TRICYCLIC 3-OXO-PROPANENITRILE DERIVATIVES AND PROCESS FOR THEIR PREPARATION

Abstract: Compounds having general formula (I), wherein X represents an oxygen atom or a -S(O)n-group, wherein n is zero, 1 or 2; R represents C1-C6 alkyl, pyridyl or substituted or unsubstituted phenyl; R2, R3 and R4 are as defined herein; and Q represents hydrogen, carboxy, C2-C7 alkoxycarbonyl or a -CON(Ra)'Rb group wherein Ra and Rb are as defined herein; and their pharmaceutically acceptable salts have immunomodulating activity and are useful in particular as immunostimulating agents, in the treatment of neoplastic diseases and acute and chronic infections of both bacterial and viral origin in mammals.

Description: TRICYCLIC 3-OXO-PROPANENITRILE DERIVATIVES AND PROCESS FOR THEIR PREPARATION The present invention relates to tricyclic 3-oxo- propanenitrile derivatives, to a process for their preparation and to pharmaceutical compositions containing them. The compounds of the invention have the general form wherein X represents an oxygen atom or a -S(0) - group, wherein n is zero, 1 or 2; R represents : -C 6 alkyl, pyridyl or phenyl, the phenyl being unsubstituted or substituted by one or two substituents chosen independently from halogen, trifluoro ethyl, C ! ~ c 6 alkyl, C 1 -C 6 alkoxy, nitro, a ino, formylamino and C 2 -C 8 alkanoylamino; R' is a.0 ), h.y..d.rogen, d,i_(.C„ x -C„ 6 alkyl ).-amino or a -CH 2 N/ \ R" group wherein R' and R", the same or different, is C 1 -C 6 alkyl or R' and R", taken together with the nitrogen atom to which they are linked, form a heterocyclic ring which is selected from N-pyrrolidinyl, N-piperazinyl , hexahydroazepin-1-yl, thiomorpholino, morpholino and piperidino and which is unsubstituted or substituted by C j -C j alkyl; b° ) CH 2 OH, CHO, COOH or C 2 -C, alkoxycarbonyl; c° ) a CONHCH-COOR d group wherein R d is hydrogen or C t -C 6 alkyl and R c is hydrogen, phenyl or the side-chain of an α-aminoacid; d° ) a group, wherein R is as defined above; e° ) a , a -CH 2 OCO(CH 2 ) n C00R d or a -NHCO(CH 2 ) n C00R d group wherein n and R d are as defined above; f c ) a -CH-N-OR^ group wherein R' χ is hydrogen or a -CH 2 COOH group; g° ) a -CH«N-NH-R' 2 group wherein R' 2 is hydrogen, -CH 2 CH 2 OH, C 2 or C 3 alkoxycarbonyl or a -(CH 2 ) p -R' 3 group wherein p is 1 or 2 and R' 3 is COOH or C 2 -C 7 alkoxycarbonyl; h° ) a -CH»N-N«CH-N group wherein R' and R" are as defined above; or k° ) a -N-CH-N group wherein R' and R" are as defined \ R n above; 1°) a C -C alkoxycarbonyl group substituted by a -N group vfaerein R « and R" are as defined above; each of R 2 and R 3 is independently: a) hydrogen, halogen or C j -C 8 alkyl; b) hydroxy, C j -C 8 alkoxy or C 3 or C 4 alkenyloxy; or c) nitro, a ino, formylamino or C 2 -C β alkanoylamino; R 4 represents hydrogen or C l -C 6 alkyl; and Q represents hydrogen, carboxy, C 2 -C 7 alkoxycarbonyl or a R -CO group wherein β represents hydrogen or C 1 -C 2 r ) alkyl and R b represents C 1 -C a0 alkyl, a -CH-COOR d group R = wherein R c and R d are as defined above or a -(A)_ . -R 5 group wherein m is zero or 1, A is a C 1 -C fi alkylene chain and R 5 is: a') C 5 -C β cycloalkyl; b' ) pyridyl, unsubstituted or substituted by one or two substituents chosen independently from halogen, C χ -C 6 alkyl and C 1 -C 6 alkoxy; c') phenyl, unsubstituted or substituted by one or two substituents independently chosen from halogen, CF 3 , Q χ -C 6 alkyl, C 1 -Z 6 alkoxy, amino, nitro, formylamino, C 2 -C a alkanoylamino, ditC j -C 8 alkyl )-amino, hydroxy, formyloxy and C 2 ~ C 8 alkanoyloxy; d') phenyl substituted by a -CH 2 0H, COOH, C 2 -C 7 R' alkoxycarbonyl or a -CH 2 -N group wherein R' and R" are as \ R „ defined above and optionally by another substituent chosen from halogen, C χ -C 8 alkyl, C 1 -C 8 alkoxy, amino, nitro, formylamino, 2 -C 8 alkanoylamino, hydroxy, formyloxy and C 2 -C 8 alkanoyloxy, or e') 2-thienyl, 2-furyl or 1- { C 1 -C 6 alkyl)-pyrrol-2-yl; or f) a heterocyclic ring which is selected from 2-pyrimidyl, 2-thiazolyl and 3-isoxazolyl and which is unsubstituted or substituted by ^-C 8 alkyl; and the pharmaceutically acceptable salts thereof; and wherein, when R 1 is hydrogen, then Q is only a -CON[ group in which R β is as defined above and either R b is a -CH-COOR d group wherein R c and R d are as defined above or R b is a") a -(CH 2 ),-R' 5 group wherein z is zero, 1 or 2 and R' 5 is as R 5 defined above under d'), e') or f) or b") a CH-R 5 or -A'-R 5 group, wherein A' is a C 3 -C 8 alkylene CH 3 chain and R 5 is as defined above. The present invention includes within its scope all possible isomers, stereoisomers and optical iso ers and their mixtures, and the metabolites and the metabolic precursors or biprecursors of the compounds of formula (I). It has to be noticed that the compounds of formula (I) may be represented also by a tautomeric structure, namely the enol structure of formula (la) wherein X, R, R 1# R 2 , R3, R4 and Q are as defined above. However, the compounds of formula (la) , which fall within the scope of the present invention too, are described in the present specification as cαipσunds of formula (I) . A halogen atom is preferably chlorine or fluorine. The alkyl, alkylene, alkanoyloxy, alkoxy and al-kanαylamino groups may be branched or straight chain groups. A C--L-C20 alkyl group is preferably a C^-CQ alkyl group. A O^- g alkyl group is, e.g., methyl, ethyl, propyl, iscpropyl, butyl or tert.butyl, more preferably methyl, ethyl or tert.butyl, in particular methyl or ethyl. A C 3 or C 4 alkenyloxy group is preferably allyloxy. A C-^-Cg alkoxy group is, e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy or tert.butoxy, preferably it is methoxy, ethoxy or propoxy. A di(Cι-Cg alkyl)-amino is preferably a di(Cι~C4 alkyl)-amino group, in particular a di(C j or C2 alkyl)-amino one. A C5-C3 cycloalkyl group is preferably cyclσpentyl or cyclohexyl. A C 2 -C 8 alkanoylamino group is preferably acetylamino or propionyl- amino. A C 2 -C8 alkanoyloxy group is preferably acetoxy or propionyloxy. A C2-C alkoxycarbonyl group is preferably a C2-C5 alkoxycarbonyl group, in particular a C 2 or C3 alkoxycarbonyl one. A C 1 -C 6 alkylene chain is preferably a C-^^ alkylene chain, such as a —CH2-, ~( CH 2)2~' ~( CH 2)3~' ~ CH ~ or ~ H ~ c^ai 11 - CH3 C2H5 A C3-C6 alkylene chain is preferably a C 3 alkylene chain, in particular a -(CH 2 )3~ or a -CH-chain. In a -CH-COOR j j group, wherein is as C2H5 Rc defined above and ς , is as defined above except hydrogen, the asymmetric carbon atom to which -R j -, and -COOR jj are linked may have either the R or S configuration. The side-chain of an α-aminoacid is specifically the residue obtained from an α-aminoacid by removing the amino and the carboxy groups together with the α-carbon atom to which they are linked. The side-chain of an α-aminoacid as defined above is preferably the side-chain deriving from a naturally occurring aminoacid. Examples of such aminoacids are alanine, valine, leucine, isoleucine, phenylalanine, proline, hydroxyproline, serine threonine, cysteine, cystine, methionine, tryptcphan, tyrosine, asparagine, glut-amine, aspartic acid, glutamic acid, lysine, arginine, histidine and phenylserine. Preferred examples of side chains of the above mentioned, aminoacids are -CH 3 (deriving from alanine), -CH 2 CH(CH3) 2 (deriving from leucine) and -CH 2 CgH5 (deriving from phenylalanine) . Examples of pharmaceutically acceptable salts are either those with inorganic bases, such as sodium, potassium, calcium and alum__nium hydroxides, or with organic bases, such as lysine, arginine, N-methyl- glucamine, triei_hylamine, triei_harolamine, dibenzylamine, methyl- benzylamine, di-(2-etlιyl-he_^l)-amine, piperidine, N-ethylpiperidine, N-ethyl-morpholine, 3-jΛenethylamine, N-ben_^l-/3-phenethylamine, N-benzyl-N,N-di_tethylamine and the other acceptable organic amines, as well as the salts with inorganic, e.g., hydrochloric, hydrdbrcaiiic and sulphuric acids and wit organic acids, e.g. citric, tartaric, aleic, malic, fumaric, methanesulphonic and ethanesulphonic 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 bicprecursors (otherwise known as pro- drugs) of the cc∑trpounds of formula (I) , i.e., ccaipounds which have a different formula to formula (I) above, but which nevertheless upon administration to a human being are converted directly or in irectly in vivo into a cαtrpound. of formula (I) . Preferred. compounds of the invention are the ccnpounds of formula (I) , vzherein X is oxygen or a -S(0)p-group, in viiich p is zero or 1; R represents unsubstituted pyridyl or phenyl, unsubstituted or substituted by one or two substituents chosen -independently frcm halogen, trifluorαxiethyl, C 1 -C 4 alkyl, C1-C alkoxy, nitro, amino and C 2 -C 8 a___ka_rκ_ylamino; R.2 is a βo ) hydrogen, COOH, CHO, CH 2 0H, C 2 -θ7 alkoxycarbonyl or a or C alkyl, or R" ' and R 1 ^, taken together with the nitrogen atom to which they are linked, form a N-pyrrolidinyl, N-piperazinyl, morpholino or piperidino ring which is urisubstituted or substituted by methyl; b°°) a -CQNHCH-COOI^ group wherein I- is hydrogen or C^-Cg alkyl and R. *c is hydrogen, phenyl or the side-chain of an α-aminoacid as defined above; c°°) a -NHC0CH-NH 2 group, vrtierein R-. is as defined above; *c d°°) a -CH OO0(CH 2 ) n O0OR d or a -NHO0(CH 2 ) n O0OR c 3 group, wherein n and R- j are as defined above; e°°) a -OMI-OR^ group, wherein R'^ is hydrogen or a -CH 2 α00H group; f°°) a -CB=N-NHR'2 group, wherein R' 2 is hydrogen or -CH 2 CH2Η; g°°) a are as defined above; h°°) a C 2 -C 4 group substituted by a group, wherein R 111 and R^ are as defined above; R 2 and R 3 each ind-^endently is hydrogen, halogen, nitro, amino, hydroxy, C1-C alkyl or ^-C^ alkoxy; 4 represents hydrogen or C--L-C4 alkyl; Q represents hydrogen, C 2 -C 5 alkoxycarbonyl or a -CONR'aR'b group, wherein R' a is hydrogen or C^-Cg alkyl and R' j -, is C-^-Cg alkyl or a -CH-OOORg group, wherein Rg is hydrogen or C-^^ alkyl and R ς , is as *c defined above; or R' j -, is a -(A") m -R"5 group, wherein m is zero or 1, A" is a C1- 3 alkylene chain and R" 5 is: a' ' ') urisubstituted pyridyl or phenyl, unsubstituted or substituted by one or two substituents chosen independently from halogen, CF 3 , Cy-C^ alkyl, C ] - 4 alkoxy, hydroxy, nitro and di-^---^ alkyl) amino; R « • • b* ' ' ) phenyl, substituted by -CH 2 OH, OOOH or a -CH 2 -N / group, V wherein R* ' • and R 1 ^ are as defined above, and optionally by another substituent chosen frαm C1-C4 alkyl, C1-C alkoxy, hydroxy, formyloxy and C 2 -C 6 alkanoyloxy; or c 1 ' ') 2-thieπyl or 2-furyl; or d 1 * ') 2-thiazolyl or 3-isoxazolyl, wherein said heterocyclic rings may be unsubstituted or substituted by methyl; and the pharmaceutically acceptable salts thereof; and wherein, when -^ is hydrogen, then Q is only a -OOt-r group, wherein R' a is as defined above and R' j -, is (1) a -CH-COORg group wherein 1 . and Eg are as e defined above or (2) a -(CH^Jz- s' * ' group, vflierein z is zero, 1 or 2 and R5' • ' is as R" 5 defined above under b' • ') , c 1 ' ') and d' « •) , or (3) a -CH-R ,I 5 group (_H 3 wherein R H 5 is as defined above. More preferred ∞mpounds of the invention are the cc∑n σunds of formula (I) wherein X is oxygen or sulphur; R is phenyl, unsubstituted or substituted by a substituent selected frcm nitro, halogen, CF 3 , C1-C4 alkyl and C 1 -C 4 alkoxy; R;L is a 000 ) hydrogen, -COOH, -CHO, C -*---C5-alkoxyca_d-or-yl, or a wherein R' ' * and RT i V V are as defined above; each of R 2 and R 3 independently is hydrogen, halogen, nitro, amino, hydroxy, C1-C4 alkyl or C^-C^ alkoxy; b ooβ ) a -O-JNHCH-OOOR 1 ^ group, wherein R'^ is hydrogen or OL-C4 alkyl and Rς. is as defined above; c°°°) a -NHCDCH-NH 2 group wherein R-, is as defined above; , d oβo ) a -CH 2 0O0(CH2) n C0OR l d or a -NHO0(CH 2 ) n COOR' d group, wherein n and R' d are as defined above; e° 00 ) a group, wherein R 111 and R 1 are as defined above; R III f * "") a C2-C4 alkoxycarbonyl group substituted by a -N group, wherein R 111 and R 1 ^ are as defined above; R4 repre-sents hydrogen or methyl; Q represents hydrogen or a -αθNR" a R ,l ] - ) group, wherein R" a is hydrogen or C- j _-C 4 alkyl and R 11 ] -, is 0^-04 alkyl or a -CH-COOlg group wherein r^- and Rg are as defined above; *c or R"]-, is a -(CH 2 ) ~JR5 IV g^o p, wherein z is zero, 1 or 2 and R 1 ^ is a 1 ^) unsubstituted pyridyl or phenyl, unsubstituted or substituted by a substituent chosen from nitro, halogen, CF 3 , C1-C4 -alkyl, C--L-C alkoxy and di(C!-C alkyl)-amino; R l l l b 3 ^) phenyl, substituted by -CH 2 0H, -COOH or a -CH 2 N group, wherein R 1 ' * and * ^ are as defined above, and optionally by another substituent chosen from hydroxy and L-C4 alkoxy; or P 7 ) 2-thienyl or 2-furyl; d *) 2-thiazolyl or 3-isoxazolyl, iinsubstitu ed or substituted by methyl; and the pharmaceutically acceptable salts thereof; and wherein, when R j is hydrogen, then Q is a -α-WR ll a R ll j - ) group, wherein R" a is as defined above and R 11 ]-, is (1) a -CH-C0ORg group, wherein R ς . and g axe as defined above; or (2) a -(CH ) Z -R V 5 group, wherein z is as defined above and R V 5 is as R 1 ^ defined above under b 1 ^) , F ) or d 7 ) . Examples of preferred compounds of the invention are: N-[2-cyano-3-(1,4-dihydro-l-phenyl-[1]-benzσthiopyrano[4,3-c]pyrazol- 3-yl]-3-oxo-prqpanσyl]-glycine, methyl ester; N-[2-cyarκ_>-3-(l,4-d-_hyd__O-l-phenyl^ yl]-3-oxo-propar_qyl]-DL-leucine, methyl ester; N-[2-cyano-3- (1, 4-d__hyd__o-l-pher^l-[l]-benzo1_hic-pyrano[4 , 3-c]pyrazol-3- yl]-3-<)jα^p-_t-paι^l]-D] pherylalanine, methyl ester; N- [2-cyano-3- (1 , 4-d_ihydro-l-phenyl- [1] -benzσthicpyrano [4 , 3-c] pyrazol-3- yl]-3-oxc^propan ^l]-DIj-pher lglyc-lne, methyl ester; 2-cyano-3- (1, 4-dihydro-l-phenyl- [1] -benzσthiopyrano[4 , 3-c]pyrazol-3- yl] -3-oxo-N- (2-theπyl) -prcpanamide; 2-cyano-N- (2-furfuryl) -3- (1, 4-d-lhydro-l-pheπyl- [1] -benzothicpyrano [4, 3-c]pyrazol-3-yl) -3-oxo-prcpanamide; 2-cyano-3-(8-fluo__o-l,4-d__hyd-_x>-6-mo--phol-lncs^^ pyrano [4 , 3-c]pyrazol-3-yl) -3-oxo-N-phenyl-propanamide; 2-cyano-3- (1, 4-*--'d_ihyd__x -8--To:i-ph^ [ 1] -benzσpyrano [4 , 3-c]pyrazol-3-yl) -3-oxo-N-phenyl-propanamide; 2-cyano-3-(1,4-d_Lhydro-l-phenyl-[l]-benzσthicpyrano[4,3-c]pyrazol-3- yl)-N-(2-mo__pholincπιethyl-benzyl)-3-oxo-propanamide; N-[2-cyano-3-(1,4-*---d-Lhydro-l-pheπyl-[1]-benzothicpyrano[4,3-c]pyrazol-3- yl)-3-oxo-prαpanc5yl]-DIr-leucine; 2-cyano-3-(8-ethoxycarbonyl-l,4-d-lhydro-l-phenyl-[1]-benzσthiopyrano [4,3-c]pyrazol-3-yl)-3-oxo-N-phenyl-prcpanamide; 2-cyano-3-(6-ethoxy-carbonyl-l,4-d-lhydro-l-phenyl-[1]-benzαthiqpyrano [4,3-c]pyrazol-3-yl)-3-oxo-N-phenyl-propanamide; N-[l,4-dihydro-l-phenyl-3-(2-phenylcari-am-yl-cyanoa<--etyl)-[1]-benzo- tbάcpyrarκD[4,3-c]py--azol-8-yl]Cei-±xD-^l'^lyc-Lne methyl ester; N- [1, 4-d-iiiydro-l-phenyl-3- (2-phenyl- a_ Damqyl- yanoacetyl) - [1 ] -benzo- t_r_iopyrano[4,3-c]pyrazol-6-yl]ca-dx>-γl-^lycine methyl ester; 2-cyano-3- ( 8-^thoxalylamino-l , 4-dihydro-l-phenyl- [1] -benzothicpyrano [4 ,3-c]pyrazol-3-yl) -3- 3Xo-N-pher^l-p--t-panamide; 2-cyano-3-(1,4-dihyd__x3-8-oxalaπ no-l-phenyl-[1]-benzothicpyrano[4,3-c] pyrazol-3-yl) -3-oxo-N-pherιyl-prcpanamide ; 2-cyano-3- (1, 4-d_ihyd__x_>-8-N,N-d-imethylaιr_inoethoxy^ - benzσthicpyraiK) [4 , 3-c]pyrazol-3-yl) -3-oxo-N-pherγl-prc_ρanamide; 2-cyano-3- (1, 4-^_l__hyd__x>-6-N,N-d___rethylam____κ_^^ - benzothicpyrano[4,3-c]pyrazol-3-yl)-3-oxo-N-pherιyl-propanamide; and the pha__maceutically acceptable salts thereof, in particular the sodium and the potassium salts. The ccrapσunds of formula (I) and the salts thereof can be prepared by a process comprising; a) reacting a compound of formula (II) wherein X, R, R , R , R and R are as defined above and Y is carboxy or a reactive derivative of a carboxy group, with a compound of formula (III) wherein 0' is as 0 defined above, except carboxy, so obtaining a compound of formula (I), wherein Q is as defined above ex¬ cept carboxy; or b) reacting a compound of formula (IV) COCHIN (IV) - 12 - whereir X, R, R , R , R and R are as defined above, with a compound of formula (V) R -N=C=0 (V) 0 wherein R is as defined above, so obtaining a compound of formula (I) wherein 0 is a -CONHR. group, wherein R is as defined -- b b above; or c; reacting a compound of formula (VI) wherein X, R, R , R , R and R are as defined above and Z is a react¬ ive derivative of a carboxy group, with a compound of formula (VII) (VII) wherein R a and fc are as defined above, so obtaining a cxmpαund of formula (I) wherein Q is a and are as defined above; or d) hydrolysing a compound of formula (I) , wherein Q is C 2 -Cy alkoxy¬ carbonyl or a -O0N CH-COOR^ group, in which R a and R ς . are as • Ra c defined above and ^ is C^-Cg alkyl, so as to obtain the corresponding compound of formula (I) , wherein Q is a free carboxy group or a -αoN — CH-αooH I I R a -Re group, in which R a and ϊ . axe as defined above; and, if desired, converting a compound of formula (I) into another compound of formula (I) and or, if desired, converting a cαπpound of formula (I) into a pharmaceutically acceptable salt and/or, if desired, converting a salt into a free ccapound, and/or, if desired, separating a mixture of isomers of a compound of formula (I) , into the single isomers. When Y is a reactive derivative of a carboxy group, it is, for example, a halocarbonyl group, preferably a chlorocarbonyl group, or a C 2 -C 7 al-koxycarbonyl group, preferably a C 2 or C 3 alkoxycarbonyl group. The reaction between a compound of formula (II) wherein Y is carboxy and a compound of formula (III) may be carried cut, for example, in the presence of a condensing agent such as diethyl cyanophosphonate, in the presence of a base such as triethylamine, in an inert solvent such as d-lmethylformamide at a terrperature varying between about 0°C and about 50 °C. The reaction between a ccurpound of formula (II) wherein Y is a reactive derivative of a carboxy group and a compound of formula (III) may be carried out, for example, in the presence of a strong base such as sodium hydride, potassium t.butoxide, thallous ethoxide, in an inert solvent such as 1,2-dimethoxyethane, dioxane, d-L-ret-hylfonnamide, at a temperature varying between about 0°C and about 100°C. The reaction between a cαπpαund of formula (IV) and a compound of formula (V) may be carried cut, for example, in the presence of a base such as sodium hydride or triethylamine, in an inert solvent such as toluene, dioxane, tetrahydrofuran, diirethylfoπtiamide, at a temperature varying between about 0°C and about 100°C. In the compounds of formula (VT) , Z is, for example, a halocarbonyl group, preferably a chlorocarboπyl group, or a C - alkoxycarbonyl group, preferably a C -C3.alkoxycarbonyl group. The reaction between a compound of formula (VT) , where Z is a halocarbonyl group, and a compcund of formula (VTI) may be carried out, for example, in an inert solvent such as dichloroethane, dioxane, dimethylformamide, in the presence of pyridine or triethylamine as acid acceptor, at a temperature varying between about 0°C and about 100°C. The reaction between a compound of formula (VT) , wherein Z is C^-Cg alkyl ester, and a compound of formula (VII) may be carried cut, for example, by heating at the reflux temperature in an aromatic hydrocarbon such as toluene or xylene, preferably distilling off slowly together with the diluent the free C j _-Cg alkyl alcohol generated during the reaction. Hydrolysis of a compound of formula (I) , wherein Q is a C 2 -C7 alkoxy¬ carbonyl group or a -CON CH-OOOI- group in which R a and R ς . are as a , defined above and R- j is O^-Cg alkyl, according to process-variant d) above, may be performed by selective basic hydrolysis, using e.g. aqueous sodium or potassium hydroxide in a solvent such as ethanol or d_Lmethylfo__mamide, at a teπperature varying between about 0°C and about 80°C. A α_3_rpσund of formula (I) may be converted, as stated above, into another compound of formula (I) by known methods; for example, in a ccsrpcund of formula (I) a nitro group may be converted into an amino group by treatment, for example, with stannσus chloride in concentrated hydrochloric acid, using, if necessary, an organic oosolvent such as acetic acid, dioxane, tet_rahyd__Ofuran, at a temperature varying between room teirperature and about 100°C. Furthermore, for example, an amino group may be converted into a formylamino or a C -Cg alkancylamino group, for example by reacting with formic acid or with the suitable C -C 8 alkancyl anhydride, without any solvent or in an organic solvent such as dioxane, di-methylformamide, tetrahydrofuran, usually in the presence of a base such as pyridine or triethylamine, at a temperature varying between 0°C and about 100 β C. Furthermore, for example, a -NH 2 or a or into a R 1 -CIMϊ-l^=CH-N group, wherein R* and R" axe as defined above, R" respectively, by reaction with a quaternary nitrogen compound of formula (VTIa) R' \(+) ( " ) N N _HC1 Cl (Vila) / R" wherein R' and R" are as defined above, in an organic inert solvent, such as dioxane, tetrahydrofuran, chloroform, dichloromethane, 1,2- dichloroethane, benzene or toluene, in the presence of a tertiary amine, such as triethylamine, at a temperature varying between about -20°C and room terrperature, according to the experimental procedure described in GB-A-1,293,590 and in US-A-4,447,432. Furthermore, for example, an amino group may be converted into a -NH00CHNH 2 group, Be wherein ς - is as defined above, by reaction with a suitably protected α-aminoacid of formula H0OC-CH-NHE, wherein R- is as defined above and e E is a protective group, such as a benzyloxycarbonyl or a tert-butoxy- carbonyl group, in the presence of dlcyclc-he-^lcarbodiimide as condensing agent, in an inert organic solvent such as dioxane, tetra¬ hydrofuran or acetonitrile, at a temperature varying between about 0 β C and room temperature, so as to obtain the protected -NHCXXHNHE group, Re wherein R<-. and E are as defined above, which in turn is deprotected using well known methods in organic chemistry. Furthermore, for example, a carboxy group may be converted into a -CC ICHCOOH group, e wherein R ζ , is as defined above, by reaction with an esterified α-aminoacid of formula HN--* H-α0OR l d , wherein R' d is ^-Cg alkyl and R-, *c is as defined above, in the presence of dicyclohexylc-arbodi-lmide as condensing agent, in an inert organic solvent such as dioxane, tetra- hydrofuran or acetonitrile, at a teπperature varying between about 0°C and room teπperature, so as to obtain the esterified -CC-WHCH-COOR' fj *c group, wherein R. and R* are as defined above, which in turn is hydrolyzed to give the -C ICH-OCx-H group, wherein R Q is as defined Re above, following methods well knewn in the art, for example, those described for the process variant d) above. Furthermore, for example, an group, a -CH 2 OO0(CH 2 ) n C0OR l d group or a -NHC0(CH 2 ) I1 σ00R , d group, wherein n and R' are as defined above, may be converted into the corresponding -COOH, -CHO00(CH 2 ) n O0CH and -NHOO(CH 2 ) n G0CH group, respectively, wherein n is as defined above, by treatment with aqueous sodium or potassium hydroxide in a solvent such as dioxane, methanol, ethanol or dimethyl- for amide, at a temperature varying between about 0°C and about 80°C. The optional esterification of a free carboxy group as well as the optional conversion of a carboxylic ester into the free carboxy derivative may be carried cut according to knewn methods in organic chemistry. Process-variants b) and c) described above may be considered as examples of conversions of a compound of formula (I) into another compound of formula (I) too. Also the optional salification of a compound of formula (I) as well as the conversion of a salt into the free cempound and the separation of a mixture of isαxers into the single iscπers may be carried cut by conventional methods. For example, the separation of optical isomers may be carried out by salification with an optically active base or acid and by subsequent fractional crystallization of the diastereoiscπeric salts, followed by recovery of the optically active iscπeric acids or, respectively, bases. The compounds of formula (II) , wherein Y is a C 2 -C 7 alkoxycarbonyl group, may be prepared, according to the methods described in EP-A-274443, for example, by reacting a ccπpcund of formula (VIII) wherein X, R;L, R 2 , R 3 and R4 are as defined above and Rg is C- j^ -C alkyl, preferably C 1 -C 2 alkyl, with a ccπpcund of formula (IX) R-NH H 2 (IX) wherein R is as defined above. The reaction between a compound of formula (VTII) and a cx-mpcund of formula (IX) may be carried cut, for example, in a solvent such as C j -Cg alkyl alcohol, dioxane, tetrahydrofuran, dimethylformamide, acetic acid, at a temperature varying between about 0°C and about 150°C. The cxjmpσunds of formula (II) , wherein Y is carboxy may be prepared, for example, by hydrolysis of the «_χjrresponding compounds of formula (II) wherein Y is C 2 -C 7 alkoxycarbonyl, a<_x_ording to standard methods well known in the art, for example, by basic hydrolysis, carried out e.g. by treatment with sodium or potassium hydroxide in a solvent such as water, O^-Cg alkyl alcohol, dioxane, diirethylformamide and their inixtures, at a terrperature varying between about 0°C and about 80°C. The ccmpounds of formula (II) , wherein Y is halocarbonyl, preferably chlorocarbonyl, may be prepared, for example, fcy reaction of the corresponding ccmpσund of formula (II) , wherein Y is carboxy, with a suitable acid halide, for example oxalyl chloride, thioπyl chloride, PCI3, PBr 3 , in an inert solvent such as ether, benzene, dichloro- ethane, dioxane or without any solvent, at a temperature varying between about 0°C and about 100°C. The cx-mpσunds of formula (III) are, in seme cases, commercially available products, or may be prepared by methods well kncrøn in the art. For example, a ccsrpcund of formula (III), wherein Q is a i_y reacting cyanoacetic acid with a compound of formula (VII) in the presence of a condensing agent such as dicyclchexlcarixx_li-_mide, 1,1- car--∞r-yldiimadazole and the like, in an inert organic solvent such as benzene, dioxane, acetonitrile, at a l^mperature varying between about 0°C and about 50°C. The ccmpounds of formula (IV) are ccmpounds of general formula (I) , wherein Q is hydrogen and may be obtained by process a) above, for example, by reacting a cσmpαund of formula (II) , wherein Y is C 2 -C 7 with acetonitrile, in the presence of a strong base e.g. , sodium hydride, potassium tert.butoxide, in an inert organic solvent such as benzene, dioxane, tetøahydrofuran, at a teirperature varying between about 0°C and about 100°C. The compounds of formula (VI) , wherein Z is C 2 -C 7 alkoxycarborryl, are compounds of general formula (I) wherein Q is C 2 -C 7 alkoxycarbonyl and may be obtained by process a) above, for example, by reacting a cαrrpound of formula (II) with a -compound of formula (X) he ein R 7 is C^-Cg alkyl, using the -same experimental conditions as described above for the reaction between a compound of formula (II) and a cσmpαund of foππula (III) . The cxxtpounds of formula (IV) , wherein Z is halocarbonyl, may be prepared, for example, by basic hydrolysis of a cσmpcund of formula (VI) , wherein Z is C 2 -C 7 alkoxycarbonyl, using, for example, the same e-φerimental conditions described above for the hydrolysis of the compounds of formula (II) , wherein Y is C 2 -C 7 alkoxycarbonyl, in order to obtain the corresponding carboxy derivative, which in turn may be transformed into a cαπpound of formula (VI) , wherein Z is halocarbonyl, preferably chlorocarbonyl, using, for example, the same experimental conditions described above for the preparation of the compounds of formula (II) , wherein Y is halocarbonyl. The compounds of formula (VTII) may be prepared, for example, by reacting a compound of formula (XI) 9/12638 - 20 — wherein X, R , R , R and are as defined above, with a compound of formula (XII) wherein each of R and R', being the same or different, is C -C c 8 8 1 6 alkyl, preferably methyl or ethyl. The reaction between a compound of formula (XI) and a compound of formula (XII) may be carried out, for example, in the presence of a strong base such as sodium methoxide, sodium ethoxide, sodium hydride, potassium tert.butoxide, in an organic solvent such as C 1-Cb_ alkyl alcohol, benzene, dioxane, dimethylformamide, at a temperature varying between about 0°C and about 100°C. The ccmpounds of formula (XE) may be prepared by synthetic methods well known in the art, for example, according to the methods described in J.A.C.S. 76, 5065 (1954) and in "Advances in Heterocyclic <_hem-Lst--y", 18, 59 (1975). The ccmpounds of foππula (V) , (VII) , (IX) , (X) and (XII) are known products and may be prepared fcy conventional methods: in some cases they are cxsmmercially available products. When in the ccmpounds of the present invention and in the intermediate products thereof, groups are present, such as COOH, NH 2 , CHO and/or OH, which need to be protected before submitting them to the reactions described above, they may be protected before the reactions take place and then deprσtected, according to well known methods in organic chemistry. The ccmpounds of foππula (I) possess -lmmur _modulating activity and can be used, for example, as -Lmn inostimπαlating agents e.g. , in the treatment of acute and chronic infections of both bacterial and viral origin, alone or in association with antibiotic agents, and in the treatment of neoplastic diseases, alone or in association with antitumoral agents, in mammals. The -LmrrD__ncaιιodulating activity of the compounds of the invention is proved, for example, by the fact that they are effective in potentiating the cytotoxic activity of the macrophages towards tumour cells in vitro. The experimental procedure to evaluate this activity is as follows: groups of 4 mice are treated i.p. with the tested compounds and then, seven days later, peritoneal cells are collected and plated for 2 hours at 37 "C. After this period the walls are washed to eliminate the non adherent cells, tumour target cells are then added and the incubation is prolonged for 48 hours. At the end of this period the target cells viability is evaluated by a colorimetric method and quantified at 570 nm. The cσmpcunds of the invention can be safely used in medicine by virtue of their negligible toxicity. The therapeutic regimen for the dif erent clinical syndromes must be adapted to the type of pathology taking into account, as usual, also the route of administration, the form in which the compound is administered and the age, weight and conditions of the subject involved. The oral route is employed, in general, for all conditions requiring such compounds. Preference is given to intravenous injection or infusion for the treatment of acute infections. For the maintenance regimens the oral or parenteral, e.g., -Intramuscular or suibcutaneous, route is preferred. For these purposes the compounds of the invention can be administered orally at doses ranging e.g. , from about 0.5 to about 10 g/kg of body weight per day in adult humans. Doses of active ccmpounds ranging e.g., frcm about 0.2 to about 5 mg/kg of body weight can be used for parenteral administration in adult humans. Of course, these dosage regimens may be adjusted to provide the optimal therapeutic response. The nature of the pharmaceutical compositions containing the ccmpounds of this invention in .association with pharmaceutically 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 compounds of the invention may be ad nistered in the form of aqueous or oily solutions or suspension, tablets, pills, gelatine capsules, syrups, drops or suppositories. Thus, for oral administration, the pharmaceutical compositions containing the ccmpounds 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, carbojcyethylcellulose, gum-arabic, tragacanth, polyvinylpyrrolidone; 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 kncwn manner, for example by means of mixing, granulating, tabletting, su_gar-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, carbσxy- ethylcellulose, or polyvinyl alcohol. The suspensions or solutions for iπtramαscular injections may contain together with the active compound a pharmaceutically acceptable carrier, e.g., sterile water, olive oil, ethyl oleate, glycols, e.g., prcpylene glycol, and if desired, a suitable amount of licodaine 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 aqueous isotonic saline solutions. The suppositions may contain together with the active compound a pharmaceutically acceptable carrier, e.g., α-x_x»-butter, polyethylene glycol, a polyoxyethylene sorbitan fatty acid ester surfactant or lecithin. The following examples illustrate but do not limit the invention: Example 1 l,4-D-ihydro-l-phenyl-[l]-benzσthi^^ acid (2 g) is reacted with thionyl chloride (1 ml) in dioxane (40 ml) at reflux teπperature for 2 hours. After cooling the solution is evaporated to dryness in vacuo to give l,4-dihydro-l-phenyl-[l]- benzothicpyι_ano[4,3-c]pyrazole-3-carbonyl chloride as crystalline residue. The crude product is dissolved in anhydrous dioxane (15 ml) and reacted for 2 h under stirring at room temperature with the carbanion obtained by treatment of cyanacetic acid, 2-morphol-Lncmethyl- benzylamide (1.95 g) with 50% sodium hydride (0.39 g) in anhydrous dioxare/d-lmethylformamide 9:1 (20 ml) at room teπperature. The reaction mixture is then diluted with ice water and acidified to pH 3 with citric acid. The precipitate is filtered and dissolved in CHCI3. The organic solution is washed with 2% citric acid solution and then with water. Evaporation to dryness in vacuo gives a residue which is purified over a flash column using <-hloroform^methanol 10:0.5 as eluent. Final crystallization from chloroforiηmethanol yields 1.1 g of 2-cyano-3-(1,4-dihydro-l-phenyl-[1]-benzothicpyrano[4,3-c]pyrazol-3- yl)-N-(2-mo-_pholincmethyl-benzyl)-3-oxo-p--opanam m.p. 243-245°C. By proceeding analogously the following cxmpounds can be prepared: 2-cyano-3-(1,4-dihydro-l-phenyl-[1]-benzothicpyrano[4,3-c]pyrazol-3- yl)-N-(3-morpholinσmethyl-benzyl)-3-oxo-propanamide, mp.150°C dec. ; 2-cyano-3-(1,4-dihydro-l-phenyl-[1]-benzothiopyrano[4,3-c]-pyrazol-3- yl)-N-(3-d_uιethylam--τcιrrethyl-benzyl)-3-oxo-propanamide; 2-cyano-3- ( 1 , 4-dihydro-l-phenyl- C J-benzothiopyrano C 4 , 3-c] pyrazol-3-yl ) -N- ( 2-me thoxy-3-morpholinome thylbenzyl ) -3-oxo- prop n amide ; 2-cyano-3-(1,4-dihydro-l-phenyl- -Q-benzothiopyrano£4,3-c pyrazol-3-yl)-N-(4-methoxy-3-morpholinomethylbenzyl)-3-oxo- propa amide; 2-cyano-3- ( 1 , 4-dihydro-l-phenyl- £l] -benzothiopyrano £4 , 3-c] pyrazol-3-yl)-N- £2-(4-π_ethyl-piperazin-l-yl )methyl-benzylJ- 3-oxo-propanamide ; 2-cyano-3- ( 1 , 4-dihydro-l-phenyl- £l -benzothiopyrano C-4 , 3-cH pyrazol-3-yl )-3-oxo-N- £2- (pyrrolidin-1-yl ) methyl-benzyl] - propanamide ; 2-cyano-3- (1,4-d-Lhydro-l-phenyl- [1] -benzothicpyrano [4 , 3-c]pyrazol-3- yl) -N- (2-morphol.Lncmethyl-pheπyl) -3-<_sco-propanamide; 2-cyano-3-(l,4-*'-'dihydro-l-phenyl-^ yl) -N- (3-mo-_r£ιol-lncmethyl-pheπyl) -3-oxc>-prcpanam-ide ; 2-cyano-3- (1, 4-dihydro-l-pheπyl- [1] -benzothicpyrano [4 , 3-c]pyrazol-3- yl) -N- (3-d___-ethylam ncmethyl-pherιyl) -3-oxo-prαpanamide; 2-cyano-3- (1, 4-dihydro-l-pheryl- [1] -benzothiopyrano [4 , 3-c]pyrazol-3- yl) -N- (2 , d_i_ιethyl-3mιir-cιctethyl-pheπyl) -3-oxo-propanamide ; 2-cyano-3- (1 , 4-dihydro-l-pheπyl- [ 1] -bexιzothicpyrano[4,3-c]pyrazol-3- yl) -N- (2-metho-^-3-mo-^oliιιcmethylphenyl) -3-oxo-prcpanamide; 2-cyano-3- ( 1 , 4-dihydro-l-phenyl- [ 1] -benzc± cpyrano[4,3-c]pyrazol-3- - yl) -N- (2 ,hydro^-3-mo-τholincϊ_rethyl-pherτyl) -3-oxo-propanamide; 2-cyano-3- ( 1 , 4-dihydro-l-phenyl- Dl-benzothiopyrano 4 , 3-c] pyrazol-3-yl )-N-(4-methoxy-3-morpholinomethylphenyl )-3-oxo- prop an amide; 2-cyano-3- ( 1 , 4-dihydro-l-phenyl- [l] -benzothiopyrano £ , 3-c pyrazol-3-yl)-N-(3-hydroxy-4-hydroxymethyl-phenyl )-3-oxo- propanamide; and 2-cyano-3- ( 1 , 4-dihydro-l-phenyl- D] -benzothiopyrano £4 , 3-c] pyrazol-3-yl )-N- ( 3-hydroxy-4-hydroxymethyl-benzyl )-3-oxo- propan amide. Example 2 By proceeding according to Example 1, by reaction with suitable cyanacetamides, the following ccmpounds can be prepared: 2-cyano-N- ( 2-f urf uryl )-3- ( 1 , 4-dihydro-l-phenyl- [l] -benzothio¬ pyrano [4, 3-c pyrazol-3-yl )-3-oxo-propanamide , m.p. 236-238°C; 2-cyano-3- ( 1 , 4-dihydro-l-phenyl- l -benzothiopyrano £4 , 3-6 pyrazol-3-yl )-3-oxo-N- ( 2-thenyl )-propanamide ; 2-cyano-3- ( 1 , 4-dihydro-l-phenyl- Dl -benzoth iopyrano £4 , 3-ς] pyrazol-3-yl)-N-[2-(l-methyl-pyrrol-2-yl^^ m.p. 171-176°C; 2-cyano-3- ( 1 , 4-dihydro-l-phenyl- £l -benzothiopyrano £4 , 3-c] pyrazol-3-yl)-3-oxo-N-(2-thiazolyl)-propanamide; 2-cyano-3- ( 1 , 4-dihydro-l-phenyl- D] -benzothiopyrano £4 , 3-cJ pyrazol-3-yl ) -N- ( 3-isoxazolyl )-3-oxo-propanamide ; and 2-cyano-3- ( 1 , -dihydro-l-phenyl- l-benzothiopyrano [4 , 3-c] pyrazol-3-yl)-3-oxo-N-(l-^enylethyl)-prtpanamide, m.p. 228-230°C. Example 3 By proceeding according to Example 2, starting frcm suitable substituted l,4--*-*-d-lhydro-[l]-benz.pyran^ acids the following ccmpounds can be prepared: 2-cyano-3-(8-fluoro-l,4-d--hvdro-6-morr_hol-Lncmethyl-l-pheι^l-[1]- benzcpyrano[4,3-c]pyrazol-3-yl)-3-oxo-N-pherτyl-prcpanamide, m.p. 249-253°; 2-cyano-3-(1,4-dJLhydro-8-mo-_phol--ncme1^^ [4,3-c]r^?razol-3-yl)-3-oxo-N-phenyl-pπ-p3namide, m.p. 200-210^ dec; 2-cyano-3- (8-f luoro-l , 4-d-lhydro-6-ι-lirrethylamιinαmeτ^^ [1] - benzcpyrano[4,3-c]pyrazol-3-yl)-3-oxo-N-phenyl-pπ-panamide; 2-cyano-3- [ 8-f luoro-l , 4-dihydro-6- (4-methyl-piperazin-l-yl) -1-phenyl- [ 1] -benzcpyrano [ 4 , 3 -c] pyrazol-3 -yl ] -3-oxo-N-phenyl-prx-pan-_m_ide; 2-cyano-3- [8-f luoro-l , 4-dihydro-l-phenyl-6- (pyrrolidin-1-yl) - [1] - benzcpyrano [4, -c]pyrazol-3-yl]-3-oxc>-N-rΛeryl-propanamide; 2-cyano-3- [1, 4-dihydro-8- (4-methyl-piperazin-l-yl) -1-phenyl- [ 1] - benzcpyrano [4 , 3-c]pyrazol-3-yl ] -3-oxo-N-phenyl-prcpanamide ; 2-cyano-3- [ 1 , 4-d__hydro-l-phenyl-8- (pyrrolidin-1-yl) - [1] -benzcpyrano [ 4 , 3-c] pyrazol-3-yl ] -3-oxo-N-phe- l-prcpanamide ; N-ben-^l-2-cyano-3- (8-f luoro-l, 4-dihydro-6-morpholincHiethyl-l-ϊ-henyl- [l]-benzcpyrano[4,3-c]pyrazol-3-yl)-3-oxo-p__o anamide; N-benzyl-2-cyano— 3- (1 , 4-dihydro-8-mo-^olir-cmethyl-l-phenyl- [1] -benzo- pyrano [4 , 3-c]pyrazol-3-yl) -3-oxo-prcpanamide; 2-cyano-N-(4-fluoro-phenyl)-3-(1,4-d_lhyd__x-8-mo-^olincmeth.yl-l-j-henyl- [l]-benzcpyrano[4,3-c]pyrazol-3-yl)-3-oxo-prσpanamide; and, N-(3- hloro-phenyl)-2-cyano-3-(1,4-dihydπ -8-m -^ol-lnomethyl-l-phenyl- [1]-benzcpyrano[4,3-c]pyrazol-3-yl)-3-oxo-prcpanamide. Example 4 l,4-dihydro-l-ph€^yl-[l]-benzothicpyrano[4,3-c]pyrazole-3-carboj!ylic acid, ethyl ester (3,2 g) is heated with 1% KDH solution in ethanol (80 ml) under reflux for 30 minutes. The reaction mixture is diluted with ice water and acidified to pH 3 with 37% HC1. The precipitate is filtered, washed with water and dried in vacuo at 50°C to give 1,4-dihydro-l-phenyl-[1]-benzothiopyrano[4,3-c]pyrazole-3-carbθ5^1ic acid (2.6 g) which is reacted with thionyl chloride (0.9 ml) in dioxane (50 ml) under reflux for 2 hours. After cooling, the solution is evaporated to dryness in vacuo to give 1,4-dihydro-l-j-henyl-[l]-benzo¬ thicpyrano[4,3-c]pyrazole-3-carbonyl chloride as a crystalline residue. The crude product is dissolved in anhydrous dioxane (35 ml) and reacted for 1 hour under stirring at room teπperature with the carbanion obtained by treatment of N-cyanoacetylglycine, methyl ester (1.44 «g) with 50% sodium hydride (0.54 g) in anhydrous dimethylfoπramάde/dioxane 1:1 (30 ml) at room temperature. The reaction mixture is then diluted with ice water and acidified to pH 2 with N HC1. The precipitate is filtered and dissolved in ethyl acetate, then the organic solution is washed with N HCl and then with water until neutral. Evaporation to dryness yields a residue which is purified over a Flash column using chlorofoπιv'methanol/30% NH 4 0H 80:20:0.5 as eluent. Final treatment with acetone of the purified fractions gives 1.65 g of N-[2-cyano-3- (1,4-dihydπ--l-Fhenyl-[l]-benzot opyrano[4,3-c]pyrazol-3-yl)-3-oxo- propanoyl]-glycine,methyl ester, m.p. 208-210°C, NMR (CDC1 3 ) δpprn: 3.81(S) (3H, -OOOCH3), 4.18 (d) (2H, -OCMiαj 2 -) , 4.21(s) (2H, -S-CH 2 -) , 6.82(t) (1H, -ODNH<--H 2 ), 6.85-7.7 (m) (9H, phenyl protons) , 16.32(s) (1H, -OR) . By proceeding analogously the following ccmpounds can be prepared: N-[2-cyano-3- (1, 4-d_-hydro-l-pheπyl-[l] -benzσthicpyrano [4 , 3-c]pyrazol-3- yl)-3-c_xo-prcpancyl]-DL-leucine, methyl ester, m.p. 115-125°C; N- [2-cyano-3- (1 , 4-d-Lhydro-l-phenyl- [1] -berizcthiαpyrano [4 , 3-c] pyrazol-3- yl)-3-oxo-p--τ-panαyl]-DI_-phenylglycine, methyl ester, m.p. 180-182 °C; N- [2-cyano-3- (1,4-dihydro-l-phenyl- [1] -benzothiopyrano [4, 3-c] pyrazol-3- yl)-3-oxo-pr -pancyl]-DL-phenyleilanine, methyl ester; and N- [2-cyano-3- (1, 4-dihydro-l-phenyl- [1] -benzothicpyrano [4 , 3-c]pyrazol-3- yl)-3-oxo-pπ-panσyl]-D -isoleucine, methyl ester. Similarly the pure D and L enantiσmers of the above-listed ccmpounds can be prepared. Example 5 N-[2-cyano-3-(1,4-dihydro-l-phenyl-[1]-benzothiopyrano[4 ,3-c]pyrazol- 3-yl)-3-oxo-prcpanoyl]-glycine, methyl ester (1.9 g) , is suspended in 1% YCH. solution in 95% ethanol (61 ml) and heated under stirri-r-g under reflux for 30 minutes. After cooling the precipitate is filtered and washed with ethanol, then dissolved in water. The aqueous basic solution is extracted with ethyl acetate and then acidified to pH 2 with 2N HCl. Ωie precipitate is extracted with ethyl acetate and the organic solution washed with N HCl and then with water until neutral. Evaporation to dryness in vacuo gives a residue which is crumbled with ethanol to yield 1.35 g of N-[2-cyano-3-(l,4-dihydro-l-phenyl-[l]- benzot-hiσpyrarκ3[4,S-^p r zol-S-yl)-^ m.p. 224-226°C, NMR (EMSO d6) <5ppm: 3.94(s) (2H, -C0NHCH 2 -) , 4.19(s) (2H, -S-CH 2 ), 6.8-7.7(m) (9H, phenyl protons) . By proceeding analogously the following ccmpounds can be prepared: N-[2-cyano-3-(1,4-dihydro-l-pheπyl-[1]-benzothiopyrano[4,3-^]pyrazol-3- yl)-3-oxo-prcpanqyl]-DL-leucine, m.p. 220-222 β C; N-[2-cyano-3-(1,4-dihydro-l-phenyl-[l]-benzothicpyrano[4,3-c]pyrazol-3- yl)-3-oxo-propanσyl]-DL-pheπylalanine; N-[2-cyano-3-(1,4-dihydro-l-phenyl-[1]-benzothiopyrano[4,3-c]pyrazol- 3-yl)-3-oxo-propanoyl]-DL-phenylglycine, m.p. 210-213°C; and N-[2-cyano-3-(1,4-dihydro-l-phenyl-[1]-benzothicpyrano[4,3-c] yrazol-3- yl)-3-oxo-prcpanσyl]-DL-isoleucine. Similarly the pure D and L enantiσmers of the above-listed ccmpounds can be obtained. Example 6 8-fluoro-l,4-d-ihydπ^6-morph^ ,3-c] pyrazole-3-carboxylic acid, ethyl ester (5.6 g) is reacted with acetonitrile (15 ml) in dioxane (15 ml) in the presence of 50% sodium hydride (0.6 g) under stirring at 60°C for 30 minutes. After cooling the reaction mixture is diluted with ice water and acidified to pH 3 with citric acid. The precipitate is extracted with ethyl acetate and the organic phase washed with water until neutral and then evaporated to dryness in vacuo. The residue is purified over a Si0 2 column using cMoroform πethanol 95:5 as eluent to give 2.4 g of 3-(8-fluoro-l,4- άUhydro-6-morpholinσmtethyl-l-phenyl-[1]-benzcpyrano[4,3-c]pyrazol-3- yl)-3-oxo-propanenitrile, m.p. 187-189°C. By proceeding analogously the following compound can be prepared; 3-(1,4-dihydro-8-mo-^oli-v-ι_rethyl-l-pher-yl-[1]-benzcpyrano[4,3-c] pyrazol-3-yl)-3-oxo-prqpanenitrile, m.p. 189-190°C. Example 7 3-(8-fluoro-l,4-dihydro-6-morpholinomethyl-l-phenyl-[l]- benzopyrano[4,3-c]pyrazol-3-yl)-3-oxo-propanenitrile (2.8 g) is reacted with phenylisocyanate (0.8 g) in dimethylformamide (20 ml) in the presence of triethylamine (0.7 g) at 25-30°C for 30 min. The reaction mixture is diluted with ice water and acidified with citric acid to pH 3. The precipitate is filtered and dissolved in chloroform. The organic solution is washed with 2% citric acid solution and then with water until neutral. Evaporation to dryness in vacuo gives a residue which is crystallized from chloroform/ethanol to yield 1.9 g of 2-cyano-3-(8-fluoro-l,4-dihydro-6-morpholino- methyl-1-phenyl-[1]-benzopyrano[4,3-c] pyrazol-3-yl)-3-oxo-N- phenyl-propanamide, m.p. 249-253°C. By proceeding analogously the following compound can be prepared: 2-cyano-3-(1,4-dihydro-8-morpholinomethyl-l-phenyl-[1]- benzopyrano[4,3-c]pyrazol-3-yl)-3-oxo-N-phenyl-propanamide, m.p. 200-210°C dec. Example 8 2, 3-Dihydro-4-oxo-4H- £l] -benzothiopyran-6-carboxylic acid, m.p. 223-225°C (40.5 g) is reacted with thionyl chloride (46.3 g) in anhydrous dioxane (810 ml) at reflux temperature for 4 hours. After cooling the solution is evaporated to dryness in vacuo and the residue of crude 2 ,3-dihydro-4-oxo- 4H- l] -benzothiopyran-6-carbonyl chloride is dissolved in anhydrous benzene (500 ml). This solution is added under ni¬ trogen at room temperature to a stirred mixture of anhy- drous tert-butanol (300 ml) in benzene (500 ml) and pyridine (470 ml). The reaction mixture is allowed to react for 20 hours at room temperature and then is evaporated to dryness in vacuo. The residue is dissolved in ethyl acetate and the organic solution is washed with 5 'ό citric acid solution, then with water until neutral and finally evaporated tc dry¬ ness in vacuo. The residue is purified over a Si0» column using hexane/ethyl acetate 90/10 as eluent. The recovered product is treated with hexane under stirring to give 2 , 3-dihydro-4-oxo-4H- [ll -benzothiopyran-6-carboxylic acid, tert-butyl ester, m.p. 125-127°C (34.5 g), which is reacted with diethyl oxalate (83.8 g) in anhydrous ethanol (1000 ml) in the presence of sodium ethoxide (31 g) under stirring at room temperature for 2 hours. The reaction mix¬ ture is diluted with ice water and acidified to pH 4 with citric acid. The precipitate is filtered, washed with water and then dissolved in ethyl acetate. The organic solution is evaporated to dryness in vacuo to yield 3-ethoxalyl-2,3-di- hydro-4-oxo-4H- ]-benzothiopyran-5-carboxylic acid, tert- butyl ester (45 g) , which is reacted with phenylhydrazine (15 g) in acetic acid (1560 ml) at 25-30°C for 90 minutes. The reaction mixture is diluted with ice water and the pre¬ cipitate is filtered, dissolved in chloroform and washed with water. After evaporation of the solvent in vacuo, the residue is purified by treatment with isopropyl ether under stirring to yield 8-tert-butoxycarbonyl-l,4-dihydro-l-phenyl- D]-benzothiopyrano [4 ,3-c]pyrazole-3-carboxylic acid, ethyl ester, m.p. 146-149°C (27.5 g), which is hydrolyzed by treat¬ ment with potassium hydroxide (5.3 g) in 95 % ethanol (1200 ml) under stirring at room temperature for 20 hours. The re- action mixture is diluted with ice water and acidified to pH 4 with citric acid. The precipitate is filtered, washed with water until neutral and dried in vacuo at 80°C to give 8-tert-butoxycarbonyl-l,4-dihydro-l-phenyl-[ΪJ-benzothiopy- rano[4,3-c]pyrazole-3-carboxylic acid, m.p.295-297°C (23.9 g) ' which is dissolved in anhydrous dioxane (1000 ml) arid react¬ ed with oxalyl chloride (16.3 g) in the presence of a cata¬ lytic amount of d-_met_hylfonramide (70 mg) at room teπperature for 4 hours. The reaction mixture is evaporated to dryness in vacuo and the residue, 8-tert-butoxycarbonyl-l,4-dihydro- 1-phenyl- [l -benzothiopyrano [4 ,3-c]pyrazole-3-carbonyl chlo- ride (24.8 g), is dissolved in anhydrous dioxane (980 ml) and added under stirring to the suspension obtained by treat¬ ment of cyanoacetanilide (10.28 g) with 50 % sodium hydride (3.75 g) in anhydrous dioxane (1230 ml) at room temperature. The reaction mixture is kept under stirring at room tempe¬ rature for 1 hour and then diluted with ice water and aci¬ dified to pH 3 with 2N HCl. The precipitate is filtered and dissolved in ethyl acetate, the organic solution is washed with IN HCl and then with water until neutral. Evaporation to dryness in vacuo gives a residue which is purified by treatment with ethanol under reflux. After cooling the pre¬ cipitate is filtered and washed with ethanol to yield 3-(8- tert-butoxycarbonyl-1,4-dihydro-l-phenyl-[l -benzothiopyrano [4,3-c]pyrazol-3-yl)-2-cyano-3-oxo-N-phenyl-prcpanamide, m.p. 229-230°C (12.8 g), which is reacted with trifluoroace- tic acid (128 ml) under stirring at room temperature for 1 hour. The reaction mixture is diluted with ethanol (128 ml) and the precipitate is filtered and washed with ethanol to yield 11.3 g of 3-(8-carboxy-l,4-dihydro-l-phenyl-[l]-benzo- thiopyrano[.4,3-c]pyrazol-3-yl)-2-cyano-3-oxo-N-phenyl-pro- pana ide, m.p. 284-287°C. By proceeding analogously the following cαrpσunds can be prepared: 3-(6-carboxy-l ,4-dihydro-l-phenyl-[l] -benzothiopyrano [ ,3-cJ pyrazol-3-yl)-2-cyano-3-oxo-N-phenyl-propanamide, m.p. 283- 287°C; 3- ( 8-carboxy-l , 4-dihydro-l-phenyl- [±] -benzopyrano [4 , 3-c] pyrazol-3-yl ) -2-cyano-3-oxo-N-phenyl-propanamide ; and 3-(6-carboxy-l , 4-dihydro-l-phenyl- [l] -benzothiopyrano [4 , 3-c " ] pyrazol-3-yl ) -2-cyano-N- ( 4-f luoro-phenyl ) -3-oxo-propanamide . Example 9 3-(8-Carboxy-l,4-dihydro-l-phenyl-[l]-benzothiopyrano[4,3-c] pyrazol-3-yl)-2-cyano-3-oxo-N-phenyl-propanamide (0.65 g) dissolved in dimethylformamide (50 ml) is reacted with methyl iodide (0.37 g) in the presence of anhydrous potassium car¬ bonate (0.36 g) under stirring at room temperature for 2 hours. The reaction mixture is diluted with ice water and the precipitate is filtered, dissolved in chloroform and washed with IN HCl and then with water. Evaporation of the solvent in vacuo gives a residue which is crystallized from CK Cl ? / me hanol to yield 0.48 g of 2-cyano-3-(l,4-dihydro-8-methoxy- carbonyl-1-phenyl- lj-benzothiopyrano £4 ,3-c]pyrazol-3-yl)- 3-oxo-N-phenyl-propanamide, m.p. 228-230°C. By proceeding analogously the following compounds can be pre¬ pared: 2-cyano-3-(8-ethoxycarbonyl-l,4-dihydro-l-phenyl-[l]-benzo¬ thiopyrano £4 ,3-c]pyrazol-3-yl)-3-oxo-N-phenyl-propanamide, m.p. 241-242°C; 2-cyano-3-(6-ethoxycarbonyl-l ,4-dihydro-l-phenyl- Dl-benzo¬ thiopyrano [.4, 3-c]pyrazol-3-yl )-3-oxo-N-phenyl-propanamide , m.p. 263-264°C; N-(3-chloro-phenyl )-2-cyano-3-(6-ethoxycarbonyl-l , 4-dihydro- 1-phenyl- [l] -benzothiopyrano [4 , 3-c] pyrazol-3-yl ) -3-oxo-pro- panamide ; 2-cyano-3- ( 6-ethoxycarbonyl-l , 4-dihydro-l-phenyl- l] -benzo¬ thiopyrano £4 , 3-c] pyrazol-3-yl )-N-(4-f luoro-phenyl )-3-oxo- propanamide ; 2-cyano-3-(6-ethoxycarbonyl-l , 4-dihydro-l -phenyl- C-J -benzo¬ thiopyrano [4 , 3-c] pyrazol-3-yl )-3-oxo-N- ( 3-fi rif luoromethyl- pheny 1 ) -3-oxo-propanamide ; 2-cyano-3- [6-ethoxycarbonyl-l-(4-f luoro-phenyl )-l ,4-dihydro- [l] -benzothiopyrano [4 , 3-c] pyrazol-3-yl] -3-oxo-N-phenyl-pro- panamide; and 2-cyano-3-( 8-ethoxycarbonyl-l , 4-dihydro-l-phenyl- [l] benzo¬ pyrano 4 , 3-c] pyrazol-3-yl )-3-oxo-N-phenyl-propanamide . Example 10 Glycine methyl ester hydrochloride (0.7 g) suspended in an- hydrous acetonitrile (250 ml) is treated with triethylamine (0.56 g) under stirring at room temperature. To the suspen¬ sion first 3-(8-carboxy-l,4-dihydro-l-phenyl-[l]-benzothio- pyrano [4 ,3-c]pyrazol-3-yl)-2-cyano-3-oxo-N-phenyl-propana- mide (2.5 g) and then dicyclohexylcarbodiimide (1.25 g) are added. The reaction mixture is kept under stirring at room temperature for 4 hours and then is basified to pH 8 by add- ing dimethylaminoethanol. The precipitate is filtered, wash¬ ed with acetonitrile and then eliminated. The organic solu¬ tion is concentrated in vacuo to a small volume, diluted with water, acidified to pH 2 with IN HCl and finally basi¬ fied to pH 8 with IN NaOH. The obtained precipitate is fil- tered, washed with water, dissolved in chloroform and washed with IN HCl and then with water until neutral. The organic solution is evaporated in vacuo to dryness and the residue is purified over a SiO column using chloroform/methanol 90/10 as eluent. Final crystallization from CH ? C1 /ethyl acetate yields 1.48 g of N-[l,4-dihydro-l-phenyl-3-(2-phenyl- carbamoyl-cyanoacetyl)- ] -benzothiopyrano [4,3-c]pyrazol-8- yljcarbonyl glycine methyl ester, m.p. 253-256°C. By proceeding analogously the following compounds can be pre¬ pared: N-D,4-dihydro-l-phenyl-3-(2-phenylcarbamoyl-cyanoacetyl) - l] -benzothiopyrano[4,3-c]pyrazol-6-yl]carbonyl-glycine me¬ thyl ester, m.p.268-273°C dec; N- l , 4-dihydro-l-phenyl-3-( 2-phenylcarbamoyl-cyanoacetyl )- D -benzothiopyrano [4 , 3-cJ pyrazol-8-ylJ carbonyl-L-alanine methyl ester; N- ,4-di hydro- 1-pheny 1-3- ( 2-phenylcarbamoyl-cyanoacetyl )- D] -benzothiopyrano , 3-c] pyrazol-6-yl] carbonyl-L-alanine methyl ester; N- [1 ,4-dihydro-l-phenyl-3-(2-phenylcarbamoyl-cyanoacetyl )- [l] -benzothiopyrano , 3-c]pyrazol-8-yl] carbonyl-L-leucine methyl ester; N- fl ,4-dihydro-l-phenyl-3-( 2-phenylcarbamoyl-cyanoacetyl )- fl] -benzothiopyrano [4 , 3-c] pyrazol-6-yl] carbonyl-L-leucine methyl ester; N- [l ,4-dihydro-l-phenyl-3-(2-phenylcarbamoyl-cyanoace yl )- Dl-benzothiopyrano [_4 , 3-c]pyrazol-6-yl] -carbonyl-L-phenyl- aianine methyl ester; and N- 13- 2-(4-f luorophenylcarbamoyl ) -cyanoacetyl -1 , 4-dihydro- 1-phenyl- [l] -benzothiopyrano [4 , 3-c] pyrazol-8-yl V carbonyi- glycine methyl ester. Example 11 N-|~1,4-Dihydro-l-phenyl-3-(2-phenylcarbamoyl-cyanoacetyl)- D]-benzothiopyrano[4,3-c]pyrazol-8-yϊ]carbonyl-glycine me¬ thyl ester (0.9 g) is suspended in 1 % KOH solution in 95 % ethanol (22.3 ml) and heated under stirring at the reflux temperature for 30 minutes. After cooling the reaction mix¬ ture is acidified to pH 2 with 23 % HCl and then diluted with ice water. The precipitate is filtered, washed with water and then crystallized from CHC1 /ethanol to yield 0.73 g of N-| L,4-dihydro-l-phenyl-3-(2-phenylcarbamoyl- cyanoacetyl)-Dj -benzothiopyrano \_4 ,3-c]pyrazol-8-ylJcarbo- nyl glycine, m.p. 244-250°C. By proceeding analogously the following compounds can be prepared: N- i4-dihydro-l-phenyl-3-(2-phenylcarbamoyl-cyanoacetyl)- D]-benzothiopyrano [4,3-c]pyrazol-6-yl carbonyl-glycine; N-[l ,4-dihydro-l-phenyl-3-(2-phenylcarbamoyl-cyanoacetyl)- D]-benzothiopyrano [ 4 ,3-cJpyrazol-8-ylJ carbonyl-L-alanine; - > L,4-dihydro-l-phenyl-3-(2-phenylcarbamoyl-cyanoacetyl .- Dj-benzothiopyrano £4 ,3-cJpyrazol-6-yl] carbonyl-L-alanine ; N-Ll,4-dihydro-l-phenyl-3-(2-phenylcarbamoyl-cyanoacetyi)- Dj,-benzothiopyrano ,3-c]pyrazol-8-yl]carbonyl-L-leucine ; N~D,4-dihydro-l-phenyl-3-(2-phenylcarbamoyl-cyanoacetyl )- D]- Deπ * zo ' fc - rι iopyrano [4 ,3-c]pyrazol-6-ylJ carbonyl-L-leucine ; and N- ι 4-dihydro-l-phenyl-3-( 2-phenylcarbamoyl-cyanoacetyl ) - Dl-benzothiopyranof4 , 3-cJpyrazol-6-yll carbonyl-L-phenyl- alanine . Example 12 3 - (8 -amino- l ,4-dihydro- l -phenyl-[1]-benzothicpyrano[4,3-c]pyrazol-3-yl )■ 2-cyano-3-oxo-N-phenyl-propanamide (1.1 g) dissolved in an¬ hydrous tetrahydrofuran (23 ml) is reacted with succinic an¬ hydride (0.71 g) at the reflux temperature under stirring for 3 hours. After cooling the reaction mixture is diluted with ice water. The precipitate is filtered and washed with water. Crystallization from CHCl_/methanol yields 0.9 g of 3-|_8-(3-carboxy-propanoyl mino)-l,4-dihydro-l-phenyl- l] - benzothiopyranof_4,3-c]pyrazol-3-yl]-2-cyano-3-oxo-N-phenyl- propanamide, m.p. 230-233°C. By proceeding analogously the following compounds can be prepared: 3- j_6- ( 3-carboxy-propanoylamino ) -l , 4-dihydro- l-phenyl- [ϊ] - benzothiopyrano |_4 , 3-c] pyrazol-3-yl )-2-cyano-3-oxo-N-phenyl- propanamide ; 3- 8- ( 2-carboxy-ace tylamino ) -l , 4-dihydro-l -phenyl- l -benzo¬ thiopyrano £4 , 3-c] pyrazol-3-yl] -2-cyano-3-oxo-N-phenyl -pro- pana ide ; and 3- r8- ( 3-carboxy-propanoylamino ) -l , 4-dihydro-l-phenyl- l] - benzopyrano [4,3-c]pyrazol-3-ylJ-2-cyano-3-oxo-N-phenyl-pro- panamide. Examp le 13 3-(8-Amino-l,4-dihydro-l-phenyl- ]-benzothiopyrano [4,3-c! pyrazol-3-yl)-2-cyano-3-oxo-N-phenyl-propanamide (1.2 g) dis¬ solved in anhydrous dimethylformamide (70 ml) containing py- ridine (1 ml) is reacted with ethyl oxalyl chloride (0.7 g) under stirring at room temperature for 6 hours. The reaction mixture- is diluted with ice water and acidified to pH 4 with citric acid. The precipitate is filtered and washed with water. Crystallization from CHCl_/ethanol yields 1.2 g of 2-cyano-3-(8-ethoxalylamino-l,4-dihydro-l-phenyl-j_l]-benzo- thiopyrano 4 ,3-c]pyrazol-3-yi)-3-oxo-N-phenyl-propanamide, m.p. 273-277°C. By proceeding analogously the following compounds can be prepared: 2-cyano-3-(6-ethoxalylamino-l,4-dihydro-l-phenyl-DJ-benzo¬ thiopyrano £4 ,3-cQpyrazol-3-yl)-3-oxo-N-phenyl-propanamide; 2-cyano-3-(8-ethoxalylamino-l,4-dihydro-l-phenyl- ]-benzo¬ thiopyranoC4,3-c]pyrazol-3-yl)-N-(4-fluoro-phenyl)-3-oxo- propanamide; N-(3-chloro-phenyl)-2-cyano-3-(3-ethoxalylamino-1,4-dihydro- 1-phenyl- l-benzothiopyrano £4 ,3-cJpyrazol-3-yl)-3-oxo-pro- pan mide; 2-cyano-3-(8-ethoxalylamino-l,4-dihydro-l-phenyl-Dl-benzo¬ thiopyrano[4,3-c]pyrazol-3-y1)-N-(3-nitro-pheny1)-3-oxo- propanamide; 2-cyano-3- ( 8-e thoxalylamino-l , 4-dihydro-l-phenyl— l] -benzo¬ thiopyrano C4 , 3-c] pyrazol-3-yl ) -3-oxo-N- ( 3-tri fluoromethyl- phenyl ) -propanamide and 2-cyano-3- | 8-ethoxalylamino-l- ( 4-f luoro-phenyl ) -l , 4-dihydro- l -benzothiopyrano 4 , 3-c | pyrazol-3-yl] -3-oxo-N-phenyl-pro- panamide . Example 14 2-Cyano-3-(8-ethoxalylamino-l,4-dihydro-l-phenyl- £l] -benz - thiopyrano[4,3-c]pyrazol-3-yl)-3-oxo-N-phenyl-propanamide (1.1 g) is treated with 1 % KOH solution in 95 % ethanol (28.6 ml) diluted with 95 % ethanol (50 ml) under stirring at room temperature for 3 hours. The reaction mixture is concentrated in vacuo to a small volume and then diluted with ice water and acidified to pH 4 with citric acid. The precipitate is filtered and washed with water. Crystalli¬ zation from CHCl 3 /ethanol yields 0.7 g of 2-cyano-3-(l ,4- dihydro-8-oxalamino-l-phenyl-[l]-benzothiopyrano £4 ,3-c]pyra- zol-3-yl)-3-oxo-N-phenyl-propanamide, m.p. 236-242°C dec. By proceeding analogously the following compounds can be prepared: 2-cyano-3-(1 ,4-dihydro-6-oxalamino-l-phenyl- ]-benzothio¬ pyrano £ ,3-c]pyrazol-3-yl)-3-oxo-N-pheny1-propanamide; 2-cyano-N- ( 4-f luoro-phenyl ) -3- ( 1 , 4-dihydro-8-oxalamino-l- phenyl- j -benzothiopyrano [4 , 3-cJpyrazol-3-yl ) -3-oxo-pro- panamide ; N- ( 3-chloro-phenyl ) -2-cyano-3- ( 1 , 4-dihydro-8-oxalamino-l- phenyl- lj -benzothiopyrano [4 , 3-cJ pyrazol-3-yl ) -3-oxo-propa- namide ; 2-cyano-3- fl- ( 4-f luoro-phenyl ) -1 , 4-dihydro-8-oxalamino-l- phenyl- £ϊ -benzothiopyrano [4 , 3-cJpyrazol-3-yl] -3-oxo-propa- namide ; and 2-cyano-3- ( l , 4-dihydro-8-oxalamino-l-phenyl- Dl -benzopyrano 4, 3-c] pyrazol-3-yl ) -3-oxo-N-phenyl-propanamide . Example 15 8-Tert-rxιtoxycarbonyl-l , 4-dihydro-l-phenyl- [1] -benzσthicpyrano £4 ,3-c]pyrazole-3-carboxylic acid ethyl ester (11.9 g), pre- pared according to Example 8, is treated under stirring with trifluoroacetic acid (132 ml) at room temperature for 3 hours. The reaction mixture is diluted with ice water and the preci¬ pitate is filtered and washed with water until neutral. Crys¬ tallization from isopropanol yields 3-ethoxycarbonyl-l,4- dihydro-1-phenyl- £lj-benzothiopyrano £4 ,3-cJpyrazole-8-car- boxylic acid, m.p. 222-225°C (9.2 g) , which is reacted with thionyl chloride (5.3 ml) in anhydrous dioxane (90 ml) at the reflux temperature for 2 hours. After cooling, the solu- tion is evaporated to dryness in vacuo and the residue, 3- ethoxycarbonyl-1 ,4-dihydro-l-phenyl- (lj -benzothiopyrano £4 , 3-cJpyrazole-8-carbonyl chloride, is dissolved in anhy¬ drous diglyme (100 ml) and added dropwise, under inert atmosphere, to a stirred solution of lithium tri-tert-butoxy- aluminum."hydride (15.4 g) in anhydrous diglyme (90 nil) in such a way as to maintain the temperature between 0°C and 4°C. The reaction mixture is allowed to react at about 0°C under stirring for 1 hour and then is diluted with ice water, acidified to pH 1 with 23 % HCl and extracted with chloro¬ form. The organic solution is washed v/ith water and then eva¬ porated to dryness in vacuc . The residue is purified over a SiO column using hexane/ethyl acetate 7/3 as eluent. Crys¬ tallization from CH C1 /isopropyl ether yields pure 1,4-di- hydro-8-hydroxymethyl-l-phenyl-D]-benzothiopyrano [→ , 3-c] pyrazole-3-carboxylic acid ethyl ester, m.p. 160-152°C (4.2 g), which is reacted with 2-methoxyethoxymethyl chloride (2.13 g) in methylene chloride (60 ml) in the presence of diisopropylethylamine (2.96 ml) at room temperature for 20 hours. The reaction mixture is washed in a separatory fun¬ nel first with 5 % Na HPO solution and then with water un¬ til neutral. The organic phase is evaporated to dryness in vacuo and the residue is crystallized from isopropyl ether to yield 1 ,4-dihydro-8-(2-methoxyethoxymethoxy)methyl-l- phenyl- [l] -benzothiopyrano [4,3-clpyrazole-3-carboxylic acid ethyl ester, m.p. 66-68°C (5 g) , which is treated with KOH (0.4 g) in 95 % ethanol (52 ml) under stirring at 45°C for 40 minutes. The reaction mixture is then diluted with ice water and acidified to pH 4 with citric acid. The precipi- tate is filtered, washed with water until neutral and dried in vacuo at 80°C to yield l,4-dihydro-8-(2-methoxyethoxy- methoxy)-methyl-l-phenyl- l-benzothiopyrano3»3-cJpyrazole- 3-carboxylic acid, m.p. 136-139°C (4.26 g) , which is dissolv¬ ed in anhydrous dioxane (50 ml) and reacted with oxalyl chloride (1.9 ml) in the presence of d-uret_hylformam-ide (11 mg) at room temperature for 1 hour. The reaction mixture is eva¬ porated to dryness in vacuo and the residue, crude 1,4-di- hydro-8-(2-methoxyethoxymethox ) methyl-1-phenyl- ]-benzo¬ thiopyrano £4 ,3-c]pyrazole-3-carbonyl chloride, is dissolved in anhydrous dioxane (50 ml) and reacted for 1 hour under stirring at room temperature with the carbanion obtained by treatment of cyano-acetanilide (1.76 g) with 50 % sodium hydride (0.6 g) in anhydrous dioxane (140 ml). The reaction mixture is then diluted with ice water and acidified " to pH 3 with 2N HCl. The precipitate is filtered, washed with water and crystal¬ lized from CH C1 /isopropanόl to yield 2-cyano-3-{jL,4}-dihydro- 8-(2-methoxyethoxymethoxy)methyl-l-phenyl-[i]-benzothiopyrano [4,3-c]pyrazol-3-yl]-3-oxo-N-phenyl-propanamide, m.p. 150- 153°C (1.6 g) , which is suspended under stirring in methanol (800 ml) containing 37 % HCl (8 ml) and heated at 45°C for 20 hours. After cooling the reaction mdxture is concentrated in vacuo to a small volume and diluted with ice water. The precipitate is filtered and washed with water until neutral. Crystallization from C^Cl^m thanol yields l.l g of 2-cyano-3-(l,4-d-Lhydro-8-hydroxrrethyl- l-pheπyl-[1]-benzothio-pyrano[4,3-c]pyrazol-3-yl)-3-oxo-N-phenyl- prcpanamide, m.p. 153-158°C dec. By proceeding analogously the following compounds can be prepared: 2-cyano-3-(1,4-d-lhyd-π>-6-hydrojiymethyl-l-pheηyl-[1]-benzothiopyrano [4,3-c]pyrazol-3-yl)-3-oxo-N-pheryl-proparamιide; 2-c_yaιτo-3-(l,4- * ' * --d-_hydro-8-hy^^ pyrazol-3-yl)-3-oxo-N-prcpanamide; 2-cyano-N- (4-f luorophenyl ) -3- (1 , 4-dihyd__O-8-hyd__Oxyιιethyl-l-ϊ3henyl- [ 1 ] - benzot ςpyrarκ->[4,3-c]pyrazol-3-yl)-3-oxo-proparaιώ and N- ( 3- hloro-j-henyl ) -2-cyano-3- (1,4 -d-Lhydro-8-hydroxymethyl-l-j-henyl- [1]-benzothiopyrano[4,3-c]pyrazol-3-yl)-3-oxo-prcparamide. Example 16 3-(8-Carboxy-l,4-d-Lhydro-l-phenyl-[1]-benzothiopyrano[4,3-c]pyrazol-3- yl)-2-cyar_^3-oxo-N-phenyl-prcparamιide (1.35 g) dissolved in anhydrous acetonitrile (110 ml) is reacted with N,N-dimethylaminoethanol (0.73 g), in the presence of di- cyclσhexylcarbodiimide (1.12 g) and 4-dimethylaminopyridine (0.265 g), under stirring at room temperature for 24 hours. The precipitate is filtered off and the organic solution is concentrated in vacuo to a small volume. The residue is di¬ luted with water, acidified to pH 2 with NHCl and then basi- fied to.pH 8 with N NaOH. The precipitate is filtered and purified over a SiO column using chloroform/methanol/30 % NH OH 80/20/0.3 as eluent. The recovered product is dissolv- ed in dimethylformamide (20 ml), acidified to pH 2 with 2N HCl, diluted with water (50 ml), and then basified to pH 8 with 2N NaOH. The precipitate is filtered and washed with water to yield 0.4 g of 2-cyano-3-(l,4-^iihydro-8-N,N-di-ιethyl^ ■ carix)nyl-l-phenyl-[l]-benzot cpyrano[4 , 3-c]pyrazol-3-yl) -3-oxo-N- pher l-pr panamide, m.p. 217-220°C. 3y proceeding analogously the following compounds can be prepared : 2-cyano-3-(l,4-dihydro-ό-N,N-dimethylamincethoxycarbonyl- 1-phenyl- D] -benzothiopyrano £4 , 3-cJpyrazol-3-yl ) -3-oxo-N- phenyl-propanamide , m. p . 210-217 ° C dec ; 2-cyano-3-(1,4-dihydro-8-morpholinoethoxycarbonyl-1-phenyl- D!-benzothiopyrano £4,3-c]pyrazol-3-yl)-3-oxo-N-phenyl-pro- panamide; and 2-cyano-3-(8- , -diethylaminopropoxycarbonyl-1,4-dihydro-l- phenyl- J-benzothiopyrano £ ,3-c]pyrazol-3-y1)-3-oxo-N- phenyl-propanamide. Example 17 N-Formylmorpholine (7.58 g) dissolved in anhydrous ethyl ether (200 mi) is reacted with oxalyl chloride (8.02 g) under stirring at room temperature for 20 hours. The precipitate is filtered, washed with anhydrous ethyl ether and dried in va¬ cuo at room temperature for 1 hour to yield 8.9 g of 4-chlo- romethylene-morpholinium chloride. This compound (5.47 g) is added portionwise at -15°C to a stirred solution of 3-(8- amino-1 ,4-dihydro-l-phenyl- [lj -benzothiopyrano 4 , 3-c] pyrazol- 3-yl )-2-cyano-3-oxo-N-phenyl-propanamide (3 g) in anhydrous tetrahydrofuran (130 ml) containing triethylamine (8.96 ml). The reaction mixture is kept under stirring at -15°C for 2 hours and then at about 0°C for 2 hours again. Finally it is diluted with ice water and actified to pH 4 with citric acid. The precipitate is filtered, dried in vacuo at 50°C and then purified over a SiO.. column using chlorofcrm/methancl/30 % NH OH 85/12/0.5 as eluent. The recovered product is crystal¬ lized frcm methanol to yield 1.4 g of 2-cyano-3(l,4-dihydrc»- 3-c]pyrazol- 3-yl)-3-oxo-N-phenyl-prσpanamide, m.p. 205-210°C. By proceeding analogously the following compounds can be prepared: 2-cyano-3-(l ,4-dihydro-6-morpholinomethyleneamino-1-phenyl- l]-benzothiopyrano 4,3-c]pyrazol-3-yl)-3-oxo-N-phenyl-pro- panamide; 2-cyano-3-(1,4-dihydro-l-phenyl-8-piperidinomethyleneamino- l-benzothiopyrano [4 ,3-c]pyrazol-3-yl)-3-oxo-N-phenyl- propanamide; and 2-cyano-3-(1,4-dihydro-8-dimethylaminomethyleneamino-l- phenyl-Dl-benzothiopyrano[3,3-clpyrazol-3-yl)-3-oxo-N- phenyl-propanamide. Example 18 3- ( 8-Amino-l , 4-dihydro-l-phenyl- Dl -benzothiopyrano [4 , 3-cJ pyrazol-3-yl ) -2-cyano-3-oxo-N-phenyl-propanamide ( 1 g ) dis- solved in anhydrous acetonitrile ( 10 ml ) is reacted wi th N- tert-butoxy-carbonylglycine (0.41 g) in the presence of dicyclohexylcarbodiimide (0. 53 g ) under stirring at room temperature for 2 hours . The precipitate is filtered, washed with acetonitrile and then eliminated . The organic solution is evaporated in vacuo to dryness and the residue is extract¬ ed with ethyl acetate ( 2 x 100 ml ) . The insoluble residue is filtered off and the clear organic solution is evaporated in vacuo to dryness . The crude product is purified over a flash column using chloroform/methanol/acetic acid 85/15/0.5 as eluent. The recovered product is crystallized frcm d__lo__ofo--m-ethyl acetate to yield 3-[8-(N-t-ert-burtoxycar-x>nylglyc^^ phenyl-[l]-benz.-thiαpy-_Bno[4 , 3-c]pyrazo p_n_panamide, m.p. 190-200°C (0.36 g) , which is suspended in ethyl acetate containing gaseous HCl (about 2.5 N solution) and kept under stirring at room tem¬ perature for 4 hours. The precipitate is filtered, washed with ethyl acetate, suspended in water and treated with 15 % NH OH until pH 8. The suspension is kept under stirring at room temperature and then the precipitate is filtered and washed with water. Purification with methanol at the reflux temperature yields 0.2 g of 2-cyano-3-(8-glycylamino-l ,4- dihydro-1-phenyl- l]-benzothiopyrano[4,3-c!pyrazol-3-yl)-3- oxo-N-phenyl-propanamide, m.p. 218-221°C. By proceeding analogously the following compounds can be pre¬ pared: 2-cyano-3-(6-glycylamino-1,4-dihydro-1-phenyl- -benzoth o¬ yrano 4,3-c] yrazol-3-yl)-3-oxo-N-phenyl-propanamide; and 3-(8-L-alanylamino-l ,4-dihydro-1-phenyl- l-benzothiopyrano £4,3-c]pyrazol-3-yl)-3-oxo-N-phenyl-propanamide. Example 19 2-Cyano-3-(1,4-dihydro-6-hydroxymethyl-l-phenyl- l)-benzo¬ thiopyrano 4 ,3-c]pyrazol-3-yl)-3-oxo-N-phenyl-propanamide (1.2 g) is reacted with succinic anhydride (0.8 g) in an- hydrous -pyridine (40 ml) under stirring at 45°C for 20. hours, After cooling the reaction mixture is diluted in ice water and the precipitate is filtered and washed with water. Crystallization from CH Cl /isopropanol yields 0.95 g of 3-L6-(3-carboxy-propanoyloxymethyl)-l,4-dihydro-l-phenyl- D.I-benzothiopyrano £4 ,3-c]pyrazol-3-ylJ-2-cyano-3-oxo-N- phenyl-propanamide. By proceeding analogusly the following compound can be pre¬ pared: 3- [β-(3-carboxy-propanoyioxymethyi)-1,4-dihydro-l-phenyl- l-benzothiopyrano [4,3-cJpyrazoi-3-yl7-2-cyano-3-cxo-N- phenyl-propanamide. Example 20 N-[2-cyano-3-(1,4-d-lhydro-l-phenyl-[1]-benzothicpyrano[4,3-c]pyrazol-3- yl)-3-oxo-prσpanqyl]-glycine, methyl ester is dissolved by treatment with the stoic icβTetric amount of sodium ethoxide in ethanol. The solution is evaporated to dryness in vacuo and the product is crumbled with acetone. Filtration and washing with acetone yields the pure sodium salt of N-[2-cyano-3-(l,4-d-ihydro-l-pher l-[l]-benzothio- py__ar_o[4,3-c]pyrazol-3-yl)-3-^xo-prσpar_yl]-^lycine, methyl ester, m.p. > 260°C. Example 21 Tablets, each weighing 150 mg and containing 50 mg of active substance, can be manufactured as follows: Composition (for 10,000 tablets) N-[2-cyano-3-(1,4-dihydro-l-j-henyl-[1]-benzothiopyrano[4,3-c]pyrazol-3- yl)-3-oxo-prqpanoyl]-glycine, methyl ester 500 g Lactose 710 g Corn starch 238 g Talc powder 36 g Magnesium stearate 16 g N-[2-c-yano-3-(l,4-dihydro-l-phenyl-[l]-benzothicpy-_^^ yl)-3-oxo-prcpanqyl]-glycine, methyl ester and half of the corn starch are mixed, the mixture is then forced through a sieve of 0.5 mm openings. Corn starch (18 g) is suspended in warm water (180 ml) . The resulting paste is used to granulate the pcwder. The granules are dried, ccmminurted on a sieve of sieve size 1.4 mm, then the remaining quantity of starch, talc and magnesium stearate is added, carefully mixed and processed into tablets using punches of 8 mm diameter.

Claims: CLAIMS 1. A compound of formula (I) wherein X represents an oxygen atom or a -S(0) B - group, wherein n is zero, 1 or 2; R represents C χ -C 3 alkyl, pyridyl or phenyl, the phenyl being unsubstituted or substituted by one or two substituents chosen independently from halogen, trifluoroaethyl, C j -C 8 alkyl, C v -C fi alkoxy, nitro, amino, formylamino and C 2 -C, alkanoylamino; R' is a ) hydrogen, di(C 1 -C β alkyl)-aaino or a -CH 2 N/ \ R" group wherein R' and R" , the saae or different, is C l -C β alkyl or R' and R" , taken together with the nitrogen atom to which they are linked, fora a heterocyclic ring which is selected from N-pyrrolidinyl, N-piperazinyl, hexahydroazepin-1-yl, thiomorpholino, morpholino and piperidino and which is unsubstituted or substituted by C.-C 8 alkyl; b° ) CH j OH, CHO, COOH or C. -C. alkoxycarbonyl; c° ) a CONHCH-COOR d group whe rein R d is hydrogen or C 1 -C 6 «c alkyl and R c is hydrogen, phenyl or the side-chain of an α-aminoacid; d° ) a NHCOCH-NH. group, wherein R c is as defined above; R c e° ) a , a -CH 2 OCO ( CH 2 ) n COOR d or a -NHCO ( CH j ) n COOR d group whe re in n and d a re as de f ined above ; f° ) a -CH-N-OR' j group wherein W is hydrogen or a -CH 2 COOH group; g° ) a -CH-N-NH-R' 2 group wherein R' 2 is hydrogen, -CH 2 CH 2 OH, C 2 or C j alkoxycarbonyl or a -(CH 2 ) p -R' 3 group wherein p is 1 or 2 and R' 3 is COOH or C 2 -C 7 alkoxycarbonyl; h° ) a -CH-N-N-CH-N group wherein R' and R" are as defined above; or k° ) a -N-CH-N group wherein R' and R" are as defined \ R n above; _^R' 1°) a C -C alkoxycarbonyl group substituted by a -N (1 grou wherein R 1 and R" are as defined above; each of R 2 and R 3 is independently: a) hydrogen, halogen or C -C 6 alkyl; b) hydroxy, C j -C 8 alkoxy or C 3 or C 4 alkenyloxy; or c) nitro, aaino, formylamino or C 2 -C ( alkanoylamino; R 4 represents hydrogen or C χ -C β alkyl; and Q represents hydrogen, carboxy, C 2 -C 7 alkoxycarbonyl or a /*. -CON group wherein R β represents hydrogen or ^-C j ,, R b alkyl and R,. represents C 1 -C 2β alkyl, a -CH-COOR. d group wherein R and R. are as defined above or a -(A) -R. group wherein m is zero or 1, A is a C χ -C 6 alkylene chain and R 5 is: a') C 5 -C, cycloalkyl; b r ) pyridyl, unsubstituted or substituted by one or two substituents chosen independently from halogen, C 1 -C 6 alkyl and C j -C j alkoxy; C) phenyl, unsubstituted or substituted by one or two substituents independently chosen from halogen, CF 3 , C χ -C 8 alkyl, C r -C 6 alkoxy, amino, nitro, formylamino, C 2 -C 8 alkanoylamino, d C j -C 8 alkyl)-amino, hydroxy, formyloxy and C 2 ~ c β alkanoyloxy; d') phenyl substituted by a -CH 2 OH, COOH, C 2 -C 7 R' alkoxycarbonyl or a -CH ∑ -N group wherein R' and R" are as defined above and optionally by another substituent chosen from halogen, C χ -C 6 alkyl, C χ -C 6 alkoxy, amino, nitro, formylamino, C 2 -C $ alkanoylamino, hydroxy, formyloxy and C 2 -C, alkanoyloxy, or e') 2-thienyl, 2-furyl or 1- C^-C 8 alkyl)-pyrrol-2-yl; or f) a heterocyclic ring which is selected from 2-pyrimidyl, 2-thiazolyl and 3-isoxazolyl and which is unsubstituted or substituted by C χ -C 6 alkyl; and the pharmaceutically acceptable salts thereof; and wherein, when : is hydrogen, then Q is only a / -CON group in which R4 is as defined above and either R j -, is a -CH-COOR^ group wherein 1 . and R^ are as defined above or R j -, is a") a R-, -(CH 2 ) Z -R' 5 group wherein z is zero, 1 or 2 and R's is as R5 defined above under d') , e 1 ) or f•) or b") a CH-R5 or -A'-Rs group, wherein A 1 CH 3 is a C3~Cg alkylene chain and R5 is as defined above. 2. A ∞rrpound of formula (I) according to claim 1, wherein X is oxygen or a -S(0)p-grσup, in which p is zero or 1; R represents umsubstituted pyridyl, or phenyl unsubstituted or substituted by one or two substituents chosen independently from halogen, trifluorcmethyl, CyC^ alkyl, C^-C^ alkoxy, nitro, amino and C 2 -C 8 a-Uancylam no; is a ") hydrogen, COOH, CHO, CH 2 0H, C 2 -C 7 alkoxycarbonyl or a wherei ■ n each of R" ' and RI x V v independently is C± or C alkyl, or R' • ' and Εt 7 , taken together with the nitrogen atom to which they are linked, form a N-pyrrolidinyl, N-piperazinyl, morpholino or piperidino ring which is urisub-Ξtituted or -=a_bstit-uted ty methyl; b βo ) a -XMJCH-COORα group wherein R- j is hydrogen or ^-Cg alkyl and R,-, *c is hydrogen, phenyl or the side-chain of an α-aminoacid as defined above; c β " ) a -NHO0CH-NH 2 group, wherein R ς , is as defined above; d° ° ) a -CH OCO(CH 2 ) n C0OR c or a -l^ O(CH2) c∞R d ( 3 rcΛJ Pι wherein n and tare as defined above; e° °) a -σ^N-OR 1 ! group, wherein R'-^ is hydrogen or a -CH 2 O00H group; f o β ) a -a§=N-NHR' group, wherein R' is hydrogen or -CH 2 CH 2 OH; R HI g° ° ) a -NH=€H-N group, vdierein R 111 and R 1 ^ are as defined above; h 00 ) a C 2 -C 4 alkoxycarbonyl group substituted by a wherein R 111 and R- 1 -^ are as defined above; R 2 and R 3 each. -Independently is hydrogen, halogen, nitro, amino, hydroxy, C^-C^ alkyl or L-C4 alkoxy; R4 represents hydrogen or C--L- 4 alkyl; Q represents hydrogen, C 2 -C 5 alkoxycar- iπyl or a -α-WR' g R' j ., group, v_herein R' a is hydrogen or C-^-Cg alkyl and R' j -, is C 1 -C 6 alkyl or a -CH-C00Rg group, wherein Rg is hydrogen or C 1 -C alkyl a . c is " as c defined above; or R' p is a -(A") m -R H 5 group, wherein is zero or 1, A" is a L-C3 alkylene chain and R" 5 is: a 1 * ') unsubstituted pyridyl or phenyl, unsubstituted or substituted by one or two -substituents chosen j_ndeperriently from halogen, CF3, ^-C -. alkyl, C-J-C alkoxy, hydroxy, nitro and di-(C 1 -C 4 alkyl) amino; R » " / b' ' ' ) phenyl, substituted by -CH 2 CH, OOOH or a -CH 2 -N group, R IV wherein R 1 • ' and R * ^ are as defined above, and optionally by another substituent chosen frcm C 1 -C 4 alkyl, ±-C^ alkoxy, hydroxy, formyloxy and C 2 -Cg alkanoyloxy; or c' 11 ) 2-thienyl or 2-furyl; or d' ' ') 2-thiazolyl or 3-isoxazolyl, wherein said heterocyclic rings may be ι_r_su_bstituted or -substituted by methyl; and the pharmaceutically acceptable salts thereof; .and wherein when R R' / is hydrogen, then Q is only a -CON a group, wherein R' a is as defined \ , R'b above and R' j -, is (1) a -CH-COORg group wherein R-, and Rg are as Rc defined above or (2) a -(CH 2 ) 2 -R5' ' ' group, wherein z is zero, 1 or 2 and R5 1 ' ' is as R" 5 defined above under b' * «) , c 1 ") and d' • ') , or (3) a -CH-R"5 group, vftierein R π 5 is as defined above. CH 3 3. A compound of formula (I) , according to claim 1, wherein X is oxygen or sulphur; R is phenyl, unsubstituted and substituted by a substituent selected from nitro, halogen, CF 3 , C- - ^ alkyl and C-^-K-^ alkoxy; ^ ia a 00β ) hydrogen, -COOH, -CHO, -CH 2 0H, C 2 -C5-alkoj!_ycarbonyl, or a R" • —CH 2 N group, wherein R 1 ' ' and R 7 axe as defined above; \R IV each of R 2 and R 3 independently is hydrogen, halogen, nitro, amino, hydroxy, C 1 -C alkyl or C 1 -C4 alkoxy; b βo °) a -CONHCH-COOR'^ group, wherein R'^ is hydrogen or C-^^ alkyl Rc and Rc is as defined above; c βββ ) a -NHOOCH-NH 2 group wherein Rc is as defined above; Rc d 000 ) a -CH000(CH 2 ) n 000R l (j or a -NHOO(CH ) n C0O group, wherein n and R'£ are as defined above; e°°") a ; f°°°) a wherein R 111 and R 1 ^ are as defined above; R represents hydrogen or methyl; Q represents hydrogen or a -O0NR" a R l - D group, wherein R 1 ' a is hydrogen or C1-C alkyl and R" ] -, is C-L-C4 alkyl or a -CH-O00I^ group wherein Rc and Rg are as defined above; Rc or R 11 ]- ) is a -(CH^g-R 1 ^ group, wherein z is zero, 1 or 2 and p 5 is aP?) unsuibstituted pyridyl or phenyl, unsubstituted or substituted by a substituent chosen from nitro, halogen, CF , C1-C4 alkyl, C1-C4 alkoxy and di(C 1 -C 2 alkyl)-amino; wherein R 1 ' • and R 1 ^ are as defined above, and optionally by another substituent chosen frcm hydroxy and C^-*^ alkoxy; or o ?) 2-thienyl or 2-furyl; dP 7 ) 2-thiazolyl or 3-isoxazolyl, imsubstituted or substituted by methyl; and the pharmaceutically acceptable salts thereof; and wherein, when Ri is hydrogen, then Q is a -CONR" a R" r , group, wherein R" a is as defined above and R" ] -, is (1) a -CH-COORg group, wherein Rc and Rg -are as defined above; Rc or (2) a -(CH 2 ) Z -R V 5 group wherein z is as defined above and R v 5 is as RP 7 5 defined above under b 1 ) , cP 7 ) or d 1 ^ . 4. A ccmpσund according to claim 1 selected from: N-[2-cyano-3-(1,4-dihydro-l-phenyl-[1]-benzothicpyrano[4,3-c]pyrazol-3- yl)-3-oxo-propanσyl]-glycine, methyl ester; N-[2-cyano-3-(1,4-dihydro-l-pheryl-[1]-benzσthicpyrano[4,3-c]pyrazol-3- yl)-3-oxo-prcpanoyl]-D -leucine, methyl ester; N-[2-cyano-3-(1,4-dihydro-l-phenyl-[1]-benzσthicpyrano[4,3-c]pyrazol-3- yl)-3-oxo-p- pancyl]-D] pherylalanine, methyl ester; N- [2-cyano-3- (1, 4-dihydro-l-pheιψl-[l] -benzσthicpyrano [4 , 3-c]pyrazol-3- yl)-3-αxo-prσpanσyl]-DIr-phenylglycine, methyl ester; 2-cyano-3- (1, 4-dihydro-l-phenyl- [1] -benzσthicpyrano [4 , 3-c]pyrazol-3- yl)-3-oxo-N-(2-thenyl)-prcpanamide; 2-cyano-N- (2-fu-rruryl) -3- (1, 4-dihydro-l-phenyl- [1] -berizothiσpyrano [4 , 3-c]pyrazol-3-yl) -3-oxc>-prσpanamide; 2-cyano-3- (8-f luoro-l, 4-d-Lhydro-6-mo-_pholincmethyl-l-E>henyl- [1] -benzo- pyrano[4, 3-c]pyrazol-3-yl) -3-oxo-N-phenyl-propanamide; 2-cyano-3- (1, 4-dilιydro-8-morrΛolincxιethyl-l-phenyl- [1] -benzopyrano [4, 3-c]pyrazol-3-yl) -3-oxo-N-phenyl-prcpc3namide; 2-cyano-3- (1 , 4-dihydro-l-pherιyl- [1] -benzothicpyrano [4 , 3-c] pyrazol-3- yl) -N- (2-mo--pholir-o-ιethyl-benzyl) -3-oxo-propanamide; N- [2-cyano-3- (1, 4-<i-lιydro-l-phenyl-[l] -benzσthiopyrano[4 , 3-c]pyrazol-3- yl) -3-oxo-propancyl] -DL-leucine; 2-cyano-3- (8-ethoxycarbonyl-l, 4-dihyd_ro-l-pher^l-[l]---enzot cpyraι-o [4, 3-c]pyrazol-3-yl) -3-oxo-N-pheπyl-prcpanamide; - 63 - 2-cyano-3-(6-ethoxycarbonyl-l ,4-dihydro-l-phenyl- [l] -benzo¬ thiopyrano [ , 3-c] pyrazol-3-yl ) -3-oxo-N-pnenyl-propanamide ; N- [l ,4-dihydro-l-phenyl-3-(2-phenylcarbamoyl-cyanoacetyl )- [l] -benzothiopyrano [4 , 3-c] pyrazol-8-ylJ carbonyl-glycine methyl ester; N- fl ,4-dihydro-l-phenyl-3-( 2-phenylcarbamoyl-cyanoacetyl )- [1] -benzσthicpyrano [4 , 3-c] yrazol-6-yl] carbonyl-glycine methylester ; 2-cyano-3-( 8-ethoxalylamino-l , 4-dihydro-l-phenyl- [lj -benzo- thiopyrano [4 , 3-c3pyrazol-3-yl)-3-oxo-N-p_ienyl-propanamide ; 2-cyano-3-( 1 , 4-dihydro-8-oxalamino-l-phenyl- [lj -benzothio¬ pyrano [4 , 3-c] pyrazol-3-yl )-3-oxo-N-phenyl-propanamide ; 2-cyano-3-(l , 4-dihydro-8-N,N- dime thy laminoethoxyc arbony 1-1- phenyl- [lj -benzothiopyrano Q4,3-c]pyrazol-3-yl )-3-oxo-N- phenyl-propanamide ; 2-cyano-3-( 1 , 4-dihydro-6-N,N-dime thy laminoethoxyc arbony 1-1- phenyl- [l] -benzothiopyrano £4, 3-c pyrazol-3-yl )-3-oxo-N- phenyl-propanamide ; and the pharmaceutically acceptable salts thereof. 5. A process for the preparation of a compound of formula (I) , or a pharmaceutically acceptable salt thereof, as claimed in claim 1, which process comprises; /12638 - 64 - a) reacting a compound of formula (II) whereiπ claim 1 X , R , R , R , R and R are as defined in/ and Y is carboxy or a reactive derivative of a carboxy group , with a compound of formula (III ) wherein , . claim 1 0 * is as 0 defined in/ , except carboxy, so obtaining a • cαπpσund of formula (I) , wherein Q is as defined in claim 1 excep ^ carboxy; or b ) reacting a compound of formula ( IV) ( IV) wherein c.lai.m 1 X, R, R , R , R and R are as defined in/ , with a compound of formula (V) R -N=C=0 (V) b wherein claim 1 R is as defined in/ , so obtaining a compound of formula (I) wherein 0 is a -CONHR. group, wherein R is as defined b t in claim 1; or c) reacting a compound of formula (VI) wherein claim 1 X, R, R , R , R and R are as defined in/ and Z is a react¬ ive derivative of a carboxy group, with a compound of formula (VII) (VII) wherein Ra and R j -, are as defined in claim 1, so obtaining a compound of formula (I) wherein Q is a -CO group, wherein R & and R j -, are as defined in claim 1; or d) hydrolysing a compound of foππula (I), wherein Q is C 2 -C 7 alkoxy- c-t^l « a -a* - CH-O^ w . in vfri* - H. „ as R a Rc defined in claim 1 and R^ is C^-Cg -alkyl, so as to obtain the corresponding cαxpcund of formula (I), wherein Q is a free carboxy group or a -CON CH-C00H group, in which R=, and ^, are as defined in I f Ra c claim 1; and, if desired, converting a compound of formula (I) into another compound of formula (I) and/or, if desired, converting a compound of foππula (I) into a pharmaceutically acceptable salt and or, if desired, converting a salt into a free compound, and/or, if desired, separating a mixture of isomers of a compound of formula (I) , into the single isomers. 6. A pharmaceutical ccmposition ccataining a pharmaceutically acceptable carrier and/or diluent and, as an active principle, a cc pσund of foππula (I), or a pharmaceutically acceptable salt thereof, as claimed in claim 1. 7. A compound of foππula (I) , or a pharmaceutically acceptable salt thereof, according to claim 1, for use as an irnnmunostimulating agent. 8. A compound of foππula (I) or salt thereof according to claim 7, for use in the treatment of an acute or chronic infection of bacterial or viral origin. 9. A ccπpound of foππula (I) or salt thereof according to claim 7, for use in the treatment of a neαplastic disease. 10. Use of a compound of formula (I) , or pharmaceutically acceptable salt thereof, as claimed in claim 1, in the preparation of a medicament for use as an -Lmmu_no-_timo-ιlating agent.

Inventors: DORIA GIANFEDERICO, FERRARI MARIO, ISETTA ANNA MARIA, TRIZIO DOMENICO, DORIA, GIANFEDERICO, FERRARI, MARIO, ISETTA, ANNA, MARIA, TRIZIO, DOMENICO
Applicants: ERBA CARLO SPA, FARMITALIA CARLO ERBA S.R.L.
Application year: 1989
Main classification: C07D491
IPC codes: A61K31, A61P35, A61P37, C07D491, C07D495