.g.: to humans, depends on the age, weight, conditions of the patient and on the administration route; for example, the dosage adopted for oral administration e.g. for one representative compound of the invention PNU 155154A may range from about 10 to about 500 mg pro dose, from 1 to 5 times daily. The compounds of the invention can be administered in a variety of dosage forms, e.g. orally, in the form of tablets, capsules, sugar or film coated tablets, liquid solutions or suspensions; rectally in the form of suppositories; parenterally, e.g. intramuscularly, or by intravenous and/or intrathecal and/or intraspinal injection or infusion. The invention includes also pharmaceutical compositions comprising a compound of the invention or a pharmaceutically acceptable salt thereof in association with a pharmaceutically acceptable excipient (which can be a carrier or a diluent). The pharmaceutical compositions containing the compounds of the invention are usually prepared following conventional methods and are administered in a pharmaceutically suitable form. For example, the solid oral forms may contain, together with the active compound, diluents, e.g. lactose, dextrose, saccharose, sucrose, cellulose, corn starch or potato starch; lubricants, e.g. silica, talc, stearic acid, magnesium or calcium stearate, and/or polyethylene glycols; binding agents, e.g. starches, arabic gum, gelatin, methylcellulose, carboxymethylcellulose or polyvinyl pyrrolidone; desegregating agents, e.g. a starch, alginic acid, alginates or 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 suspension or solutions for intramuscolar 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 desidered, a suitable amount of lidocaine hydrochloride. The solutions for intravenous injections or infusions may contain as carrier, for example, sterile water or preferably they may be in the form of sterile, acqueous, isotonic saline solutions or they may contain as a carrier propylene glycol. 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 invention. Example 1 Preparation of 2-Cvano-N-phenyl-3-(7-methyl-2.3,7.9b-tetrahvdro-lH-acenaphthoπ .2- c]pyrazol-9-yl -3-oxo-propanamide 7-Methyl-2,3,7,9b-tetahydro-lH-acenaphtho[l,2-c]pyrazole-9-carboxylic acid (2.1 g; 0.0083 moles) was reacted with thionyl chloride (1.97 g; 0.0166 moles) in anhydrous dioxane at the reflux temperature for 1.5 h. After cooling the solution was evaporated to dryness and the crude 7-Methyl-2,3,7,9b-tetahydro-lH-acenaphtho[l,2-c]pyrazole-9- carbonyl chloride was dissolved in anhydrous dioxane (60 mL). this solution was added under stirring at room temperature under inert atmosphere to the suspension of the carbanion obtained by treatment of phenylcarbamoylacetonitrile (1.47 g; 0.0091 moles) with 50% sodium hydride (0.6 g; 0.0125 moles) in anhydrous dioxane (130 mL). The reaction mixture was allowed to react at room temperature for 1.5 h, then acidified to pH 2 with 2N HC1 and diluted with ice water. The precipitate was collected by filtration, washed with water until neutral and then dried. Crystallization from methanol gave 1.2 g of the desired product as a beige solid (m.p. 267-270 °C). C 24 H 20 N 4 O 2 ; required: C= 72,71; H= 5.08; N= 14.13; found: C= 72.40; H= 5.06; N= 14.02. Analogously the following products can be prepared: 2-Cyano-N-(4-methoxy-pheny l)-3 -(7-methy 1-2,3 ,7,9b-tetrahydro- 1 H-acenaphtho [ 1 ,2- c]pyrazol-9-yl)-3-oxo-propanamide m.p. 258-261°C; 2-Cyano-N-(4-fluoro-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro- 1 H-acenaphtho [1 ,2- c]pyrazol-9-yl)-3-oxo-propanamide m.p. 289-290°C; 2-Cy ano-N-(3 -nitro-pheny l)-3 -(7-methy 1-2,3 ,7,9b-tetrahydro- 1 H-acenaphtho [ 1 ,2- c]pyrazol-9-yl)-3-oxo-propanamide m.p. 251-253°C; 2-Cyano-N-(3-trifluoromethyl-phenyl)-3-(7-methyl-2,3 ,7,9b-tetrahydro- 1 H- acenaphtho[ 1 ,2-c]pyrazol-9-yl)-3-oxo-propanamide; 2-Cyano-N-(3-methyl-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro- 1 H-acenaρhtho[ 1 ,2- c]pyrazol-9-yl)-3-oxo-propanamide m.p. 245-250°C; 2-Cyano-N-(3-chloro-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2- c]pyrazol-9-yl)-3-oxo-propanamide 270-272°C; 3-(6-Chloro-7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2-c]pyrazol-9-yl)-2-cyano-3- oxo-N-phenyl-propanamide 275-278°C; 3-(6-Methoxy-7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2-c]pyrazol-9-yl)-2-cyano- 3 -oxo-N-pheny 1-propanamide; 2-Cyano-3 -( 1 -methyl- 1 ,4-dihydro-indeno[ 1 ,2-c]pyrazol-3 -y l)-N-pheny 1-3 -oxo- propanamide m.p. 240°C dec; 2-Cyano-3-(l -methyl-1 ,4-dihydro-indeno[l ,2-c]pyrazol-3-yl)-N-(4-methoxy-phenyl)-3- oxo-propanamide; 2-Cyano-3-(7-fluoro- 1 -methyl- 1 ,4-dihydro-indeno[ 1 ,2-c]pyrazol-3-yl)-N-phenyl-3-oxo- propanamide; 2-Benzenesulfonyl-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2-c]pyrazol-9-yl)- 3-oxo-propanenitrile m.p. 189-192°C; 2-Benzoyl-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l ,2-c]pyrazol-9-yl)-3-oxo- propanenitrile m.p. 175-177°C; 2-Cyano-N-phenyl-3-( 1,2,3, 9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)- 3-oxo-propanamide; 2-Benzenesulfonyl-3-( 1 -methyl- 1 ,4-dihydro-indeno[ 1 ,2-c]pyrazol-3-yl)-3-oxo- propanenitrile; 2-Benzoyl-3-(l -methyl- l,4-dihydro-indeno[l,2-c]pyrazol-3-yl)-3-oxo-propanenitrile; 2-Cyano-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-N-phenyl-3-oxo-propanamide; 2-Benzenesulfonyl-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-3-oxo-propanenitrile; 2-Benzoyl-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-3-oxo-propanenitrile; 2-Benzoyl-3-(l ,2,3,9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)-3-oxo- propanenitrile; 2-Benzenesulfonyl-3-(l,2,3,9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)- 3-oxo-propanenitrile; 2-Cyano-3-(7-methyl-l,2,7,9b-tetrahydro-3-oxa-7,8-diaza-cyclopenta[a]acenaphthylen-9- yl)-N-phenyl-3-oxo-propanamide; 2-Cyano-3 -(6-methoxy-7-methyl- 1 ,2,7,9b-tetrahydro-3 -oxa-7, 8-diaza- cyclopenta[a]acenaphthylen-9-yl)-N-phenyl-3-oxo-propanamide m.p. 262-264°C; 2-Benzoyl-3-(7-methyl-l,2,7,9b-tetrahydro-3-oxa-7,8-diaza-cyclopenta[a]acenaphthylen- 9-yl) -3-oxo- propanenitrile; 2-Benzenesulfonyl-3-(7-methyl-l,2,7,9b-tetrahydro-3-oxa-7,8-diaza- cyclopenta[a]acenaphthylen-9-yl)-3-oxo-propanenitrile; 2-Cyano-N-phenyl-3-[7-(tetrahydro-pyran-2-yl)-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2- c]pyrazol-9-yl]-3-oxo-propanamide m.p. 202-205°C; 2-Cyano-N-phenyl-3-(7-phenyl-2,3,7,9b-tetrahydro- 1 H-acenaphtho[ 1 ,2-c]pyrazol-9-yl)-3- oxo-propanamide m.p. 250-252°C; 2-Cyano-3-(l -phenyl- 1 ,4-dihydro-indeno[l ,2-c]pyrazol-3-yl)-N-(4-methoxy-phenyl)-3- oxo-propanamide ; 2-Cyano-3 -( 1 -phenyl- 1 ,4-dihydro-indeno [ 1 ,2-c]pyrazol-3 -yl)-N-phenyl-3 - oxo -propanamide; 2-Cyano-3-(7-fluoro-l-phenyl-l ,4-dihydro-indeno[l ,2-c]pyrazol-3-yl)-N-phenyl-3-oxo- propionamide 259-263°C; 2-Cyano-3-(7-methyl-7H-acenaphtho[l,2-c]pyrazol-9-yl)-3-oxo-N-phenyl-propanamide m.p. 275-278°C; 2-Cyano-3-(7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)-3-oxo-N-phenyl-propanamide; 2-Benzoyl-3-(7-methyl-7H-acenaphtho[l ,2-c]pyrazol-9-yl)-3-oxo-propanenitrile; 2-Benzenesulfonyl-3-(7-methyl-7H-acenaphtho[ 1 ,2-c]pyrazol-9-yl)-3-oxo-propanenitrile; 2-Cyano-3-(2,9b-dihydro-lH-3,7-dioxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)-3-oxo-N- phenyl-propanamide; 2-Cyano-N-benzyl-3-(7-methyl-2,3,7,9b-tetrahydro- l H-acenaphtho[l ,2-c]pyrazol-9-yl)-3- oxo-propanamide; 2-Cyano-N-butyl-3-(7-methyl-2,3,7,9b-tetrahydro- 1 H-acenaphtho[ 1 ,2-c]pyrazol-9-yl)-3- oxo-propanamide; 2-Cyano-3-( 1 -methyl- 1 ,4-dihydro-indeno[ 1 ,2-c]pyrazol-3 -y l)-N-benzyl-3-oxo- propanamide; 2-Cyano-3-(l -methyl- l,4-dihydro-indeno[ l ,2-c]pyrazol-3-yl)-N-butyl-3-oxo- propanamide; 2-Cyano-N-benzyl-3-( 1 ,2,3, 9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)- 3-oxo-propanamide; 2-Cyano-N-butyl-3-(l ,2,3,9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)-3- oxo-propanamide; 2-Cyano-3-(8H-3-oxa-2-aza-cyclopenta[a]inden- 1 -yl)-N-benzyl-3-oxo-propanamide; 2-Cyano-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l -yl)-N-butyl-3-oxo-propanamide. Example 2 Preparation of 2-Cvano-3-(l -methyl- 1.4-dihydro-indenoπ ,2-clpyrazol-3-vO-N-phenyl-3- oxo-propanamide Triethylamine (2.6 mL; 0.0186 moles) and phenylisocyanate (1.9 mL; 0.0177 moles) dissolved in dimethylformamide (20 mL) were added to a solution of 3-(l-Methyl-l,4- dihydro-indeno-[l,2-c]pyrazol-3-yl)-3-oxo-propanenitrile (4 g; 0.0169 moles) in anhydrous dimethylformamide (100 mL). The reaction mixture was allowed to react at room temperature for 30' then acidified to pH 2 with 2 N HCl and diluted with ice water. The precipitate was collected by filtration, washed with water until neutral and then dried. Crystallization from methanol gave 4.48 g of the desired product as a beige solid (m.p. 240 °C dec). C 21 H 16 N 4 O 2 ; required: C= 70,77; H= 4.52; N= 15.72; found: C= 71.08; H= 4.89; N= 15.38. Analogously the following products can be prepared: 2-Cyano-N-phenyl-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l ,2-c]pyrazol-9-yl)- 3-oxo-propanamide m.p. 267-270 °C; 2-Cyano-N-(4-methoxy-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-l H-acenaphtho[l,2- c]pyrazol-9-yl)-3-oxo-propanamide m.p. 258-261 °C; 2-Cyano-N-(4-fluoro-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2- c]pyrazol-9-yl)-3-oxo-propanamide m.p. 289-290 °C; 2-Cyano-N-(3 -nitro-phenyl)-3 -(7-methyl-2,3 ,7,9b-tetrahydro- 1 H-acenaphtho [1,2- c]pyrazol-9-yl)-3-oxo-propanamide m.p. 251-253 °C; 2-Cyano-N-(3-trifluoromethyl-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH- acenaphtho[ 1 ,2-c]pyrazol-9-yl)-3-oxo-propanamide; 2-Cyano-N-(3-methyl-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2- c]pyrazol-9-yl)-3-oxo-propanamide m.p. 245-250 °C; 2-Cyano-N-(3-chloro-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-l H-acenaphtho [1 ,2- c]pyrazol-9-yl)-3-oxo-propanamide m.p. 270-272 °C; 3-(6-Chloro-7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2-c]pyrazol-9-yl)-2-cyano-3- oxo-N-phenyl-propanamide m.p. 275-278 °C; 3-(6-Methoxy-7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l ,2-c]pyrazol-9-yl)-2-cyano- 3-oxo-N-phenyl-propanamide; 2-Cyano-3-( 1 -methyl- 1 ,4-dihydro-indeno [ 1 ,2-c]pyrazol-3 -y l)-N-(4-methoxy-pheny l)-3 - oxo-propanamide; 2-Cyano-3-(7-fluoro-l-methyl-l,4-dihydro-indeno[l ,2-c]pyrazol-3-yl)-N-phenyl-3-oxo- propanamide; 2-Benzoyl-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l ,2-c]pyrazol-9-yl)-3-oxo- propanenitrile m.p. 175-177 °C; 2-Cyano-N-phenyl-3-(l,2,3,9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)- 3 -oxo-propanamide ; 2-Benzoyl-3-(l-methyl-l,4-dihydro-indeno[l,2-c]pyrazol-3-yl)-3-oxo- propanenitrile; 2-Cyano-3-(8H-3-oxa-2-aza-cyclopenta[a]inden- 1 -yl)-N-phenyl-3-oxo-propanamide; 2-Benzoyl-3-(8H-3-oxa-2-aza-cyclopenta[a]inden- 1 -yl)-3-oxo- propanenitrile; 2-Benzoyl-3-(l,2,3,9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)-3oxo- propanenitrile; 2-Cyano-3-(7-methyl-l,2,7,9b-tetrahydro-3-oxa-7,8-diaza-cyclopenta[a]acenaphthylen-9- yl)-N-phenyl-3-oxo-propanamide; 2-Cyano-3-(6-methoxy-7-methyl-l,2,7,9b-tetrahydro-3-oxa-7,8-diaza- cyclopenta[a]acenaphthylen-9-yl)-N-phenyl-3-oxo-propanamide m.p. 262-264 °C; 2-Benzoyl-3-(7-methyl-l,2,7,9b-tetrahydro-3-oxa-7,8-diaza- cyclopenta[a]acenaphthylen-9-yl)-3-oxo- propanenitrile; 2-Cyano-N-phenyl-3-[7-(tetrahydro-pyran-2-yl)-2,3,7,9b-tetrahydro-lH- acenaphtho[l,2- c]pyrazol-9-yl]-3-oxo-propanamide m.p. 202-205 °C; 2-Cyano-N-phenyl-3-(7-phenyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2- c]pyrazol-9-yl)-3-oxo-propanamide m.p. 250-252 °C; 2-Cyano-3-(l -phenyl- l ,4-dihydro-indeno[l,2-c]pyrazol-3-yl)-N-(4-methoxy-phenyl)-3- oxo-propanamide; 2-Cyano-3-(l -phenyl- l,4-dihydro-indeno[l,2-c]pyrazol-3-yl)-N-phenyl-3- oxo-propanamide ; 2-Cyano-3-(7-fluoro- 1 -phenyl- 1 ,4-dihydro-indeno[ 1 ,2-c]pyrazol-3-yl)-N-phenyl-3-oxo- propanamide m.p. 259-263 °C; 2-Cyano-3-(7-methyl-7H-acenaphtho[l ,2-c]pyrazol-9-yl)-3-oxo-N-phenyl-propanamide m.p. 275-278 °C; 2-Cyano-3-(7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)-3-oxo-N-phenyl-propanamide; 2-Benzoyl-3-(7-methyl-7H-acenaphtho[l,2-c]pyrazol-9-yl)-3-oxo-propanenitrile; 2-Cyano-3-(2,9b-dihydro-lH-3,7-dioxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)-3-oxo-N- phenyl-propanamide; 2-Cyano-N-benzyl-3-(7-methyl-2,3,7,9b-tetrahydro-l H-acenaphtho[l,2-c]pyrazol-9-yl)-3- oxo-propanamide; 2-Cyano-N-butyl-3-(7-methyl-2,3,7,9b-tetrahydro-l H-acenaphtho[l,2-c]pyrazol-9-yl)-3- oxo-propanamide; 2-Cyano-3-( 1 -methyl- 1 ,4-dihydro-indeno[ 1 ,2-c]pyrazol-3-yl)-N-benzyl-3-oxo- propanamide; 2-Cyano-3-( 1 -methyl- 1 ,4-dihydro-indeno[ 1 ,2-c]pyrazol-3-yl)-N-butyl-3-oxo- propanamide; 2-Cyano-N-benzyl-3-( 1,2,3, 9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)- 3-oxo-propanamide; 2-Cyano-N-butyl-3-(l ,2,3,9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)-3- oxo-propanamide; 2-Cyano-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-N-benzyl-3-oxo-propanamide; 2-Cyano-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-N-butyl-3-oxo-propanamide. Example 3 Preparation of 2-Cvano-N-phenyl-3-(2,3 .9b-tetrahvdro-lH-acenaphthorL2-c1pyrazol-9- yl ' )-3-oxo-propanamide 20 2 N HCl (2 mL) was added to a solution of 2-Cyano-N-phenyl-3-[7-(tetrahydro-pyran-2- yl)-2,3,7,9b-tetrahydro- 1 H- acenaphtho[ 1 ,2-c]pyrazol-9-yl]-3-oxo-propanamide (3 g; 0.0064 moles) and the solution was stirred 10 h at 40 °C. The mixture was poured into ice water and extracted with ethyl acetate then the organic layer washed with water, dried over anhydrous sodium sulfate and evaporated to dryness. The crude product was ground with diisopropyl ether to give 2.6 g of the desired compound (m.p.>293 °C dec). C 23 H Ig N 4 O 2 ; required: C= 72,24; H= 4.74; N= 14.65; found: C= 70.52; H= 4.94; N= 14.29. Analogously the following products can be prepared: 2-Cyano-N-(4-methoxy-phenyl)-3-(2,3,7,9b-tetrahydro-lH-acenaphtho[l,2-c]pyrazol-9- yl)-3 -oxo-propanamide; 2-Cyano-N-(4-fluoro-phenyl)-3-(2,3,7,9b-tetrahydro- 1 H-acenaphthof 1 ,2-c]pyrazol-9-yl)- 3 -oxo-propanamide; 2-Cyano-N-(3-nitro-phenyl)-3-(2,3,7,9b-tetrahydro-l H-acenaphtho[l ,2-c]pyrazol-9-yl)-3- oxo-propanamide; 2-Cyano-N-(3-trifluoromethyl-phenyl)-3-(2,3,7,9b-tetrahydro-lH-acenaphtho[l,2- c]pyrazol-9-yl)-3-oxo-propanamide; 2-Cyano-N-(3-methyl-phenyl)-3-(2,3,7,9b-tetrahydro- 1 H-acenaphtho [1 ,2-c]pyrazol-9-yl)- 3 -oxo-propanamide; 2-Cyano-N-(3-chloro-phenyl)-3-(2,3,7,9b-tetrahydro- 1 H-acenaphtho[ 1 ,2-c]pyrazol-9-yl)- 3-oxo-propanamide; 3-(6-Chloro-2,3,7,9b-tetrahydro-lH-acenaphtho[l ,2-c]pyrazol-9-yl)-2-cyano-3-oxo-N- phenyl-propanamide; 3-(6-Methoxy-2,3,7,9b-tetrahydro-lH-acenaphtho[l ,2-c]pyrazol-9-yl)-2-cyano-3-oxo-N- phenyl-propanamide; 2-Cyano-3-(l ,4-dihydro-indeno[l,2-c]pyrazol-3-yl)-N-phenyl-3-oxo-propanamide; 2-Benzenesulfonyl-3-(2,3,7,9b-tetrahydro-lH-acenaphtho[l ,2-c]pyrazol-9-yl)-3-oxo- propanenitrile; 2-Benzoyl-3-(2,3,7,9b-tetrahydro-lH-acenaphtho[l ,2-c]pyrazol-9-yl)-3-oxo- propanenitrile; 2-Benzenesulfonyl-3-(l ,4-dihydro-indeno[l ,2-c]pyrazol-3-yl)-3-oxo- propanenitrile; 2-Benzoyl-3-(l ,4-dihydro-indeno[l ,2-c]pyrazol-3-yl)-3-oxo- propanenitrile; 2-Cyano-3-hydroxy-3-(l,2,7,9b-tetrahydro-3-oxa-7,8-diaza-cyclopenta[a]acenaphthylen- 9-yl)-N-phenyl-3-oxo-propanamide; 2-Cyano-3-(-7H-acenaphtho[l,2-c]pyrazol-9-yl)-3-oxo-N-phenyl-propanamide; 3-(7H-Acenaphtho[ 1 ,2-c]pyrazol-9-yl)-2-cyano-3 -oxo-N-phenyl-propanamide; 2-Cyano-N-benzyl-3-(2,3,7,9b-tetrahydro- 1 H-acenaphtho[ 1 ,2-c]pyrazol-9-yl)-3-oxo- propanamide; 2-Cyano-3 -( 1 ,4-dihydro-indeno[ 1 ,2-c]pyrazol-3 -y l)-N-phenyl-3 -oxo-propanamide. Example 4 Preparation of 8H-3-Oxa-2-aza-cyclopenta[ " alindene-l-carboxylic acid ethyl ester Hydroxylamine hydrochloride (2.48 g; 0.0357 moles) was added to a solution of Oxo-(3- oxo-indan-2-yl)-acetic acid ethyl ester (8 g; 0.0344 moles) in acetic acid (50 mL). The solution was stirred at 60 °C for 8 h then poured into ice water. The precipitate was collected by filtration, washed with water and dried. The crude product was ground with diisopropyl ether give 5.2 g of the desired compound as a beige solid. C, 3 H π NO 3 ; required: C= 68.1 1 ; H= 4.84; N= 6.11 ; found: C= 67.85; H= 4.99; N= 5.89. Analogously the following products can be prepared: l,2,3,9b-Tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylene-9-carboxylic acid ethyl ester; 2,9b-Dihydro-l H-3,7-dioxa-8-aza-cyclopenta[a]acenaphthylene-9-carboxylic acid ethyl ester; 7-Oxa-8-aza-cyclopenta[a]acenaphthylene-9-carboxylic acid ethyl ester. Example 5 Preparation of 3-(8H-3-Oxa-2-aza-cyclopenta a1inden- 1 -yl)-3-oxo-propanenitrile To the suspension of 55% NaH (0.51 g; 0.01 17 moles) in anhydrous dioxane (10 mL) 8H- 3-Oxa-2-aza-cyclopenta[a]indene-l-carboxylic acid ethyl ester (1.4 g; 0.0061 moles) and acetonitrile (10 mL) were added under stirring at room temperature under nitrogen atmosphere. The mixture was heated at 50 °C for 30' then poured into ice water. The solution was acidified to pH 3.5 with 2 N HCl and the precipitate was collected by filtration, washed with water until neutral and dried. Crystallization from methanol afforded 1.1 g of the desired product as a beige solid. C, 3 H 8 N 2 0 2 ; required: C=69.64; H= 3.60; N= 12.49; found: 69.30; H= 3.87; N= 12.06. Analogously the following products can be prepared: 3-Oxo-3-( 1,2,3, 9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)- propanenitrile; 3-7-Oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl-3-oxo-propanenitrile; 3-(2,9b-Dihydro-lH-3,7-dioxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)-3-oxo- propanenitrile. Example 6 Preparation of 2-Cyano-3-hydroxy-N-phenyl-3-(7-methyl-2,3 .9b-tetrahydro- 1 H- acenaphtho[L2-clpyrazol-9-yl)-acrylamide. sodium salt hydrate 2-Cyano-N-phenyl-3-(7-methyl-2,3,7,9b-tetrahydro- 1 H-acenaphtho[ 1 ,2-c]pyrazol-9-yl)- 3-oxo-propionamide (0.505 g; 0.00127 moles) was dissolved in ethanol (50 mL) and 0.1 N NaOH (12.7 mL; 0.00127 moles) was added. The solution was evaporated to dryness to obtain the desired compound (m.p. 222.7-235.3 °C).C 24 H 19 N 4 NaO 2 .H 2 O; required: C= 66.04; H= 4.85; N= 12.84; found: C=66.36; H=5.02; N=12.84. Analogously the following products can be prepared: 2-Cyano-3-hydroxy-N-(4-methoxy-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH- acenaphtho[l,2-c]pyrazol-9-yl)-acrylamide, sodium salt; 2-Cyano-3-hydroxy-N-(4-fluoro-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH- acenaphtho[l,2-c]pyrazol-9-yl)-acrylamide, sodium salt hydrate; 2-Cyano-3-hydroxy-N-(3-nitro-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH- acenaphtho[l,2-c]pyrazol-9-yl)-acrylamide, sodium salt; 2-Cyano-3-hydroxy-N-(3-trifluoromethyl-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH- acenaphtho[l,2-c]pyrazol-9-yl)-acrylamide, sodium salt; 2-Cyano-3-hydroxy-N-(3-methyl-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH- acenaphtho[l,2-c]pyrazol-9-yl)-acrylamide, sodium salt; 2-Cyano-3-hydroxy-N-(3-chloro-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH- acenaphtho[l,2-c]pyrazol-9-yl)-acrylamide, sodium salt; 3-(6-Chloro-7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l ,2-c]pyrazol-9-yl)-2-cyano-3- hydroxy-N-phenyl-acrylamide, sodium salt; 3-(6-Methoxy-7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2-c]pyrazol-9-yl)-2-cyano- 3 -hydroxy -N-phenyl-acrylamide, sodium salt; 2-Cyano-3-hydroxy-3-(l -methyl- l,4-dihydro-indeno[ l ,2-c]pyrazol-3-yl)-N-phenyl- acrylamide, sodium salt m.p. 341 °C dec; 2-Cyano-3-hydroxy-3-(l -methyl- l ,4-dihydro-indeno[l ,2-c]pyrazol-3-yl)-N-(4-methoxy- phenyl)-acrylamide, sodium salt; 2-Cyano-3-hydroxy-3-(l-phenyl-l,4-dihydro-indeno[l ,2-c]pyrazol-3-yl)-N-phenyl- acrylamide, sodium salt; 2-Cyano-3 -hydroxy-3-(7-fluoro- 1 -methyl- 1 ,4-dihydro-indeno [ 1 ,2-c]pyrazol-3 -yl)-N- phenyl-acrylamide, sodium salt; 2-Benzenesulfonyl-3-hydroxy-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2- c]pyrazol-9-yl)-acrylonitrile, sodium salt dihydrate m.p. 215 °C dec; 2-Cyano-3-hydroxy-N-phenyl-3-(l,2,3,9b-tetrahydro-7-oxa-8-aza- cyclopenta[a]acenaphthylen-9-yl)-acrylamide, sodium salt; 2-Benzenesulfonyl-3-hydroxy-3-(l-methyl-l,4-dihydro-indeno[l,2-c]pyrazol-3-yl)- acrylonitrile, sodium salt; 2-Cyano-3-hydroxy-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-N-phenyl-acrylamide, sodium salt; 2-Benzenesulfonyl-3-hydroxy-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-acrylonitrile, sodium salt; 2-Benzenesulfonyl-3-hydroxy-3-(l ,2,3,9b-tetrahydro-7-oxa-8-aza- cyclopenta[a]acenaphthylen-9-yl)-acrylonitrile, sodium salt; 2-Cyano-3-hydroxy-3-(7-methyl-l,2,7,9b-tetrahydro-3-oxa-7,8-diaza- cyclopenta[a]acenaphthylen-9-yl)-N-phenyl-acrylamide, sodium salt; 2-Cyano-3-hydroxy-3-(6-methoxy-7-methyl-l,2,7,9b-tetrahydro-3-oxa-7,8-diaza- cyclopenta[a]acenaphthylen-9-yl)-N-phenyl-acrylamide, sodium salt; 2-Benzenesulfonyl-3-hydroxy-3-(7-methyl-l,2,7,9b-tetrahydro-3-oxa-7,8-diaza- cyclopenta[a]acenaphthylen-9-yl)-acrylonitrile, sodium salt; 2-Cyano-3-hydroxy-N-phenyl-3-(7-phenyl-2,3,7,9b-tetrahydro- 1 H-acenaphtho [1 ,2- c]pyrazol-9-yl)-acrylamide, sodium salt; 2-Cyano-3-hydroxy-3-( 1 -phenyl- 1 ,4-dihydro-indeno[l ,2-c]pyrazol-3-yl)-N-(4-methoxy- phenyl)-acrylamide, sodium salt; 2-Cyano-3-hydroxy-3-(7-fluoro- 1 -phenyl- 1 ,4-dihydro-indeno[ 1 ,2-c]pyrazol-3-yl)-N- phenyl-acrylamide, sodium salt; 2-Cyano-3-hydroxy-3-(7-methyl-7H-acenaphtho[l ,2-c]pyrazol-9-yl)-N-phenyl- acrylamide, sodium salt; 2-Cyano-3-hydroxy-(7-oxa-8-azo-cyclopenta[a]acenaphthylen-9-yl)-N-phenyl- acrylamide, sodium salt; 2-Benzenesulfonyl-3-hydroxy-3-(7-methyl-7H-acenaphtho[l,2-c]pyrazol-9-yl)- acrylonitrile, sodium salt ; 2-Cyano-3-hydroxy-N-benzyl-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2- c]pyrazol-9-yl)-acrylamide, sodium salt; 2-Cyano-3-hydroxy-N-butyl-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2- c]pyrazol-9-yl)-acrylamide, sodium salt; 2-Cyano-3-hydroxy-3-( 1 -methyl- 1 ,4-dihydro-indeno[ 1 ,2-c]pyrazol-3-yl)-N-benzy 1- acrylamide, sodium salt; 2-Cyano-3-hydroxy-3-( 1 -methyl- 1 ,4-dihydro-indeno[l ,2-c]pyrazol-3-yl)-N-butyl- acrylamide, sodium salt; 2-Cyano-3-hydroxy-N-benzyl-3-(l,2,3,9b-tetrahydro-7-oxa-8-aza- cyclopenta[a]acenaphthylen-9-yl)-acrylamide, sodium salt; 2-Cyano-3-hydroxy-N-butyl-3-(l ,2,3,9b-tetrahydro-7-oxa-8-aza- cyclopenta[a]acenaphthylen-9-yl)-acrylamide, sodium salt; 2-Cyano-3-hydroxy-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-N-benzyl-acrylamide, sodium salt; 2-Cyano-3-hydroxy-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-N-butyl-acrylamide, sodium salt. Example 7 Capsule, each weighing 0.23 g and containing 50 mg of the active substance can be prepared as follow: Composition for 500 capsules: 2-Cyano-3-hydroxy-N-phenyl-3-(7-methyl-2,3,7,9b-tetrahydro-lH- acenaphtho[l,2-c]pyrazol-9-yl)-acrylamide, sodium salt hydrate 25 g Lactose 80 g Corn starch 5 g Magnesium stearate 5 g This formulation can be encapsulated in two hard gelatin capsules of two pieces, each with each capsule weighing 0.23 g. Example 8 Intramuscular injection of 50 mg/mL A pharmaceutical injectable composition can be manufactured dissolving 50 g of 2- Cyano-3-hydroxy-N-phenyl-3-(7-methyl-2,3,7,9b-tetrahydro-l H-acenaphtho[l ,2- c]pyrazol-9-yl)-acrylamide, sodium salt in sterile propylenglycol (1000 mL) and sealed in 1-5 ampoules. Legend to Figure 1 IDO = Indolamineoxigenase; KYN = Kynurenine; KYN-OH = Kynurenine-3-hydroxylase; KYNA = Kynurenic acid; 3-OHAA = 3-Hydroxy anthranilic acid; KYNase - Kynureninase; QUIN = Quinolinic acid; 3-HAO - 3-Hydroxy anthranilic acid deoxygenase; KAT = Kynurenine amino transferase; 3-OH-KYN = 3-Hydroxy-kynurenine.

Claims: CLAIMS 1. Use of a compound which is a condensed pyrazole derivative of formula (I) wherein W is -CONH-, -SO 2 - or -CO-; X is -O- or -NR 4 - in which R 4 is hydrogen, C,-C 6 alkyl, benzyl, pyridyl, tetrahydropyranyl or a phenyl ring, the phenyl ring being unsubstituted or substituted by one or two substituents which are the same or different and are chosen independently from halogen, trifluoromethyl, C,-C 6 alkyl, C,-C 6 alkoxy, nitro, amino, hydroxy, formylamino, C 2 -C 6 alkanoylamino and C,-C 6 alkoxy-carbonyl; each of R, R,, and R 2 , which are the same or different, is independently hydrogen, halogen, hydroxy, trifluoromethyl, nitro, amino, phenyl, benzyl, C,-C 6 alkyl, C,-C 6 alkoxy, C 2 -C 6 alkanoylamino, formylamino or C,-C 6 alkoxy-carbonyl; and R 3 is hydrogen; or R 2 and R 3 taken together form a C 2 -C 6 alkylene, -CH=CH-CH= or -0-(CH 2 ) n - chain in which n is 1, 2 or 3; m is zero or an integer of 1 to 6; and Q is C,-C 14 alkyl, a phenyl ring or an unsaturated pentatomic heteromono-cyclic ring containing two or three heteroatoms which are the same or different and are chosen independently from oxygen, sulphur and nitrogen, wherein the phenyl ring and the heteromonocyclic ring are unsubstituted or substituted by one or two substituents which are the same or different amd are chosen independently from halogen, hydroxy, trifluoromethyl, nitro, amino, phenyl, benzyl, C,-C 6 alkyl, C,-C 6 alkoxy, C 2 -C 6 alkanoylamino, formylamino and C,-C 6 alkoxy-carbonyl; or a pharmaceutically acceptable salt thereof; in the manufacture of a medicament for use as a kynurenine-3- hydroxylase inhibitor. 2. Use according to claim 1 wherein, in formula (I) W is as defined in claim 1 ; X is O or NR 4 , wherein R 4 is hydrogen, C,-C 4 alkyl, benzyl, pyridyl, tetrahydropyranyl or phenyl, the phenyl ring being unsubstituted or substituted by one or two substituents which are the same or different and are chosen independently from halogen, trifluoromethyl, C,-C 4 alkyl, C,-C 4 alkoxy, nitro, amino, hydroxy, formylamino, C 2 -C 4 alkanoylamino and C,-C 4 alkoxy-carbonyl; each of R, R, and R 2 , which are the same or different, is independently hydrogen, halogen, hydroxy, trifluoromethyl, amino, C,-C 4 alkyl, C,-C 4 alkoxy, C 2 -C 4 alkanoylamino, or C,- C 4 alkoxy-carbonyl; and R 3 is hydrogen; or R 2 and R 3 taken together form a C 2 -C 4 alkylene, -CH=CH-CH= or -O-(CH 2 ) n - group in which n is 1 or 2; m is zero or 1 ; and Q is C,-C 4 alkyl or a phenyl, oxazole, isoxazole, thiazole, pyrazole, imidazole, 1,2,3- triazole, 1 ,2,4-triazole, 1,2,4-oxadiazole or 1,3,4-thiadiazole ring unsubstituted or substituted by one or two substituents which are the same or different and are selected independently from halogen, hydroxy, trifluoromethyl, nitro, amino, C,-C 4 alkyl, C,-C 4 alkoxy, C 2 -C 4 alkanoylamino and C,-C 4 alkoxy-carbonyl. 3. Use according to claim 1, wherein the compound is selected from 2-Cyano-N-phenyl-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2-c]pyrazol-9-yl)- 3 -oxo-propanamide; 2-Cyano-N-(4-methoxy-phenyl)-3 -(7-methy 1-2,3 ,7,9b-tetrahydro- 1 H-acenaphtho [ 1 ,2- c]pyrazol-9-yl)-3-oxo-propanamide; 2-Cyano-N-(4-fluoro-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2- c]pyrazol-9-yl)-3-oxo-propanamide; 2-Cyano-N-(3-nitro-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2- c]pyrazol-9-yl)-3-oxo-propanamide; 2-Cyano-N-(3-trifluoromethyl-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH- acenaphthof 1 ,2-c]pyrazol-9-yl)-3-oxo-propanamide; 2-Cyano-N-(3-methyl-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2- c]pyrazol-9-yl)-3-oxo-propanamide; 2-Cyano-N-(3-chloro-phenyl)-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2- c]pyrazol-9-yl)-3-oxo-propanamide; 3-(6-Chloro-7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l ,2-c]pyrazol-9-yl)-2-cyano-3- oxo-N-phenyl-propanamide; 3-(6-Methoxy-7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2-c]pyrazol-9-yl)-2-cyano- 3-oxo-N-phenyl-propanamide; 2-Cyano-3 -( 1 -methyl- 1 ,4-dihydro-indeno [ 1 ,2-c]pyrazol-3 -yl)-N-pheny 1-3 -oxo- propanamide; 2-Cyano-3-(l-methyl-l,4-dihydro-indeno[l,2-c]pyrazol-3-yl)-N-(4-methoxy-phenyl)-3- oxo-propanamide ; 2-Cyano-3-( 1 -phenyl- 1 ,4-dihydro-indeno [1 ,2-c]pyrazol-3-yl)-N-(4-methoxy-phenyl)-3- oxo-propanamide; 2-Cyano-3-(7-fluoro- 1 -methyl-1 ,4-dihydro-indeno[l ,2-c]pyrazol-3-yl)-N-phenyl-3-oxo- propanamide; 2-Benzenesulfonyl-3-(7-methyl-2,3,7,9b-tetrahydro- 1 H-acenaphtho[ 1 ,2-c]pyrazol-9-yl)- 3-oxo-propanenitrile; 2-Benzoyl-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2-c]pyrazol-9-yl)-3-oxo- propanenitrile; 2-Cyano-N-phenyl-3-(l,2,3,9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)- 3-oxo-propanamide; 2-Benzenesulfonyl-3-(l -methyl-1 ,4-dihydro-indeno[l ,2-c]pyrazol-3-yl)-3-oxo- propanenitrile; 2-Benzoyl-3-(l -methyl- 1 ,4-dihydro-indeno[ 1 ,2-c]pyrazol-3-yl)-3-oxo-propanenitrile; 2-Cyano-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-N-phenyl-3-oxo-propanamide; 2-Benzenesulfonyl-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-3-oxo-propanenitrile; 2-Benzoyl-3-(8H-3-oxa-2-aza-cyclopenta[a]inden- 1 -yl)-3-oxo-propanenitrile; 2-Benzoyl-3-(l,2,3,9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)-3-oxo- propanenitrile; 2-Benzenesulfonyl-3-( 1 ,2,3 ,9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)- 3-oxo-propanenitrile; 2-Cyano-3-(7-methyl-l,2,7,9b-tetrahydro-3-oxa-7,8-diaza-cyclopenta[a]acenaphthylen-9- yl)-N-phenyl-3-oxo-propanamide; 2-Cyano-3-(6-methoxy-7-methyl-l,2,7,9b-tetrahydro-3-oxa-7,8-diaza- cyclopenta[a]acenaphthylen-9-yl)-N-phenyl-3-oxo-propanamide; 2-Benzoyl-3-(7-methyl-l,2,7,9b-tetrahydro-3-oxa-7,8-diaza-cyclopenta[a]acenaphthylen- 9-yl)-3-oxo-propanenitrile; 2-Benzenesulfonyl-3-(7-methyl-l,2,7,9b-tetrahydro-3-oxa-7,8-diaza- cyclopenta[a]acenaphthylen-9-yl)-3-oxo-propanenitrile; 2-Cyano-3-(7-methyl-7H-acenaphtho[l,2-c]pyrazol-9-yl)-3-oxo-N-phenyl-propanamide; 2-Cyano-3-(7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)-3-oxo-N-phenyl-propanamide; 2-Benzoyl-3-(7-methyl-7H-acenaphtho[l,2-c]pyrazol-9-yl)-3-oxo-propanenitrile; 2-Benzenesulfonyl-3-(7-methyl-7H-acenaphtho[l,2-c]pyrazol-9-yl)-3-oxo-propanenitrile; 2-Cyano-N-benzyl-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2-c]pyrazol-9-yl)-3- oxo-propanamide; 2-Cyano-N-butyl-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2-c]pyrazol-9-yl)-3- oxo-propanamide; 2-Cyano-3-(l-methyl-l,4-dihydro-indeno[l,2-c]pyrazol-3-yl)-N-benzyl-3-oxo- propanamide; and 2-Cyano-3-(l -methyl- l,4-dihydro-indeno[l,2-c]pyrazol-3-yl)-N-butyl-3-oxo- propanamide; and the pharmaceutically acceptable salts thereof. 4. A method of treating a mammal, including a human, in need of a kynurenine-3- hydroxylase inhibitor, which method comprises administering thereto a therapeutically effective amount of a compound as defined in claim 1. 5. A compound which is a condensed pyrazole derivative of formula (I A) wherein W is -CONH-, -S0 2 - or -CO-; X is -0- , or -NR 4 - in which R 4 is hydrogen, C,-C 6 alkyl, benzyl, pyridyl, tetrahydropyranyl or a phenyl ring, the phenyl ring being unsubstituted or substituted by one or two substituents which are the same or different and are chosen independently from halogen, trifluoromethyl, C,-C 6 alkyl, C,-C 6 alkoxy, nitro, amino, hydroxy, formylamino, C 2 -C 6 alkanoylamino and C,-C 6 alkoxy-carbonyl; each of R, R„ and R 2 , which is the same or different, is independently hydrogen, halogen, hydroxy, trifluoromethyl, nitro, amino, phenyl, benzyl, C,-C 6 alkyl, C,-C 6 alkoxy, C 2 -C 6 alkanoylamino, formylamino or C r C 6 alkoxy-carbonyl; and R 3 is hydrogen; or R 2 and R 3 taken together form a C 2 -C 6 alkylene, -CH=CH-CH= or -O-(CH 2 ) n - chain in which n is 1, 2 or 3; m is zero or an integer of 1 to 6; and Q is C,-C 14 alkyl, a phenyl ring or an unsaturated pentatomic heteromono-cyclic ring containing two or three heteroatoms which are the same or different and are chosen independently from oxygen, sulphur and nitrogen, wherein the phenyl ring and the heteromonocyclic ring are unsubstituted or substituted by one or two substituents which are the same or different and are chosen independently from halogen, hydroxy, trifluoromethyl, nitro, amino, phenyl, benzyl, C,-C 6 alkyl, C,-C 6 alkoxy, C 2 -C 6 alkanoylamino, formylamino and C,-C 6 alkoxy-carbonyl; or a pharmaceutically acceptable salt thereof; and wherein, when at the same time X is -NR 4 in which R 4 is C,- C 6 alkyl, pyridyl or a phenyl ring unsubstituted or substituted by one or two substituents which are the same or different and are chosen from halogen, C,-C 6 alkyl, C,-C 6 alkoxy, nitro, amino, formylamino, C 2 -C 6 alkanoylamino, C,-C 6 alkoxy-carbonyl and trifluoromethyl; R and R, are hydrogen, hydroxy, halogen, trifluoromethyl, nitro, amino, C,-C 6 alkyl, C,-C 6 alkoxy, C 2 -C 6 alkanoylamino, formylamino or C,-C 6 alkoxy-carbonyl; R 2 and R 3 are hydrogen; m is zero or an integer of 1 to 6 and Q is C,-C 14 alkyl or a phenyl ring optionally substituted by one or two substituents which are the same or different and are chosen from halogen, hydroxy, trifluoromethyl, nitro, amino, C,-C 6 alkyl, C,-C 6 alkoxy, C 2 -C 6 alkanoylamino, formylamino and C,-C 6 alkoxy-carbonyl; then W is other than -CONH-; and wherein when at the same time X is -NR 4 -, in which R 4 is C,-C 6 alkyl, benzyl, pyridyl or a phenyl ring optionally substituted by one or two substituents chosen from halogen, C,-C 6 alkyl, C,-C 6 alkoxy, nitro, amino, formylamino, C 2 -C 6 alkanoylamino or trifluoromethyl; R and R, are hydrogen, halogen, hydroxy, nitro, amino, C,-C 6 alkyl, C,-C 6 alkoxy, formylamino and C 2 -C 6 alkanoylamino; R 2 and R 3 taken together form a C 2 -C 6 alkylene -CH=CH-CH= or -O-(CH 2 ) n - chain as defined above; m is zero or an integer of 1 to 6 and Q is C,-C, 4 alkyl, or m is zero, 1 or 2 and Q is phenyl ring optionally substituted by one or two substituents chosen from halogen, hydroxy, trifluoromethyl, nitro, amino, C,-C 6 alkyl, C,-C 6 alkoxy, C 2 -C 6 alkanoylamino and formylamino; then W is other than -CONH-. 6. A compound as defined in claim 5 wherein, in formula (IA), W is -CONH-, -SO 2 - or -CO- X is O or NR 4 , wherein R 4 represents hydrogen, C,-C 4 alkyl, benzyl, pyridyl, tetrahydropyranyl or phenyl, the phenyl being unsubstituted or substituted by one or two substituents, which are the same or different and are chosen independently from halogen, trifluoromethyl, C,-C 4 alkyl, C,-C 4 alkoxy, nitro, amino, hydroxy, formylamino, C 2 -C 4 alkanoylamino and C,-C 4 alkoxy-carbonyl.; each of R, R, and R 2 , which are the same or different, is independently: hydrogen, halogen, hydroxy, trifluoromethyl, amino, C,-C 4 alkyl, C,-C 4 alkoxy, C 2 -C 4 alkanoylamino or C,-C 4 alkoxycarbonyl; and R 3 is hydrogen; or R 2 and R 3 taken together form a C 2 -C 4 alkylene , -CH=€H-CH= or -O-(CH 2 ) n - group in which n is 1 or 2; m is zero or 1 ; and Q is C,-C 4 alkyl or a phenyl, oxazole, isoxazole, thiazole, pyrazole, imidazole, 1,2,3- triazole, 1,2,4-triazole, 1,2,4-oxadiazole or 1 ,3,4-thiadiazole ring unsubstituted or substituted by one or two substituents which are the same or different and are selected from halogen, hydroxy, trifluoromethyl, nitro, amino, C,-C 4 alkyl, C,-C 4 alkoxy, C 2 -C 4 alkanoylamino and C,-C 4 alkoxy-carbonyl. 7. A compound as defined in claim 5 wherein, in formula (IA), X is -NR 4 - in which R 4 is as defined in claim 5, W is -CONH-, Q is a heteromonocyclic ring, containing two or three heteroatoms chosen from oxygen and nitrogen, optionally substituted by one or two substituents which are the same or different and are independently chosen from halogen, hydroxy, trifluoromethyl, nitro, amino, phenyl, benzyl, C,-C 6 alkyl, C,-C 6 alkoxy, C 2 -C 6 alkanoylamino, formylamino and C,-C 6 alkoxy-carbonyl; and m, R, R,, R 2 and R 3 are as defined in claim 5. 8. A compound as defined in claim 5 wherein, in formula (IA), W is -SO 2 - or -CO-, X is -0- or -NR 4 - in which R 4 is as defined in claim 5 and m, R, R„ R 2 , R 3 and Q are as defined in claim 5.. 9. A compound as defined in claim which is selected from 2-Benzenesulfonyl-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2-c]pyrazol-9-yl)- 3 -oxo-propanenitrile; 2-Benzoyl-3-(7-methyl-2,3,7,9b-tetrahydro-lH-acenaphtho[l,2-c]pyrazol-9-yl)-3-oxo- propanenitrile; 2-Cyano-N-phenyl-3-(l,2,3,9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)- 3 -oxo-propanamide ; 2-Benzenesulfonyl-3-(l -methyl- l ,4-dihydro indeno[l,2-c]pyrazol-3-yl)-3-oxo- propanenitrile; 2-Benzoyl-3-(l -methyl- 1 ,4-dihydro-indeno[l,2-c]pyrazol-3-yl)-3-oxo-propanenitrile; 2-Cyano-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-N-phenyl-3-oxo-propanamide; 2-Benzenesulfonyl-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-3-oxo-propanenitrile; 2-Benzoyl-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-3-oxo-propanenitrile; 2-Benzoyl-3-(l ,2,3,9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)-3-oxo- propanenitrile; 2-Benzenesulfonyl-3-(l ,2,3,9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)- 3-oxo-propanenitrile; 2-Benzoyl-3-(7-methyl-l ,2,7,9b-tetrahydro-3-oxa-7,8-diaza-cyclopenta[a]acenaphthylen- 9-yl)-3-oxo-propanenitrile; 2-Benzenesulfonyl-3-(7-methyl-l,2,7,9b-tetrahydro-3-oxa-7,8-diaza- cyclopenta[a]acenaphthylen-9-yl)-3-oxo-propanenitrile; 2-Cyano-3-(7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)-3-oxo-N-phenyl-propanamide; 2-Benzoyl-3-(7-methyl-7H-acenaphtho[l,2-c]pyrazol-9-yl)-3-oxo-propanenitrile; 2-Benzenesulfonyl-3-(7-methyl-7H-acenaphtho[l,2-c]pyrazol-9-yl)-3-oxo-propanenitrile; 2-Cyano-N-benzyl-3-( 1 ,2,3,9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)- 3 -oxo-propanamide; 2-Cyano-N-butyl-3-(l ,2,3,9b-tetrahydro-7-oxa-8-aza-cyclopenta[a]acenaphthylen-9-yl)-3- oxo-propanamide; 2-Cyano-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l-yl)-N-benzyl-3-oxo-propanamide; and 2-Cyano-3-(8H-3-oxa-2-aza-cyclopenta[a]inden-l -yl)-N-butyl-3 -oxo-propanamide; and the pharmaceutically acceptable salts thereof. 10. A compound selected from 2-Cyano-3-(l -methyl- 1 ,4-dihydro-indeno [ 1 ,2-c]pyrazol-3-yl)-N-(4-methoxy-phenyl)-3- oxo-propanamide; 2-Cyano-3 -(7-fluoro- 1 -methyl- 1 ,4-dihydro-indeno [ 1 ,2-c]pyrazol-3-yl)-N-pheny 1-3 -oxo- propanamide; 2-Cyano-3 -(1 -methyl- 1 ,4-dihydro-indeno[ 1 ,2-c]pyrazol-3-yl)-N-benzyl-3-oxo- propanamide; and 2-Cyano-3-(l -methyl- l,4-dihydro-indeno[l,2-c]pyrazol-3-yl)-N-butyl-3-oxo- propanamide; and the pharmaceutically acceptable salts thereof. 1 1. A compound as defined in claim 5 or 10, for use in a method of treatment of the human or animal body by therapy. 12. A compound as claimed in claim 1 1 for use as a kynurenine-3-hydroxylase inhibitor. 13. A pharmaceutically composition which comprises a pharmaceutically acceptable carrier and/or diluent and, as an active principle, a compound as defined in claim 5 or claim 10 14. A compound of formula (II) wherein X is O and R, R,, R 2 and R 3 are as defined as in claim 1 and Z is a derivative of a carboxy group, provided that when R 2 and R 3 taken together form a -CH=CH-CH= chain, and R and R, are hydrogen, then Z is other than C,-C 2 alkoxy-carbonyl. 15. A compound of formula (IV) wherein X is O and R, R„ R 2 and R 3 are as defined in claim 1.

Inventors: HEIDEMPERGHER FRANCO, PEVARELLO PAOLO, SPECIALE CARMELA, TOMA SALVATORE, VARASI MARIO, HEIDEMPERGHER, FRANCO, PEVARELLO, PAOLO, SPECIALE, CARMELA, TOMA, SALVATORE, VARASI, MARIO
Applicants: HEIDEMPERGHER FRANCO, PEVARELLO PAOLO, PHARMACIA & UPJOHN SPA, SPECIALE CARMELA, TOMA SALVATORE, VARASI MARIO, HEIDEMPERGHER, FRANCO, PEVARELLO, PAOLO, PHARMACIA & UPJOHN S.P.A., SPECIALE, CARMELA, TOMA, SALVATORE, VARASI, MARIO
Application year: 1998
Main classification: C07D231
IPC codes: A61K31, A61P25, A61P43, C07D231, C07D261, C07D491, C07D498