MXPA02008535A - 5 alkylpyrido[2,3 d]pyrimidines tyrosine kinase inhibitors. - Google Patents

Abstract

Disclosed are compounds of the formula (I) wherein: R2 is hydrogen, alkyl, or cycloalkyl; R3 is hydrogen, lower alkyl, lower alkoxy, halogen, trifluoromethyl, lower alkynyl, lower alkenyl, nitrile, nitro, COR4, CO2R4, CONR4R5, CONR4OR5, SO2NR4R5, SO2NR4R5, SO2R4, SO3R4, formula (II), or NR4R5; Y is N or CR7; R9 is lower alkyl, haloalkyl, or aryl; X and Z are independently hydrogen, halogen, lower alkyl, lower alkoxy, trifluoromethyl, hydroxy, nitrile, nitro, NR4R5, N(O)R4R5, NR4R5R6W, SR4, C(O)R4, CO2R4, CONR4R5, SO2NR4R5, SO2R4, SO3R4, P(O)(OR4)(OR5), T(CH2)mQR4, C(O)T(CH2)mQR4, or NR4C(O)T(CH2)mQR5; m is 1 to 6. These compounds are useful for treating cell proliferative disorders, such as cancer, atherosclerosis, and restenosis. These compounds are potent inhibitors of cyclin dependent kinases (cdks) and growth factor mediated kinases.

Description

INHIBITORS OF 5-ALQUILPIRID0r2.3-cMPIRIMIDINAS TIROSINA QU INASA FIELD OF THE INVENTION This invention relates to 5-alkylpyridopyrimidines as inhibitors of cyclin-dependent kinases, particularly cyclin-dependent kinase 4. The compounds of the invention are useful for the treatment of inflammation, cell proliferative diseases such as cancer and restenosis, and neurodegenerative diseases such as Alzheimer's disease.

SUMMARY OF THE RELATED ART Cyclin dependent kinases and related serine / threonine protein kinases are cellular enzymes that perform essential functions in regulating cell division and proliferation. The cyclin-dependent kinase catalytic units, of which nine have been identified, are activated by regulatory units known as c? Clins. Cyclin dependent kinases include (Cdk) Cdk1, Cdk2, Cdk4, Cdk5, Cdk6 and Wee-1 kinase. The increased activity or temporarily abnormal activation of these kinases results in the development of human tumors and other proliferative disorders such as restenosis. Compounds that inhibit Cdks, either by blocking the interaction between a cyclin and its coadjunction kinase, or by binding a, and inactivating the kinase, causes the inhibition of cell proliferation and thus are useful for treating tumors and other abnormal proliferation cells. Various compounds that inhibit Cdks have demonstrated preclinical and clinical anti-tumor activity. For example, flavopiridol is a flavonoid that is a potent inhibitor of Cdk2 and Cdk4, and has been shown to inhibit various types of breast and lung cancer cells (Kaur et al., J. Natl. Cancer Inst., 1992; : 1736-1740; Kaur et al., Int. J. Oncol., 1996; 9: 1 143-1 168). In addition, Olomoucin [2- (hydroxyethylamine) -6-benzylamine-9-methyipurine] is a potent inhibitor of Cdk2 and Cdk5 (Vesely et al., Eur. J. Biochem, 1994; 224: 771-786), and has been shown to inhibit proliferation of approximately 60 different human tumor cell lines used by the National Cancer Institute (NCI) to be screened by new cancer therapies (Abraham et al., Biol., Cell, 1995; 83: 105-120). In addition to treating cancer, Cdk inhibitors have been shown to treat cardiovascular disorders such as restenosis and atherosclerosis. Other diseases in which Cdk inhibitors are useful include those caused by a variety of infectious agents, including DNA and RNA viruses, and inflammatory disorders such as rheumatoid arthritis. It is an object of this invention to provide a group of small molecular weight organic compounds which are potent Cdk inhibitors, and as such are useful to avoid and treat diseases caused by abnormal proliferative cells.

BRIEF DESCRIPTION OF THE INVENTION This invention provides 5-alkyl pyridopyrimidines which are used to treat inflammation, cell proliferative diseases such as cancer and restenosis, and neurodegenerative diseases such as Alzheimer's disease. The compounds of the invention show unexpected improvements in pharmacokinetic properties over the prior art compounds, including unanticipated metabolic stability and low cleaning rates. In addition, the compounds of the invention are unexpectedly selective inhibitors of Cdk4. The compounds of the invention are readily synthesized, and can be administered to patients by a variety of methods. The compounds of the invention are those having the structure of Formula I: and pharmaceutically acceptable salts, esters, amides and prodrugs thereof, wherein: R is (a) hydrogen; (b) lower alkyl optionally substituted with one, two or three groups independently selected from halogen, hydroxy, lower alkoxy, amino, mono- or dialkylamino, carboxy, alkoxycarbonyl, thioalkyl, nitrile, aryl, heteroaryl, or a carbocyclic group containing 3 to 7 members, up to two of whose members are optionally heteroatoms independently selected from oxygen, sulfur and nitrogen; or (c) a carbocyclic group containing from 3 to 7 members, up to two of which members are optionally heteroatoms selected independently of oxygen, sulfur and nitrogen, wherein the carbocyclic group is substituted or unsubstituted with one, two or three groups independently selected from halogen, hydroxy, lower alkyl, lower alkoxy, amino, mono- or dialkylamino, aryl and heteroaryl; R3 is hydrogen, lower alkyl, lower alkoxy, halogen, trifluoromethyl, lower alkynyl, lower alkenyl, nitrile, nitro, -COR4, -CO2R4, -CONR4R5, CONOR5, - R 'SO2NR4R5, -SO2R4, -SO3R4, P (O) (OR4) (OR5), or -NR4R5; And it is N or CR7; R9 is lower alkyl, haloalkyl or aryl; X and Z are independently hydrogen, halogen, lower alkyl, lower alkoxy, trifluoromethyl, hydroxy, nitrile, nitro, -NR4R5, -N (O) R4R5, -NR4R6R6W, -SR4, -C (O) R4, -CO2R4, -CO N R 4 R 5, -SO 2 N R 44 DR 5 °, SO 2 R 4, -SO 3 R 4, P (O) (OR) (O R) 5, -T (CH2) mQR4, -C (0) T (CH2) mQR4 4, or _ m is 1 -6; n is 0-6; T is O, S, N R 4, N (O) R 4, N R 4 R 5 W, or CR 4 R 5; Q is O, S, NR4, N (0) R4, NR4R5W, CO2 or a carbocyclic group containing from 3 to 7 members, up to four of which members are optionally heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the carbocyclic group is unsubstituted or substituted with one, two or three groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalqui it, trifluoromethyl, N-hydroxyacetamide, trifluoromethylalkyl, amino or mono or dialkylamino; R6 is lower alkyl, haloalkyl or aryl; R7 is NR4R5, N (O) R4R5, NR4R5R9X, OH, OR4, SR4, halo, COR4, (CH2) nR4, CO2R4, CON R4R5, C (O) NR4SO2R5, S (O) R4, SO2R4, SO2N R4R5, SO3R4 , (CH2) nP (O) (OR4) 2, N R4SO2R5, aldeh gone, nitrile, nitro, alkyl, alkoxyalkyl, T (CH2) mQR4, C (O) T (CH2) mQR4, N R4C (O) T ( CH2) mQR5, or T (CH2) mCO2R4; W is an anion; R4 and R5 are independently hydrogen, lower alkyl, lower alkenyl, lower alkynyl, (CH2) nAr, arylalkyl, aryl, heteroaryl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, or heteroaryl, or R4 and R5 together with the nitrogen to which they are attached form a carbocyclic ring containing 3 to 8 members, up to four of which members are optionally carbonyl groups or heteroatoms independently selected from oxygen, sulfur, S (O), S (O) 2, and nitrogen, wherein the carbocyclic group is substituted or unsubstituted with one, two, three, or four groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, aminoalkylcarbonyl, trifluoromethyl, trifluoromethylalkyl, trifluorometilalquilaminoalquilo, amino, mono- or dialkylamino, N-hydroxyacetamido, aryl, heteroaryl, carboxyalkyl, NR10SO2R1 1, C (O) NR1 0R1 1, NR1 0C ( O) R 1 1, C (O) OR 10, C (O) N R 10 SO 2 R 1 1, (CH 2) n S (O) n R 10, (CH 2) n-heteroaryl, O (CH 2) n-heteroaryl, (CH2) nC (O) NR10R1 1, O (CH2) nC (O) OR10; and R 4 may additionally be substituted or unsubstituted alkyl with one, two, or three groups independently selected from halogen, 5-oxo-4,5-dihydro-1 H-1, 2,4-triazoI-3-yl-sulfanyl, 5-oxo-4,5-dihydro-1 H-1, 2,4-triazol-3-yl-sulfinyl, 5-oxo-4,5-dihydro-1 H-1, 2,4-triazole-3- il-sulfonyl or a carbocyclic group containing from 3 to 7 members, up to four of which members are optionally heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the carbocyclic group is substituted or unsubstituted substituted with one, two or three groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alcoxicarboni so, what alquilcarboni, alkylcarbonylamino, aminoalkyl, trifluoromethyl, N-hydroxyacetamide, trifluoromethylalkyl, amino or mono- or lamino dialqui; and when Y is CR7, it is part of the structure of the part where R7 and Z are as defined previously, or they can be taken together with the carbons to which they are attached to form wherein: G and J are independently CH2, NH, or O; B is NH, S, CH2, or O; D is C or N, with the proviso that R1 0 is nothing when D is N; and R1 0 and R1 1 are independently hydrogen, halogen, lower alkyl, lower alkoxy, or alkylcarbonyl.

Preferred compounds have Formula I wherein Y is CR7. Of this group, the preferred compounds are those wherein R7 is NR4R5, and R4 and R5 are taken together with N to which they are attached to form a ring such as piperazine, piperidine, pyrrolidine, morpholine, each of which may be optionally substituted. The present invention also provides pharmaceutical compositions comprising a compound of Formula I together with a pharmaceutically acceptable diluent, carrier or excipient. The present invention also provides methods for inhibiting cyclin-dependent kinase and kinase enzymes mediated by growth factor. The present invention also provides a method for treating subjects suffering from diseases caused by cell proliferation. The method involves inhibiting proliferation of tumorigenic cells of epithelial origin and proliferation of vascular smooth muscle, and / or cell migration by administering therapeutically effective amounts of a compound of Formula I to a subject in need of treatment. The invention also provides compounds useful in the diagnosis and treatment of cancer, psoriasis, vascular smooth muscle cell proliferation associated with atherosclerosis and post-surgical stenosis and vascular restenosis in mammals.

The present invention also provides a method for treating subjects suffering from diseases caused by DNA tumor viruses such as herpes viruses.

DETAILED DESCRIPTION OF THE INVENTION The novel compounds encompassed by the present invention are those described by the general Formula I set out in the above, and pharmaceutically acceptable salts, esters, amides and prodrugs thereof. In addition to the compounds of Formula I, the invention encompasses, in a preferred embodiment, compounds of Formula II: wherein X, Y, Z and R3 are as defined above for Formula I. Preferred compounds of Formula II are those in which X and Z are independently hydrogen, Cl, or F; And it's CR7; and R3 is hydrogen, Cl, F, Br or CN. In addition, the present invention also encompasses preferred compounds of Formula III: Especially preferred compounds of Formula 11 are those in which X and Z are independently hydrogen, Cl, or F; And it's CR7; and R3 is hydrogen, Cl, F, Br, or CN. In addition, the present invention also encompasses, as a further preferred embodiment, compounds of Formula IV: Preferred compounds of Formula IV are those in which X and Z are independently hydrogen, Cl, or F; And it's CR7; and R3 is hydrogen, Cl, F, Br or CN. The most preferred compounds of the invention have Formula V wherein: R2 is alkyl or cycloalkyl; R3 is hydrogen or halo; R9 is alkyl; X and Z independently are hydrogen or halo; R7 is NR4R5; and R4 and R5 are taken together with the nitrogen to which they are attached to form a 5- or 6-membered carbocyclic ring, optionally containing an oxygen, nitrogen, or sulfur heteroatom, and optionally substituted with alkyl or substituted alkyl groups. Especially preferred compounds of Formula V are those wherein R7 is and such groups are replaced optionally by alkyl, acyl, amide, or the like.

Unless clearly stated otherwise, the following definitions are adhered to throughout this description. By "alkyl", "lower alkyl" and "C1-C10 alkyl" in the present invention is represented a linear or branched hydrocarbon radical having from 1 to 10 carbon atoms and includes, for example, methyl, ethyl, n- propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, iso-pentyl, n-hexyl, and the like. By the term "halogen" in the present invention, straight or branched chain alkoxy groups having 1-10 carbon atoms are represented, such as, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy, ter-butoxy, pentoxy, 2-pentoxy, isopentoxy, neopentoxy, hexoxy, 2-hexoxy, 3-hexoxy and 3-methylpentoxy. In addition, alkoxy refers to polyethers such as -O- (CH2) 2-O-CH3- and the like. "Alkanoyl" groups are alkyl groups attached through a carbonyl, ie, C? -Cs-C (O) -. Such groups include formyl, acetyl, propionyl, butyl, and isobutyryl. "Acyl" means an alkyl or aryl (Ar) group linked through a carbonyl group, ie, R-C (O) -. For example, acyl includes a Ci-Cß alkanoyl, including substituted alkanoyl, wherein the alkyl portion may be substituted by NR4R5 or a carboxyl or heterocyclic group. Typical acyl groups include acetyl, benzoyl and the like.

"Amide" is an amino carbonyl group such as -CONR4R5. The alkyl, alkenyl, alkoxy and alkynyl groups described above are optionally substituted, preferably by 1 to 3 groups selected from NR4R5, phenyl, substituted phenyl, Ci-e-thioalkyl, Ci-C-alkoxy, hydroxy, carboxy, Ci-alkoxycarbonyl. Cß, halo, nitrile, cycloalkyl and a 5 or 6 membered carbocyclic ring or heterocyclic ring having 1 or 2 heteroatoms selected from nitrogen, substituted nitrogen, oxygen and sulfur. "Substituted nitrogen" means nitrogen that supports Ci-Cß alkyl (CH 2) nPh where n is 1, 2 or 3. It also includes the substitution of perhalo and polyhalo. Examples of substituted alkyl groups include 2-aminoethyl, 2-hydroxyethyl, pentachloromethyl, trifluoromethyl, 2-diethylaminoethyl, 2-dimethylaminopropyl, ethoxycarbonylmethyl, 3-phenylbutyl, methanesulfanylmethyl, methoxymethyl, 3-hydroxypentyl, 2-carboxybutyl, 4-chlorobutyl, 3- cyclopropylpropyl, pentafluoroethyl, 3-morpholinopropyl, piperazinylmethyl, and 2- (4-methylpiperazinyl) ethyl. Examples of substituted alkyl groups include 2-methoxyethynyl, 2-ethylsulfanythynyl, 4- (1-piperazinyl) -3- (butynyl), 3-phenyl-5-hexynyl, 3-diethylamino-3-butynyl, 4-chloro-3- butynyl, 4-cyclobutyl-4-hexenyl and the like. Typical substituted alkoxy groups include aminomethoxy, trifluoromethoxy, 2-diethylaminoethoxy, 2-ethoxycarbonylethoxy, 3-hydroxypropoxy, 6-carbohexyloxy, and the like.

In addition, examples of substituted alkyl, alkenyl and aikinyl groups include dimethylaminomethyl, carboxymethyl, 4-dimethylamino-3-buten-1-yl, 5-ethylmethylamino-3-pentyl-1-yl, 4-morphinobutyl, 4-tetrahydropyridinylbutyl, 3-imidazole in-1-ylpropylo, 4-tetrahydrothiazol-3-yl-butyl, phenylmethyl, 3-chlorophenylmethyl and the like. The term "anion" means a negatively charged counterion such as chloride, bromide, trifluoroacetate and triethylammonium. By "heteroaryl" is represented one or more aromatic ring systems of 5-, 6- or 7-membered rings containing at least one and up to four heteroatoms selected from nitrogen, oxygen or sulfur. Such heteroaryl groups include, for example, thienyl, furanyl, thiazolyl, triazolyl, imidazolyl, (is) oxazolyl, oxadiazolyl, tetrazolyl, pyridyl, thiadiazolyl, oxadiazolyl, oxathiadiazolyl, triatriazolyl, pyrimidinyl, (iso) quinolinyl, naphthyridinyl, phthalimidyl, benzimidazolyl and benzoxazolyl. A preferred heteroaryl is pyridine. By "aryl" is represented an aromatic carbocyclic group having a single ring (e.g., phenyl), multiple rings (e.g., biphenyl), or condensed multiple rings in which at least one is aromatic (e.g., 1, 2,3,4-tetrahydronaphthyl, naphthyl, anthryl, or phenanthryl), which may be mono-, di-, or trisubstituted with, for example, halogen, alkyl, or lower, lower alkoxy, lower alkylthio, trifluoromethyl, lower acyloxy, aryl, heteroaryl and hydroxy. A preferred aryl is phenyl. The term "cancer" includes, but is not limited to, the following cancers: breast, ovarian, cervical, prostate, testes, esophagus, glioblastoma, neuroblastoma, stomach, skin, keratoacanthoma, lung, squamous cell carcinoma, large cell carcinoma , adenocarcinoma, bone, colon, adenocarcinoma, adenoma, pancreas, adenocarcinoma, thyroid, follicular carcinoma, undifferentiated carcinoma, papillary carcinoma, seminoma, melanoma, sarcoma, bladder carcinoma, liver carcinoma, and biliary passage, kidney carcinoma, disorders of myeloid, lymphoid disorders, Hodgkin, hairy cells, oral cavity and pharynx (oral), lip, tongue, mouth, pharynx, small intestine, colo-rectum, large intestine, rectum, brain and central nervous system and leukemia. The term "pharmaceutically acceptable salts, esters, amides, and prodrugs" as used herein refers to those carboxylate salts, amino acid addition salts, esters, amides, and prodrugs of the compounds of the present invention which are, within of the scope of legitimate medical judgment, suitable for use in contact with the tissues of patients without undue toxicity, irritation, allergic response, and the like, in proportion to a reasonable benefit / risk ratio, and effective for their intended use, as well as zwitterionic forms, when possible, of the compounds of the invention. The term "salts" refers to the relatively non-toxic organic and inorganic acid addition salts of the compounds of the present invention. These salts can be prepared in situ during the isolation and final purification of the compounds or by separately reacting the purified compound in its free base form with a suitable organic and inorganic acid and isolating the salts thus formed. Representative salts include the salts hydrobromide, hydrochloride, sulfate, bisulfate, nitrate, acetate, oxalate, valerate, oleate, palmitate, stearate, laurate, borate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, naphthylate, mesylate, glucoheptanoate, lactobionate and laurisulfatonate, and the like. These may include cations based on alkali and alkaline earth metals, such as sodium, lithium, potassium, calcium, magnesium and the like, as well as non-toxic ammonium, quaternary ammonium, and amine cations including, but not limited to, ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine and the like (See, for example, Berge S.M. et al., "Pharmaceutical Salts," J. Pharm. Sci., 1977; 66: 1-19 which is incorporated in the present for reference). Examples of non-toxic pharmaceutically acceptable esters of the compounds of this invention include Ci-β alkyl esters wherein the alkyl group is a straight or branched chain. Acceptable esters also include C5-C7 cycloalkyl esters as well as arylalkyl esters such as, but not limited to, benzyl. Alkyl esters of C are preferred? -C4- The esters of the compounds of the present invention can be prepared according to conventional methods. Examples of pharmaceutically acceptable non-toxic amides of the compounds of this invention include amides derived from ammonia, primary Ci-β-alkylamines and secondary Ci-β-dialkylamines wherein the alkyl groups are straight or branched chain. In the case of secondary amines the amine may also be in the form of a 5- or 6-membered heterocycle containing a nitrogen atom. Amides derived from ammonia, primary C1-C3 alkylamines and secondary C1-C2 diamines are preferred. The amides of the compounds of the invention can be prepared according to conventional methods. The term "prodrug" refers to compounds that rapidly transform in vivo to produce the parent compound of the above formulas, for example, by hydrolysis in blood. A full discussion is provided in T. Higuchi and V. Stella, "Pro-drugs as Novel Delivery Systems," Vol. 14 of the A. C. S. Symposium Series, and in Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987, both of which are incorporated herein by reference.

Representative compounds of the invention are shown later in Table 1. ABLA i 12 13 TABLE 1 (cont.) 19 22 27 34 35 TABLE 1 (cont.) 36 37 38 40 TABLE 1 (cont.) TABLE 1 (cont.) 91 102 TABLE 1 (cont.) mess 129 TABLE 1 (cont.) TABLE 1 (cont.) 192 202 TABLE 1 (cont.) TABLE 1 (cont.) TABLE 1 (cont.) 235 TABLE 1 (cont.) TABLE 1 (cont.) TABLE 1 (cont.) TABLE 1 (cont.) The compounds of the present invention are useful for treating cancer (e.g., leukemia and cancer of the lung, breast, prostate and skin such as melanoma) and other proliferative diseases including, but limited to, psoriasis, HSV, HIV, restenosis, and atherosclerosis. To use a compound of the present invention to treat cancer, a patient having cancer is administered a therapeutically effective amount of a pharmaceutically acceptable composition comprising a compound of the invention. A further embodiment of this invention is a method for treating subjects suffering from diseases caused by vascular smooth muscle cell proliferation. Compounds within the scope of the present invention effectively inhibit proliferation and cell migration of vascular smooth muscle. The method involves inhibiting vascular smooth muscle proliferation and / or migration by administering an amount effective of a compound of formula I to a subject in need of such treatment. The compounds of the present invention can be formulated and administered in a variety of oral and parenteral dosage forms, including transdermal and rectal administration. It will be recognized by those skilled in the art that the following dosage forms may comprise as the active component, either a compound of Formula I or a corresponding pharmaceutically acceptable salt, ester, amide, prodrug, or solvate of a compound of the Formula I. A further embodiment of this invention is a pharmaceutical composition comprising a compound of Formula I together with a pharmaceutically acceptable carrier, diluent, or excipient thereof. To prepare pharmaceutical compositions with the compounds of the present invention, pharmaceutically acceptable carriers can be either solid or liquid. Solid form preparations include powders, tablets, pills, capsules, wafers, suppositories, and dispersible granules. A solid carrier may be one or more substances which may also act as diluents, flavoring agents, binders, preservatives, tablet disintegrating agents or an encapsulating material. In powders, the carrier is a finely divided solid such as talc or starch which is in a mixture with the finely divided active component. In tablets, the component Active is mixed with the carrier having the necessary binding properties in suitable proportions and compacted in the desired shape and size. The compositions of this invention preferably contain from about 5% to about 70% or more of the active compound. Suitable carriers include magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, a low melting wax, cocoa butter, and the like. A preferred form for oral use are capsules, which include the formulation of the active compound with encapsulating material as a carrier providing a capsule in which the active component with or without other carriers, is surrounded by a carrier, which is thus in association with the. Similarly, wafers and rhombuses are included. Tablets, powders, capsules, pills, wafers and diamonds can be used as solid dosage forms suitable for oral administration. To prepare suppositories, a low melting wax, such as a mixture of fatty acid glycerides or cocoa butter, is first melted and the active component is dispersed homogeneously in the present, as by agitation. The molten homogeneous mixture is then poured into molds of suitable size, allowed to cool, and therefore solidify.

Liquid form preparations include solutions, suspensions, and emulsions such as water or water / propylene glycol solutions. For parenteral injection, the liquid preparations can be formulated in aqueous polyethylene glycol solution, isotonic saline solution, 5% aqueous glucose, and the like. Aqueous solutions suitable for oral use can be prepared by dissolving the active component in water and adding suitable colorants, flavors, stabilizers and thickening agents as desired. Aqueous suspensions suitable for oral use can be made by dispersing the finely divided active component in water and mixing with a viscous material, such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, or other well-known suspending agents. Also included are the solid form preparations which are intended to be converted, shortly before use, to liquid form preparations for oral administration. Such liquid forms include solutions, suspensions and emulsions. These preparations may contain, in addition to the active component, colorants, flavors, stabilizers, regulators, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like. Waxes, polymers, microparticles and the like can be used to prepare sustained release dosage forms. Also, the osmotic groups they can be used to supply the active compound uniformly over a prolonged period. The pharmaceutical preparations of the invention are preferably in unit dose form. In such form, the preparation is subdivided into unit doses containing appropriate quantities of the active component. The dosage unit form can be a packaged preparation, the package containing discrete quantities of preparation, such as packed tablets, capsules, and powders in vials or ampules. Also, the dosage unit form can be a capsule, tablet, wafer, or rhombus thereof, or it can be the appropriate number of any of this in packaged form. The therapeutically effective dose of a compound of Formula I will generally be from about 1 mg / kg to about 100 mg / kg of body weight per day. The typical adult dose will be approximately 50 mg to approximately 800 mg per day. The amount of the active component in a unit dose preparation may vary or be adjusted from about 0.1 mg to about 500 mg, preferably from about 0.5 mg to 100 mg according to the particular application and potency of the active component. The composition may, if desired, also contain other compatible therapeutic agents. A subject in need of treatment with a compound of Formula I is administered a dose of about 1 mg to about 500 mg per day, either single or in multiple doses over a 24-hour period. The compounds of the present invention are capable of binding to and inhibiting the activity of proteins that have the ability to phosphorylate other proteins, such as cdks, PDGFr, FGFr, c-Src, and EGFr-FL. Cdks form complexes with cyclins, and these complexes phosphorylate key proteins that allow cells to proceed through the cell cycle (Meijer L., Progess in Cell Cycle Research, 1995; 1: 351-363). The compounds of this invention inhibit this phosphorylation and therefore can be used as anti-proliferative agents for the treatment of cancer and / or restenosis and other proliferative diseases. Due to their inhibitory activity against cdks and other kinases, the compounds of the present invention are also useful research tools for studying the mechanism of action of those kinases, both in vitro and in vivo. The examples presented below are intended to illustrate particular embodiments of the invention, and are not intended to limit the scope of the specification or the claims in any way. An illustration of the preparation of the compounds of the present invention is shown in Schemes 1 and 2.

Scheme 1 (TO) jP (O) CH, C0 ^ t | NaH Y 1. Toxaziridine 2. Boo-Pip-aniline Scheme 2 Those of skill in the art will recognize that the starting materials may be varied and the additional steps employed to produce compounds encompassed by the present invention, as demonstrated by the following examples. As shown in Schemes 1 and 2, a 4-substituted amino-2-methanesulfanyl-pyrimidine-5-carboxaldehyde is reacted with an organometallic compound, such as, for example, a Grignard reagent, to produce the corresponding secondary alcohol. The alcohol is subsequently oxidized to the ketone. The ketone is then reacted with a trialkyl phosphonoacetate in the presence of the base to produce 5-alkyl-2-methylsulfanyl-8H-pyrido [2,3-d] pyrimidn-7-one 8 replaced. The pyrido-pyrimidine can then be halogenated in the 6-position with a common halogenating agent, such as, for example, N-bromosuccinimide (NBS). The 2-methylsulfanyl derivative is oxidized to the corresponding methylsulfoxide, which is subsequently treated with a desired aniline to produce the compound of the invention 2-phenylamino. When carrying out various reactions to prepare the compounds of the invention, it may be desirable to derive reactive groups such as amines, alcohols, and acids, with protecting groups that are easily eliminated when desired. Such protection groups simply avoid unwanted side reactions. The use of protection groups is common in the technique of organic chemistry, as described by Greeve and Wuts in Protective Groups in Organic Synthesis, John Wiley and Sons, New York (2nd ed, 1991). Typical hydroxy protecting groups include either forming groups such as benzyl, and acyl groups such as tert-butoxycarbonyl (Boc), formyl, and acetyl. Amino-protecting groups include benzyl, acyl groups such as acetyl and tria I qui I ifyl. The carboxylic acid groups are normally protected by conversion to an ester which can be easily hydrolyzed, for example, trichloroethyl, tert-butyl, benzyl and the like. Some of the compounds of the invention have one or more chiral centers and thus may exist as individual optical isomers and mixtures thereof. Compound 246 (Table 1), for example, can exist as an RS racemate, or as the individual R or S isomer. All individual isomers and mixtures thereof are included in this invention. The individual isomers are readily prepared by a chiral synthesis, or by conventional resolution techniques well known to those skilled in the art. The invention is further illustrated by the following detailed examples that are not constructed as limiting the invention in the scope or spirit of the specific procedures described therein. The starting materials and various intermediates used in the synthesis of the compounds of the invention can be obtained from commercial sources, prepared from organic compounds commercially. available, or prepared using well-known synthetic methods. The descriptions in this application of all articles and references, including patents, are incorporated herein by reference.

EXAMPLE 1 8-C / c / opei? Í # 7-6-f / í oro-5-? Peí / 7-2- ef // sü / fan / 7-8W-p / r o'o'2, 3-djp i rim idin-7-ona NaH (771 mg, 19.3 mmol) is suspended in dry THF (20 mL), and the mixture is cooled to 0 ° C in an ice bath. Triethyl 2-fluoro-2-phosphonoacetate (3.9 ml, 19.3 mmol) is added dropwise with stirring, and the solution is stirred at room temperature for 30 minutes. A solution of 1- (4-cyclopentylamino-2-methylsulfanyl-pyrimidin-4-yl) -ethanone in dry THF (40 mL) is added through a cannula, and the reaction mixture is stirred at 24 ° C for 12 hours. hours. The reaction is abruptly quenched by the addition of H2O (0.5 mL), and the THF is evaporated to the vacuum The residue is partitioned between ethyl acetate and saturated aqueous sodium chloride. The aqueous layer is extracted twice with fresh acetate, and the combined organic layers are dried over MgSO4. After removing the drying agent and evaporating the solvent, the unpurified product is purified by chromatography on silica gel (eluting with 20% / 30% ethyl acetate in hexanes) to give the title compound as a colorless solid (0.61 g, 23%).

EJ EM PLO 2 8-cyclopentyl-6-fluoro-2-methansulfinyl-5-methyl-8H-pyrido [2,3-d] p i rim idin -7 -o na 8-Cyclopentyl-6-fluoro-5-methyl-2-methylsulfanyl-8H-pyrido [2,3-d] pyrimidin-7-one (0.61 g, 2.08 m moles) is dissolved from Example 1 and 3 -pheni l-1-p-nitropheni lsu lfoni loxizi ridine (0.65 g, 2.5 mmol) in CH2Cl2 (20 mL) and stir for 12 hours at 24 ° C. The next evaporation of the solvent, the unpurified product is purified by gel-gel chromatography (eluting with 80% -100% ethyl acetate in hexanes) to give the sulfoxide product as a white solid (0.55 g, 86%).

EXAM PLO 3 4- [4- (8-Cyclopentyl-6-fluoro-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylammonic acid tert-butylester) yphenyl] -piperazine-1-carboxylic acid 8-cyclopentyl-6-fluoro-2-methanesulfini-l-5-methyl-8H-pyrido- [2,3-d] pyrimidin-7-one (0.3 g, 0.97 mmol) is suspended from Example 2 and 4- (? / - Boc-piperazin-1-yl) aniline (0.548 g, 1.94 mmoles) in 1,4-dioxane (5 mL) and heated at 80 ° C for 12 hours. Anhydrous DMSO (2.5 mL) is added, and the temperature is raised to 100 ° C. Heating is continued for 24 hours, after which the reaction mixture is cooled to 24 ° C and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer is separated and washed with H2O and then with saturated aqueous sodium chloride. After drying over anhydrous MgSO 4, the solvent is evaporated, and the residue is purified by silica gel chromatography to provide the title compound as a yellow solid (0.23 g, 45%).

EXAMPLE 4 8-Cyclopentyl-6-fluoro-5-methyl-2- (4-piperazin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7y? Na It dissolves 4- [4- (8-cyclopentyl-6-fluoro-5-methyl-7-oxo-7,8-d ihydro-pyrido [2,3-d] pyrimidine-butyl ester id i n- 2-i lami no) -phenyl] -piperazin-1-carboxylic acid (0.23 g, 0.44 mmol) from Example 3 in a 1: 1 mixture of trifluoroacetic acid (TFA) / CHCl2 (20 mL) and stirred at room temperature for 1 hour. Evaporation of the solvents, followed by the addition of anhydrous diethyl ether, gives an orange solid (compound 34) which is collected by filtration (0.21 g, 74%). Mp 254-255 ° C. C23H27N6OF 1.93 TFA: Calculated C, 50.21; H, 4.54; N, 13.08. Found: C, 49.83; H, 4.45; N, 12.99.

EXAMPLE 5 6-Bromo-8-cyclopentyl-5-metH-2-methylsulfanyl-8H-pyrido [2,3-d] pyrimidin-7-one Dissolve 8-cyclopentyl-5-methyl-2-methylsulfanyl-8H-pyrido [2,3-d] pyrimidin-7-one (1 g, 3.64 mmole) in dry DMF (15 mL) and? / - bromosuccinimide (0.97) g, 5.45 mmol) followed by benzoyl peroxide (0.13 g, 0.5 mmol). The resulting solution is stirred for 12 hours at 24 ° C. The mixture is then divided between ethyl acetate and H2O. The organic layer is washed with H2O, and then with saturated aqueous sodium chloride solution and dried over MgSO4. Removal of the drying agent and evaporation of the solvent gives the desired title product (0.86 g, 66%) which is used without further purification.

EXAM PLO 6 6-Bro o-8-cyclopentyl-5-methyl-2- (4-piperazin-1-yl-phenylamino) -8 H -pyrido [2,3-d] pyrimidin-7-one Oxide is oxidized 6-bromo-8-cyclopentyl-5-methyl-2-methylsulfanyl-8H-pyrido [2,3-d] pyrimidin-7-one as described in Example 2. The sulfoxide is reacted with 4- ( N-Boc-piperazin-1-yl) aniline as described in Example 3. The N-Boc protection group is removed by hydrolysis as described above for 8-cyclopentyl-6-fluoro-5-methyl-2- methylsulfanyl-8H-pyrido [2,3-d] pyrimidin-7-one to provide 6-bromo-8-cyclopentyl-5-methyl- 2- (4-piperazin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (compound 35). Pf > 200 ° C (decomposition). C23H27N6OBr 1.9 TFA: Calculated C, 45.90; H, 4.15; N, 11.97. Found: C, 45.53; H, 4.09; N, 11.76.

EXAMPLE 7 1- (4-Cyclopentylamino? And 2-methylsulfanyl-pyrimidin-5-yl) -ethan-1-ol 4-Cyclopentylamino-2-methanesulfanyl-pyrimidine-5-carboxaldehyde (1.1 g, 4.64 mmol) is dissolved in tetrahydrofuran (30 mL) under nitrogen and then cooled with an ice bath. To this clear solution is slowly added methylmagnesium bromide (4.4 ml, 13.2 mmol, 3 M in ether). The reaction is stirred for 1 hour with the ice bath still in place. The reaction is quenched with a small amount of saturated aqueous ammonium chloride and then partitioned between water and ethyl acetate. The layers are separated, and the aqueous layer is extracted with ethyl acetate. The organic layers are wash with brine and then dry over magnesium sulfate. After filtration, the solvent is removed in vacuo to yield the title compound as an oil (1.09 g, 90%). 1 H NMR (400 MHz, CDCl 3): d 1.42-1.59 (m, 5H), 1.60-1.76 (m, 4H), 2.04-2.06 (m, 2H), 2.49 (s, 3H), 4.38-4.43 (m, 1H), 4.59-4.74 (m, 1H), 6.28-6.30 (d, 1H), 7.57 (s, 1H).

EXAMPLE 8 1- (4-Cyclopentylamino-2-methylsulfanyl-pyrimidin-5-yl) -ethanone It is dissolved in 100 ml of dichloromethane 1- (4-cyclopentylamino-2-methylsulfanyl-pyrimidin-5-yl) -ethan-1-ol (1.09 g, 4.3 mmole) from Example 7. The solution is purged by bubbling gas from nitrogen through it for 2 minutes. To the reaction solution are added, in order: powdered molecular sieves (4 angstroms),? -methyl oxide (1.07 g, 8.6 g), and tetrapropylammonium perruthenate (0.227 g, 0.645 mmol). The reaction mixture is stirred at 24 ° C for 2 hours, and small Additional catalyst quantities are added periodically. The reaction mixture is run through a silica column (1: 1, ethyl acetate: hexanes) to yield the title compound as a light yellow solid (0.74 g, 70%). 1 H NMR (400 MHz, CDCl 3). d 1.51-1.78 (m, 6H), 2.02-2.08 (m, 2H), 2.49 (s, 3H), 2.53 (s, 3H), 4.47-4.53 (m, 1H), 8.53 (s, 1H), 9.21 (s, 1H); MS (M + 1) 252.2.

EXAMPLE 9 8-Cyclopentyl-5-methyl-2-methylsulfanyl-8Hypyrido [2,3yd] pyrimidin-7-one A cooled flask (5 ° C) containing tetrahydrofuran (50 mL) is charged with sodium hydride (1.05 g, 26.3 mmol, 60% dispersion in mineral oil) under nitrogen, and 1.0 g of triethyl phosphonoacetate is added. The cooling bath is removed, and the mixture is stirred at 24 ° C until it becomes a homogeneous solution. The solution is diluted by drip addition of a solution of 1- (4-cyclopentylamino-2-methylsulfanyl-pyrimidin-5-yl) -ethanone (3.0 g, 11.9 mmol) in tetrahydrofuran (25 mL). The reaction mixture is refluxed for 2 hours. The reaction mixture is cooled to 24 ° C, and 50 ml of water and 50 ml of ethyl acetate are diluted. Following the separation of the layers, the organic layer is dried over magnesium sulfate and concentrated in vacuo to near dryness. Hexane is added, and the solid is stirred vigorously for 5 minutes before being filtered to yield the title compound as a pale light orange solid (3.01 g, 92%). 1 H NMR (400 MHz, CDCl 3): d 1.63-2.36 (m, 8H), 2.38 (s, 3H), 2.59 (s, 3H), 5.84-5.93 (m, 1H), 6.39 (s, 1H), 8.66 (s, 1H).

EXAMPLE 10 8-Cyclopentyl-2-methansulfinyl-5-methyl-8H-pyrid [2,3-dJ-pyrimidin-7-one Dissolve in dichloromethane (15 mL) 8-cyclopentyl-5-2-methylsulfanyl-8H-pyrido [2,3-d] pyrimidin-7-one (1.0 g, 3.63 mmol) from Example 9, and add ( ±) -fra /? S-2- (phenylsulfonyl) -3-phenyloxaziridine. The reaction mixture is stirred at 24 ° C for 12 hours, and then the solution is passed through a silica column (2% MeOH in CH 2 Cl 2) to yield the title sulfoxide as a white solid (0.67 g, 64%). %). 1 H NMR (400 MHz, DMSO-dβ) d 1.53-2.19 (m, 8H), 2.45 (s, 3H), 2.87 (s, 3H), 5.75-5.84 (m, 1H), 6.64 (s, 1H), 9.19 (s, 1H).

EXAMPLE 11 4- [4y (8-Cyclopentyl-5-metily7y? Xo-7J8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) -f-nyl] -piperazine-1-carboxylic acid tert -butylester.

Dissolve in dimethylsulfoxide (8 mL) and warm at 90 ° C overnight 8-cyclopentyl-2-methansulfinyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (0.7 g, 2.4 mmoles) from Example 10 and 4- (4 '-? - Boc-piperazinyl) -aniline. The mixture of The reaction is cooled to room temperature and partitioned between water and ethyl acetate. The organic layer is washed with sodium hydrogen carbonate, brine, and then dried over magnesium sulfate. Removal of the drying agent and concentration in vacuo gives the title product as a yellow solid which is recrystallized from water and acetonitrile (0.55 g, 45%). 1 H NMR (400 MHz, CDCl 3): d 1.45 (s, 9H), 1.556.87 (m, 6H), 2.23-2.28 (m, 2H), 2.31 (s, 3H), 3.07 (m, 4H), 3.55 (m, 4H), 5.77-5.81 (m, 1 H), 6.19 (s, 1 H), 6.90 (d, 2H), 7.42-7.44 (d, 2H), 7.47 (s) , 1 H), 8.55 (s, 1 H); MS (M + 1) 505.1. The protecting group is removed by stirring in a 1: 1 mixture of trifluoroacetic acid / dichloromethane to give (Compound 1). Pf > 21 5 ° C (decomposition).

EXAM PLO 12 8-Cyclopentyl-5-ethyl-2- (4-piperazin-1-yl-phenylamino) -8 H -pyrido [2,3-a] pyrimidin-7-one (Compound 193) 1 - . 1- (4-Cyclopentylamino-2-methylsulfanyl-1-pyrimidin-5-yl) -propan-1-ol. 4-Cyclopentylamino-2-methylsulfanyl-pyrimidine-5-carbaldehyde (4.07 g, 17.1 mmol) was dissolved in TH F (60 mL) under nitrogen, then cooled with an ice bath. EtMgBr (1 3.4 ml, 40.3 mmol, 3 M Aldrich in ether) was slowly added to this clear solution. The reaction was stirred for 15 minutes with the ice bath still in place. The reaction was quenched with a small amount of saturated aqueous H 4 Cl, then partitioned between water and EtOAc. The layers were separated, the organic layer was dried over MgSO4, and after filtration, the solvent was removed in vacuo to yield 1- (4-cyclopentylamino-2-methylsulfanyl-pyrimidin-5-yl) -propan-1-ol. as an oil (4.55 g, 99%) which was used without further purification. 1- (4-Cyclopentylamino-2-methylsulfanyl-pyrimidin-5-yl) -propan-1-one. 1 - (4-Cyclopentylamino-2-methylsulfanyl-pyrimidin-5-yl) -propan-ol (4.55 g, 17.1 mmol) was dissolved in toluene (80 μL) to which manganese (IV) oxide was subsequently added (3.72). g, 42.8 mmol, Aldrich <5 microns, activated, (-85%) .The reaction was brought to reflux for 16 hours.The reaction was cooled to room temperature and filtered through a pad of celite. it was concentrated in vacuo to yield the product as a light yellow oil (3.79 g, 84%) 8-Cyclopentyl-5-ethyl-2-methylsulfanyl-8H-pyrido [2,3-d] pyrimidin-7-one. charged under nitrogen, a flask cooled with THF (50 mL) with NaH (1.23 g, 30.7 mmol, 60% dispersion in mineral oil) to which triethyl phosphonoacetate (6.09 ml, 30.7 mmol) was added. The cooling bath was removed, and the reaction mixture was stirred at room temperature until all was dissolved. A solution of 1- (4-cyclopentylamino-2-methylsulfanyl-pyrimidin-5-yl) -propan-1 -one (3.0 g, 11.9 mmol) in THF (70 mL) was added slowly to the preformed anion. . Then the reaction mixture is refluxed for 60 hours. The reaction was cooled to room temperature and diluted with water and EtOAc. The layers separated, and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give a waxy solid. The solid residue was triturated with hexanes to give a white solid after filtration (2.67 g, 66%). 8-Cyclopentyl-5-ethyl-2-methanesulfinyl-8H-pyrido [2,3-d] pyrimidin-7-one. 8-Cyclopentyl-5-ethyl-2-methylsulfanyl-8H-pyrido [2,3-d] pyrimidin-7-one (2.57 g, 8.88 mmol) was dissolved in CH2Cl2 (50 mL) and 2-benzenesulfonyl was added. -3-phenyl-oxaziridine. The reaction mixture was stirred for 16 hours at room temperature. Then the solution was evaporated in vacuo to give an orange oil. EtOAc was added and a white precipitate formed. This precipitate was filtered and washed with hexanes to yield a white solid (2.12 g, 78%). 4- [4- (8-Cyclopentyl-5-ethyl-7-oxo-7-, 8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) -phenyl] -piperazine-1-butyl ester -carboxylic Sulfoxide, 8-cyclopentyl-5-ethyl-2- was dissolved methansulfinyl-8H-pyrido [2,3-d] pyrimidin-7-one (0.2 g, 0.654 mmol) and 4- (4'-A / -Boc-piperazinyl) -aniline in DMSO (5 mL) and warmed to 70 ° C for 16 hours. The reaction mixture was cooled to room temperature and partitioned between water and EtOAc. The organic layer was washed with brine, then dried over MgSO 4. After filtration and concentrated in vacuo, an orange solid was obtained which was purified by column chromatography to produce the product as a yellow solid (0.160 g). , 47%). 8-cyclopentyl-5-ethyl-2- (4-piperazin-1-yl-f-amino) -8H-pyrido [2,3-d] pyrimidin-7-one (235). It was dissolved in dichloromethane (2 mL) 4- [4- (8-cyclopentyl-5-ethyl-7-oxo-7,8-dihydro-piido [2,3-d] pi] -butylester. -2-i lami no) -f eni l -piperazin-1-carboxylic acid, and trifluoroacetic acid (0.5 mL) was added. This mixture was stirred at room temperature for 15 hours. The solvent was evaporated, then the solid was suspended in diethyl ether and filtered to give a fluffy gray solid (128 mg, 75%), 1 H NMR (400 MHz, DMSO-c / 6): d 1.17 (m, 3H) , 1.52-1.83 (m, 6H), 2.20 (m, 2H), 2.75 (m, 2H), 3.22 (m, 4H), 5.78 (m, 1H), 6.10 (s, 1H), 6.95 (d, 2H) ), 7.53 (d, 2H), 8.73 (s, 2H), 8.79 (s, 1H), 9.76 (s, 1H); CHN for C23H30N6O + 1.21 TFA.

EXAM PLO 13 2- [4- (4-Acetyl-piperazin-1-yl) -phenylamino] -8-cyclopentyl-5-methyl-8H-pyrido [2,3-] pyrimidin-7-one (Compound 198) They were dissolved in DMSO (5 mL) and heated at 70 ° C for 16 hours 1 - [4- (4-Amino-phenyl) -piperazin-1-yl-ethane (0.075 g, 0.343 mmol) and 8-cyclopentyl-5 methyl-2-methansulfinyl-8H-pyrido [2,3-d] pyrimidin-7-one (0.100 g, 0.343 mmol). At this point, an additional 20 mg of the aniline was added, and heating was continued for an additional 4 hours. The reaction was cooled to room temperature and partitioned between water and EtOAc. The organic layer was washed with brine, then dried over MgSO 4. Filtration and concentration in vacuo gave an orange solid which was purified by column chromatography to yield a yellow solid (0.049 g, 32%). Mp 261-263 ° C.

EXAM PLO 14 2- [4- (3Rl4S) -aminomethyl-trifluoromethyl-pyrrolidin-1-yl) -phenylamino] -8y-Cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 216) tert-butylester of the acid. { (3R), 4S) -1- (4-Amino-phenyl) -trifluoromethyl-pyrrolidin-3-ylmethyl} -carbámico They were dissolved in acetonitrile (10 mL) and ((3S, 4S) -4-trifluoromethyl-pyrrolidin-3-ylmethyl) -carbamic acid (1 .0 g, 3.72 mmol) was brought to reflux for 24 hours, p-fluoro-nitrobenzene (0.36 ml, 3.38 mmole) and diisopropylethylamine (0.65 ml, 3.72 mmole). The solvent was removed, and the mixture was triturated with hexanes and filtered to yield an unpurified yellow solid (1.4 g). This product was dissolved in THF and heated with Raney N-nick under a hydrogen atmosphere until no further change in pressure was observed. Following the removal of the catalyst by filtration, obtained the aniline of the product by evaporation of the solvent and was used without further purification. tert-butylester of the acid. { (3R, 4S) - [4- (8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-a] pyrimidin-2-ylamino) -phenyl] -trifluoromethyl-pyrrolidin- 3-ylmethyl} -carbámico (222). [(3R, 4S) -1- (4-amino-phenyl) -trifluoromethyl-pyrroidin-3-ylmethyl] -carbamic acid and 8-cyclopentyl-5 were coupled and deprotected as described previously by Example 11 -methyl-2-methansulfinyl-8 -.- pyrido [2,3-d] pyrimidin-7-one. CHN for C25H29N6O1F3 + 1.6 TFA, pf > 130 ° C (decomposition).

EXAMPLE 15 8-Cyclopentyl-5-methyl-2-. { 4- [2- (4H- [1,2,4] triazol-3-ylsulfonyl) -ethyl] and f nylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 222) 4- [2- (4 H- [1, 2, 4] triazol-3-ylsulfanyl) -ethyl] -1'-enylamine. To a suspension of hexane rinsed in 60% sodium hydride (0.83 g), in dimethylformamide (5 mL) at 0 ° C, an solution of 3-mercapto-1, 2,4-triazole (2.0 g) in dimethylformamide (10 mL) in portions. After 45 minutes 4-nitrofenethyl bromide (4.1 g) was added, and the reaction mixture was stirred at room temperature for 18 hours. 1 M hydrochloric acid (70 mL) was added and the aqueous phase was extracted with diethyl ether (3 x 100 mL), and the combined organic extracts were concentrated to dryness. The resulting solid was collected, washed with diethyl ether (2 x 10 mL) and dried to yield the nitrobenzene intermediate (3.17 g). EM: MH-; 2.51; MH- 248.9. A solution of this intermediate (1.0 g) was reduced using Raney Nickel (0.5 g) and hydrogen in THF (100 μL). The sample was concentrated to dryness to yield the title compound (0.88 g). MS: MH +, 221; MH- 219. 8-cyclopentyl-5-methyl-2-. { 4- [2- (4H- [1, 2, 4] triazol-3-Hsulfanyl) -ethyl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one. A solution of 8-cyclopentyl-5-methyl-2-methanesulfinyl-8H-pyrido [2,3-d] pyrimidin-7-one (0.02 g) was heated at 80 ° C for 18 hours. . { 2 (4H- [1, 2-4] triazoI-3-ylsulfanyl) -ethyl] -phenylamine (0.0166 g) and trifluoroacetic acid (0.06 mL) in acetonitrile (2 mL). The reaction mixture was cooled and the solvent removed in vacuo. 1 M sodium hydroxide (4 mL) was added and the aqueous phase was extracted with diethyl ether (3 x 4 mL); Sodium chloride (20 mg) was added after the first extraction. The aqueous layer was acidified to pH = 1 and extracted with a mixture of ethyl acetate / dichloromethane (9: 1) (3 x 4 mL). The combined ethyl acetate / dichloromethane extracts they were concentrated to dryness and purified by column chromatography using a gradient of 60% to 100% ethyl acetate in hexanes. Concentration of the appropriate fractions yielded Compound 222 (0.014 g). 1 H NMR (d6-DMSO): d 1.58 (2H, m), 1.7 (2H, m), 1.88 (2H, m), 2.2 (2H, m), 2.38 (3H, s) , 2.9 (2H, m), 3.4 (2H, m), 5.7 (1H, s) 5.8 (1H, m), 7.18 (2H, d, J = 9), 7.6 (2H, d, J = 9 ), 8.78 (1 H, s).

EXAM PLO 16 8-Cyclopentyl-5-methyl-2- [4y (1 H- [1,2,4] triazol-3-ylsulfanyl) -f in ylamino] -8 H -pyrido [2,3-d] pyrimidine -7 -or na (Compound 223) 4- (1H- [1, 2,4] triazol-3-ylsulfanyl-phenylamine To a suspension of hexanes rinsed in 60% sodium hydride (1.16 g) in dimethylformamide (10 μL) at 0 ° C A solution of 3-mercapto-1, 2,4-triazole (4.0 g) in dimethylformamide (20 mL) was added dropwise After 20 minutes, 1-fluoro-4-nitrobenzene was added. (5 g) in dimethylformamide (20 mL), and the reaction mixture was stirred at room temperature for 2 hrs, then at 60 ° C for 18 hrs. 1 M hydrochloric acid (1000 m L) was added, and the solid was collected and dried. A second crop of solid (2.1 g) was recovered by crystallization from the mother liquors. Dichloromethane (300 mL) and 1 M sodium hydroxide (200 mL) were added to the combined solids. The dichloromethane was further extracted with 1 M sodium hydroxide (100 mL). The combined aqueous phases were extracted with dichloromethane (2 x 300 mL) then acidified to pH = 1. The solid formed was collected and dried to yield the nitrobenzene derivative (1.96 g). This product was reduced using Raney Nickel and hydrogen in tetrahydrofuran (100 mL). Following the removal of the catalyst, the sample was concentrated to dryness to yield the desired product (1.7 g). MS: MH +; 192.9; M H-, 1 90.0. 8-cyclopentyl-5-methyl-2- [4- (1 H) - [1, 2,4] triazol-3-ylsulfanyl) -phenylamino] -8H-pyrido [2,3-d] pyrimidinone. This compound was prepared from 4- (1 H- [1, 2,4] triazol-3-ylsulfanyl) -phenylamine and 8-cyclopentyl-5-methyl-2-methanesulfinyl-8H-pyrido [2, 3-d] pyrimidin-7-one by the procedure of Example 1 to give Compound 223. 1 H NMR (De-DMSO): d 1.58 (2H, m), 1.75 (2H, m), 1.90 (2H, m), 2.2 (2H, m), 2.38 (3H, s), 5.82 (1H, m), 6.20 (1H, s), 7.4 (2H, d, J = 9), 7.73 (2H, d, J = 9), 8.85 (1 H, bs), 8.82 (1 H, s).

EXAMPLE 17 8-Cyclopentyl-5-methyl-7-oxo-2- (4-piperazin-1-yl-phenylamino) -7,8-dihydro-pyrido [2,3'd] pyrimidine-6-carboxylic acid methyl ester (Compound 224) They were combined in methanol and pressurized to 500 PSI in CO-4- (4- (6-Bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido) fer-butylester gas [2, 3 -d] pyrimidin-2-ylamino) -phenyl] -piperazine-1-carboxylic acid (300 mg, 0.515 mmol), Pd (OAc) 2 (23 mg, 0.05 mmol), 1,2-bis (diphenylphosphino) -propane (64 mg, 0.155 mmol), and triethylamine (0.18 ml, 1.29 mmol). The reaction mixture was heated to 100 ° C and stirred for 14 hours, then allowed to cool to 24 ° C. Evaporation of the solvent, followed by chromatography on SiO2 (45% -50% EtOAc in Hexanes) gave a yellow oil. This oil was dissolved in CH2Cl2 (10 μL) and treated with 2 M HCl in diethyl ether (10 mL) at room temperature. A white precipitate formed. After stirring for 3 hours at room temperature, the solvent was evaporated. The residue was resuspended in anhydrous diethyl ether and filtered to give the title compound as a yellow solid (34 mg), mp 195-105 ° C. 1 H NMR (de-DMSO): d 1.52 (br s, 2H), 1.71 (br s, 2H), 1.82 (br s, 2H), 2.14 (br s, 2H), 2.30 ( s, 3H), 3.18 (s, 4H), 3.27 (s, 4H), 3.76 (s, 3H), 5.8 (s, 1 H), 6.96 (d, J = 8 Hz, 2H), 7.53 (d, J = 8 Hz, 2H), 8.85 (s, 1 H), 9.04 (s, 1 H), 9.97 (s, 1 H).

EXAMPLE 18 The following compounds were prepared essentially according to the procedures described in Examples 1 to 17 and as illustrated in Schemes 1 and 2: (a) 8-Cyclopentyl-5-methyl-2- ( 4-piperazin-1-yl-phenylamido. -8H-pyrido [2,3-d] -pyrimidin-7-one trifluoroacetic acid.

(Compound 1), pf > 215 ° C (dec); (b) 8- (1-Methylethyl) -5-methyl-2- (4-piperazin-1-yl-phenylamino) -8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 2), mp > 235 ° C: (dec); (c) 8-Cyclopentyl-5-methyl-2- (4-fluoro-3-methylphenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 3); (d) 8- (1-Methylethyl) -5-methyl-2- (4-f-U-3-met i Ifen i lami) -8H-pyrido [2,3-d] pyrimidin-7-one ( Compound 4); (e) 8-Cyclohexyl-5-methyl-2- (4-fluoro-3-methyl-phenylamino-8H-prido [2,3-d] pyrimidin-7-one (Compound 5); (f) 8-Cyclohexyl- 5-methyl-2- [4- (4-propanoi-l-piperazin-1-yl) -phenylimino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 6); (g) 8-Cyclopentyl-5-methyl-2- [4- (4-propanoylpiperazin-1-yl) phenylamino] -8H-pyridyl [2,3-d] pyrimidin-7-one trifluoroacetic acid salt ( Compound 7), mp 235-237 ° C; (h) 8- (1 -Meti I ethyl) -5-met i l-2- [4- (propane i I piperazi n-1-yl) phenylamino-8 H -pyrido [2,3-d] pyrimidin-7 -one (Compound 8); (i) 8-Cyclohexyl-5-methyl-2- (4-piperazin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 9); (j) 8-Cyclopentyl-5-methyl-2- (4-pyridylphenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 10); (k) 8- (1-Methylethyl) -5-methyl-2- (4-pyridylphenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 11); (I) 8-Cyclopentyl-5-methyl-2- [4- (3-aminopyrrolidinyl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one trifluoroacetic acid salt (Compound 12), mp > 195 ° C (dec); (m) 8- (1-Methylethyl) -5-methyl-2- [4- (3-aminopyrrolidinyl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 13), mp > 227-229 ° C; (n) N- (1- { 4 - [(8-cyclopentyl-5-methyl-7-oxo (8-hydropyridino [2,3-d] -pyrimidin-2-yl)) amino] phenyl .}. pyrrolidin-3-yl) -3,3-dimethylbutanamide (Compound 14); (o) N- (1- { 4 - [(5-methyl-8- (1-methyethi) -7-oxo (8-hydropyridino [2,3-d] -pyrimidin-2-yl)) amino ] phenyl] pyrrolidin-3-yl) -3,3-dimethylbutanamide (Compound 15); (p) 8- (Cyclopentyl-5-methyl-2- (3-chloro-4-piperazin-1-yl-phenylamino) -8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 16), mp 234-237 ° C; (q) 8-Cyclohexyl-5-methyl-2- (3-chloro-4-piperazin-1-yl-phenylamino) -8 H -pyrido [2,3-d] pyrimidin-7 ona (Compound 17); (r) 8- (1-Methylethyl) -5-methyl-2- (3-chloro-4-pi perazin-1 -i I-fieni-amino-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 18); (s) 8-Cyclopentyl-6-fluoro-5-methyl-2- (3-chloro-4-piperazin-1-yl-phenylamino) -8H-pyrido [2, 3-d] pyrimidin-7-one (Compound 19); (t) 8-Cyclohexyl-6-fluoro-5-methyl-2- (3-chloro-4-piperazin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 21); (u) 8- (1-methylethii) -6-fluoro-5-methyl-2- (3-chloro-4-piperazin-1-yl) phenylamino) -8H-pyrido [213-d] pyrimidin-7-one (Compound 20); (v) 8-Cyclopentyl l-5-methyl-2- (3-chloro-4-morpholine in-4-i) phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 22); (w) 8- (1-Methylethyl) -5-methyl-2- (3-chloro-4-morpholine- 4-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 23); (x) 8-Cyclohexyl- 5-methyl-2- (3-chloro-4-morpholin-4-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 24); (y) 2- ( { 3-chloro-4- [4- (3-morpholin-4-ylpropyl) piperidyl] phenyl} -amino) -8-cyclopentyl-5-methyl-8-hydropyridino [2 , 3-d] pyrimidin-7-one (Compound 25); (z) 2- ( { 3-Chloro-4- [4- (3-morpholin-4-ylpropyl) piperidylJphenyl] -amino) -8- (1-methylethyl) -5-methyl-8-hydropyridino [2,3-d] pyrimidin-7-one (Compound 26), (aa) 2- (. {3-chloro-4- [4- (3-morpholin-4-ylpropyl) piperidyl] -phenyl}. amino) -8-cyclohexyl-5-methyl-8-hydropyridino [2,3-d] pyrimidin-7-one (Compound 27); (bb) 2- ( { 3-Chloro-4- [4- (3-piperazinylpropyl) piperidyl] phenyl} amino) -8-cyclopentyl-6-fluoro-5-methyl-8-hydropyridino [ 2,3-d] pyrimidi? -7-one (Compound 28); (cc) 2- ( { 3-Chloro-4-l4- (3-piperazinylpropyl) piperidyl] phenyl} -amino) -8- (1-methylethyl) -6-fluoro-5-methyl-8- hydropyridino [2,3-d] pyrimidin-7-one (Compound 29); (dd) 2- ( { 3-chloro-4- [4- (3-piperazinylpropyl) piperidyl] -phenyl} arnino) -8-cyclohexyl-6-fluoro-5-methyl-8-hydropyridino [2 , 3-d] -pyrimidin-7-one (Compound 30), pf > 80 ° C (dec); (ee) 2- ( { 3-chloro-4- [4- (3-piperazinylpropyl) piperidyl] -phenyi}. amino) -8-cyclopentyl-5-methyl-8-hydropyridino [2,3-d ] pyrimidin-7-one (Compound 31); (ff) 2- ( { 3-Chloro-4- [4- (3-piperazinylpropyl) piperidyl] phenyl} -amino) -8- (1-methylethyl) -5-methyl-8-hydropyridino [2 , 3-d] pyrimidin-7-one (Compound 32); (99) 2- ( { 3-Chloro-4- [4- (3-piperazinylpropyl) piperidyl] phenyl} -amino) -8-cyclohexyl-5-methyl-8-hydropyridino [2,3-d ] pyrimidin-7-one (Compound 33); (gg2) 8-Cyclopentyl-2- [4- (piperazin-1 -i [(2-phenylamino) -6-fluoro-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one trifluoroacetate ( Compound 34), mp 254-255 ° C; (gg3) 8-Cyclopentyl-2- [4- (piperazin-1-yl) -phenylamino] -6-bromo-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one trifluoroacetate pf > 200 ° C; (hh) 8-Cyclopentyl l-2- [4- (3,5-d.methyl-piperazin-1-l) -phenylamino] -6-fluoro-5-methyl-8H-pyridohydrochloride [2] , 3-d] pyrimidin-7-one (Compound 36), pf > 220 ° C; (ii) 8-Cyclopentyl-2- (3-fluoro-4-piperazin-1-yl-phenylamino) -5-methyl-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 37); (jj) 6-Bromo-8-cyclopentyl-2- [4- (3,5-dimethyl-piperazin-1-yl) -phenylamino] -5-methyl-8H-pyridohydrochloride [2, 3-d] - pyrimidin-7-one (Compound 38), pf > 230 ° C; (kk) 8-Cyclopentyl-6-fluoro-2- (3-fluoro-4-piperazin-1-yl-phenylamino) -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 39); (II) 6-Bromo-8-cyclopentyl-2- (3-fluoro-4-piperazin-1-yl-phenylamino) -5-methyl-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 40); (mm) 8-Cyclopentyl-2- [4- (3,5-dimethyl-piperazin-1-yl) -phenylamino] -5-methyl-8H-pyrido [2,3-d] pyridinium hydrochloride -7-one (Compound 41); (nn) 2- (3-Chloro-4-piperazin-1-yl-phenylamino) -8-cyclopentyl-5-methyl-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 42); (oo) 2- (3-Chloro-4-piperazin-1-yl-phenylamino) -8-cyclopentyl-6-fluoro-5-methyl-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 43); (pp) 6-Bromo-2- (3-chloro-4-piperazin-1-yl-phenylamino) -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 44); (qq) 8-Cyclopentyl-5-methyl-2- (4-morpholin-4-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one trifluoroacetate (Compound 45), mp 227- 229 ° C; (rr) 8-Cyclopentyl-6-fluoro-5-methyl-2- (4-morpholin-4-yl-phenylamino) -8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 46); (ss) 6-B rom o-8-cyclopentyl-5-m ethyl -2- (4-morphol-4-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 47); (tt) 8-Cyclopentyl-2- (3-fluoro-4-morpholin-4-yl-phenylamino) -5-methyl-8 H -pyrido [2,3-dlpyrimidin-7-one (Compound 48); (uu) 8-Cyclopentyl-6-fluoro-2- (3-fluoro-4-morpholin-4-yl-phenylamino) -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 49); (vv) 6-Bromo-8-cyclopentyl-2- (3-fluoro-4-morpholin-4-yl-phenylamino) -5-methyl-8H-pyridono [2,3-d] pyrimidine-7 -one (Compound fifty); (ww) 2- (3-Chloro-4-morpholin-4-yl-phenylamino) -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyridin-7-one (Compound 51); (xx) 2- (3-Chloro-4-morpholin-4-yl-phenylamino) -8-cyclopentyl-6-fluoro-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 52); (y) 6-Bromo-2- (3-chloro-4-morpholin-4-yl-phenylamino) -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 53); (zz) 8-Cyclopentyl-5-methyl-2-. { 4- [4- (2, 2, 2-trifluoro-ethyl) -piperazin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 54), mp 198-199 ° C; (aaa) 8-Cyclopentyl-6-fluoro-5-methyl-2-. { 4- [4- (2,2,2-trifluoro-ethyl) -piperazin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 55); (bbb) 6-Bromo-8-cyclopentyl-5-methyl-2-. { 4- [4- (2,2,2-trifluoro-ethyl) -piperazin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 56); (ccc) 8-Cyclopentyl-5-methyl-2- trifluoroacetate. { 4- [4- (3-piperazin-1-yl-propyl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 57), pf > 80 ° C (dec); (ddd) 8-Cyclopentyl-6-fluoro-5-methyl-2-. { 4- [4- (3-piperazin-1-yl-propyl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 58) pf > 230 ° C; (eee) 6-Bromo-5-cyclopentyl-5-methyl-2-. { 4- [4- (3-piperazin-1-yl-propyl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 59); (fff) 8-Cyclopentyl-5-methyl-2-. { 4- [4- (3-morpholin-4-yl-propyl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 60); (ggg) 8-Cyclopentyl-6-fluoro-5-metM-2-. { 4- [4- (3-morpholin-4-yl-propyl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 61); (hhh) 6-Bromo-8-cyclopentyl-5-methyl-2-. { 4- [4- (3-morpholin-4-yl-propyl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 62); (iii) 6-Bromo-8-cyclopentyl-5-methyl-2-. { 4- [4- (3-morpholin-4-yl-propyl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 63); (jjj) 2- (4- { 4- [3- (3-Amino-pyrrolidin-1 -i I) -propyl] -piperi din-Ai l.}. -f eni lami) -8-cyclopentyl -5-methyl-8H-pyrido [2,3-d] pi rim id n-7-one (Compound 64); (kkk) 2- (4- { 4- [3- (3-Amino-pyrrolidin-1-yl) -propyl] -piperidin-1-yl} - phenylamino) -8-cyclopentyl-6-fluoro -5-methy1-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 65); (III) 2- (4- { 4- [3- (3-Amino-pyrrolidin-1-yl) -propyl] -piperidin-1-yl}. Phenylamino) -6-bromo-8-cyclopentyl -5-methyl-8H-pyrido [2,3-d] -pyrimidin-7-one (Compound 66); (mmm) 8-Cyclopentyl-2-. { 3-fluoro-4- [4- (3-piperazin-1-yl-propyl) -piperidin-1-yl] -phenylamino} -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 67); (nnn) 8-Cyclopentyl-6-fluoro-2-. { 3-fluoro-4- [4- (3-piperazin-1-yl-propyl) -piperidin-1-yl] -phenylamino} -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 68); (ooo) 6-Bromo-8-cyclopentyl-2-. { 3-fluoro-4- [4- (3-piperazin-1-yl-propyl) -piperidin-1-yl] -phenylamino} -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 69); (ppp) 8-Cyclopentyl-2-. { 3-fluoro-4- [4- (3-morpholin-4-yl-propyl) -piperidin-1-yl] -phenylamino} -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 70); (qqq) 8-Cyclopentyl-6-fluoro-2-. { 3-fluoro-4- [4- (3-morpholin-4-yl-propyl) -piperidin-1-yl] -phenylamino} -5-methyl-8H-pyrido [2,3-d] -pyrimidin-7-one (Compound 71); (rrr) 6-Bromo-8-cyclopentyl-2-. { 3-fluoro-4- [4- (3-morpholin-4-yl-propyl) -piperidin-1-yl] -phenylamino} -5-methyl-8H-pyrido [2,3-d] -pyrimidin-7-one (Compound 72); (sss) 2- [4- (3-Amino-pyrrolidin-1-yl) -phenylamino] -8-c-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 73), pf > 915 ° C (dec); (ttt) 2- [4- (3-Amino-? irolidin-1-yl) -phenylaminoj-8-cyclopentyl-6-fluoro-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 74); (uu) 2- [4- (3-Amino-pyrrolidin-1-yl) -phenylamino] -6-bromo-8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 75); (vvv) 2- [4- (3-Amino-pyrrolidin-1-yl) -3-fluoro-phenylamido] -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 76); (www) 2- [4- (3-Amino-pyrrolidin-1-l) -3-fluoro-phenylamino] -8-cyclopentyl-6-fluoro-5-methyl-8H-pyrid [ 2,3-d] -pyrim? Din-7-one (Compound 77); (xxx) 2- [4- (3-Amino-pyrrolidin-1 -i I) -3-f luoro-f in i I amin or] -6-bromo-8-cyclopentyl-5-methylene- 8H-pyridono [2,3-d] pyrimidin-7-one (Compound 78); (yyy) 8-Cyclopentyl-5-methyl-2-trifluoroacetate. { 4- [3- (2,2,2-trifluoro-ethylamino) -pyrrolidin-1-yl] -phenylamino} -8H-pyrido- [2,3-d] pyrimidin-7-one (Compound 79), pf > 160 ° C (dec); (zzz) 8-Cyclopentyl-6-fluoro-5-methyl-2-. { 4- [3- (2,2,2-trifluoro-ethylamino) -pyrimidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] -pyrimidin-7-one (Compound 80); (aaa) 6-Bromo-8-cyclopentyl-5-methyl-2-. { 4- [3- (2,2,2-trifluoro-ethylamino) -pyrrolidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] -pyrimidin-7-one (Compound 81); (bbbb) 2- [4- (3-Amino-pyrrole-idin-1-yl) -3-chloro-phenylamino] -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidine trifluoroacetate 7-one (Compound 82), pf > 215 ° C (dec): (cccc) 2- [4- (3-Amino-pyrrolidin-1-yl) -3-chloro-f in i lami] -8-cyclopentyl-6-fluoro-5 -methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 83), mp 221 ° C; (dddd) 2- [4- (3-Amino-pyrrolidin-1-yl) -3-chloro-phenylamino] -6-bromo-8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] - pyrimidin-7-one (Compound 84); (eeee) 2- [4- (3-Am i no met i I -4-trif luorometi l-pyrrolidi n-1 -i I) -phenylamino] -8-cyclopentyl-5-methyl-8H-pyrido [2, 3-d] pyrimidin-7-one (Compound 85); (ffff) 2- [4- (3-Am i no met i I -4-trif luorometi l-pyrrolidi n-1 -i I) -phenylamino] -8-cyclopentyl-6-fluoro-5-methyl-8H- pyrido [2,3-d] pyrimidin-7-one (Compound 86); (gggg) 2- [4- (3-Aminomethyl-4-trifluoromethyl-pyrrolidin-1-yl) -phenylamino] -6-bromo-8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidine -7-one (Compound 87); (hhhh) 2- [4- (3-Trifloroethylaminomethyl-pyrrolidin-1-yl) -phenylamino] -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 88); (i iii) 2- [4- (3-Trifloroethylaminomethyl-pyrrolidin-1-yl) -phenylamino] -8-cyclopentyl-6-fluoro-5-methyl-8H-pyrido [2,3-d] pyrimidin-7- ona (Compound 89); (jjjj) 2- [4- (3-Trifloroethylaminomethyl-pyrrolidin-1-yl) -phenylamino] -6-bromo-8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 90); (kkkk) 8-Cyclopentyl-2- [4- (3,3-dimethyl-piperazin-1-yl) -phenylamino] -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one hydrochloride (Compound 91), pf > 1 50 ° C (dec); (llll) 8-Cyclopentyl-2- [4-3,3-dimethyl-piperazin-1-yl) -phenylamino] -6-fluoro-5-methyl-8H-pyrido [2,3-d] pyrimidin-7- ona (Compound 92); (mmmm) 6-Bromo-8-cyclopentyl-2- [4- (3,3-dimethyl-piperazin-1-yl) -phenylamino] -5-methyl-8H-pyrido [2,3-d] - hydrochloride pyrimidin-7-one (Compound 93), pf > 200 ° C (dec); (nnnn) 8-Cyclopentyl-5-methyl-2- [4- (3,3,4-trimethyl-piperazin-1-yl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 94); (oooo) 8-Cyclopentyl-6-fluoro-5-methyl-2- [4- (3,3,4-trimethyl-piperazin-1-yl) -phenylaminoj-8H-pyrido [2,3-d] pyrimidine- 7-one (Compound 95); (pppp) 6-Bromo-8-cyclopentone I -5-met i l-2- [4- (3, 3, 3-trimethyl-piperazin-1-yl) -phenylamino] -8H-pyrido [2 , 3-d] pyrimidin-7-one (Compound 96); (qqqq) 2- [4- (4-Acetyl-piperidin-1-yl) phenylamino] -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 97); (rrrr) 2- [4- (4-Acetyl-piperazin-1-yl) -phenylamino] -8-cyclopentyl-6-fluoro-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 98), mp 267-269 ° C; (ssss) 2- [4- (4-Acetyl-piperazin-1-yl) -phenylamino] -6-bromo-8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 99); (tttt) 8-Cyclopentyl-2-. { 4- [4- (2-hydroxy-ethyl) -3,5-dimethyl-1-piperazin-1-yl] -phenylamino} -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 100), mp 156-1 59 ° C; (uuuu) 8-Cyclopentyl-6-fluoro-2-. { 4- [4 (2-hydroxy-ethyl) -3,5-di methi I -piperazi n-1 -yl] -f eni lami non-5-methyl-8H-pyrido [2, 3-d] pi rim idi n-7-one (Compound 101); (vvvv) 6-Bromo-8-cyclopeni! -2-. { 4- [4- (2-hydroxy-ethyl) -3,5-d i meti I -piperazi n-1 -i l] -f eni lami no} -5-methyl-8H-pyrido [2,3-d] -pyrimidin-7-one (Compound 102); (wwww) 8-Cyclopentyl-5-methyl-2- (4-perhydro-1,4-diazepin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one hydrochloride (Compound 103), mp 172 ° C (dec); (xxxx) 8-Cyclopentyl-6-fluoro-5-methyl-2- (4-perhydro-1,4-diazepin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-hydrochloride -one (Compound 104), mp 192 ° C (dec); (yyyy) 6-Bromo-8-cyclopentyl-5-methyl-2- (4-perhydro-1,4-diazepin-1-yl-phenylamino) -8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 105); (zzzz) 8-Cyclopentyl-5-methyl-2- [4- (4-methyl-piperazin-1 -yl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 106), mp 21-1-213 ° C; (aaaaa) 8-Cyclopentyl-6-fluoro-5-methyl-2- [4- (4-methyl-piperazin-1-yl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 107); (bbbbb) 6-Bromo-8-cyclopentyl-5-methyl-2- [4- (4-methyl-piperazin-1-yl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7 -one (Compound 108); (cecee) 8-Cyclopentyl-5-methyl-2- [4- (4-methyl-perhydro-1,4-diazepin-1-yl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7 -one (Compound 109), pf > 185 ° C (dec); (ddddd) 8-Cyclopentyl-6-fluoro-5-methyl-2- [4- (4-methyl-perhydro-1 -4-diazepin-1-yl) -phenylamino] -8H-pyrido [2, 3-d ] pyrimidin-7-one (Compound 110); (eeeee) 6-Bromo-8-cyclopentyl-5-methyl-2- [4- (4-methyl-perhydro-1,4-diazepin-1-yl) -phenylamino] -8H-pyrido [2,3-d] ] pyrimidin-7-one (CompouDd 111); (ffff) Acid. { 4- [4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) -phenyl] -piperazin-1-yl} -acetic (Compound 112); () Acid. { 4- [4- (8-Cyclopentyl-6-fluoro-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) -phenyl] -piperazin-1 - il} -acetic (Compound (113); (hhhhh) Acid { 4- [4- (6-Bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro pyrido [2,3-d] pyrimidin-2-ylamino) -phenyl] -piperazin-1-yl.} -acetic acid (Compound 114); (iiiii) 8-Cyclopentyl-5-methyl-2- (4-. {4- [3- ( 1 H-tetrazol-5-yl) -propyl] -piperidin-1-yl.} - phenylamino! -8 H -pyrido [2,3-d-] pyrimidin-7-one (Compound 115); (jjjjj) 8-Cyclopentyl-6-fluoro-5-methyl-2- (4-. {4- [3- (1 H -tetrazol-5-yl) -propyl] -piperidin-1-yl}. phenylamino) -8H-pyrido [2,3-d] -pyrimidin-7-one (Compound 116); (kkkkk) 6-Bromo-8-cyclopentyl-5-methyl-2- (4-. {4- [3- (1 H -tetrazol-5-yl) -propyl] -piperidin-1-yl} .phen i lami no) -8H-pyrido [2,3-d] -pyrimidin-7-one (Compound 117); (lllll) 8-Cyclopentyl-5-methyl-2- (4- { 4- [3- (5-oxo-4,5-dihydro-IH-l ^^ -triazol-S-ylsulfanyl-J-propyl-piperidin -li ^ -phenylamino-J-pyrido [2,3-d] pyrimidin-7-one (Compound 118); (mmmmm) 8-Cyclopentyl-6-fluoro-5-methyl-2- (4-. {4 - [3- (5-oxo-4,5-dihydro-1 H-1, 2,4-triazol-3-ylsulfanyl) -propyl] -piperidin-1-yl.} - phenylamino) -8H-pyrido [ 2,3-d] pyrimidin-7-one (Compound 119); (nnnnn) 6-Bromo-8-cyclopentyl-5-methyl-2- (4-. {4- [3- (5-oxo -4,5-dihydro-1 H-1, 2,4-triazol-3-ylsulfanyl) -propyl] -piperidin-1-yl.}. -phenylamino) -8H-pyrido [2,3-d] pyrimidine- 7-one (Compound 120); (ooooo) 8-C-chloropentyl-5-methyl -2- (4- { 4- [3- (5-oxo-4, 5-dihydro-1H-1, 2, 4-triazole-3-sulfinyl) -propyl] -piperidin-1-yl.} - phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 121); (ppppp) 8-Cyclopentyl -6-fluoro-5-methyl-2- (4- { 4- [3- (5-oxo-4,5-dihydro-1 H-1, 2,4-triazol-3-sulfinyl) -propyl ] -piperidin-1 -yl.}. phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 122); (qqqq) 6-B rom o-8-ci clopent i I - 5-met il- 2 - (4-. { 4- [3- (5-oxo-4,5-dihydro-1 H-1, 2,4-triazol-3-sulfinyl) -propyl] -piperidin-1-yl} phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 123); (rrrrr) 8-Cyclopentyl-5-methyl-2- (4-. {4- [3- (5-oxo-4,5-dihydro-1 H-1 l, 2,4-triazole-3-onyl) - propyl] -piperidin-1-yl.}. - phenylamino) -8H-pyrido [2,3-d-pyrimidin-7-one (Compound 124); (sssss) 8-Cyclopentyl-6-fluoro-5-methyl-2- (4- { 4- [3- (5-oxo-4,5-dihydro-1H-1, 2,4-triazole-3 -onyl) -propyl] -piperidin-1 -yl.}. phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 125); (ttttt) 6-Bromo-8-cyclopentyl-5-methyl-2- (4- { 4- [3- (5-oxo-4,5-dihydro-1 H-1, 2,4-triazole- 3-onyl) -propyl] -piperidin-1-yl.} - phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 126); (uuuuu) N- (2- { 1- [4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) - phenyl] -piperidin-4-yl.}. -ethyl) -N-hydroxy-acetamide (Compound 127); (vvvvv) N- (2- { 1- [4- (8-Cyclopentyl-6-fluoro-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2 -ylamino) -phenyl] -piperidin-4-yl.}. -ethyl) -N-hydroxy-acetamide (Compound 128); (wwwww) N- (2- { 1- [4- (6-Bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2 -ylamino) -phenyl] -piperidin-4-yl.}. -ethyl) -N-hydroxy-acetamide (Compound 129); (xxxxx) N- (3- { 1- [4- (8-Cyclopentyl-5-methyl-1-7-0X0-7,8-dihydro-pyrido [2,3-d] -pyrimidin-2-ylamino ) -phenyl] -piperidin-4-yl.}. -propyl) -N-hydroxy-acetamide (Compound 130); (yyyyy) N- (3- { 1- (4- (8-Cyclopentyl-6-fluoro-5-medyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidine -2-ylamino) -phenyl] -piperidin-4-yl.}. -propyl) -N-hydroxy-acetamide (Compound 131); (zzzzz) N- (3- { 1 - [4- (6-Brom o-8-ci clopent i I -5-met i l-7-oxo-7,8-dihydro-pyrido [2,3 -d] pyrimidin-2-ylamino) -phenyl] -piperidn-4-yl.} - propyl) -N-hydroxy-acetamide- (Compound 132); (aaaaaa) 2- (Benzofuran-5-i lami no) -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 133); (bbbbbb) 8-cyclopentyl-2- (1 H -indol-5-ylamino) -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 134); (cccccc) 2- (Benzo [b] thiophen-5-i! amino) -8-cyclopentyl-5-methyl-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 135); (dddddd) 8-Cyclopentyl-2- (2,3-dimethyl-1 H -indol-5-ylamino) -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 136); (eeeeee) 2- (9 H -Carbazol-3-yl ami no) -8-ci clopent i I -5-methyI-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 137); (fffff) 8-Cyclopentyl-2- (1 H -indazol-5-ylamino) -5-methyl-8 H -pyrido [9.3-d] pyrimidin-7-one (Compound 138); (gg) 2- (2-AcetM-benzofuran-5-ylamino) -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 139); (hhhhhh) 8-Cyclopentyl-5-methyl-2- (4-morpholin-4-yl-phenylamine) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 140), mp 227-929 ° C; (i iiiii) 8-Cyclopentyl-2- [4- (3,5-dimethyl-1-piperazin-1-yl) -phenylamino] -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 141); (jiiiii) 2- (3-Chloro-4-piperazin-1-yl-phenylamino) -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one trifluoroacetate (Compound 142) , mp 234-237 ° C; (kkkkkk) 8-Cyclopentyl-5-methyl-2- (4-piperidin-1-yl-phenylamino) -8 H -pyrido [2,3-d]? irimidin-7-one (Compound 143); (lily) 8-Cyclopentyl-5-methyl-2- [4- (4-methyl-piperazin-1 -yl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 144); (mmmmmm) N-. { 1 - [4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) -phenyl] -piperidin-4-yl} -acetamide (Compound 145); (nnnnnn) 8-Cyclopentyl-l-5-methyl-2- (4-piperazin-1-yl-phenylamine) -8H-pyrido [2,3-d] pyrimidin-7-one trifluoroacetate (Compound 146), mp 237 -240 ° C; (oooooo) 8-C i clopent i l-6-f I uoro-5-m ethyl -2- (piperazin-1-yl-phenylamino) -8 H -pyrido [2,3-d] pyrimidin-7-one ( Compound 147), mp 254-255 ° C; (pppppp) 6-iodo-8-cyclopentyl-5-methyl-2- (4-piperazin-1-yl-phenylamine) -8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 148); (qq) 2- [3-chloro-4- (3-amino-pyrro I id i n-1-yl) -phenylamino] -8-cyclopentyl-5-methyl-8H-pyrido trifluoroacetate [2,3-d] ] pyrimidin-7-one (Compound 149), pf > 21 5 ° C (dec); (rrrrrr) 8-Cyclopentyl-5-methyl-2- [4- (4- (2, 2, 2-trifluoroethyl) -piperazin-1-yl) -phenylamine] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 150), mp 198-199 ° C; (ssssss) 8-Cyclopentyl-2- (4-fluoro-phenylamine) -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 151), mp 217-220 ° C; (tttttt) 8-Cyclopentyl-5-methyll-2-phenylamino-8H-pyrido [2,3-d] pyrimid-7-one (Compound 152), mp 180-183 ° C; (uuuuuu) 8-Cyclopentyl-2- (3,4-dichlorophenylamino) -5-methyl-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 153), mp 225-230 ° C; (vvvvvv) 8-lsopropyl-5-methyl-2- (4-piperazin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one trifluoroacetate (Compound 154), mp; 235 ° C (dec); (wwwwww) 8-lsopropyl-5-methyl-2- [4- (4-propionyl-piperazin-1-yl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 155 ); (xxxxxx) 8-Cyclohexyl-5-methyl-2- (4-piperazin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 156); (yyyyyy) 2-. { 4- [4- (3-Morpholin-4-yl-propyl) -piperidin-1-yl] -phenylamino} -8-cyclohexyl-6-fluoro-5-methyl-8H-pyrido [2,3-d] pyrimidine-7-one (Compound 157), mp 206-209 ° C; (zzzzzz) 8-Cyclopentyl-5-methyl-2- [4- (2H-1, 2,4-triazol-3-ylsufanylmethyl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound158); (aaaaaaa) 8-Cyclopentyl-5-methyl-2- [4- (2H-1, 2,4-triazol-3-sulfinylmethyl) -phenlamino] -8H-pyrido [2,3-d] pyrimidin-7 -one (Compound 159); (bbbbbbb) 8-Cyclopentyl-5-methyl-2- [4- (2H-1, 2,4-triazol-3-suphonylmethyl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 160); (ccccccc) 8-Cyclopentyl-5-methyl-2- [4- (5-oxo-4,5-dihydro-1, 2,4-oxadiazol-3-ylmethyl) -phenylamino] -8H-pyrido [2 , 3-d] pyrimidin-7-one (Compound 161); (ddddddd) 8-Cyclopentyl-5-methyl-2-. { 4- [2- (2H-1, 2,4-triazol-3-ylsulfanyl) -ethyl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 162); (eeeeeee) 8-Cyclopentyl-5-medyl-2-. { 4- (2- (2H-1, 2,4-triazole-3-sulfinyl) -ethyl] -phenylamino} - 8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 163), ( fffffff) 8-Cyclopentyl-5-methyl-2- { 4- [2- (2H-1, 2,4-triazole-3-sulfonyl) -ethyl] -phenylamino} -8-pyrido [2, 3-d] pyrimidine-7-one (Compound 164); (g) 8-Cyclopentyl-5-methyl-2-. {4- (2- (5-oxo-4,5-dihydro-1,2, 4, -oxadiazol-3-yl) -ethyl] -phenylamino.} - 8H-pyrido [2,3-d] pyrimidin-7-one (Compound 165); (hhhhhhh) 8-Cyclopentyl-5-methyl-2 - [4- (3H-1, 2,3-triazol-4-ylsulfanylmethyl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 166); (iiiii? I) 8- Cyclopentyl-5-methyl-2- {4- [2- (3H-1,2,3-triazol-4-ylsulfanyl) -ethyl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 167); (iii iii) 8-Cyclopentyl-5-methyl-2-. { 4- [4- (5-oxo-4,5-dihydro-1, 2,4-oxadiazol-3-yl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 168); (kkkkkkk) 8-Cyclopentyl-5-methyl-2-. { 4- [4- (2H-1, 2,4-triazol-3-ylsulfanyl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimido-7-one (Compound 169); 8-Cyclopentyl-5-methyl-2-. { 4- (2H-1, 2,4-triazol-3-sulfinl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 170); (mmmmmmm) 8-Cyclopentyl-5-methyl-2-. { 4- [4- (2H-1, 2,4-triazoI-3-sulfonyl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 171), mp 235-237 ° C: (nnnnnnn) 8-Cyclopentyl-5-methyl-2-. { 4- [4- (2H-tetrazol-5-yl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 172); (ooooooo) Acid (1 H-tetrazol-5-yl) -amidca of 1- [4- (8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidine -2-amino) -phenyl] -piperidine-4-carboxylic acid (Compound 173); (ppppppp) 8-Cyclopentyl-5-methyl-2-. { 4- [4- (3H-1, 2,3-triazol-4-ylsulfanyl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 173); (qq) 3- [4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) -phenyl] -N- (1 H) -te trace I-5-yl) -propionanamide (Compound 174); (rrrrrrr) 2- [4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) -phenoxy] -N- (1 H -tetrazol-5-yl) -acetamide (Compound 175); (sssssss) 8-Cyclopentyl-5-methyl-2- [4- (5-oxo-4,5-dihydro-1, 2,4-oxadiazol-3-ylmethoxy) -phenylamino] -8H-pyrido [2,3 -d] pyrimidin-7-one (Compound 176), pf > 195 ° C (dec); (ttttttt) 8-Cyclopentyl-5-methyl-2- (4- { 4- [2- (2H-1, 2,4-triazol-3-sulfinyl) -ethyl] -p -peridin-1-yl .}. phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 177); (uuuuuuu) 8-Cyclopentyl-5-methyl-2- (4-. {4- [2- (2H-1,2,4-triazole-3-sulfonyl) -ethyl] -piperidin-1-yl} .phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 178); (vvvvvvv) 8-Cyclopentyl-5-methyl-2- (4- { 4- [2- (3H-1, 2,4-triazol-4-ylsulfanyl) -ethyl] -piperidin-1-yl}. .phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 179); (wwwwwww) 8-Cyclopentyl-5-methyl-2- (4-. {4- [2- (2H-1,2,4-triazole-3-sulfanyl) -ethyl] -piperidin-1-yl} .phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 180), mp 234-237 ° C; (xxxxxxx) 8-Cyclopentyl-5-methyl-2- (4- { 4- [2- (5-oxo-4,5-dihydro-1 ^ A-oxadiazol-S-yl-ethyl-piperidin-li ^ -phenylaminoJ-dH-pyrido [2,3-d] pyrimidin-7-one (Compound 181); (yyyyyyy) 8-Cyclopentyl-5-methyl-2-. {4- [4- (2-oxo- 2,3-dihydro-1,2,3,5-oxathiadiazol-4-yl) -pi pend i n-1-yl] -f in i lami no.}. -8H-pyrido [2,3-d] ] pyrimidin-7-one (Compound 182); (zzzzzzz) 8-Cyclopentyl-2-. { 4- [4- (2,2-dioxo-2,3-dihydro-1, 2,3,5-oxathiadiazol-4-yl) -piperidin-1-yl] -phenylamino} -5-methy1-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 183); (aaaaaaaa) 8- (Cyclopentyl-5-methyl-2- { 4- [4- (1-oxo-2,5-dihydro-1H-1, 2,3,5-thiatriazol-4-yl) - piperidin-1-yl] -phenylamino.}. -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 184); (bbbbbbbb) 8- (Cyclopentyl-2- { 4- [4- (1, 1-dioxo-2,5-dihydro-1 H-1, 2,3,5-thiatriazol-4-yl) -piperidine -1-yl] -phenylamino.} - 5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 185); (cccccccc) N- { 1- [4- (8 Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) -phenyl] -piperidine-2-carbonyl} - methanesulfonamide (Compound 186); (dddddddd) 8-Cyclopentyl-5-methyl-2- { 4- [3- (2H-1,2,4-tnazol-3-ylsulfanyl) -pyridinidin-1-yl] -phenylamino} -8H - pyrido [2,3-d] pyrimidin-7-one (Compound 187); (eeeeeeee) 8-Cyclopentyl-5-methyl-2-. {4- [3- (2H-1,2,4-triazole -3-sulfinyl) pyrrolidin-1-yl] -phenylamino.} - 8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 188); (ffffffff) 8-Cyclopentyl-5-methyl-2- {. 4- [3- (2H-1, 2,4-triazol-3-sulfonyl) -pyrrolidin-1-yl] -phenylamino}. -8H-pyrido [2,3-d] pyrimidin-7- ona (Compound 189); (gggggggg) 8-Cyclopentyl-5-methyl-2- { 4- [3- (3H-1,2,3-triazoI-4-ylsulfanyl) -pyrrolidin-1-yl] - phenylamino.} - 8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 190); (hhhhhhhh) 8-Cyclopentyl-5-methyl-2-. { 4- [3- (5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl) -pyrrolidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 191); (iiiiiiii) 8-Cyclopentyl-5-methyl-2-trifluoroacetate. { 4- [4- (3-hydroxypropyl) piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 192), mp 180-184 ° C; (jjjjjjjj) 8-Cyclopentyl-5-propyl-2- (4-piperazin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one trifluoroacetate (Compound 193); (kkkkkkkk) 8-cyclopentyl-5-ethyl-2- (4-piperazin-1-yl-phenylamino) -8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 194); 8- (1-Methylethyl) -5-ethyl-2- (4-piperazin-1-yl-phenylamino) -8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 195), pf > 235 ° C (dec); (mmmmmmmm) 8- (1-Methylethyl) -5-ethyl-2- (4-piperazin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one trifluoroacetate (Compound 196) , pf > 235 ° C (dec); (nnnnnnnn) 8-Cyclopentyl-5-methyl-2- [4- (3-hydroxypyrrolidin-1-yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 197), mp 225 -226 ° C; (oooooooo) 8-Cyclopentyl-5-ethyl-2- [4- (4-acetylpiperazin-1-yl) phenylamino] -8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 198), (pppppppp) 8-Cyclopentyl-5-methyl-6-fluoro-2- [4- (4-acetylpiper? din-1-yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one ( Compound 199), mp 267-269 ° C; (qq) 8-Cyclopropyl-5-methyl-2- [4- (4-acetamidopiperidin-1-yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 200), mp 291 ° C (dec); (qqr) 8-Cyclopropyl-5-methyl-6-fluoro-2- [4- (4-acetamidopiperidin-1-yl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 201), pf > 250 ° C; (rrrrrrrr) 8-Cyclopentyl-5-methyl-2- [4- (homopiperazin-1 -yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one hydrochloride (Compound 202), mp 1 72 ° C (dec); (ssssssss) 8-Cyclopentyl-5-methyl-6-fluoro-2- [4- (homopiperazin-1 -yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one hydrochloride (Compound 203 ), mp 192 ° C (foam); (tttttttt) 8-Cyclopentyl-5-methyl-6-fluoro-2- [4- (3,3-dimethyl-4-acetylpiperazin-1-yl) phenylamino] -8H-pyrido [2,3-d] pyrimidine- 7-one (Compound 204), mp 200-204 ° C; (uuuuuuuu) 8-Cyclopentyl-5-methyl-2- [4- (3,3-dimethyl-4-acet i I piperazi n-1 -yl) phenylamino] -8H-pyrido [2,3-d] pyrimidine- 7-one (Compound 205), mp 192-196 ° C; (vvvvvvvv) 8-Cyclopentyl-5-methyl-6-fluoro-2- [4- (4-methylpiperazin-1-yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one trifluoroacetate (Compound 206); (wwwwwwww) 8-Cyclopentyl l-5-methyl-2- [4- (N-methylacetamido) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 207), mp 185-1 87 ° C; (xxxxxxxx) 8-Cyclopentyl-5-methyl-2-. { 4- [2- (2-hydroxyethoxy) ethylamino] phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 208), mp 122-126 ° C; (yyyyyyyy) 8-Cyclopentyl-5-methyl-2- [4- (3-oxopiperazin-1-yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 209), pf > 235 ° C (dec); (zzzzzzzz) 8-Cyclopentyl-5-methyl-2- [4- (2-methoxyethoxy) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 210), mp 156-157 ° C; (aaaaaaaaa) 8-Cyclopentyl-5-methyl-2- (9H-carbazol-3-yl-amino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 211); (bbbbbbbbb) 8-Cyclopentyl-5-methyl-2- (1 H -indazol-5-yl) amino-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 212); (ccccccccc) 8-C icl openti I -5-met il-2 - (2 -acet i I benzofuran-5-yl) amino-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 213 ); (ddddddddd) 8-Cyclopentyl-5-methyl-2 - [(4-piperidin-1-yl) phenylamino] -8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 214); (eeeeeeeee) 8-Cyclopentyl-5-methyl-2- (2,3-dimethylindole-5-yl) amino-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 215); (fffffffff) 8-Cyclopentyl-5-isopropyl-2- [4- (3,5-methyl-4R-amine-pyridin-1-yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 216); (ggggggg ^ g) 8-cciopentji-5-metii-2-. { 4- [4- (2-hydroxyethyl) piperazin-1-yl]] phenylamino} -8H-pyrido [2,3-d] pyrimidi? -7-one (Compound 217), mp 1 71 -1 73 ° C; (hhhhhhh h) Salt of 8-Cyclopentyl-5-methyl acid | -2-. { 4- [4- (3-morphol inopropyl) piperidin-1-yl] phenylamino} -8H- irido [2,3-d] pyrj m idin-7-one trifluoroacetic (Compound 218), mp 1 78-1 81 ° C; (iiiiiiiii) β-Cyclopentyl-5-methyl-2- (benzofurap-5-yl) amino-3 H -pyrido [2,3-d] pyrif idjn-7-one (Compound 219); (jjjjjjjjj) 8-Cyclopentyl l-5-methyl-2- (indol-5-yl) amino-8H-pyrid, or [2,3-d] pyrimidin-7-one (Compound 220) - y ( kkkkkkkkk) 8-Cyclopentyl-5-methyl-2- (thionefjep-5-yl) amy? 8-pyrido [2,3-d] pyrimidin-7-one (Compound 221);. 8-Cyclopentyl-6-iodo-5-methyl-2- (4-piperazin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimid-7-one (Compound 225), mp 185-198 ° C (dec); 8 C Clopentil-2-. { 4- [1 - (3, 5-d.methyl-piper ^ jn-1 -yl) -m.ta.noyl] -phenylamino} -5-metM-8H-pyrido [2,3-d-] pyrimidjn-7-one (Compound 226), mp 181 (foam); 8-Cyclopentyl-2- [4- (3, 5-dimethyl-piperazin-1-yl) -phenylamino] -5-trifluoromethyl-8H-pyrido [2,3-d] pyrirr) idin-7-one ( Compound 227), mp 200 (foam); 6-Bromo-8-cyclopentyl-2- [4- (3,3-dimethyl-piperazin-1-yl) -phenylamino] -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one ( Compound 228), pf > 200 (dec); 8-Cyclopentyl-2- [4- (3,5-dimethyl-piperazin-1-yl) -phenylamino] -6-iodo-5-methyl-8H-pyrido [2,3-d] pyrimidin-7- ona (Compound 229), mp 225-226 ° C (dec); 6-Chloro-8-cyclopentyl-2- [4- (3,5-dimethyl-piperazin-1-yl) -phenylamino] -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one ( Compound 230), pf > 50 ° C; 8-Cyclopentyl-5-methyl-2- [4- (1 H- [1,2,4] tr.iazol-3-ylsulfanyl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7 -one (Compound 231); 4- [4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) -phenyl] -piperazine-1-carbaldehyde (Compound 232 ), mp 244-247 ° C; 8-Cyclopentyl-2- (4-piperazin-1-yl-phenylamino) -5-trifluoromethyl-8-pyrido [2,3-d] pyrimidin-7-one (Compound 233), pf > 275 ° C (dec); 8- (1-Ethyl-propyl) -5-methyl-2- (4-piperazin-1-yl-phenylamino) -8 /-.- pyrido [2,3-d] -piperidin-7-one (Compound 234 ), pf > 1 80 ° C (dec); Acid [4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-dlpyrimidin-2-ylamino) -benzyl] -phosphonic acid (Compound 235), pf > 253 ° C; 6-Chloro-8-cyclopentyl-5-methyl-2- (4-piperazin-1-yl-phenylamino) -8 / -pyrido- [2,3-d] pyrimidin-7-one (Compound 236), mp 188 ° C (dec); 2- [4- (3,5-Dimethyl-piperazin-1-yl) -phenylamino] -8- (1-ethyl-propyl) -5-methyl-8H-pyrido [2,3-d] pyrimidin-7- ona (Compound 237), pf > 185 ° C (dec): 8-Cyclopentyl-2- [4- (2-hydroxy-ethylamino) -phenylamino] -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 238), mp 197-200 ° C; 3- [4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) -phenyl] -?,? / - diethyl-propionamide (Compound 239), mp 138-140 ° C; 8-Cyclopentyl] -6-fluoro-2- [4- (2-hydroxy-ethyl) -phenylamino] -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 240), mp 241-244 ° C; 8-Cyclopentyl-2- [4- (2-hydroxy-ethyl) -phenylamino] -5-methyl-8H-pyrido [2,3-d] -pyrimidin-7-one (Compound 241), mp 191-194 ° C; 4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) -benzoic acid (Compound 242); 8-Cyclopentyl-2- [4- (3,3-dimethyl-piperazin-1-yl) -phenylamino] -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 243), pf > 150 ° C (dec); [4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-β-arido [2,3-d] pyrimidin-2-ylamino) -benzyl] -f-osphonic acid diethyl ester (Compound 244 ), pf > 250 ° C (foam); 8-Cyclopentyl-6-fluoro-2- [4- (2-methoxy-ethylamino) -phenylamino] -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 245), mp 147-149 ° C; Acid (S) -2-Amino-3- [4- (8-cyclopentyl-6-fluoro-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino ) -phenyl] -propionic (Compound 246), mp 238 ° C (dec); 8-Cyclopentyl-2- [4- (2-methoxy-ethoxy) -phenylamino] -5-methyl-8 / - / - pyrido [2,3-d] -pyrimidin-7-one (Compound 247), mp 156 -157 ° C; S-Cyclopentyl-2- (4-isopropylamino-phenylamino) -5-methyl-8 H -pyrido [2,3-d] -pyrimidin-7-one (Compound 248), mp 216-220 ° C; 8-C icl opent i I -2- (4-hydroxy-3, 5-di met i I -fen i I ami) -5-methyl-8H-pyrido [2,3-d] -pyrimidin-7 -one (Compound 249), mp 252-254 ° C; 8-Cyclopentyl-6-fluoro-2- (4-hydroxy-3,5-dimethyl-phenylamino) -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 250), mp 241-248 ° C; 8-Cyclopentyl-6-fluoro-2- (4-hydroxy-3,5-dimethyl-phenylamino) -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 251), mp 240 ° C (dec).

EXAMPLE 19 Biological Assays Several of the compounds of the invention have been evaluated in standard assays commonly used to measure the inhibition of cyclin-dependent kinase enzymes and other serine / threonine protein kinases. The tests were carried out as follows: Enzyme Cdk1 and Cdk2 assays for IC50 determination and kinetic evaluation were performed as follows. 96-well filter plate (Millipore MADVN6550) was used. The total volume is 0.1 mL. 20 mM TRIS (pH 7.4), 50 mM NaCl, 1 mM dithiothreitol, 10 mM MgCl2, 12 mM ATP containing 0.25 μCi [32 P] ATP, 20 ng enzyme (Cdk2 / cyclin E, Cdk2 / cyclin A , or Cdk1 / cyclin B), 1 μg of retinoblastoma protein, and appropriate dilutions of the particular compound of the invention. All components except ATP are added to the wells, and the plate is placed in a plate mixer for 2 minutes. The reaction is initiated by the addition of [32 P] ATP, and the plate was incubated at 25 ° C for 15 minutes. The reaction is terminated by the addition of 0.1 ml of 20% TCA. The plate is kept at 4 ° C for at least 1 hour to allow the substrate to precipitate. The wells are then washed five times with 0.2 ml 10% TCA, and 32P incorporation is determined with a beta plate counter (Wallac Inc., Gaithersburg, MD). The Cdk4 enzyme assay for IC50 determination and kinetic evaluation is performed as follows. 96-well filter plates (Millipore MADVN6550) are used. The total volume is 0.1 ml, which contains a final concentration of 20 mM TRIS (tris [hydroxymethyl] aminomethane) (pH 7.4), 50 mM NaCl, 1 mM dithiothreitol, 10 mM MgCl2, 25 μM ATP containing 0.25 μCi [32 P] ATP, 20 ng of Cdk4, 1 μg of retinoblastoma protein, and appropriate dilutions of a compound of the present invention.

All components except ATP are added to the wells, and the plate is placed in a plate mixer for 2 minutes. The reaction is started by adding [32 P] ATP, and the plate is incubated at 25 ° C for 15 minutes. The reaction is terminated by the addition of 0.1 ml of 20% trifluoroacetic acid (TCA). The plate was kept at 4 ° C for at least 1 hour to allow the substrate to precipitate. The wells are then washed five times with 0.2 ml of 10% TCA, and the 32 P incorporation is determined with a beta plate counter (Wallac Inc., Gaithersburg, MD). For tyrosine kinase assays of the PDGF receptor (PDGFr) and FGF receptor (FGFr), the full-length cDNAs for the mouse receptor tyrosine kinases PDGF-β and human FGF1 (flg) are obtained from J. Escobedo and prepared as previously described (Escobed et al. ., J. Biol .. Chem., 1988; 262-1482-1487). PCR primers are designed by augmenting a DNA fragment encoding the intracellular tyrosine kinase domain. The fragment is inserted into a baculovirus vector, co-transferred with AcMN PV DNA, and the recombinant virus is isolated. The SF9 insect cells are infected with the virus to overexpress the protein, and the cell lysate is used for the assay. Enzyme PDGFr and FGFr assays are performed in 96-well plates (100 μL / well / well), and conditions are optimized to measure 32P incorporation from [? 32P] ATP in a glutamate copolymer substrate. tyrosine. Briefly, a each well is added 82.5 μl, the incubation buffer containing 25 mM Hepes (pH 7.0), 150 mM NaCl, 0.1% Triton X-100, 0.2 mM PMSF, 0.2 mM Na3VO4, 10 mM MnCl2, and 750 μg / ml of Poly (4: 1) glutamate-tyrosine followed by 2.5 μl of the inhibitor and 5 μl of enzyme lysate (7.5 μg / μL FGFr or 6.0 μg / μL of PDGFr) to initiate the reaction. Following a 10 minute incubation at 25 ° C, 10 ml [? 32P] ATP (0.4 μCi plus 50 μM ATP) is added to each well, and the samples are incubated for an additional 10 minutes at 25 ° C. The reaction is terminated by the addition of 100 μL, 30% trifluoroacetic acid (TCA) containing 20 mM sodium pyrophosphate and the precipitation of the material in glass fiber mats (Wallac). The filters are washed three times with 15% TCA containing 100 mM sodium pyrophosphate, and the radioactivity retained in the filters is counted in a Wallac 1250 Betaplate reader. The non-specific activity is defined as radioactivity retained in the filters following the incubation of samples with regulator only (without enzyme). The specific enzymatic activity (enzyme plus regulator) is defined as total activity minus non-specific activity. The concentration of a compound that inhibits specific activity by 50% (ICso) is determined based on the inhibition curve. The c-Src protein kinase assay is carried out as follows. The c-Src kinase is purified from the baculovirus infected with insect cell lysates using a monoclonal antibody of antipeptide directed against the N-terminal amino acids (amino acids 2-17) of c-Src. The antibody, covalently bound to 0.65 μm latex beads, is added to an insect cell lysis regulator suspension comprising 150 mM NaCl, 50 mM Tris (pH 7.5), 1 mM DTT, 1% NP-40, 2 mM EGTA, 1 mM sodium vanadate, 1 mM PMSF, 1 μg / ml each of leupeptin, pepstatin, and aprotinin. The insect cell lysate containing the c-Src protein is incubated with these beads for 3 to 4 hours at 4 ° C with rotation. At the end of the lysate incubation, the beads are rinsed three times in lysis buffer, resuspended in lysis buffer containing 10% glycerol, and frozen. These latex beads were thawed, rinsed three times in regulator assays (40 mM Tris (pH 7.5), 5 mM g of C) and suspended in the same buffer. In a 96-well Millipore plate with 0.65 μg of polyvinylidine bottom membrane, the reaction components are added: 10 μL of c-Src beads, 10 μl of 2.5 mg / ml of poly GluTyr substrate, 5 μM of ATP containing 0.2 μCi [32 P] ATP, 5 μL of DMSO containing inhibitors or, as a solvent control, and regulator to make the final volume 125 μL. The reaction is started at room temperature by the addition of ATP and abruptly extinguished 10 minutes later by the addition of 125 μL of 30% TCA, 0.1 M sodium pyrophosphate for 5 minutes on ice. The plate is then filtered and the wells are washed with two 250 ml aliquots of 15% TCA, 0.1 M pyrophosphate. The filters were then chopped, counted in a liquid scintillation counter, and the data examined for the inhibitory activity compared to a known inhibitor such as erbstatin. The method has been described by Thompson et al. , J. Med. Chem., 1994; 37: 598-609. The results of the above tests for several representative compounds of the invention are presented in Table 1. The metabolic stability of the representative Compounds was evaluated in human liver microsomes (HLM) and given in Table 1 as the time in minutes (Half T) required for one half of the parent compound to disappear after being added to a HLM homoglute.

Table 1 (page 1 of 3) Compound PF CYCKIB CYCK2A CYCK2E CYCK4 FOF CSRC T HALF No. degrees Q K'50 1C50 1C50 IC50 IC50 IC50 HLM μM μM μM μM μM μM nuil 1 > 215 (dec) > 5 > 5 > 5 0.007 1,077 NA 83 2 > 235 (dec) > 5 > 5 > 5 0.265 NA NA NA 7 235-237 > 1.5 > 1.7 > 5 NA NA NA 6 12 > 1 5 (dec) > 5 > 1.7 > 5 0.064 NA NA 43 16 234-237 > 5 > 5 > 5 0.028 NA NA 67 45 227-229 I .I2 5.38 > 5 NA 36.7 NA N? 57 > 80 (dec) > 5 > 5 > 5 0.151 NA 6.08 NA 58 > 230 > 5 > 5 > 5 0.154 35.7 73 > 2l5 (dec) > 1.7 > 1.7 > 5 0.061 > 5 NA 80 or 79 > 1 0 (dec) > 5 > 5 > 5 0.975 NA 34 8 co 82 > 215 (dcc) > 1.7 > 1.7 > 5 0.061 > 5 NA 100 156-159 5.44 1.2468 106 211-213 > 5 > 5 > 5 0.018 1.96 109 > 185 (dec) > 5 13 > 5 0.040 1.15 NA NA 147 254-255 > 5 > 5 > 5 0.03 NA NA 61 148 > 200 2.615 0.439 0.95 0.005 NA NA 73 150 198-199 > 5 > 5 > 5 0.295 NA NA NA 151 217-220 > 1.7 6.98 39 2.45 NA > 50 11 152 180-183 > 1.7 4.91 > 5 2.15 NA > 50 4 153 225-230 > 1.7 > 5 > 5 '> 5 NA > 50 24 157 206-209 > 40 > 40 NA 21.5 > 50 > 50 11 192 180-184 > 5 > 5 > 5 0.114 NA NA NA N ~ Data not available Table 1 196 > 235 (dec) 1.64 > 5 > 5 2.8 197 225-226 > 5 > 5 > 5 0.26 198 261-263 > 5 13.5 > 5 0.103 43.6 199 267-269 > 5 44.8 > 5 0.141 16.5 200 221 (deu) > 5 > 5 > 5 0.285 19.3 201 > 250 > 5 6.94 > 5 0.175 202 172 (dec) > 5 9.305 > 5 0.052 O 203 192 24.5 17.565 > 5 0.085 or 204 200-204 > 5 > 5 > 5 0.31 205 192-196 > 5 - 5 > 5 0.37 206 > 5 > 5 > 5 0.042 207 185-187 > 5 > 5 > 5 0.480 208 122-126 > 5 > 5 5 0.450 216 > 130 { dec) > 5 10.2 217 171-173 > 5 > 5 > 5 0.035 218 178-181 8.12 > 5 > 5 0.46 18.75 15.2 222 > 5 2.9 > 5 1.35 225 185-198 (dec) 1,865 0.4425 0.365 0.005 22fi 181 > 5 2.85 3.65 0.17 227 200 > 5 > 5 > 5 > 5 228 > 200 (dec) > 5 1.33 2.05 (1.02 NA = Data not available Table 1 241 191494 > 5 > 5 3.4 0.423 245 147-149 > 5 > 5 > 5 0.375 246 238 (dec) > 5 19.4 > 5 1.05 250 246-248 > 5 > 5 > 5 > 5 251 > 240 (dec) 5 6.52 4.7 0.27 NA = Data not available Various properties of the preferred 5-methylpyridopyrimidin-7-ones such as 8-cyclopentyl-5-methyl-2 - [(4-piperazinophenyl) -amino] -8-hydro? Iridino [2,3-d] pyrimidin-7- One (Compound 1), including IC50, stability, and clarity rate, are displayed in Tala 2. Table 2 Compound 5-Mß ICs0 (μM) TVi m Clarity Cdki / CdlO CdKt / Cdk4 FGFr or-Src PDGFr HLM (mL ? nin / fcg) cyclin B clcline, A cyclin (min) 1 Si > 5 > 5 5 0.007 1.077 13 2S.5 (n - 2) 57 YES > 5 > 5 > 5 0.151 6.0Í 73 If > 1.7 > 1.7 > 5 0.061 > 5 SO 79 YES > 5 > 5 5 0.975 NA 34 8 152 Yes > 1.7 4.91 > 5 2.15 NA > 50 4 From the results shown in Table 2, it is clear that Compound 1 and other compounds of the invention specifically inhibit Cdk4, and have relatively little effect on Cdk1 and Cdk2. In addition, Compound 1 is relatively more stable, and clear at a slower rate, compared to the prior art compounds. These results indicate that the methyl group at position 5 confers unique properties on pyridopyrimidine and is a preferred embodiment.

Formulation Examples As noted above, the compounds of the invention will normally be formulated with common excipients, diluents, and carriers to provide compositions that are well suited for convenient administration to mammals The following examples illustrate typical compositions that are provided in a further embodiment of this invention. EXAMPLE 20 Tablet Formulation Ingredient Quantity Compound 12 50 mg Lactose 80 mg Corn starch (for mixing) 1 0 mg Corn starch (for pasta) 8 mg Magnesium stearate (1%) 2 mg 150 mg Compound 12 is mixed with lactose and corn starch (for mixing) and mixed for uniformity as a powder. The corn starch (for pasta) is suspended in 6 ml of water and heated with agitation to form a paste. The paste is added to the mixed powder, and the mixture is granulated. The wet granules are passed through a hard sieve No. 8 and dried at 50 ° C. The mixture is lubricated with 1% magnesium stearate and compressed into a tablet. The tablets are administered to a patient at a rate of 1 to 4 per day for the prevention and treatment of atherosclerosis.

EXAMPLE 21 Parenteral Solution 20.0 g of Compound 38 is added in a solution of 700 ml of propylene glycol and 200 ml of water for injection. The mixture is stirred and the pH is adjusted to 5.5 with hydrochloric acid. The volume is adjusted to 1000 ml with water for injection. The solution is sterilized, filled into 5.0 ml ampules, each containing 2.0 ml (40 mg of Compound 38), and sealed under nitrogen. The solution is administered by injection to a patient suffering from cancer and in need of treatment. The invention and the manner and process of carrying it out and using it, are now described in such complete, clear, concise and accurate terms as to enable any person skilled in the art to which it belongs, to make and use it. It will be understood that the above described preferred embodiments of the present invention and that the modifications may be made herein without departing from the spirit and scope of the present invention as set forth in the claims. To particularly indicate and claim differently the subject matter with respect to the invention, the following claims conclude this specification.

Claims (1)

1. REVIVAL DICTION IS 1. A compound of the formula and pharmaceutically acceptable salts, esters, amides and prodrugs thereof, characterized in that: R 2 is (a) hydrogen; (b) lower alkyl optionally substituted with one, two or three groups independently selected from halogen, hydroxy, lower alkoxy, amino, mono- or dialkylamino, carboxy, alkoxycarbonyl, thioaikyl, nitrile, aryl, heteroaryl, or a carbocyclic group containing 3 to 7 members, up to two of whose members are optionally heteroatoms independently selected from oxygen, sulfur and nitrogen; or (c) a carbocyclic group containing from 3 to 7 members, up to two of which members are optionally heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the carbocyclic group is substituted or unsubstituted with one, two or three groups independently selected from halogen, hydroxy, lower alkyl, lower alkoxy, amino, mono- or dialkylamino, aryl and heteroaryl; Rc is hydrogen, lower alkyl, lower alkoxy, halogen, trifluoromethyl, lower alkynyl, lower alkenyl, nitrile, nitro, -COR4, -CO2R4, -CONR4R5, CON R4OR5, R 4 -SO 2 N R 4 R 5, -SO 2 R 4, -SO 3 R 4, P (O) (OR 4) (OR 5), or -NR 4 R 5; And it is N or CR7; R9 is lower alkyl, haloalkyl or aryl; X and Z are independently hydrogen, halogen, lower alkyl, lower alkoxy, trifluoromethyl, hydroxy, nitrile, nitro, -NR4R5, -N (O) R4R5, -NR4R6R6W, -SR4, -C (0) R4, -CO2R4, -CON R4R5, -SO2N R4R5, -SO R4, -SO3R4, P (O) (OR R4) (OR) 5, -T (CH2) mQR4, -C (O) T (CH2) mQR4, or -NR4C ( O) T (CH2) mQR5; m is 1 -6; n is 0-6; T is O, S, NR 4, N (O) R 4, N R 4 R 5 W, or CR 4 R 5; Q is O, S, NR4, N (O) R4, NR4R5W, CO2 or a carbocyclic group containing from 3 to 7 members, up to four of which members are optionally heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the carbocyclic group is substituted or unsubstituted with one, two or three groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, trifluoromethyl, N-hydroxyacetamide, trifluoromethylalkyl, amino or mono or dialkylamino; R6 is lower alkyl, haloalkyl or aryl; R7 is NR4R5, N (O) R4R5, NR4R5R9X, OH, OR4, SR4, halo, COR4, (CH2) nR4, C02R4, CONR4R5, C (0) NR4S02R5, S (0) R4, SO2R4, S02N R4R5, SO3R4, (CH2) nP (0) (OR4) 2, NR4S02R5, aldehyde, nitrile, nitro, alkyl, alkoxyalkyl, T (CH2) mQR4, C (O) T (CH2) mQR4, NR4C (0) T (CH2) mQRs, or T (CH2) mC02R4; n is 0 to 6; W is an anion; R4 and R5 are independently hydrogen, lower alkyl, lower alkenyl, lower alkynyl, (CH2) nAr, arylalkyl, aryl, heteroaryl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, or heteroaryl, or R4 and R5 together with the nitrogen to which they are attached form a carbocyclic ring containing 3 to 8 members, up to four of which members are optionally carbonyl groups or heteroatoms independently selected from oxygen, sulfur, S (O), S (O) 2, and nitrogen, wherein the carbocyclic group is substituted or unsubstituted substituted with one, two, three, or four selected groups independently of halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, aminoalkylcarbonyl, trifluoromethyl, trifluoromethylalkyl, trifluoromethylalkylaminoalkyl, amino, mono- or dialkylamino, N-hydroxyacetamido, aryl, heteroaryl, carboxyalkyl, NR1 0SO2R1 1, C (O) NR 10 R 1 1, N R 1 0 C (O) R 1 1, C (O) OR 10, C (O) N R 10 SO 2 R 1 1, (CH2) nS (O) nR10, (CH2) n-heteroaryl, O (CH2) n-heteroaryl, (CH2) nC (O) NR10R1 1, O (CH2) nC (O) OR1 0; and R 4 may additionally be substituted or unsubstituted alkyl with one, two, or three groups independently selected from halogen, 5-oxo-4,5-dihydro-1 / - / - 1, 2,4-triazole-3-yl- Sulfanyl, 5-oxo-4,5-dihydro-1 H-1, 2,4-triazol-3-yl-sulfinyl, 5-oxo-4, 5-dihydro-1 H-1, 2,4-triazol-3-ylsulfonyl or a carbocyclic group containing from 3 to 7 members, up to four of which members are optionally heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the carbocyclic group is substituted or unsubstituted with one, two or three groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, trifluoromethyl, N-hydroxyacetamide, trifluoromethylalkyl , amino or mono- or dialkylamino; and R 10 and R 1 1 are independently hydrogen, halogen, lower alkyl, lower alkoxy or alkylcarbonyl. 2. A compound of Formula I I II and pharmaceutically acceptable salts, esters, amides, and prodrugs thereof, characterized in that: R3 is hydrogen, lower alkyl, lower alkoxy, halogen, trifluoromethyl, lower alkynyl, lower alkenyl, nitro, nitro, -COR4, -CO2R4, - CONR4R5, CONR4OR5, R 4 -SO 2 NR 4 R 5, -S0 2 R 4, -SO 3 R 4, P (O) (OR 4) (OR 5), or -NR 4 R 5; And it is N or CR7; X and Z are independently hydrogen, halogen, lower alkyl, lower alkoxy, trifluoromethyl, hydroxy, nitrile, nitro, -NR4R5, -N (0) R4R5, -NR4R6R6W, -SR4, -C (0) R4, -C02R4, - CONR4R5, -SO2NR4R5, -SO2R4, -SO3R4, P (O) (OR4) (OR) 5, -T (CH2) mQR4, -C (O) T (CH2) mQR4, or -NR4C (0) T (CH2) mQR5; m is 1-6; T is O, S, NR 4, N (O) R 4, NR 4 R 5 W, or CR 4 R 5; Q is O, S, NR4, N (O) R4, NR4R5W, CO2 or a carbocyclic group containing from 3 to 7 members, up to four of which members are optionally heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the The carbocyclic group is substituted or unsubstituted with one, two or three groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, trifluoromethyl, N-hydroxyacetamide, trifluoromethylalkyl, amino or mono or dialkylamino; R6 is lower alkyl, haloalkyl or aryl; R7 is NR4R5, N (O) R4R5, NR4R5R9X, OH, OR4, SR4, halo, COR4, (CH2) nR4, C02R4, CONR4R5, C (0) NR4S02R5, S (0) R4, S02R4, S02NR4R5, S03R4, ( CH2) nP (0) (OR4) 2, NR4S02R5, aldehyde, nitrile, nitro, alkyl, alkoxyalkyl, T (CH2) mQR4, C (O) T (CH2) mQR4, NR4C (0) T (CH2) mQR10, or T (CH2) mC02R4; n is 0 to 6; W is an anion; R4 and R5 are independently hydrogen, lower alkyl, lower alkenyl, lower alkynyl, (CH2) nAr, arylalkyl, aryl, heteroaryl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, or heteroaryl, or R4 and R5 together with the nitrogen to which they are attached form a carbocyclic ring containing 3 to 8 members, up to four of which members are optionally carbonyl groups or heteroatoms independently selected from oxygen, sulfur, S (O), S (O) 2, and nitrogen, wherein the carbocyclic group is substituted or unsubstituted substituted with one, two, three, or four groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, aminoalkylcarbonyl, trifluoromethyl, trifluoromethylalkyl, trifluoromethylalkylaminoalkyl, amino, mono- or dialkylamino, N -hydroxyacetamido, aryl, heteroaryl, carboxyalkyl, NR10SO2R11, C (O) NR10R11, NR10C (O) R11, C (0) OR10, C (O) NR10SO2R11, (CH2) nS (0) nR10, (CH2) n-heteroaryl, 0 (CH2) n-heteroaryl, (CH2) nC (O) NR10R11, 0 (CH2) nC (0) OR10; R9 is lower alkyl, haloalkyl, or aryl; and R4 may additionally be substituted or unsubstituted alkyl with one, two, or three groups selected independently from halogen, 5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl-sulf añilo , 5-oxo-4,5-dihydro-1H-1, 2,4-triazol-3-yl-sulfinyl, 5-oxo-4,5-dihydro-1H-1, 2,4-triazol-3-yl -sulfonyl or a carbocyclic group containing from 3 to 7 members, up to four of which members are optionally heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the carbocyclic group is substituted or unsubstituted with one, two or three groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, trifluoromethyl, N-hydroxyacetamide, trifluoromethylalkyl, amino or mono- or dialkylamino; and when Y is CR7, it is part of the structure of dialkylamino; and when Y is CR7, it is part of the structure of the part where R7 and Z are as defined previously, or they can be taken together with the carbons to which they are attached to form wherein: G and J are independently CH2, NH, or O; B is NH, S, CH2I or O; D is C or N, with the proviso that R10 is nothing when D is N; and R1 0 and R1 1 are independently hydrogen, halogen, lower alkyl, lower alkoxy, or alkylcarbonyl. 3. A compound of Formula ll l III and pharmaceutically acceptable salts, esters, amides, and prodrugs thereof, characterized in that: R3 is hydrogen, lower alkyl, lower alkoxy, halogen, trifluoromethyl, lower alkynyl, lower alkenyl, nitrile, nitro, -COR4, -CO2R4, -CONR4R5, CONR4OR5, - R4 SO2NR4R5, -SO2R4, -SO3R4, P (O) (OR4) (OR5), or -NR4R5; And it is N or CR7; X and Z are independently hydrogen, halogen, lower alkyl, lower alkoxy, trifluoromethyl, hydroxy, nitrile, nitro, -NR4R5, -N (0) R4Rs, -NR4R6R6W, -SR4, -C (0) R4, -CO2R4, - CONR4R5, -SO2NR4R5, -SO2R4, -SO3R4, P (O) (OR4) (OR) 5, -T (CH2) mQR4, -C (O) T (CH2) mQR4, or -NR4C (O) T (CH2) mQR5; m is 1-6; T is O, S, NR 4, N (O) R 4, NR 4 R 5 W, or CR 4 R 5; Q is O, S, NR4, N (O) R4, NR4R5W, CO2 or a carbocyclic group containing from 3 to 7 members, up to four of which members are optionally heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the The carbocyclic group is substituted or unsubstituted with one, two or three groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, trifluoromethyl, N-hydroxyacetamide, trifluoromethyl lalkyl, amino or mono or dialkylamino; Rβ is lower alkyl, haloalkyl or aryl; R7 is NR4R5, N (O) R4R5, NR4R5R9X, OH, OR4, SR4, halo, COR4, (CH2) nR4, CO2R4, CONR4R5, C (O) N R4SO2R5, S (O) R4, SO2R4, SO2N R4R5, SO3R4 , (CH2) nP (O) (OR4) 2, NR4SO2R5, aldehyde, nitrile, nitro, alkyl, alkoxyalkyl, T (CH2) mQR4, C (O) T (CH2) mQR4, NR4C (O) T (CH2) mQR10 , or T (CH2) mCO2R4; n is 0 to 6; W is an anion; R4 and R5 are independently hydrogen, lower alkyl, lower alkenyl, lower alkynyl, (CH2) nAr, arylalkyl, aryl, heteroaryl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, or heteroaryl, or R4 and R5 together with the nitrogen to which they are attached form a carbocyclic ring containing 3 to 8 members, up to four of which members are optionally carbonyl groups or heteroatoms independently selected from oxygen, sulfur, S (O), S (0) 2, and nitrogen, wherein the carbocyclic group is substituted or unsubstituted substituted with one, two, three, or four groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, aminoalkylcarbonyl, trifluoromethyl, trifluoromethylalkyl, trifluoromethylalkylaminoalkyl, amino, mono- or dialkylamino, N -hydroxyacetamido, aryl, heteroaryl, carboxyalkyl, NR1 0SO2R1 1, C (O) NR10R11, NR10C (O) R11, C (O) OR10, C (O) NR10SO2R11, (CH2) nS (O) nR10, (CH2) n-heteroaryl, 0 (CH2) n-heteroaryl, (CH2) nC (O) NR10R11, 0 (CH2) nC (0) OR1 °; and R4 may additionally be substituted or unsubstituted alkyl with one, two, or three groups independently selected from halogen, 5-oxo-4,5-dihydro-1H-1, 2,4-triazol-3-yl-sulfanyl, -oxo-4,5-dihydro-1 H-1, 2,4-triazol-3-yl-sulfinyl, 5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-yl- sulfonyl or a carbocyclic group containing from 3 to 7 members, up to four of which members are optionally heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the carbocyclic group is substituted or unsubstituted with one, two or three groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, trifluoromethyl, N-hydroxyacetamide, trifluoromethylalkyl, amino or mono- or dialkylamino; and when Y is CR7, it is part of the structure of dialkylamino; and when Y is CR7, is it part of the? ???? structure of the part / where R7 and Z are as previously defined, or can be taken along with the carbons to the which are united to form wherein: G and J are independently CH2, N H, or O; B is NH, S, CH2, or O; D is C or N, with the proviso that R10 is nothing when D is N; and R9 is lower alkyl, haloalkyl or aryl; R1 0 and R1 1 are independently hydrogen, halogen, lower alkyl, lower alkoxy, or alkylcarbonyl. 4. A compound of Formula IV and pharmaceutically acceptable salts, esters, amides, and prodrugs thereof, characterized in that: R3 is hydrogen, lower alkyl, lower alkoxy, halogen, trifluoromethyl, lower alkynyl, lower alkenyl, nitrile, nitro, -COR4, -CO2R4, -CONR4R5, CONR4OR5, - R4 SO2NR4R5, -SO2R4, -SO3R4, P (O) (OR4) (OR5), or -NR4R5; And it is N or CR7; X and Z are independently hydrogen, halogen, lower alkyl, lower alkoxy, trifluoromethyl, hydroxy, nitrile, nitro, -NR4R5, -N (O) R4R5, -NR4R6R6W, -SR4, -C (O) R4, -CO2R4, - CONR4Rs, -SO2NR4R5, -S02R4, -SO3R4, P (O) (OR4) (OR) 5, -T (CH2) mQR4, -C (O) T (CH2) mQR4, or -NR4C (O) T (CH2) ) mQR5; m is 1-6; T is O, S, NR 4, N (O) R 4, NR 4 R 5 W, or CR 4 R 5; Q is O, S, NR4, N (O) R4, NR4R5W, CO2 or a carbocyclic group containing from 3 to 7 members, up to four of which members are optionally heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the carbocyclic group is substituted or unsubstituted with one, two or three groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, trifluoromethyl, N-hydroxyacetamide, trifluoromethylalkyl, amino or mono or dialkylamino; R6 is lower alkyl, haloalkyl or aryl; R7 is NR4R5, N (O) R4R5, NR4R5R9X, OH, OR4, SR4, halo, COR4, (CH2) nR4, CO2R4, CONR4R5, C (O) NR4SO2R5, S (O) R4, S02R4, SO2NR4R5, SO3R4, (CH2) nP (O) (OR4) 2, NR4SO2R5, aldehyde, nitrile, nitro, alkyl, alkoxyalkyl, T (CH2) mQR4, C (O) T (CH2) mQR4, NR4C (O) T (CH2) mQR10, or T (CH2) mCO2R4; n is 0 to 6; W is an anion; R4 and R5 are independently hydrogen, lower alkyl, lower alkenyl, lower alkynyl, (CH2) nAr, arylalkyl, aryl, heteroaryl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, or heteroaryl, or R4 and R5 together with the nitrogen to which they are attached form a carbocyclic ring containing 3 to 8 members, up to four of which members are optionally carbonyl groups or heteroatoms independently selected from oxygen, sulfur, S (O), S (O) 2, and nitrogen, wherein the carbocyclic group is substituted or unsubstituted substituted with one, two, three, or four groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, aminoalkylcarbonyl, trifiuoromethyl, trifluoromethyl-alkanoy, trifluoromethylalkylaminoalkyl, amino, mono- or dialkylamino, N -hydroxyacetamido, aryl, heteroaryl, carboxyalkyl, NR10SO2R11, C (O) NR10R11, NR10C (O) R11, C (O) OR10, C ( O) NR10SO2R11, (CH2) nS (0) nR10, (CH2) n-heteroaryl, 0 (CH2) n-heteroaryl, (CH2) nC (O) NR10R1 1, O (CH2) nC (O) OR1 0; and R 4 may additionally be substituted or unsubstituted alkyl with one, two, or three groups independently selected from halogen, 5-oxo-4,5-dihydro-1 H-1, 2,4-tri azo I-3-yl- sulfonyl, 5-oxo-4,5-dihydro-1 H-1, 2,4-triazol-3-yl-sulfinyl, 5-oxo-4,5-dihydro-1 H-1,2,4-triazole -3-yl-sulfonyl or a carbocyclic group containing from 3 to 7 members, up to four of which members are optionally heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the carbocyclic group is substituted or unsubstituted with one, two or three groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, trifluoromethyl, N-hydroxyacetamide, trifluoromethylalkyl, amino or mono- or dialkylamino; and when Y is CR7, it is part of the structure of dialkylamino; and when Y is CR7, it is part of the structure of the part where R7 and Z are as defined previously, or they can be taken together with the carbons to which they are attached to form wherein: G and J are independently CH2, NH, or O; B is NH, S, C H2, or O; D is C or N, with the proviso that R10 is nothing when D is N; R is lower alkyl, haloalkyl or ary; and R1 0 and R1 1 are independently hydrogen, halogen, lower alkyl, lower alkoxy, or alkylcarbonyl. 5. A compound of Formula V V and pharmaceutically acceptable salts, esters, amides, and prodrugs thereof, characterized in that: R 2 is (a) hydrogen; (b) lower alkyl optionally substituted with one, two or three groups independently selected from halogen, hydroxy, lower alkoxy, amino, mono- or dialkylamino, carboxy, alkoxycarbonyl, thioalkyl, nitrile, aryl, heteroaryl, or a carbocyclic group which it contains from 3 to 7 members, up to two of which members are optionally heteroatoms independently selected from oxygen, sulfur and nitrogen; or (c) a carbocyclic group containing from 3 to 7 members, up to two of which members are optionally heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the carbocyclic group is substituted or unsubstituted with one, two or three groups independently selected from halogen, hydroxy, lower alkyl, lower alkoxy, amino, mono- or dialkylamino, aryl and heteroarylo; R3 is hydrogen, lower alkyl, lower alkoxy, halogen, trifluoromethyl, lower alkyne, lower alkenyl, nitrile, nitro, -COR4, -CO2R4, -CONR4R5, CONR OR5, - R 4 SO 2 NR 4 R 5, -SO 2 R 4, -SO 3 R 4, P (O) (OR 4) (O R 5), or -N R 4 R 5; R9 is lower alkyl, haloalkyl or aryl; X and Z are independently hydrogen, halogen, lower alkyl, lower alkoxy, trifluoromethyl, hydroxy, nitrile, nitro, -NR4R5, -N (O) R4R5, -NR4R6R6W, -SR4, -C (O) R4, -CO2R4, - CONR4R5, -SO2NR4R5, -SO2R4, -SO3R4, P (O) (OR4) (OR) 5, -T (CH2) mQR4, -C (O) T (CH2) mQR4, or -NR4C (O) T (CH2) mQR5; m is 1 a6; T is O, S, NR 4, N (O) R 4, NR 4 R 5 W, or CR 4 R 5; Q is O, S, NR4, N (O) R4, NR4R5W, CO2 or a carbocyclic group containing from 3 to 7 members, up to four of which members are optionally heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the carbocyclic group is substituted or unsubstituted with one, two or three groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, trifluoromethyl, N-hydroxyacetamide, trifluoromethylalkyl, amino or mono or dialkylamino; R6 is lower alkyl, haioalkyl or aryl; R7 is NR4R5, N (0) R4R5, NR R5R9X, OH, OR4, SR4, halo, COR4, (CH2) nR4, CO2R4, CONR R5, C (O) NR4SO2R5, S (O) R4, SO2R4, SO2NR4R5, SO3R4, (CH2) nP (O) (OR4) 2, NR4SO2R5, aldehyde, n-thyl, nitro, alkyl, alkoxyalkyl, T (CH2) mQR4, C (O) T (CH2) mQR4, NR4C (O) T (CH2) mQR5, or T (CH2) mCO2R4; n is 0 to 6; W is an anion; R4 and R5 are independently hydrogen, lower alkyl, lower alkenyl, lower alkynyl, (CH2) nAr, arylalkyl, aryl, heteroaryl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, or heteroaryl, or R4 and R5 together with the nitrogen to which they are attached form a carbocyclic ring containing 3 to 8 members, up to four of which members are optionally carbonyl groups or heteroatoms independently selected from oxygen, sulfur, S (O), S (O) 2, and nitrogen, wherein the carbocyclic group is substituted or unsubstituted with one, two, three, or four groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, aminoalkylcarbonyl, trifluoromethyl, trifluoromethylalkyl, trifluoromethylalkylaminoalkyl, amino, mono- or dialkylamino, N-hydroxyacetamido. aryl, heteroaryl, carboxyalkyl, NR1 0SO2R1 1, C (O) NRi 0R1 1, NR1 0C (O) R1 1, C (O) OR10, C (O) NR10SO2R1 \ (CH2) nS (O) nR10, (CH2) n-heteroaryl, O (CH2) n-heteroaryl, (CH2) nC (O) NR10R1 1, O (CH2) nC (O) OR10; and R 4 may additionally be substituted or unsubstituted alkyl with one, two, or three groups independently selected from halogen, 5-oxo-4,5-dihydro-1 H-1, 2,4-triazol-3-yl-sulfanyl, 5-oxo-4,5-dihydro-1 H-1, 2,4-triazol-3-yl-sulfinyl, 5-oxo-4,5-dihydro-1 H-1, 2,4-triazole-3- il-sulfonyl or a carbocyclic group containing from 3 to 7 members, up to four of whose members are optionally heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the carbocyclic group is substituted or unsubstituted with one, two or three groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, trifluoromethyl, N-hydroxyacetamide, trifluoromethylalkyl, amino or mono- or dialkylamino; and R 10 and R 1 1 are independently hydrogen, halogen, lower alkyl, lower alkoxy or alkylcarbonyl. 6. A compound according to claim 5, characterized in that R7 is selected from and wherein such groups are optionally substituted by alkyl, aryl or amide. 7. A compound selected from the group consisting of: (a) 8-Cyclopentyl-5-methyl-2- (4-piperazin-1-yl-phenylamido.) -8H-pyrido [2,3-d] -pyrimidin -7-one (Compound 1); (b) 8- (1-Methylethyl) -5-methyl-2- (4-piperazin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidine- 7-one (Compound 2); (c) 8-Cyclopentyl-5-methyl-2- (4-fluoro-3-methylphenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 3); (d) 8- (1-Methylethyl) -5-methyl-2- (4-fluoro-3-methylphenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 4); (e) 8-Cyclohexyl-5-methyl-2- (4-fluoro-3-methylphenylamino-8H-prido [2,3-d] pyrimidin-7-one (Compound 5); (f) 8-Cyclohexyl-5 -methyl-2- [4- (4-propane i I piperazi n-1 -ii) phenylamino] -8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 6); (g) 8-Cyclopentyl 5-methyl-2- [4- (4-propanoylpiperazin-1-yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 7); (h) 8- (1 - Methylethyl) -5-met i I -2- [4- (propane i I piperazi n-1 -yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 8); 8-Cyclohexyl-5-methyl-2- (4-piperazin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 9); (j) 8-Cyclopentyl- 5-methyl-2- (4-pyridylphenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 10); (k) 8- (1-Methylethyl) -5-methyl-2- ( 4-pyridylphenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 11); (I) 8-Cyclopentyl-5-methyl-2- [4- (3-aminopyrrolidinyl) phenylamino] -8H pyrido [2,3-d] pyrimidin-7-one (Compound 12); (m) 8- (1-Methylethyl) -5-methyl-2- [4- (3-aminopyridinomethyl) phenylamino] -8H- pyrido [2,3-d] pyrirnidin-7-one (Com position 13); (n) N- (1- { 4 - [(8-cyclopentyl-5-methyl-7-oxo (8-hydropyridino [2,3-d] -pyrimidin-2-yl)) amino] phenyl} pyrrolidin-3-yl) -3,3-dimethylbutanamide (Compound 14); (o) N- (1- { 4 - [(5-methyl-8- (1-methylethyl) -7-oxo (8-hydropyridino [2,3-d] -pyrimidin-2-yl)) amino ] phenyl] pyrrolidin-3-yl) -3,3-dimethylbutanamide (Compound 15); (p) 8- (Cyclopentyl-5-met i I -2- (3-chloro-4-pi-perazin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 16); (q) 8-Cyclohexyl-5-methyl-2- (3-chloro-4-piperazin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one ( Compound 17); (r) 8- (1-Methylethyl) -5-methyl-2- (3-chloro-4-piperazin-1 -i I-fienylamino-8H-pyrido [2,3-d] pyrimidin-7 -one (Compound 18); (s) 8-Cyclopentyl-6-fluoro-5-methyl-2- (3-chloro-4-piperazin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 19); (t) 8-Cyclohexyl-6-fluoro-5-methyl-2- (3-chloro-4-piperazin-1-yl-phenylamino) -8H-pyrido [2,3 -d] pyrimidin-7-one (Compound 21); (u) 8- (1-Methylethyl) -6-fluoro-5-methyl-2- (3-chloro-4-piperazin-1-yl-phenylamino) - 8H-pyrido [2,3-d] pyrimidin-7-one (Compound 20); (v) 8-Cyclopentyl-5-methyl-2- (3-chloro-4-morfoin-4-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 22); (w) 8- (1-Methylethyl) -5-methyl-2- (3-chloro-4-morpholin-4-i) I-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 23); (x) 8-Cyclohexyl-5-methyl-2- (3-chloro-4-morpholin-4-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 24); (y) 2- ( { 3-chloro-4- [4- (3-morpholin-4-ylpropyl) piperidyl] phenyl} -amino) -8-cyclopentyl-5-methyl-8-hydropyridino [2 , 3-d] pyrimidin-7-one (Compound 25); (z) 2- ( { 3-chloro-4- [4- (3-morpholin-4-ylpropyl) piperidyl] phenyl} -amino) -8- (1-methyl-ethyl) -5-methyl-8 -hydropyridino [2,3-d] pyrimidin-7-one (Compound 26), (aa) 2- (. {3-cyoro-4- [4- (3-morpholin-4-ylpropyl) pperidyl) ] -phenyl.} amino) -8-cyclohexyl-5-methyl-8-hydropyridino [2,3-d] pyrimidin-7-one (Compound 27); (bb) 2- ( { 3-Chloro-4- [4- (3-piperazinylpropyl) piperidyl] phenyl} amino) -8-cyclopentyl-6-fluoro-5-methyl-8-hydropyridino [2, 3-d] pyrimidin-7-one (Compound 28); (cc) 2- ( { 3-chloro-4-l4- (3-piperazinylpropyl) piperidyl] phenyl.}. -amino) -8- (1-methyl-ethyl) -6-fluoro-5-methyl-8- hydropyridino [2,3-d] pyrimidin-7-one (Compound 29); (dd) 2- ( { 3-chloro-4- [4- (3-piperazinylpropyl) piperidyl] -phenyl} arnino) -8-cyclohexyl-6-fluoro-5-methyl-8-hydropyridino [2 , 3-d] -pyrimidin-7-one (Compound 30); (ee) 2- ( { 3-chloro-4- [4- (3-piperazinylpropyl) piperidyl] -phenyl} amino) -8-cyclopentyl-5-methyl-8-hydropyridino [2,3-d ] pyrimidin-7-one (Compound 31); (ff) 2- ( { 3-chloro-4- [4- (3-piperazyl nylpropi I) piperid il] f eni I.}. -amino) -8- (1-methylethyl) -5-methyl- 8-hydropyridino [2,3-d] pyrimidin-7-one (Compound 32); (gg) 2- ( { 3-Chloro-4- [4- (3-piperazyl nylpropi I) piperidyl] f eni I.] -amino) -8-cyclohexyl-5-methyl-8-hydropyridino [ 2,3-d] pyrimidin-7-one (Compound 33); (gg2) 8-Cyclopentyl-2- [4- (piperazin-1-yl) -phenylamino] -6-fluoro-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one trifluoroacetate ( Compound 34); (gg3) 8-Cyclopentyl-2- [4- (piperazin-1-yl) -phenylamino] -6-bromo-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one trifluoroacetate (Compound 35); (hh) 8-Cyclopentyl-2- [4- (3,5-dimethyl-piperazin-1-yl) -phenylamino] -6-fluoro-5-methyl-8H-pyrido [2,3-d] pyrimidin hydrochloride -7-one (Compound 36); (ii) 8-Cyclopentyl-2- (3-fluoro-4-piperazin-1-yl-phenylamino) -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 37); (jj) 6-Bromo-8-cyclopentyl-2- [4- (3,5-dimethyl-piperazin-1-yl) -phenylamino] -5-methyl-8H-pyrido hydrochloride [2,3-d] - pyrimidin-7-one (Compound 38); (kk) 8-Cyclopentyl-6-fluoro-2- (3-fluoro-4-piperazin-1-yl-phenylamino) -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 39); (II) 6-B romo-8-ci clopent i l-2- (3-f luo ro-4-pi perazin-1-yl-phenylamino) -5-methyl-8 H -pyrido [2,3- d] pi rim id in-7-one (Composite 40); (mm) 8-Cyclopentyl-2- [4- (3,5-dimethyl-piperazin-1-yl) -phenylamino] -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 41); (nn) 2- (3-Chloro-4-piperazin-1-yl-phenylamino) -8-cyclopentyl-5-methyl-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 42); (oo) 2- (3-chloro-4-piperazin-1-yl-phenylamino) -8-cyclopentyl-6-fluoro-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 43); (pp) 6-Bromo-2- (3-chloro-4-piperazin-1-yl-phenylamino) -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 44); (qq) 8-Cyclopentyl-5-methyl-2- (4-morpholin-4-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one trifluoroacetate (Compound 45); (rr) 8-Cyclopentyl-6-fluoro-5-methyl-2- (4-morpholin-4-yl-phenylamino) -8H-pyrido [2) 3-d] pyrimidin-7-one (Compound 46); (ss) 6-Bromo-8-cyclopentyl-5-methyl-2- (4-morpholin-4-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 47); (tt) 8-Cyclopentyl-2- (3-fluoro-4-morpholin-4-yl-phenylamino) -5-methyl-8 H -pyrido [2,3-dlpyrimidin-7-one (Compound 48); (uu) 8-Cyclopentyl-6-fluoro-2- (3-fluoro-4-morpholin-4-yl-phenylamino) -5-methyl-8H-pyrido [2,3-d] pyrimido-7-one ( Compound 49); (vv) 6-Bromo-8-cycylpentyl-2- (3-fluoro-4-morpholin-4-yl-phenylamino) -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound fifty); (ww) 2- (3-Chloro-4-morpholin-4-yl-phenylamino) -8-cyclopentyl-5-methyl-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 51); (xx) 2- (3-Chloro-4-morpholin-4-yl-phenylamino) -8-cyclopentyl-6-fluoro-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 52); (y) 6-Bromo-2- (3-chloro-4-morpholin-4-yl-phenylamino) -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 53); (zz) 8-Cyclopentyl-5-methyl-2-. { 4- [4- (2, 2, 2-trifluoro-ethyl) -piperazin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 54); (aaa) 8-Cyclopentyl-6-fluoro-5-methyl-2-. { 4- [4- (2,2,2-trifluoro-ethyl) -piperazin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 55); (bbb) 6-Bromo-8-cyclopentyl-5-methyl-2-. { 4- [4- (2,2,2-trifluoro-ethyl) -piperazin-1-yl] -phenylamino} -8H-pyrido [2) 3-d] pyrimidin-7-one (Compound 56); (ccc) 8-Cyclopentyl-5-methyl-2- trifluoroacetate. { 4- [4- (3-piperazin-1-yl-propyl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 57); (ddd) 8-Cyclopentyl-6-fluoro-5-metii-2-. { 4- [4- (3-piperazin-1-yl-propyl) -piperidin-1-yl] -phenylamino} -8H-pyrid [2,3-d] pyrimidin-7-one (Compound 58); (eee) 6-Bromo-5-cyclopentyl-5-methyl-2-. { 4- [4- (3-piperazin-1-yl-propyl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 59); (fff) 8-Cyclopentyl-5-methyl-2-. { 4- [4- (3-morpholin-4-yl-propyl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 60); (ggg) 8-Cyclopentyl-6-fluoro-5-methyl-2-. { 4- [4- (3-morpholin-4-yl-propyl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 61); (hhh) 6-Bromo-8-cyclopentyl-5-methyl-2-. { 4- [4- (3-morpholin-4-yl-propyl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 62); (iii) 6-Bromo-8-cyclopentyl-5-methyl-2-. { 4- [4- (3-morpholin-4-yl-propyl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 63); (jjj) 2- (4- { 4- [3- (3-Amino-pyrrolidin-1-yl) -propyl] -piperidin-1-yl} -phenylamino) -8-cyclopentyl-5-methyl -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 64); (kkk) 2- (4- { 4- [3- (3-Amino-pyrrolidin-1-yl) -propyl] -piperidin-1-yl] -phenylamino) -8-cyclopentyl-6-fluoro -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 65); (III) 2- (4- { 4- [3- (3-Amino-pyrrolidin-1-yl) -propyl] -piperidin-1-yl}. phenylamino) -6-bromo-8-cyclopentyl -5-methyl-8H-pyrido [2,3-d] -pyrimidin-7-one (Compound 66); (mmm) 8-Cyclopentyl-2-. { 3-fluoro-4- [4- (3-piperazin-1-yl-propyl) -piperidin-1-yl] -phenylamino} -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 67); (nnn) 8-Cyclopentyl-6-fluoro-2-. { 3-fluoro-4- [4- (3-piperazin-1-yl-propyl) -piperidin-1-yl] -phenylamino} -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 68); (ooo) 6-Bromo-8-cyclopentyl-2-. { 3-fluoro-4- [4- (3-piperazin-1-yl-propyl) -piperidin-1-yl] -phenylamino} -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 69); (ppp) 8-Cyclopentyl-2-. { 3-fluoro-4- [4- (3-morpholin-4-yl-propii) -piperidin-1-yl] -phenylamino} -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 70); (qqq) 8-Cyclopentyl-6-fluoro-2-. { 3-fluoro-4- [4- (3-morpholin-4-yl-propyl) -piperidin-1-yl] -phenylamino} -5-methyl-8H-pyrido [2,3-d] -pyrimidin-7-one (Compound 71); (rrr) 6-Bromo-8-cyclopentyl-2-. { 3-fluoro-4- [4- (3-morphol-4-yl-propyl) -piperidin-1-yl] -phenylamino} -5-methyl-8H-pyrido [2,3-d] -pyrimidin-7-one (Compound 72); (sss) 2- [4- (3-Amino-pyrrol-idin-1-yl) -phenylamino] -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 73); (ttt) 2- [4- (3-Amino-pyrrolidin-1-yl) -phenylamino] -8-cyclopentyl-6-fluoro-5-methyl-8H-pyrido [2,3-d] pyrimidin-7 -one (Compound 74); (uu) 2- [4- (3-Amino-pyrrolidin-1-yl) -phenylamino] -6-bromo-8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 75); (vvv) 2- [4- (3-Amino-pyrrolidin-1-yl) -3-fluoro-phenylamido] - 8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 76); (www) 2- [4- (3-Amino-pi rrol idi n-1-yl) -3-fluoro-phenylami] -8-cyclopentyl-6-fluoro-5-m ethi-8H-pyrido [ 2, 3-d] -pyrimidin-7-one (Compound 77); (xxx) 2- [4- (3-Amino-pyrrolidin-1-yl) -3-fluoro-phenylamino] -6-bromo-8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidine -7-one (Compound 78); (yyy) 8-Cyclopentyl-5-methyl-2-trifluoroacetate. { 4- [3- (2,2,2-trifluoro-ethylamino) -pyrrolidin-1-yl] -phenylamino} -8H-pyrido- [2,3-djpyrimidin-7-one (Compound 79); (zzz) 8-Cyclopentyl-6-fluoro-5-methyl-2-. { 4- [3- (2,2,2-trifluoro-ethylamino) -pyrimidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] -pyr? Midin-7-one (Compound 80); (aaa) 6-Bromo-8-cyclopentyl-5-methyl-2-. { 4- [3- (2,2,2-trifluoro-ethylamino) -pyridinidin-1-yl] -phenylamine} -8H-pyrido [2,3-d] -pyr? Midin-7-one (Compound 81); (bbbb) 2- [4- (3-Amino-pyrrolidin-1-yl) -3-chloro-phenylamino] -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7 trifluoroacetate -one (Compound 82); (cccc) 2- [4- (3-Amino-pyrrolidin-1-yl) -3-chloro-phenylamino] -8-cyclopentyl-6-fluoro-5-methyl-8H-pyrido [2,3-d] pyrimidine -7-one (Compound 83); (dddd) 2- [4- (3-Amino-pyrrolidin-1-yl) -3-chloro-phenylamino] -6-bromo-8-cyclopentyl-5-methyl-8H-pyrido [2, 3-d] - pyrimidin-7-one (Compound 84); (eeee) 2- [4- (3-Aminomethyl-4-trifluoromethyl-pyrrolidin-1-yl) -phenylamino] -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 85); (ffff) 2- [4- (3-Am i no met i I-trifluoromethyl l-pyrrolidin-1 -i I) -phenyl] -8-cyclopentyl-6-fluoro-5-methyl -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 86); (gggg) 2- [4- (3-Aminomethyl-4-trifluoromethyl-pyrrolidin-1-yl) -phenylamino] -6-bromo-8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidine -7-one (Compound 87); (hhhh) 2- [4- (3-Trifloroeti laminomethyl-pyrrolidin-1-yl) -phenylamino] -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 88 ); (i iii) 2- [4- (3-Trifloroeti lam i nometi l-pyrrolidi n-1 -i I) -phenylamino] -8-cyclopentyl-6-fluoro-5-methyl-8H-pyrido [2,3 -d] pyrimidin-7-one (Compound 89); (jjjj) 2- [4- (3-Trif loroeti lam i nometi l-pyrrolidi n-1 -i I) -phenylamino] -6-bromo-8-cyclopentyl-5-methyl-8H-pyrido [2,3 -d] pirim id n-7-one (Compound 90); (kkkk) 8-Cyclopentyl-2- [4- (3,3-dimethyl-piperazin-1-yl) -phenylamino] -5-methyl-8H-pyrido [2,3-d] pyrimidin-7 hydrochloride -one (Compound 91); (1111) 8-Cyclopentyl-2- [4-3,3-dimethyl-piperazin-1-yl) -phenylamino] -6-fluoro-5-methyl-8H-pyrido [2,3-d] pyrimidin-7 -one (Compound 92); (mmmm) 6-Bromo-8-cyclopentyl-2- [4- (3,3-dimethyl-piperazin-1-yl) -phenylamino] -5-methyl-8H-pyrido [2,3-d] hydrochloride ] -pyrimidin-7-one (Compound 93); (nnnn) 8-C-chloropentyl-5-methyl-2- [4- (3, 3, 4-trimethyl-piperazin-1-yl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7- ona (Compound 94); (oooo) 8-Cyclopentyl-6-fluoro-5-methyl-2- [4- (3, 3,4-trimethyl-piperazin-1-yl) -phenylamino] -8H-pyrido [2,3-d] pyrimidine -7-one (Compound 95); (pppp) 6-Bromo-8-cyclopentyl-5-methyl-2- [4- (3, 3,4-trimethyl-p-pperazin-1-yl) -phenylamino] -8H-pyrido [2,3-d] ] pyrimidin-7-one (Compound 96); (qqqq) 2- [4- (4-Acetyl-piperidin-1-yl) phenylamino] -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 97); (rrrr) 2- [4- (4-Acetyl-piperazin-1-yl) -phenylamino] -8-cyclopentyl-6-fluoro-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 98); (ssss) 2- [4- (4-Aceti I -piperazi n-1-yl) -f in i lami no] -6-bro mo-8-cyclopentyl-5-methyl-8H-pyrido [2,3- d] pyrimidin-7-one (Compound 99); (tttt) 8-Cyclopentyl-2-. { 4- [4- (2-hydroxy-ethyl) -3,5-dimethyl-piperazin-1-yl] -phenylamino} -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 100); (uuuu) 8-Cyclopentyl-6-fluoro-2-. { 4- [4 (2-hydroxy-ethyl) -3,5-dimethyl-piperazin-1-yl] -phenylamino-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 101); (vvvv) 6-Bromo-8-cyclopenil-2-. { 4- [4- (2-hydroxy-ethyl) -3,5-dimethyl-piperazin-1-yl] -phenylamino} -5-methyl-8H-pyrid [2,3-d] -pyrimidin-7-one (Compound 102); (wwww) 8-Cyclopentyl-5-methyl-2- (4-perhydro-1,4-diazepin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one hydrochloride (Compound 103); (xxxx) 8-Cyclopentyl-6-fluoro-5-methyl-2- (4-perhydro-1,4-diazepin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-hydrochloride -one (Compound 104); (yyyy) 6-Bromo-8-cyclopentyl-5-methyl-2- (4-perhydro-1,4-diazepin-1-yl-phenylamino) -8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 105); (zzzz) 8-Cyclopentyl-5-methyl-2- [4- (4-methyl-piperazin-1-yl) -phenylaminoj-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 106); (aaaaa) 8-Cyclopentyl-6-fluoro-5-methyl-2- [4- (4-methyl-piperazin-1-yl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 107); \ (bbbbb) 6-Bromo-8-cyclopentyl-5-methyl-2- [4- (4-methyl-piperazin-1 -yl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7- ona (Compound 108); (cecee) 8-Cyclopentyl-5-methyl-2- [4- (4-methyl-perhydro-1,4-diazepin-1-yl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7 -one (Compound 109); (ddddd). 8-Cyclopentyl-6-fluoro-5-methyl-2- [4- (4-methyl-1-perhydro-1 -4-diazepin-1-yl) -f-en-lami] -8H-pyrido [2,3- d] pi rim idi n-7-one (Compound 110); (eeeee) 6-Bromo-8-cyclopentyl-5-methyl-2- [4- (4-methyl-perhydro-1,4-diazepin-1-yl) -phenylamino] -8H-pyrido [2,3- d] pyrimidin-7-one (CompouDd 111); (ffff) Acid. { 4- [4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) -phenyl] -piperazin-1-yl} -acetic (Compound 112); () Acid. { 4- [4- (8-Cyclopentyl-6-fluoro-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) -phenyl] -piperazin-1 - il} -acetic (Compound (113); (hhhhh) Acid { 4- [4- (6-Bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro pyrido [2,3-d] pyrimidin-2-ylamino) -phenyl] -piperazin-1-yl.) -acetic (Compound 114); (iiiii) 8-Cyclopentyl-5-methyl-2- (4-. {4- [3- ( 1 H-tetrazol-5-yl) -propyl] -piperidin-1-yl.}. Phenylamino! -8 H -pyrido [2,3-d-] pyrimidin-7-one (Compound 115); (jjjjj) 8 -Cyclopentyl-6-fluoro-5-methyl-2- (4-. {4- [3- (1 H -tetrazol-5-yl) -propyl] -piperidin-1-yl] -phenylamino) - 8H-pyrido [2,3-d] -pyrimidin-7-one (Compound 116); (kkkkk) 6-Bromo-8-cyclopentyl-5-metii-2- (4-. {4- [3- ( 1 H-tetrazol-5-yl) -propyl] -piperidin-1-yl]. Phenylamino) -8 H -pyrido [2,3-d] -pyrimidin-7-one (Compound 117); (IIIll) -Cyclopentyl-5-methyl-2- (4- { 4- [3- (5-oxo-4, 5-dihydro-1 H-1, 2,4-triazo-3-ylsulfanyl) -propyl ] -piperidin-1 -yl.}. phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 118); (mmmmm) 8-Cyclopentyl-6-fluoro-5-methyl-2 - (4- { 4- [3- (5-oxo-4,5-dihydro-1 H-1, 2,4-triazol-3-ylsulfanyl) -propyl] -piperidin-1 - il} phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 119); (nnnnn) 6-B rom o-8-cyclopenti I -5-methyl -2- (4- { 4- [3- (5-oxo-4,5-dihydro-1 H-1, 2.4 -triazol-3-ylsulfanyl) -propyl] -piperidin-1-yl.} - phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 120); (ooooo) 8-Cyclopentyl-5-methyl-2- (4- { 4- [3- (5-oxo-4,5-dihydro-1 H-1, 2,4-triazole-3-sulfinyl) -propyl] -piperidin-1 -yl.}. phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 121); (ppppp) 8-Cyclopentyl-6-fluoro-5-methyl-2- (4- { 4- [3- (5-oxo-4,5-dihydro-1 H-1, 2,4-triazole- 3-sulfinyl) -propyl] -piperidin-1 -ii.}. - phenylamino) -8H-? Irido [2,3-d] pyrimidin-7-one (Compound 122); (qq) 6-B rom o-8-ci clopent i l-5-m ethyl -2- (4-. {4- [3- (5-oxo-4,5-dihydro-1H-1, 2,4-triazole-3-sulfinyl) -propyl] -piperidin-1-yl] -phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 123); (rrrrr) 8-Cyclopentyl-5-methyl-2- (4-. {4- [3- (5-oxo-4,5-dihydro-1 H-1, 2,4-triazole-3-sulfonyl) -propyl] -piperidin-1 -yl.}. phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 124); (sssss) 8-Cyclopentyl-6-fluoro-5-methyl-2- (4-. {4- [3- (5-oxo-4,5-dihydro-1 H-1,2,4-triazole-3-) sulfonyl) -propyl] -piperidin-1 -yl.}. phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 125); (ttttt) 6-Bromo-8-cyclopentyl-5-methyl-2- (4- { 4- [3- (5-oxo-4,5-dihydro-1 H-1, 2,4-triazole- 3-sulfonyl) -propyl] -piperidin-1 -yl.}. Phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 126); (uuuuu) N- (2- { 1 - [4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) - phenyl] -piperidin-4-yl.}. -ethyl) -N-hydroxy-acetamide (Compound 127); (vvvvv) N- (2- { 1 - [4- (8-Cyclopentyl-6-fluoro-5-methyl-7-oxo-718-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino ) -phenyl] -piperidin-4-yl.}. -ethyl) -N-hydroxy-acetamide (Compound 128); (wwwww) N- (2- { 1 - [4- (6-Bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2 -ylamino) -phenyl] -piperidin-4-yl.}. -ethyl) -N-hydroxy-acetamide (Compound 129); (xxxxx) N- (3- { 1 - [4- (8-Cyclopentyl-5-methyl-1-7-0X0-7,8-dihydro-pyrido [2,3-d] -pyrimidin-2-ylamino ) -phenyl] -piperidin-4-yl.}. -propyl) -N-hydroxy-acetamide (Compound 130); (yyyyy) N- (3- { 1 - (4- (8-Cyclopentyl-6-fluoro-5-medyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidine- 2-ylamino) -phenyl] -piperidin-4-yl.}. -propyl) -N-hydroxy-acetamide (Compound 131); (zzzzz) N- (3- { 1 - [4- (6-Bromo -8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrid [213-d] pyrimidin-2-ylamino) -phenyl] -piperidin-4-yl.} - propi l) -N -hid roxi -acetam i da- (Compu this 132); (aaaaaa) 2- (Benzofuran-5-ylamino) -8-cyclopentyl-5-methyl-8H-pyrido [2, 3-d ] pyrimidin-7-one (Compound 133); (bbbbbb) 8-cyclopentyl-2- (1 H -indol-5-ylamino) -5-methyl-8H-pyrido [2,3-d] pyrimidin-7 -one (Compound 134); (cccccc) 2- (Benzo [b] thiophen-5-ylamino) -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 135) ); (dddddd) 8-Cyclopentyl-2- (2,3-dimethyl-1 H -indol-5-ylamino) -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 136 ); (eeeeee) 2- (9H-Carbazol-3-ylamino) -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 137); (fffff) 8 - Cycle? Entyl-2- (1 H-indazol-5-ylamino) -5-methyl-8H-pyrido [9.3-d] pyri midin-7-one (Compound 138); (ggg) 2- (2-Acetyl-benzofuran-5-ylamino) -8-cyclopenty-5-methyl-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 139); (hhhhhh) 8-Cyclopentyl-5-methyl-2- (4-morpholin-4-yl-phenylamine) -8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 140); (iiiiii) 8-Cyclopentyl-2- [4- (3,5-dimethyl-piperazin-1-yl) -phenylamino] -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 141); (jiiiii) 2- (3-Chloro-4-piperazin-1-yl-phenylamino) -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one trifluoroacetate (Compound 142); (kkkkkk) 8-Cyclopentyl-5-methyl-2- (4-piperidin-1-yl-phenylamino) -8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 143); (lily) 8-Cyclopentyl-5-methyl-2- [4- (4-methyl-piperazin-1 -yl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 144); (mmmmmm) N-. { 1 - [4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) -phenyl] -piperidin-4-yl} -acetamide (Compound 145); (nnnnnn) 8-Cyclopentyl-5-methyl-2- (4-piperazn-1-yl-phenylamine) -8H-pyrido [2,3-d] pyrimidin-7-one trifluoroacetate (Compound 146); (oooooo) 8-Cyclopentyl-6-fluoro-5-methyl-2- (piperazin-1-yl-phenylamino) -8H-pyrido [2I3-d] pyrimidin-7-one (Compound 147); (pppppp) 6-iodo-8-cyclopentyl-l-5-methyl-2- (4-piperazin-1-yl-phenylammene) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 148 ); (qq) 2- [3-Chloro-4- (3-amino-pyrroidin-1-yl) -phenylamino] -8-cyclopentyl-5-methyl-8H-pyrido [2,3-d] pyrimidin-7 trifluoroacetate -one (Compound 149); (rrrrrr) 8-Cyclopentyl-5-methyl-2- [4- (4- (2, 2, 2-trifluoroethyl) -piperazin-1-yl) -phenylamine] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 150); (ssssss) 8-Cyclopentyl-2- (4-f luoro-f in i lamine) -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 151); (tttttt) 8-Cyclopentyl-5-methyll-2-phenyiyaniino-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 152); (uuuuuu) 8-Cicl opent il-2- (3,4-iclorofeni lami) -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 153); (vvvvvv) 8-lsopropyl-5-methyl-2- (4-piperazin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one trifluoroacetate (Compound 154); (wwwwww) 8-lsopropyl-5-methyl-2- [4- (4-propionyl-piperazin-1 -yl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 155); (xxxxxx) 8-Cyclohexyl-5-methyl-2- (4-piperazin-1-l-phenylamino) -8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 156); (yyyyyy) 2-. { 4- [4- (3-Morpholin-4-yl-propyl) -piperidin-1-yl] -phenylamino} -8-cyclohexyl-6-fluoro-5-methyl-8H-pyrido [2,3-d] pyrimidine-7-one (Compound 157); (zzzzzz) 8-Cyclopentyl-5-methyl-2- [4- (2H-1, 2,4-triazol-3-ylsulfanylmethyl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 158); (aaaaaaa) 8-Cyclo? entyl-5-methyl-2- [4- (2H-1, 2,4-triazol-3-sulfinylmethyl) -phenylamino] -8H-pyrido [2,3-d] pyrimidine-7 -one (Compound 159); (bbbbbbb) 8-Cyclopentyl-5-methyl-2- [4- (2H-1, 2,4-triazole-3-sulfonylmethyl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 160); (ccccccc) 8-Cyclopentyl-5-methyl-2- [4- (5-oxo-4,5-dihydro-1, 2,4-oxadiazol-3-ylmethyl) -phenylamino] -8H-pyrido [2,3 -d] pyrimidin-7-one (Compound 161); (ddddddd) 8-Cyclopentyl-5-methyl-2-. { 4- [2- (2H-1, 2,4-triazol-3-ylsulfanyl) -ethyl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 162); (eeeeeee) 8-Cyclopentyl-5-medyl-2-. { 4- (2- (2H-1, 2,4-triazol-3-suityfin) -ethyl] -phenylamino} - 8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 163), ( fffffff) 8-Cyclopentyl-5-methyl-2- { 4- [2- (2H-1, 2,4-triazole-3-sulfonyl) -ethyl] -phenylamino} -8-pyrido [2, 3-d] pyrimidine-7-one (Compound 164); (gg gg) 8-Cyclopentyl-5-methyl-2-. {4- (2- (5-oxo-4,5-dihdro-1,2) , 4, -oxadiazol-3-yl) -ethyl] -phenylamino.} - 8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 165); (hhhhhhh) 8-Cyclopentyl-5-methyl-2- [4- (3H-1, 2,3-triazol-4-ylsulfanylmethyl) -phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 166); (iiiiiii) 8-Cyclopentyl-5-methyl-2-. { 4-t2- (3H-1, 2,3-triazol-4-ylsulfanyl) -ethyl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 167); (iiiiiii) 8-Cyclopentyl-5-methyl-2-. { 4- [4- (5-oxo-4,5-dihydro-1, 2,4-oxadiazol-3-yl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 168); (kkkkkkk) 8-Cyclopentyl-5-methyl-2-. { 4- [4- (2H-1, 2,4-triazol-3-ylsulfanyl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 169); 8-Cyclopentyl-5-methyl-2-. { 4- (2H-1, 2,4-triazole-3-sulfinl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 170); (mmmmmmm) 8-Cyclopentyl-5-methyl-2-. { 4- [4- (2H-1, 2,4-triazole-3-sulfonyl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 171), mp 235-237 ° C: (nnnnnnn) 8-Cyclopentyl-5-methyl-2 ~. { 4- [4- (2H-tetrazol-5-yl) -piperidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 172); (ooooooo) Acid (1 H-tetrazol-5-yl) -amidca of 1 - [4- (8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidine -2-ylamino) -phenyl] -piperidine-4-carboxylic acid (Compound 173); (ppppppp) 8-Cyclopentyl-5-methyl-2-. { 4- [4- (3H-1, 2,3-triazol-4-ylsulfanyl) -piperidin-1-l] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 173); (qq) 3- [4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) -phenyl] -N- (1 H) -tetrazol-5-yl) -propionanamide (Compound 174); (rrrrrrr) 2- [4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) -phenoxy] -N- (1 H -tetrazol-5-yl) -acetamide (Compound 175); (sssssss) 8-Cyclopentyl-5-methyl-2- [4- (5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl-methoxy) -f-en-amino] -8H-pyrido [ 2,3-d] pi rim id n-7-one (Compound 176); (ttttttt) 8-Cyclopentyl-5-methyl-2- (4-. {4- [2- (2H-1, 2,4-triazole-3-sulfinyl) -ethyl] -piperidin-1-yl} phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 177); (uuuuuuu) 8-Cyclopentyl-5-methyl-2- (4- { 4- [2- (2H-1, 2,4-triazol-3-sulfonyl) -ethyl] -piperidin-1-yl.} .phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 178); (vvvvvvv) 8-Cyclopentyl-5-methyl-2- (4- { 4- [2- (3H-1, 2,4-triazol-4-ylsulfanyl) -ethyl] -piperidin-1-yl.} .phenylamino) -8H-pyrido [2,3-dpyrimidin-7-one (Compound 179); (wwwwwww) 8-Cyclopentyl-5-methyl-2- (4-. {4- [2- (2H-1, 2,4-triazole-3-sulfanyl) -ethyl] -piperidin-1-yl} phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 180); (xxxxxxx) 8-Cyclopentyl-5-methyl-2- (4-. {4- [2- (5-oxo-4,5-dihydro-1, 2,4-oxadiazol-3-yl) -ethyl] -piperidin-1 -M.}. -phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 181); (yyyyyyy) 8-Cyclopentyl-5-methyl-2-. { 4- [4- (2-oxo-2,3-di-idro-1, 2,3,5-oxathiadiazol-4-yl) -pipendin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 182); (zzzzzzz) 8-Cyclopentyl-2-. { 4- [4- (2, 2-dioxo-2,3-dihydro-1, 2,3,5-oxathiadiazol-4-yl) -piperidin-1-yl] -phenylamino} -5-methyl-8H-pyrido [2,3-d] pyridin-7-one (Compound 183); (aaaaaaaa) 8- (Cyclopentyl-5-methyl-2- { 4- [4- (1-oxo-2,5-dihydro-1 H-1, 2,3,5-thiatriazol-4-yl) -piperidin-1-yl] -phenylamino.}. -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 184); (bbbbbbbb) 8- (Cyclopentyl-2- { 4- [4 - (1,1-dioxo-2,5-dihydro-1 H-1, 2,3,5-thiatriazol-4-yl) -piperidin-1-yl] -phenylamino.} - 5-methyl-8H- pyrido [2,3-d] pyrimidin-7-one (Compound 185); (cccccccc) N- { 1 - [4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido [2,3-d] pyrimidin-2-ylamino) -phenyl] -piperidine-2-carbonyl.] - methanesulfonamide (Compound 186); (dddddddd) 8-Cyclopentyl-5-methyl-2-. {4 - [3- (2H-1, 2,4-tnazol-3-ylsulfanyl) -pyridinidin-1-yl] -phenylamino] -8H-pyrido [2,3-d-pyrimidin-7-one (Compound 187); (eeeeeeee) 8-Cyclopentyl-5-methyl-2- { 4- [3- (2H-1, 2,4-triazol-3-sulfinyl) pyrrolidin-1-yl] -phenylamino} -8H- pyrido [2,3-d] pyrimidin-7-one (Compound 188); (ffffffff) 8-Cyclopentyl-5-methyl-2-. { 4- [3- (2H-1, 2,4-triazole-3-sulfonyl) -pyrrolidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 189); (ggggg gg) 8-Cyclopentyl-5-methyl-2-. { 4- [3- (3 H-1,2,3-triazol-4-ylsulfanyl) -pyrrolidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 190); (hhhhhhhh) 8-Cyclopentyl-5-methyl-2-. { 4- [3- (5-oxo-4,5-dihydro-1, 2,4-oxadiazol-3-yl) -pyrrolidin-1-yl] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 191); (iiiiiiii) 8-Cyclopentyl-5-methyl-2-trifluoroacetate. { 4- [4- (3-h i droxi propi I) piperidin-1-yl] -f in i lami no} -8H-p irido [2,3-d] pyrimidin-7-one (Compound 192); Giijjjjj) 8-Cyclopentyl-5-propyl-2- (4-piperazin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one trifluoroacetate (Compound 193); (kkkkkkkk) 8-cyclopentyl-l-5-ethyl-2- (4-pi pe razin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 194); 8- (1-Methylethyl) -5-ethyl-2- (4-piperazin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 195); (mmmmmmmm) 8- (1-Methylethyl) -5-ethyl-2- (4-piperazin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidin-7-one trifluoroacetate (Compound 196); (nnnnnnnn) 8-Cyclopentyl-5-methyl-2- [4- (3-hydroxypyrrolidin-1-yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 197); (oooooooo) 8-Cyclopentyl-5-ethyl-2- [4- (4-acetylpiperazin-1-yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 198), (pppppppp) 8-Cyclopentyl-5-methyl-6-fluoro-2- [4- (4-acetylpiperidin-1-yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 199) ); (qq) 8-Cyclopropyl-5-methyl-2- [4- (4-acetamidopiperidin-1-yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 200) (rrrrrrrr) 8-Cyclopentyl-5-methyl-2- [4- (homopiperazin-1 -yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one hydrochloride (Compound 202); (ssssssss) 8-Cyclopentyl-5-methyl-6-fluoro-2- [4- (homopiperazin-1-yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one hydrochloride Compound 203); (tttttttt) 8-Cyclopentyl-5-methyl-6-fluoro-2- [4- (3,3-dimethyl-4-acetylpiperazin-1-yl) phenylamino] -8H-pyrido [2,3-d] pyrimidine- 7-one (Compound 204); (uuuuuuuu) 8-Cyclopentyl-5-methyl-2- [4- (3,3-dimethyl-4-acetylpiperazin-1-yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one ( Compound 205); (vvvvvvvv) Trifluoroacetate 8-cyclopentyl-5-methyl-6-fluoro-2- [4- (4-methyl piperazi- n-1 -yl) f eni lami] -8H-pyrido [2, 3-d] pyrimidin-7-one (Compound 206); (wwwwwwww) 8-Cyclopentyl-5-methyl-2- [4- (N-methylacetamido) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 207); (xxxxxxxx) 8-Cyclopentyl-5-metii-2-. { 4- [2- (2-hydroxyethoxy) ethylamino] -phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 208); (yyyyyyyy) 8-Cyclopentyl-5-methyl-2- [4- (3-oxopiperazin-1-yl) phenylamino] -8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 209); (zzzzzzzz) 8-Cyclopentyl-5-methyl-2- [4- (2-methoxyethoxy) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 210); (aaaaaaaaa) 8-Cyclopentyl l-5-methyl-2- (9H-carbazol-3-ylamino) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 211); (bbbbbbbbb) 8-Cyclopentyl-5-methyl-2- (1 H -indazol-5-yl) amino-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 212); (ccccccccc) 8-Cyclopentyl l-5-methyl-2- (2-acetylbenzofuran-5-yl) amino-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 213); (ddddddddd) 8-Cyclopentyl-5-methyl-2 - [(4-piperidin-1-yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 214); (eeeeeeeee) 8-Cyclopentyl-5-methyl-2- (2,3-dimethylindol-5-yl) amino-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 215); (fffffffff) 8-Cyclopentyl-5-isopropyl-2- [4- (3,5-methyl-4R-am? nomethyl-pyrrolidin-1-yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7- ona (Compound 216); (ggggggggg) 8-c¡ciopentii-5-met¡? -2-. { 4- [4- (2-hydroxyethyl) piperazin-1-yl]] phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 217); (hhhhhhhhh) Salt of 8-Cyclopentyl-5-methyl-2- acid. { 4- [4- (3-morpholinopropyl) piperidin-1-yl] phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one trifluoroacetic acid (Compound 218); (iiiiiiiii) 8-Cyclopentyl-5-methyl-2- (benzofuran-5-yl) amino-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 219); (jjjjjjjjj) 8-Cyclopentyl-5-methyl-2- (indol-5-yl) amino-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 220); and (kkkkkkkkk) 8-Cyclopentyl-5-methyl-2- (thionephth-5-yl) amino-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 221); 8. A compound selected from the group consisting of: 8-Cyclo? Entyl-6-iodo-5-methyl-2- (4? -perazin-1-yl-phenylamino) -8H-pyrido [2,3-d] pyrimidine- 7-one (Compound 225); 8 Cyclopentyl-2-. { 4- [1 - (3,5-dimethyl-piperazin-1-yl) -methanoyl] -phenylamino} -5-methyl-8H-pyrido [2,3-d-] pyrimidin-7-one (Compound 226); 8-Cyclopentyl-2- [4- (3,5-dimethyl-piperazin-1-yl) -phenylamino] -5-trifluoromethyl-8H-pyrido [2,3, -d] pyrimidin-7-one (Compound 227); 6-Bromo-8-cyclopentyl-2- [4- (3, 3-d imeti l-piperazin-1-yl) -phenylamino] -5-methyl-8H-pyrido [2,3-c] pyrimidine -7-one (Compound 228); 8-Cyclopentyl-2- [4- (3,5-dimethyl-piperazin-1-yl) -phenylamino-6-iodo-5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 229); 6-Chloro-8-cyclopentyl-2- [4- (3,5-dimethyl-piperazin-1-yl) -phenylamino] -5-methyl-8H-pyrido [2,3-c.] Pyrimidin-7-one (Compound 230); 8-Cyclopentyl-5-methyl-2- [4- (1 H- [1, 2,4] tr.iazol-3-ylsulfanyl) -phenylamino] -8H-pyrido [2,3-o '] pyrimidin-7 -one (Compound 231); 4- [4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-o '] pyrimidin-2-ylamino) -phenyl] -piperazine -1-carbaIdehyde (Compound 232); 8-Cyclopentyl-2- (4-piperazin-1-yl-phenylamine) -5-trifluoromethyl-8H-pyrido [2,3-c.] Pyrimidin-7-one (Compound 233); 8- (1-Ethyl-propyl) -5-methyl-2- (4-piperazin-1-yl-phenylamino) -8 / -pyrido [2,3-c.] - piperidin-7-one (Compound 234) ); Acid [4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyr [do-2,3-dl-pyrimidin-2-ylamino] -benzyl] -phosphonic acid (Compound 235); 6-Chloro-8-cyclopentyl-5-methyl-2- (4-piperazin-1-yl-phenylamino) -8 / - / - pyrido- [2,3-c] pyrimidin-7-one (Compound 236); 2- [4- (3,5-Dimethyl-piperazin-1-yl) -phenylamino] -8- (1-ethyl-propyl) -5-methyl-8H-pyrido [2,3-d] pyrimidin-7- ona (Compound 237); 8-Cyclopentyl-2- [4- (2-hydroxy-ethylamino) -phenylamino] -5-methyl-8-pyrido [2,3-d] pyrimidin-7-one (Compound 238); 3- [4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) -phenyl] - / V ,? -diethyl-propionamide (Compound 239); 8-Cyclopentyl] -6-fluoro-2- [4- (2-hydroxy-ethyl) -phenylamino] -5-methyl-8 / - -pyrido [2,3-d] pyrimidin-7-one (Compound 240); 8-Cyclopentyl-2- [4- (2-hydroxy-ethyl) -phenylamino] -5-methyl-8H-pyrido [2,3-d] -pyrimidin-7-one (Compound 241); 4- (8-Cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-ylamino) -benzoic acid (Compound 242); 8-Cyclopentyl-2- [4- (3,3-dimethyl-piperazin-1-yl) -phenylamino-3-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 243); [4- (8-Cyclopentyl-5-methyl-7-oxo-7, 8-dih-idro-pyrido [2,3-d] pi-di-2-ylamino) -benziI] -f osf ion (Compound 244); 8-C i clopent i I -6-f I uoro-2- [4- (2-methoxy-eti la no) -phenylamino] -5-methy1-8H-pyrido [2,3-d] pyrimidine- 7-one (Composite 245); (S) -2-Amino-3- [4- (8-cyclopentyl-6-fluoro-5-methyl-7-oxo-7,8-dihydro-pyrido [2,3-d] pyrimidin-2-acid] ilamino) -phenyl] -propionic (Compound 246); 8-C iclopentyl-2- [4- (2-methoxy-ethoxy) -f eni lami] -5-methyl-8H-? Irido [2, 3-d] -? Irimidin-7-one (Compound 247); S-Cyclopentyl-2- (4-isopropylamino-f eni lami) -5-methyl-8 H -pyrido [2,3-d] -pyrimidin-7-one (Compound 248); 8-Cyclopentyl-2- (4-hydroxy-3,5-dimethyl-l-phenylamino) -5-methyl-8 H -pyrido [2,3-d] -pyrimidin-7-one (Compound 249); 8-Cyclopentyl-6-fluoro-2- (4-hydroxy-3,5-dimethyl-1-phenylamino) -5-methyl-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 250); 8-C icl opent i I -6-f I uoro-2- (4-hydroxy-3,5-di-methyl-phenyl-amino) -5-methyl-8H-pyrido [2,3-d] pyrimidin-7- ona (Compound 251); 9. A pharmaceutical composition, characterized in that it comprises a compound selected according to claim 1, in combination with a pharmaceutically acceptable carrier, diluent, or excipient. 10. A method for controlling proliferative disorders selected from the group consisting of cancer, psoriasis, isovascular vascular muscle proliferation, associated with a disorder selected from the group consisting of atherosclerosis, postoperative vascular stenosis, and restenosis in mammals that comprises administering to said mammal a therapeutically effective amount of a compound according to claim 1. eleven . A method for inhibiting a cyclin-dependent kinase, characterized in that it comprises contacting the cyclin-dependent kinase with a compound selected according to claim 1. 12. A method according to claim 1, characterized in that such a cyclin-dependent kinase is cdk4. 13. A method for inhibiting a growth factor-mediated tyrosine kinase, characterized in that it comprises contacting such a growth factor-mediated kinase with a compound selected according to claim 1. 14. A method according to claim 13, characterized in that such tyrosine kinase mediated by growth factor is platelet-derived growth factor (PDGF). 15. A method according to claim 1 3, characterized in that such growth factor-mediated tyrosine kinase is fibroblast growth factor (FGF). 16. A method for treating a subject suffering from diseases caused by vascular smooth muscle cell proliferation, characterized in that it comprises administering to said subject a therapeutically effective amount of a compound selected in accordance with claim 1. 17. A method for treating a subject suffering from cancer, characterized in that it comprises administering to said subject a therapeutically effective amount of a compound selected according to claim 1. 18. 6-Bromo-8-ci clopent j | -2- (4- (3, 5-di meti I piperazi p-1-yl) -phenylamino) -5-methyl-8H-pyrido [2, 3-d ] pyrimidin-7-one. 19. 8-Cjclopentyl-6-fluoro-5-metii-2- [4- (piperazin-1 -jl) -phenylamino] -8H-pyrido [2,3-d | pyrimidin-7-one. 20. 8 ^ Cyclopentyl-5-methyl-2- (carbazol-3-yl) -8H-pyrido [2,3-d] pyrimidin-7-one. twenty-one . A compound selected from 8-Cyclopentyl-5-methyl-2- (9H-parbazol-3-yl-amine) -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 211); 8-C i clopenti I -5-met i I -2- (1 H -indazol-5-yl) amino-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 212); 8-Cyclopentyl-5-methyl-2- (2-acetylbenzofuran-5-yl) amino-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 213); 8-Cyclopentyl-5-methyl-2 - [(4-pi'peridin-1-yl) phenylamino] -8 H -pyrido [2,3-d] -pyrimidin-7-one (Compound 214); 8-Cyclopentyl-5-methyl-2- (2,3-dimethylindol-5-yl) amino-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 215); 8-Cyclopentyl-5-isopropyl-2- [4- (3,5-methyl-4R-aminomethylpyrrolidin-1-yl) phenylamino] -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 216); 8-Cyclopentyl-5-methyl-2-. { 4- [4- (2-hydroxyethyl) piperazin-1-yl]] phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 217),; 8-Cyclopentyl-5-methyl-2-. { 4- [4- (3-morfoinopropyl) piperidin-1-yl] phenylamino} -8H-pyrido [2,3-d] pyrimidin-7-one (Compound 217); 8-Cyclopentyl-5-methyl-2- (benzofuran-5-yl) amino-8 H -pyrido [2,3-d] pyrimidin-7-one (Compound 219); 8-Cyclopentyl-5-methyl-2- (indol-5-yl) amino-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 220); and 8-Cyclopentyl-5-metii-2- (thionaphth-5-yl) amino-8H-pyrido [2,3-d] pyrimidin-7-one (Compound 221);