GB2157285A

GB2157285A - 1H,7H-pyrazolo1,5-a pyrimidine-7-one derivatives and process for their preparation

Info

Publication number: GB2157285A
Application number: GB08409424A
Authority: GB
Inventors: Gianfederico Doria; Carlo Passarotti; Roberto Sala; Alessandro Rossi
Original assignee: Farmitalia Carlo Erba SRL
Current assignee: Pfizer Italia SRL
Priority date: 1984-04-11
Filing date: 1984-04-11
Publication date: 1985-10-23
Also published as: GB8409424D0; GB2157285B; JPS60228483A; BE902150A; DE3510134A1

Abstract

1H,7H-Pyrazolo[1,5-a]pyrimidine-7-one derivatives of formula (I> <IMAGE> wherein R1 is: a) C1-C6 alkyl or benzyl; b) pyridyl, unsubstituted or substituted by C1-C6 alkyl; c) phenyl, unsubstituted or substituted by one or more substituents chosen from halogen,trihalo-methyl, C1-C6 alkyl, C1-C6 alkoxy, hydroxy, formyloxy C2-C6 alkanoyloxy, nitro, amino, formylamino and C2-C6 alkanoylamino; R2 is a) pyridyl; or b) phenyl, unsubstituted or substituted by one or more substituents chosen from halogen, trihalomethyl, nitro, C1-C6 alkoxy and C1-C6 alkyl; R3 is hydrogen or C1-C6 alkyl, unsubstituted or substituted by one or more substituents chosen from halogen, hydroxy, C1-C6 alkoxy, formyloxy, C2-C6 alkanoyloxy and the <IMAGE> group, wherein each of R5 and R6 is independently hydrogen, C1-C6 alkyl, phenyl or benzyl, or R5 and R6, taken together with the nitrogen atom to which they are linked, forms heterocyclic ring chosen from N-imidazolyl, hexahydro-N-azepinyl, N-pyrrolidinyl, N-piperazinyl, piperidino, thiomorpholino and morpholino, each of the heterocyclic rings being unsubstituted or substituted by C1-C6 alkyl; R4 is hydrogen, halogen, C1-C6 alkyl, hydroxy, C1-C6 alkoxy, C3-C4 alkenoyloxy, formyloxy or C2-C6 alkanoyloxy; and the pharmaceutically acceptable salts thereof; are central nervous system depressants.

Description

SPECIFICATION 1 H,7H-Pyrazolo[1,5-a]pyrimidine-7-one derivatives and process for their preparation The present invention relates to new 1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one derivatives, to a process for their preparation and to pharmaceutical compositions containing them.The invention provides compounds having the following general formula (I)

wherein R1 is: a) C1-C6 alkyl or benzyl; b) pyridyl, unsubstituted or substituted by C,-C6 alkyl; c) phenyl, unsubstituted or substituted by one or more substituents chosen from halogen, trihalo-methyl, C,-C6 alkyl, C,-C6 alkoxy, hydroxy, formyloxy, C2-C6 alkanoyloxy, nitro, amino, formylamino and C2-C6 alkanoylamino; R2 is a) pyridyl; or b) phenyl, unsubstituted or substituted by one or more substituents chosen from halogen, trihalomethyl, nitro, C1-C6 alkoxy and C1-06 alkyl; R3 is hydrogen or C1 -C6 alkyl, unsubstituted or substituted by one or more substituents chosen from halogen, hydroxy, C1 -C6 alkoxy, formyloxy, C2-C6 alkanoyloxy and the

group, wherein each of R5 and R6 is independently hydrogen, C1-C6 alkyl, phenyl or benzyl, or R5 and R6, taken together with the nitrogen atom to which they are linked, form a heterocyclic ring chosen from N-imidazolyl, hexahydro-N-azepinyl, N-pyrrolidinyl, N-piperazinyl, piperidino, thiomorpholino and morpholino, each of the heterocyclic rings being unsubstituted or substituted by C1-C6 alkyl;; R4 is hydrogen, halogen, C1-C6 alkyl, hydroxy, C1-C6 alkoxy, C3-C4 alkenoyloxy, formyloxy or C2-C6 alkanoyloxy; and the pharmaceutically acceptable salts thereof.

The present invention includes also the metabolites and the metabolic precursor of the compounds of formula (I) and all the possible isomers of the compounds of formula (I), e.g. optical isomers, and the mixtures thereof.

The alkyl, alkoxy, alkanoyloxy and alkanoylamino groups may be branched or straight chain groups.

A halogen atom is, for example, chlorine, bromine or fluorine, preferably it is chlorine or fluorine.

A trihalomethyl group is preferably a trifluoromethyl groups.

A C2-C6 alkanoyloxy group is, for example, acetoxy, propionyloxy, butyryloxy or valeryloxy, preferably it is acetoxy.

AC1-C6 alkyl group is preferably a C1C4 alkyl group, in particular, methyl, ethyl, propyl ortert.butyl.

A C-C6 alkoxy group is preferably C-C4 alkoxy, in particular, methoxy, ethoxy, propoxy or butoxy.

A C2-C6 alkanoylamino group is, for example, acetylamino, propionylamino, butyrylamino or valerylamino; preferably it is acetylamino.

When R1 and/or R2 is phenyl, substituted as defined above, or Rg is C,-C6 alkyl, substituted as defined above, they are preferably substituted by one, two or three substituents.

When R1 is a C-C6 alkyl group, it is, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl, preferably it is methyl, ethyl, propyl ortert-butyl.

When R1 is a pyridyl group substituted by a C-C6 alkyl group, the alkyl group may be, for example, methyl, ethyl or propyl, preferably it is methyl.

When R1 and/or P2 is a phenyl ring substituted as defined above, it is more preferably substituted by one or two substituents chosen from halogen, nitro, trifluoromethyl, C-C4 alkyl and C1-C4 alkoxy.

When P3 andlor R4 is an unsubstituted C,-C6 alkyl group, it is, for example, methyl, ethyl, propyl, isopropyl or butyl, preferably it is methyl, ethyl, propyl or isopropyl.

When P3 is a C-C6 alkyl group substituted by one or more halogen atoms, it is preferably a C-C3 alkyl group substituted by one to three chlorine or fluorine atoms.

When P3 is a C-C6 alkyl group substituted by one or more C-C6 alkoxy groups, it is preferably a C-C3 alkyl group substituted by one to three C-C2 alkoxy group.

When R4 is a halogen atom it is, e.g., chlorine, bromine or fluorine, preferably it is chlorine or bromine. When R4 is a C-C6 alkoxy group, it is, for example, methoxy, ethoxy, propoxy, isopropoxy or butoxy, preferably it is methoxy, ethoxy or propoxy.

When one or both of R5 and R6, being the same or different, is a C-C6 alkyl group, it is for example methyl, ethyl, propyl, isopropyl or butyl; preferably it is methyl, ethyl, propyl or isopropyl.

When P5 and R6, taken together with the nitrogen atom to which they are linked, form a heterocyclic ring as defined above and said ring is substituted by C,-C6 alkyl, the alkyl group is preferably C1-C4 alkyl, in particular methyl or ethyl.

Preferred compounds of the invention are those of formula (I) wherein Rlis: a') C-C4 alkyl or benzyl; b') pyridyl, unsubstituted or substituted by one or two substituents chosen from halogen, trifluoromethyl, C-C4 alkyl, C1-C4 alkoxy, nitro, amino, formylamino and C2-C6 alkanoylamino; R2 is phenyl, unsubstituted or substituted by one or two substituents chosen from chlorine, fluorine, trifluoromethyl, nitro, C1-C4 alkyl and C1-C4 alkoxy;; R3 is hydrogen or Ca-C4 alkyl, unsubstituted or substituted by one to three substituents chosen from chlorine, fluorine, hydroxy, C1-C4 alkoxy, formyloxy, C2-C6 alkanoyloxy and the

group wherein each of R5 and P6 is independently hydrogen, C1-C4 alkyl or phenyl, or P5 and P6 taken together with the nitrogen atom to which they are linked, form a heterocyclic ring chosen from N-imidazolyl, hexahydro-N-azepinyl, N-pyrrolidinyl, N-piperazinyl, piperidino, thiomorpholino and morpholino, each of the heterocyclic rings being unsubstituted or substituted by C1-C3 alkyl;; R4 is hydrogen, halogen, C1C4 alkyl, hydroxy, C1-C4 alkoxy, C3-C4 alkenyloxy or C2-C6 alkanoyloxy; and the pharmaceutically acceptable salts thereof.

More preferred compounds of the invention are those of formula (I) wherein P1 is: a") C1-C4 alkyl, benzyl or pyridyl; b") phenyl, unsubstituted or substituted by one or two substituents chosen from chlorine, fluorine, trifluoromethyl, methyl, C1-C2 alkoxy, nitro, amino, formylamino and C2-C4 alkanoylamino; R2 is phenyl, unsubstituted or substituted by one or two substituents chosen from halogen, trifluoromethyl, nitro, C1-C4 alkyl and C1-C4 alkoxy;; P3 is hydrogen or Ca-C4 alkyl, unsubstituted or substituted by one to three substituents chosen from halogen, hydroxy, C1-C2 alkoy, formyloxy, C2-4 alkanoyloxy and the

group, wherein each of P5 and P6 is independently hydrogen or C1-C4 alkyl, or P5 and R6, taken together with nitrogen atom to which they are linked, form a heterocyclic ring chosen from unsubstituted N-imidazolyl, unsubstituted hexahydro-N-azepinyl, unsubstituted N-pyrrolidinyl, N-piperazinyl unsubstituted or substituted by Ca-C3 alkyl, piperidino and morpholino, each being unsubstituted or substituted by methyl and unsubstituted thiomorpholino; R4 is hydrogen, halogen, C1-C4 alkyl, hydroxy, C1-C3 alkoxy, allyloxy or C2-C4 alkanoyloxy; and the pharmaceutically acceptable salts thereof.

Examples of pharmaceutically acceptable salts are the salts with inorganic acids, e.g. nitric, hydrochloric, hydrobromic and sulphuric acids and the salts with organic acid, e.g. citric, tartaric, maleic, malic, fumaric, methanesulphonic and ethanesulphonic acids.

Examples of particularly preferred compounds of the invention are: 1 ,2-diphenyl-5-methyl-i H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1,2-diphenyl-5-trifluoromethyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1 ,2-diphenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 5-methyl-1-(4-methyl-phenyl)-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 5-methyl-1-(4-nitro-phenyl)-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(4-chloro-phenyl)-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1 -(3-chloro-phenyl)-5-methyl-2-phenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1-(4-fluoro-phenyl)-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 5-methyl-2-phenyl-1 -(3-trifluoromethyl-phenyl)-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one;; 1 -benzyl-5-methyl-2-phenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1 -tert.butyl-5-methyl-2-phenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1 ,5-dimethyl-2-phenyl-1 H,7H-pyrazolo[i ,5-a]pyrimidine-7-one; 5-methyl-2-phenyl-1-(2-pyridyl)-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 5-methyl-2-phenyl-1 -(3-pyridyl)-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1 ,2-bis-(3-chloro-phenyl)-5-methyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1-(3-chloro-phenyl)-2-(4-methoxy-phenyl)-5-methyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1 ,2-diphenyl-5,6-dimethyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 6-chloro-1 ,2-diphenyl-5-methyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one;; 1 ,2-diphenyl-6-methoxy-5-methyl-1 H,7H-pyrazolo [1 ,5-a]pyrimidine-7-one; 1 ,2-diphenyl-6-ethoxy-5-methyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 5-(N,N-diethylamino-methyl)-1 ,2-diphenyl-i H,7H-pyrazolo[1 ,5-a] pyrimidine-7-one; 1,2-diphenyl-5-(pyrrolidin-1-yl-methyl)-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1 ,2-diphenyl-5-(imidazol-1-yl-methyl)-1 H,7H-pyrazolol ,5-a]pyrimidine-7-one; 1,2-diphenyl-5-methoxymethyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; and the pharmaceutically acceptable salts thereof.

The compounds of the invention can be prepared by a process comprising: a) cyclization of a compound of formula (II)

wherein P1, R2, R3 and R4 are as defined above and R7 is a nucleophile group which is capable of being cleaved from the carbon atom to which it is attached during the cyclisation of the compound of formula (II), or a salt thereof;; b) decarboxylation of a compound of formula (III)

wherein R1 and R2 are as defined above and R8 is hydrogen or unsubstituted C-C6 alkyl, so obtaining compounds of formula (I) wherein P3 is hydrogen or unsubstituted C-C6 alkyl and 4 is hydrogen, or c) thermal cyclisation of a compound of formula (IV)

wherein R1, R2 and P8 are as defined above and each of Rg and Rlo is independently Ci-Ce alkyl, so obtaining compounds of formula (I) wherein P3 is hydrogen or unsubstituted C1-C6 alkyl and R4 is hydrogen, and if desired, converting a compound of formula (I) into another compound of formula (I) andSor, if desired, converting a compound of formula (I) into a pharmaceutically acceptable salt thereof and/or, if desired, obtaining a free compound of formula (I) from a salt thereof and/or, if desired, separating a mixture of isomers into the single isomers. When R7 is a nucleophile group as defined above, it is, for example, hydroxy, tri-(C,-C6)alkyl-silyloxy, or C,-C6 alkoxy.

The compounds of formula (II) may also be represented by the tautomeric formula (lla)

wherein P1, R2, R3, R4 and R7 are as defined above.

Preferred salts of the compounds of formula (II) are, for example, those with inorganic acids such as hydrochloric, hydrobromic, hydroiodic, phosphoric and sulphuric acid.

The cyclization of a compound of formula (II) may be, for example, carried out by treatment with an acid condensing agent such as polyphosphoric acid (alone or in the presence of phorphorus oxychloride), sulphuric acid, hydrochloric acid, methanesulphonic acid or p-toluenesulphonic acid, at a temperature ranging preferably between about 50"C and about 150 C; the reaction may be carried out in an organic solvent such as dimethylformamide, dimethylacetamide, dimethylsulphoxide, benzene, toluene, xylene, ethylene glycol monomethylether or dichloroethane, but it is preferably carried out in the absence of a solvent.

Alternatively, the cyclization of a compound of formula (II) may be carried out by heating the compound at a temperature ranging between about 15000 and about 350 C, preferably between 200 C and 300 C, in an inert high boiling organic solvent such as diphenyl ether, or in the absence of a solvent.

The decarboxylation of a compound of formula (III) may be, for example, carried out by heating in a solvent such as quinoline in the presence of copper powder at a temperature varying between 15000 and 200 C, or alternatively by melting in the presence of CuO at a temperature varying between 200 C and 300 C.

The termal cyclization of a compound of formula (IV) may be, for example, carried out by melting or alternatively by heating in an inert solvent such as nitrobenzene, diethylphthalate mineral oil, diphenyl ether or Dowtherm A (eutectic mixture of diphenyl and diphenyl ether), at a temperature varying between 200 C and 300 C, preferably varying between 230 C and 270 C.

A compound of formula (I) may be converted, as stated above, into another compound of formula (I) by known methods: for example, free hydroxy groups may be etherified by reacting with a suitable alkyl halide in the presence of a base such as NaOH, KOH, Na2CO3, NaH, NaNH2, sodium methoxide, K2CO3 or sodium ethoxide, in a solvent selected from the group consisting, for example, of methanol, ethanol, dioxane, acetone, dimethylformamide, hexamethylphosphorotriamide, tetrahydrofuran, water and their mixtures at a temperature ranging preferably between about 0"C and about 150"C.

Furthermore the etherified hydroxy groups may be converted into free hydroxy groups, for example, by treatment with pyridine hydrochloride or with a strong acid such as HCI, HBr, or HI, or with a Lewis acid such as AICI3 or BBr3. Furthermore, for example, a nitro group may be converted into an amino group by treatment, for example, with stanous chloride in concentrated hydrochloric acid, using, if necessary, an organic cosolvent such as acetic acid, dioxane, tetrahydrofuran at a temperature varying between room temperature and about 100"C.

Furthermore, for example, an amino or hydroxy group may be converted respectively into a formylamino, C2-C6 alkanoylamino or CrCe alkanoyloxy group, for example by reaction with formic acid or with the corresponding alkanoyl anhydride without any solvent or in an organic solvent such as dioxane, dimethylformamide, tetrahydrofuran, usually in the presence of a base such as pyridine or triethylamine at a temperature varying between 0 C and about 1 OO"C.

Furthermore, for example, a compound of formula (I) wherein R4 is hydrogen may be converted into a compound of formula (I) wherein R4 is chlorine or bromine by reaction with a suitable halogenating agent such as chlorosuccinimide or bromosuccinimide, SO2Cl2 or pyridinium bromide perbromide, operating at a temperature ranging from 0 C to 100"C and using, for example, as solvent CC14 or dichloroethane in the reaction with SO2Cl2, pyridine in the reaction with pyridinium bromide perbromide and benzene in the reaction with a halosuccinimide.

Furthermore, for example, a compound of formula (I) wherein P3 is a C1-C6 alkyl group substituted by a halogen atom may be converted into a compound of formula (I) wherein P3 is a C1-CB alkyl group substituted buy a group

wherein P5 and P6 are as defined above, by reaction with a compound of formula

wherein P5 and Rg are as defined above, in an organic solvent such as methylethylketone, toluene, xylene, dimethylformamide, dimethylacetamide, at a temperature varying between 20"C and 150"C.

Also the optional salification of a compound of formula (I) as well as the conversion of a salt into a free compound and the separation of a mixture of isomers into the single isomers may be carried out by conventional methods.

For example, the separation of a mixture of optical isomers into the individual isomers may be carried out by salification with an optically active base or acid and subsequent fractional crystallization.

The compounds of formula (II) may be prepared, for example, by reacting a compound of formula (V)

wherein R, and P2 are as defined above, or a salt thereof, with a compound of formula (Vl)

wherein R3, R4 and R7 are as defined above and R is a reactive group chosen, preferably, from hydroxy, amino, C1-Cg alkoxy, ortri-(C-C6)alkyl-silyloxy.

Preferred salts of a compound of formula (V) are, for example, those with inorganic acids such as hydrochloric, hydrobromic, phosphoric and sulphuric acid.

The reaction between a compound of formula (V) and a compound of formula (VI) may be carried out, for example, by heating in solvents such as dioxane, toluene, xylene, acetonitrile, C1-C4 alkyl alcohols, acetic acid, dimethylformamide, dimethylacetamide, diphenylether or in the absence of a solvent, at a temperature varying from room temperature to about 200"C. Preferably, when R11 is hydroxy, the reaction between a compound of formula (V) and a compound of formula (VI) is carried out in the presence of an acid condensing agent such as polyphosphoric acid, methanesulphonic acid, p-toluenesulphonic acid or acetic acid using the same experimental conditions, as described above, for the cyclization of the compounds of formula (II).

Under these specific conditionsthe reaction of a compound of formula (V) with a compound of formula (Vl) may be carried out till a compound of formula (I) is obtained without the need to isolate the intermediate product of formula (II) formed during the reaction.

The compounds of formula (III) may be prepared, for example, by hydrolyzing a compound of formula (VII)

wherein P1, R2 and R3 are as defined above and R,2 is cyano or an esterified carboxy group or a tri-(C1-C6)alkyl-silyloxy-carbonyl group, by treatment, for example, with a mineral acid such as HCI, HBr, HI in water or in acetic acid or dioxane or their mixtures at a temperature varying between room temperature and about 1 200C.

The compounds of formula (IV) may be prepared, for example, by reacting a compound of formula (V) with the mixture of a compound of formula (VIII) R8-C(OR13)3 (VIII) wherein R8 is as defined above and P13 is C1-C6 alkyl, and a compound of formula (IX)

wherein Rg and R0 are as defined above.The reaction between a compound of formula (IV) and the mixture of a compound of formula (VIII) and a compound of formula (IX), may be carried out, for example, without a solvent or in the presence of an inert solvent such as benzene, ethanol, dioxane, tetrahydrofuran, acetonitrile, dimethylformamide, at a temperature varying between room temperature and about 150"C. The compound of formula (VIII) may be prepared by cyclizing a compound of formula (X)

wherein R1, R2, R3, R7 and P12 are as defined above, using the same experimental conditions specified above for the cyclization of a compound of formula (II).

The compounds of formula (V), (VI), (VIII) and (IX) are known compounds or may be prepared by conventional methods: in some cases they are commercially availabie products. The compounds of the invention are active on the central nervous system (CNS), in particular as central nervous systems depressants, i.e. as sedative, anticonvulsive agents, minor tranquilizers, and as sleep-inducing agents. The activity on the ONS of the compounds of the invention was evaluated, for example, in the experimental framework of the behavioural assessment by the Irwin's technique [Irwin, S., Psychopharmacologia (Berl.), 13, 222, 1968]. In this test, the compounds of the invention, proved to be active as CNS depressants, in particular as sedative agents and as minor tranquilizers, and in inducing hypnosis e.g. in mice and rats.The animals, treated with oral doses ranging from 5 to 100 mg/kg body weight, showed loss of righting reflex, without contemporary depression of muscle-tone, respiratory frequency, rectal temperature and of otherless indicative reflexes.

The toxicity of the compounds of the invention is negligible, therefore they can be safely used in therapy.

Nine hours food deprived mice and rats were treated orally with single administration of increasing doses, then housed and normally fed. The orientative acute toxicity (LD50) was assessed on the seventh day after the treatment and resulted, in general, higher than 600 mg/kg.

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 injection or infusion.

The dosage depends on the age, weight, conditions of the patient and administration route; for example the dosage adopted for oral administration to adult humans may range from about 10 to about 100 mg pro dose, from 1 to 5 times daily.

The invention includes pharmaceutical compositions comprising a compound of the invention in association with a pharmaceutically acceptable excipient (which can be a carrier or diluent).

The pharmaceutical compositions containing the compounds ofthe 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, cellulose, corn starch or potato starch; lubricants, e.g. silica, talc, stearic acid, magneisum or calcium stearate, and/or polyethylene glycols; binding agents, e.g. starches, arabic gums, gelatin, methylcellulose, carboxymethyl cellulose or polyvinyl pyrrolidone; disaggregating 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 andlor mannitol and/or sorbitol; in particular a syrup to be administered to diabetic patients can contain as carriers only products not metabolizable to glucose, or metabolizable in very small amount to glucose, for example sorbitol.

The suspensions and the emulsions may contain as carrier, for example, a natural gum, agar, sodium alginate, pectin, methylcellulose, carboxymethylcellulose, or polyvinyl alcohol.

The suspensions or solutions for intramuscular injections may contain together with the active compound a pharmaceutically acceptable carrier, e.g. sterile water, olive oil, ethyl oleate, glycols, e.g. propylene glycol, and if desired, a suitable amount of lidocaine hydrochloride. The solutions for intavenous 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 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 3-amino-1 5-diphenyl-pyrazole (5.2 g) was reacted with ethyl acetoacetate (4.4 g) in polyphosphoric acid (52 g: 28 g of H3PO4 and 24 g of P2O5) under stirring at 100 C for 1.5 hours. After cooling the reaction mixture was diluted with ice water and neutralized with 35% NaOH. The solution was extracted with ethyl acetate and then the organic phase was evaporated in vacuo to dryness. Crystallization from chloroform-isopropyl ether gave 2.5 g of 1 ,2-diphenyl-5-methyl-1 H,7H-pyrazolo[1,5-a]pyrimidin-7-one, m.p. 147-1480C, NMR (CDC3) #ppm:2.37(s) (3H,CH3), 5.91(bs) (1H, C-6 proton), 6.55(s) (1H,C-3 proton), 7.40 (m) (10H, phenyl protons).

By proceeding analogously the following compounds were prepared; 5-methyl-1-(2-methylphenyl)-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 5-methyl-1-(2-nitro-phenyl)-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(2-chloro-phenyl)-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(2,4-dichloro-phenyl)-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(2,5-dichloro-phenyl)-5-methyl-2-phenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 5-methyl-2-phenyl-1 -(2-trifluoromethyl-phenyl)-1 H,7H-pyrazolo[l ,5-a]pyrimidine-7-one; 5-methyl-1-(3-methyl-phenyl)-2-phenyl-1 H,7H-pyrazolo[l ,5-a]pyrimidine-7-one; 5-methyl-1-(3-nitro-phenyl)-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(4-methoxy-phenyl)-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-1]pyrimidine-7-one;; 1-(2,6-dichloro-phenyl)-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(3-fluoro-phenyl)-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 5-methyl-2-phenyl-1-(3-trifluoromethyl-phenyl)-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one, m.p. 149-150 C; 5-methyl-1-(4-methyl-phenyl)-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 5-methyl-1-(4-nitro-phenyl)-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(4-chloro-phenyl)-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(3-chloro-phenyl)-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(4-fluoro-phenyl)-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 5-methyl-2-phenyl-1-(4-trifluoromethyl-phenyl)-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-benzyl-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1 -tert.butyl-5-methyl-2-phenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one;; 1,5-dimethyl-2-phenyl-1H-7H-pyrazolo[1,5-a]pyrimidine-7-one; 5-methyl-2-phenyl-1 -(2-pyridyl )-1 H,7H-pyrazolo [1,5-a]pyrimidine-7-one; 5-methyl-2-phenyl-1 -(3-pyridyl)-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 2-(4-chloro-phenyl)-1-phenyl-5-methyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 2-(4-methoxy-phenyl)-1 -phenyl-5-methyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 5-methyl-1-phenyl-2-(3-pyridyl)-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1,2-bis-(3-chloro-phenyl)-5-methyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; and 1-(3-chloro-phenyl)-2-(4-methoxy-phenyl)-5-methyl-1 H,7H-pyrazolo[1 ,5-ajpyrimidine-7-one.

Example 2 By proceeding according to Example 1, using suitable substituted acetoacetates, the following compounds were prepared: 1,2-diphenyl-5-trifluoromethyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one, m.p. 142-143 C 1 ,2-diphenyl-6-ethyl-5-methyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1 ,2-diphenyl-5-methyl-6-propyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1,2-diphenyl-6-isopropyl-5-methyl-1H,7H-pyrazolo[1,5-s]pyrimidine-7-one; 5,6-dimethyl-1 ,2-diphenyl-1 H,7H-pyrazolo[l ,5-a]pyrimidine-7-one; 6-chloro-1,2-diphenyl-5-methyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one, m.p. 208-210 C 1 ,2-diphenyl-6-methoxy-5-methyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1,2-diphenyl-6-ethoxy-5-methyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1,2-diphenyl-6-hydroxy-5-5-methyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one;; 6-acetoxy-1 ,2-diphenyl-5-methyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1,2-diphenyl-6-isopropoxy-5-methyl-1H,7H-pyrazolo-1,5-a]pyrimidine-7-one; 1,2-diphenyl-5-methyl-6-propoxy-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 6-allyloxy-1 ,2-diphenyl-5-methyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1,2-diphenyl-5-ethyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one, 1 ,2-diphenyl-5-propyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1,2-diphenyl-5-isopropyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 5-chloromethyl-1,2-diphenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one, m.p. 138-140 C; 5-dichloromethyl-1 ,2-diphenyl-1 H,7H-pyrazolo[l ,5-a]pyrimidine-7-one; 1 ,2-diphenyl-5-methoxymethyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1,2-diphenyl-5-ethoxymethyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one;; 5-diethoxymethyl-1,2-diphenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1,2-diphenyl-5-hydroxymethyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 5-acetoxymethyl-1 ,2-diphenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1-(4-methylphenyl)-2-phenyl-5-trifluoromethyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1-(4-nitro-phenyl)-2-phenyl-5-trifluoromethyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(4-chloro-phenyl)-2-phenyl-5-trifluoromethyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1-(3-chloro-phenyl)-2-phenyl-5-trifluoromethyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1 -(4-fluoro-phenyl)-2-phenyl-5-trifluoromethyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 2-phenyl-5-trifluoromethyl-1 -(3-trifluoromethyl-phenyl)-1 H,7H-pyrazolo[l ,5-a]pyrimidine-7-one;; 1,2-bis-(3-chloro-phenyl)-5-trifluoromethyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(3-chloro-phenyl)-2-(4-methoxy-phenyl)-5-trifluoromethyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 6-chloro-5-methyl-1-(4-methyl-phenyl)-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 6-chloro-5-methyl-1 -(4-nitro-phenyl)-2-phenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 6-chloro-1 -(4-chloro-phenyl)-5-methyl-2-phenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 6-chloro-1-(3-chloro-phenyl)-6-methyl-2-phenyl-1H,7H-pyrazolo[1,6-a]pyrimidine-7-one; 6-chloro-1-(4-fluoro-phenyl)-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 6-chloro-5-methyl-2-phenyl-1 -(3-trifluoromethyl-phenyl)-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one;; 6-chloro-1,2-bis-(3-chloro-phenyl)-5-methyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 6-chloro-1 -(3-chloro-phenyl)-2-(4-methoxy-phenyl)-5-methyl-1 H,7H-pyrazolo[l ,5-a]pyrimidine-7-one; 5,6-dimethyl-1 -(4-methyl-phenyl)-2-phenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 5,6-dimethyl-1-(4-nitro-phenyl)-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(4-chloro-phenyl)-5,6-dimethyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(3-chloro-phenyl)-5,6-dimethyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(4-fluoro-phenyl)-5,6-dimethyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 5,6-dimethyl-2-phenyl-1-(3-trifluoromethyl-phenyl)-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1,2-bis-(3-chloro-phenyl)-5,6-dimethyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one;; 1-(3-chloro-phenyl)-2-(4-methoxy-phenyl)-5,6-dimethyl-1 H,7H-pyrazolo[l ,5-a]pyrimidine-7-one; 6-methoxy-5-methyl-1 -(4-methyl-phenyl)-2-phenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 6-methoxy-5-methyl-1 -(4-nitro-phenyl)-2-phenyl-1 H-7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1-(4-chloro-phenyl)-6-methoxy-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(3-chloro-phenyl)-6-methoxy-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(4-fluoro-phenyl)-6-methoxy-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 6-methoxy-5-methyl-2-phenyl-1 -(3-trifluoromethyl-phenyl)-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1,2-bis-(3-chloro-phenyl)-6-methoxy-5-methyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; and 1 -(3-chloro-phenyl )-6-methoxy-2-(4-methoxy-phenyl)-5-methyl-1 H,7H-pyrazolo[1 ,5-a]pyri midine-7-one.

Example 3 Isopropylidene-N-(1,2-diphenyl-pyrazol-3-yl)-amino-methylenemalonate, m.p. 235-237 (3g), dissolved in diphenylether (30 ml) was heated at the reflux temperature for 8 minutes. After cooling the solvent was distilled off in vacuo and the residue was purified over a flash column using ethyl acetate as eluent. The purified product was crystallized fromCH2Cl2/isopropyl ether to give 0.9 g of 1,2-diphenyl-1 H,7Hpyrazolo[1,5-a]pyrimidine-7-one, m.p. 146-1480C, NMR (CDCl3) 8 ppm: 5.91(d) (lH, C-6 proton), 6.52(s) (1H, C-3 proton), 7.22(m) (10H, phenyl protons), 7.88(d), (1H, C-5 proton).

By proceeding analogously the following compounds were prepared: 1-(4-methyl-phenyl)-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(4-nitro-phenyl)-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(4-chloro-phenyl)-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1 -(3-chloro-phenyl)-2-phenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1-(4-fluoro-phenyl)-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 2-phenyl-1-(3-trifluoromethyl-phenyl)-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-benzyl-2-phenyl-1 H,7H-pyrazolo[1,5-a] pyrimidine-7-one; 1-phenyl-2-(3-pyridyl)-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 2-phenyl-i -(2-pyridyl)-1 H,7H-pyrazolo[1 5-a] pyrimidine-7-one; 1,2-bis-(3-chloro-phenyl)-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; and 1-methyl-2-phenyl-1 H,7H-pyrazolo[1,5-a]pyrimidine-7-one.

Example 4 1,2-diphenyl-5-methyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one (1.4g) dissolved in benzene (50 ml) was reacted with N-bromo-succinimide (0.95 g) under stirring at room temperature for 2 hours. The precipitate was dissolved by adding chloroform and the solution was washed with water. Evaporation in vacuo to dryness and crystallization of the residue from chloroform/ispropy alcohol gave 1.6 g of 6-bromo-1,2diphenyl-5-methyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one.

By proceeding analogously the following compounds were prepared: 6-bromo-1 ,2-diphenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 6-bromo-1,2-diphenyl-5-trifluoromethyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 6-bromo-5-methyl-1-(4-methyl-phenyl)-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 6-bromo-5-methyl-1 -(4-nitro-phenyl)-2-phenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 6-bromo-1-(4-chloro-phenyl)-5-methyl-2-pheyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 6-bromo-1 -(3-chloro-phenyl )-5-methyl-2-phenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 6-bromo-1-(4-fluoro-phenyl)-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 6-bromo-5-methyl-2-phenyl-1 -(3-trifluoromethyl-phenyl )-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one;; 6-chloro-1 ,2-diphenyl-1 H,7H-pyrazolo[1,5-a]pyrimidine-7-one; and 6-chloro-1,2-diphenyl-5-trifluoromethyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one.

Example 5 5-Methyl-1-(4-nitrophenyl)-2-phenyl-1 H,7H-pyrazolo[1,5-a]pyrimidine-7-one (4 g) was reacted with SnCl2.2H2O (25 g) in 37% HCI (15 ml) and acetic acid (45 ml) under stirring at 60 C for 2 hours. After cooling the precipitate was filtered and washed with water and then suspended under stirring in 2N NaOH: the product was filtered, washed with water until neutral and then crystallized from chloroform-ethanol to give 2.8g of 1-(4-amino-phenyl)-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one.

By proceeding analogously the following compounds were prepared: 1 -(4-amino-phenyl)-2-phenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1-(4-amino-phenyl)-2-phenyl-5-trifluoromethyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(4-amino-phenyl)-5,6-dimethyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1 -(4-amino-phenyl )-6-ch loro-5-methyl-2-phenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; and 1-(4-amino-phenyl)-6-methoxy-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; Example 6 5-Chloromethyl-1 ,2-diphenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one, m.p. 138-140 C. (2.2 g) was reacted with pyrrolidine (1 g) in 2-butanone (150 ml) at the reflux temperature for 16 hours.After cooling the solution was evaporated in vacuo to dryness and the residue was purified over a SiO2 column using chloroform/ methanol 97:3 as eluent. Crystallization of the recovered product from CH2Cl2-isopropyl ether gave 1.6 g of 1 ,2-diphenyl-5-(pyrrolidin-1 -yl-methyl)-1 H,7H-pyrazolo[l ,5-a]pyrimidine-7-one.

By proceeding analogously the following compounds were prepared: 5-(N,N-diethylamino-methyl)-1 ,2-diphenyl-1 H,7H-pyrazolo[l ,5-a]pyrimidine-7-one; 1 ,2-diphenyl-5-(morpholino-methyl)-1 H,7H-pyrazolo[l ,5-a]pyrimidine-7-one; 5-(N,N-dimethylamino-methyl)-1,2-diphenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1 ,2-diphenyl-5-(thiomorpholino-methyl)-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 5-(N-isopropylamino-methyl)-1,2-diphenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1 ,2-diphenyl-5-(imidazol-1 -yl-methyl)-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 5-(N-tert.butylamino-methyl)-1,2-diphenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1,2-diphenyl-5-(piperidino-methyl)-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 5-(hexahydro-1H-azepin-1-yl-methyl)-1,2-diphenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one ; and 1 ,2-diphenyl-5-[(4-methyl-piperazin-1 -yl)-methyl]-1 H,7H-pyrazol[1 ,5-a]pyrimidine-7-one.

Example 7 1 -(4-Amino-phenyl)-5-methyl-2-phenyl-1 H,7H-pyrazolo[1,5-a]pyrimidine-7-one (29) was heated under stirring in acetic acid (30 ml) containing 37% HCI (5 ml) at 60 C for 1 hour. After cooling the precipitate was filtered and washed with acetic acid and then with water to give 1.9 g of 1-(4-amino-phenyl)-5-methyl-2phenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one hydrochloride, m.p. > 350 C.

By proceeding analogously the following compounds were prepared: 1-(4-amino-phenyl)-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one hydrochloride; and 1-(4-amino-phenyl)-2-phenyl-5-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-7-one hydrochloride.

Example 8 Tablets, each weighing 75 mg and containing 25 mg of the active substance are manufactured as following: Compositions (for 10000 tablets) 1,2-diphenyl-5-methyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one 250 g Lactose 355 g Corn starch 120 g Talc powder 17.5g Magnesium stearate 7.5 9 1,2-diphenyl-5-methyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one, lactose and a half of the corn starch are mixed; the mixture is then forced through a sieve of 0.5 mm openings. Corn starch (lOg) is suspended in warm water (100 ml). The resulting paste is used to granulate the powder. The granules are dried, comminuted 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 6 mm diameter.

Claims

1. A compound of the following general formula (I)

wherein P1 is: a)C1-C6 alkyl or benzyl; b) pyridyl, unsubstituted or substituted by C1-C6 alkyl; c) phenyl, unsubstituted or substituted by one or more substituents chosen from halogen, trihalo-methyl, C1-C6 alkyl, C1-C6 alkoxy, hydroxy, formyloxy, C2-C6 alkanoyloxy, nitro, amino, formylamino and C2-C6 alkanoylamino; R2 is a) pyridyl; orb) phenyl, unsubstituted or substituted by one or more substituents chosen from halogen, trihalomethyl, nitro, C1-C6 alkoxy and C1 -C6 alkyl; R3 is hydrogen or C1 -C6 alkyl, unsubstituted or substituted by one or more substituents chosen from halogen, hydroxy, C1-C6 alkoxy, formyloxy, C2-C6 alkanoyloxy and the

group, wherein each of P5 and P6 is independently hydrogen, C,-C6 alkyl, phenyl or benzyl, or R5 and R6, taken together with the nitrogen atom to which they are linked, form a heterocyclic ring chosen from N-irnidazolyl, hexahydro-N-azepinyl, N-pyrrolidinyl, N-piperazinyl, piperidino, thiomorpholino and morpholino, each of the heterocyclic rings being unsubstituted or substituted by C1-C6 alkyl; R4 is hydrogen, halogen, C1-C6 alkyl, hydroxy, C1-C6 alkoxy, C3-C4 alkenoyloxy, formyloxy or C2-C6 alkanoyloxy; and the pharmaceutically acceptable salts thereof.

2. A compound of formula (I), according to claim 1, wherein: P1 is: a') C1-C4 alkyl or benzyl; b') pyridyl, unsubstituted or substituted by methyl; c') phenyl, unsubstituted or substituted by one or two substituents chosen from halogen, trifluoromethyl, C1-C4 alkyl, C1-C4 alkoxy, nitro, amino, formylamino and C2-C6 alkanoylamino; R2 is phenyl, unsubstituted or substituted by one or two substituents chosen from chlorine, fluorine, trifluoromethyl, nitro, C1 -C4 alkyl and C1-C4 alkoxy;; P3 is hydrogen or C1-C4 alkyl, unsubstituted or substituted by one to three substituents chosen from chlorine, fluorine, hydroxy, C1-C4 alkoxy, formyloxy, C2-C6 alkanoyloxy and the

group wherein each of P5 and P6 is independently hydrogen, C1-C4 alkyl or phenyl, or P5 and P6 taken together with the nitrogen atom to which they are linked, form a heterocyclic ring chosen from N-imidazolyl, hexahydro-N-azepinyl, N-pyrrolidinyl, N-piperazinyl, piperidino, thiomorpholino and morpholino, each of the heterocyclic rings being unsubstituted or substituted by C1-C3 alkyl; R4 is hydrogen, halogen, C1-C4 alkyl, hydroxy, C1-C4 alkoxy, C3-C4 alkenyloxy or C2-C6 alkanoyloxy; and the pharmaceutically acceptable salts thereof.

3. A compound of formula (I), according to claim 1, wherein: R1 is: a") C1-C4 alkyl, benzyl or pyridyl; b") phenyl, unsubstituted or substituted by one or two substituents chosen from chlorine, fluorine, trifluoromethyl, methyl, C1 -C2 alkoxy, nitro, amino, formylamino and C2-C4 alkanoylamino; P2 is phenyl, unsubstituted or substituted by one or two substituents chosen from halogen, trifluoromethyl, nitro, C1-C4 alkyl and C1 -C4 alkoxy;; R3 is hydrogen or C1-C4 alkyl, unsubstituted or substituted by one to three substituents chosen from halogen, hydroxy, C1-C2 alkoxy, formyloxy, C2-C4 alkanoyloxy and the

group, wherein each of P5 and P6 is independently hydrogen or C1-C4 alkyl, or P5 and R6, taken together with nitrogen atom to which they are linked, form a heterocyclic ring chosen from unsubstituted N-imidazolyl, unsu bstituted hexahydro-N-azepinyl, u nsubstituted N-pyrrolidinyl, N-piperazinyl unsu bstituted or substituted by C1-C3 alkyl, piperidino and morpholino each being unsubstituted or substituted by methyl and unsubstituted thiomorpholino;; R4 is hydrogen, halogen, C1-C4 alkyl, hydroxy, C1-C3 alkoxy, allyloxy or C2-C4 alkanoyloxy; and the pharmaceutically acceptable salts thereof.

4. A compound selected from the group consisting of: 1 ,2-diphenyl-5-methyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1 ,2-diphenyl-5-trifluoromethyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1,2-diphenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 5-methyl-1-(4-methyl-phenyl)-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 5-methyl-1 -(4-nitro-phenyl)-2-phenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1 -(4-chloro-phenyl)-5-methyl-2-phenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1-(3-chloro-phenyl)-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-(4-fluoro-phenyl)-5-methyl-2-phenyl-1 H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 5-methyl-2-phenyl-1-(3-trifluoromethyl-phenyl)-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1-benzyl-5-methyl-2-phenyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one;; 1-tert.butyl-5-methyl-2-phenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1 ,5-dimethyl-2-phenyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 5-methyl-2-phenyl-1 -(2-pyridyl)-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 5-methyl-2-phenyl-1 -(3-pyridyl)-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1 ,2-bis-(3-chloro-phenyl)-5-methyl-l H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1 -(3-chloro-phenyl)-2-(4-methoxy-phenyl)-5-methyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 1 ,2-diphenyl-5,6-dimethyl-1 H,7H-pyrazolo[1 ,5-a]pyrimidine-7-one; 6-chloro-1 ,2-diphenyl-5-methyl-1 H,7H-pyrazolo[1 ,5-ajpyrimidie-7-one; 1,2-diphenyl-6-methoxy-5-methyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; ; 1,2-diphenyl-6-ethoxy-5-methyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 5-(N,N-diethylamino-methyl)-1 ,2-diphenyl-1 H,7H-pyrazolo[l ,5-a]pyrimidine-7-one; 1,2-diphenyl-5-(pyrrolidin-1-yl-methyl)-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1,2-diphenyl-5-(imidazol-1-yl-methyl)-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; 1,2-diphenyl-5-methoxymethyl-1H,7H-pyrazolo[1,5-a]pyrimidine-7-one; and the pharmaceutically acceptable salts thereof.

5. A process for the preparation of a compound of formula (I) and the pharmaceutically acceptable salts thereof, according to claim 1, the process comprising: a) cyclization of a compound of formula (II)

wherein R1, R2, R3 and R4 are as defined in claim 1 and R7 is a nucleophile group which is capable of being cleaved from the carbon atom to which it is attached during the cyclization of the compound of formula (II), or a salt thereof;; b) decarboxylation of a compound of formula (III)

wherein R1 und R2 are as defined in claim 1 and P8 is hydrogen or unsubstituted C1 -C6 alkyl, so obtaining compounds of formula (I) wherein P3 is hydrogen or unsubstituted C1-C6 alkyl and R4 is hydrogen, or c) thermal cyclization of a compound of formula (IV)

wherein R1 and R2 are as defined in claim 1, R8 is as defined above and each of Rg and R10 is independently C1-C6 alkyl, so obtaining compounds of formula (I) wherein P3 is hydrogen or unsubstituted C1-C6 alkyl and R4 is hydrogen, and if desired, converting a compound of formula (I) into another compound of formula (I) and/or, if desired, converting a compound of formula (I) into a pharmaceutically acceptable salt thereof and/or, if desired, obtaining a free compound of formula (I) from a salt thereof and/or, if desired, separating a mixture of isomers into the single isomers.

6. A pharmaceutical composition containing a suitable carrier and/or diluent and, as an active principle, a compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof.

7. A compound of formula (I) as defined in claim 1, or a pharmaceutically acceptable salt thereof, hereinbefore specified other than a compound or salt claimed in claim 4.

8. A compound of formula (I) as defined in claim 1, or a pharmaceutically acceptable salt thereof, for use in a method of treatment of the human or animal body in therapy.

9. A compound of formula (I) or salt thereof according to claim 8 for use as a central nervous system depressant.

10. A process for the preparation of a compound of formula (I) as defined in claim 1, said process being substantially as hereinbefore described in any one of Examples 1 to 6.

11. A process for the preparation of a pharmaceutically acceptable salt of a compound of formula (I) as defined in claim 1, said process being substantially as hereinbefore described in Example 7.

12. A pharmaceutical composition substantially as hereinbefore described in Example 8.