MXPA99011792A

MXPA99011792A - Naphthyridinones for inhibiting protein tyrosine kinase and cell cycle kinase mediated cellular proliferation

Info

Publication number: MXPA99011792A
Application number: MXPA/A/1999/011792A
Authority: MX
Inventors: Alexander Denny William; Myra Dobrusin Ellen; Robert Barvian Mark; Daniel Hollis Showalter Howard; Mark Thompson Andrew; Wu Zhipei; Marino Hamby James; Thomas Winters Roy
Original assignee: Robert Barvian Mark; Alexander Denny William; Myra Dobrusin Ellen; Marino Hamby James; Daniel Hollis Showalter Howard; Mark Thompson Andrew; Warnerlambert Company; Thomas Winters Roy; Wu Zhipei
Priority date: 1997-08-20
Filing date: 1999-12-15
Publication date: 2000-06-01

Abstract

Naphthyridinones of Formula (I) are inhibitors of PTKs and cell cycle kinases, and are useful in treating cellular proliferation. The compounds are especially useful in treating cancer, atherosclerosis, restenosis, and psoriasis.

Description

NAFTIR1DINONES TO INHIBIT THE PROLIFERATION C1NASA, = - l T? ROSIN A AND THE CELL PHONE CYCLE AD URANTE LA \ t CELL PROLIFERATION 'i - • 1 FIELD OF THE INVENTION This invention refers to the inhibition of cell proliferation mediated by the = 7"'Protein tyrosine kinase (PTK) and cell cycle kinase More specifically, this invention relates to NAFTIRIDINONES and their use in the inhibition of cell proliferation and the enzymatic activity of PTK or cell cycle kinase, t BACKGROUND OF THE INVENTION Many disease states are characterized by the uncontrolled proliferation and differentiation of the cells.These disease states encompass a variety of types of cells and diseases such as cancer, atherosclerosis, restenosis and psoriasis. Growth factor stimulation, autophosphorylation and phosphorylation of intracellular protein substrates are biological events. important in the pathomechanisms of proliferative diseases.

In normal cells, phosphorylation of tyrosine residues on protein substrates serves a critical function in the growth signaling pathways 11. _ > Intracellular initiation by extracellular growth factor receptors For example, the association of growth factors such as the platelet derived growth factor (PDGF), fibroplast growth factor (FGF) and t epidermal growth factor ( EGF) with its respective extracellular receptors, PDGFr, FGFr and EGFr, activates the domains of the intracellular tyrosine kinase enzyme of these receptors, which catalyses the phosphorylation of any receptor substrates intracellular eyes. per se. Phosphorylation of growth factor receptors in response to ligand binding is known as autophosphorylation.

For example, the EGF receptor has its two most important ligands, EGF and the transforming growth factor a, (TGFa). The receptors appear to have as much (only minor functions in normal adult humans, but are involved in the disease processes). of a large portion of all cancers, especially colon cancer and breast cancer. Closely related receptors Erb-B2 and Erb-B3 have a family of heregulins as their major ligands, and overexpression and mutation 4 of the receptor are have shown no room for mistakes as the major risk factor in breast cancer of poor prognosis Dilecta proliferation and migration of vascular smooth muscle cells f I (VSMC) on important components in processes such as vascular remodeling, restenosis and atherosclerosis Platelet-derived growth factor has been identified as one of the mitogens and Endogenous VSMC chemoattractants, more potent. The high expression of vascular mRNA chains of PDGF-A and -B and PDGF receptors has been observed in balloon-induced rat carotid arteries (J Cell, Biol., 1990, 1111: 2149-2188). Infection, PDGF infusion also greatly increases thickening and intimate migration of VSMC (J Clin Invest, 1992.89 507-51 1) In addition, the antiquarian drugs that ncuti align PDGF i significantly promote intimate fattening after the balloon injury (Science, 1991,25371129 - 1132). Tyrosine kinase inhibitors of the trifostinyl receptor that block the path of transduction of the PDGF signal have been shown to inhibit Phosphorylation of receptor tyrosine kinase stimulated with PDGF m alive in the lesion model. of wives in rats (Drug Develop Res, 1993,29 158 - 166) The growth factor of acidic fibroblasts (aFGF) and at the same time the growth factor of basic fibroblasts (bFGF) have many biological activities, including the ability to promote cell proliferation and differentiation. It has been reported as direct evidence of the support of the intervention of FGF in VSMC by Lindner and ~ Reidy (Proc Nati Acad Sci USA, 88 3739-3743 (1991)), who demonstrated that systemic injection of a neutralizing antibody against bFGF prior to balloon angioplasty of the rat cayotid arteries inhibited SMC proliferation = ~ r mean induced by the lesion in more than 80% when measured 2 days after the injury It is likely that the bFGF released by damaged cells is acting in an i paracrine fashion to induce the growth of VSMC. Recently, Lindnei and Reidy (Cir.

Res, 199 and 3.73 589-595) demonstrated a higher expression of mRNA for bFGF and FG! FR-1 in the epile of VSMCs and endothelium in facet preparations of balloon-induced rat carotid arteries The data provide evidence that in injured arteries the ligand / receptor system of bFGF and FGFR-1 may be involved in the response 1 Proliferative proliferative of VSMCs which leads to neointima formation Buchdunger, et al, Proc Nati Acad Sci, 1995.92 2558-2562, reported the inhibition of the transduction pathway of the PDGF signal at the same time or in vitro and in vivo by an inhibitor of the protein tyrosine kinase receptor reagent of PDGF The compound demonstrated antitumor activity in tumor model using astrocytoma cell lines Thus, EGF, PDGF, FGF and other growth factors play central roles in the pathomechanisms of cell proliferative diseases such as cancer. * i atherosclerosis, and restenosis After association with their respective receptors, these [growth factors stimulate tyrosine kinase activity as one of the initial biochemical events that lead to DNA synthesis and cell division. Thus it follows that Compounds that inhibit PTKs related to the signal transduction pathways of intracellular growth factor are useful as agents for the treatment of cellular proliferative diseases We have now discovered that certain NADPHYRIDINONES inhibit PTKs, and are useful in the treatment and prevention of atherosclerosis , restenosis and cancer The Src family of tyrosine kinases is involved in a number of cell signaling pathways. For example, Sic is involved in the growth factor receptor signaling, enterograde mediated signaling, T- and B cell activation and activation. osteoclast It is known that Src binds to several receptor tyrosine kinases and does not key receptors such as tyrosine kinases that contain receptors for PDGF, EGF, HER2 / Neu (an oncogene form of EGF), fibroplast growth factor, focal adhesion kinase, pl30 protein, and p68 protein Furthermore, it has been shown that pp60 - src is involved in the regulation of DNA synthesis, mitosis and other cellular activities «- -t The kinases of the cell cycle are enzymes of natural occurrence involved in the regulation of the cell cycle (Meijer L," chemical inhibitors of cyclin-dependent kinases ", Progress in Cell Cycle Research, 1995,1 351 - 363 ) Typical f enzymes include the cyclin-dependent kinases (cdk) cdkl, cdk2, cdl < 4, cdk5, cdkó and kinase wee - 1 It has been shown that the increased activity or temporary abnormal activation of these kinases results in the development of human tumors and other proliferative disorders such as restenosis i1 Compounds that inhibit cdks, either by blocking the interaction between a cyclin and its respective kinase, or via co-linkage and inactivation of the kinase, cause the inhibition of cell proliferation, and are thus useful for treating tumors or other cells in abnormal proliferation, Several compounds that inhibit cdks have shown activity at the same time =. i preclinical and clinical antitumor For example, flavopiridol is a flavonoid that has been shown to be a potent inhibitor of cancerous types of breast and lung cancer cells (Kaur, et al - J natl cancer Inst, 1992,84 1736 - 1740, lat J Oncol , 1996.9 1143-1168) The compound has been shown to inhibit cdk2 and cdk4 Olomoucin, [2- (hydroethylamine) -6-benzylamine-9-methylpurine is a potent inhibitor! of cdk2 and cdk5 (Vesely, et al, Eur J Biochem, 1994,224 • - 771-786), and has shown inhibition of the proliferation of approximately 60 different human tumor cell lines used by the National Cancer Institute (NCI) to select new therapies against cancer (Abraham, et al, Cell Biology, 1995,83 105-120) In spite of the progress that has been made, the search for low molecular weight compounds that are orally bioavailable and useful for treating a wide variety of human tumors and other proliferative disorders such as stenosis and iherosclerosis IZ 1 + continues. The present invention provides compounds that inhibit PTKs and cell cycle kinases.

SUMMARY OF THE INVENTION The present invention provides compounds that have the Formula where: - it is absent or a link: R1 is 2 is C, -C6 alkyl, cycloalkyl, or bicycloalkyl CN, 2, "each R1 is independently liidiogenic or C-C alkyl," each n is independently from 0 to 7; I rent / \ -o- (CH2) n- - N N K \ / / \ -O- (CIl2) lT-N, N-C c. I rent \ / R • 3 / -O- (CH2) lT-N c - c j C () alkyl II (CH2) n COC j C6 i n | q? Li | 0 II (Ci? 2) n - with, Xes, R5 is hydrogen, halogen, anl, substituted aliyl, heteioaiyl or substituted heteioaiyl faimaceulicamenle acceptable salts thereof In an illicit example of the compounds of Foimula I, I Iood exemplified pieclileclo, and is.-O (CII2) "- X.

In otio ejemplai piedilccto, In olio ejemplai piedilccto, , R3 R3 / / IV is; - N - (CII2) n - N \ 3 RJ N olioejemphii piedileclo, R1 is - NI I - (CT I2) "- N (CIICTI,) 2 In olio exemplai piedilecto, R5 is phenyl or substituted phenyl In otio ejcmplai piedilecto, R is 2,6-dicloiofenil _En otio Exemplary piedileclo, R2 is methyl nitrile exemplary piedilecto, R5 is 2,6-dicloiofenil and R2 is methyl In olio exemplary piedilecto, the present invention piopoiciona compounds _7-amino-3 - (2,6-dichloiolenyl) -1-methyl-III- [l, 6Jnalli? Id'n-2-one, -3- (2,0-clicloioenil) - 7 - di niel i la my no - I -mctil - 111 - | l, 6 | napi? iclin - 2? - ona, 3 - . 3 - (2,6-Dichloiophenyl) -7- [2 - (diethylamino) ethylamino-1-methyl I-1H - [1,1,6-naphthi? Idi? - 2-one, 3 - (2,6-dichloiophenyl) - 7 - [3 - (diethylamido) ethylamino - 1 - metif - 1 H [1, 6] nalyi - idin - 2 - one, 3 - (2,6 - dicyclophenyl) -7- | l-dictylamino) ethylamino-I-mctyl-III [l, 6]? allyichyl-2-one, 3 - (2,6-dicl ioyenyl) -7- [5 - ( diethylamino) ethylamino-1-methyl 1H- [1, 6] nalli? idin-2-one, 3 - (2,6-dicl? iiophenyl) -1-methyl-7 - [3 - (4-methyl-piperazin-1- il) piopilamino] - III - f 1, 6] nafli? iclin -2 -ona, 3 - (2,6 - icloi? lenil) - I - inelil - 7 - [4 - (4 - melilpipeiazin - I - il) piopilaminoj f II - [I, 6] nalli ?? d? n -2 -one, 3 - . 3 - (2,6-Dichlorophenyl) -1-methyl-7 - [5 - (4-methylpiperazin-1-yl) propylamino] -1H- [1,6] nañiridin-2-one, 3 - (2.6 - dichlorophenyl) - 1-methyl-7 - [3 - (4-morpholino) propylamino] -1H - [1, 6] naphthyridin-2-one, 'l 3 - (2,6-dichlorophenyl) - 7 - [3 - (imidazol-1-yl) propylamino] - 1 H - [1,6] naphthyridine! - 2-one, 3 - (2,6-dichlorophenyl) -1-methyl-7 - (phenylamino) -1H - [1, 6] naphthyridin-2-one, 3 - (2,6-dichlorophenyl) -1 - methyl-7 - (4-pyridylamino) -1H - [1, 6] naphthyridin-2-s, 1-one, 3- (2,6-dichlorophenyl) -7 - [(4-methoxyphenyl) amino] -1H - [1, 6] naftipdin-2-one, 3 - (2,6-dichlorophenyl) -7 - [(4 - (2-diethylamino) ethoxy) phenylamino] 1-methyl-1 H [1, 6] naphthyridin-2 - ona, 3 - (2,6-dichlorophenyl) -1-methyl-7 - [4 - (4-moi-folino) butylamino] -1H - [1, 6] naphthyridin-2-one, 1 3 - (2, 6-dichlorophenyl) -7 - [(4 - (3-dieylamino) propoxy) phenyl) amino] 1-methyl-1 H - [1,6] naphthyridin-2-one, 3 - (2,6-dichlorophenyl) - 1-methyl-7 - [(4 - (2 - (4-methylpiperazin-1-yl) ethoxy) phenyl) amino] -1H - [l, 6] naphthyridin-2-one,, 3 - - (2,6-dichlorophenyl) -1-methyl-7 - [(4 - (3 - (4-met ylpiperazin-1-yl) propó ixi) phenyl) amino] - 1 H - [1, 6] naphthyridin-2-one,! 3 -172,6-dichlorophenyl) -1-methyl-7 - [(4 - (4 - (4-methylpipeiazin-1-yl) propoxy) t-phenyl) amino] -1 H - [1,6] naphthyridine - 2 - ona, _ _ f 7-amino-1 H - [1, 6] naphthyridin-2-one, 7-amino-1-ethyl-1 H - [1,6] naphthyridin-2-one, 7-fluoro-1 - ethyl-1 H - [1,6] naphthyridin-2-one, 1 - . 1 - . 1-ethyl-7-phenylamino-1 H - [1,6] naphthyrin-2-one, 1-ethyl-7 - (4-methoxyphenylamino) - 1 H - [1,6] naphthyridin-2-one, 1-ethyl - 7 - [4 - (4-Methylpiperazin-1-yl) phenylamino] - 1 H - [1, 6] naphthyridin-2-one. 1 ^ ethyl-7 - (4 - (morpholin-4-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one, 1-ethyl-7 - (4 - (piperidin-1-yl) phenylamino) - 1 H - [1, 6] naphthyridin-2-one, 1-ethyl-7-phenylamino-3,4-dihydro-1 H - [1, 6] naphthyridin-2-one, 7 n [4 - (2 - ( diethylamino) ethoxy) phenylamino] -1-ethyl-1 H - [1,6] naphthyridin-2-oria, 7 - [4 - (3 - (diethylamino) ethoxy) phenylamino] -1-ethyl-1H- [1,6 ] naphthyridin-2-one, 1 1 -ethyl-7 - [4 - (2 - (4-methylpiperazin-1-yl) ethoxy) phenylamino] -1,6-naphyridin 2 - . 2-one, 1-ethyl-7 - [4 - (3 - (4-methylpiperazin-1-yl) ethoxy) phenylamino] -1,6-naphthyridin-2-one. 1-ethyl-7 - (4-pyridylamino) -1H - [1, 6] naphthyridin-2-one, 1-netyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] - 1H - [l , 6] nañiridin - 2 ona. 1-isopropyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] -1H - [1, 6] nañiridin-i 2 -one,? 1-Isopentyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] -1H - [1, 6] naphthyridin-i 2-one, [ 7 -. 7 -. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylphenylamino} - 1 - isopropyl-1H [1, 6] naphthyridin-2-one,! r 7 -. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylphenylamino} - 1 - isopentyl - 1H [1, 6] naffiridin-2-one, 1-cyclopentyl-7-. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylphenylamino} - 1 HOUR [1, 6-nañiridin-2-one, 1-cyclohexyl-7-. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylphenylamino} - l'H [l, 6] naphthyridin-2-one, 1-cyclopentyl-7 -. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-yl] phenylamino} - 1H - [1, 6] naphthyridin-2-one, ___ i i. t 1 - ^ bicyclop 2 ljhept - 2 - il - 7 -. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-yl] phenylamino} - 1 H - [1, 6] naphthyridin-2-one, 1-methyl-7 - (4 - (pyrazol-1-yl) enylamino) -1H - [1, 6] naphthi? Idin-2-one, 1 - ethyl-7 - (4 - (pyrazol-1-yl) phenylamino) - 1 H - [1, 6] naphthyridin-2-one, - 1-jsopropyl-7 - (4 - (pyrazol-1-yl) phenylamino) - 1 H - [1, 6] naphthyridin-2-one,, 1-isopentyl-7 - (4 - (pyrazol-1-yl) phenylamino) - 1 H - [1, 6] naphthyridin-2-one,,, 1 f 1 -cyclopentyl-7 - (4 - (pyrazol-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one, i 1-cyclohexyl-7 - (4 - (pyrazol-1-yl ) phenylamino) -1H - [1, 6] naphthyridin-2-one, 1-cycloheptyl-7 - (4 - (pyrazol-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one , 1-bicyclo [2 2 ljhept-2-yl-7 - (4 - (pyrazol-1-yl) phenylamino) -1H • [1, 6] naphthyridin-2-one, 7 - (4-fluorophenylamino) -1-methyl-1H- [1, 6] naphthyridin-2-one, 1-ethyl-7 - (4-fluorophenylamino) -1H - [1, 6] naphthyridin-2-one, 7 - (4-fluorophenylamino) -1-isopropyl-1H- [1, 6] naphthyridin-2-one, 7 - (4-fluorophenylamino) -1-isopentyl-1H - [I, 6nailirid? N - 2 - one, 1-Cyclopentyl-7 - (4-fluorophenylamino) -1H - [1, 6] naphthyridin-2-one, 1-cyclohexyl-7 - (4-fluorophenylamino) -1H - [1, 6] naphthyridin-2-one, 1-cycloheptyl-7 - (4-fluorophenylamino) -1H - [1, 6] naphthyridin-2-one, F 1 -bicyclo [2 2 ljhept-2-yl-7- (4-fluorophenylamino) -1H- [l , 6] naphthyridin-2-one; 7 - "[4 - (4 - (hydroxy) piperidin-1-yl) phenylaminoj-1 H - [1,6] naphthyridin-2-one,!" * ~ - I 1 - ethyl - 7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylaminoj - 1 H - [1,6] naphthyridin? - 2 _ I - ona; (- - f 7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] -1-isopropyl-1 H - -: i [1, 6] naphthyridin-2-one; 7 - [4 - ( 4 - (hydroxy) piperidin-1-yl) phenylamino] -1-isopentyl-1H-í [1, 6] naphthyridin-2-one; 1-cyclopentyl-7 - [4 - (4 - (hydroxy) pipeiidin-1-yl) phenylamino] - 1 H - [1,1,6-naphyridin-2-one, '1-cyclohexyl-7 - [4 - (4 - (hydroxy ) piperidin-1-yl) phenylamino] - 1H-r [ [1, 6] naphthyridin-2-one; 1-cycloheptyl-7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] -1H - [1, 6] naphthyridin-2-one, 1 -J > iciclo [2 2 ljhept-2-il-7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] -1H - [l, 6] naphthyridin-2-one; 7 = 7 [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino-1-methyl-1 H - [1,6] naphthyridin-2-one, 1-ethyl-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino] -lH [l, 6] naphthyridin-2-one, 7 -. 7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino] -1-isopropyl-1H [1,1-nañiridin-2-one, 7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl] ) phenylamino] -1-isopentyl-1H- [1,1,6-naphthyridin-2-one, 1-cyclopentyl-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino] -1H [1, 6] nañiridin - 2-one, 1-cyclohexyl-7 - [4 - (3 - (hydroxymethyl) piperidin-1-ll) phenylaminoj-1H [1, 6] naphthyrid-n-2-one, 1-cycloheptyl-7 - [4 - (3 - (hydroxymethyl) pipepdin-1-yl) femlamino] - 1 H [1, 6] nañiridin-2-one, 1-bicyclo [2 2 ljhept-2-yl-7 - [4 - (3 - (hydroxymethyl ) pipepdin - 1 -f il) phenylaminoj - 1H - [1, 6] nañiridin-2-one, 1-methyl-7 - [4 - (2H-tetrazol-5-ü) phenylamino] - 1H - [1, 6Jnaft ? t? d? n-2-ona, - \ 1 -ethyl-7 - [4 - (2H-tetrazol-5-yl) phenylamino] -1H - [1, 6] naft? pd? n-2-one , 1 - "isopropyl-7 - [4 - (2H-tetrazol-5-yl) phenylamino] - 1H - [1, 6] nañipd? N - 2 ona, 1 - isopentyl - 7 - [4 - (2H - tetrazol-5-yl) phenylamino] - 1 H - [1, 6] naft? pd? n-2-one, 1-cyclopentyl-7 - [4 - (2 H -tetrazol-5-yl) phenylamino] - 1 H - [ 1, 6] naft? pdin ona, t 1 -jsyclohexyl-7 - [4 - (2H-tetrazol-5-ll) phenylamino] -1H - [1, 6] naft? pd? n -, 2 ^ -one, í 1 - . 1 - . 1 - . 1 - . 1-Cycloheptyl-7 - [4 - (2H-tetiazol-5-yl) phenylamino] -1H - [1, 6] nañn? D? N -one, 1 - . 1 - bicyclo [2 2 ljhept-2-fl-7 - [4 - (2 H -tetrazol-5-yl) phenylamino] -1H [1, 6-naphthyridin-2-one, 1-methyl-7 - (4 - (piperidin-1-yl) phenylamino) - 1 H - [1, 6] naphthyridin-2-one, - fi 1-isopropyl-7 - ( 4 - (piperidin-1-yl) phenylamino) - 1 H - [1, 6] naphthyrid? N-2-one, 1-isopentyl-7 - (4 - (piperidin-1-yl) f -e * n "ylamino ) - 1 H - [1, 6] naphthyridin-2-one, 1-cyclopentyl-7 - (4 - (piperidin-1-yl) phenylamino) - 1 H - [1, 6] naphthyridin-2-one, 1-cyclohexyl-7 - (4 - (piperidin-1-yl) phenylamino) - 1 H - [1, 6] naphthyridin-2 - or fna, 1-cycloheptyl-7 - (4 - (piperidin-1-yl) phenylamino ) - 1 H - [1, 6-naphthyridin-2-one, 1-bicyclo [2 2 ljhept-2-yl-7 - (4 - (piperidin-1-yl) phenylamino) -1 H - [1, 6] naphthyridin-2-one, r 1-methyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) -1 H - [1, 6] naphthyridin-2-one, i 17? 1-ethyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one, l'-r 1 -isopropyl-7 - (4 - (pyrrolidin-1- il) phenylamino) - 1H - [1, 6] naftit? din - 2 - otia, t - 1-Isopentyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) -1 H - [1, 6] naphthyridin-2-one, I 1-cyclopentyl-7 - (4 - (pyrrolidin-1-yl) phenylamino ) - 1 H - [1, 6] naphthyridin-2-one, 1 - ^ iclohexyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) - 1 H - [1,1,6-naphthyridin-2-one, 1-cycloheptyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) - 1 H - [1, 6] naftipdin-ir 2 -one, 1 ^ bicyclo [2 2 l] hept-2-yl - - 7 - (4 - (pyrrolidin - 1-yl) phenylamino) -1H [1, 6] naphthipdin-2-one, 1-methyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] -3,4-dihydro-1.? [1, 6] naphthyridin-2-one,, t 1 -ethyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] -3,4-dihydro-1H t [1, 6] naphthyridin-2-one, i l .r. isopropyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] -3,4-dihydro-1H r [1, 6] naphthyridin-2-one, '1-isopentyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] -3,4-dihydro-1H [1, 6] naphthyridin-2-one , [l, 6j [l, 6j [1, 6] naphthyridin-2-one, i 1-bicyclo [2.2 ljhept-2-yl-7 - [4 - (4-methyl-piperazin-1-yl) -phenylamino-3-yl, 4-dihydro-LH - [l, 6] naphthyridin-2-one, 1-methyl-7 - (4 - [4 - (3-moifolin-4-yl) piopyl) pipeiidin-I-yl-phenylamino} 3,4-dihydro-1 H - [1,1,6-nañiridin-2-one, > 1-ethyl-7 -. { 4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-ylj-phenylamino} 3,4-dihydro-1H- [1, 6] naphthyridin-2-one, r 1-_-isopropyl-7-. { 4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-yl] -phenylamino} - 3,4-dihydro-1H - [1, 6] naphthyridin-2-one, '1-isopentyl-7 - (4 - [4 - (3 - (morpholin-4-yl) propyl) pipepdin - 1 - ilj • phenylamino.} - 3,4-dihydro-1H - [1, 6] naphthyridin-2-one, 77 * = 7 r 1 - "cyclopentyl-7 - (4 - [4 - (3 - (morpholine - 4 - il) propyl) piperidin-1-ylj • phenylamino.} - 3,4-dihydro-1H - [1, 6] naphthyridin-2-one, I 1 «. 1 1 - cyclohexyl - 7 -. - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-yl] phenylamino} - 3,4-dihydro-1 H - [l, 6] naphlhydin-2-one, - 1 - cycloheptyl - 7 -. { 4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-ylj-phenylamino} 3,4-dihydro-1H- [1, 6] naphthyridin-2-one, l 1 ^ bicyclo.2 2 ljhept-2-yl-7-. { 4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin1-1 - il] - phenylamino} - 3,4-dihydro-1H- [1, 6] naphthyridin-2-one, 1-methyl-7 -. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylj-phenylamino} - 3 > , '"• dihydro-1H- [1, 6] naphthyridin-2-one, 1-ethyl-7 -. {4 - [4 - (3 - (hydroxy) propyl) piperidin-1-yl] -phenylamino} - 3 ^ 4-dihydro-1H - [1, 6] naphthyridin-2-one, 7 -. {4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylj-phenylamino}. - 1 - isopropyl-3,4-dihydro-1H- [1,1,6-naphthyridin-2-one, ™ rt 7 - (4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylj-phenylamino}. - 1 - isopentyl - 3.4 - ~ * * dihydro - 1H - [1, 6] naphthyridin - 2 - one, 1 - = cyclopentyl - 7 -. {4 - [4 - (3 - (hydroxy) propyl) piperidine - l - ilj - phenylamino. -. - 3,4 - dihydro - 1 H - [1, 6] nañiridin - 2 - one,, 1 - . 1-ethyl-7 - (4 - (pyrazol-1-yl) phenylamino) -3,4-dihydro-1H- [1, 6] naphthyridin-bone, 1 - . 1-isopropyl-7 - (4 - (pyrazol-1-yl) phenylamino) -3,4-dihydro-1H r [1, 6] naphthyridin-2-one, 1-isopentyl-7 - (4 - (pyrazol-1-yl) phenylamino) -3,4-dihydro-1H [1, 6] naphthyridin-2-one, 1-cyclopentyl-7 - (4 - (pyrazol-1-yl) phenylamino) -3,4-dihydro-1 [1, 6] naphthyridin-2-one, 1-cyclohexyl-7 - (4 - (pyrazol-1-yl) phenylamino) -3,4-dihydro-1H-r [1, 6] nañiridin-2-one, 1-cycloheptyl-7 - (4 - (pyrazol-1-yl) phenylamino) -3,4-dihydro-1H- [1, 6] naphthyridin-2-one, tt 1 - bicyclo [2 2 l] hept-2-yl-7 - (4 - (pyrazol-1-yl) phenylamino) -3,4-dihydro-1 H - [1,1,6-naphthyridin-2-one, I 7 -. 7 - (4-fluoophenylamino) -1-methyl-3,4-dihydro-1H- | _l, 6jnatti? D-n-2-one, 1-ethyl-7 - (4-flurophenylamino) -3,4-dihydro-1H- [1,1,6-naphthyridin-2-one, I [7 - (4-flurophenylamino) - 1 - isopropyl-3,4-dihydro-1H- [1, 6] naphthyridin-2-on fa, 3- ^ 4 F 7 -__ (4-flurophenylamino) -1-isopentyl-3,4-dihydro-1H - [l , 6] naphthipdan-2-one, 1-cyclopentyl-7 - (4-flurophenylamino ^ - 3,4-dihydro-1H - [1, 6] naphthyridinone, 1-cyclohexyl-7 - (4-flurophenylamino) 3,4-dihydro-1H- [1,1-naphyridin-2-one, 1-cycloheptyl-7- (4-flurophenylamino) -3,4-dihydro-1H- [1, 6] naphthyridin-2-one. - bicyclo [2 2 ljhept-2-yl 7 - (4-flurophenylamino) -3,4-dihydro-1H [1, 6] nañiridin - 2 - one, i 7 -. 7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] -1-methyl-3,4-lH [l, 6] nañiridin-2-one, 1-ethyl-7 - [4 - ( 4 - (hydroxy) piperidin-1-yl) phenylaminoj-3,4-lH [l, 6] naphthyridin-2-one, ¡7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylaminoj - 1 - isopropyl - 3,4 - 1H 1 1 p, 6] naphthyridin-2-one, __ 7 - [4 - (4 - (hydroxy) piperidin - 1 - yl) phenylaminoj - 1 - isopentyl - 3,4 - 1 H [1, 6] naphthyridine - 2 - ona, . 1-cyclopentyl-7 - [4 - (4 - (hydroxy) piperidin-1-yl) femlaminoj-3,4-1H i [1, 6] naphthyridin-2-one, 1-cyclohexyl-7 - [4 - ( 4 - (hydroxy) piperidin-1-yl) phenylamino] -3,4-lH [l, 6] naphthyridin-2-one, 1-cycloheptyl-7 - [4 - (4 - (hydroxy) piperidin-1-yl) ) phenylamino] - 3,4 - 1 H [1, 6] naphthyridin-2-one, - 1-bicyclo [2 2 ljhept-2-yl-7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] 3,4 - 1 H - [1, 6] naphthyridin-2-one, 7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylaminoj-1-methyl-3,4-lH [l, 6-naphthyridine - 2-one, 1-ethyl-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino] -3,4-1H [1, 6] naphthyridin-2-one, 7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylaminoj-1-isopiopil-3,4-lH [l, 6] naffhidin-2-one, 7 - [4 - (3 - (hydroxymethyl) piperidin - 1 - il) phenylamino] -1-isopentyl-3,4-lH [l, 6] naphthyridin-2-one, 1 - . 1 - . 1-cyclopentyl-7 - [4 - (3 - (hydroxymethyl) pipendin-1-yl) phenylamino] -3,4-1H- [1, 6] naphthyridin-2-one, 1-cyclohexyl-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino] - 3,4 - 1H f [1, 6] naphthyridin-2-one, j-f 1-cycloheptyl-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylaminoj-3,4-1H-f [1, 6] naphthyridin-2-one, '1-bicyclo [2-ljhept-2-yl-7 - [4 * - (3 - (hydroxymethyl) pipepdin-1-yl) phenylamino] -3,4-1H - [1, 6] naphthyridin-2-one, 1-methyl-7 - [4 - (2H-tetrazol-5-yl) "phenylamino] - 3,4 - 1 H - [1, 6] naft? ridin - 2 ina, 1 ^ ethyl-7 - [4 - (2H-tetrazol-5-yl) phenylaminoj-3,4-1H - [1.6] naphthyrid? n-2-one, 1-gisopropyl-7 - [4 - (2H - tetrazol-5-yl) phenylamino] -3,4-lH- [l, 6Jnaft? pdin-2-one,? 1-isopentyl-7 - [4 - (2H-tetrazol-5-yl) phenylamino] -3 , 4 - 1H - [l, 6] nañipdin - ri 2 - . 2 -one, 1-cyclopentyl-7 - [4 - (2H-tetrazol-5-ll) phenylaminoj-3,4-1H - [1, 6Jnaftipdin - 2-one, 1-cyclohexyl-7 - [4 - (2H-tetrazol-5-yl) phenylaminoj-3,4-lH- [l, 6-naphthyridin-2-one, 1-cycloheptyl-7 - [4 - ( 2H-tetrazol-5 ^ il) phenylamino] -3,4-1 H - [1, 6] naphthyrid? Nf - 2 - ona,! ^ t 1 - bicyclo [2 2 ljhept-2-yl-7 - [4 - (2H-tetrazol-5-ll) phenylaminoj-3,4-lH- [l, 6-naphthyridin-2-one, l-, methyl - 7 - (4 - (piperidin-1-yl) phenylamino) -3,4-1H- [1,1,6-naphthyridin-2-one, 1-ethyl-7 - (4 - (piperidin-1-yl) phenylamino) -3,4-1H- [1,1,6-naphthipdin-2-one, 1 - . 1 - . 1 - . 1-isopropyl-7 - (4 - (piperidin-1-yl) phenylamino) -3,4-lH- [l, 6] naphthyridin-2-one. f 1-Isopentyl-7 - (4 - (piperidin-1-yl) phenylamino) -3,4-lH- [l, 6] naphthyridin-2-one, 1 -.cyclopentyl-7 - (4 - (piperidin-1) - il) phenylamino) - 3,4 - 1 H - [1,1,6-naphthyridin-2-one. 1-cyclohexyl-7 - (4 - (piperidin-1-yl) phenylamino) -3,4-lH- [l, 6-naphthyridin-2-one, 1-cycloheptyl-7 - (4 - (piperidin-1-yl) phenylamino) -3,4-lH- [1,1,6-naphthyridin-2-one; 1-bicyclo [2 2 ljhept-2-yl-7 - (4 - (piperidin-1-yl) phenylamino) -3,4- 1 H [l, 6-naphthyridin-2-one, 1-methyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) -3,4-lH- [l, 6] naphthyridin-2-one 1 - "ethyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) - 3,4 - 1 H - [1, 6-naphthyridin-2-one, l 1-isopropyl-7 - (4 - (pyrrolidin - 1 - yl) phenylamino) - 3,4 - 1 H - [1,1,6-naphthyridin-, 2-one, 1-isopentyl - 7 - (4 - (pyrrolidin - 1 - yl) phenylamino) - 3,4 - 1 H - [1, 6] nañiridin-2-one, 1-cyclopentyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) - 3,4 - 1 H - [1, 6] naphthyridin-2-one 1-cyclohexyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) -3,4-1H- [1,1,6-naphthyridin-2-one, 1-cycloheptyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) -3,4-lH- [1,1,6-naphthyridin-2-one, l ^ bicido [2 2 ljhept-2-yl-7 - (4 - (pyrrolidin-1-yl) phenylamino) -3,4-lH [l, 6-naphthyridin-2-one, 3-fluoro-1-methyl-7 - [4 - (4-methylpiperazin-1-yl) phenylaminoj - 1 H - [1,6] naphthyridin-2-one, 1-ethyl-3-fluoro-7 - [4 - (4-methylpiperazin-1-yl) phenylaminoj - 1H - I- ~ [1, 6-naphthyridin-2-one, 3 - . 3-fluoro-1-isopropyl-7 - [4 - (4-jnethylpiperazin-1-yl) phenylamino] H [l, 6-naphthyridin-2-one, 3-fluoro-1-isopentyl-7 - [4 - (4-methylpiperazine - 1 - yl) phenylamino] - 1 H - [1, 6] nañiridin-2-one, i 1-cyclopentyl-3-fluoro-7 - [4 - (4-methylpiperazin-1-yl) phenylaminoj - 1H - [l, 6-Naphthyridin-2-one, i 1-cyclohexyl-3-fluoro-7 - [4 - (4-methyl-piperazin-1-yl) -phenylamino-1H-cyclopentyl-3-fluoro-3-naphyridin-2-one, 1-cyclopentyl-3-fluoro - 7 - [4 - (4-Methylpiperazin-1-yl) phenylamino] -1H-F t [1, 6] naphthyridin-2-one, 1-bicyclo [2 2 ljhept-2-yl-3-fluoro-7] - [4 - (4-methylpiperazin-1-yl) phenylaminoj-1 H - [1,1,6-naphthyridin-2-one,! 3-fluoro-1-methyl-7 -. { 4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-ylphenylamino} - 1 H - [1, 6-naphthyridin-2-one, 1-ethyl-3-fluoro-7 -. { 4 - [4 - (3 - (morpholin-4-yl) pi opyl) piperidinylphenylamino} - 1H - [1, 6-naphthyridin-2-one, _ | 3-fluoro-1-isopropyl-7-. { 4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-ylphenylamino} - 1H - [l, 6Jnañiridin - 2 - one, 3_- fluoro-1-isopentyl-7 -. { 4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-ylphenylamino} - 1 H - [1,16-Naphthyridin-2-one, 1-cyclopentyl-3-fluoro-7 - (4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin'-1-ylphenylamino} - 1H - [1, 6-Naphthyridin-2-one; 1-cyclohexyl-3-fluoro-7 -. {4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-ylphenylamino} - 1H - [1, 6-Naphthyridin-2-one; 1-cycloheptyl-3-fluoro-7 -. {4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-, 1-ylphenylamino} - 1 H - [1, 6] naphthyridin-2-one, 1 ^ bicyclo [2 2 ljhept-2-yl-3-fluoro ^ 7 -. {4 - [4 - (3 - (morpholin-4-yl) propyl] ) piperidin-1-ylphenylamino} - 1 H - [1,1,6-naphthyridin-2-one, i 3-fluoro-1-methyl-7 -. {4 - [4 - (3 - (hydroxy) propyl) piperidin-1-yl] -1-phenylamino., - 1 H - [1,1,6-naphthyridin-2-one;, ^ -_ [< ~ - 1 1 -ethyl-3-fluoro-7 - { 4 - [ 4 - (3 - (hydroxy) propyl) piperidin-1-yl-phenylamino} - 1 H - [1, 6] naphthyridin-2-one; i 3-fluoro-7 -. {4 - [4 - ( 3 - (hydroxy) propyl) piperidin-1-ylj-phenylamino} - 1-isopropyl-1H - [1, 6] naphthyridin-2-one, -. - 3 i fluoro - 7 -. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-yl] -phenylamino} -, 1-Isopentyl - 1 H - [1, 6] naphthyridin-2-one; I 1 f cyclopentyl-3-fluoro-7 -. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-yl] phenylamino} - 1H - [1, 6] naphthyridin-2-one, 1-cyclohexyl-3-fluoro-7 - (4 - [4 - (3 - (hydroxy) propyl) piperidin-1-yl] phenylamino. - 1H - [1, 6] naphthyridin-2-one; 1-cycloheptyl-3-fluoro-7 -. {4 - [4 - (3 - (hydroxy) propyl) piperidin-1-1-phenylamino} - 1H - [1, 6-naphthyridin-2-one, 1 - . 1 - bicycles [2.2. ljhept-2-yl-3-fluoro-7 -. { 4 - [4 - (3 - (hydroxy) propyl) piperidin - 1-ylj-jphenylamino} - 1H - [1,1,6-naphthyridin-2-one; 3-fluoro-1-methyl-7- (4-pyrazol-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one; 1-ethyl-3-fluoro-7 - (4-pyrazol-1-yl) phenylamino) -1H - [1,1,6-naphthyridin-2-one; 3-fluoro-1-isopropyl-7 - (4-pyrazof-1-yl) phenylamino) - 1H - [1,1,6-naphthyridine 2 - . 2 - . 2 - . 2 - ona; - 3 ^ fluoro-1-isopentyl-7 - (4-pyrazol-1-yl) phenylamino) -1H - [1,1,6-nañirididin-2-one; 1-cyclopentyl-3-fluoro-7 - (4-pyrazol-1-yl) phenylamino) -1H - [1,6] naphthyridine 2 - ona; 1-cyclohexyl-3-fluoro-7- (4-pyrazol-1-yl) phenylamino) -111- [1, 6-naphthyridine 2 - ona; 1-cycloheptyl-3-fluoro-7 - (4-pyrazol-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one; 1 - bicycles [2.2. ljhept-2-yl-3-fluoro-7 - (4-pyrazol-1-yl) phenylamino) -1H [l, 6-naphthyridin-2-one; 3-fluoro-7 - (4-fluorophenylamino) -1-methyl-1H- [1, 6] naphthyridin-2-one, 1-ethyl-3-fluoro-7 - (4-fluorophenylamino) - 1H - [1, 6-naphthyridin-2-one; ! ~ 1 i 3 fluoro-7 - (4-fluorophenylamino) -1-isopropyl-1H - [1, 6] naphthyridin-2-one; 3-fluoro-7 - (4-fluorophenylamino) -1-isopentyl-1H- [1,6] nañiridin-2-cyclopentyl-3-fluoro-7 - (4-fluorophenylamino) -1H - [1,6] naphthyridine - 1 - . 1-cyclohexyl-3-fluoro-7 - (4-fluorophenylamino) -1H - [1,1,6-naphthyridin-2-one; 1-cycloheptyl-3-fluoro-7 - (4-fluorophenylamino) -1H - [1,1,6-naphyridin-2-oha; 1 - . 1-bicyclo [2 2 ljhept-2-yl-3-fluoro-7 - (4 ^ fluorophenylamino) - ^ H i [1, 6] naphthyridin-2-one, 3-fluoro-7 - [4 - (4 - (hydroxy) pipeiidin-1-yl) phenylaminoj-1 H - [1,1,6-naphthyridin i 2-one, 1-ethyl-3-fluoro-7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylaminoj - 1H [1, 6] naphthyridin-2-one, 3-fluoro-7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] -1-isopropyl-1H-r [1, 6] naffiridin - 2-one, '- I 3-fluoro-7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylaminoj-1-isopentyl-1 H - [1,6] nañiridin-2-one, [1 - cyclopentyl-3-fluoro-7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] -1H - [1.6] naphthyridin-2-one,. 1-Cyclohexyl-3-fluoro-7 - [4 - (4 - (hydroxy) pipcy idin - I - yl) phenylaminoj - 1 H - [1,1-N-narynidin-2-one, i 1-cycloheptyl-3-fluoro-7 - [4 - (4 - (hydroxy) piperidin - 1 - yl) phenylaminoj - - [1, 6] naphthyridin-2-one, j 1 ^ bicyclo [2 2 ljhept-2-yl-3-fluoro-7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylaminoj - 1 H - [ 1, 6] naphthyridin-2-one, 3-fluoro-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino-1-methyl-1H-T "* i [1, 6-naphthyridin-2 - nona, 1-ethyl-3-fluoro-7 - [4 - (3 - (hydroxymethyl) pipendin - 1 - yl) _enaminoam - 1 H - [1,1,6-naphthyridin-2-one, 3-fluoro-7 - [ 4- (3 - (hydroxymethyl) piperidin-1-yl) phenylaminoj-1-isopropyl-L 1 H - [1,1,6-naphthyridin-2-one, 3 - . 3-fluoro-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) enylaminoj-1-isopentyl 1H - [1, 6] naphthyridin-2-one, 1-cyclopentyl-3-fluoro-7 - [ 4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino] 1H - [1, 6-naphthyridin-2-one, I 1-cyclohexyl-3-fluoro-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino] - -r t. ^ r 1 H - [1, 6] naphthyridin-2-one, [thi 1-cycloheptyl-3-fluoro-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino] -1H - [1, 6-naphthyridin-2] - ona, '1 - bicyclo [2 2 ljhept-2-yl-3-fluoro - - [4 - (3 - (hydroxymethyl) piperidin-1-yl) l] phenylamino] - 1 H - [1,1,6-naphthyridin-2 - ona, 3-fluoro-1-methyl-7 - [4 - (2H-tetrazol-5-yl) phenylaminoj - 1H - [1, 6] naphthyridine - 2-one, 1-ethyl-3-fluoro-7 - [4 - (2H-tetrazoL-5-yl) phenylaminoj - 1 H - [1, 6] naphthyridin-I 2-one, j 3-fluoro-1 - isopropyl-7 - [4 - (2H-tetrazol-5-yl) phenylamino] -1H - [1, 6] naphthyridin-2-one, [3-fluoro-1-isopentyl-7 - [4 - (2H-tetrazole - 5 - yl) phenylaminoj - 1H - [1, 6] naftifidin-2-one, 1 G cyclopentyl-3-fluoro-7 - [4 - (2H-tetrazol-5-yl) phenylamino] - 1H - [1, 6] naphthyridin-2-one, f 1-cyclohexyl-3-fluoro-7 - [4 - (2H-tetrazol-5-yl) phenylaminoj-1 H - [1, 6] naphthyridin-2-one,, t 1 - cycloheptyl-3-fluoro-7 - [4 - (2H-tetrazol-5-yl) phenylamino] -1H - [1, 6] nañiridin-2-one, f - bicycles [2.2. ljhept-2-yl-3-fluoro-7 - [4 - (2 H -tetrazol-5-yl) phenylamino] 1 H - [1, 6] naphthyridin-2-one; i 3-fluoro-1-methyl-7 - (4 - (piperidin-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2 - ona; 1-ethyl-3-fluoro-7 - (4 - (piperidin-1-yl) phenylamino) -1H - [1, 6] naphthyridinone; 3_- fluoro-1-isopropyl-7 - (4 - (piperidin-1-yl) phenylamino) - 1H - [1,1,6-naphthyridine] - 2 - ona; 3-fluoro-1-isopentyl-7 - (4 - (piperidin-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one; - L 1 -cyclopentyl-3-fluoro-7 - (4 - (piperidin-1-yl) phenylamino) -1H-i * [1,1,6-naphthyridin-2-one; 1-Cyclohexyl-3-fluoro-7 - (4 - (piperidin-1-yl) phenylamino) -1 H [1, 6] naphthyridin-2-one; 1 ~ cycloheptyl-3-fluoro-7 - (4 - (piperidin-1-yl) phenylamino) -1H [1, 6] naphthyridin-2-one; 1 ~ - bicycles [2.2. ljhept-2-yl-3-fiuoro-7 - (4 - (piperidin-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one; 3-fluoro-1-methyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one; 1-ethyl-3-fluoro-7 - (4 - (pyrrolidin-J_-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one; 3-fluoro-1-isopropyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) -LH - [l, 6] naphthyridin-2-one; .1 . 3-fluoro-1-isopentyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) - 1 H - [1,6] naphthyridine - - \ 2 - . 2 - ona. 1-Cyclopentyl-3-fluoro-7 - (4 - (pyrrolidin-1-yl) phenylamino) H [1, 6] naphthyridin-2-one, 1-cyclohexyl-3-fluoro-7 - (4 - (pyrrolidin - 1-yl) phenylamino) H - [1, 6] naphthyridin-2-one; 1-cycloheptyl-3-fluoro-7 - (4 _- (pyrrolidin-1-yl) phenylamino) H [1, 6] naphthyridin-2-one; 1 * - ~ bicyclo [2 2 ljhept-2-yl-3-fluoro-7 - (4 - (pyrrolidin-1-yl) phenylamino) ± 1 H - [1, 6] naphthyridin-2-one; '3 - (2,6-dichlorophenyl) -7- (4-fluoro-3-methylphenylamino) -1-methyl-1H- [l? 6j- ] - naphthyridin-2-one, 3 - (2,6-dichlorophenyl) -7 - [4 - (2 - (morphifin-4-yl) ethoxy) phenylamino] -1H - [1,6] - naphthyridine - 2-one, 3 - (2,6-dichlorophenyl) -7- [4 - (2 - (piperidin-1-yl) ethoxy) phenylamino] -1 [1 H - [1,6] - naphthyridin-2-one; i 3 - ^ (2,6-Dichlorophenyl) - 7 - [4 - (4 - (methylpiperazin-1-yl) methyl) phenylamino] -1 1 I methyl-1H - [1,6] - naphthyridin-2-one , [ 3 - . 3 - (2,6-dichlorophenyl) -7- [4 - (2 - (dimethylamino) ethoxy) phenylaminoj-1-methyl 1 H - [1,6J-naphthyridin-2-one; i 3 - [3 - (2,6-dichlorophenyl) -1-methyl-2-oxo-1,2-dihydro- [1,6] naphthyridin 7 -. 7-ylamino] -benzoic acid; 3 - (2,6-dichlorophenyl) -7- [3 - (2 - (diethylamino) ethoxy) phenylamino] -1-methyl-1 H -yl] [1,6] -naphthyridin-2-one, N - ( 2 - { 4 - [3 - (2,6-dichlorophenyl) -1-methyl-2-oxo-1,2-dihydro- [l, 6] naphthyridin-7-ylamino] phenoxy} ethyl) - N-ethyl-acetamide, acid. { 4 - [3 - (2,6-Dichlorophenyl) -1-methyl-2-oxo-1,2-dihydro- [1, 6] naphthyridin-7-ylamino-phenyl} - acetic acid, 3- (2,6-dichlorophenyl) -1-ethyl-7 - [1, 6] naphthyridin-2-one; 3 - . 3 - (2,6-Dichlorophenyl) -7- (4-ethoxyphenylamino) -1-ethyl-1H- [1, 6] naphthyridin-2-one, * r 3-α (2,6-dichlorophenyl) -1 - ethyl-7 - (3-hydroxymethyl) phenylamino-1H [1,6] naphthyridin-2-one, 3- (2,6-dichlorophenyl) -1-ethyl-7 - (4 - (morpholin-4-yl) phenylamino-1H [1, 6] naphthyridin-2-one, 3 - (2,6-dichlorophenyl) -7- [4 - (2-diethylamino) ethoxy) phenylamino] -1-ethyl-1H [l, 6] ] naphthyridin-2-one, * 3 - . 3 - . 3 - . 3 - . 3 - . 3 - (2,6-dichlorophenyl) -1-ethyl-7 - [4 - (2 - (morpholin-4-yl) ethoxy) phenylaminoy-1 H - [1,1,6-naphthyridin-2-one, i 3 r ( 2,6-dichlorophenyl) -1-ethyl-7 - [4 - - (2 - (piperidin-1-yl) ethoxy) phenylamin _joj r 1H - [1, 6] naft? Pd? N-2-one,. 3 - . 3 - (2,6-dichlorophenyl) -1-ethyl-7 - [4 - (4 - (methylpiperazin-1-yl) methyl) phenylamino] -1H - [1, 6] naphthyridin-2-one; • - I I 3 - (2,6-dichlorophenyl) -7- [4 - (2 - (dimethylamino) ethoxy) phenylaminoj-1-ethyl-1H-i [1, 6] naphthyridin-2-one; ! 3 - [3 - (2,6-Dichlorophenyl) -1-ethyl-2-oxo-1,2-dihydro- [1, 6-naphthyridin-7 acid - [ - ilamino] - benzoic; 3 - (2,6-dichlorophenyl) -7- [3 - (2 - (diethylamino) ethoxy) phenylaminoj-1-ethyl-1H- [1,1,6-naphthyridin-2-one, i N - (2 -. {4 - [3 - (2,6-dichlorophenyl) -1-ethyl-2-oxo-1,2-dihydro- [1, 6] naphthyridin-7-ylamino-phenoxy] ethyl) -N-ethyl-acetamide; 3 - (2,6-Dichlorophenyl) -1-ethyl-7 - (4-pyridylamino) -1H - [1,6] -naphthyridinyl-1-ene, 1,3- (2,6-dichlorophenyl) -1 - ethyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] - 1H - [1, 6] naphthyridin-2-one; . acid { 4 - [3 - 3 - (2,6-Dichlorophenyl) -1-ethyl-2-oxo-1,2-dihydro - [1, 6] naphthyridin-7-ylamino-phenyl} - acetic; 3 - (3,5-Dimethoxyphenyl) -1-methyl-7 - [3 - (4-methylpiperazin-1-yl) propylamino] r - 1H - [1, 6] naphthyridin-2-one; _ ^ 3 ^ (3,5-dimethoxyphenyl) -1-ethyl-7 - [3 - (4-methylpiperazin-1-yl) propylamino] -1H - [1, 6] naphthyridin-2-one, 7 - (4 - (diethylamino) butylamino) -3- (3,5-dimethoxyphenyl) -1-methyl-1 H [1, 6-naphthyridin-2-one; 'r 7 - (4 - (diethylamino) butylamino) -3- (3,5-dimethoxyphenyl) -1-ethyl-1H-2 t [l, 6Jnaftiri_din - 2 - ona,, 7 -. 7 -. [4 - (2 - (diethylamino) ethoxy) phenylaminoj -3- (3,5-dimethoxyphenyl) -1-ethyl-1 [1, 6-Naphthyridin-2-one, 7 - [4 - (2 - (diethylamino) ethoxy) phenylaminoj -3- (3,5-dimethoxyphenyl) -1-methyl-1H- [1,1,6-naphthyridin-2-one, 3 - (3,5-dimethoxyphenyl) -1-ethyl-7- (4-pyridylamino) -1H - [1, 6] naphthyridin-2-one, 3- (3,5-dimethoxyphenyl) -1-methyl-7- (4-pyridylamino) -1H - [1, 6-naphthyridin-2-one, 3- (2,6-dichloro-3,5-dimethoxyphenyl) -1- methyl - 7 - [3 - (4-methylpiperazin-1-yl) - t-propylamino] - 1 H - [1, 6-naphthyridin-2-one, I ;; t 3 - (2-Chloro-3,5-dimethoxyphenyl) -1-methyl-7 - [3- (4-methyl-piperazin-1-yl) -propylamino-1H- [1,1,6-naphthyridin-2-one, r 3 - (2,6-dimethyl-3,5-dimethoxyphenyl) -1-methyl-7 - [3 - (4-methylpipeiazin-1-yl) ** ^ r propylamino] - 1 H - [1,1,6-naphthyridin-2-one, t Z i 1-methyl-3 - (2-methyl-3,5-dimethoxyphenyl-7 - [3- (4-methyl-piperazin-1-yl) -propylamino] -1H - [1,1,6-naphthyridin-2-one, f 3 - . 3 - . 3 - (72,6-dichloro-3,5-dimethoxyphenyl) -1-ethyl-7 - [3 - (4-methylpiperazin-1-yl) ir i propylamino] -1H - [1, 6] naphthyridine - 2 - ona, 3 - (2-chloro-3,5-dimethoxyphenyl) -1-ethyl-7 - [3 - (4-methylpiperazin-1-yl) i propylaminoj-1 H - [1,1,6-naphthyridin-2-one, 3 - (2,6-dimethyl-3,5-dimethoxyphenyl) -1-ethyl-7 - [3- (4-methylpiperazin-1-yl) propylaminoj-1 H - [1,1,6-naphthyridin-2-one, 1-ethyl-3 - (2-methyl-3,5-dimethoxyphenyl) -7 - [3 - (4-methylpiperazin-1-l) propylaminoj-1 H - [1,1,6-naphthyridin-2-one, 3_- (2,6-dichloro-3,5-dimethoxyphenyl) -7- (4 - (diethylamino) butylamino) -1-methyl ^ r ~~ i - 1 H - [1, 6] naphthyridin-2-one, 3 - (2-chloro-3,5-dimethoxyphenyl) -7- (4 - (diethylamino) butylamino) -1-methyl 1H- [1,1,6-naphthyridin-2] - ona, 7 - (4 - (diethylamino) butylamino) -1-methyl-3 - (2-methyl-3,5-dimethoxy-phenyl-1-yl) -1H - [1, 6] naphthyridin-2-one, 3 - (2,6-Dimethyl-3,5-dimethoxyphenyl) -7- (4 - (diethylamino) butylamino) -1-methyl - 1H - [1, 6] naphthyridin-2-one, 3 - (2,6-dichloro-3,5-dimethoxyphenyl) -7- (4 - (diethylamino) butylamino) -1-ethyl-1H- [1, 6 ^] naphthyridin-2-one, 1 i 3 - (2-chloro-3,5-dimethoxyphenyl) -7- (4 - (diethylamino) butylamino) -1-ethyl-1H- [1,6] naphthyridin-2 - ona, I 7 - (4 - (diethylamino) butylamino) -1-ethyl-3 - (2-methyl-3,5-dimethoxyphenyl) -1H - [1,1,6-naphthyridin-2-one, 7 - (4 - ( diethylamino) butylamino) -3- (2,6-dimethyl-3,5-dimethoxyphenyl) -1-ethyl-1H- [1, 6] naphthyridin-2-one, I 3 ^ (2,6-dichloro-3, 5-dimethoxyphenyl) - 7 - [4 - (2-diethylamino) ethoxy) phenylamino] 1 - . 1 - . 1 - . 1-methyl-1 H - [1,1,6-naphthyridin-2-one, 3 - (2-chloro-3,5-dimethoxyphenyl) -7- [4 - (2-diethylamino) ethoxy) phenylamino] -1-methyl-1H- [ 1, 6-naphthyridin-2-one, 7 - [4 - (2 - (diethylamino) ethoxy) phenylaminoj-1-methyl-3 - (2-methyl-3,5-dimethoxyphenyl) -1H - [1,1,6-naphthyridin-2-one] , μ 3 - (2,6-dimethyl-3,5-dimethoxyphenyl) - 7 - [4 - (2-diethylamino) ethoxy) phenylamino - f 1-methyl-1H- [1,1,6-naphthyridin-2-one, 3 - . 3 - (2,6-Dichloro-3,5-dimethoxyphenyl) -7- [4 - (2-diethylamino) ethoxy) phenylamino] 1-ethyl-1H- [1,1,6-naphthyridin-2-one, 3 - (2-chloro-3,5-dimethoxyphenyl) -7- [4 - (2-diethylamino) ethoxy) phenylaminoj 1 ethyl-1H- [1, 6-Naphthyridin-2-one, 7 - [4 - (2 - (diethylamino) ethoxy) phenylamino] -1-ethyl-3 - (2-methyl-3,5-dimethoxyphenyl) -1H - [1,1,6-naphthyridin-2-one] , 7 - [4 - (2 - (diethylamino) ethoxy) phenylaminoj -3- (.2,6-dimethyl-3,5-dimethoxife il) - 1 - ethyl - 1H - [1,1,6-naphthyridin-2-one,! -i 1-methyl-7 - [3 - (4-methylpiperazin-1-yl) propylamino] - 3 - (2,3,5,6 - f tetramethylphenyl) - 1 H - [1, 6] naphthyridin-2-one, 1 ^ ethyl-7 - [3 - (4-methylpiperazin-1-yl) propylamino] -3- (2,3,5,6- tetramethylphenyl) - 1 H - [1, 6] naphthyridin-2-one, 7-(4 - (diethylamino) butylamino) -1-methyl-3 - (2,3,5,6-tetramethyl) - 1H - [l , 6] naphthyridin-2-one, l [7-_ (4 - (diethylamino) butylamino) -1-ethyl-3 - (2,3,5,6-tetramethylphenyl) -1H [1, 6-naphthyridin-2-one, 7 - [4 - (2 - (diethylamino) ethoxy) phenylamino] -1-ethyl-3 - (2,3,5,6-tetramethylphene) 1 H - [1, 6] naphthyridin-2-one, 7 - [4 - (2 - (diethylamino) ethoxy) phenylam-1 H - [1,6] naphthyridin-2-one, 1-methyl-7 - [3 - (4-methylpiperazi [1, 6] naphthyridin-2-one, 1 - . 1-ethyl-7 - [3 - (4-methylpiperazin-1-yl) propylaminoj-3-phenyl-1 H - _ _ i- [1, 6] naphthyridin-2-one,, - f 7 - (4 - (diethylamino) butylamino) -1-methyl-3-phenyl-1H- [1, 6] naft? pdin-2-one, - - - - - - - -, - -, j 7 - [4 - (2-Dielilammo) ethoxy) lenila inoj - 1 - ethyl - 3 - phenyl - III - [1, 6] naphthidin - 2 - one, 7 - [4 - (2-diethylamino) eloxi) enylamino] -1-methyl-3-phenyl-III- [1, 6-naphthyridine - III - - 1 HOUR - , 6] naphthyridin-2-one, and 7 -. 7 - [4 - (2 - (dielylamino) ethoxy) enylaminoj - I - ethyl - 3 - (lyoen - 2 - i) - 1H - [1, 6] nalli? Idm - 2 - one In a piedilecto example of the compounds of Formula I, is absent In otio exemplai piedilecto, it is a link ¡^ * : In other examples, R is CII2CIh In olio ejemplai piedileclo, .RJ R- / / R1 is - N -N ai ilo substituted aryl where aiil is phenyl and ai i I substituted is phenyl substituted In olio ejemplai piedilecto, -? R > 2 is cp2c ?? 3 In olio ejemplai piedilccto, R is hydrogen R'es-NH2, -F, -NH-phenyl, - NI I - substituted phenyl, / \ -N- • C? 2C? 2CH2 - N, N C1I3 'II, CH2CII3 / -N- c? I Ci cmcp N, or II \ c ?? 7cp3 lín a cjemplai more piedilccto, the picsenle nvencón piopoicona com Formula I where is a link or absent, R1 is-Nl, -I7, -NH- phenyl, *. NHH-substituted enyl, -N- / / \ -N O II / = / V_V -N _LL "??? L Rs is hydrogen _ the faimaceutically acceptable salts thereof Also the picsente invention a method paia tiatat the cancer, and The method comprises administering to a patient having cancer a quantitatively therapeutically elective amount of a compound of Formula I.

A method is also available for you to bind or prevent atherosclerosis, the method includes administration to a patient with atherosclerosis or at risk. of atherosclerosis have a therapeutically effective amount of a compound of the Fói mile I ~ I A method for treating or preventing restenosis is also provided, comprising administering to a patient having atherosclerosis or being at risk restenosis a therapeutically effective amount of a compound of Formula I, i? Also provided by the present invention is a method for treating psoriasis, the method comprising administering to a patient having psoriasis a therapeutically effective amount of a compound of Formula I A method for inhibiting protein tyrosine kinases is also provided, the method comprising administering to a patient in need of protein kinase and tyrosine inhibition an inhibitory amount of protein tyrosine kinase of Formula I In a preferred example of the method to inhibit protein tyrosine kinases, the protein tyrosine I kinase is c-Src ' In another favorite, the protein tyrosine kinase is PDGFr In a preferred specimen of the method to inhibit cell cycle kinases, cell cycle kinase I is CDK4, CDK2 or CDK1. I Also provided in the present invention is a pharmaceutical composition comprising a compound of Formula I DETAILED DESCRIPTION OF THE INVENTION The term "alkyl" means a straight or branched chain hydrocarbon. Representative examples of the alkyl groups are methyl, ethyl, propyl, isopropyl, isobutyl, i-butyl, tert-butyl, sec-butyl, pentyl and hexyl. i The term "halogen" includes chlorine, fluorine, bromine and iodine.

The term "alkenyl" means a straight or branched chain hydrocarbon having one or more carbon-carbon double bonds. I 1 The term "aryl" means an aromatic hydrocarbon. Representative examples r of the aryl groups include phenyl and naphthyl. í The term "heteroatom" includes oxygen, nitrogen and sulfur The term "heteroaryl" means an aryl group in which one or more carbon atoms of the aromatic hydrocarbon has been replaced with a heteroatom. of heteroaryl radicals include, but are not limited to, pyridyl, imidazolyl, pinolyl, thienyl, furyl, pyranyl, pyrimidinyl, pyridazinyl, indolyl, quinolyl, naphthyridinyl and isoxazolyl The term "cycloalkyl" means a cyclic hydrocarbon Examples of the [cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl The symbol "-" means a link The term "patient" means all animals, including humans. Examples! of patients include humans, cows, dogs, cats, goats, sheep and pigs.

The term "substituted" means that the organic base radical has one or more substitutes. For example, substituted aryl means an aryl radical such as benzene having one or more substitutes. Substitutes include, but are not limited to, halogen, alkyl.

C_ - Cg alkyl, - CN, CF3, - NO2, - NH2, - NHC, - Cg alkyl, - N (C_ - Cg alkyl) 2, - OCi O O 1 -C8 alkyl, -OH, -COH or -COCi-C6 alkyl The term "heterocycle" means a cycloalkyl group in which one or more 1 2 1 carbon atoms are replaced with a heteroatom. Examples of heterocycles include, but - [not limited to, pyrrolidinyl, piperidyl and piperazinyl The term "bicycloalkyl" means a cyclic hydrocarbon having the formula where each p is independently from 1 to 4 Those skilled in the art are readily able to identify patients who have cancer, atherosclerosis, psoriasis, restenosis or are at risk of having atherosclerosis or restenosis. For example, patients who are in danger of having restenosis include, but are not limited to, patients who have suffered from balloon or other vascular surgical procedure A therapeutically effective amount is an amount of a compound of the Formula I, which when administered to a patient, ameliorates a symptom of the disease The term "cancer" includes, but is not limited to, the following cancers: breast, cervical ovaries, prostate, testis, esophagus, glioblastoma, nearoblastoma, stomach, skin, keratoacanthoma, lung, epidermal carcinoma, large cell carcinoma, adenocarcinoma, bone, colon, adenocarcinoma, adenoma, pancreas, adenocarcinoma, thyroid, follicular carcinoma, undifferentiated carcinoma, papillary carcinoma, seminoma, melanoma, sarcoma, bladder carcinoma, carcinoma of the liver and bile passages, carcinoma of the kidney, myeloid disorders, lymphoid disorders, Hosgkins disease, capillary cells, oral cavity and pharynx (oral), lip, tongue, mouth, pharynx, small intestine, colon - rectum, large intestine, rectum, brain and central nervous system, and leukemia The compounds of the present invention can be administered to a patient either alone, or as part of a pharmaceutical composition. The compositions can be administered to patients either orally, rectally, parenterally (intravenously, intramuscularly or subcutaneously), intracisternally, intravaginally, intraperitonally. , intravesicular, or localme Inte (powders, ointments or drops) or as a mouth rinse or mouthwash Compositions suitable for parenteral injection may comprise sterile physiologically acceptable sterile aqueous or non-aqueous solutions, dispersions, suspensions or emulsions, and sterile powders for reconstitution of sterile injectable solutions or dispersions Examples of aqueous or non-aqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (propylene glycol, polyethylene glycol, glycerol and the like), appropriate mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate. The proper fluidity can be maintained by, for example, the use of a cover such as lecithin, by maintaining the required particle size in the case of dispersions and by the use of surfactants I > These compositions may also contain adjuvants such as preserving agents, humectants, emulsifiers and dispersants. The prevention of the action of microorganisms can be ensured by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid and the like. it is desirable to include isotonic agents, for example, sugars, sodium chloride and the like. The irolonged absorption of the injectable pharmaceutical form can be obtained by the use of agents delaying absorption, for example, aluminum monostearate and gelatin.

Solid dosage forms for oral administration include capsules, pills, powders and granules. In the solid dose forms, the active compound is mixed with at least one customary inert excipient (or carrier) such as sodium citrate or dicalcium phosphate; (a) fillers or extenders, such as, for example, starches, lactose, sucrose, glucose, mannitol and silicic acid, (b) bonds, such as, for example, cathoxymethylcellulose, alignates, gelatin, polyvinylpyrrolidone, sucrose and acacia, (c) humectants, such as, for example, glycerol, (d) disintegrating agents, such as, for example, agar-agar, calcium carbonate of calcium, potato or acacia starch, alginic acid, certain complex silicates and sodium carbonate, (e) solution retarders, such as paraffin, (f) absorption accelerators, such as, for example, quaternary ammonium compounds, (g) wetting agents, such as, for example, cetyl alcohol and monostearate of glycerol, (h) absorbents, such as, for example, kaolin and bentonite, and (i) lubricants, such as, for example, talc, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, or mixtures thereof. capsules, tablets and pills, dosage forms can also comprise regulatory agents Solid compositions of a similar type can also be used as fillers in soft and hard filled gelatin capsules using excipients such as lactose or milk sugar as well as high molecular weight polyethyleneglycols and the like Solid dosage forms such as tablets, pills, capsules, pills and granules can be prepared with shells and shells, such as enteric shells and others well known in the art. They can contain opacifying agents, and can also be of such a composition. The active compounds or compounds are released in a certain part of the intestinal tract in a delayed manner. Examples of compositions that may be used are polymeric substances and waxes. The active compounds may also have the microencapsulated form, when appropriate, with one or more than the aforementioned excipients Liquid dosage forms for oral administration include emulsions,! pharmaceutically acceptable solutions, suspensions, syrups and elixirs In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art, such as water and other solvents, solubilizing agents and emulsifiers, such as, for example, ethyl alcohol, alcohol isopropyl, ethyl carbonate, ethyl acetate, benzyl alcohol, benzoate benzyl, propylene glycol, 1,3-butylene glycol, dimethylformamide, oil, in particular, cottonseed oil, peanut oil, corn germ oil, olive oil , castor oil and sesame oil, glycerol, alcohol - I tetrahydrofurfuryl, polyethylene glycols and esters of fatty acids or mixtures of these substances, and the like.

In addition to the inert diluents, the composition may also include adjuvants, such as wetting agents, emulsifying and suspending agents, flavoring and perfume agents.

The suspensions, in addition to the active compounds, may contain suspending agents, such as, for example, ethoxylated isistearyl alcohols, esters of sorbitol and sorbitan polyoxyethylene, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar - agar and tragacanth, or mixtures of these substances and the like. \! which are prepared to mix the compounds in the present invention with non-irritating carrier excipients such as cocoa butter, polyethylene glycol or suppository wax, which are solid at ordinary temperature but liquid at the temperature of the body and therefore, melt in the rectum or in the vaginal cavity and release the active component.

Dosage forms for topical administration of a compound of the present invention include ointments, powders, sprays and inhalants. The active compound is mixed under sterile conditions with a physiologically acceptable carrier and any condoms, regulators or propellants as required. Ophthalmic formulations, eye ointments, powders and solutions are also contemplated as part of the scope of this invention. -_ The term "pharmaceutically acceptable salts, esters, amides and prodrugs" as used herein are those carboxylate salts, amino acid addition salts, esters, amides and prodrugs of the compounds of the present invention which are, within the scope of the healthy medical judgment, suitable for use in contact with the tissues of patients without unnecessary toxicity, irritation, allergic response and the like, in proportion to a reasonable benefit / risk ratio, and effective in their intended use, as well as the zwitterionic forms, where possible, of the compounds of the invention. The term "salts" refers to the non-toxic, organic or inorganic acid addition salts of the compounds of the present invention. These salts can be prepared in situ during the i lauryl sulfonate and the like These may include cations based on alkali metal and alkaline earth metal, such as sodium, lithium, potassium, calcium magnesium and the like, as well as non-toxic ammonium cations, ammonium quaternary and amine, but not limited to ammonia, tetramethylammonia, tetraethylammonia, methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine and the like (See, for example, SM Berge, et al, "Sales I Pharmaceuticals "J Pharm Sci, 1977,66 1 - 19 that is incorporated into the present amanera [de I - t reference] Examples of pharmaceutically acceptable non-toxic esters of the compounds C5-C7 as well as arylalkyl esters, but not limited to benzyl C 1 -C 4 alkyl esters are preferred 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 amines of Ci-C6 alkyl and secondary dialkyl amides C_-C6 wherein the alkyl groups are straight or branched chain. secondary amines the amine can also take the form of Z - \ a 5- or 6-membered heterocycle containing a nitrogen atom amides derived from ammonia, primary amines of Ci-C3 alkyl and the secondary amines dialkyl Ct-C2 are preferred Amides of the compounds of the invention can be prepared according to conventional methods The term "prodrug" refers to compounds that are rapidly transduced in vivo to produce the parent compound of the above formulas, for example, by t "hydrolysis in the blood. A complete study is provided by T Higuchi and V Stella, 2 '! "Prodrogas as Innovative Supply Systems", volume 14 of the Sene of the 1st Symposium A C S, American Pharmaceutical Association and Pergamon Press, 1987, both are incorporated herein by reference In addition, the compounds of the present invention can exist in either dissolved or undissolved forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. In general, the dissolved forms are considered equivalent to the non-dissolved forms. for the purposes of the present invention The compounds of the present invention can exist in different stereoisomeric forms by virtue of the presence of asymmetric centers in the compounds I contemplated that all the stereoisomeric forms of the compounds, as well as the mixtures of them including racemic mixtures, form part of this invention The compounds of the present invention can be administered to a patient at dosage levels in the range of about 0 1 to about 1,000 mg per day. For a normal human having a body weight of about 70 kilograms, a dose in the range from about 0 to about 100 mg per kilogram of body weight per day is preferable. The specific dose used, however, may vary For example, the dose may depend on a number of factors including the patient's requirements, the severity of the condition being treated and the activity pharmacological of the compound used. The determination of optimal doses for a particular patient is well known to those skilled in the art.

In addition, it is intended that the present invention cover compounds already made by the use of standard organic synthetic techniques, including combinatorial chemistry or by biological methods, such as through metabolism. r -. '? The examples presented below are intended to illustrate particular examples of the invention and are not intended to limit the scope of the description, including the claims, in any form.

EXAMPLES The compound of Formula I can be prepared by the process described in scheme 1 below.

General Synthesis The dimerisation of malononitrile in the presence of HBr gives 2-bromo-3-cyan? Raney provides the key intermediate 4,6-diamino-3-pyridylcayloxyaldehyde [(IV) as previously described in U.S. Patent No. 5,620,981 issued April 15, 1997, which is incorporated herein by way of reference Depending on ~ f the degree of the catalyst used, it may be preferable to use small and multiple additions of fresh catalyst for several days of reaction. The product can be isolated and purified in good yield typically 70%) by carrying out multriple extractions of the aqueous solution (filtered and neutralized) with an organic solvent, for example ethyl acetate - The aldehyde can then be directly condensed with an aryl acetonitrile to provide a 3-aryl-2,7-diamino-1,6-naphthyridine (VI), also described in U.S. Patent No. 5,260,981, after the manner described by Hawes et al, [Hawes EM, Gorecki DKJ, J Heterocyclic Chem, 1972, 9703] This reaction is typically achieved in a boiling alcohol (preferably 2-ethoxyethanol) and in the presence of an alkoxide base (preferably 2-ethoxyethoxide) of sodium), which can be generated in situ by the addition of sodium metal or sodium hydride to the alcohol solvent Despite the fact that the use of only one equivalent of aryl acetonitrile and a catalytic amount of the base (preferably 0 4 equivalents) in a minimum amount of solvent is enough to complete the reaction, better yields can be obtained (74% - 81%) with two equivalents of nitrile and base equally The desired product is separated by chroma Tography on a solid support (preferably silica gel) from a material derived from the reagent and a minor derivative The derivative is a 7-amino-2 - (arylmethyl)? pyrido [4,3-djpyrimidine (V), which results from a condensation reaction involving nitrile itself r 3-Aryl-2,7-diamino-1,6-naphthyridine can be converted to a 3-apl-7-fluoro-1H- [1, 6] naphthyridin-2-one, (VII) in reasonable production (typically 50% - rt 60%) by a diazotization reaction in 50% aqueous fluoro acid, using a large excess (up to 8 equvalent) of solid sodium nitrite at low temperature (-5 ° C or less) for several days, following the manner previously described [Rewcastle GW, fi_ i Palmer B D, Thompson A M, Bridges A J, Cody D R, Zhou H, Fry D J, McMichael A, ; _ í Denny WA, J Med Chem, 1996, 39, 1823] The product of this reaction is obtained by extraction in an organic solvent (preferably ethyl acetate), after careful I neutralization at low temperature with an inorganic base (preferably sodium carbonate), then the separation of the product dione (VIII) by chromatography. This intermediate naphthyridin-2-one can be N-alkylated in high yield by treatment with an alkyl iodide in the presence of a base (preferably sodium hydride). sodium) in a suitable dry and non-active solvent (preferably dimethylformamide) at from 0 ° to 20 ° C A small amount of the product (X) of the O-alkylation can also be obtained and removed by chromatography. The 1-alkyl- ~ - i 3 - . 3-aryl-7-fluoro-lH [1, 6] naphthyridin-2-one (IX) is a reactant and stocking intermediate that can be directly reacted with any aliphatic amines in an appropriate solvent I (preferably 2-pentanol or the case of gaseous amines in 2-piopa? ol using an appropriate pressure vessel) or with certain aryl amines at temperatures of 90 to 175 ° C for between 30 minutes to 3 days will provide the compounds of the Formula I wherein R5 is an aryl group and the dotted line is a bond As an alternative, the same fluorine intermediate can be treated with the lithium anion of t-aryl amyria in a suitable dry and non-reactive solvent (preferably tetrahydi ofuran ) at - 78 ° CI up to 20 ° C for up to 3 days to give more compounds of Formula I These The compounds of Formula 1 can also be prepared by process I described in scheme 2 below i The key intermediate 4,6-diamino-3-pyridylcarboxaldehyde (IV) can be reacted with either a stabilized phosphorane or a phosphonate ester in the presence of a + base, or any alternative Wittig or Horner-Emmos reagent to provide the ester I without corresponding saturation The resulting double bond can be trans, cis or a mixture1 of | i both. For example, the reaction of a 4,6-diamino-3-pyridylcarboxaldehyde with an excessive amount of the stabilized phosphorane (ca -rhoxymethylene) triphenylphosphorane at 1.4 f-1! dioxane at reflux temperature gives mainly, or in some cases exclusively, 1 the The unsaturated ethyl ester trans (XI) After the base treatment, chain closure occurs to make the desired 7-amino-1,6-naphthyridin-2-one (XII) This reaction can be carried out using a tertiary amine such as triethylamine or, offereeness, N, N-diisopropylmethylamine as a solvent, with d: from 1 to 190 equivalents of 1,8-diazabicyclo [5.4 Ojundec-7-ene present The reaction is carried It is usually carried out at 2 to 24 hours as an alternative, 4,6-diamino-3-pyridylcarboxaldehyde can be reacted with a phosphonate ester such as bis (2,2,2-trifluoroethyl) ( methoxycarbonyl-methyl) -phosphonate using a strong non-related base (Tetrahedron Lett., 1983 4405) to give predominantly, but not exclusively, the unsaturated cis ester After treatment with a base under the conditions described above, chain closure occurs The intermediate naphthyridin-2-one (XII) can be N-alkylated in good yield by treatment with an alkyl iodide in the presence of a base (preferably sodium hydride) in a suitable non-reactive dry solvent (preferably N, N-dimethylformamide) at 0 ° C to 20 ° C. A small amount of the product (XIV) of the O-alkylation can also be obtained and removed by chromatography. The 1-alkyl-7-amino-1,6-naphthyridine-2- The resulting (XIII) can be converted to 1-alkyl-7-fluoro-1,6-naphthyridin-2-one (XV) at reasonable yield (typically between 50% -60%) by a diazotization reaction in aqueous fluoro acid 50%, using an excess of solid sodium nitrite at low temperatures (-5 ° C or less) for several hours. The product of this reaction is obtained by extraction in an organic solvent (preferably ethyl acetate), following careful neutralization at low temperature with an inorganic base (preferably sodium carbonate), then purification by chromatography. The 1-alkyl-7 - fluoro-1,6-naphthyridin-2-bna appropriate pressure) or with certain aryl amines at temperatures from 90 to 175 ° C between 30 I minutes to 3 days to provide the compounds of Formula I wherein R5 is. hydrogen and the dotted line is a bond As an alternative, the XV intermediate can be treated with the lithium anion of the aryl amines in a suitable solvent, dry and non-reactive (preferably tetrahydrofuran) at -781 ° to 20 ° C for up to 3 days to give more compounds of Formula I These compounds are typically purified by chromatography on silica gel and / or alumina and then crystallization at from appropriate solvents. The compounds of Formula I can then be transformed into the dihydro freezer of Formula I, where R is hydrogen and the dotted line is absent, by standard reaction methods. The preferred method is to use catalytic hydrogenation with a standard catalyst such as palladium or Raney carbon or nickel A range of solvents is possible for this transformation including minor alcohols, ethers and amides Allocation meiioies Esla tiansloimacion can also be carried out in a tempeiatuias iango and piesiones 215 5-218.5 ° C [W J Middleton, United es Patent, Chem Abstracts, ± 957,: f 2, 790, 806 (51) P 14829 melting point record (EtOH) 255 ° C, Carboni R A, t Coffman DD, Howard EG, J Am Chem Soc, 1958, 80 38287 melting point 260-265 ° C dec] 1 H NMR [(CD3) 2 SO] d 6 66, 6 54 (2 br s, 2 x 2 H, 2 NH2), 5 60 (s, 1H, H -? 5) 13 C NMR d 160 66, 157 46 (2 s, C - 4, 6), 143 73 (s, C - 2), 11T00 (s, CN ), 86 37 ^ (d, c - 5), 85 31 (s, C - 3) Experiment 2 Anhydrous HBr (90 g, 11 mole) is concentrated in a Parr reactor containing 1, 1, 2 dichloromethane (500 mL) at 0 ° C Malononitrile (40 g, 0 605 mol) is added, the The reactor and the resulting mixture were stirred at 100 ° C for 16 hours. The solution was cooled C) and the solid is collected by filtration, The suspension is adjusted to a pH of 9 with concentrated aqueous ammonia hydroxide, stirred for 2 hours and then filtered. The collected solid is washed well with water and dried to give 2-bromo-3-cyano-4,6-diaminopyridine. (II) (42 4 g, 66%) melting point (water) 215 5-218 ° C [WJ Middleton, United es Patent, Chem.

Abstracts, 1957, 2, 790, 806 (51) P14829 point records of Carboni R A, Coffman D D, Howard E G, J Am Chem Soc, 1958, 80 2838 record H I of melting point 260 - 265 ° C dec] The spectral data were the same as those observed in Experiment 1 A solution of (II) (15 1 g, 0 071 mol), KOAc (7.0 g, 0.071 mol) and 5% Pd / G (4 g) in THF (tetrahydrofuran) (130 mL) and MeOH (methanol) ) (70 mL) are hydrogenated (55 psi / 20 ° C for 7 days. The resulting solution is filtered over Céhte, washed with THF / MeOH and the solvents are removed under reduced pressure. The residue is dissolved in - -? i HCl diluted and then the solution is neutralized with NaOH at 40% melting point 197 - 198 ° C [Metzger R, Oberdorfer J, Schwager C, Thielecke W, Boldt, Liebigs Ann Chem, 1980, 946-953 melting point record (benzene) 205 ° CJ 1H NMR [(CD3) 2 SOJ d 7 91 (s, 1H, H-2), 153 86 (d, C-2), 118 10 (s, CN), 87 71 (d, C-5), 83 84 (sj C-3) Extraction of the remaining liquor with EtOAc (4 x 200 mL) produces additional (III) (2 12 g, 22%) A solution of (III) (5 00 g, 37 3 mmol) and W - 7 Raney - Nickel freshly prepared * ~ \ / 120 mg of wet catalyst in absolute EtOH [ethanolj in 99% formic acid (150 f mL) and water (40 mL) is hydrogenated (60 psi / 20 ° C) for 2 days Fresh catalyst is added (130 mg) and the reaction is continued for 5 days, then additional catalyst I (207 mg) is added and the reaction is continued for 2 days. The resulting solution is filtered on Celite, washed with formic acid and then the solvents are filtered. Remove under reduced pressure. The residue is diluted with water (150 mL), then an excess of Na2CO3 r1 is added and the solution is extracted with EtOAc (ethyl acetate) (15 x 100 mL). Removal of the solvent produces a solid (3 65 g, 71%) which is used directly Chromatography of a sample on neutral alumina, eluting with MeOH of 1-3% / CHCl3, produces 4,6-diamino-3-pyridylcarboxaldehyde (IV) melting point (MeOH / CHCl3 / light oil) i 343 ° C 1 H NMR [(CD 3) 2 SOJ d 9 48 (s, 1 H, CHO), 8 04 (s, 1 H, H-2), 7 12, 6 46 (2 br s, 2 x 2 H, 2 NH 2), 555 (s, 1 H, H-5) 113 J C NMR d 19027 (d, CHO), 16234 (s, C-4 or 6), 15977 (dfC-2), 15514 (s , C - 4 or 6), 11045 (s, C - 3), 8698 d, C - 5) Analysis calculated for C6H7N3OHCl requires: C, 41.5; H, 4.7; N, 24.2% Found: C, 41.5; H, 4.6; N, 24.1%.

To a solution of sodium (31.5 mg, 1.37 mmol) dissolved in 2-ethoxyethanol (1.3 mL) was added 2,6-dichlorophenyl-acetonitrile (0.70 g, 3.76 mmol) and (IV) (467 mg, 3.41 mmol) and (IV) (467 mg, 3.41 mmol) and then the mixture is stirred at reflux for 2 hours. The solvent is removed under reduced pressure and then the residue is diluted: (br s, 2H, NH2), 6.36 (s, 1H, H-8), 4.55 (s, 2H, CH2). 13 C NMR d 166 88 (s, C - 2), i 162. 45 (s, C-7), 160.45 (d, C-4), 154.27 (d, C_- 5), 153.96 (s, C-8a), 13564 (s, 2C, (C -2 '- 6' ), 134.12 (s, C-1 '), 1239.23 (d, C-4'), 128.22 (d, 2C, C-3 ', 5'), 112.88 (s, C -4a), 95.0Í (d , C-8), 40.86 (t, CH2).

Analysis calculated for C14H? Or C12N4 requires: C, 55.1; H, 3.3, N, 18 4% l Found: C, 55.2; H, 3.0; N, 18.6%.

A larger elution with 0.5-3% MeOH / CHC13 produces 2,7,7-diamino-3 - (2,6-dichlorophenyl) - [1,6] naphthyridine (VI) (708 mg, 68%): melting point ( CH2C12 / light oil) 218-213 ° C. 1HNMR [(CD3) 2SO] d 8.40 (s, 1H, H-5), 7.59 (d, J = 7.8 Hz, 2H, H-3'-5'j. 7.59 (s, 1H, H-4), 7.46 (dd, J = 8 7, 7.4 Hz, 1H, H-4 '), 6 29 (s, 1H, H-8), Analysis calculated for C8H7C12N requires. C, 47.1; H, 3.4; N, 6 9% Semen against: C, 47.3; H, 3.5; N, 7.1%.

Further crystallization of the liquors produces (V) (42 mg, 4%) Additional elution of the column with 4 - 4 5% MeOH / CH2C12 produces (VI) (920 mg, 82%) A suspension of (VI) (1 55 g, 5 08 mmol) in 50% HBF 4 (75 mL) at -5 ° C is treated with solid NaNO 2 (3.0 g, 43 5 mmol added in small portions for 5 hours. ), then kept at -20 ° C for 5 days The resulting mixture is neutralized with Na2C? 3 / solid ice, keeping the temperature below -10 ° C and extracted with EtOAc (4_x 150 mL) of silica, eluting it fluoro-1 H - [1,6] naphthyridin-2-one, (VII) (0 91 g, 58%) melting point (CH2Cl2 / light oil) 254 5 - 255 5 ° C ' 'H NMR [(CH3) 2SO] d 12 54 (br s, 1H, NH), 8 66 (s, 1H7H ^ - 5), 8 13 (s, 1H), H -4), 7 61 (d, J = 8 2 Hz, 2 H, H - 3 ', 5'), 7 49 (dd, 7 = 8 8, 7 4 Hz, 1 H, H - 4 '), 6 98 (s, 1 H, H ! 13C NMR d 163 55 (d, Jc _ F = 234 Hz, C-7), 159 77 (s, C-2), 148 95 (dd, Jc.) F = 19 Hz, C-5), 147 69 (d, Jc-F = 12 Hz, C-8a), 138 13 (d, C-4), 134 51 (s, 2C, C-2 \ V), 133 51 (s, C-1 '), 130 85 (d, C-4'), 129 61 (d, Jc-F = 2 5 Hz, C-3), 128 08 (d, 2C, C 3 ', 5'), 114 34 (d, JC_F = 2 5 Hz, C-4a), 92 95 (dd, JC_F = 42 Hz, C-8) 1 Analysis calculated for C? 4H7Cl2FN2O requires C, 54 4, H, 2 3, N, 9 1, F, 6 2% Found C, 54 0, H, 2 0, N, 9 2, F, 6 1% Additional elution with 10-12% MeOH / CH2C12 / produces 3 - (2, '6-dichlorophenyl) -1H, 6H- [1,6] naphthyridine-2 7-dione, (VIII) (0 45 g, 29 & amp;;) melting point (MeOH / CHCl3) 363 - 369 ° C dec ' 1 H NMR [(CD_) 2 SO] d 12 07, 11 55 (2 br s, 2 H, 2 NH), 8 10 (s, 1 H, H-5), 7 67 (s, í 1 H, H-4J, 7 56 (d, J = 8 1 Hz, 2H, H-3 ', 5'), 7 44 (dd, J = 8 8, 7 5 Hz, 1H, H-4 '), 5 90 (s, 1H, ? - 8) 13C NMR d 161 84, 160 38 (2s, C-2, 7), 147 87 (s, C-8a), 139 65 (br d, C -r 5), 138 60 (d, C-4), 134 90 (s, 2C, C-2 '-6'), 133 90 (s, C-1 '), 130 50 (d, C-4'), 12 / 97 (d, 2C, C .- 3 ', 5'), 124 18 (s, C-3), 105 09 (s, C-4 '), 95 50 (d, C-8). 4, Analysis calculated for C? 4HgCl2N2O2 requires C, 54 7, H, 2 6, N, 9 1% C, 54 6, H, 2 5, N, 9 0% r was found To a stirred solution of (VII) (2 00 g, 6 47 mmol) and dry DMF (50 mL) at 0 ° C is added 60% NaH (0 31 g, 7 75 mmol), followed by Mel ( 0 48 mL, 8 03 mmol) and the mixture is stirred at 0 ° C for 2 hours. The solvent is removed under reduced pressure, then the residue is diluted with mL) and extracted with EtOAc (3 x 150 mL) The solvent is removed, then the chromatography of the residue on silica gel, * I eluting it with 33% light petroleum / CH2Cl2, produces first 3 - (2, 6 -? dichlorophenyl) -7-fluoro-2-methoxy- [1,6] naftp idine (X, where R ~ is methyl) (39 mg, 1.2%) melting point (CH2Cl2 / crude oil) 165-165 5 ° C 1HNMR [(CD3) 2SOd 9.05 (s, 1H, H -3), 8.51 (s, 1H, H-4), 7.66 (d, J = 8.2 ^ Hz, 2H, H-3 \ 5 '), 7.53 ( dd, J = 8.6, 7.6 Hz, 1H, _ - 4 '), 7.49 (s, 1H, H-8), 402 (s, 3H), OCH3). 13 3 / CNMRd 163.68 (d, Jc _F = 234 Hz, C- 7), 162.59 (s, C - 2), 15293 (d, JC_F = 13 Hz, C - 8a), 150.80 (dd, JC - F = 18 Hz, C-5), 139.53 (d, C-4), 13433 (s, 2C, C-2 ', 6 '), 133.02 (s.C-1'), 131.11 (d, C-4 '), 128.27 (d, 2 C, C -3', 5 '), 12219 (d, JC_F = 2.4"- - 1 - Hz, C - 3), 119.46 (d, JC_F = 3.0 Hz, C - 4a), 102.52 (dd, JC_F = 37 Hz, (C - 8), 54.58 (q, Analysis calculated for Ci5H9Cl2FN2O requires C, 55 8, H, 2 8, N, 8 7, F, 5 9% C was found, 55 8, H, 2 5, N, 8 5, F, 5 9% A solution of compound IX, (where R 2 is methyl) (80 mg, 0 25 mmo 1 r), 25% ammonium hydroxide (5 0 mL, 66 mmol) in 2-propanol (30 mL) is saturated with ammonia (gas). ) and stirred at 170 ° C in a pressure flask for 3 days. The solvent is removed, then the residue is diluted with Na 2 CO 3 (50 mL) and extracted with CH 2 Cl 2 (3 x 50 mL) The solvent is removed, then the chromatography of the residue on silica gel,! i eluting with 1 - 2% MeOH / CH2Cl2, produces 7-amino-3- (2,6-dichlorophenyl) -1-methyl-1H- [1,6] naphthyridin-2-one, (70 mg, 88% ) melting point 239 - 240 ° C 1 H NMR [(CD 3) 2 SO] d 8 37 (s, 1 H, H-5), 7 76 (s, 1 H, H-4), 7 56 (d, J = 8 2 Hz, F 2 H, H- 3 ', 5'), 7 43 (dd, J = 8 7, 7 4 Hz, 1H, H - 4), 6 65 (br s, 2 H, NH 2), 6 30 (s, ÍH ^ H -8) , 63 49 (s, 3H, NCH3) ^ 13C NMR d 161 24, 159 76 (2s, C-2, 7), 150 91 (d, C-5), 146 26 (s, C-8a), 138 32 (df (C-4), 135 07 (s, 2C, C-2 ', 6'), 135 03 (s, C-1 '), 130 23 (d, C-4'), 127 96 (d, 2C, C-3 ', 5'), 122 19 (s, C-3), 108 18 (s, _C-4a), 88 28 (d ^ C-8), 28 76 (q, NCH3 ) ff Analysis calculated for C15H11CI2N3O requires C, 56 3, H, 3 5, N, 13 1% 'Found "C, 56 1, H, 3 3, N, 13 1% [ EXAMPLE B Preparation of 3 - (2,6-dichlorophenyl) -1-methyl-7-methylamino-1H- [1,6] I naphthyridin-2-one A solution of compound IX, (where R 2 is methyl) (103 mg, 0 32 mmol), and 40% aqueous methylamino (5 0 mL, 58 mmol) in 2-propanol (30 mL) is stirred at 100 ° C in a pressure vessel for 5 hours The solvent is removed, then the residue is diluted with aqueous Na2CO3 (50 mL) and extracted with CH2C12 (50 mL) and extracted with CH2C1-((3 x 50 mL) by removing the solvent 3 - (2,6-dichlorophenyl) -1-methyl-7-methyl-amino-1H- [1,6] naphthyridin-2-one, (103 mg, 97%) melting point is produced 13832 (d, C-4), 13505 (s, 2C, C-2 ', 6'), lJ504 (s, C-1 '), 13019 (d, C-4'), 12793! (d, 2C, C-3 ', 5'), 122 03 (s, C-3), 108 03 (s, C-4a), 86 98 (br d, C-8), 28 82, 28 83 ^ ^ í * ^ (2q, 2NCH3) Analysis calculated for C? 6H? 3Cl2N3O requires C, 57 5, H, 3 9, N, 12 6% Found C, 57 5, H, 4 0, N, 12 6% EXAMPLE C Preparation of 3- (2,6-dichlorophenyl) -7-dimethylamino-1-methyl-1H- [1,6] naphthyridin-2-one; i A solution of compound IX (where R is methyl) 102 mg, 0 32 mmol) and 40% aqueous dimethylamino (50 mL, 40 mmol) in 2-propanol (50 mL) is stirred at 90 ° C in a pressure for 30 minutes. The solvent is removed, then the residue is diluted with Na2CO3 (50 mL) and extracted with EtOAc (4 x 50 mL). Removal of the solvent yields 3- (2,6-dichlorophenyl) -7-dimethylamino-1-methyl. - 1H - [1, 6] naphthyridin-2-one; (107 mg, 97%) melting point (CH2C12 / light oil) 265 - 1266 ° C. 1H NMR (CDC13) d 8.40 (s, 1H, H-5), 7 54 (s, 1H, H-4), 7 39 (d, J = 8 2 Hz, 2H, 'H- 3 ', 5'), 7 24 (dd, J = 8.6, 7.7 Hz, 1H, H - 4 '), 6 09 (s, 1H, H - 8), 3 67 (s, 3H, H, NCH3) , -_ j 3. 22 (s, 6H, N (CH3) 2) 13 C NMR d 160 90, 160.02 2 s, C-2, 7), 150.15 (d, C-5), 146 95 (s, C-8a), 138. 29 (d, C-4), 135.88 (s, 2C, C-2 ', 6'), 135 01 (s, C-1 '), 129 48 (d, C-4'), 127 91 r (d, 2C, C-3 ', 5'), 123.80 (s, C-3), 108 33 (s, C-4a), 86 64 (d, C-8), 38 40 (q, 2C, L2 C, - - 1 .

C-3 '- 5 123 80 (s, C-3), 108 33 (s, C-4a), 86 64 (d, C-8), 38 40 (q 2C, N (CH 3) 2), 1 29. 27 (q, NCH3) Analysis calculated for C? 7H? 5Cl2N3O requires C, 58 6, H, 4 3, N, 12 1%) Found C, 58 9, H, 4 2; N, 12 4% EXAMPLE D Preparation of 3- (2,6-dichlorophenyl) -7 - [2 - (dimethylamino) ethylaminoj-1 [methyl-1 H - [1,6J-naphthyridin-2-one, A solution of the compound (IX), (where R is methyl) (101 mg, 0 31 mmol) and N, N-diethylethylenediamine (0 45 mL, 3 21 mmol) in 2-pentanol (10 mL) is stirred at 115 °. C H - 3 ', 5'), 724 (dd, J = 85, 77 Hz, 1H, H - 4 '), 607 (s, 1H, H - 8), 567 (br s, 1H, NH), i 365 (s, 3H, NCH3), 338 (q, J = 56 Hz, 2H, NHCH2), 275 (t, J = 60? Z, 2 ?, NCH2), 260 t (q, J = 7 ~ 1 Hz, 4H, N (CH2) 2), 106 (t, J = 71 Hz, 6H, 2CH3) 13C NMR d 16080, 15993 (2s, C-2 ^ 7), 15077 (d, C-5), 14716 (s, C-8a), t 13831 (d, C-4), 13586 (s, 2C, C-2 ', 6'), 13491 (s, C-1 '), 12951 (d, C-4'), 12792 (d, 2C, C-3 '-5'), 12398 (s, C-3), 10927 (s, C-4a), 8723 (d, C-8), 5116 (t, NGH2), 4653 (t, JC, N (CH2) 2), 3976 (t, NCH2), 2937 (q, NCH3), 1169 q, 2C, 2CH3) Analysis calculated for C2iH24Cl2N O requires C, 60 2, H, 5 8, N, 13 4% C was found, 60 1, H, 5 6, N, 13 2% i EXAMPLE E Preparation of 3- (2,6-dichlorophenyl) -7- [3 - (diethylamino) propylamino] -1-methyl-1H- [1,6] naphthyridin-2-one, A solution of compound IX (where R 2 is methyl) (101 mg, 0 31 mmol) and 3 - (diethylamino) propylamine (0 50 mL, 3 18 mmol) in 2-pentanol (10 mL) was stirred at reflux for 17 h. hours The solvent is removed under reduced pressure, then the residue is diluted with aqueous Na2CO3 (50 mL) and extracted with EtOAc (4 x 50 mL). The solvent is removed, then the chromatography of the residue on silica gel, eluting with MeOH to the 2 - . 2 - 4% / CH2Cl2 containing 0 3% Et3N, produces a crude product, which is treated with Na2CO3 aqueous and extracted with CH2C12 (3 x 50 mL) to give 3- (2,6-dichlorophenyl) -7- [3-diethylamine) propylamino] -1-methyl-1H- [1,6] naphthyridine-2- ona, (127 mg, 94%) melting point (CH2Cl2 / light oil) 118-120 ° C 1 H NMR (CDCl 3) d 8 33 (s, 1 H, H-5), 7 51 (s, 1 H, H-4), 7 39 (d, J = 8 3 Hz, 2 H, H-3 ', 5' ), 7 24 (dd, J = 8 6, 7 7 Hz, 1H, H - 4 '), 6 36 (br s, 1H, NH), 6 01 (s, 1H, H? 8), 3 64 (s, 3 H, NCH 3), 3 43 (td, J = 6 1, 5 3 Hz, 2 H, NHCH), 2 60 (i, J = 6 3 Hz, 2 H, NCH 2), 2 57 (q, J = 7 1 Hz, 4H, N (CH2) 2), 1 83 (pentet, J = 6 3 Hz, 2H, CH2), 1 07 (t, J = 7 1 Hz, 6H, 2CH3 ) '" 13C NMR d 160 82, 160 05 (2s, C-2, 7), 150 87 (d, C-5), 147 14 (s, C- | 8a), 138 36 (d, C-4), 135 88 (s, 2C, C-2 ', 6'), 134 96 (s, C-1 '), 129 48 (d, C-4'), 12 * 7 91 (d, 2C, C-3 ', 5'), 12372 (s, C-3), 10911 (s, C-4a), 8665 (d, C-8), 5187 (t, NCH2), 4701 (t, 2C, N (CH_) 2, 4234 (t, NCH2), 2932_ (q, NCH3), 2595 (t, CH2), 1181 (wq, 2C, 2 CH3) Analysis calculated for C22H26Cl2N O requires C, 61 0, H, 6 1, N, 12 9% f Found "C, 61 0, H, 5 9, N, 12 8% 1 EXAMPLE F Preparation of 3- (2,6-dichlorophenyl) -7- [4 - (diethylamino) butylamino] -1-methyl-1H- [1,6] naphthyridin-2-one, A solution of compound IX (where R 2 is methyl) (104 mg, 0 32 mmol) and 4 - (diethylamino) butylamino (0 51 g, 3 54 mmol) in 2-pentanol (10 mL) is stirred at reflux for one day The solvent is removed under reduced pressure, then the residue is diluted with aqueous Na 2 CO 3 (50 mL) and extracted with EtOAc (3 x 50 mL). The solvent is removed, f after chromatography of the residue on silica gel, eluting with 2 - 5% MeOH / CH2Cl2 containing 0 3% Et3N, produces a crude product, which is treated with aqueous Na2CO3 and extracted with CH2C12 (4 x 50 mL). The solvent is removed, then the chromatography of the residue on alumina, eluting with 0-5-1% MeOH / CH2Cl2, produces 3- (2,6-dichlorophenyl-7 - [4 - (diethylamino) butylamino] -1-methyl-1H- [1, 6] naftaridin-2-one, (125 mg, 87%) melting point (pentane) 123-124 5 ° C [1 H NMR (CDCb) d 8 32 (s, 1 H, H-5), 7 52 (s , 1H, H - 4), 7 39 (d, J = 8 4 Hz, 2H, H - 3 ', 51), 1 24 (dd, J = 8 5, 7 6 FIz, 1H, H - 4 *), 6 03 (s, 1H, H - 8), 5 59 (br s, 1H, NH), - _ 3 64 (s, 3H, NCH3), 3 35 (td, J = 6 5, 4 6 Hz, 2H, NHCHV), 2 56 (q, J = 7 2? Z, 4 ?, N (CH2) 2), 2 49 (t, J = 7 1 Hz, 2H, NCH2), 1 74 (pentet, J = 7 0 Hz, 2H, CH2), 1 62 (pentet, J = 7 0 Hz, 2H, CH2) , 1 05 (t, J = 7 1 Hz, 6H, 2 CH3) 13 3 3 / C. NMR d 160 81, 159 92 (2 s, C-2 -7), 150 80 (d C-5), 147 17 (s, C-8a), -? L. t 13832 (^ 0-4), 13586 (S, 2C, C-2 ', 6'), 13492 (S, C-1 '), 12951 (d, C-4'), 12791 (d, 2C, C - 3 ', 5'), 12389 (s, C - 3), 10921 (s, C - 4a), 8672 (d, C - 8), 5257 (t, NCH2), 4669 (tic, N (CH2) 2), 4247 (t, NCH2), 2934 (q, NCH3, 2737, 2491 (2 t, 2 CH2), 1.47 -Item (q, 2C, 2 CH3) | Analysis calculated for C23H2gCl2N4O requires C, 61 8, H, 6 3, N, 12 5% C was found, 61 6, H, 6 5, N, 124% [ EXAMPLE G? Preparation of 3- (2,6-dichlorophenyl) -7- [5 - (diethylamino) pentylamino] 1-methyl-1H- [1,6] naphthyridin-2-one, A solution of compound IX (where R2 is methyl) (94 mg, 0 29 mmol) and 5-i (diethylamino) pentylamino (052 g of ca 90%, 2.96 mmol) in 2-pentanol (10 mL) is stirred at reflux for 18 hours. The solvent is removed under reduced pressure, then the residue is diluted with aqueous Na2CO3 (50 mL). piL) and extracted with EtOAc (4 x 50 mL) The solvent is removed, then the chromatography of the residue on silica gel, eluting with 1-2% MeOH / CH2C12 containing Et3, produces a crude product, which is treated t with Na2CO3 and extracted with CH2C12 (4 x 50 mL) The solvent is removed, then chromatography of the residue over alumina, eluting with 1% EtOH > / CHC13, produces 3 - (2,6-dichlorophenyl) -7- [5-diethylamino) pentylaminoj-1-methyl-1H- [1,6] naphthyridine - 2 - ona; (125 mg, 93%): foam. I 1 H NMR (CDCl 3) d 8.32 (s, 1 H, H-5), 7.52 (s, 1 H, H-4J, 7.40 (d, J = 8.0 Hz, 2H, 3 ', 5'), 7.52 (dd, J = 8.6, 7.7 Hz, 1H, H - 4 '), 6.04 (s, 1H, H - 8), 5.06 (br t, J = 5.4 Hz, ¡1H, NHCH2), ~ 3.65 (s, 3H, NCH3), 3.34 (td, J = 6.975.1 Hz, 2H, NHCH2), 2.53 (q, J = 7 2 Hz, 4H, N (CH2) 2), 2.44 ( t, J = 7.4 Hz, 2H, NCH2f 1.73 (pentet, J = 7.2, 2H, CH2), 1.54, 1.46 (2 pentet, J = 7.5 Hz, 2 x 2 H, 2 CH2), 1.03 (t, J = Hz, 6H, 2 CH_). ~ 7-_ ~~~ "I 13C NMR d 160.78, 159.86 (2s, C-2, 7), 150.76 (d, C-5), 147 25 (s, C - 8a), 138. 28 (d, C-4), 135.85 (s, 2C, C-2 ', 6'), 134.87 (s, C-1 '), 129.53 (d, C-4'), 127.92 (d, 2C, C-3 ', 5'), 124.05 (s, C-3), 109.30 (s, C-4a), 86.61 (d, C-8), 52.73 (t, NCH2), 46. 86 (t, 2C, N (CH2) 2), 42.47 (t, NCH2), 29.38 q, NCH3), 29.15, 26.85, 25.07 (3t, 3 CH2), t t 11. 59 (q, 2 C, 2 CH_). Analysis calculated for C24H30C12N4O requires: C, 62.5; H, 6.6; N, 12.1% Found: C, 62.2; H, 6.7; N, 11.8%. ": I EXAMPLE H r Preparation of 3- (2,6-dichlorophenyl) -1-methyl-7 - [3 - (4-methylpiperazi? -1 - il) propylamino] - 1 H - [1,6] naphthyridin-2-one; ? .- A solution of compound IX (where R2 is methyl) (80 mg, 0.25 mmol) and 1- (3-aminopropyl) -4-methylpiperazine (0.42 g, 2.66 mmol) in 2-pentanol (10 mL) is stir at 1 reflux for 16 hours. The solvent is removed under reduced pressure, then the residue is diluted with Na 2 CO 3 (50 mL) and extracted with EtOAc (3 x 50 mL). The solvent is removed, then the chromatography of the residue on silica gel, eluting it with 3 - 6% MeOH / CH2Cl2 containing 0 3% Et3N, gives a dropped product, which is treated with Na2CO3 and extracted with EtOAc (3 x 50 mL) to give 3- (2,6-dichlorophenyl) -1-methyl-7 - [3- (4-methylpiperazin-1-yl) propylamino] -1H- [1,6 Naphthyridin-2-one, (99 mg, 87%): melting point (CH2Cl2 / hexane) 164-166 ° C. 1 H NMR [(CD3) 2 SO] d 8 40 (s, 1H, H = 5) , 7 74 (s, 1H, H - 4), 7 56 (d, J = 7 9 Hz, 13C NMR d 160 15, 159.80 (2s, C-2T 7), 150 73 (d, C-5), 146 07 (s, C-8a), zi 138.32 (d, C-4), 135.07 (s, 3C, C-1 ', 2', 6 '), 13023 (d, C-4'), 12797 (d, 2C.C-3 ', 5'), 12204 (s, C-3), 10810 ( s, C-4a), 8773 ~ (br d, C-8), 5553"(t, NCH2), 5470, 52.66 (2t, 2 x 2C, N (CH2) 4N), 45.67 (q, NCH3), 3943 (t, NCH2), 2881 (q, NCH3), 26 ¿7 (t, CH_). t _ r Analysis calculated for C 23 H 27 Cl 2 N 5 O requires C, 60 0, H, 5 9, N, 15 2% C was found, 59.8; H, 6 2, N, 15 0% ' EXAMPLE I; i I Preparation of 3 - (2,6-dichlorophenyl) -1-methyl-7 - [4 - (4-methylpiperazine-1 - il) butylamino] - 1 H - [1,6] naphthyridin-2-one, t U - a solution of compound LX (where -e R2 is methyl) (101 mg, 0.31 nimol) and 1 - (4 - aniinobiitip-4-methylpiperazine (0.55 g 3.22 minol) in 2-pentanol (10 niL) is stirred at reflux for 16 hours. The solvent is removed under reduced pressure, then the residue is diluted with aqueous Na2CO3 (50 L) and extracted with EtOAc (3 x 50 mL). The solvent is removed, then the chromatography of the residue on alumina, eluvéndoio with EtOH at 1 - 2% / CHCL. produces 3 - (2,6-dichlorophenyl) -1-methyl-7 - [4 - (4-methylpiperazin-1-yl) butylamino-1H-fl, 61-naphthyridin-2-one; (140 7., | mg, 94%): foam. 1 H NMR (CDCb) d 8.32 (s, 1 H, H-5), 7.52 (s, 1 H, H-4), 7 39 (d, J = 8.1 Hz, 2 H, H-3 ', 5'); 7 23 (dd, J = 8.6, 7.7 Hz, 1H, h ~ 4 ') 6.03 (s, 1H, H-8); 5 54 (br s,? H, f NHCH 2), 3.64 (s, 3 H, NCH 3), 3.36 (td, J = 6.2, 4.4 Hz, 1 H NHCH 2); 2.8 - 2.2 (br s, 8H, N (CH2) 4 N); 2.42 (t, J = 7.1 Hz, 2H, NCH2); 2.30 (s, 3H, NCH2), 1.75 (pentet, = 6 7 Hz, 2H, CH2); 1.66 (pentet, J = 6.9 Hz, 2H, CH_). '13C NMR d 160.75, 159.85 (2s, C-2.7), 150.74 (d, C-5); 147 13 (s, C-8a); 138. 27 (d, C-4) 135.8 (s; 2C, C-2 ', 6'), 134.85"(s, C-1 '); 129.49 (d, C-4'); 127.88 (d, 2C, C-3 ', 5'); 123.88 (s, C-3); 109.19 (s, C-4a); 86.67 (d, C-8); 57.90 (t, NCH2); L 55.02, 53.11 (2 t, 2x2C, N (CH2) 4N) "; 46.00 (q, NCH3); 42.35 (t, NCH2); 29.34 (q, NCH3); 27.08, 24.47 (2t, 2CH2). - "*" I Analysis calculated for C24H2 Cl2N5O 1 0.5 H2O requires: C, 59.6; H, 6.3; N, 14.5%. "'L Found: C, 59.6; H, 5.9; N, 14.5%.

EXAMPLE J Preparation of 3- (2,6-dichlorophenyl) -1-methyl-7 - [5 - (4-methyl-pperazin-1-yl) -pentylamino-1 H - [1,6-naphthyridin-2-one; A. Solution of compound IX (where R is methyl) (102 mg, 0 32 mmol) and 1 - ([5-aminopentyl) -4-methylpiperazine (0.56 g 3 03 mmol) in 2-pentanol (10 mL) is stirred at reflux for one day. The solvent is removed under reduced pressure, then the residue is diluted with aqueous Na 2 CO 3 (50 mL) and extracted with EtOAc (4"x 50 mL).

Then, chromatograph the residue on silica gel, eluting it with MeOH 2 - . 2-4% / CH 2 Cl 2, which contains 0.3% Et 3 N, produces a crude product, which is treated with Na 2 CO 3 and extracted with CH 2 Cl 2 (4 x 50 mL). The solvent is removed, then chromatography of the residue on alumina, eluting it with 0 25-0.5% MeOH / CH2Cl2 yields 3- (2,6-dichlorophenyl) -1-methyl-7 - [5 - (4-methylpiperazine- 1-yl) pentylamino] -1 H - [1,6] naphthyridin-2-one, (109 mg, 71%): 1 H NMR (CDCl 3) d 8.32 (s, 1 H, H-5), 7.52 (s, 1H, H - 4), 7 40 (d, J = 8 0Hz, 2H, H - 3 ', 5'); 7.24 (dd, J = 8.6, 7.8 Hz, 1H, H - 4 '), 6.03 (s, 1H, H - 8), 5.01 (br t, J = 5.4 Hz,' 1H, NHCH2), 3.65 (s, 3H, NCHs), 3.34 (td, J = 6.9, 5.8 Hz, 2H, NHCH_), 2.8-21 (br s, 8H, N (CH2) 4N), 2.37ÍT, J = 7.6 Hz, 2H NCH2), 2.29 (s, 3H, NCH3), 1.73 (pentet, J = 7 3 Hz, 2H, CH2). 1 58 (pentet, J = 7.5 Hz, 2H, CH2), 1.47 (pentet, J = 7 4 Hz, 2H, CH2) 1 13C NMR d 160.78, 150.84 (2 s, C-2.7), 150.77 (d, C - 5), 147.26 (s, C a), 138.27 (d, C-4), 135.85 (s, 2 C, C-2 '6'), 134 86 (s, C-1 '), 129 55 (d , C-4 '), 127 93 (d, 2C, C-3 *', 5 '). 124.10 (s, C - 3), 109.33 (s, C - a), 86.62 (d, C - 8), 58 45 (t, NCH2), 55.11, 53.26 (2tT2x2 C, N (CH2) 4N), 46.04 (q, NCH3), 42.43 (t, NCH3), 29 40 (q, NCH3), 29 11, 26.60 24798 (3t, 3CH2).

Analysis calculated for C 25 H 31 Cl 2 N 5 O ^ 0.75 H 2 O requires C, 59 8, H, 6.5, N, 14.0%. ! It was found. C, 59.7; H, 6.5; N, 13.8%. 1 I Analysis calculated for C6ll7N3OHCl lequieie. C, 41 5, II, 4 7, N, 24 2% Found: C, 41.5; H, 4.6; N, 24.1%. " EXAMPLE K Preparation of 3- (2,6-dichlorophenyl) -1-methyl-7 - [3 - (4-morpholino) propylamino] -1 H - [1,6] naphthyridin-2-one; A solution of compound IX (where R2 is methyl) (103 mg, 0.32 mmol) and 4- (3-aminopropyl) morpholino (0.47 mL 3.22 mmol) is stirred at reflux for 16 hours. He The solvent is removed under reduced pressure, then the residue is diluted with aqueous Na 2 CO 3. (50 mL) and extracted with EtOAc (3 x 50 mL), the solvent is removed, then [chromatography of the residue on silica gel, eluting with 3 to 5% MeOH / CH 2 Cl 2, - = ^ 1 produces a crude product, which is treated with aqueous Na2CO3 and extracted with CH2CI2 (3 x 1 [ 50 mL) to give 3 - (2,6-dichlorophenyl) -1-methyl-7 - [3 - (4-morpholino) propylamino] -1H - [1,6] naphthyridin-2-one; (133 mg, 93%): melting point (CH2Cl2 / light oil) 157-159 ° C. R 1H NMR (CDCl3) d 8.33 (s, 1H, H-5), 1.52 (s, 1H, H-4). ), 7.40 (d, J = 7.9 Hz, 2H " H - 3 '- 5'), 7.24 (dd, J = 8.6, 7.6 Hz, 1H, H - 4), 6.03 (s, 1H, H - 8), 5.87 (br t, J = 5.2 Hz, 1H, NHCH2), 3.77 (t, J = 4.7 Hz 4H, O (CH2) 2), 3.65 (s, 3H, NCH3), 3 45 (q, J = 6.1 Hz 2H, NHCH2), 2 54 (t, J = 6.6 Hz, 2H, NCH2), 2750 (br m, 4H, N (CH2) 2), 1.87 (pentet, J = 6. 5 HZ, 2H, CH2). 13 C NMR d 160.77, 159.95 (2s, C-2, 7), 150.82 (d, C-5), 147.18 (s, c-8a), 138.29 (d, C-4% 165.83 (s, 2C, C - 2 ', 6'), 134.86 (s, C - 1 '), 129.53 (d, C - 4') 127 92 (d, 2C, C - 3 ', 5'), 123.99 (s, C - 3 ), 109.27 (s, C-4a), 86.73 (d, C-8), 67.02 (t, 2C, O (CH2) 2), 57.20 (t, NCH_), 53.77 (t, 2C, N (CH2) 2), 41.61 (t, NC? 2), 29.36 (q NCH3), 25 29 (t, CH2) Analysis calculated for C22H24Cl N4O2 requires: C, 59.1; H, 5 4, N, 12.5% Found: C , 59.1; H, 5.4; N, 12 5%. "~ EXAMPLE L Preparation of 3- (2,6-dichlorophenyl) -7- [3 - (imidazol-1-yl) propylamino] -1-methyl-1 H - [1,6] naphthyridin-2-one; A solution of compound IX (where R 2 is methyl) (107 mg, 0.33 mmol) and 1 - (3-I-α-aminopropyl) imidazole (0.40 mL 3.36 mmol) in 2-pentanol (10 mL) is stirred at reflux for 16 hours. The solvent is removed under reduced pressure, then the residue is diluted with aqueous Na2CO3 (50 mL) and extracted with EtOAc (3 x 50 mL). The solvent is removed, then chromatography of the residue twice on silica gel, eluting with 3-6% MeOH i / CH2C12, gives a crude product, which is treated with aqueous NaCO3 and extracted with CH2Cl2 (3 x 50 mL) to give 3- (2,6-dichlorophenyl) -7- [3 - (imidazol-1-yl) propylamino] -1-methyl-1 H - [1,6] naphthyridin-2-one; (116 mg, 82% o). melting point f (CH2Cl2 / hexane / ET2O) 175-178 ° C 1H NMR (CDC13) d 8.34 (S, 1H, H-5), "7.54, 7.53 (2s, 2H, H-4.2"), 7.39 (d, J = t 8. 1 Hz, 2H, H-3 '. 5 '), 7.24 (dd, J = 8.5, 7.6"Hz, 1H, H - 4'), 7.11, 6.97 (2s, 2H, H - t 4", 5"), 6.03 (s, 1H, H - 8), 5.09 (br t J = 5.8 Hz, 1H, NHCH2), 4.11 (t, J = 6.8 Hz, '2H, - I NCH), 3.61 (s, 3H, NCH3), 3.41 (q; J = 6.4 Hz, 2H, NHCH2), 2.17 (pentet, J = 6.7 Hz, '1H, ~ \ CH2). 13C NMR d 160.69, 159.52 (2s, C-2.7), 150.61 (d, C-5), 147.10 (s, C-8a), 138.17 (d, C-4), 137.18 (d, C-2"), 135.77 (s, 2C, C-2 ', 6'), 134.72 (s, C-1 '), 129.83, 129.61 (2d, C - 4 ', 4"), 127.93 (d, 2C, C - 3', 5 '), 124.65 (s, C - 3), 118.76 (d, C - 5"), 109.72 (s, C - 4a) , 87.76 (d, C-8), 44.32, 39.02 (2t, 2NCH2)? 30.82 (t, CH2), 29.39 (q, NCH3) l Analysis calculated for C2? H? 9Cl N5O requires: C, 58 9; H, 4.5; N, 16.4%, found: C, 58.5; H, 4.5; N, 16.0%. ~ EXAMPLE M Preparation of 3- (2,6-dichlorophenyl) -1-methyl-7 - (phenylamino) -1H - [1,6] naphthyridin-2-one; A solution of compound IX (where R2 is methyl) (86 mg, 0.27 mmol) and aniline (1.0 mL and 1.0 mmol) is stirred at 175 ° C for 100 minutes. The resulting mixture is diluted with aqueous Na 2 CO 3 (50 mL) and extracted with CH 2 Cl 2, (2 x 50 mL). The solvent is removed, followed by chromatography of the residue on silica gel, eluting with MeOH at room temperature. 1% / CH 2 Cl 2, produces 3 - (2,6-dichlorophenyl) -1-methyl-7 (phenylamino) -1H - [1,6] -r naphthyridin-2-one; (88 mg, 83%): melting point (CH2Cl2 /? Light oil) 237-239 ° C. 1 H NMR [(CD 3) 2 SO] d 9.52 (br s, 1 H, NH,) 8.59 (s, 1 H, H-5) 7.89 (s, 1 H, H-4), J 'I 7. 68 (d, J = 7.7 Hz, 2H, H - 2".6"), 7.58 (d, J = 8.2Hz, 2H, H - 3 '. 5'), 7.45) dd, J = '8.8, 7.5 Hz, 1H, H - 4 '), 7.32 (t, J = 7.9 Hz, H - 3", 5"), 6.98 (t, J = 7.3 Hz, 1H, H - 4"), 6.73 (s, 1H, H-8), 3.56 (s, 3H, NCH3). '' '13C NMR d 159.60, 156.99 (2s, C-2.7), 150.07 (d, C-5), 145.91 (s, C-8a), 140.77 (s, C -, 138.01 (d, C - 4), 134.88 (s, 2X, C - 2 ', 6'), 134.71 (s, C -1 '), 130.38 (d, C -, 4') , -- 1 128. 70 (d, 2C, C-3".5"), 127.97 (d, 2C, C-37.5 '), 124.08 (s, C-3), 121.44 (d, C-4"), 118. 94 (d72C, C-3", 6"), 109.84 (s, C-4a), 91.30 (d, C-8), 28.83 (q, NCH3). 1 Analysis calculated for C2? H15Cl2N3O • 0.75 H2O requires: C, 61.5; H, 4.0; N, 1 10.3%. ~ Found: C, 61.4; H, 3.6; N, 10.2%. ~ i EXAMPLE N Preparation of 3- (2,6-dichlorophenyl) -1-methyl-7- (4-pyridylamino) -1H-t [1,6] -naphthyridin-2-one; A stirred solution of compound IX (where R 2 is methyl) (100 mg, 0 31 mmol) and 4 - . 4-aminopyridine (87 mg, 0.93 mmol) in THF (5.0 mL) under nitrogen at -78 ° C is treated with a solution of LDA in cyclohexane (L2 mL of 1.5 M, 1.8 mmol), then the temperature is increased to 20 ° C and the mixture is stirred at 20 ° C for 2 days. The resulting solution is treated with aqueous NaCO3 and extracted with EtOAc (4 x 50 mL), then the insoluble material is collected by filtration and combined with the above extracts. The solvent is removed, then the chromatography of the residue on silica gel eluting it with 0.5 - 5% MeOH / EtOAc yields 3- (¿T 6 -dichlorophenyl) -1-methyl-7- (4-ι-pyridylamino) -1H - [1,6] -naphthyridin-2-one; (58 mg, 47%): melting point (MeOH / CHCl 3 / light oil) 275-277 ° C. "I 1 H NMR [(CD3) 2 SO] d 9.99 (br s, 1H, NH), 8.70 (s, 1H, H-5), 8.36 (d, J = 5.8 Hz, I 2H, H-3", 5"), 7.98 (s, 1H, H-4), 7.71 (d, J = 5.6 Hz, 2H, H - 2".6"), 7.59 (d, J = 8.1 I Hz, 2H,? - 3'.5 '), 7.47 (dd, J = 8.8, 7.4 Hz, 1H, H - 4'), 6.86 (¿, 1H, H - 8), 3.60 (s 2H, NCH3) .13C NMR d 159.55, 156.01 (2s, C - 2, 7) 149.93 (d, 2C, C - 3".5"), 149.78 (d, C-5), 147.fi (s, C-1"), 145.96 (s, C-8a), 137.97 (d, C-4); 134.80 (s, 2C, C-276 '), 134.51 (s, C-1'), 130.59 (d, C-4 '), 128.05 (df2C, C-3'. 5 '), 125.58 (s, C - 3), 112.25 (d, r 2C, C-2".6"), 110.87 (s, C-4a), 93.79 (d, C-8), 29.03 (q, NCH3). Analysis calculated for C2oH? 4Cl2N4O • 0.5 CH3OH requires: C, 59.6; H, 3.9; N, 13.6%. ^. It was found: C, 59.8; H, 3.8; N, 13.8% (MeOH detected by NMR) EXAMPLE O Preparation of 3- (2,6-dichlorophenyl) -1 - [(4-methoxyphenyl) -1-methyl-1H- [1, 6] naphthyridin-2-one; A mixture of compound IX (where R2 is methyl) (200 mg, 0.62 mmol) and p -anisidine -46 g 11.9 mmol) is stirred at 175 ° C for 4 hours.The resulting mixture is diluted with aqueous Na2CO3 (50 mL). ) and extracted with CH2Cl2, (3 x 50 mL) The solvent is removed, then successive chromatography of the residue on silica gel (3 x), eluting it with 0 to 1% MeOH / CH2C12, yields 3 - (2 , 6-dichlorophenyl) -7 - [(4-methoxyphenyl) -1-metiT-1H- [1,6] naphthyridin-2-one, (99 mg, 38%) melting point (CH_Cl_ / light oil) 173-175 ° C. ~~ 1 H NMR (CDCl 3) d 8 39 (s, 1 H, H-4), 7.40 (d, J = 8.1 Hz, 2 H, H-3 '5') 7 30 (d, J 7 I = 8.9 Hz, 2H, H - 2".6"), 7.24 (dd, J = 8 6, 7.7 Hz, 1H, H - 4"), 6 97 (d, J = 8 8 Hz, 1H, H 1 - 3". 5") ', 5.95 (br s, 1H, NH), 6.40 (s, 1H, H-8), 3 85 (s, 3H, OCH3), 3 54 (s, 3H, NCH3). l 13CNMR d 160.67, 158.79 (2s, C - 2.7), 157.24 (s, C - 4"), 150 74 (d, C - 5), 147 23 (s, C - 8a), 138.00 (d, C - 4), 135.77 (s, 2C, C-2'.6 '), 134 71 (s, C-1'), 131 88 (s, C-'l "), 129.63 (d, C-4 ') , 127 94 (d, 2C, C - 3", 5"), FIO 25 (S, c - 4a), 87 97 (d, C - 8), 55.53 (q, OCH3), 29.41 (q, NCH3) Analysis calculated for C22H? 7Cl2N3? 2 required C, 62 0, H, 4 0, N, 9 9% Found C, 61.8; H, 3.9; N, 10.1%.

EXAMPLE P 1 Preparation of 3- (2,6-dichlorophenyl) -7 - [(4 - (2 - (diethylamino) ethoxy) phenyl) amino j - 1 - methyl - 1 H - [1,6] naphthyridine - 2 - ona; I A solution of compound IX (where R 2 is methyl) (100 mg, 0 31 mmol) and 4 - [2-I diethylamino) ethoxy] aniline (1.18 mL 5.67 mmol) is stirred at 170 ° C for 2 5 hours The resulting mixture is diluted with aqueous Na2CO3 (50 mL) and extracted with CH2C12, (4 x 50 mL). The solvent is removed, then the chromatography of the residue on silica gel, eluting it with 0.25% MeOH / CH2Cl2, produces a crude oil This is purified additionally by reversible preparatory phase (C-18) HPLC (56% CH3CN / aqueous HCO2NH4 buffer, pH 4.5), then by chromatography on alumina (due to partial oxidation during the previous purification), eluting it with 1% MeOH / CH2Cl2, to give 3 - (2,6-dichlorophenyl) -7 - [(4 - (2 - (diethylamino) ethoxy) phenyl) amino] -1-methyl-1H- [1,6] naphthyridin-2-one; (31 mg, 20%): melting point (hexane / Et 2 O) 149 - 150 ° C. _! 'H NMR (CDCl 3) d d 8.40 (s, 1H, H-5), 7O5 (s, 1H, H-5), 7 40 (d, J = 8 0 Hz, 2H, H 1 - 3'.5 '). 7.28 (d, J = 8.9 Hz, 2H, H - 2".6"), 7.25 (dd, J = 8.5, 7.6 Hz, 1H, H - 4 '), 6 97 (d, J = 8.9 Hz, 2H , H - 3". 5"), 6.67 (br s, 1H, NH), 6.39 (s, 1H, H - 8) r 4.09 (t, J = 6.2 Hz, 2H, OCH2), 3 54 (s, 3H, NCH3), 2 91 (t, J = 6.2 Hz, 2H, NCH2), 2.67 (q, J = 7 1 Hz, 4H N (CH2) 2), 1.09 (t, J = 7.1 Hz, 6H, 2CH3). - t 13CNMR d 160.67, 158.79 (2s, C - 2.7), 156.55 (s, C - 4"), 150 72 (d.C - 5) 147 24 (s.C - 8a). 138.00 (d, _C) - 4), 135 77 (s, 2C, C-2'.6 '), 134.71 (s, C 7f'), 131 84 (s, C-1"), 129.63 (d.C-4"). 127.95 (d, 2C, C-3", 5"), 125.25 (d, 2C, C-2".6"), 125 05 (s, C-3), 115.58 (d, 2C, C-3"5"). 110 26 (s.C-4a). i 87. 99 (d, C-8), 66.84 (t, OCH 2), 51.72 (t, NCH 2), 47,873 (t 2C, N (CH 2) -,), 29 41 (q NCH 3). 11 74 (q 2C. _ T 2CH3). 'Analysis calculated for C27H2 Cl2N4? 2 requires: C, 63 4; H, 5 5, N, 1 1 0% i. r I know found; C, 63.5; H, 5.8; N, 11.1% EXAMPLE Q Preparation of 3- (2,6-dichlorophenyl) -1-methyl-7 - [4- (4-morpholino) dimethylamino) butylamino] -1 H - [1,6] -naphthyridin-2-one, A solution of compound (IX), (where j * eT R n 2 is methyl) (100 mg, 0 31 mmol) and 4 - (4 i * - r aminoobutyl) morpholino (050 g, 3 16 mmol) in 2-pentanol (10 mL) is stirred at reflux for 15 hours The solvent is removed under reduced pressure, then the residue is diluted with aqueous Na2CO3 (50 mL) and extract with EtOAc (5 x 5 mL) The solvent is removed, then chromatographed on the residue three times on silica gel, eluted with 2 5 - 4% MeOH / CH 2 Cl 2 containing 0 3% Et 3N, produces a raw product, the - which is treated with aqueous Na2CO3 and extracted with CH2C12 (4 x 50 mL) to give 3- (2,6-dichlorophenyl) -1-methyl-7 - [4- (4-morpholino) dimethylamino) butylamino] - 1H - [1, 6] - naphthyridin-2-one, (135 mg, 95%) foam 1 H NMR (CDCl 3) d 8 32 (s, 1 H, H-5), 7 52 (s, 1 H, H-4), 7 39 (d, J = 8 1 Hz, '2H, H - 3' 5r), 7 24 (dd, J = 8 6, 7 7 Hz, 1H, H - 4 '), 6 02 (s, 1H, H - 8), 5 48 (br s lH, NhCH2), 3 75 (t, J = 4 6 Hz, 4 H, O (CH 2) 2), 3 65 (s, 3 H, NCH 3), 3 36 (br t, J = 6 6 Hz, 2 H, NHCH 2) , 2 47 (br m, 4 H, N (CH 2) 2), 41 (t, J = 7 1 HZ, 2 H, NCH 2), 1 76, 1 66 (2 pentet, J - 7 0 Hz, 2x2 H, 2CH2) '13 C NMR d 160 76, 159 85 (2 s, C-2.7), ~ 150 76 (d, C-5), 147 18 (s, C-8a), 138 27 (d, C-4 135 81 (s, 2C, C-2 '6'), 134 84 (s, C-1 '), 129 52 (d, C-4'), 127 89 (d, 2C, C-3 '5'), 123 97 (s, C-3), 109 23 (s, C-4a), 86 61 (d, C-8), 66 88 (t, 2C, O (CH 2) 2 ), 58 37 (t, NCH2 7), 53 66 (t, 2C, N (CH2) 2), 42 36 (t, N 1CH2), 29 34 (Q, NCH3), 27 02, 24 l _ I (2t, I 2CH2 ) Analysis calculated for C23H26Cl2N4? 2 requires C, 57 6, H, 5 9, N, 11 7% C, 57 3, H, 5 6, N, 1 1 5% was found - 1 r- t EXAMPLE R Preparation of 3- (2,6-dichlorophenyl) -7 - [(4 - (3 - (diethylamino) propoxy) phenyl) aminojl-methyl-1H- [1,6] -naftindin-2-one,, i A solution stirring of compound IX (where R is methyl) (82 mg, 0 25 mmol) and 4 - [3 ^ (diethylammo) propoxij aniline (0 17 mg, 0 77 mmol) in THF (5.0 mL) under nitrogen at -78 ° C is treated with a solution of LDA in cyclohexane (10 mL of 15 M, 15 mmol), then the temperature is increased to 20 ° C and the mixture is evolved at 20 ° C during the 43 hours The resulting solution is treated with aqueous Na2CO3 and extracted with EtOAc (4 50 mL). The solvent is removed, then chromatography of the residue over alumina eluting it with 0 35-0.5% MeOH / EtOAc yields 3 - (2 , 6-dichlorophemethyl) - 7 - [(4 - (3-f (diethylamino) propoxy) phenyl) aminojl-methyl-1H- [1,6] -naphthipdin-2-one, (67 mg, 50%) melting point (CH 2 Cl 2 / hexane) 151 - "1 52 ° C [1 H NMR (CDCl 3) d 8 39 (s, 1 H, H 5), 7 55 (s, 1 H, H - 4), 7 40 ( d, J = 8 3 Hz, 2 H, H - I 3 ', 5'), 7 27 (d, J = 9 0 Hz, 2 H, H - 2", 6"), 7 25 * (dd, JN = 8 7, 7 7 Hz, 1H, H - 4 '), 6 97' (d, J = 9 0 Hz, 2 H, H - 3"5"), 6 86 br s, 1 H, NH), 6 39 / s, 1 H, H - 8), 4 05 (t, J = 6 4 Hz, 2 H, t OCH2), 3 54 (S, 3H, NCH3), 2 63 (t, J = 7 3Hz, 2H, NCH2), 2 56 (q, J = 7 2 Hz, '4H, N (CH2) 2 1 95 (pentet, J = 6 8 Hz, 2H, CH_), 1 05 (t, J = 7 1 Hz, 6H, 2CH3) 13C NMR d 160 68, 158 84 (2s, C - 2.7), 156 81 ( s, C-4"), 150 76 (d, C-5), i 147 254 (s, C-8a), 138 01 (d, C-4), 135 78 (s, 2C, C-2 ' 6 '), 134 73 (Sm c-1'), 131 67 (S, c-1"), 129 63 (d, C-4), 127 95 (d, 2C, C-3 '5'), 125 29 (d, 2C, C-2" 6"), 125 01 (s, C-3), 115 56 (d, 2C, C-3"5'7), 110 24 (s, C-4a), 87 92 (d, C-8), 66 71 (t, OCH2), 49 38 (t, íCH2), 47 00 (t, 2C, N (CH2) 2), 29 41 (q, NCH3), 27 05 (t, CH2), 1 1 77 (q, 2C, 2CH3) Analysis calculated for C2gH3oCl2N4? 2 Fequiere C, 64 0, H, 5 8, N, 10 7% Found C, 63 9, H, 5 6, N, 11 0% - * 1 r EXAMPLE S Preparation of 3- (2,6-dichlorophenyl) -1-methyl-7 - [(4 - (2 - (4-f methylpiperazin-1-yl) ethoxy) phenyl) amino] -1H- [1,6 ] - naphthyridin-2-one; A stirred solution of compound IX (where R 2 is methyl) (100 mg, 0.31 mmol) and 4 - . 4 - [2 - (4-Methylpiperazin-1-yl) ethoxy] aniline (0.26 mg, 1.12 mmol) in THF (5.0 mL) Under nitrogen at -78 ° C it is treated with a solution of LDA in cyclohexane (0.8 mL of 1.5 M, 1.2 mmol), then the temperature is slowly increased to 20 ° C and the mixture is stirred at 20 ° C for 2.5 hours. days. The resulting solution is cooled to -78 ° C and then treated with AcOH (0.5 mL), then treated at 20 ° C with aqueous Na 3 CO 3 and extracted with EtOAc (5"x 50 mL) .The solvent is removed, After chromatography of the residue on alumina by eluting it with CH2Cl2, it first gives compound IX recovered, where R2 is methyl (49 mg, 49%) .An additional elution with 0.25-0.5% MeOH / CH2C12 produces a crude oil, which is again subjected to chromatography on alumina, eluting it with 0.25-0.5% MeOH / CH2C12, to give 3 - (2,6-dichlorophenyl) -1-methyl-7 - [(4 - (2 - (4-methylpiperazine - 1 - yl) ethoxy) phenyl) amino] - 1 H - [1,6] - naphthyridin-2-one (27 mg, 16%): melting point (CH2C12 / hexane) 170-171.5 ° C. 1H NMR (CDCb) d 8.40 (s, 1H, H-5), 7.55 (s, 1H, H-4), 7.40 (d, J = 8 4 Hz, 2H, H - 3'.5 ') I7.28 (d, J = 8.9 Hz, 2H, H - 2".6"), 7.25 (dd, J = 7.7 Hz, 1H, H - 4'), 6.97 (d. , J = 8.9 Hz, ~ 2H, H - 3".5"), 6.83 (br s, 1H, NH), f .40 (s, 1H, H - 8), 4.14 (t, J = 5.8 Hz, 2H, OCH2), 3.54 (s, 3H, NCH3), 2.86 (t, J = 5.8 Hz, 2H, NCH2), 2 66, 2.50 (2br s, 2 x 4 H, N (CH2) 4Ñ), 2.31 (s, 3H, NCH 3). * l I 13C NMR d 160.66, 158.71 (2s, C-2.7), 156.43 (s, C-4"), 150.74 (d, C-5), 147.23 (s, C-8a), 137.99 (d , C - 4), 135 77 (s, 2C, C - 2'.6 '), 134.71 (s, C - 1'), 131 97 (s, C-1"), 129.64 (d, C-4 '), 127.95 (d, 2C, C-3 \ 6'), 125.17 (d, 2C, C-2" .6"), 12508 (s i C - 3), 115.66 (d, 2C, C - 3", 5"), 110.29 (s, C - 4a), 88.02 (d, C - ~ 8), 66.25 (t, OCH2), 57.15 (t, NCH2), 55.02, 53.56 (2t, 2 x 2C, N (CH2) 4), 46.01 (q, NCH3), 29 43 (q, NCH3) Analysis calculated for C2gH29Cl2N5? 2 requires: C, 62 5; H, 5 4; N, 13 0%. Found: C, 62.5; H, 5.7; N, 13.1%.

EXAMPLE T Preparation of 3- (2,6-dichlorophenyl) -1-methyl-7 - [(4 - (4 - (4-methylpiperazin-1-yl) propoxy) phenyl) amino] -1H- [1,6] - naphthyridin-2-one, a stirred solution of compound IX (where R2 is methyl) (103 mg, 0 32 mmol) and t 4 - [3 - (4-methylpiperazin-1-yl) propoxy] aniline (0 31 mg, 1.24 mmol) in THF (5.0 mL) under nitrogen at -78 ° C is treated with a solution of LDA in cyclohexane (0.9 mL of 1.5 M, 1.35 mmol), then the temperature is slowly increased to 20 ° C and the mixture Ia is stirred at 20 ° C for 2.5 days. The resulting solution is treated with aqueous Na2CO3 and extracted with EtOAc (5 x 50 mL). The solvent is removed, then the chromatography of the residue on alumina eluting with 0-3-0.5% MeOH / CH2C12. produces 3 - (2,6-dichlorophenyl) -1-methyl-7 - [(4 - (3 - (4-methylpiperazin-1-yl) propoxy) phenyl) amino] -1 H - [1,6] -naphthyridine - 2 -one (111 mg, 63%) melting point (CH2C12 / hexane) 159-160 ° C. 'T 1H NMR (CDC13) d 8 39 (s, 1H, H-5), 7.55 (s, 1H, H - 4), 7 40 (d, J = 7 8 Hz, 2H, JH - 3'.5 '), 7.28 (d, J = 8 8 Hz, 2H, H - 2"6"), 7 25 ( dd, J = 8 7, 7 7 Hz, 1 H, H - 4 '), 6 96 (d, J = 8.8 ~ Hz, 2H, H - 3"5"), 6 90 (br s, 1H, NH), 6 40 (s, 1H, H - 8), 4 05 (t, J = 6 4 Hz,! 2H, OCH2), 3.54 (s, 3H, NCH3), 2 8 - 2.2 (br s, 8H, N (CH2) 4N), 2.56 (t, J = 7 4 Hz, 2H, 1 NCH2), 2.30 (s, 3 H, NCH3), 2.00 (pentet, J = 6.9 Hz, 2H, CH2). ' 13C NMR d 16066, 15879 (2s, C-2.7) ~ 15669 (s, C-4"), 15074 (d, C-5), 14723 (s, C-8a), 13800 (d, C-4), 13576 (s / 2C, C-2 '6'), 13471 (s, C-1 '), 13176 (s, C-1"), 12963 (d, C-4 '), 12794 (d, 2C, C-V 6'), 12523 (d, 2C, C-2" 6"), 12501 (s) C-3), 11555 (d, 2C, C-3", 5"), 11024 (s, C-4a), 8794 (d, C-8), 6659 (t, OCH2), 5513 (t, J3C, NCH2, N (CH2) 2), 5323 (t, 2C, N (CH2) 2), 4604 (q, NCH3), 2941 (q, NCH3), 2679 (t, CH2) Analysis calculated for G_9H31Cl2N5? 2 required C, 63 0, H, 5 7, N, 12 7% C was found, 62 9, H, 5 7, N, 13 0% * r EXAMPLE U 1 - - r Preparation of 3 - (2,6-dichlorophenyl) -1-methyl-7 - [(4 - (4-methylpiperazine-1) - il) phenyl) amino] - 1 H - [1,6] - naphthyridin-2-one, I; I A stirred solution of compound IX (where R2 is methyl) (100 mg, 0 31 mmol) and : t 4 - (4 ^ methylpiperazin-1-yl) aniline (177 mg, 0.93 mmol) in THF (5.0 mL) under nitrogen at -78 ° C is treated with a solution of LDA in cyclohexane (1 2 mL of 1.5 M, 1.8 mmol), then the temperature is slowly increased to 20 ° C and the mixture is stirred at 20 ° C.

C for 40 hours The resulting solution is treated with aqueous Na2CO3 and extracted with EtOAc (3 x 50 mL) The solvent is removed, then chromatography of the residue on alumina by eluting with 0-25-0.5% MeOH > / CH2CI2, then on silica gel, eluting with 0-25-0.5% MeOH / CH2Cl2 gives a crude product which is treated with - I I \ Na2CO3 aqueous and extracted with EtOAc (2 x 50 mL), to give 3- (2,6-dichlorophemethyl) -1-. I methyl-7 - [(4 - (4-methylpiperazin-1-yl) phenyl) aminoj - 1H - [1, 6] - naphthyridin-2-7 T one (56 mg, 37%) melting point (CH2C12 / hexane) 153 - 161 ° C 1 H NMR (CDCl 3) d 8.40 (s, 1 H, H-5), 7.55 (s, 1 H, H-4), 7.40 (d, J = 7.8 Hz, '2 H, H - 375 '), 7.26 (d, J = 9.0 Hz, 2H, H - 2.76") r7.25 (dd, J = 8.6, 7.6 Hz, 1H, H - 4'), 6.99 (d, J = 9.0 Hz, 2H, H-3.75"), 6.68 (br s, 1H, NH), 6.43 (s, 1H, H-8), 3.54 (s, 3H, NCH3), 3. 25 (t, J = 5.0 Hz, 4H, N (CH2) 2), 2.62 (t, J = 4j9 Hz, 4H, N (CH2) 2), 2.38 (s, 3 H, NCH3). 13C NMR d 160.68, 158.69 (2s, C-2/7), 150.75 (d, C-5), 148.86 (s, C-4"), 147. 22 (s-8a), 138.01 (d, C-4), 135.78 (s, 2C, C-2'.6 '), 134.74 (s, C-1'), 130.93 (s, í C - 1" ), 129.61 (d, C-4 '), 127.94 (d, 2C, C-375'), 124.93 (s-C-3), 124.66 (d, 2C, C-2'76"), H7.06 (d, 2C, C-3", 5"), 110.21 (s, C-4a), 87.95 (d, C-8), 55.03 (t, 2C, N (CH2) 2). 49.14 (t, 2C, N (CH2) 2), 46.05 (q, NCH3), 29.44 (q, NCH3). Analysis calculated for C 26 H 25 Cl 2 N 5 O requires: C, 62.0; H, 5.2; N, 13 9%. I Found: C, 61.8; H, 5.3; N, 13.5% EXAMPLE V Preparation of 7-fluoro-1-ethyl-1H- [1,6] -naphthyridin-2-one. A solution of compound IV (1.0 g, 7.3 mmol) in dioxane (10 mL) is treated with carboxymethylene triphenylphosphorane (5.1 g, 14.7 mmol) and heated to a gentle reflux for 2.5 hours. The cold reaction mixture is rapidly filtered through a pad of silica gel eluting with 0% to 5% methanol in ethyl acetate. Evaporation of the solvent and recrystallization (1: 1 methylene chloride ethyl acetate) of the resulting residue yields ethyl 3- (4,6-diamino-3-pyridyl) acrylate (XI) as a solid (? '. 72 g, 48 %): melting point 151 - 152 ° C. '1 H NMR [(CD3) 2 SO] d 8.01 (s, Ih, H-2), 7.68 (d, 1H, I = 15.9 Hz), 6 17 (d. 1H, J = 15.8 Hz), 5.99 ^ 5.87 (2br s, 2 x 2 H, 2NH2), 5.62 (s, IHTH - 5), 4.13 (q 2H, J = 7 23 Hz, CH2). 1.23 (t, 3H, J = 7.23 Hz, CH3). - 7 [Analysis calculated for C? OH? 3N3O2 requires: C, 57 96; H, 6.32; N, 20.28% Found: C, 57.90; H, 6.21; N, 20.34%.

A suspension of (XI) (4.7 g, 22.7 mmol) in 1,8-diazabicyclo [5.4.0J undec-7-ene (22 mL) is heated at 165 ° C under nitrogen for 16 hours. The compound 1, 8-L diazabicyclo [5.4.0] undec-7-ene is distilled under vacuum to leave a residue that is triturated r-I in hot hexane (2 x 100 mL). The solid is then triturated in ethyl acetate: methanol and heated in a ratio of 5: 1 to give a whitish solid which is filtered and then washed with ethyl acetate. The filtrates are concentrated, purified by chromatography with silica gel and further processed as above to leave an additional product. The cultures are combined to give 7-amino-1 H - [1,6] naphthyridin-2-one (XII) (2.55 g, 70%): melting point >; 275 ° C. ~ 1 H NMR [(CD3) 2 SO] d 11.42 (bs, 1H, NHC = O), 8.24 (s, __lli H-5), 7.68 (d, 1H, J = 9.49 Hz), 6.37 (bs, 2H, NH2), 6.13 (s, 1H, H - 8), 6.06 (d, 1H, J = 9.40 Hz). MS (APCI) m / z 162 (M + H, 100%). i To a stirred solution of compound XII (2.1 g, 13 mmol) in dry DMF (65 mL), cesium carbonate (6.4 g, 19.6 mmol) was added followed by ethyl iodide (1 71 mL, 21.4 f mmol) and the mixture is stirred at 60 ° C for 4.5 hours. The cooled mixture is filtered and the filtrate is diluted with ethyl acetate. The solution is washed with saline, dried and concentrated to give an orange residue which is purified by chromatography with silica gel, eluting with ethyl acetate: hexanes in a ratio of 1: 1 and then ethyl acetate. The concentration of the product fractions yield 7-amino-1-ethyl-1H- [1,6] naphthyridin-2-one (XIII) (1.3 g, 53%). ~ " 1H NMR [(CD3) 2SOJ d 8.23 (s, 1H, H-5), 7.64 (d, 1H, J = 9.28 Hz), 6.40 (bs, 2H, ^ i NH2), 6.26 (s, 1H, H-8), 6.11 (d, 1H, J 9.28 Hz) 3.98 (q, 2H, J = 7.08 Hz, CH2), l.l1 (t, A suspension of compound XIII (1.1 g, 5.8 mmol) in 48% aqueous HBF4 (20 g.

- ^ I mL) at -10 ° C is treated with NaNO2 (0.44 g, 6.38 mmol, added in small portions 7 \ for 3 hours). The resulting mixture is neutralized (pH 7) with solid Na 2 CO 3 - - 1 carefully, keeping the temperature below 0 ° C, and extract with EtOAc (3 x 75 mL). The solvent is removed, then the chromatography of the residue on silica gel, 7- f eluting with ethyl acetate, produces 7-fluoro-1-ethyl-1H- [1,6] naphthyridin-2-one (XV) (0.72 g, 64%). 1H NMR [(CD3) 2SO] d 8.57 (s, 1H, H-5), 7.95 (d, 1H, J = _9.52 Hz), 7.30 (s, ÍH), H-8), 6711 (d, 1H, J = 9.52 Hz), 4.15 (q, 2H, J = 7.08 Hz, CH2), 1.12 (t, 3H, J = 7.08 Hz, CH3). - I MS (APCI) m / z 193 (M + H, 100%).

EXAMPLE W Preparation of 1-ethyl-7-phenylamino-1 H - [1,6] -naphthyridin-2-one; 7-L A stirred solution of compound XV (where R2 is ethyl) (100 mg, 0.52 mmol) and - I aniline (120 mg, 1.3 mmol) in THF (5.0 piLow nitrogen at -78 ° C is treated with a solution of LDA in cyclohexane (1.2 mL of 1.5 M, 1.8 mmol), then the temperature is slowly increased to 20 The resulting solution is treated with 3 drops of glacial acetic acid and concentrated until a brown residue is left which is purified by chromatography with silica gel eluting with EtOAc. pool and concentrate until a solid remains which crystallizes to give 1-ethyl-7-phenylamino-1 H - [1,6] naphthyridin-2-one (33 mg, 24%): melting point (8: 1 hexanes dichloromethane) 174-175 ° C. 1 H NMR (CDC13) d 9.37 (bs, 1H, NH), d 8.52 (s, 1H, H-5). 7.81 (d, 1H, I = 9.40 Hz), 7.66 (d, 2H, J = 8.44 Hz), 7.30 (t, 2H, J = 7.47 Hz), 6.95 (t, 1H, J = 7.47 Hz), 6.72 (s, i 1H), 6.32 (d, 1H, J = 9.40 Hz), 4.10 (q, 2H, J = 7.23 Hz, CH2), 1.23 (t, 3H, J = 7.23 'Hz, CH3). - IR (KBR) 1624 crn- 7 'MS (APC?) M / z 266.1. _ Analysis calculated for C16H15N3O • 0.30 H2O requires: C, 70.99; H, 5.81 N. 15.52%. "Found: C, 71.01, H, 5.62; N, 15.35% 7 * EXAMPLE X Preparation of -1-ethyl-7- (4-methoxyphenylamino) -1H- [1,6] -naphthyridinone; A stirred solution of compound XV (where R is ethyl) (100 mg, 0.52 mmol) and p-anisidTna (160 mg, 1.3 mmol) in THF (5.0 mL) under nitrogen at -78 ° C is treated with a solution? E LDA in cyclohexane (1.2 mL of .5 M, 1 8 mmol), then the temperature is increased slowly to 20 ° C overnight. The resulting solution is treated with 3 drops of glacial acetic acid and concentrated until a brown residue remains which is purified by chromatography with silica gel eluting with hexanes (L 1) and then in EtOAc. * = "- I" The product fractions are pooled and concentrated until a solid remains which crystallizes to give 1-ethyl-7- (4-methoxypheniiamino) -1H- [1, 6] -naphthyridin-2-one, (87 mg, 57 %) melting point (2-propanol) 165 - 166 ° C 1 H NMR (CDCl 3) d 9.17 (bs, 1 H, NH), d 8.46 (s, 1 H, H-5) 7 77 (d, 1 H, J = 9 40 7 f Hz), 7.52 (d, 2H, J = 8.92 Hz), 6.90 (d, 2H, J = 8.92Hz), 6.59 (s, 1H), 6 28 (d, 1H, J = 9.40 Hz), 4.07 q, 2H, J = 6.99 Hz, CH_), 1.20 (t, 3H, 'j = 6.99 Hz, CH3).

IR (KBR) 1619 crn- MS (APCI) m / z 296.0. ~~ - Analysis calculated for C17H? 7N3O2 requires: C, 69.14, H, 5.80, N, 14 23% Found: C, 69.14; H, 5.84; N, 13.99%.

EXAMPLE Y ~ - - t Preparation of 1-ethyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] -1H - [1,6] -naphthifidin-2-one; A stirred solution of compound XV (where R 2 is ethyl) 00 mg, 0 52 mmol) and 4 - . 4- (4-methyl-1-piperazinyl) aniline (0.26 g, 1.12 mmol) in THF (5.0 mL) under nitrogen at -78 ° C is treated with a solution of LDA in cyclohexane (0.8 mL of 1.5 M, 1.2 mmol). ), then the temperature is increased slowly to 20 ° C overnight. The resulting solution is treated with 3 drops of glacial acetic acid and concentrated until! ! a dark residue is left which is purified by chromatography with silica gel eluting with EtOAc: MeOH: NELiOH (90: 9: 1). The fractions of the product come together and are concentrated. The solid is collected and crystallized to give 1-ethyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] - 1H - [1, 6] -naphthyridin-2-one, (84 mg, 44%): melting point (CH2Cl2 / hexanes) 188-189 ° C \ 1 H NMR [(CD3) 2 SO] d 9.10 (bs, 1H , NH), d 8.44 (s, 1H, H - 5) .7 76 (d, 1H, J = 9. 40 Hz), 7.45 (d, 2H, J = 8.92 Hz), 6.91 (d, 2H J = 9 16 Hz), 6 57 (s, 1H), 6 26 (d, 1H, J = i 9. 40 Hz) "4.08 (q, 2H, J = 6.99 Hz, CH2), 3.05 - 3.08 (m, 4H, CH2), 2 44 -2 46 (m, 4H, CH2), 2.22 (s, 3H, NCH3), 1.20 (t, 3H, J = 6.99 Hz, CH3). f ~ 7 I 1R (KBR) 1619 cm "M% (APCI) m / z 364.2 Analysis calculated for GJIHISNSO 0.7 H2O requires: C, 67.07; H, 7 08; N, 18.62%. ^ "Semen against: C, 67.22; H, 6.70; N, 18, 39%.

^ E EMPLO Z Preparation of 1-ethyl-7- (4-morpholin-1-yl) phenylaminoj-1 H - [1,6] f 1 naphthyridin-2-one; 7 ^ | Nail solution of compound XV (where R2 is ethyl) (100 mg, 0.52 mmol) and 4 - (4-morpholinyl) aniline (0.26 g, 1.1 mmol) in THF (5.0 mL) under nitrogen at -78 ° C is treated With a solution of LDA in cyclohexane (0 8 mL of 15 M, 1.2 mmol), the temperature is then slowly increased to 20 ° C overnight. The resulting solution is treated with 3 drops of glacial acetic acid and concentrated until a dark residue remains which is purified by chromatography with silica gel eluting with EtOAc The fractions of the product are combined and concentrated in a solid which is crystallized for give 1-ethyl-7- (4-morpholin-7-yl) phenylamino] -1H - [1,6] -naphthyridin-2-one, (94 mg, 52%) melting point (2'-propanol) / hexanes) 219 - 223 ° C 1 H NMR [(CD 3) 2 SO] d 9.13 (bs, 1H, NH), d 8 45 (s, 1H, H-5) 7 77 (d, 1H, 'J = 9.40 Hz), 7.48 (d, 2H, J = 8.92 Hz), 6.92 (d, 2H.J = 8.92 Hz), 6 58 (s, 1H), 6 27 (d, 1H, J = 9.40 Hz); 4.06 (q, 2H, J = 6.99 Hz, CH2), 3 68 - 3 78 (m, 4H, CH2), 3 06 -3 03 (m, 4H, 1 CH2), 1.2 > (t, 3H, J = 6.99 Hz, CH3) ~ '' IR (KBR) 1619 cm - "i MS (APCI) t ?? / z 351.2. Analysis calculated for C2oH22N4O2 0.3 H2O requires C, 67 44, H, 6.41; N, . 73%. It was found. C, 67.45; H, 6.16; N, 15.35%.

EXAMPLE AA (Preparation of 1-ethyl-7 - (4 - (piperidin-1-yl) phenylamino) -1H - [1,6] - - I naphthyridin-2-one, purify by chromatography with silica gel eluting with EtOAc. The product fractions are combined and concentrated in a solid which is crystallized to give 1-ethyl-7- (4-piperidinyl) phenylamino) -1H - [1,6] -naphthyridin-2-one; (79 mg, 44%): melting point (CH2Cl2 / hexanes) 137-139 ° C. 7 1 H NMR [(CD3) 2 SO] d 9.09 (bs, 1H, NH), d 8.44 (s, 1H, H - 5) 7.76 (d, 1H, J = 9.40 Hz) 77.43 (d, 2H, J = 8.92 Hz), 6.90 (d, 2H J = 9.16 Hz), 6.57 (s, 1H), 6 26 (d, 1H, J = 9.16 HzL 4 06 (q, 2H, J = 6 99 Hz, CH2), 3.03 - 3 06 (m, 4H, CH2NCH2), 1 66 - 1 6u (m, 4H, CH2J 1.50 - 1.54 (m, 2H , CH_), 1 20 (t, 3H, J = 6.99 Hz, CH3) IR (KBR) 1620 cm "7 MS (APCI) m / z 349.2.

Analysis calculated for C2? H24N4O? • 0.2 H2O requires: C, 71.65; H, 6.99; Neither . 91%. ' Found: C, 71.72; H, 6.81; N, 15.93%.

EXAMPLE BB Preparation of 1-ethyl-7-phenylamino-3,4-dihydro-1H- [1,6] naphthyridin-2 -one - - f A suspension of 1-ethyl-7-phenylamino-1H - [1, " 6] naphthyridin-2-one from Example W (75 mg, 0.29 mmol), 0.6 g of Raney Nickel and 50 mL of ethanol is stirred under 50 psi of hydrogen at room temperature for 23 hours. The suspension is filtered and the filtrate is concentrated until a solid residue remains which is purified by preparative thin layer chromatography to give 1-ethyl-7-phenylamino-3,4-dihydro-1H- [1, 6] Naphthyridin-2-one (10 mg, 13% yield) - mp 137 f - 138 ° C7 ^ NMR [(CD3) 2SOJ d 1.10 (t, 3H, J = 7 Hz), 2.50 (t, 2H, J = 7 Hz), 2 71 (t, 2H ^ J = 7 Hz), 3776 (q, 2H, J = 7 Hz), 6.47 (s, 1H), 6.75 (t, 1H, J = 7 Hz), 7.18 (t, 2H, J = 8 Hz), 7. 58 (d, 2H, J = 8 Hz), 7.89 (s, 1H), 8.89 (s, 1H) 7 MS (APCI) »// 268 (M + 1). ^ Analysis calculated for C16H17Ñ3O • 0.15 C4H8O2 requires: C, 70.62, H, 6.57; N, 14.88%. Found: C, 70.90; H, 6.26; N, 14 56% Purification of the tyrosine kinases Receptor of the Epidermal Growth Factor (EGFr). The tyrosine kinase of the human EGF receptor is isolated from cells with A431 human epidermoid carcinoma by The following method Cells are grown in revolving bottles in Eagle medium I modified Dulbecco and 50% HAM F-12 nutrient medium (Gibco) containing serum * _ [of 10% fetal calf. Approximately 109 cells are lysed in two volumes of [buffer containing 20 mM of 2- (4N- [4-hydroxymethyl] piperazin-1-yl) ethanesulfonic acid (Hepes), pH 74.5 mM of ethylene glycol bis (2) acid. - aminoethyl ether) N, N, N ', N' - etraacetic, Triton 1% > X-100, 10% glycerol, 0.1 mM sodium orthovanadate, 5 mM sodium fluoride, 4 mM pyrophosphate, 4 mM benzamide, lmM dithiothreitol (DTT), 80 μg / mL aprotinin, 40 μg / mL of leupeptin and 1 mM of phenylmethylsulfonyl fluoride (PMSF). After centrifugation at 25,000 x g for 10 minutes,. - j the supernatant is applied to a Q Sepharose fast column (Pharmacia) and eluted with a linear + gradient of 0 1 M NaCl to 0 4 M NaCl in 50 mM Hepes, 10% glycerol > Y . r pH of 7 ~ 4 Enzymatic active fractions are combined, divided into aliquots and stored at -100 ° C Platelets Derived from the Growth Factor Receptor (PDGFr) and the Receptor 7 l of the Fibroblast Growth Factor (FGFr) The cDNAs for the mouse PDGF - β and the tyrosine kinases of the human FGF - 1 (flg) are obtained from J Escobedo and are prepared as described in J Biol Chem, 1991, 262 1482-1487. The first PCRs are designed to amplify a DNA fragment encoding the intracellular tyrosine kinase i domain. The fragment is fused to a vaculovirus vector, cotransfected with - I "5*" ' AcMNPV DNA and the recombinant virus is isolated The SF9 insect cells are infected with the virus to overexpress the protein and the Used cell is used for the experiment Other Kinases The c-Src kinase is purified from the cells of insect cells infected with baculovirus using an anti-peptide monoclonal antibody directed against amino acids 2-17 amino-terminals as previously described by Fry, et al.

Anticancer Drug Design, 1994, 9 331-351 Protein C (PKC) kinase is obtained as a rat brain preparation from Promega Experiments with kinase i. 'EGFr Enzyme experiments for IC50 determinations are carried out on 1 1 96-well filter plates (Millipore MSADVN6550) The total volume is 0 1 mL containing 20 mM Hepes, pH 7.4, 50 μM sodium vanadate, 40 mM chloride 7 _ 'magnesium, 10 μM of ATP containing 0 5"μCi of [32P] of ATP, 20 μg of \ polyglutamic acid / tyrosine (Sigma Chemical Co. St Louis, MO), 10 ng of the tyrosine kinase of EGF and appropriate dilutions of the inhibitor All components except ATP are added to the well and the plate is incubated while stirring for 10 minutes at 25 ° C. The reaction is started by adding [32Pj of ATP and the plate is incubated at 25 ° C. for 10 minutes t The reaction is terminated by the addition of 0 1 mL of 20% trichloroacetic acid (TCA). The plate is kept at 4 ° C for at least 15 minutes to allow the substrate to precipitate. The wells are then washed five times with 0 2. mL of 10% TCA and the incorporation of 32 P is determined with a beta-d ~ e plate counter Wallac ' PDGFr and PGFr The experiments are carried out in 96"well plates (100 μL / incubation / well) and the conditions are optimized to measure the incorporation of P of [? 32P] ATP on a substrate with glutamate-tyrosine copolymer Briefly, each well is 7 -. 7 - t is added 82 5 μtL of incubation buffer containing 25 mM Hepes (pH 7 0), 150 mM NaCl, 0 1% Triton X-100, 0 2 mM PMSF, 0 2 mM sodium vanadate, 10 mM manganese chloride and 750 μg / mL poly (4 1) glutamate-tyrosine followed by 2. 5 μL of the inhibitor and 5 μL of enzyme lysate (7 5 μg / μL FGFR - TK or 6 0 μg / μL i PDGFR-TK) to start the reaction After a 10 minute incubation at 25 ° C, μL of [? 32P] ATP (0 4 μCi plus 50 μM of ATP) are 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 of 30% trichloroacetic acid (TCA) containing 20 mM sodium pyrophosphate and precipitation of the material on glass fiber filter cloths (Wallac) The filters are washed three times with 15% TCA containing 100 mM of sodium pyrophosphate and the radioactivity retained on the filters is counted with a Betaplate 1250 reader Wallac The non-specific activity is defined as the radioactivity retained on the I \ filters after the incubation of the samples only with regulator, (not enzyme) The specific enzymatic activity is defined as the total activity (enzyme plus regulator) minus the activity not Specific The concentration of a compound that inhibits specific activity by 50% (IC50) or is determined based on the c-Src inhibition curve. The tr antibody, covalently bound to 0 65 ^ μm latex beads, is added to a suspension of an insect cell lysis regulator comprising 150 mM NaCl, 50 mM Tris with a pH of 7.5, 1 mM DTT, 1% NP-40, 2 mM EGTA, 1 mM of - Sodium vanate, 1 mM PMSF, 1 μg / mL of each of the following compounds FI leupeptin, pepstatin and aprotinin The insect cell lysate containing the c-Src protein is incubated with these beads for 3 to 4 hours hoi sa 4 ° C with allocation 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 are thawed, rinsed three times in regulator of the experiment the (which contains 40 mM of tris with a pH of 7.5 5 mM of magnesium chloride and is suspended in the same buffer. In a Millipore 96-well plate with a polyvinylidine membrane button of 0 65 μm is added to the compounds of the reaction 10 μL of beads c - 1 Src, 10 μU of 2 5 mg / mL of polyglutamate-tyrosine substrate, 5 μM of ATP containing 32P - ATP labeled with 0 2 μCi, 5 μL of DMSO containing inhibitors or as a control of solvent and regulator to make the final volume of 125 μL The reaction starts at room temperature when ATP is added and turned off 10 minutes later by the addition of 125 μL of 30% TCA), 0 1 M sodium pyrophosphate for 15 minutes on ice The plate is then filtered and the wells are washed with two aliquots of 250 μL of 15% TCA and 0-1 M pyrophosphate. The filters are emptied, counted in a liquid scintillation counter and the data examined for inhibitory activity in comparison to a known inhibitor ^ such as erbstatin The method is described in more detail in J Med, Chem, 7 i 1994, 37"598 - 609 Cascade experiment for inhibitors of the MAP Kinase Pathway (APPE experiment [Incorporation of 32P into the myelin basic protein (MBP) is experienced in the presence of glutathione, fusion protein S-transferase containing p44MAP kinase (GST-MAPK) and glutathione, fusion protein S-transferase containing p45MEK ( GST-MEK) The solution of the experiment contains 20 mM Hepes, pH 7 4, 10 mM of magnesium chloride, 1 mM manganese chloride, 1 mM EGTA, 50 μM of [? 32P] ATP, 10 μg of GST-MEK, 0 5 μg of GST-MAPK and 40 μg of MBP in a final volume of 100 μL As reactions are stopped after 20 minutes by the addition of trichloroacetic acid and filtered through a GF / C filter The 32P retained in the filter is determined using a betaplate 1205. Compounds are set at 10 μM for the ability to inhibit 332 P incorporation.

To ensure if the compounds are inhibiting GST-MEK or GST-MAPK, two additional protocols are employed. In the first protocol, the compounds are added to tubes containing GST-MEK, followed by the addition of GST-MAPK, MBP and [α 32 P] ATP. In the second protocol, the compounds are added to tubes containing both compounds: GST-MEK and GST-MAPK, followed by MBP and [? 3 P] ATP. Compounds showing activity in both protocols are labeled MAPKL inhibitors, while compounds that show activity only in the first protocol are labeled as MEK inhibitors.

Other Kinases An experiment using the intracellular kinase domains of the insulin receptor (INSr) is performed as described for the EGF receptor, except that 10 mM of manganese chloride is included in the reaction. The PKC experiment is carried out as previously described by Martiny-Baron, et al, J Biol Chem, 1993; 268. 9194 ~ - 9197.

TABLE 1 Inhibition of Protein Kinase solubility of the compound. Appropriate DMSO controls are evaluated simultaneously with the test compounds.

Soft muscle aortic cells are grown to confluence in 100 mm plates. The growth medium is removed and replaced with a serum-free medium and the cells are incubated at 37 ° C for an additional 24 hours. The test compounds are then added directly to the medium and the cells are incubated for an additional 2 hours. After 2 hours, PDGF-BB is added to a final concentration of 30 ng / mL for 5"minutes at 37 ° C to stimulate autophosphorylation of PDGF receptors After treatment with growth factor, the medium is removed and the cells are washed with phosphate buffered saline and immediately used with 1 mL of lysis buffer (50 mM Hepes, pH 7.5, 150 mM NaCl, 10% glycerol, Triton X-100 1%, 1 mM EDTA, 1 mM EGTA, 50 mM NaF, 1 mM sodium ortho vanadate, 30 mM phosphate-p-nitrophenyl, 10 mM sodium pyrophosphate, 1 mM phenylmetif sulfonyl fluoride, 10 μM / mL of aprotinin and 10 μg / mL of leupeptin). The lysates are centrifuged at 10,000 x g for 10 minutes. The supernatants are incubated with 10 μL of T = antibodies to rabbit anti-human PDGF type AB receptor (1: 1000) for 2 hours.

After incubation, the protein counts. - A - sepharose are added for 2 hours ~ Z r i while mixing continuously and complexes are attached to the beads washed four times with 1 mL of lysis wash buffer. The immune complexes are solubilized in 40 μL of Laemmli sample regulator and electrophoresis in SD I polyacrylamide gel from 8% to 16% > . After electrophoresis, the separated proteins are transferred to the nitrocellulose and immunostained with a 1: 1000 dilution of anti-phosphotyrosine monoclonal antibody (clone UBI; 4G10; # 05 - 321) After the ND = Not Determined.

Cell culture. Autophosphorylation experiment of the PDGF receptor. Soft muscle cells are isolated from the rat aorta (RASMC) of the thoracic aorta of rats and are explanted by 7"-i according to the method of Ross, J. Cell, Biol., 1971; 30: 172-186. The cells are cultured in Dulbecco's modified Eagle's medium (DMEM, Gibco) containing 10% fetal calf serum (FBS, Hyclone, Logan, Utah), 1% glutamine (Gibco) and I 1% penicillin / streptomycin (Gibco). The cells are identified as soft muscle cells by their "growth pattern of" ridges and valleys "and by fluorescent staining with a specific monoclonal antibody to SMC μ-actin (Sigma). The RASMC is used between conduits 5 and 20 for all experiments The test compounds are prepared in dimethylsulfoxide (DMSO) to achieve consistency in the vehicle and to assure the solubility of the compound. Appropriate DMSO controls are evaluated simultaneously with the test compounds. t l Aortic soft muscle cells are grown for confluence in 100 mm plates. The growth medium is removed and replaced with a serum-free medium and the cells are incubated at 37 ° C for an additional 24 hours. The test compounds are then added directly to the medium and the cells are incubated for an additional 2 hours. After 2 hours, PDGF-BB is added to a final concentration of 30 ng / mL for 5 minutes at 37 ° C to stimulate autophosphorylation of the PDGF receptors. After treatment with growth factor, the medium is removed and the cells are washed with phosphate-buffered saline and immediately lysed with 1 mL of regulator - l j of lysis (50 mM Hepes, pH 7.5, 150 mM NaCl, 10% glycerol, Triton X-100 al 1%, 1 mM EDTA, 1 mM EGTA, 50 mM NaF, 1 mM sodium orthovanadate, 30 mM p-nitrophenyl phosphate, 10 mM sodium pyrophosphate, 1 mM phenylmethyl sulfonyl fluoride , 10 μM / mL of aprotinin and 10 μg / mL of leupeptin). The lysates are -? centrifuge at 10,000 x g for 10 minutes. The supernatants are incubated with 10 μL of The antibodies of rabbit anti-human PDGF type AB receptor (1: 1000) for 2 hours. After incubation, the protease-A-Sepharose beads are added for 2 hours while continuously mixing and the complexes are bound to the beads washed four times with 1 mL of lysis wash buffer. The immune complexes are solubilized in! 40 μL of Laemmli sample regulator and electrophoresis in 8% SDS polyacrylamide gel > to 16% > . After electrophoresis, the separated proteins are transferred to the nitrocellulose and immunostained with a dilution of 1: 1000 of anti-phosphotyrosine monoclonal antibody (clone UBI, 4G10; # 05-321). After the extensive washing with PBS - 0 2 ° / o tween - 20, the spots are incubated with goat anti - mouse immunoglobulin i - __ '' labeled with peroxidase (1 5000, Bio - Rad Inc, Hercules, CA) and protein levels are detected by the enhanced chemiluminescence (ECL) detection system according to the manufacturer's instructions (Amersham Inc, Arlington Heights, IL) The density of protein bands is determined using NIH Image software (v 1 56) ~ and the IC50 values are generated from the densitometric data I! I I TABLE 2 Inhibition of Autophosphorylation of the Receptor Stimulated by PDGF Human Column Carcinoma Growth Delay Experiment Human colon carcinoma cells are seeded in tissue culture plates of 96 1 t wells in a final volume of 180 μL of 10% fetal bovine serum containing growth medium and allowed to incubate overnight (37 ° C, 5% CO2, 95% air) Cells from the SW-620 cell line are seeded at 0 - 1 5 x 10 04 cells per well Cells from the HCT cell line - 8 and HT - 29 are sown at 2 - 4 x 103 cells per well Solutions of the serially diluted drug are prepared in growth medium a - i! 10-fold concentration, 20 μL of these solutions are added to duplicate the wells and incubated with these cells for 3 days in a cell culture incubator. At the end of the incubation period, the cells are fixed with 100 μL per well of tcloroacetic acid at the end of the incubation period. % after removing the culture medium / drug The plates are washed 5 times with water from ___. These are stained with 100 μL per well of sulfophylline B 0.075% in acetic acid and 1% for 10 minutes.The plates are rinsed 4 times and dried with air. Wells are solubilized by the addition of 10 mM of Tris base without regulator and the absorbance is read in an optical microtiter plate reader.Inhibition of cell growth is calculated from the absorbance data of the treated cells compared to! cells of the untreated control group.

Clonogenic Experiment of Human Colon Carcinoma. Human colon carcinoma cells are seeded in 6-well plates in 3 mL volumes and allowed to incubate overnight (37 ° C, 5% CO2>, 95% air). The SW-620 cells are seeded at 7 x 105 per well; HCT - 8 cells are seeded at 5 x 105 per well, - r HT-29 cells are seeded at 4 x 105 per well. Serially diluted drugs are prepared at 200 times the final concentration and 15 μL are added to each of the wells; i duplicates. The cells are incubated with drug for 2 days, rinsed once with 1 mL t of trypsin + EDTA and then trypsinized with the same trypsin solution.

~? After trituration and centrifugation at 750 x g for 3 minutes, the cells are suspended in serum free growth medium and counted using an electronic particle counter. A mixture of agarose suitable for the cloning of each cell line is made using 10% fetal bovine serum in growth medium (SW - 620 - agarose al 0. 35%, HCT-8 and HT-29 - agarose at? 4%). An appropriate volume of medium containing the drug treated cells is suspended in the agarose-serum mixture to give the final cell concentrations in 2.5 mL of 1.75 x 104 SW-620, 1 25 x 10 HCT-; t 8 and 7.5 x 103 HT - 29. One milliliter of each of these cell suspensions is added to duplicate wells of 6-well plates previously prepared with 10% serum / growth medium / 1% agarose. The cells in these plates are incubated for approximately 2 weeks in the incubator and stained with 1 mL per 1 mg / mL well.

I of violet stain of iodonitrotetrazolium. The visible colonies are counted with an electronic optical colony counter and the clonogenicity of the treated cells is calculated in comparison to the untreated control cells.

TABLE 3 Inhibition of Growth of the Human Colon Carcinoma Cell Line ND = Not Determined The compounds of this invention are inhibitors of cyclin-dependent kinases and, therefore, are useful in the treatment and prevention of arteriesclerosis and other cellular proliferative disorders such as cancer. The compounds have exhibited inhibitory activity "i" against a wide variety of kinases that depend on the cyclin, all in itself. - - t of experiments routinely used to measure this activity Experiment of Cylinase 4 dependent on Ciclin (cdk4 / cylin D) i Enzymatic experiments for IC50 determinations and kinetic evaluation are carried out Z e_n 96-well filter plates (Millip "ore MADVN6550) The total volume fu 0. 1 mL containing a final concentration of 20 mM TRIS (tris [hydroxymethyl] aminomethane), at a pH of 7.4, 50 mM NaCl, 1 mM dithiothreitol, 10 mM MgCl2, 25 μM ATP containing 0.25 μCi of [32 P] of ATP, 20 ng of cdk4 / cyclin D, 1 μg of retinoblastoma and appropriate dilutions of a compound of the present invention All compounds except ATP are added to the wells and the plate is placed in a mixer of plates for 2 minutes The reaction is started by adding [2P] of ATP and the plate is incubated at 25 ° C for 15 minutes The reaction is terminated by the addition of 0 1 __ ^ mL of trichloroacetic acid (TCA) The plate is kept at 4 ° C for at least 1 hour to allow the substrate to precipitate. Then, the wells are washed 5 times with 0 2 mL of 10% TCA > and the incorporation of 32P is determined with a beta plate counter (Wallace Inc Gaithersburg, MD) Kinease Experiments that Depend on Cyclin (cdk / cichn E, cdk2 / c? Cl A, i cdkl / ciclin B) i Enzymatic experiments for IC50 determinations and kinetic evaluation are performed on a 96 well filter plate (Millipore MADVN6550 ) in a ? total volume of 0 1 mL of 20 mM TRIS (tris [hydroxymethyl] aminomethane), at a pH of ^ t 7 4, 50 mM NaCl, 1 mM dithiothreitol, 10 mM MgCl2, 12 mM ATP containing -t 0 25 μCi of [32P] of ATP, 20 ng of enzyme (either cdk / ciclin E, cdk2 / c? Clm A, or cdkl / ciclin B), 1 μg of retinoblastoma and appropriate dilutions of the invention in particular II All compounds except ATP are added to the wells and the plate is placed in a plate ironer for 2 minutes The reaction is started by the addition of [^ 32 P] f of 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% TCA The plate is kept at 4 ° C For at least 1 hour to allow the substrate to precipitate. Then, the wells are washed 5 times with 0 2 mL of TCA at 10% and incorporation of 32P is determined with a beta-plate counter (Wallace Inc Gaithersburg, MD) The results of these cell cycles (CDK) are shown in Table 4 below: l ^ TABLE 4 ND = Not Determined

Claims

CLAIMS: 1. 1. A compound that has: Formula I where: it is absent or a link; or, uido II is C 1 -C 1 alkyl, C 3 -C 6 cycloalkyl or C 1 -C 2 -cyclonyl alkyl, each R 3 is independently hydrogen or Ci-C 6 alkyl; each n is independently 0 0 hasla 7; R3 / - O- (CII2) lT- ^ C - Cj C6 alkyl O (CH2) n COC, C6 a? Quilo OR II (Ci? 2) n - COI I, R, 3- __ü- (CH2) lT-N V R: (CH2) n-N r ~ \ O, o - N R5 is hydrogen, halogen, aryl, substituted aryl, heteroaryl or substituted heteroaryl and the pharmaceutically acceptable salts thereof 2 A compound confound to Claim 1 wherein R- / yR is __0 __ (cp2)? R- N V R- A compound confumed to Claim 1 where yir'es .Q (CII) n-X. A compound confuted me to Claim 1 where A compound according to Claim 1 wherein / ~? R4 is - N C, c6 alkyl? A compound confuted me to Claim 1 where 7. A compound according to Claim 1 wherein R1 is - NI I - (CH2) n-N (CH2CH3) 2"_ 8. A compound confound to Claim 1 wherein R is phenyl or phenyl replaced 9. A compound coníoinie to Claim 1 wherein R5 is 2,6- 4 dicloiofeiiil t A compound confound to Claim 1 wherein R2 is methy A compound according to Claim 1 wherein Rs is 2,6- 7-dichloiophenyl and R 2 is melil. 12 The compounds 7-amino-3 - (2,6-dichloiophenyl) -1-niel i I-111 - [1,6] naphyrin-2-one, 3 -, (2,6-dichloiolenyl) -1 - mctyl - 7 - dimethylamino - III - [1, 6] naíü? idin - 2 - one, 3 - 2 ^ 6 - dichloiolenyl) - 7 - dimethylamino - 1 - methyl - 111 - [1, 6 | nalVn ¡din - 2-one, 3 - (2,6-dichloiophenyl) -7- [2 - (diethylamino) -ylamino-1-methyl-III [1, 6] nafíi? id? n - 2 -ona, t 3 - . 3 - (2,6-dichlorophenyl) -7- [3 - (diethylamino) propylaminoj-1-methyl-1H [1, 6] naphthyridin-2-one, i 3 - (2,6-dichlorophenyl) -7- [4 - (diethylamino) butylamino] -1-methyl-1H [1,1,6-naphthyridin-2-one, 3 __- ( 2,6-dichlorophenyl) -7- [5 - (diethylamino) pentylaminoj-1-methyl-1 H [1,6-naphthyridin-2-one; i 3 - (2,6-Dichlorophenyl) -1-methyl-7 - [3 - (4-methylpiperazin-1-yl) propylaminoj 1 H - [1, 6] naphthyridin-2-one; - i 3 - (2,6-dichlorophenyl) -1-methyl-7 - [4 - (4-methylpiperazin-1-yl) pentylaminoy t 1 H - [1,6 J naphthyridin-2-one; and 3 - (2,6-dichlorophenyl) -1-methyl-7 - [5 - (4-methylpiperazin-1-yl) propylamino) - ~ I 1H - [1, 6] naphthyridin-2-one. 13. The compounds • 3 - (2,6-dichlorophenyl) -1-methyl-7 - [3 - (4-morpholino) propylamino-1 H - [1,6-naphthyridin-2-one; 3 - (2,6-Dichlorophenyl) -7- [3 - (imidazol-1-yl) propylamino] -1-methyl-1H-i [1, 6] naphthyridin-2-one; 3 - (2,6-dichlorophenyl) -1-methyl-7 - (phenylamino) -1H - [1, 6-naphthyridin-2-one, 3 - (2,6-dichlorophenyl) -1-methyl-7 - (4 - pyridylamino) - 1 H - [1, 6] naphthyridin-2-one; I 3 - (2,6-dichlorophenyl) -7 - [(4-methoxyphenyl) amino] -1-methyl-1H- [1, 6] naphthyridine 1-: f - 2 - ona; ~~ - f = - 3 3 - (2,6-dichlorophenyl) -7 - [(4 - (2-diethylamino) ethoxy) phenylamino] -1-methyl-1H-[[1, 6] naphthyridin-2-one; 3 - . 3 - (2,6-dichlorophenyl) -1-methyl-7 - [4 - (4-morpholino) butylaminoj-1H-i [1,6] naphthyridin-2-one; 3 - (2,6-dichlorophenyl) -7 - [(4 - (3-diethylamino) propoxy) phenyl) amino] 1-methyl-1H- [1,1,6-naphthyridin-2-one; t 3 - (2,6-dichlorophenyl) -1-methyl-7 - [_ (4 - (2 - (4-methylpiperazin-1-yl) ethoxy) phenyl) aminoj-1 H - [1,6] naphthyridin-2 - ona; 3 - (2,6-Dichlorophenyl) -1-methyl-7 - [(4 - (3 - (4-methylpiperazin-1-yl) propoxy) phenyl) aminoj-1 H - [1,6] naphthyridin-2-one; and 3 (2,6-dichlorophenyl) -1-methyl-7 - [(4 - (4 - (4-methylpiperazin-1-yl) propoxy) phenyl) aminoj-1 H - [1,6] naphthyridin-2-one . 14. The compounds: 7-amino-1H- [1,1,6-naphthyridin-2-one; 7-amino-1-ethyl-1H- [1, 6] naphthyridin-2-one; 7-fluoro-1-ethyl-1H- [1, 6] naphthyridin-2-one; 1-ethyl-7-phenylamino-1 H - [1, 6] naphthyridin-2-one; f 1 -ethyl-7- (4-methoxyphenylamino) -1H - [1, 6] naphthyridin-2-one; 1-ethyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] -1H - [1,1,6-naphthyridin-2-one; -I 1 - . 1-ethyl-7 - (4 - (morpholin-4-yl) phenylamino) -1H - [1,6] naphthyridin-2-one; i 1 7 ethyl-7 - (4 - (piperidin-1-yl) phenylamino) -1H - [1,1,6-naphthyridin-2-one; and 1 - "ethyl-7-phenylamino-3,4-dihydro-1H- [1,1,6-naphthyridin-2-one. 15. The compounds: l 7 - [4 - (2 - (diethylamino) ethoxy) phenylaminoj-1-ethyl-1 H - [I, 6] naphthyridin-2-one; 7 -. 7 - [4 - (3 - (diethylamino) ethoxy) phenylamino] -1-ethyl-1H- [1,6] naphthyridin-2-one, ___. t 1 -ethyl-7 - [4 - (2 - (4-methylpiperazin-1-yl) ethoxy) phenylamino] -1,6-naphthyridine 2 - . 2 - ona; 1 ^ 7 ethyl-7 - [4 - (3 - (4-methylpiperazin-1-yl) ethoxy) phenylamino] -1,6-naphthyridin-i-2-one; 1-ethyl-7- (4-pyridylamino) -1H - [1, 6] naphthyridin-2-one; 1-methyl-7 - [4 - (4-methyl-piperazin-1-yl) -phenylamino] -lH- [1, 6] naphthyridin-2-one; 1. i 1-isopropyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] -1H - [1, 6] naphthyridin-2-one; 1 = - isopentyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] -1H - [1, 6] naphthyridin-l-2-one; 4 _ > 'l ^ cyclopentyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] - 1H - [1, 6] naphthyridine 1 - 2 - ona; and 1-cyclohexyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] -1H - [1, 6] naphthyridin-I 2-one. 16. The compounds: 1-cycloheptyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] -1H - [1, 6] naphthyridin-2-one; 1-bicyclo [2 2. ljhept-2-yl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] -1 H - [1,6] naphthyridin-2-one; i 1-methyl-7 - (4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-ylphenylamino} - f 1 H - [1, 6] naphthyridin-2-one; * * - ethyl-7 - (4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-ylphenylamino.} - 1H - [1, 6-Naphthyridin-2-one, i 1-isopropyl-7 - (4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-ylphenylamino}. - 1 H - [1, 6-naphthyridin-2-one, 1-isopentyl-7 -. { 4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-ylphenylamino} - 1H - [l, > Jnaftiridin - 2 - one, 1 ^. cyclopentyl - 7 -. { 4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-ylphenylamino} - 1 H - [1,6] naphthyridin-2-one, 1-cyclohexyl-7 -. { 4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-ylphenylamino} - 1 H - [1, 6-naphthyridin-2-one, V-cycloheptyl-7 - (4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-ylphenylamino} - 1H - [1, 6] naphthyridin-2-one, and 1"-bicyclo [2 2 ljhept-2-yl-7 - (4 - [4 - (3 - (morpholin-4-yl) propyl) pipeiidin-1 - iljphenylamino} - 1 H - [1, 6 J naphthyridin-2-one 1 7 t 17 The compounds -t j 1 _-. methyl - 7 -. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylphenylamino} - 1H - [1, 6-naphthyridin-2-one, 1-ethyl-7 -. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylphenylamino} - 1 H - i [1, 6-naphthyridin-2-one, t 7 -. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylphenylamino} - 1 - isopi opyl-1 H - [1,6] naphthyridin-2-one, 7 -. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylphfemlamino} - 1 - isopentyl - 1H - I [1, 6] naphthyridin - 2 - one, 1 - . 1-cyclopentyl-7-. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylphenylamino} - 1 HOUR [1, 6] naft ridin-2-one, 1-cyclohexyl-7-. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylphenylamino} - 1H [1, 6-naphthyridin-2-one, 1-cycloheptyl-7-. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylphenylamino} - 1 H [1, 6-naphthyridin-2-one, 1-bicyclo [2 2 ljhept-2-yl-7-. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylphenylamino} - 1 H - [1,6] naphthyridin-2-one, 1-methyl-7 - (4 - (pyrazol-1-yl) phenylamino) - 1 H - [1, 6] naphthyridin-2-one, and! 1 - . 1 - . 1 - . 1 - . 1 - . 1-ethyl-7 - (4 - (pyrazol-1-yl) phenylamino) - 1 H - [1,6] naphthyridin-2-one 18 The compounds 17-isopropyl-7 - (4 - (pyrazol-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one, - a - I 1-Isopentyl-7 - (4 - (pyrazol-1-yl) phenylamino) -1H - [1, 6-naphthyridin-2-one, 1-cyclopentyl-7 - (4 - (pyrazol-1-yl) phenylamino) -1H - [l, 6jnaftiridin - 2 - one, 1-Cyclohexyl-7 - (4 - (pyrazol-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one, 1-cycloheptyl-7 - (4 - (pyrazol-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one, "~ - i 1-bicyclo [2 2 ljhept-2-yl-7 - (4 - (pyrazol-1-yl) phenylamino) -1H - 1 [1, 6-naphthyridin-2-one, = i 7 - (4-fluorophenylamino) -1-yl-1H- [1, 6] naphthyridin-2-one, f 1 ^ 7 -ethyl-7 - (4-fluorophenylamino) - 1 H - [1, 6] naphthi? Idin-2-one, 7 - (4-fluorophenylamino) -1-isopropyl-1H- [1, 6] naphthyridin-2-one, and 7 - (4-fluorophenylamino) - 1 - isopentyl - 1H - [1,1,6-naphthyridin 12 -one 19 The compounds 17-cyclopentyl-7 - (4-fluorophenylamino) -1H - [1, 6] naphthyridin-2-one, 1-cyclohexyl-7 - (4-fluorophenylamino) -1H - [1, 6] naphthyridrn-2-one, 1-cycloheptyl-7 - (4-fluorophenylamino) -1H - [1, 6] naphthyridin-2-one, 1-bicyclo [2.2 ljhept-2-yl-7 - (4-fluorophenylamino) -1H - [1,6 ] naphthyridin-2-t _. I ona, ~ ^ I 7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] - 1 H - [1, 6] naphthyridin-2-one, l-ethyl-7 - [4 - ( 4 - (hydroxy) piperidin-1-yl) phenylamino] - 1 H - [1,6] naphthyridin-2 - ona, 7"- [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] -1-isopropyl 1H [1, 6] naphthyridin-2-one, ___ 't 7 - [4 - (4 - (hydroxy) piperidin - 1 - yl) phenylaminoj - 1 - isopentyl - 1 H - ~ t [1,6] naphthyridine - 2 - ona, 1-cyclopentyl-7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] - 1 H - [1, 6] naphthyridin-2-one, and 1-cyclohexyl-7 - [4 - ( 4 - (hydroxy) piperidin-1-yl) phenylamino] - 1 tH - [1, 6] naphthyridin-2-one The compounds 1-cycloheptyl-7 - [4 - (4 - (hydroxy) piperidin-1-yl) femlamino] - 1H [1,1,6-naphthyridin-2-one, 1-bicyclo [2 2 ljhept-2-il - 7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] f 1 H - [1, 6"] naphthyridin-2-one, 7j_t [4 - (3 - (hydroxyyl) piperidin-1-yl) phenylamino-1-yl-1H [ [1, 6] naphthyridin-2-one, _ 1 - ethyl-7 - [4 - (3 - (hydroxyyl) piperidin-1-yl) phenylaminoj - 1H - »- - ' [1, 6 J naphthyridin-2-one, t 7.- [4 - (3 - (hydroxyyl) piperidin-1-yl) phenylamino] -1-isopropyl-1H- [1,1,6-naphthyridin-2-one; 7 ^ [4 - (3 - (hydroxyyl) piperidin-1-yl) phenylaminoj-1-isopentyl-1H- [1,1,6-naphthyridin-2-one, 7 ^ 11-cyclopentyl-7 - [4 - (3 - (hydroxyyl ) piperidin-1-yl) phenylaminoj-1 H - [1,1,6-naphthyridin-2-one,! t-1-cyclohexyl-7 - [4 - (3 - (hydroxyyl) piperidin-1-yl) phenylaminoj - 1 H - [1,1,6-naphthyridin-2-one, 1 7-cycloheptyl-7 - [4 - (3 - (hydroxyyl ) piperidin-1-yl) phenylamino] -1H - [1, 6] naphthyridin-2-one; and 1"" - bicycles [2.2. ljhept-2-yl-7 - [4 - (3 - (hydroxyyl) piperidin-1-yl) phenylamino] - 1 H - [1, 6] naphthyridin-2-one ._ * 21. The compounds. [1-yl-7 - [4 - (2H-tetrazol-5-yl) phenylamino] - 1 H - [1, 6] naphthyridin-2-one, 1-ethyl-7 - [4 - (2H-tetrazole-5 - il) phenylaminoj - 1H - [1, 6] nañiridin-2-one, 1-isopropyl-7 - [4 - (2H-tetrazol-5-yl) phenylamino] - 1 H - [1, 6] naphthyridine - 2 - ona, 1-isopentyl-7 - [4 - (2H-tetrazol-5-yl) phenylamino] -1H - [I, 6-naphthyridin-2-one; 1-cyclopentyl-7 - [4 - (2H-tetrazol-5-yl) phenylamino] -1H - [1,6] naphthyridin-2-one, 1 - . 1-cyclohexyl-7 - [4 - (2H-tetrazol-5-yl) phenylamino] -1 H - [1, 6] naphthyridin-2-one; 1-cycloheptyl-7 - [4 - (2H-tetrazol-5-yl) phenylamino] -1H - [1, 6] naphthyridin-2-one; 1 '- bicycle [2.2. ljhept-2-yl-7 - [4 - (2 H -tetrazol-5-yl) phenylaminoj-1 H - [1, 6] naphthyridin-2-one; 1-yl-7 - (4 - (piperidin-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one; and 1 ^ isopropyl-7 - (4 - (piperidin-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one. 22. The compounds: 1-Isopentyl-7 - (4 - (piperidin-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one; 1 ^ cyclopentyl-7 - (4 - (piperidin-1-yl) enylamino) -1H - [1, 6] naphthyridin-2-one; 1 - . 1-cyclohexyl-7 - (4 - (piperidin-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one; t 1-cycloheptyl-7 - (4 - (piperidin-1-yl) phenylamino) -1H - [1,1,6-naphthyridin-2-one; l '- bicycles [2.2. ljhept-2-yl-7 - (4 - (piperidin-1-yl) phenylamino) - 1 H - [I, 6Jnaffiridin-2-one; 1-methyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one; T-ethyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) -1H - [1,1,6-naphthyridin-2-one; 1-isopropyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one; "-? 1 - sopentyl - 7 - (4 - (pyrrolidin - 1 - yl) phenylamino) - 1 H - [1,1,6-naphthyridin-2-one; and I 1 ^ cyclopentyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) - 1 H - [1,1,6-naphthyridin-2-one. The compounds: i 1-cyclohexyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) -1H - [1,6] naphthyridin-2-one; 1 - . 1-cycloheptyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) - 1 H - [1, 6] naphthyridin-2-one, 1 bicyclo [2.2 ljhept-2-yl - - 7 - (4 - (pyrrolidin - 1 - yl) phenylamino) - 1 H [1,1,6-naphthyridin-2-one; 1-methyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino) -3,4-dihydro-1H [1, 6] naphthyridin-2-one, 1-ethyl-7 - [4 - (4-methylpiperazin-1-yl) phenylaminoj-3,4-dihydro-1H = f [1, 6] naphthyridin-2-one; _. "'1-isopropyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] -3,4-dihydro-1H [l, 6-naphthyridin-2-one, r 1 -isopentyl-7 - [4 - ( 4-methylpiperazirf-1-yl) phenylamino] -3,4-dihydro-1H [1, 6] naphthyridin-2-one; 1 ^ cyclopentyl-7 - [4 - (4-methylpiperazin-1-yl) phenylaminoj-3 , 4 - dihydro - 1H [1, 6] naphthyridin-2-one, [i 1 ^ cyclohexyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] -3,4-dihydro-1H [1, 6] naphthyridin-2-one; and 1-cycloheptyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] -3,4-dihydro-1H [1, 6] naphthyridin-2-one L ~ 'I 24. The compounds. ~ il 1 - bicyclo [2 2 ljhept-2-yl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] - 3,4 I dihydro-1 H - [1,6] naphthyridin-2-one, 1-methyl-7 - (4 - [4 - (3-morpholin-4-yl) propyl) piperidin-1-yl] -phenylamino} 3,4-dihydro-1H - [1, 6] naphthyridin-2-one, 1 - . 1-ethyl-7 - (4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-yl] -phenylamino} - 3,4-dihydro-1 H - [1,6] naphthyridine - 2 - one, 1 ^ - isopropyl-7 - { 4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-yl] -phenylamino.} - 3,4-dihydro- 1 H - [1, 6] naphthyridin-2-one, t 1 -isopentyl-7 -. {4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-ylj-phenylamino) -3 , 4-dihydro-1H - [1,6] naphthyridin-2-one, t 1-cyclopentyl-7 -. { 4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-yl] -phenylamino} - 3,4-dihydro-1H - [1, 6] naphthyridin-2-one, 1"-cyclohexyl-7 - (4 - [4 - (3 - (morpholin-4-yl) propyl) prperidm-1-yl ] -phenylamino.} - 3,4-dihydro-1H - [1,6] naphthyridin-2-one, I 1 -cycloheptyl-7 - (4 - [4 - (3 - (morpholin-4-yl) propyl] ) piperidin-1-yl-phenylamino.} - 3,4-dihydro-1 H - [1, 6] naphthyridin-2-one, 1-bicyclo [2 2 ljhept-2-yl-7 - (4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1 - il] - phenylamino} 3,4-dihydro-1H- [1,1,6-naphthyridin-2-one, and 71'-t-1-methyl-7-. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-yl] -phenylamino} - 3,4-dihydro-TH - [1, 6] naphthyridin-2-one r 25 The compounds - - i 1 ___ ethyl - 7 -. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylj-phenylamino} - 3,4-dihydro -? H - [1, 6] naphthyridin-2-one, 77. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-yl] -phenylamino} - 1 - isopropyl - 3,4 - dihydro-1 H - [1, 6] naphthyridin-2-one, 7 - (4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylj-phenylamino} - 1-isopentyl-3,4 -dihydro - 1 H - [1, 6] naphthyridin-2-one, L - cyclopentyl - 7 -. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylj-phenylamino} - - t 3,4-dihydro-1H- [1, 6] naphthyridin-2-one, 1-cyclohexyl-7 - (4 - [4 - (3 - (hydroxy) pyl-pyl) piperidin-1-yl-phenylamino. 3,4 - dihydro-1 H - [1,1,6-naphthyridin-2-one, f 1 -cycloheptyl-7-. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylj-phenylamino} - 3,4-dihydro-1H - [1, 6] naphthyridin-2-one, 1-bicyclo [2 2 ljhept-2-yl-7-. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-yl] -phenylamino} 3,4-dihydro-1H- [1, 6] naphthyridin-2-one, 1-methyl-7 - (4 - (pyrazol-1-yl) phenylamino) -3,4-dihydro-1H- [1, 6] naphthyridin-2-one, 1-ethyl-7 - (4 - (pyrazol-1-yl) phenylamino) -3,4-dihydro-1H- [1, 6] naphthyridin-2-one, and 1-isopropyl- 7 - (4 - (pyrazol-1-yl) phenylamino) -3,4-dihydro-1H- [1, 6] naphthyridin-2-one 26. The compounds 1-isopentyl-7 - (4 - (pyrazol-1-yl) phenylamino) -3,4-dihydro 1H [1, 6] naphthyridin-2-one, t 1 - . 1 - . 1-Cyclopentyl-7 - (4 - (pyrazol-1-yl) phenylamino) -3,4-dihydro-1H [1,6-naphthyridin-2-one, f 1-cyclohexyl-7 - (4 - (pyrazole-1 - il) phenylamino) - 3,4-dihydro IH [l, 6-naphthyridin-2-one, 1-cycloheptyl-7 - (4 - (pyrazol-1-yl) phenylamino) -3,4-dihydro 1H [l, 6] naphthyridin-2-one, 1 - . 1-bicyclo [2 2 ljhept-2-yl-7 - (4 - (pyrazol-1-yl) phenylamino) -3,4-dihydro-1H - [1,1,6-naphthyridin-2-one; 1 7 -. 7 -. 7 -. 7 - (4-flurophenylamino) -1-methyl-3,4-dihydro-1H- [1,1,6-naphthyridin-2-one, 1-ethyl-7- (4-flurophenylamino) -3,4-dihydro-1H - [ 1, 6] naphthyridin-2-one, 7 - (4-flurophenylamino) -1-isopropyl-3,4-dihydro-1H- [1, 6] naphthyridin-2-one, 7 - (4-flurophenylamino) -1 - isopentyl-3,4-dihydro-1H - [1, 6] naphthyridin-2-one, 1-cyclopentyl-7 - (4-flurophenylamino) -3,4-dihydro-1H- [1, 6] naphthyridin-2-one 27 The compounds 1-c? Clohexyl-7 - (4-flurophenylamino) -3,4-dihydro-1H- [1, 6-naphthyrid? N-2-one, 1-cycloheptyl-7 - (4-flurophenylamino) -3,4 - dihydro-1 H - [1, 6] naphthyridin-2-one, 1} 1 - bicyclo [2 2 ljhept-2-yl 7 - (4-flurophenylamino) -3,4-dihydro-1H [1, 6-naphthyridin-2-one, 7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] -1-methyl-3,4-1H [1,6] naphthyridin-2-one, 1-ethyl-7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] - 3,4 - 1 H i I I [1, 6] naphthyridin-2-one, - i 7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] -1-isopropyl-3,4-1H f [1, 6] naphthyridin-2-one, - - t 7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] -1-isopentyl-3,4-1H I [1, 6] naphthyridin-2-one, 1 .- cyclopentyl-7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] -3,4-1H-i [1, 6] naphthyridin-2-one; 1"cyclohexyl-7 - [4 - (4 - (hydroxy) piperidin-1-yl) -inylaminoj-3,4-1H \ [1, 6] naphthyridin-2-one; and f 1-cycloheptyl-7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] -3,4-1H [l, 6-naphthyridin-2-one 28. The compounds: 1-bicyclo [2-ljhept-2-yl-7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] 3,4-lH- [l, 6-naphthyridin-2-one]; _ 7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylaminoj-1-methyl-3,4-lH t [1, 6] naphthyridin-2-one; 1-ethyl-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylaminoj-3,4-lH [l, 6] naphthyridin-2-one, a- -. + 7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino] -1-isopropyl-3,4-1H - - i [1,6] naphthyridin-2-one, I 7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino] -1-isopentyl-3,4-1H [1, 6] naphthyridin-2-one, 1-cyclopentyl-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino] -3,4-lH [l, 6-naphthipin-2-one; 1-Cyclohexyl-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino] -3,4-1H I [1, 6] naphthyridin-2-one; 1-cycloheptyl-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino] -3,4-lH [l, 6] naphthyridin-2-one; 1 L bicyclo [2 2 ljhept-2-yl-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino] -3,4-lH- [l, 6] naphthyridin-2-one, and 1-methyl-7 - [4 - (2H-tetrazol-5-yl) phenylaminoj-3,4-1H - [1, 6] naft? Pd? N - 2 - = * i-one 29 The compounds 1-ethyl-7 - [4 - (2H-tetrazol-5-yl) phenylaminoj-3,4-1 H - [1,6] naphthyridin-2-one, 1-isopropyl-7 - [4 - ( 2H-tetrazol-5-yl) phenylamino] -3,4-1H- [1, 6] naphthyridine ii 2 - . 2 - . 2 -one, I \ 1 - isopentyl-7 - [4 - (2H-tetrazol-5-yl) phenylamino] -3,4-1H - [1, 6] naft? Pd? N 2-one, 1-cyclopentyl-7 - [4 - (2H-tetrazol-5-yl) phenylamino] -3,4-lH - [L 6] naphthyridine - 2-one, ~ - i 1 - cyclohexyl-7 - [4 - (2H-tetrazol-5-yl) phenylamino] -3,4-lH - [l, 6] naphthyridine - I 2 -one , 1-cycloheptyl-7 - [4 - (2H-tetrazol-5"yl) phenylamino] -3,4-1H - [1, 6-naphthyridin - 2 - one, 1 - bicyclo [2 2 ljhept - 2 - yl - 7 - [4 - (2 H - tetrazol - 5 - yl) phenylamino] - 3,4 - 1 H - [1,6 J naphthyridin - 2 - one , 1-methyl-7 - (4 - (piperidin-1-yl) phenylamino) -3,4-lH - [l, 6] naphthyridin-2-one, 1-ethyl-7 - (4 - (piperidine - 1 - yl) phenylamino) - 3,4 - 1H - [1, 6Jnaft? Ridin - 2 - one, and 1 - isopropyl - 7 - (4 - (piperidin - 1 - ll) phenylamino) - 3,4 - 1H - [l, 6Jnaftipd? n - 2 ona. The compounds 1-isopentyl-7 - (4 - (piperidin-1-yl) phenylamino) -3,4-1H- [1, 6] naphthyridin-2-yne, 1-cyclopentyl-7 - (4 - (piperidin-1-yl) phenylamino) -3,4-lH- [1,6 J naphthyridin-2-one, I 1-cyclohexyl-7 - (4 - (piperidin-1-yl) phenylamino) -3,4 - 1 H - [1,6] naphthyridin-2-I ona, I 1-cycloheptyl-7 - (4 - (piperidin-1-yl) phenylamino) -3,4-1 H - [1, 6] naphthyridine - 2 - ona; 1-bicyclo [2 2 ljhept-2-yl-7 - (4 - (piperidin-1-yl) phenylamino) -3,4-lH- [l, 6-naphthyridin-2-one, 1-methyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) -3,4-lH - [l, 6-naphthyridin-2-one, 1-ethyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) - 3,4 - 1 H - [l, 6] nafti? idin-2-one, 1-isopropyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) -3,4-lH- [l, 6-naphthyridin-2-one, 1-isopentyl-7 - (4 - ( pyrrolidin-1-yl) phenylamino) -3,4-lH- [l, 6-naphthyridin-2-one, and 1-cyclopentyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) -3,4-lH- [1, 6] naphthyridin-2-one. I 1 f 31 The compounds 1-cyclohexyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) -3,4-1 H - [1, 6] naphthyridin-2-one, 1-cycloheptyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) -3,4-lH- [l, 6] naphthyridin-2-one, 1 - . 1 - bicycles [2.2. ljhept-2-yl-7 - (4 - (pyrrolidin-1-yl) phenylamino) -3,4-1H [1, 6-naphthyr-din-2-one; i 3-fluoro-1-methyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] -1H [1, 6] naphthyridin-2-one; 1-ethyl-3-fluoro-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] - 1H - i [1, 6] naphthyridin-2-one; - I 3-fluoro-1-isopropyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] - 1H i [1, 6] naphthyridin-2-one; 3-fluoro-1-isopentyl-7 - [4 - (4-methylpiperazin-1-yl) phenylaminoj-1H [1,1,6-naphthyridin-2-one; l 1 - . 1-cyclopentyl-3-fluoro-7 - [4 - (4-methylpiperazin-1-yl) phenylaminoj-1 H [1, 6] naphthyridin-2-one; 1-cyclohexyl-3-fluoro-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] - 1H l [1, 6] naphthyridin-2-one; and l 1 ^ cyclopentyl-3-fluoro-7 - [4 - (4-methylpiperazin-1-yl) phenylaminoj-1H [1, 6 J naphthyridin-2-one. 32. The compounds: 1 - bicyclo [2.2. ljhept-2-yl-3-fluo -ro-7 - [4 - (4-m-ethyl-piperazin-1-yl) -t-phenylamino] -1H- [1, 6] naphthyr-d-n-2-one; 3 ^ fluoro-1-methyl-7-. { 4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-yl-phenylamino} - 1 H - [1,6] naphthyridin-2-one; 1-ethyl-3-fluoro-7 -. { 4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1 -! iljphenylamino} - 1 H - [1,6] naphthyridin-2-one; 3 - . 3-fluoro-1-isopropyl-7-. { 4 - [4 - (3 ~ - (morpholin-4-yl) propyl) piperidin-1-ylphenylamino} - 1H - [1, 6] naphthyridin-2-one, i 3-fluoro-1-isopentyl-7 - (4 - [4 - (3"* - (morpholin-4-yl) propyl) piperidin-1-ylphenylamino} - 1H - [1, 6] naphthyridin-2-one, i 1-cyclopentyl-3-fluoro-7 -. {4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-ylphenylamino} . - 1 H - [1, 6] naphthyridin-2-one, 1-cyclohexyl-3-fluoro-7 - { 4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-ylphenylamino .} - 1H - [1, 6] naphthyridin-2-one, 1-cycloheptyl-3-fluoro-7 -. {4 - [4 - (37- (morpholin-4-yl) propyl) piperidin-1 - [il-phenylamino.} - 1H - [1, 6] naphthyridin-2-one, - f 1 - . 1 - . 1 - . 1 - . 1 - bicyclo [2 2 ljhept-2-yl-3-fluoro-7 -. { 4 - [4 - (3 - (morpholin-4-yl) propyl) piperidin-1-ylphenylamino} - 1 H - [1, 6] naphthyridin-2-one, and t. l 3-fluoro-1-methyl-7 -. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylj-phenylamino) -1H- [1,1,6-naphthyridin-2-one] The compounds t 1 -ethyl-3-fluoro-7 -. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-yl] -phenylamino} - 1 H - [1, 6] naphthyridin-2-one, 3-fluoro-7 -. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-yl] -phenylamino} - 1-isopropyl-1H- [1, 6] naphthyridin-2-one, 3-fluoro-7 -. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-yl] -phenylamino} - 1-Isopentyl - H - [1,6] naphthyridin-2-one, "^ i 1-cyclopentyl-3-fluoro-7 -. {4 - [4 - (3 - (hydroxy) propyl) piperidin-1 - il] -4-phenylamino.} - 1 H - [1, 6] naphthyridin-2-one, 1 - . 1 - . 1-cyclohexyl-3-fluoro-7 -. { 4 - [4 - (3 - (hydroxy) propyl) piperidin-1-ylj-phenylamino} - 1 H - [1,1,6-naphthyridin-2-one; 1 1 - "cycloheptyl-3-fluoro-7 -. {4 - [4 - (3 - (hydroxy) propyl) piperidin-1-yl] -phenylamino} - 1 H - [1,6] naphthyridin-2 - ona, 1 - bicyclo [2.2.ljhept-2-yl-3-fluoro-7 - { 4 - [4 - (3 - (hydroxy) propyl) piperidin i - 1-ylj-phenylamino} - 1H - [1,1,6-naphthyridin-2-one; I 3-fluoro-1-methyl-7 - (4-pyrazol-1-yl) phenylamino) -1H - [1,6] naphthyridin-2-one; 1-ethyl-3-fluoro-7 - (4-pyrazol-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one; and 3-fluoro-1-isopropyl-7- (4-pyrazol-1-yl) phenylamino) - 1H - [1,1,6-naphthyridine] 2 - . 2 - . 2 - ona. 34. The compounds: 3-fluoro-1-isopentyl-7- (4-pyrazol-1-yl) phenylamino) -1H - [1,6] naphthyridin-2-one; i 1-cyclopentyl-3-fluoro-7 - (4-pyrazol-1-yl) phenylamino) -1H - [1, 6] naftindin 2 - ona; F 1 1 -cyclohexyl-3-fluoro-7 - (4-pyrazol-1-yl) phenylamino) -1H - [1,1,6-naphthyridin-r-2-one; 1-cycloheptyl-3-fluoro-7 - (4-pyrazol-1-yl) phenylamino) -1H - [1, 6] naphthyridin-I 2-one; 1 ^ bicycles [2.2. ljhept-2-yl-3-fluoro-7 - (4-pyrazol-1-yl) phenylamino) -1 H - [1,6 J naphthyridin-2-one; 3-fluoro-7 - (4-fluorophenylamino) -1-methyl-1H- [1, 6] naphthyridin-2-one, 1-ethyl-3-fluoro-7 - (4-fluorophenylamino) -1H - [1, 6] naphthi? Idin-2-one, 3-Tluoro-7- (4-fluorophenylamino) -1-isopropyl-1H - [ 1, 6] naphthyridin-2-one, 3-fluoro-7- (4-fluorophenylamino) -1-stypent-1H- [1,1,6-naphthnidin-2-one, and 1-cyclopentyl-3-fluoro-7 - (4-fluorophenylamino) -1H - [1,1,6-naphthyridin-2-one] 35. The compounds] 1-cyclohexyl-3-fluoro-7 - (4-fluorophenylamino) -1H - [1,1,6-naphthyridin-2-one, 1-cycloheptyl-3-fluoro-7 - (4-fluorophenylamino) -1H - [1,6] aftiridin-2-one, t 1-bicyclo [2 2 l] hept-2-yl-3-fluoro-7 - (4-fluorophenylamino) -1H- [1, 6] naphthyridin-2-one, 3-fluoro-7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] - 1 H - [1, 6] naphthyridin-2-one, l 1-ethyl-3-fluoro-7 - [4 - (4 - (hydroxy) piperidin - 1 - il) phenylamino] - 1 H - [1, 6] naphthyridin-2-one, __ i 3 - . 3-fluoro-7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] -1-isopropyl-1H- [1, 6] naphthyridin-2-one, 3-fluoro-7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] -1-isopentyl-1 H - [1, 6] naphthyridin-2-one, 1-cyclopentyl-3-fluoro-7 - [4 - (4 - (hydroxy ) piperidin-1-yl) phenylaminoj - 1 H - [1,6] naphthyridin-2-one, 1-cyclohexyl-3-fluoro-7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] r [1, 6] naphthyridin-2-one; and 1-cycloheptyl-3-fluoro-7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylamino] -1H [1, 6] naphthyridin-2-one i 7 í 36. The compounds. 1 - bicycles [2.2. ljhept-2-yl-3-fluoro-7 - [4 - (4 - (hydroxy) piperidin-1-yl) phenylaminoj-1 H - [1,6] naphthyridin-2-one; 3-Fluoro-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino-1-methyl-1 H - [1,6] naphthyridin-2-one; 1-ethyl-3-fluoro-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino] -1H - [1, 6] naphthyridin-2-one; 3-fluoro-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino] -1-isopropyl-1 H - [1, 6] naphthyrid? N-2-one; _ i 3 -? fuoro-7 - [4 - (3 - (hydroxymethyl) pipéridin-1-yl) phenylamino] -1-isopentyl-1 H - [1, 6] naphthyridin-2-one; 1-cyclopentyl-3-fluoro-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino] -1H - [1,1,6-naphthyridin-2-one; 1-cyclohexyl-3-fluoro-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylaminoj -1H - [1, 6] naphthyridin-2-one; 1-Cycloheptyl-3-fluoro-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino] -1H - [1, 6] naphthyridin-2-one; 1-b? Cycle [2 2. l] he? T -2-yl-3-fluoro-7 - [4 - (3 - (hydroxymethyl) piperidin-1-yl) phenylamino] - 1 H - [1,6] aftiridin-2-one; and 3 -Huoro-1-methyl-7 - [4 - (2H-tetrazoT-5-yl) phenylamino] - 1 H - [1,6] naphthyridine - 2 - ona. 37. The compounds: 1-ethyl-3-fluoro-7 - [4 - (2H-tetrazoL-5-yl) phenylamino] -1H - [1, 6] naphthyridin-2-one; 3 - . 3-fluoro-1-isopropyl-7 - [4 - (2H-tetrazol-5-yl) phenylaminoj - 1H - ~ "i [1, 6] naphthyridin-2-one, 3-fluoro-1-isopentyl-7 - [4 - (2 H -tetrazol-5-yl) phenylamino] -1H-y [1, 6] naphthyridin-2-one, i 1-cyclopentyl-3-fluoro-7 - [4 - (2H-tetrazol-5-yl) phenylamino] - 1H - I [1, 6] naphthyridin-2-one, 1-cyclohexyl-3-fluoro-7 - [4 - (2H-tetrazol-5-yl) phenylaminoj-1H-i [1, 6] naphthyridin-2-one; 1-cycloheptyl-3-fluoro-7 - [4 - (2H-tetrazol-5-yl) phenylamino] - 1H - -_ ~ | [1, 6-naphthyridin-2-one; 1-J) iciclo [2 2. ljhept-2-yl-3-fluoro-7 - [4 - (2 H -tetrazol-5-yl) phenylamino] -1H - [l, 6] naphthyridin-2-one; 3-fluoro-1-methyl-7 - (4 - (piperidin-1-yl) phenylamino) - 1 H - [1,6] naphthyridin-2 - ona; f \ 1 -ethyl-3-fluoro-7 - (4 - (piperidin-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one; and 3-fluoro-1-isopropyl-7 - (4 - (piperidin-1-yl) phenylamino) - 1H - [1,1,6-naphthyridine] 2 - . 2 - . 2 - ona. 38 The compounds. _ "3-fluoro-1-isopentyl-7 - (4 - (piperidin-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one, '- r 1 - . 1-cyclopentyl-3-fluoro-7 - (4 - (piperidin-1-yl) phenylamino) - 1H - i [1, 6 J naphthyridin-2-one; _ 1 ^ cyclohexyl-3-fluoro-1 - (4 - (piperidin-1-yl) phenylamino) - 1H - __ I [1, 6-naphthyridin-2-one, i 1 7. cycloheptyl-3-fluoro-7 - (4 - "(piperidin-1-yl) phenylamino) - 1H - _ l [l, 6Jnaftindin - 2 - ona, 1 - bicycles [2.2. ljhept-2-yl-3-fluoro-7 - (4 - (piperidin-1-yl) phenylamino) -1H - [1, 6-naphthyridin-2-one, 3-fluoro-1-methyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) - 1 H - [1,1,6-naphthyridin-2] - ona; L 1 -ethyl-3-fluoro-7 - (4 - (pyrrolidin-1-yl) phenylamino) -1H - [1,1,6-naphthyridin-2-one; 3-Fluoro-1-isopropyl-7 - (4 - (pyrrolidin-1-yl) phenylamino) - 1 H - [1,1,6-naphthyridin-2-one, 3-fluoro-1-isopentyl-7 - (4 - (pyrrolidin - 1-yl) phenylamino) - 1H - [1,1,6-naphthyridine - 2 - one, and i 1 - cyclopentyl - 3 - fluoro - 7 - (4 - (pyrrolidin - 1 - yl) phenylamino) - 1 H - f [1,1,6-naphthyridin-2-one. 39 'The compounds \ 1-cyclohexyl-3-fluoro-7 - (4 - (pyrrolidin-1-yl) phenylamino) -1H - [1,1,6-naphthyridin-2-one; 1-cycloheptyl-3-fluoro-7 - (4 - (pyrrolidin-1-yl) phenylamino) - 1H - [1, 6] naphthyridin-2-one, 1-bicyclo [2-ljhept-2-yl-3-fluoro-7 - (4 - (pyrrolidin-1-yl) phenylamino) -1H - [1, 6] naphthyridin-2-one, 3 - . 3 - (2,6-Dichlorophenyl) -7- (4-fluoro-3-methylphenylamino) -1-methyl-1H- [1,6] -f-naphthyridin-2-one, 3 - (2,6-dichlorolenol) - 7 - (4-ethoxylenylamino) -1-methyl-111 - [1,6J-naphthiiidin - 7. ' 2 - ona; 3 3-((2,6-dichlorophenyl) -7- (3 - (hydroxymethyl) phenylamino) -1-methyl-1 H - [1,6] -naphthyridin-2-one; I- 3 - (2,6-dichlorophenyl) -1-methyl-7 - (4-morpholin-4-yl) phenylamino) - 1 H - [1,6] l - naphthyridin-2-one; 3-T2,6-dichlorophenyl) -1-methyl-7 - [4 - (2 - (morpholin-4-yl) ethoxy) phenylamino] -1H - [1,6] -naphthyridin-2-one; 3 - (2,6-Dichlorophenyl) -1-methyl-7 - [4 - (2 - (piperidin-1-yl) ethoxy) phenylamino] - 1 H - [1,6] - naphthyridin-2-one, yi 3 - (2,6-dichlorophenyl) -1-methyl-7 - [4 - (4 - (methylpiperazin-1-yl) methyl) phenylamino] -1H- [1,6] -naphthyridin-2-one. i: l 40. Compounds: 3 ^ (2,6-dichlorophenyl) -7 - [4 - (2 - (dimethylamino) ethoxy) phenylamino] -1-methyl -1H - [1,6] _-naphthyridin-2 - ona; 3 - [3 - (2,6-Dichlorophenyl) -1-methyl-2-oxo-1,2-dihydro- [1, 6] naphthyridin-7-ylamino] -benzoic acid, 3 - ^ (2,6- dichlorophenyl) -7 - [3 - (2 - (diethylamino) ethoxy) phenylamino] -1-methyl-1 H - [1,6] -naphthyridin-2-one; N ~ (2 - { 4 - [3 - (2,6-dichlorophenyl) "- 1-methyl-2-oxo-1,2-dihydro- [1,1,6-naphthyridin-7-ylamino] phenoxy] ethyl ) - N-ethyl-acetamide; acid { 4 - [3 - (2,6-dichlorophenyl) -1-methyl-2-oxo-1,2-dihydro- [1, 6] naphthyridine __ f - 7 - ilamino jphenyl} - acetic, and 3 - (2,6-dichlorophenyl) -1-ethyl-7 - (4-fluoro-3-methylphenylamino) - 1H - [1, 6] nañiridin - 2 - one 41 The compounds 3 - (2,6-dichlorophenyl) -7- (4-ethoxyphenylamino) -1-ethyl-1H - 2-one, 3 - "(2,6-dichlorophenyl) -1-ethyl-7- (3-hydroxymethyl) phenylamino-1H [1, 6] naphthyridin-2-one, 3 - (2,6-dichlorophenyl) -1-ethyl-7 - (4 ^ - (morpholin-4-yl) phenylamino-1H * - [1, 6] naphthyridin-2-one, i 3 - (2,6-dichlorophenyl) -7- [4 - (2-diethylamino) ethoxy) phenylamino-1-ethyl-1H- [1, 6] naphthyridin-2-one, 3 - (2,6-dichlorophenyl) -1-ethyl-7 - [4 - (2 - (morpholin-4-yl) ethoxy) phenylamino] - I fe 1H - [1, 6] naphthyridin-2-one, 3- (2-dichlorophenyl) -1-ethyl-7 - [4 - (2 - (piperidin-1-yl) ethoxy) phenylamino] - I 1 H - [1, 6] naphthyridin-2-one, 3 - (2,6-dichlorophenyl) -1-ethyl-7 - [4 - (4 - (methylpiperazin-1-yl) methyl) r phenylamino] - 1 H - [1,6] naphthyridin-2-one, 3- (2,6-dichlorophenyl) -7- [4 - (2 - (dimethylamino) ethoxy) phenylamino] -1-ethyl-IH- [1, 6] naphthyridin-2-one, 3 - [3 - (2,6-dichlorophenyl) -1-ethyl-2-oxo-1,2-dihydro- [1, 6] naphthyridin-7 acid - ilamino] - benzoic, 3 - . 3 - (2,6-dichlorophenyl) -7- [3 - (2 - (diethylamino) ethoxy) phenylaminoj-1-ethyl-1H- [1,1,6-naphthyridin-2-one, "* ~] N - (2 - ( 4 - [3 - (2,6-dichlorophenyl) -1-ethyl-2-oxo-1,2-dihydro- [1, 6] naphthyridine i - 7 - ilaminojfenoxyjet) - N - ethyl - acetamide, i 3 - (2,6 - dichlorophenyl) - 1 - ethyl - 7 - (4 - pyridylamino) - 1 H - [1,6] - naphthyridine - 2 --one, * I 3 - (2,6-dichlorophenyl) -1-ethyl-7 - [4 - (4-methylpiperazin-1-yl) phenylamino] - '1H | T - [1, 6] naphthyridin-2-one, and acid. { 4 - [3 - 3 - (2,6-Dichlorophenyl) -1-ethyl-2-oxo-1,2-dihydro- [1, 6] naphthyridin-7-ylamino] phenyl} - acetic 42. The compounds 3 - (3,5-dimethoxyphenyl) -1-methyl-7 - [3 - (4-methylpiperazin-1-yl) propylamino] i - 1 H - [1, 6] naphthyridin-2-one, 3 - (3,5-dimethoxyphenyl) -1-ethyl-7 - [3 ^ (4-methylpiperazin-1-yl) propylamino] - 1 H - [1,6] nañiridin-2-one; 7 - (4 - (diethylamino) butylamino) -3- (3,5-dimethoxyphenyl) -1-methyl-1H- [1, 6] naphthyridin-2-one, 7 - (4 - (diethylamino) butylamino) - 3_ - (3,5-dimethoxyphenyl) -1-ethyl-1 H - [1,1,6-naphthyridin-2-one, 7 - [4 - (2 - (diethylamino) ethoxy) phenylamino] - 3 - (3,5-dimethoxyphenyl) - 1-ethyl-1H- [1,1,6-naphthyridin-2-one; 7 - [4 - (2 - (diethylamino) ethoxy) phenylamino] -3- (3,5-dimethoxyphenyl) -1-methyl-1H- [1, 6] naphthyridin-2-one; 3 - . 3 - (3,5-dimethoxyphenyl) -1-ethyl-7- (4-pyridylamino) -1H - [1, 6] naphthyridin-2-one. 3 - (3,5-dimethoxyphenyl) -1-methyl-7- (4-pyridylamino) -1H - [1,1,6-naphthyridin-2-one; 3 - (2,6-dichloro-3,5-dimethoxyphenyl) -1-methyl-7 - [3 - (4-methylpiperazin-1-yl) propylaminoj-1 H - [1,1,6-naphthyridin-2-one, and 3 - (2-Chloro-3,5-dimethoxyphenyl) -1-methyl-7 - [3 - (4-methylpiperazin-1-yl) t-propylamino-1 H - [1,6] naphthyridin-2-one. 43. The compounds 3 - (2,6-dimethyl-3,5-dimethoxyphenyl) -1-methyl-7 - [3 - (4-methylpiperazin-1-yl) propylaminoj-1H - [1,6] naphthyridin-2-one , 1-methyl-3 - (2-methyl-3,5-dimethoxy-phenyl-7 - [3- (4-methyl-piperazin-1-yl) -propylamino-1 H - [1,1,6-naphthyridin-2-one, 3 - (2, 6-dichloro-3,5-dimethoxyphenyl) -J-ethyl-7 - [3 - (4-methylpiperazin-1-yl) propylaminoj-1 H - [1,6] naphthyridin-2-one; 3 - ^ (2 - chloro-3,5-dimethoxyphenyl) -1-ethyl-7 - [3 - (4-methylpiperazin-1-yl) propylamino] -1H - [1,6] naphthyridin-2-one, 3 - (2,6 - dimethyl-3,5-dimethoxyphenyl) -1-ethyl-7 - [3- (4-methylpiperazin-1-yl) propylamino] -1H- [1,1,6-naphthyridin-2-one, 1-ethyl-3 - (2 - methyl-3,5-dimethoxyphenyl) - 7 - [3 - (4-methylpipeiazin-1-yl) propylaminoj-1 H - [1,1,6-naphthyridin-2-one, 3-j., 6-dichloro-3,5 - dimethoxyphenyl) -7- (4 - (diethylamino) butylamino) -1-methyl - 1H - [1,1,6-naphthyridin-2-one; 3 - . 3 - (2-chloro-3,5-dimethoxyphenyl) -7- (4 - (diethylamino) butylamino) -1-methyl-1H - [1, 6] naphthyridin-2-one, - (7 - (4 - (diethylamino) butylamino) -1-methyl-3 - (2-methyl-3,5-dimethoxyphenyl) - * t I 1 H - [1,1,6-naphthyridin-2-one; and 3 - (2,6-dimethyl-3 , 5-dimethoxyphenyl) - - (4 - (diethylamino) butylamino) -1-methyl-1H- [1, 6] naphthyridin-2-one 44 The compounds. 3 - (2,6-dichloro-3,5-dimethoxyphenyl) -7- (4 - (diethylamino) butylamino) -1-ethyl r e * f 1 H - [1, 6] naphthyridin-2-one; 3 - (2-Chloro-3,5-dimethoxyphenyl) -7- (4 - (diethylamino) butylamino) -1-ethyl-1 H [1, 6] naphthyridin-2-one; ! 7 - (4 - (diethylamino) butylamino) -1-ethyl-3 - (2-methyl-3,5-dimethoxyphenyl) -1H [1, 6 J naphthyridin-2-one, 7 - (4 - (diethylamino) butylamino) -3- (2,6-dimethyl-3,5-dimethoxyphenyl) -1-ethyl 1H - [1, 6-naphthyridin-2-one; - ^ = - r I 3 - (2,6-dichloro-3,5-dimethoxyphenyl) -7- [4 - (2-diethylamino) ethoxy) phenylaminoj [1-methyl-1 H - [1,6] naphthyridin-2 - ona, 3 - (2-chloro-3,5-dimethoxyphenyl) -7- [4 - (2-diethylamino) ethoxy) phenylamino] -1-methyl-1H- [1, 6] naphthyridin-2-one, I- 7-4 - (2 - (diethylamino) ethoxy) phenylamino] -1-methyl-3 - (2-methyl-3,5 i dimethoxyphenyl) -1H - [1, 6] naphthyridin-2-one; 3 - (2,6-Dimethyl-3,5-dimethoxyphenyl) -7- [4 - (2-diethylamino) ethoxy) phenylamino] 1 1 - . 1-methyl-1H- [1, 6] naphthyridin-2-one, r 3 - . 3 - (2,6-dichloro-3,5-dimethoxyphenyl) -7 * • [4 - (2-diethylamino) ethoxy) phenylaminoj 1-ethyl-1H- [1,1,6-naphthyridin-2-one; and 3 - (2-chloro-3,5-dimethoxyphenyl) -7- [4 - (2-diethylamino) ethoxy) phenylamino] -1-ethyl-1H- [1,1,6-naphthyridin-2-one] 45. The compounds. 7 -. [4 - (2 - (diethylamino) ethoxy) phenylamino] -1-ethyl-3 - (2-methyl-3,5-dimethoxyphenyl) -1H- [1,6] naphthyridin-2-one; 7 - [4 - (2 - (diethylamino) ethoxy) phenylamino] -3- (2,6-dimethyl-3,5-dimethoxyphenyl) -1-ethyl-1 H - [1,6] naphthyridin-2-one, 1 - methyl-7 - [3 - (4-methylpiperazin-1-yl) propylaminoj-3 - (2,3,5,6-tetramethylphenyl) -1H - [1, 6] naphthyridin-2-one, 1-ethyl- 7 - [3 - (4-Methylpiperazin-1-yl) propylamino] -3- (2,3,5,6-i 1-tetramethylphenyl) -1H - [1,1,6-naphthyridin-2-one, 7 - (4 - ( diethylamino) butylamino) -1-methyl-3 - (2,3,5,6-tetramethylphenyl) -1H - [1,6] naphthyridin-2-one, 7 - (4 - (diethylamino) butylamino) -1 - ethyl-3 - (2,3,5,6-tetramethylphenyl) -1H- ~ 1 [1,6] naphthyridin-2-one; 7 - [4 - (2 - (diethylamino) ethoxy) phenylamino] -1-ethyl-3 - (2,3,5,6-tetramethylphenyl-1H- [1, 6] naphyridin-2-one; ri> 7 - [4 - (2 - (diethylamino) ethoxy) phenylamino] -1-methyl-3 - (2,3,5,6-tetramethylphenyl-1H- [1,6] naphthyridin-2-one, 1-methyl-7 - [3 - (4-methylpiperazin ._-1-yl) propylaminoj-3-phenyl-1H- [1,1,6-naphthyridin-2-one, and 1 ^ ethyl-7 - [3 - (4-methylpiperazin-1-yl) propylamino] -3-phenyl 1H [l, 6-naphthyridin-2-one 46 The compounds i 7 - (4 - (diethylamino) butylamino) -1-methyl-3-phenyl-1H- [1, 6] naphthyridin-2-one, I 7 - (4 - (diethylamino) butylamino) - 1 - ethyl-3-phenyl-1H - [1,6] naphthyridin-2-one, 7 -. 7 - [4 - (2-diethylamino) ethoxy) phenylamino] -1-ethyl-3-phenyl-1H- [1, 6] naphthyridin-2-one; 7 ^ [4 - (2-diethylamino) ethoxy) phenylaminoj-1-methyl-3-phenyl-1H- [1,1,6-naphthyridine] 2 - . 2-one, 7 - [4 - (2 - (diethylamino) ethoxy) phenylamino] -1-methyl-3 - (thiophen-3-yl) -1H-I [l, 6] naphthyridin-2-one, t 7 - [4 - (2 - (diethylamino) ethoxy) phenylamino] -1-ethyl-3 - (thiophen-3-yl) - 1 H - [1,6] naphthyridin-2-one, r 7 - [4 - (2 - (diethylamino) ethoxy) phenylamino] -1-methyl-3 - (thiophen-2-yl) -1H - [1, 6] naphthyridin-2-one, and 7 - [4 - (2 - (diethylamino) ethoxy) phenylamino] -1-ethyl-3 - (thiophen-2-yl) -1H - [1, 6] naphthyridin-2-one 47. A compound according to Claim 1 wherein - is absent A compound according to claim 1 wherein - is a bond A compound according to Claim 1 wherein R2 is -CH2CH3 . .R- R- / / -N - N substituted allyl ryl wherein aiil is phenyl and substituted aryl is phenyl substituted 51 A compound consistent with Claim 1 wherein R is -CH l- Cf CIIj, liic 52 _ A compound according to Claim 1 wherein R5 is hydrogen, s. 25 -Nl, -F, -phenyl-NII, -phenyl-NII substituted, -N- - U- -N N - CU- II \ /. 54. A compound that has Formula I where: it is a link or flatter; -F, - ÑU - phenyl, NH-substituted phenyl, O-O - R5 is hydrogen the acceptable faimmeutical salts of the same 55. "A method for attaching cancer, the method comprises administering to a patient having cancer a therapeutically effective amount of a compound of the Claim 1 '^ \ 56"^ A method paia tiatai or pievenii alelloscleiosis, the method comprises administering to a patient with atherosclerosis or at risk of having atherosclerosis a teiapéulicamente eleliva amount of a compliment of the Claim 57 _ A method paia ti alai or pievenii the slenosis, the method comprises administering to a patient having stenosis or at risk of having atherosclerosis a theoretically elective amount of a compound of Claim 1 58. A method for treating psoriasis, the method comprises administering to a patient having psoriasis a therapeutically effective amount of a compound of the ~ _ ~ - I! Claim 1. i 59. A method for inhibiting protein tyrosine kinases, the method comprises administering to a patient in need of protein tyrosine kinase inhibition an protein tyrosine kinase inhibitor amount of a compound of Claim 1. 60. The method of Claim 60 wherein the tyrosine kinase is c-Src. 61. The method of Claim 60 wherein the tyrosine kinase is PDGFr. 62. The method of Claim 60 wherein the tyrosine kinase is FGFr. i 63. A method for inhibiting cell cycle kinases, the method comprises administering to a patient in need of cell cycle kinase inhibition an inhibitory amount of the cell cycle kinase of a compound of Claim 1. 64. The method of Claim 63 wherein the cell cycle kinase is CDK4, CDK2 or CDKl. 65. A pharmaceutical composition comprising a compound of Claim 1. EXTRACT OF THE INVENTION Naphthyridinones of Formula I sorT inhibitors of PTKs and cell cycle t-kinases, and are useful in the treatment of cell proliferation Compounds are especially useful in the treatment of cancer, atherosclerosis, restenosis and psoriasis