several 3 - ureido - pyrazole derivatives are known in the art as pesticides , herbicides or even as therapeutic agents . among them are , as an example , heteroaryl - pyrazoles active as p38 kinase inhibitors ( wo 9852941 , g . d . searle and co .). aryl - ureido - pyrazoles such as , for instance , phenyl - ureidopyrazoles are also known in the art as p38 kinase inhibitors ( wo 99 / 32111 , bayer co .). several 5 - aryl -( 1h - pyrazol - 5 - yl )- urea derivatives are known in the art as neuropeptide y antagonists useful as hypolipemic agents ( wo 98 // 24768 , banyu pharmaceutical co .). as will be readily apparent to one skilled in the art , the unsubstituted ring nitrogen pyrazoles , as in the compounds of the present invention , are known to rapidly equilibrate , in solution , as admixtures of both tautomers : in the following description , therefore , where only one tautomer is indicated for the compounds of formula ( i ), the other ( ia ) is also intended as within the scope of the present invention . in the present description , unless otherwise specified , with the term halogen atom includes a fluorine , chlorine , bromine or iodine atom . as used herein and unless otherwise indicated , the terms alkyl and alkoxy include c 1 - c 6 alkyl and c 1 - c 6 alkoxy groups . the term straight or branched c 1 - c 6 alkyl or c 1 - c 6 alkoxy group includes a group selected from , methyl , ethyl , npropyl . isopropyl , n - butyl , isobutyl , sec - butyl , tertbutyl , n - pentyl , n - hexyl , methoxy , ethoxy , n - propoxy , isopropoxy , n - butoxy and the like . likewise , with the term alkylthio , alkylamino , dialkylamino , alkoxycarbonyl , alkoxycarbonylamino , alkylcarbonyl , alkylsulphonyl , alkoxycarbonyl , n - alkylpiperazinyl and the like , we intend any of the aforementioned groups wherein the alkyl and alkoxy moieties stand for c 1 - c 6 alkyl or alkoxy groups . unless otherwise specified , with the term cycloalkyl includes a c 3 - c 6 cycloalkyl group such as cyclopropyl , cyclobutyl , cyclopentyl and cyclohexyl as well as cycloalkyl and bridged cycloalkyl groups with up to 10 carbon atoms . the term aryl stands for mono -, bi - or poly - carbocyclic or heterocyclic hydrocarbons with from 1 to 4 ring moieties , wherein at least one of the rings is aromatic , either fused or linked to each other by single bonds . these groups may have 5 to 20 carbon atoms , preferably 6 to 20 carbon atoms . from the foregoing , one skilled in the art will readily appreciate that the term aryl also include aromatic heterocycles otherwise referred to as heteroaryl groups . the term heterocycle refers to a 5 or 6 membered saturated or unsaturated carbocycle wherein one or more carbon atoms are replaced by one or more atoms selected from nitrogen , oxygen and sulphur . the number of heteroatoms is not limited and may be , for example , one , two , three , or more . example of aryl groups include phenyl , 1 - naphtyl , 2 - naphthyl , indanyl , indenyl , biphenyl , benzocycloalkyl , e . g . bicyclo [ 4 . 2 . 0 ] octa - 1 , 3 , 5 ,- triene , benzoheterocyclyl , e . g . benzodioxolyl , quinolyl , isoquinolyl , quinoxalyl , indolyl , optionally benzocondensed pyrrolyl , furyl , thienyl , imidazolyl , pyrazolyl , thiazolyl , oxazolyl , isoxazolyl , pyridyl , pyrazinyl , pyrimidyl and the like . example of heterocycles are pyrrolidine , piperidine , piperazine , morpholine and the like . the term c 2 - c 4 alkenyl or alkynyl includes a group selected from vinyl , allyl , 1 - propenyl , isopropenyl , 1 - butenyl , 2 - butenyl . 3 - butenyl , ethynyl . propynyl , butynyl and the like . the term perfluorinated alkyl group includes a c 1 - c 4 alkyl group further substituted by more than one fluorine atom such as , for instance , trifluoromethyl , 2 , 2 , 2 - trifluoroethyl , 1 , 1 , 2 , 2 , 2 - pentafluoroethyl and the like . pharmaceutically acceptable salts of the compounds of formula ( i ) include the acid addition salts with inorganic or organic , e . g ., nitric , hydrochloric , hydrobromic , sulphuric , perchloric , phosphoric , acetic , trifluoroacetic , propionic , glycolic , lactic , oxalic , malonic , malic , maleic , tartaric , citric , benzoic , cinnamic , mandelic , methanesulphonic , isethionic and salicylic acid , as well as the salts with inorganic or organic bases , e . g ., alkali or alkaline - earth metals , especially sodium , potassium , calcium or magnesium hydroxides , carbonates or bicarbonates , acyclic or cyclic amines , preferably methylamine , ethylamine , diethylamine , triethylamine or piperidine . the compounds of formula ( i ) may have asymmetric carbon atoms and may therefore exist either as racemic admixtures or as individual optical isomers . accordingly , the use as an antitumor agent of all the possible isomers and their admixtures and of both the metabolites and the pharmaceutically acceptable bioprecursors ( otherwise referred to as pro - drugs ) of the compounds of formula ( i ) are also within the scope of the present invention . preferred compounds of the invention of formula ( i ), are those where r is a c 3 - c 6 cycloalkyl or an optionally substituted straight or branched c 1 - c 4 alkyl group , a cycloalkyl or an aryl or arylalkyl group , and r 1 is a c 1 - c 4 alkyl group or a phenyl , phenylalkyl , heteroaryl , heteroarylalkyl or heterocyclyl group , each being optionally substituted as defined above . still more preferred compounds , are those where r is a c 3 - c 6 cycloalkyl and r 1 is a c 1 - c 4 alkyl group substituted by hydroxy or amino , or is an aryl , arylalkyl , heterocyclyl or heterocyclylalkyl , wherein the aryl or heterocyclyl moiety is selected from the group consisting of phenyl or optionally benzocondensed pyiridine , indole , thiophene , thiazole , isoxazole , furan , piperidine , morpholine , each optionally further substituted . another class of preferred compounds of formula ( i ) are those where r 1 and r 2 form an optionally substituted heterocyclyl ring such as piperidino , piperazino or morpholino . when the groups described above are substituted , the number of substituents is not particularly limited . for example , the groups described above may be substituted with , for example , one , two , three , or more of the substituents . unless , otherwise indicated , the substituents may be the same or different , i . e ., they are indepedently selected . examples of preferred compounds of the invention , which may be in the form of a pharmaceutically acceptable salt , e . g ., hydrobromide or hydrochloride salt , include the following : the compounds of formula ( i ) object of the present invention and the salts thereof can be obtained , for instance , by a process comprising : wherein r and r 1 are as defined above , thus obtaining a compound of formula ( iv ): b ) selectively hydrolyzing a compound of formula ( iv ) in a basic medium thus obtaining a compound of formula ( i );: or , alternatively , where r is described as above , with 4 - nitrophenyl chloroformate , or a polymer supported form of it , thus obtaining a compound of formula ( vi ), or a polymer supported form of it where r 1 and r 2 are defined as above , thus obtaining a compound of formula ( viii ): where r , r 1 and r 2 are defined as above , ( c ) hydrolyzing a compound of formula ( viii ) in acidic medium thus obtaining compounds of formula ( i ); and , if desired , converting a 3 - ureido - pyrazole derivative of formula ( i ) into another such derivative of formula ( i ), and / or into a salt thereof . the compounds of formula ( v ) may be obtained by a process comprising : where r is as described above and r 4 is an alkyl group , with acetonitrile in the presence of basic agents thus obtaining a compound of formula ( x ): ( b ) reacting a compound of formula ( x ) with hydrazine hydrate thus obtaining a compound of formula ( ii ): ( c ) reacting a compound of formula ( xi ) with terbutoxycarbonyl anhydride ( boc 2 o ) thus obtaining a compound of formula ( xii ): ( e ) reducing a compound of formula ( xii ) thus obtaining a compound of formula ( v ) where r is as described above . the compounds of formula ( i ) may alternatively be obtained by a process comprising : ( a ) reacting a compound of the above - described formula ( ii ) with a compound of the above - described formula ( iii ), thus obtaining a compound of formula ( xiii ): ( b ) heating at reflux in the presence of sodium hydrate , methanol and an excess of a compound of formula ( iii ), thus obtaining a compound of formula ( i ). the compounds of formula ( i ) can alternatively be obtained by a process comprising : where r is as described above , with a compound of the above formula ( iii ), thus obtaining a compound of formula ( xiv ): ( b ) hydrolyzing a compound of formula ( xiv ) in an acidic medium thus obtaining a compound of formula ( i ), where r and r 1 are as described above . the compounds of formula ( i ) can alternatively be obtained by a process comprising : ( a ) reacting a compound of the above formula ( v ) with 1 , 1 ′ carbonyldiimidazole thus obtaining compounds of formula ( xv ): where r 1 and r 2 are as above defined , thus obtaining a compound of formula ( viii ) ( c ) hydrolizing a compound of formula ( viii ) in acidic medium thus obtaining a compound of formula ( i ). the compounds of formula ( i ) can alternatively be obtained by a process comprising : ( a ) reacting the oxime resin ( xvi ) with triphosgene to give a polystyrene supported agent ( xvii ): ( b ) reacting the compound ( xvii ) with a compound of the above - described formula ( ii ), thus obtaining a compound of formula ( xviii ), where r is as described above ; ( c ) reacting the compound of formula ( xviii ) with a compound of the above - described formula ( vii ), thus obtaining the compound of formula ( i ), where r , r 1 and r 2 are as described above . as will be readily appreciated by one skilled in the art , if the compound of formula ( i ), prepared according to the above process is obtained as an admixture of isomers , its separation into the single isomers of formula ( i ) according to conventional techniques is within the scope of the present invention . likewise , the conversion into the free compound ( i ) of a corresponding salt thereof , according to well - known procedures in the art , is within the scope of the invention . the process described above may be conducted analogous to to well - known methods . the reaction between a compound of formula ( ii ) or formula ( v ) and a compound of formula ( iii ) can be carried out in the presence of sodium hydrogen carbonate or a tertiary base , such as triethylamine , n - methylmorpholine , n , n - diisopropylethylamine or pyridine , in a suitable solvent such as toluene , dichloromethane , chloroform , diethylether , tetrahydrofuran , acetonitrile , dioxane or n , n - dimethylformamide , at a temperature ranging from about 10 ° c . to reflux . the reaction of a compound of formula ( iv ) to give a compound of formula ( i ) can be carried out with a base such as sodium hydroxide , potassium hydroxide , sodium carbonate or potassium carbonate in a suitable solvent such as a mixture of methanol or ethanol and water at room temperature . the reaction of the compounds of formula ( ii ) and the compounds of formula ( iii ) to give the compounds of formula ( xiii ) can be carried out with a base such as sodium hydrogencarbonate or sodium hydrate in suitable solvent such as ethanol or methanol at room temperature . the reaction of the compounds of formula ( xiii ) to give the compounds of formula ( i ) can be carried out by heating at a temperature ranging from 60 to 80 ° c . in presence of an excess of compounds of formula ( iii ) in presence of a base such as sodium hydrate in a suitable solvent such as methanol or ethanol . the reaction of a compound of formula ( xiv ) to give a compound of formula ( i ) can be carried out with an acid such as trifluoroacetic acid , hydrochloric acid , formic acid , in a suitable solvent such as methylene chloride at a temperature ranging from − 10 ° c . to room temperature . the reaction of a compound of formula ( ix ) to give a compound of formula ( x ) may be carried out with acetonitrile and a base such as sodium hydride in a suitable solvent such as diethylether , tetrahydrofaran , dioxane at a temperature ranging from room temperature to 120 ° c . the reaction of a compound of formula ( x ) to give a compound of formula ( ii ) may be carried out with hydrazine hydrate , in a solvent such as methanol or ethanol at a temperature ranging from room temperature to 80 ° c . the reaction of a compound of formula ( ii ) to give a compound of formula ( xi ) may be carried out with oxone ® ( potassium peroxymonosulfate ) or another oxidizing agent such as hydrogen peroxide in a suitable solvent such as a mixture of water - acetone at a temperature ranging from 0 ° c . to room temperature . the reaction of a compound of formula ( xi ) to give a compound of formula ( xii ) may be carried out with terbutoxycarbonyl anhydride in a suitable solvent such as a mixture of methylene chloride - water at room temperature , in the presence of sodium hydrogen carbonate . the reaction of a compound of formula ( xii ) to give a compound of formula ( v ) may be carried out directly with hydrogen in presence of a catalyst such as palladium on charcoal in a suitable solvent such as methanol or ethanol at room temperature . the reaction of a compound of formula ( v ) to give a compound of formula ( vi ) may be carried out with 4 - nitrophenyl chloroformate or a polymer supported form of it in the presence of a tertiary base such as triethylamine , n - methylmorpholine , n , n - diisopropylethylamine or pyridine , in a suitable solvent such as toluene , dichloromethane , chloroform , diethylether , tetrahydrofuran , acetonitrile , dioxane or n , n - dimethylformamide , at a temperature ranging from about − 10 ° c . to room temperature . the reaction between a compound of formula ( vi ) or ( xv ) and a compound of formula ( vii ) to give a compound of formula ( viii ) can be carried out in a suitable solvent such as toluene , dichloromethane , chloroform , diethylether , tetrahydrofuran , acetonitrile , dioxane or n , n - dimethylformamide , at a temperature ranging from about room temperature to reflux . the reaction of a compound of formula ( viii ) to give a compound of formula ( i ) can be carried out with an acid such as trifluoroacetic acid , hydrochloric acid , formic acid , in a suitable solvent such as methylene chloride at a temperature ranging from − 10 ° c . to room temperature . the reaction of a compound of formula ( v ) to give a compound of formula ( xv ) can be carried out with 1 , 1 ′- carbonyldiimidazole , bis ( trichloromethyl ) carbonate or trichloromethyl chloroformate in the presence , if necessary , of a tertiary base such as triethyl amine , n , n - diisopropylethylamine or pyridine , in a suitable solvent such as dichloromethane , chloroform , toluene , dioxane or tetrahydrofuran at a temperature ranging from 0 ° c . to reflux . the reaction of the oxime resin ( xvi ) with triphosgene to give the compound of formula ( xvii ) can be carried out in a suitable solvent such as dichloromethane at room temperature . the reaction of the compound of formula ( xvii ) with the compound of formula ( ii ) to give a compound of formula ( xviii ) can be carried out in a suitable solvent such as dichloromethane at room temperature . the reaction of the compounds of formula ( xviii ) with the compounds of formula ( vii ) to give the compounds of formula ( i ) can be carried out in a suitable solvent such as toluene , dichloromethane , chloroform , diethylether , tetrahydrofuran , acetonitrile , dioxane or n , n - dimethylformamide at a temperature ranging from room temperature to reflux . also the optional conversion of a compound of formula ( i ) into another compound of formula ( i ) can be carried out according to known methods . the optional salification of a compound of formula ( i ) or the conversion of a salt into the free compound as well as the separation of a mixture of isomers into the single isomers may be carried out by conventional methods . the compounds of formula ( iii ), ( vii ), ( ix ) and ( x ) are known commercially available products or can be obtained according to conventional synthetic methods . when preparing the compounds of formula ( i ) according to the process object of the present invention , optional functional groups within both the starting materials or the intermediates thereof , which could give rise to unwanted side reactions , need to be properly protected according to conventional techniques . likewise , the conversion of these latter into the free deprotected compounds may be carried out according to known procedures . as will be readily appreciated by one skilled in the art , the above process for preparing the compounds of formula ( i ) may be used to prepare another compound of formula ( i ) which also include known compounds . the compounds of formula ( i ) are active as cdk / cyclin inhibitors as they gave positive results when tested according to the following procedure . the inhibiting activity of putative cdk / cyclin inhibitors and the potency of selected compounds was determined through a method of assay based on the use of the multiscreen - ph 96 well plate ( millipore ), in which a phosphocellulose filter paper was placed at each well bottom allowing binding of positive charged substrate after a washing / filtration step . when a radioactivity labeled phosphate moiety was transferred by the ser / threo kinase to the filter - bound histone , light emitted was measured in a scintillation counter . the inhibition assay of cdk2 / cyclin a activity was performed according to the following protocol : 1 . 5 . m histone h1 substrate , 25 . m atp ( 0 . 5 uci p33g - atp ), 100 ng cyclin a / cdk2 complex , 10 . m inhibitor in a final volume of 100 . 1 buffer ( tris hcl 10 mm ph 7 . 5 , mgcl 2 10 mm , 7 . 5 mm dtt ) were added to each well of a 96 u bottom well plate . after 10 min at 37 ° c . incubation , reaction was stopped by 20 . 1 edta 120 mm . 100 . 1 were transferred from each well to multiscreen plate , to allow substrate binding to phosphocellulose filter . plates were then washed 3 times with 150 . 1 / well pbs ca ++/ mg ++ free and filtered by multiscreen filtration system . filters were allowed to dry at 37 ° c ., then 100 . 1 / well scintillant were added and 33p labeled histone h1 was detected by radioactivity counting in the top - count instrument . data were analyzed and expressed as % inhibition referred to total activity of enzyme (= 100 %). all compounds showing inhibition & gt ; 50 % were further analyzed in order to study and define the kinetic - profile of inhibitor through ki calculation . the protocol used was the same described above , except for atp and substrate concentrations . either the concentration of atp and histone h1 substrate were varied : 4 , 8 , 12 , 24 , 48 . m for atp ( containing proportionally diluted p33g - atp ) and 0 . 4 , 0 . 8 , 1 . 2 , 2 . 4 , 4 . 8 . m for histone were used in absence and presence of two different , properly chosen inhibitor concentrations . experimental data were analyzed by the computer program “ sigmaplot ” for ki determination , using a random bireactant system equation : v = v   max  ( a )  ( b ) akakb 1 + ( a ) ka + ( b ) kb + ( a )  ( b ) akakb in addition , the inhibiting activity of putative cdk / cyclin inhibitors and the potency of selected compounds was determined through a method of assay based on the use of a spa ( scintillation proximity assay ) 96 well plate assay . the assay is based on the ability of streptavidin coated spa beads to capture a biotinylated peptide derived from a phosphorylation site of histone . when a radioactivity labeled phosphate moiety was transferred by the ser / threo kinase to the biotinylated histone peptide , light emitted was measured in a scintillation counter . the inhibition assay of cdk5 / p25 activity was performed according to the following protocol : 1 . 0 . m biotinylated histone peptide substrate , 0 . 25 uci p33g - atp , 4 nnm cdk2 / p25 complex , 0 - 100 . m inhibitor in a final volume of 100 . 1 buffer ( hepes 20 mm ph 7 . 5 , mgcl 2 15 mm , 1 mm dtt ) were added to each well of a 96 u bottom well plate . after 20 min at 37 ° c . incubation , the reaction was stopped by the addition of 500 ug spa beads in phosphate - buffered saline containing 0 . 1 % triton x - 100 , 50 um atp and 5 mm edta . the beads were allowed to settle , and the radioactivity incorporated in the 33p - labeled peptide was detected in a top count scintillation counter . data were analyzed and expressed as % inhibition using the formula : ic 50 values were calculated using a variation of the four parameter logistics equation : the compounds of formula ( i ) are therefore useful to restrict the unregulated proliferation of tumor cells , hence in therapy in the treatment of various tumors such as , for instance , carcinomas , e . g ., mammary carcinoma , lung carcinoma , bladder carcinoma , colon carcinoma , ovary and endometrial tumors , sarcomas , e . g . soft tissue and bone sarcomas , and the hematological malignancies such as , e . g ., leukemias . in addition , the compounds of formula ( i ) are also useful in the treatment of other cell proliferative disorders such as psoriasis , vascular smooth cell proliferation associated with atherosclerosis and post - surgical stenosis and restenosis and in the treatment of alzheimer &# 39 ; s disease . the compounds of the present invention can be administered either as single agents or , alternatively , in combination with known anticancer treatments such as radiation therapy or chemotherapy regimen in combination with cytostatic or cytotoxic agents . as an example , the above compounds can be administered in combination with one or more chemotherapeutic agents such as , for instance , taxane , taxane derivatives , cpt - 11 , camptothecin derivatives , anthracycline glycosides , e . g . doxorubicin or epirubicin , etoposide , navelbine , vinblastine , carboplatin , cisplatin and the like , optionally within liposomal formulations thereof . the compounds of formula ( i ) of the present invention , suitable for administration to a mammal , e . g ., to humans , can be administered by the usual routes and the dosage level depends upon the age , weight , conditions of the patient and the administration route . for example , a suitable dosage adopted for oral administration of a compound of formula ( i ) may range from about 10 to about 500 mg pro dose , from 1 to 5 times daily . the compounds of the invention can be administered in a variety of dosage forms , e . g . orally , in the form of tablets , capsules , sugar or film coated tablets , liquid solutions or suspensions ; rectally in the form of suppositories ; parenterally , e . g . intramuscularly , or by intravenous and / or intrathecal and / or intraspinal injection or infusion . the present invention also includes pharmaceutical compositions comprising a compound of formula ( i ) or a pharmaceutically acceptable salt thereof in association with a pharmaceutically acceptable excipient ( which can be a carrier or a diluent ). the pharmaceutical compositions containing the compounds of the invention are usually prepared following conventional methods and are administered in a pharmaceutically suitable form . for example , the solid oral forms may contain , together with the active compound , diluents , e . g . lactose , dextrose , saccharose , sucrose , cellulose , corn starch or potato starch ; lubricants , e . g . silica , talc , stearic acid , magnesium or calcium stearate , and / or polyethylene glycols ; binding agents , e . g . starches , arable gum , gelatins , methylcellulose , carboxymethylcellulose 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 , tableting , sugar - coating , or film - coating processes . the liquid dispersions for oral administration may be e . g . syrups , emulsions and suspensions . the syrups may contain as carrier , for example , saccharose or saccharose with glycerine and / or mannitol and / or sorbitol . the suspensions and the emulsions may contain as carrier , for example , a natural gum , agar , sodium alginate , pectin , methylcellulose , carboxymethylcellulose , or polyvinyl alcohol . the suspension or solutions for intramuscular injections may contain , together with the active compound , a pharmaceutically acceptable carrier , e . g . sterile water , olive oil , ethyl oleate , glycols , e . g . propylene glycol , and , if desired , a suitable amount of lidocaine hydrochloride . the solutions for intravenous 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 or they may contain as a carrier propylene glycol . the suppositories may contain together with the active compound a pharmaceutically acceptable carrier , e . g . cocoa butter , polyethylene glycol , a polyoxyethylene sorbitan fatty acid ester surfactant or lecithin . having generally described this invention , a further understanding can be obtained by reference to certain specific examples which are provided herein for purposes of illustration only and are not intended to be limiting unless otherwise specified . to 0 . 4 g ( 3 . 2 mmol ) of 3 - cyclopropyl - 5 - amino - 1h - pyrazole in 10 ml of 95 % ethanol containing 0 . 3 g of sodium hydrogencarbonate 0 . 35 ml ( 3 mmol ) of phenylisocyanate were added dropwise over several minutes . after 30 min water was added , and the solid was filtered , washed with 10 % hcl and then with water . the filtrate was concentrated in vacua . the crude was recrystallized from methanol / water to give white peddles of 5 - amino - 3 - cyclopropyl - n - phenyl - 1h - pyrazole - l - carboxamide , ms ( ei ) m / z ( rel . intensity ) 242 ( m + , 13 ), 123 ( 99 ), 119 ( 86 ), 96 ( 74 ), 91 ( 86 ), 80 ( 85 ), 77 ( 53 ), 65 ( 61 ), 64 ( 79 ), 63 ( 52 ), 51 ( 51 ). to 5 - amino - 3 - cyclopropyl - n - phenyl - 1h - pyrazole - l - carboxamide ( 0 . 5 g , 2 mmol ) in 6 ml of methanol 0 . 5 ml ( 4 . 6 mmol ) of phenylisocyanate and 2 ml of 10 % naoh were added . the mixture was refluxed for about 2h , then cooled , quenched with 10 % hcl and extracted with ethyl acetate . the organic phase was washed with 10 % hcl , water and brine . concentration and chromatography on silica gel , eluting with 8 % to 20 % acetone in methylene chloride , afforded 100 mg ( 20 % yield ) of n -( 3 - cyclopropyl - 1h - pyrazol - 5 - yl )- n ′- phenylurea as a colorless , glassy solid . 1 h nmr ( dmso - d 6 ) δ12 . 0 ( s , 1h ), 9 . 2 ( s , 1h ), 8 . 84 ( s , 1h ), 7 . 42 ( app . d , 2h ), 7 . 27 ( app . t , 2h ), 6 . 96 ( app . t , 1h ), 5 . 86 ( s , 1h ), 1 . 85 ( m , 1h ), 0 . 91 ( m , 2h ), 0 . 67 ( m , 2h ); ms ( ei ) m / z ( rel . intensity ) 242 ( m + , 9 ), 149 ( 43 ), 123 ( 89 ), 122 ( 38 ), 119 ( 89 ), 93 ( 99 ), 91 ( 54 ), 80 ( 46 ), 66 ( 47 ), 65 ( 40 ), 64 ( 34 ). 1 g ( 8 . 13 mmol ) of 3 - cyclopropyl - 5 - amino - 1h - pyrazole are dissolved in 10 ml of ethanol containing 1 . 37 g ( 16 . 26 mmol ) of sodium hydrogen carbonate and 3 . 27 g ( 16 . 26 mmol ) of 2 , 4 - dichlorobenzyl isocyanate . after 3 hours at room temperature 50 ml of water were added and the solid was filtered . the filtrate was evaporated to dryness and then redissolved with 10 ml of methanol . 8 . 2 ml of 1m sodium hydrate were added and the mixture stirred 4 h at room temperature . methanol is evaporated and the residue is dissolved with dichloromethane and washed with water . the organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo to afford 1 . 5 g ( 60 % yield ) of the title compound . 1 h nmr ( dmso - d 6 ) δ11 . 9 ( s , 1h ), 8 . 84 ( s , 1h ), 7 . 60 ( d , 1h ), 7 . 55 ( br s , 1h ), 7 . 43 ( dd , 1h ), 7 . 36 ( d , 1h ), 5 . 67 ( s , 1h ), 4 . 36 ( d , 2h ), 1 . 81 ( m , 1h ), 0 . 89 ( m , 2h ), 0 . 61 ( m , 2h ); hrms ( fab ) calcd for c 14 h 14 cl 2 n 4 o + h 325 . 0623 , found 325 . 0621 . 4 . 5 g ( 0 . 15 mol ) of sodium hydride 80 % were suspended in 200 ml of dioxane , 7 . 5 ml of acetonitrile ( 0 . 15 mol ) were dropped and , after 20 minutes , a solution of ethyl cyclopropancarboxylate ( 0 . 125 mol ) in 100 ml of the same solvent was added . the mixture was maintained at reflux for 3 hours , under stirring , then 400 ml of water were added and the unreacted starting material extracted with methylene chloride . the aqueous layer was acidified with diluted hydrochloric acid and extracted with the same solvent . the organic layer was dried over anhydrous sodium sulfate and evaporated to dryness to give a residue that , after column chromatography ( cyclohexane - ethylacetate ), afforded 7 . 8 g ( 57 % yield ) of the title compound . 1 h nmr ( 400 mhz , cdcl 3 ) δ3 . 59 ( s , 2h ), 2 . 12 ( dddd , 1h , j = 7 . 6 , 7 . 6 , 4 . 5 , 4 . 5 ), 1 . 21 ( m , 2h ), 1 . 10 ( m , 2h ). ei - ms : m / z 69 ( 85 , m - c 3 h 5 . ); m / z 39 ( 100 , c 3 h 5 + ). 5 g ( 0 . 046 mol ) of 3 - cyclopropyl - 3 - oxo - propanenitrile were dissolved in 200 ml of ethanol and 2 . 26 ml ( 0 . 046 mol ) of hydrazine hydrate were added . the solution was maintained at reflux for 5 hours and then the solvent evaporated under vacuum . the residue was redissolved with methylene chloride and washed several times with brine . the organic layer was dried over anhydrous sodium sulfate and the solvent evaporated to give 4 . 53 g ( 80 % yield ) of the title compound . 1 h nmr ( 400 mhz , cdcl 3 ) δ6 - 7 ( b , 3h , nh + nh 2 ), 5 . 02 ( s , 1h ), 1 . 68 ( dddd , 1h , j = 8 . 3 , 8 . 3 , 4 . 9 , 4 . 9 ), 0 . 76 ( m , 2h ), 0 . 54 ( m , 2h ). to a solution of 2 . 7 g of sodium hydrate in 454 ml of water 7 . 1 g ( 0 . 058 mol ) of 3 - cyclopropyl - 5 - amino - 1h - pyrazole and 46 . 5 g of sodium hydrogenocarbonate were added at 0 ° c . after 10 minutes a solution of 337 ml of acetone in 221 ml of water and a solution of 130 g ( 0 . 21 mol ) of oxone in 580 ml of water were contemporarly dropped under vigorous stirring . after 4 hours at the same temperature the reaction is quenched with a saturated solution of sodium sulfite and extracted with ethylacetate . the organic layer was dried over anhydrous sodium sulfate and evaporated to dryness to give 4 . 6 g ( 52 % yield ) of the title compound . 1 h nmr ( 400 mhz , cdcl 3 ) δ6 . 51 ( s , 1h ), 2 . 01 ( dddd , 1h , j = 8 . 2 , 8 . 2 , 5 . 1 , 5 . 1 ), 1 . 10 ( m , 2h ), 0 . 79 ( m , 2h ). 4 . 9 g ( 0 . 032 mol ) of 3 - cyclopropyl - 5 - nitro - 1h - pyrazole were dissolved in 200 ml of methylene chloride and 200 ml of a saturated solution of sodium hydrogenocarbonate were added . 35 g ( 0 . 16 mol ) of terbutoxycarbonyl anhydride were then added under stirring at room temperature . after 24 hours the layers were separated and the organic one dried over sodium sulfate and evaporated under vacuum . the residue was chromatographed on a silica gel column ( cyclohexane - ethylacetate ) to give 7 . 7 g ( 95 % yield ) of the title compound . 1 h nmr ( 400 mhz , cdcl 3 ) δ6 . 49 ( s , 1h ), 2 . 48 ( dddd , 1h , j = 8 . 5 , 8 . 5 , 5 . 3 , 5 . 3 ), 1 . 68 ( s , 9h ), 1 . 13 ( m , 2h ), 0 . 78 ( m , 2h ). esi (+) ms : m / z 276 ( 100 , mna + ); 220 [ 60 , ( mna - c 4 h 8 ) + ]. 1 . 2 g ( 4 . 74 mmol ) of tert - butyl - 3 - nitro - 5 - cyclopropyl - 1h - pyrazole - 1 - carboxylate were dissolved in 20 ml of ethanol and hydrogenated in presence of 200 mg of palladium on charcoal 10 % at 50 psi and room temperature to give , after filtration on celite and evaporation of the solvent , 0 . 96 g ( 95 % yield ) of the title compound . 1 h nmr ( 400 mhz , cdcl 3 ) δ5 . 39 ( s , 1h ), 3 . 82 ( br s , 2h ) 2 . 34 ( dddd , 1h , j = 8 . 4 , 8 . 4 , 5 . 2 , 5 . 2 ), 1 . 63 ( s , 9h ), 0 . 97 ( m , 2h ), 0 . 64 ( m , 2h ). esi (+) ms : m / z 246 ( 20 , mna + ); 168 [ 100 , ( mh - c 4 h 8 ) + ]; 124 [ 90 , ( mh - c 5 h 8 o 2 ) + ]. to a solution of 1 . 067 g ( loading 0 . 57 mmol / g , 0 . 608 mmol ) of oxime resin ( xvi ) in 10 ml of dichloromethane 241 mg ( 0 . 811 mmol ) of triphosgene in 5 ml of the same solvent were added . the reaction was agitated overnight . the resin was collected on a scintered glass funnel and washed well with dichloromethane . drying the residue in the vacuum oven afforded 1 . 085 g of resin . analysis of the resin by ft - ir showed a strong carbonyl stretch at 1800 cm − 1 . the resin was then resuspended in 10 ml of dichloromethane and 232 mg ( 1 . 88 mmol ) of 3 - cyclopropyl - 5 - aminopyrazole were added . after 12 hours under stirring the resin was collected by filtration and washed with methanol . after drying in the vacuum oven , 1 . 097 g of resin were obtained . analysis by ft - ir showed a strong carbonyl stretch at 1761 cm − 1 . 100 mg ( 0 . 1 mmol ) of oxime - carbamate resin ( xviii ) was suspended in 1 ml of dmso and 11 mg ( 0 . 08 mmol ) of 3 - methoxybenzylamine in 0 . 2 m dmso solution were added . the reaction was heated at 80 ° c . for three hours , then the resin was separated by filtration , washed with 150 μl of dichloromethane and 150 μl of meoh . the filtrate was concentrated to give , after trituration with diethylether 11 . 4 mg ( 50 % yield ) of the title compound . all compounds were characterized by mass spectrometry ( ms ). lc - ms confirmed that in each case the principle component had a molecular ion corresponding to the expected product . the compounds showed an hplc area % ranging from 70 to 100 . to a solution of 1 . 5 g ( 6 . 7 mmol ) of tert - butyl - 3 - amino - 5 - cyclopropyl - 1h - pyrazole - 1 - carboxylate in 15 ml of dichloromethane under nitrogen 1 . 41 g ( 7 mmol ) of p - nitrophenylchloroformate in a mixture of 7 ml of dichloromethane and 1 ml of pyridine were added dropwise at 0 ° c . after 12 hours at room temperature the precipitate was separated by filtration to give 1 . 95 g ( 75 % yield ) of p - nitrophenyl - tert - butyl - 3 - amino - 5 - cyclopropyl - carbamate . this intermediate ( 5 mmol ), without further purification , was suspended in 20 ml of acetonitrile and 830 mg ( 5 . 5 mmol ) of ( 1 , 3 - benzodioxol - 5 - yl )- methylamine were added . after 3 hours at 80 ° c . the suspension was filtered and the filtrate concentrated in vacua . the residue was redissolved in ethylacetate and washed with a saturated solution of sodium hydrogencaibonate and then with water . the organic layer was dried over anhydrous sodium sulfate and evaporated to dryness . the crude was purified by chromatography on a silica gel column ( hexane / ethylacetate 7 / 3 ) to give 1 . 2 g ( 60 % yield ) of n -( 3 - cyclopropyl - 1 - tert - butoxycarbonyl - pyrazol - 5 - yl )- n ′-( 1 , 3 - benzodioxol - 5 - yl - methyl ) urea . at last the previous intermediate ( 3 mmol ) was dissolved in 25 ml of a mixture 10 % v / v of trifluoroacetic acid - dichloromethane . after 1 hour at room temperature , the solvent was evaporated to dryness the residue redissolved with dichloromethane and washed with a saturated solution of sodium hydrogencarbonate . the organic layer was dried over anhydrous sodium sulfate and concentrated to give 855 mg ( 95 % yield ) of the title compound . obviously , numerous modifications and variations of the present invention are possible in light of the above teachings . it is therefore to be understood that within the scope of the appended claims , the invention may be practiced otherwise than as specifically described herein .
3 - ureido - pyrazole derivatives represented by formula : where r , r 1 and r 2 are as described herein , or pharmnaceutically acceptable salts thereof ; are useful , for example , for the treatment of cancer , cell proliferative disorders , alzheimer &# 39 ; s disease , viral infections , auto - immune diseases or neurodegenerative diseases .