SK141799A3 - 5,7-disubstituted 4-aminopyrido[2,3-d]pyrimidine compounds and their use as adenosine kinase inhibitors - Google Patents

Abstract

A method for inhibiting adenosine kinase by administering a compound having formula (I) wherein R<1> and R<2> are independently selected from H, loweralkyl, C1-C6alkoxyC1-C6alkyl, arylC1-C6alkyl, -C(O)C1-C6alkyl, -C(O)aryl, -C(O)heterocyclic or may join together with the nitrogen to which they are attached to form a 5-7 membered ring optionally containing 1-2 additional heteroatoms selected from O, N or S; R<3> is selected from the group consisting of loweralkyl, loweralkenyl, loweralkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heterocyclic group, heteroarylalkyl or heterocycloalkyl wherein the heteroaryl and heterocyclic groups are linked directly or indirectly by a ring carbon; R<4> is selected from the group consisting of loweralkyl, loweralkenyl, loweralkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heterocyclic group heteroarylalkyl or heterocycloalkyl; and a dashed line --- indicates that a double bond is optionally present provided that proper valencies are maintained, a pharmaceutical composition comprising a therapeutically effective amount of a compound thereof above in combination with a pharmaceutically acceptable carrier, and a method of treating cerebral ischemia, epilepsy, nociperception, inflammation and sepsis in a mammal in need of such treatment, comprising administering to the mammal a therapeutically effective amount of a compound thereof, a process for preparing said compounds, and compounds having the above formula wherein R<1>, R<2>, R<3> and R<4> are separately defined.

Description

N 'N ^ R ⁴

5,7-Disubstituted-4-aminopyrido [2,3-d] pyrimidine compounds, process for their preparation and their use as adenosine kinase inhibitors

Technical field

The invention relates to a method of inhibiting adenosine kinase by administering 5,7-disubstituted-4-aminopyrido [2,3-d] pyrimidine compounds, pharmaceutical compositions containing such compounds, as well as certain 5,7-disubstituted-4-aminopyrido [2,3-d] pyrimidine compounds.

BACKGROUND OF THE INVENTION

Adenosine kinase (ATP: adenosine S'-phosphotransferase, EC 2.7.1.20) is an ubiquitous enzyme that catalyzes the phosphorylation of adenosine to AMP, with ATP being preferably used as the phosphate source. Adenosine kinase has a wide tissue and species distribution and has been isolated from yeast, various mammalian sources and certain microorganisms. Their presence was detected in virtually all human tissues tested, including kidney, liver, brain, spleen, placenta and pancreas. Adenosine kinase is a key enzyme in the regulation of cellular concentrations of adenosine.

Adenosine is a purine nucleoside that mediates purine nucleotide degradation and rescue pathways. Adenosine also has many important physiological effects, many of which are mediated by the activation of specific ectocellular receptors, called Pi receptors (Bumstock, in Cell Membrane Receptors for Drugs and Hormones, 1978, (Bolis and Straub, eds.) Raven, New York, pp. 9-1). 107-118; Fredholm, et al., Pharmacol. Rev. 1994, 46: 143-156).

In the central nervous system, adenosine inhibits the release of certain neurotransmitters (Corradetti, et al. Eur. J. Pharmacol. 1984, 104: 19-26), stabilizes the membrane potential (Rudolphi, et al., Cerebrovasc. Brain Metab. Rev. 1992, 4: 346-360), acts as an endogenous anticonvulsant (Dragunow, Trends Pharmacol. Sci. 1986, 7: 128-130) and may play a role as an endogenous neuroprotective agent (Rudolphi, et al., Trends Pharmacol. Sci., 1992, 13). :

Adenosine can play a role in many central nervous system disorders such as schizophrenia, anxiety, depression and Parkinson's disease. (Williams, M, in Psychopharmacology: The Fourth Generatton of Bloom, Kupfer (eds), Raven Press, New

York, 1995, pp. 643-655

Adenosine is also involved in modulating transmission in spinal cord pain pathways (Sawynok, et al., Br. J. Pharmacol., 1986, 88: 923-930) and mediating the analgesic effects of morphine (Sweeney, et al., J. Pharmacol. Exp. Ther. 1987, 243: 657-665). In the immune system, adenosine inhibits certain neutrophil functions and exhibits anti-inflammatory effects (Cronstein, J. Appl. Physiol. 1994, 76 '5-13) The AK inhibitor has been reported to reduce paw swelling in a model of adjuvant arthritis in rats (Firestein, et al. Arthrilis and Rheumatism, 1993, 36, S48

Adenosine also exhibits various effects on the cardiovascular system, including vasodilation, worsening of atrioventricular conduction, and endogenous cardioprotection in myocardial ischemia and reperfusion (Mullane and Williams, in Adenosine and Adenosine Receptors, 1990 (Williams, ed.) Humana Press, New Jersey, pp. 289). -334). The broad action of adenosine also includes effects on the renal, respiratory, gastrointestinal and reproductive systems as well as on blood cells and adipocytes. Through activation of its A1 receptor on adipocytes, adenosine plays a role in diabetes by inhibiting lipolysis [Londos, et al., Proc. Natl. Acad. Sci. USA, 1980, 77, 2551.

Endogenous release of adenosine appears to play a role as a natural defense mechanism in various pathophysiological conditions, including cerebral and myocardial ischemia, seizures, pain, inflammation and sepsis. While in the extracellular space adenosine is normally present at low levels, its release is locally enhanced at sites of excessive cellular activity, trauma or metabolic stress. Once it enters the extracullular space, adenosine activates specific extracellular receptors, causing various responses that lead to the restoration of normal cellular function (Bruns, Nudeosides Nucleohdes, 1991, 10: 931-943, Miller and Hsu, J. Neurotrauma, 1992, 9). Adenosine has a half-life measured in seconds in extracellular fluids (Moser, et al., Am. J. Physiol. 1989, 25 C799-C806), and its endogenous action is therefore highly localized

Inhibition of adenosine kinase may result in an increase in local concentrations of adenosine in the focus of the injury, further enhancing cytoprotection. This effect is likely to be most pronounced in those areas of the tissue where trauma results in increased adenosine production and also to minimize systemic toxicity.

Pharmacological compounds, directed to the inhibition of adenosine kinase, provide potentially effective novel methods of disorder therapy, benefiting from local and time-specific potentiation of adenosine. Disorders where such compounds may be useful include ischemic conditions such as cerebral ischemia, myocardial ischemia, angina, coronary artery bypass graft surgery (CABG), percutaneous transluminal angioplasty (PTCA), stroke, other thrombological and embolic disorders, and neurological conditions such as epilepsy, anxiety, schizophrenia, nociperception including pain perception, neuropathic pain, visceral pain as well as inflammation, arthritis, immunosuppression, sepsis, diabetes and gastrointestinal dysfunction such as abnormal gastrointestinal motility.

The ability to inhibit adenosine kinase has been reported in a number of compounds. The most effective of these are 5'-amino-5'-deoxyadenosine (Miller, et al., J. Biol. Chem. 1979, 254 23392345), 5-iodo-tubercidine (Wotring and Townsend, Cancer Res. 1979, 39: 3018-3023) and 5'-deoxy-5-iodo-tubercidine (Davies, et al., Biochem. Pharmacol. 1984, 33: 347-355)

Adenosine kinase is also responsible for the activation of a number of pharmacologically active nucleosides (Miller, et al., J. Biol. Chem. 1979, 254: 2339-2345), including tubercidine, formycin, ribavirin, pyrazoftirin and 6- (methylmercapto) purine riboside. These purine nucleoside analogs analogs represent a significant class of antimetabolites having cytotoxic, anticancer and antiviral properties. They serve as substrates for adenosine kinase and are phosphorylated by the enzyme to form the active form. A decrease in adenosine kinase activity is implicated as a mechanism of cellular resistance to the pharmacological effects of these nucleoside analogs {e, g. Bennett, et al., Mol. Pharmacol., 1966, 2: 432-443; Caldwell, et al., Can. J. Biochem., 1967, 45735-744; Suttle, et al., Europe. J. Cancer, 1981, 17: 43-51). Decreased cellular levels of adenosine kinase are also associated with resistance to the toxic effects of 2'-deoxyadenosine (Hershfield and Kredich, Proc. Natl. Acad. Sci. USA, 1980, 77 4292-4296). The accumulation of deoxyadenosine triphosphate (dATP), resulting from the phosphorylation of 2-deoxyadenosine, has been implicated as a toxic mechanism in immune deficiency associated with an inherited deficiency of adenosine deaminase (Kredich and Hershfield, in The Metabohc Basis of Inhents, 1989). , McGraw-Hill, New York, pp. 1045-1075).

B.S Hurlbert e! al. (J. Med. Chem., II 711-717 (1968)) describe various 2,4-diaminopyrido [2,3-d] pyrimidine compounds useful as antibacterial agents. RK Robins et al. (Amer. Chem. Soc., 80.3449-3457 (1958)) describe methods for preparing various 2,4-dihydroxy-, 2,4-diamino-, 2-amino-4-hydroxy- and 2-mercapto 4-hydroxypyrido [2,3-d] pyrimidines with folic acid activity R Sharma et al., (Indian J. Chem., 31B 719-720 (1992)) disclose 4-amino-5- (4-chlorophenyl) -7- (4-nitrophenyl) pyrido [2,3-d] pyrimidine and 4-amino-5- (4-methoxyphenyl) -7- (4-nitrophenyl) pyrido [2,3-d] pyrimidine compounds with antibacterial activity A. Gupta et al., (J. Indian Chem. Soc., T: 635-636 (1994)) disclose 4-amino-5- (4-fluorophenyl) -7- (4-fluorophenyl) pyrido [2,3-d] pyrimidine and 4-amino-5- (4-chlorophenyl) -7- (4-fluorophenyl) pyrido [2,3-d] pyrimidine compounds with antibacterial activity L Prakash et al., Pharmazie, 48 221-222 (1993)) disclose 4-amino-5-phenyl-7- (4-aminophenyl) pyrido [2,3-d] pyrimidine, 4 amino-5-phenyl-7- (4-bromophenyl) pyrido [2,3-d] pyrimidine, 4 -amino-5- (4-methoxyphenyl) -7- (4-aminophenyl) pyrido [2,3-d] pyrimidine and 4-amino-5- (4-m ethoxyphenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine compounds with antifungal activity. P. Victory et al., Tetrahedron, 51: 1025310258 (1995)) describe the synthesis of 4-amino-5,7-diphenylpyrido [2,3-d] pyrimidine compounds from acyclic precursors. Bridges et al. (PCT Application WO 95/19774, published Jul. 27, 1995) disclose that various bicyclic heteroaromatic compounds have the ability to inhibit epidermal growth factor tyrosine kinase.

SUMMARY OF THE INVENTION

The invention provides 5,7-disubstituted-4-aminopyrido [2,3-d] pyrimidine compounds useful as adenosine kinase inhibitors.

On the one hand, the present invention provides a method of inhibiting adenosine kinase by administering a compound of formula (I)

where

R and R ² are independently selected from H, lower alkyl,.] - C alkoxyC _fi | C _ft alkyl, arylC COalkyl, -C (O) C] -C 6 alkyl, -C (O) aryl, - C (O) heterocycle or may be linked to the nitrogen to which they are attached to a 5-7 membered ring, optionally containing 1-2 additional heteroatoms selected from the group consisting of O, N or S;

R ³ is selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heterocyclic, heteroarylalkyl or heterocycloalkyl, wherein the heteroaryl and heterocyclic groups are attached directly or indirectly by a ring carbon;

R 6 is selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heterocyclic; heteroarylalkyl or heterocycloalkyl and dashed line - indicates that a double bond is optionally present as long as the proper valencies are maintained.

Specifically, the method of inhibiting adenosine kinase comprises exposing the adenosine kinase to an inhibitory effective amount of a compound of formula I of the invention. When the adenosine kinase is located in vivo, the compound is applied to the body.

In another aspect, the invention provides a method of treating ischemia, neurological disorders, nociperception, inflammation, immunosuppression, gastrointestinal dysfunction, diabetes and sepsis in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of a compound of Formula I of the invention.

In a preferred embodiment, the invention provides a method of treating cerebral ischemia, myocardial ischemia, angina, coronary artery bypass graft surgery, percutaneous transluminal angioplasty, stroke, thrombotic and embolic states, epilepsy, anxiety, schizophrenia, pain perception, visceral pain, neuropathic pain, neuropathic , sepsis, diabetes and abnormal gastrointestinal motility in a mammal in need of such treatment comprising administering to the mammal a therapeutically effective amount of a compound of formula I of the invention

The invention also encompasses the use of pharmaceutically acceptable salts and amides of the compounds of Formula 1

In another aspect, the invention provides compound (I)

where

R ¹ and R ² are independently selected from H, lower alkyl, C alkoxyCiC _{ft 6} alkyl, aryl and -COalkyl, -C (O) C] -COalkyl, -C (O) aryl, -C (O ) a heterocycle or may be linked to the nitrogen to which they are attached to a 5-7 membered ring optionally containing 1-2 additional heteroatoms selected from the group consisting of O, N or S;

R 6 is selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heterocyclic, heteroarylalkyl or heterocycloalkyl, wherein the heteroaryl and heterocyclic groups are attached directly or indirectly by a ring carbon;

R ⁴ is selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heterocyclic; heteroarylalkyl or heterocycloalkyl and dashed line - indicates that a double bond is optionally present as long as the correct valencies are maintained, with the proviso that the compound cannot be selected from the group consisting of (a) 4-amino-5- (4-chlorophenyl) -7- (4-nitrophenyl) -pyrido [2,3-d] pyrimidine;

(b) 4-amino-5- (4-methoxyphenyl) -7- (4-nitrophenyl) pyrido [2,3-d] pyrimidine;

(c) 4-amino-5- (4-fluorophenyl) -7- (4-fluorophenyl) pyrido [2,3-d] pyrimidine;

(d) 4-amino-5- (4-chlorophenyl) -7- (4-fluorophenyl) pyrido [2,3-d] pyrimidine; (e) 4-amino-5-phenyl-7- (4-aminophenyl); pyrido [2,3-d] pyrimidine;

(f) 4-amino-5-phenyl-7- (4-bromophenyl) pyrido [2,3-d] pyrimidine; (g) 4-amino-5- (4-methoxyphenyl) -7- (4-aminophenyl) pyrido [g] 2,3-d] pyrimidine, (h) 4-amino-5- (4-methoxyphenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine, and (i) 4-amino-5, 7-diphenylpyrido [2,3-d] pyrimidine.

Ί

In another aspect, the invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of the above formula 1 and a pharmaceutically acceptable carrier.

In another aspect, the invention provides a process for the preparation of adenosine kinase inhibiting compounds of formula

Rk..R ² n 3 'NR

NN j R 7, KDG 1 _and R 2 hydrogen, consisting in that, (a) a ketone of formula R ⁴ -CO-CH 3 wherein R ⁴ is as defined above, is brought under anhydrous conditions in contact with an aldehyde of formula ^R3 -CHO wherein R · * is as defined above, and malononitrile in the presence of an ammonium salt, and isolating the first intermediate structure

(b) contacting the first intermediate with formamide for about 1 to about 8 hours at reflux and isolating the compound of formula I with double bonds between positions 7 and 8 at positions 5 and 6 and optionally reducing it to a compound of formula I with partially saturated right side or fully saturated right side.

The invention relates to 5,7-disubstituted-4-aminopyrido [2,3-d] pyrimidine compounds which are useful for inhibiting adenosine kinase, pharmaceutical compositions containing them, a method of using these compounds for inhibiting adenosine kinase and novel 5,7-disubstituted- 4-aminopyrido [2,3-d] pyrimidine compounds.

In one aspect, the invention provides 5,7-disubstituted-4-amino-pyrido [2,3-d] pyrimidine compounds that are adenosine kinase inhibitors. The adenosine kinase inhibitor of the invention is a compound of the above formula I.

As mentioned above, the invention relates to a method of inhibiting adenosine kinase comprising administering a compound of formula I

(1) where

R 1 and R 2 are independently selected from the group consisting of H, lower alkyl, arylC 1 -C 6 alkyl, C (O) C 1 -C 6 alkyl, -C (O) aryl, -C (O) heterocycle or may be attached to nitrogen to which they are attached, a 5-7 membered ring optionally containing 1-2 additional heteroatoms selected from the group consisting of O, N or S;

R ³ and R 6 are independently selected from the group consisting of:

C-COalkyl,

C 2 -C 6 alkenyl,

C 2 -alkynyl,

C 3 -C 8 cycloalkyl, heteroarylC 0 -C 6 alkyl or substituted heteroaryl C 0 -C 6 alkyl, optionally substituted cycloalkyl, arylC 0 -C 6 alkyl or substituted arylC 0 -C 6 alkyl, heteroaryl C 2 -C 6 alkenyl or substituted heteroaryl C 2 -C 6 alkenyl, substituted arylC 2 -C 6 alkenyl or substituted heteroC 2 -C 6 alkenyl, -C 6 alkynyl, arylC 2 -C 6 alkynyl or substituted arylC ₂ -C 6 alkynyl wherein 1-4 heteroaryl or aryl substituents are independently selected from the group consisting of halogen, oxo, CO ₂ R ⁵ , cyanoC 1 -C 6 alkyl, heteroarylC 0 -C 6 alkyl, heterocycle C 0 -C 6 alkyl,

C 1 -C 6 alkyloxy, C 1 -C 6 alkyloxyC 1 -C 6 alkyl, arylC 0 -C 6 alkyl, arylC 1 -C 6 alkykyloxy, R ⁵ R ⁶ NC (O), cyano, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyldialkylmalonyl, CF3, HO- , C] 9

C 6 alkyloxyC 1 -C 6 alkyloxy, C 1 -C 6 alkylSOn, wherein n is 1-2, C 1 -C 6 alkylthio, C 1 -C 6 alkylacryl,

CF 3 O, CF 3, C 1 -C 4 alkylenedioxy, C 1 -C 6 alkylacryl, R 6 R 6 NCCO 3 NR 6, N-formyl (heterocycle),

NO 2, NR ⁵ R ⁶ Co-6 alkyl, (R ⁵ O) (R ⁶ O) P (O) C _t -C ₆ alkyl, wherein R 5 and R are independently selected from H, C1-COalkyl, HC (O), C 1 -C 6 alkykyloxyC 1 -C 6 alkyl, C 1 -C 6 alkykyloxy, C 1 -C 6 alkylC (O), CF 3 C (O), NR ⁷ R ⁸ C 1 -C 6 alkyl, phthalimidoC 1 -C ⁶ C (O), C 1 -C 6 alkylSO _n where n is 1-2, CNC 1 -C 6 alkyl, R ⁷ R ⁸ NC (O) NR ⁷ -, heteroaryl, NR ⁷ R ⁸ C ¹ -C 6 alkylC (O), C 1 -C 6 alkyloxycarbamidoC 1 -C 6 alkyl, wherein R ⁷ and R ⁸ are independently selected from the group consisting of the variables listed for

R5 and R6; or

R 5 and R ⁶ or R ⁷ and R ⁸ may be attached to the nitrogen atom to which they are attached to a 5-7 membered unsubstituted or substituted ring, optionally containing 1-3 additional heteroatoms selected from the group consisting of O, N or S, wherein the substituents are selected from the group consisting of C 1 -C 6 alkyl, and the dotted line - indicates that a double bond is optionally present.

Preferred compounds used in the above method of inhibiting adenosine kinase are selected from the group consisting of compounds of Formula II

wherein R 1 -R ⁸ and n are as defined above The invention also relates to compounds of formula II wherein

R ⁸ -R n are as defined, with the proviso that specifically excluded above compounds of formula I.

In a preferred embodiment, the adenosine kinase inhibitor of the invention is a compound of the above formula (II) wherein R 1 is aryl or heteroaryl and substituted versions thereof

ΙΟ

In an even more preferred embodiment, the adenosine kinase inhibitor of the invention is a compound of the above formula (II) wherein R ⁴ is aryl or heteroaryl and substituted versions thereof and R 4 'is lower alkyl, aryl, arylalkyl or heteroaryl and substituted versions thereof wherein the substituents have the above meaning.

In another preferred embodiment, the adenosine kinase inhibitor of the invention is a compound of formula (I) above wherein R ⁴ is selected from the group consisting of phenyl, thiophen-2-yl,

3-Methyl-2-oxobenzoxazolin-6-yl; 2- (dimethylamino) -5-pyrimidinyl; 2- (N-formyl-N-methylamino) -5-pyrimidinyl; 2- (N-methoxyethyl-N-methylamino) -5-pyrimidinyl; 2- (N-methylamino) -5-pyrimidinyl,

2- (1-morpholinyl) -5-pyrimidinyl; 2- (1-pyrrolidinyl) -5-pyrimidinyl; 2-dimethylamino-5-pyrimidinyl, 2-furanyl; 2-oxobenzoxazolin-6-yl; 2-pyridyl, 3- (dimethylamino) phenyl; 3-amino-4-methoxyphenyl, 3-bromo-4- (dimethylamino) phenyl; 3-methoxyphenyl, 3-methyl-4- (N-acetyl-N-methylamino) phenyl, 3-methyl-4- (N-formyl-N-methylamino) phenyl; 3-methyl-4- (N-methyl-N- (trifluoroacetyl) amino) phenyl, 3-methyl-4- (N-methylamino) phenyl; 3-methyl-4-pyrolidinylfenyI; 3-pyridyl; 3,4-dichlorophenyl; 3,4-methylenedioxyphenyl, 3,4,5-trimethoxyphenyl; 4- (acetylamino) phenyl; 4- (dimethylamino) -3-fluorophenyl; 4 (dimethylamino) phenyl; 4- (imidazol-l-yl) phenyl; 4- (methylthio) phenyl; 4- (morpholinyl) phenyl; 4- (N- (2 (dimethylamino) ethyl) amino) phenyl; 4- (N- (2-methoxyethyl,) amino) phenyl; 4- (N-acetyl-N-methylamino) phenyl; 4- (N-ethyl-N-formylamino) phenyl; 4- (N-ethylamino) phenyl; 4- (N-formyl-N- (2-methoxyethyl) amino) phenyl; 4- (N-isopropylamino) phenyl; 4- (N-methyl-N - ((2-dimethylamino) ethyl) amino) phenyl; 4- (N-methyl-N- (2- (N-phthalimidyl) acetyl) amino) phenyl; 4- (N-methyl-N- (2-cyano) ethylamino) phenyl; 4- (N-methyl-N- (2-methoxyethyl) amino) phenyl; 4- (N-methyl-N- (3-methoxy) propionylamino) phenyl; 4- (N-methyl-N-acetylamino) phenyl; 4- (N-methyl-N-formylamino) phenyl; 4- (N-methyl-N-trifluoroacetylamino) phenyl, 4- (N-morpholinyl) phenyl, 4- (thiophen-2-yl) phenyl, 4- (ureido) phenyl, 4- (2 (dimethylamino) acetylamino) phenyl; 4- (2- (2-methoxy) acetylamino) ethyl) amino) phenyl; 4- (2-methoxy) ethoxyphenyl; 4- (2-oxo-3-oxazolidinyl) phenyl, 4- (4-methoxy-2-butyl) phenyl, 4- (4-methylpiperidinyl) phenyl; 4- (5-pyrimidinyl) phenyl, 4-aminophenyl; 4-bromophenyl; 4-butoxyphenyl, 4-carboxamidophenyl; 4-chlorophenyl, 4-cyanophenyl; 4diethylaminophenyl; 4-diethylmalonylallylphenyl); 4-dimethylaminophenyl, 4-ethoxyphenyl; 4-etyIfenyl; 4-fluorophenyl; 4-hydroxyphenyl; 4-imidazolylphenyl; 4-iodophenyl, 4-isopropylphenyl, 4-methoxyphenyl; 4-methylaminophenyl; 4-methylsulfonylphenyl, 4-morpholinylphenyl; 4-N- (2- (dimethylamino) ethyl) -N-formylamino) phenyl; 4-N- (3-methoxypropionyl) -Nisopropylamino) phenyl, 4-N-ethyl-N- (2-methoxyethyl) amino) phenyl; 4-N-formylpiperazinylphenyl, 4-nitrophenyl, 4-piperidinylphenyl, 4- (3-pyridyl) phenyl, 4-pyrrolidinylphenyl; 4-t-butylacrylphenyl, 5 (dimethylamino) thiophen-2-yl; 5-amino-2-pyridyl; 5-dimethylamino-2-pyrazinyl; 3II dimethylaminopyridazin-6-yl; 5-dimethylamino-2-pyridyl; 5-pyrimidinylphenyl, 6- (N-methyl-N -formylamino) -3-pyridinyl, 6- (N-methyl-N-methoxyethylamino) -3-pyridinyl, 6- (2-oxo-3-oxazolidinyl) -3-pyridinyl; 6-dimethylamino-3-pyridinyl; 6-imidazolyl-3-pyridinyl; 6-morpholinyl-3-pyridinyl,

6-pyrrolidinyl-3-pyridinyl, 6- (2-propyl) -3-pyridinyl and (4-formylamino) phenyl

In another preferred embodiment, the adenosine kinase inhibitor of the invention is a compound of the above formula (1), wherein R p is selected from the group consisting of. (thiophen-2-yl) methyl, (thiophen-3-yl) methyl, butyl; cycloheptyl; pentyl; thiophen-2-yl; l- (3-bromophenyl) ethyl; 2- (N-phenylmethoxycarbonyl) aminophenyl, 2- (3-bromophenyl) ethyl; 2- (3-cyanophenyl) methyl, 2- (4-bromophenyl) ethyl; 2- (5-chloro-2- (thiophen-3-yl) phenyl, 2-bromophenyl; 2-furanyl; 2-methylpropyl; 2-phenylethyl; phenylmethyl; 2,3-dimethoxyphenyl, 2,3-methylenedioxyphenyl; 3- (furan) -2-yl) phenyl; 3- (thiophen-2-yl) phenyl; 3- (2-pyridyl) phenyl; 3- (3-methoxybenzyl) phenyl; 2- (3-aminopropinyl) phenylmethyl; 3-benzyloxyphenyl; 3-bromo-4 fluorophenyl; 3-bromo-5-iodophenyl; 3-bromo-5-methoxyphenyl; 3-bromophenyl, 3-bromophenylmethyl; 3-carboxamidophenyl, 3-chlorophenyl; 3-cyanophenyl; 3-diethylmalonylalylphenyl; 3dimethylaminophenyl; 3-ethoxyphenyl; -5-trifluoromethylphenyl; 3-fluorophenyl; 3-hydroxyphenyl; 3-iodophenyl; 3-methoxyethoxyphenyl; 3-methoxyphenyl; 3-methylphenyl; 3-methylsulfonylphenyl; 3-methylthiophenyl; 3-t-butylacryphenyl; 3-trifluoromethoxyphenyl; 3-trifluoromethylphenyl; 3-trifluoromethylphenyl; 4-dichlorophenyl; 3,4-dimethoxyphenyl; 3,4-methylenedioxyphenyl; 3,4,5-trimethoxyphenyl; 3,5-di (trifluoromethyl) phenyl; 3,5-dibromophenyl; 3,5-dichlorophenyl, 3,5-dimethoxyphenyl; ;

3,5-dimethyl-phenyl; 4- (2-propyl) phenyl, 4- (2-propyl) oxyphenyl; 4-benzyloxyphenyl; 4-bromophenyl; 4brómtiofen-2-yl; 4-butoxy-phenyl; 4-dimethylaminophenyl; 4-fluoro-3-trifluoromethylphenyl; 4-methoxyphenyl, 4-neopentylphenyl; 4-phenoxyphenyl; 5-bromo-thiophen-2-yl; 5-cyclohexyl; 5-cyclopropyl;

5-hexyl; 5-methyl; 5-phenyl, (2-bromo-5-chlorophenyl) methyl; (2-bromophenyl) methyl and (5-chloro-2- (3-methoxyphenyl) phenyl) methyl.

Exemplary and preferred adenosine kinase inhibitors of the invention used in the method of the invention include the following compounds wherein R 1 and R 2 in the compound of formula II are selected from the group consisting of H, the groups identified at the 5-position are included in R 4 and position 7-are included in R 1, R 1 - R 1 - have the meaning given in a particular compound

4-amino-5- (4-dimethylaminophenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (4-dimethylaminophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-methoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (4-dimethylaminophenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4- (2-propyl) phenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-neopentylphenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (4-butyloxyphenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-methoxyphenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (4- (2-propyl) phenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (4-butoxy-phenyl) -7- (4-N-formylpiperazinylfenyI) -pyrido [2,3-d] pyrimidine,

4-amino-5- (4-benzyloxyphenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-phenoxyphenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4- (2-propyl) phenyl) -7- (4-diethylmalonylallylphenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (4- (2-propyl) phenyl) -7- (4-t-butylacrylphenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3,4-dimethoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-t-butylacrylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-methoxyphenyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dimethoxyphenyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-diethylmalonylallylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-vinylpyridinylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-trifluoromethylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-carboxamidophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-cyanophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-benzyloxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-methoxyphenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4-butoxy-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3- (2-pyridyl) phenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-methylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-chlorophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-fluorophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-methoxyphenyl) -7- (4-bróinfenyl) -pyrido [2,3-d] pyrimidine ·,

4-amino-5- (3-bromophenyl) -7-phenyl-pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-ethyl-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-cyanophenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-hydroxyphenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-iodophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-ethoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidin;

4-amino "5- (3-trifluórmetyoxyfenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dichlorophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromo-4-fluorophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-hydroxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-piperidinylphenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (imidazol-l-yl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-chloro-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-isopropyl-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-trifluorophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (3,4,5-trimethoxy-phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3- (3-methoxybenzyl) phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-methoxyethyoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3,4-methylenedioxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-ethoxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- ^(2, thiophene) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-fluorophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-dimethylaminophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5-phenyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3,4,5-trimethoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-nitrophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-iodo-phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (3,4-methylenedioxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (thiophen-2-yl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3,5-dimethoxyphenyl) -7- (thiophen-2-yl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4-carboxamidophenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (2-methoxy) ethoxyphenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dimethoxyphenyl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-trifluoromethylphenyl) -7- (thiophen-2-yl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-atninofenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromo-4-fluorophenyl) -7- (thiophen-2-yl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromo-4-fluorophenyl) -7- (2-furanyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dimethoxyphenyl) -7- (4-iodo-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dimethoxyphenyl) -7- (4-imidazolylphenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dimethoxyphenyl) -7- (4- (thiophen-2-yl) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3,5-dimethoxyphenyl) -7- (4- (3-pyridyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (4-methylpiperidinyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-pyrrolidinylphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-bromothiophene -) - 7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-bromo-thiophen-2-yl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine;

4-morpholinyl-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (5-bromo-thiophen-2-yl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidin;

4-amino-5- (3-bromophenyl) -7- (4- (acetylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-Amino-5- (3-bromophenyl) -7- (4-dimethylarninophenyl) pyrido [2,3-d] pyrimidine ₁

4-amino-5- (3,5-dimethoxyphenyl) -7- (5-pyrimidinylphenyl) pyrido [2,3-d] pyrimidin;

4- (4-fluorophenyl) amino) -5- (3-bromophenyl) -7- (4-dimetylaniinofenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-bromo-thiophen-2-yl) -7- (4-pyrrolidinylphenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (4-bromo-thiophen-2-yl) -7- (thiophen-2-yl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (5- (dimethylamino) thiophen-2-yl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromo-5-iodophenyl) -7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3,5-di (trifluoromethyl) phenyl) -7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-di (trifluoromethyl) phenyl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dibromophenyl) -7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3,5-dibromophenyl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-bromo-thiophen-2-yl) -7- (4- (4-methylpiperidinyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dibromophenyl) -7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (3- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-methylsulfonylphenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (3-methoxyphenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (methylthio) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (3,4-dichlorophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N-formylamino) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromo-4-fluorophenyl) -7- (4-methylsulfonylphenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (3-amino-4-methoxy-phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (3-bromo-4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N-trifluoroacetylamino) phenyl) pyrido [2,3d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (dimethylamino) -3-fluorophenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (N-ethyl-N-formylamino) phenyl) pyrido [2,3-d] pyrimidine;

4,4-bis (acetylamino) -5- (3-bromophenyl) -7- (4- (N-methyl-N-acetylamino) phenyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (4- (N-acetyl-N-methylamino) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (N-ethylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (2-methoxyethyl) amino) phenyl) pyrido [2,3d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (N-isopropylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-N-ethyl-N- (2-methoxyethyl) amino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-N- (3-methoxypropionyl) -N-isopropyl-amino) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4-N- (2- (dimethylamino) ethyl) -N-formylamino) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (N- (2- (dimethylamino) ethyl) amino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (2-cyano) ethylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (3-methoxy) propionylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (N-formyl-N-methylamino) phenyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (N-methylamino) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (4-methoxy-2-butyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (2- (N-phthalimidyl) acetyl) amino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (N-methyl-N- (trifluoroacetyl) amino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (N-acetyl-N-methylamino) phenyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (6-dimethylamino-3-pyridinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-cyanophenyl) -7- (4-methylsulfonylphenyl) pyrido [2,3-pyrimidine;

4-amino-5- (3-cyanophenyl) -7- (4- (N-methyl-N-formylamino) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6- (N-methyl-N-formylamino) -3-pyridinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6-morpholinyl-3-pyridinyl) pyrido [2,3-pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6- (N-methyl-N-methoxy-ethylamino) -3-pyridinyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (6-pyrrolidinyl-3-pyridinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (2- (dimethylamino) -5-pyrimidinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (2- (N-methoxyethyl-N-methylamino) -5-pyrimidinyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (2- (N-foimyl-N-methylamino) -5-pyrimidinyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (2- (N-methylamino) 5-pyrimidinyl) pyrido [2 ₁ 3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (2- (l-pyrrolidinyl) -5-pyrimidinyl) pyrido [2,3-pyrimidine,

4-amino-5- (3-bromophenyl) -7- (2- (l-morpholinyl) -5-pyrimidinyl) pyrido [2,3-pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6- (2-oxo-3-oxazolidinyl) -3-pyridinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (2-pyridyl) pyrido [2,3-pyrimidine;

4-amino-5- (3-bromophenyl) -7- (3-pyridyl) pyrido [2,3-pyrimidine,

4-amino-5- (3- (thiophen-2-yl) phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3- (furan-2-yl) phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3- (3-methoxyphenyl) phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5-phenyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-chlorophenyl) -7- (4- (morpholinyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-4-fluorophenyl) -7- (4- (morpholinyl) phenyl) pyrido [2,3-d] pyrimidine, 4-amino-5- (3-chlorophenyl) -7- (4-iodophenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-chlorophenyl) -7- (4- (thiophen-2-yl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-chlorophenyl) -7- (4- (5-pyrimidinyl) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromo-4-fluorophenyl) -7- (4-iodo-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-bromo-thiophen-2-yl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) methyl-7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (2-phenylethyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (2-methylpropyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (butyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (2- (4-bromophenyl) ethyl) -7- (4-dietyIaminofenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (butyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (2- (3-cyanophenyl) methyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (2- (N-phenylmethoxycarbonyl) aminoethyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (cycloheptyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (2- (5-chloro- 2- (thiophen-3-yl) phenylmethyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (pentyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5-hexyl-7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (2- (3-bromophenyl) ethyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5 - ((2-bromophenyl) methyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5-cyclopropyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5-cyclohexyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5 - ((2-bromo-5-chlorophenyl) methyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5-methyl-7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (2,3-methylenedioxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

IX

4-amino-5- (3-fluoro-5-trifluoromethylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (2-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dimethyl-phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3,4-dichlorophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (4-fluoro-3-trifluoromethyl-phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromo-5-methoxyphenyl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromo-5-methoxyphenyl) -7- (4-pyrrolidinylphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromo-5-methoxyphenyl) -7- (4-piperidinylphenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromo-5-methoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-methylthiophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromo-5-methoxyphenyl) -7- (thiophen-2-yl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (2,3-dimethoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-methylsulfonylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-acetylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-formylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4- (methoxyacetyl) amino-5- (3-bromophenyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-Trifluoroacetylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine;

4-pentanoylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-benzoylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4- ( _N -BOC-glycyl) amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine,

4- (YV-phthalimidylglycyl) amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4- (ethoxycarbonyl) -amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4- (ethylaminocarbonyl) amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-Allylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine; 4- (2- (N, N-dimethylamino) ethylamino) -5- (4-bromophenyl) -7- (4-dimethylaminophenyl) pyrido [2,3]

d] pyrimidine;

4- (4- (N, N-dimethylamino) butylamino) -5- (3-bromophenyl) -7- (4dimetylaininofenyl) -pyrido [2,3-d] pyrimidine;

4- (N-allyl-N-formylamino) -5- (4-dimethylaminophenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine;

4-diacetylamino-5- (p-dimethylaminophenyl) -7- (4-bromophenyl) pyrido [2,3-pyrimidine,

4-amino-5- (3-bromophenyl) -7- (5-amino-2-pyridinyl) -pyrido [2 ₁ 3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (5-dimethylamino-2-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (5-dimethylamino-2-pyrazinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (2-oxobenzoxazolin-6-yl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (l-methyl-2-oxobenzoxazolin-6-yl) -pyrido [2,3-d] pyrimidine;

4-amino-5 - ((5-chloro-2- (3-methoxyphenyl) phenyl) methyl) -7- (4-dimethylaminophenyl) -pyrido [2,3djpyrimidín,

4-amino-5 - ((thiophen-2-yl) methyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5 - ((thiophen-3-yl) methyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5 - ((2-bromophenyl) methyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (N-formyl-N- (2-methoxyethyl) amino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (N- (2-methoxyethyl) amino) phenyl) pyrido [2,3-pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N - ((2-dimethylamino) ethyl) amino) phenyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (4- (2-methoxy) acetylamino) ethyl) amino) phenyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7 - ((4-formylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (2- (dimethylamino) acetylamino) phenyl) pyrido [2,3djpyrimidín,

4-amino-5- (3-bromophenyl) -7- (4- (2-oxo-3-oxazolidinyl) phenyl) pyrido [2,3-pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6- (2-propyl) -3-pyridinyl) pyrido [2,3-pyrimidine;

4-amino-5- (3-bromophenyl) -7- (3-methyl-4pyrrolidinylphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6-imidazolyl-3-pyridinyl) pyrido [2,3-d] pyrimidine,

4-amino-5-phenylmethyl-7- (4-diethylamino-phenyl) -pyrido [2,3-pyrimidine;

4-amino-5- (2- (3aminopropynyl) phenylmethyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-pyrimidine

4-amino-5- (l- (3-bromophenyl) ethyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-pyrimidine,

4-amino-5- (4-dimethylaminophenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (2-furanyl) -7- (4- (N-morpholinyl) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (2-dimethylamino-5-pyrimidinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (ureido) phenyl) pyrido [2,3-pyrimidine;

4-amino-5- (l-phenylmethyl-3-piperidinyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6- (3-methyl-5-isoxazolyl)) - 3-pyridinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6-chloro-3-pyridinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6-methoxy-3-pyridinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6- (l, 2,4-triazol-4-yl) -3-pyridinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (2-rnorfolinyl-5-pyrimidinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (2-thiazolyl) -7- (4-pyrrolidinylphenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6-pyrazolyl-3-pyridinyl)) - pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (l-methyl-ureido) phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (2-pyrimidinyl) amino) phenyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (3-fluoro-4- (N-formyl-N-methylamino) phenyl) -pyrido [2,3-d] pyrimidine;

4-formylamino-5- (3-bromophenyl) -7- (3-fluoro-4- (N-formyl-N-methylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N-methylsulfonylamino) phenyl) -pyrido [2,3djpyrimidin;

4-amino-5- (3-bromophenyl) -7- (6- (N-methyl-N-methylsulfonylamino) -3- pyridinyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (l-methyl-5-indolinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (l-methyl-5-benzimidazolyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6-dimethylamino-3-pyridazinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6-morpholinyl-3-pyridazinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6-pyrrolidinyl-3-pyridazinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (5-morpholinyl-2-pyrazinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (5- (N- (2-methoxyethyl) -N-methylamino) -2- pyrazinyl) pyrido [2,3djpyrimidin,

4-amino-5- (3-bromophenyl) -7- (4- (morpholinylmethyl) -phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (5- (N, N-bis (2-methoxyethyl) amino) -2-pyridinyl) pyrido [2,3djpyrimidin;

4-amino-5- (3-bromophenyl) -7- (4- (imidazolylmethyl) -phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (5- (l-morpholinyl) -2-pyridinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4 - ((dimethylamino) methyl) phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (5- (4-hydroxy-l-piperidinyl) -2-pyridinyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (5- (N-formyl-N-methylamino) -2-pyridinyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (5- (2-propenyl) -2-pyridinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (3- (2-methoxy-ethyl) -2-oxo-6-benzoxazolyl) pyrido [2,3djpyrimidín,

4-amino-5- (3-bromophenyl) -7- (4- (l- (N-formylamino) ethyl) phenyl) pyrido [2,3-d] pyrimidine,

4- (methylamino) -5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3djpyrimidínhydrochlorid;

4- (2-methoxy-ethylamino) -5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine hydrochloride;

4-amino-5- (3-bromophenyl) -7- (4- (l-methyl-2-imidazolyl) phenyl) pyrido [2,3-d] pyrimidíntrihydrochlorid;

4-amino-5- (3-bromophenyl) -7- (4- (aminomethyl) phenyl) pyrido [2,3-pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (2-bromo-4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (dimethylaminoethyl) phenyl) pyrido [2,3-pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (3- (dimethylamino) propynyl) phenyl) pyrido [2,3-pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (3-amino-3-methylbutynyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-dimetylfbsfonátofenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) "7- (4- (3- (metoxypropinyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-carboxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-methyl-3-oxo-2H-4H-pyrido [3,2-b] -l, 4-oxazin-7-yl) pyrido [2,3- d] pyrimidine;

4-Amino-5- (3-bromophenyl) -7- (4- (2- (dimethylamino) ethyl) -3-oxo-2H-4H-pyrido [3,2-b] -1,4-oxazin-7-yl) ) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (2,3-dihydro-3- (dimethylaminoethyl) -2- oxobenzoxazol-6-yl) -pyrido [2,3-pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-methyl-3-oxo-2H-4H-benzo-l, 4-oxazin-7-yl) -pyrido [2,3djpyrimidín.

4-amino-5- (3-bromophenyl) -7- (2,2,4-trimethyl-3-oxo-2H-4H-benzo-l, 4-oxazin-7-yl) -pyrido [2,3-d] pyrimidine ;

4-amino-5-cyclohexyl-7- (4- (2-dimethylamino) ethyl) -2-4 H -benzo-3-oxo-4-oxazin-7-yl) -pyrido [2,3-d] pyrimidine;

4-Amino-5- (3-bromophenyl) -7- (5- (1-methylethyl) -2-pyridyl) pyrido [2,3-d] pyrimidine, 4-amino-5- (3-bromophenyl) -7 - (5-piperidin-l-yl-pyridin-2-yl) -pyrido [2,3-d] pyrimidine; 4-Amino-5- (1- (4-bromophenyl) ethyl) -7- (6-morpholinylpyrid-3-yl) pyrido [2,3-d] pyrimidine, 4-amino-5- (3-bromophenyl) - 7- (4 - ((N-formylamino) methyl) phenyl) pyrido [2,3-d] pyrimidine, 4-amino-5- (3-bromophenyl) -7- (4- (1-methyl-1 - ( N-methylamino) ethyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (l-dimethylamino) -l-methylethyl) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (N-acetyl-5-indolinyl) pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (6-chloro-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (l- (2-bromophenyl) ethyl) -7- (6-diethylamino-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (l- (2-bromophenyl) ethyl) -7- (6-rnorfolinyl-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (l- (2-bromophenyl) ethyl-7- (4- (N-methyl-N-formyl) amino) phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5 - ((2-bromophenyl) methyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (4-tetrahydropyranyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d) pyrimidine,

4-amino-5-cyclohexyl-7- (6-dimethylamino-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (l-ethyl-propyl) -7- (6-dimethylamino-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-Amino-5-cyclopentyl-7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (2-chloro-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dimetyIcyklohexyl) -7- (6-dimethylamino-3-pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5 - ((N- (benzyloxycarbonyl) -4-piperidinyl) methyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (6-bromo-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (3-Cyano-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (l- (2-bromophenyl) ethyl) -7- (6-dimethylamino-3-pyridazinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6-imidazolyl-3-pyridazinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6- (azacycloheptanyl) -3-pyridazinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6-N-methyl-N- (l-methylethyl) amino) -3-pyridazinyl) pyrido [2,3djpyrimidín,

4-Amino-5- (1- (2-bromophenyl) -7- (6-morpholinyl-3-pyridazinyl) pyrido [2,3-d] pyrimidine, 4-amino-5-cyclohexyl-7- (6- (4- acetylpiperazinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6- (4-acetyl-1,4-diazacycloheptanyl) -3-pyridyl) pyrido [2, 3djpyrimidín.

4-amino-5-cyclohexyl-7- (6- (4-methyl-l, 4-diazacycloheptanyl) -3-pyridyl) pyrido [2,3djpyrimidín,

4-amino-5-cyclohexyl-7- (6- (N-methyl-N- (2- (2-pyridyl) ethyl) amino) -3-pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5-cyclohexyl-7- (6-2- (N- (N ', N'-dimetyIaminoetyl) -N-methylamino) -3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (6-azetidinyl-3-pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5-cyclohexyl-7- (6- (3- (N-methylacetamido) pyrrolidinyl) pyridyl) pyrido [2,3djpyrimidín,

4-amino-5-cyclohexyl-7- (6- (3-formamido) pyrrolidinyl) pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (4-oxo-1-phenyl-1,3,8-triazaspiro [4.5] decan-8-yl) pyrido [2,3d] pyrimidine;

4-amino-5-cyclohexyl-7- (6- (2-methoxymethyl) pyrrolidin-l-yl) pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (6- (N-methoxyethyl-N-propylamino) pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5-cyclohexyl-7- (N-methyl-N- (2,2-Dimethoxy-ethyl) amino) -pyrido [2,3-d] pyrimidine,

4-amino-5-cyclohexyl-7- (6- (4-dimethylamino) piperidinyl) pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl, 7- (6- (4-aminocarbonyl) piperidinyl) pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (N-methyl-N- (3- (diethylamino) propyl) aminopyridin-3-yl) -pyrido [2,3djpyrimidín;

4-amino-5-cyclohexyl-7- (6- (N-methyl-N- (4-pyridyl) ethylamino) pyrid-3-yl) -pyrido [2,3djpyrimidín,

4-amino-5-cyclohexyl-7- (6- (N-methyl-N- (3-pyridylmethylamino) pyrid-3-yl) -pyrido [2,3djpyrimidín,

4-amino-5- (l- (2-bromophenyl) ethyl) -7- (l-methyl-5-indolyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (1- (2-bromophenyl) ethyl) -7- (1-methyl-2,3-dioxo-5-indolyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (3-fluoro-4- (l-morpholinyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-hydroxy-3-nitrophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6- (4,4-etyléndioxypiperidinyl-3-pyridyl) pyrido [2,3djpyrimidín,

4-amino-5- (3-bromophenyl) -7- (6- (4-oxopiperidinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6- (4-formylpiperazinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6- (4-methyl piperidinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6-thiomorpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6- (4,4-dioxo-thiomorpholinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (2-bromophenyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromo-4-methoxyphenyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (4-bromophenyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-chlorophenyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (5-chloro-6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6- (N-oxidomorfoIinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6- (N- (2-hydroxyethoxyethyl) amino) -3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6- (N- (2-hydroxyethoxyethyl) -N-formylamino) -3-pyridyl) pyrido [2,3-pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6- (N- (2-hydroxyethoxyethyl) -3-pyridyl N-oxide) -pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (6- (3-hydroxy) morpholinyl) -3-pyridyl) pyrido [2,3-pyrimidine; 1- (5- (4-amino-5- (3-bromophenyl) pyrido [2,3-d] pyrimidin-7-yl) -2-pyridyl) piperidine-4-phosphate disodium salt;

4-amino-5- (3-bromophenyl) -7- (4-methylenylpiperidinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-hydroxy-4- (hydroxymethyl) piperidinyl) -3pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6- (4,4-etyléndioxypiperidinyl) -3-pyridyl) pyrido [2,3djpyrimidín,

4-amino-5-cyclohexyl-7- (6- (4-oxopiperidinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (6- (4-methylenylpiperidinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine;

4-N- (iminomethyl) amino-5-cyclohexyl-7- (6-dimethylamino-3-pyridyl) pyrido [2,3djpyrimidín;

and pharmaceutically acceptable salts and amides thereof. Partially and fully saturated versions of the above compounds are included within the scope of the method of inhibiting adenosine kinase in a patient in need of such treatment. The above compounds can be treated with hydrogen and a catalyst to form a compound of Formula I wherein the right-side double bonds are absent or there is a 5.6 carbon double bond; with carbon 6,7 or carbon 7, nitrogen 8.

Examples of compounds of the invention, again with the further specified R'-RA variables include.

4-amino-5- (4-dimethylaminophenyl) -7- (4-bromophenyl) pyrido [2,3d] pyrimidine;

4-amino-5- (4-dimethylaminophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-methoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-dimethylaminophenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4- (2-propyl) phenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-neopentyIfenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-butyloxyphenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-methoxyphenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (4- (2-propyl) phenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-butoxy-phenyl) -7- (4-N-formylpiperazinylphenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (4-benzyloxyphenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-phenoxyphenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4- (2-propyl) phenyl) -7- (4-diethylmalonylallylphenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (4- (2-propyl) phenyl) -7- (4-t-butylacrylphenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3,4-dimethoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-t-butylacrylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-methoxyphenyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dimethoxyphenyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-diethylmalonylallylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-vinylpyridinylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-trifIuórmetylfenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-carboxamidophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-cyanophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-benzyloxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-methoxyphenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4-butoxy-phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3- (2-pyridyl) phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-methylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-chlorophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-fluorophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-methoxyphenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7-phenyl-pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-ethyl-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-cyanophenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-hydroxyphenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-iodophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-ethoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-trifluórmetyoxyfenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dichlorophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromo-4-fluorophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-hydroxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-piperidinylphenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (imidazol-l-yl) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4-chloro-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-isopropyl-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-trifluoromethyl] phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (3,4,5-trimethoxy-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3- (3-methoxybenzyl) phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-methoxyethyoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3,4-methylenedioxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4-ethoxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- ^(2, thiophene) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4-fluoro-phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-dimethylaminophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5-phenyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3,4,5-trimethoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4-nitrophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4-iodo-phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (3,4-methylenedioxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (thiophen-2-yl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dimethoxyphenyl) -7- (thiophen-2-yl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-carboxamidophenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (2-methoxy) ethoxyphenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dimethoxyphenyl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-trifluoromethylphenyl) -7- (thiophen-2-yl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-amino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromo-4-fluorophenyl) -7- (thiophen-2-yl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromo-4-fluorophenyl) -7- (2-furanyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dimethoxyphenyl) -7- (4-iodophenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dimethoxyphenyl) -7- (4-imidazolylphenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dimethoxyphenyl) -7- (4- (thiophen-2-yl) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3,5 'dimethoxy-phenyl) -7- (4- (3-pyridyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (4-methylpiperidinyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-pyrrolidinylphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-bromothiophene -) - 7- (4dimethylaminophenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (4-bromo-thiophen-2-yl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine;

4-morpholinyl-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (5-bromo-thiophen-2-yl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (4-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (acetylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dimethoxyphenyl) -7- (5-pyrimidinylphenyl) pyrido [2,3-d] pyrimidine;

4- (4-fluorophenyl) amino) -5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-bromo-thiophen-2-yl) -7- (4-pyrrolidinylphenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (4-bromo-thiophen-2-yl) -7- (thiophen-2-yl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (5- (dimethylamino) thiophen-2-yl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromo-5-iodophenyl) -7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3,5-di (trifluoromethyl) phenyl) -7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-di (trifluoromethyl) phenyl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dibromophenyl) -7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3,5-dibromophenyl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-bromo-thiophen-2-yl) -7- (4- (4-methylpiperidinyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dibromophenyl) -7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (3- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-metylsulfonylfenyI) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (3-methoxyphenyl) -pyrido [2,3-d] pyrimidin;

4-amino-5- (3-bromophenyl) -7- (4- (methylthio) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (3,4-dichlorophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N-forinylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromo-4-fluorophenyl) -7- (4-methylsulfonylphenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (3-amino-4-methoxy-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (3-bromo-4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine,

4-amino "5- (3-bromophenyl) -7- (3-methyl-4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N-trifluóracetyIamino) phenyl) pyrido [2,3djpyrimidín,

4-amino-5- (3-bromophenyl) -7- (4- (dimethylamino) -3-fluorophenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (N-ethyl-N-formylamino) phenyl) pyrido [2,3-d] pyrimidine;

4,4-bis (acetylamino) -5- (3-bromophenyl) -7- (4- (N-methyl-N-acetylamino) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (N-acetyl-N-methylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (N-ethylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (2-methoxyethyl) amino) phenyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (4- (N-isopropylamino) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4-N-ethyl-N- (2-methoxyethyl) amino) phenyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (4-N- (3-methoxypropionyl) -N-isopropyl-amino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-N- (2- (dimethylamino) ethyl) -N-formylamino) phenyl) pyrido [2,3-pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (N- (2- (dimethylamino) ethyl) amino) phenyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (2-cyano) ethylamino) phenyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (3-methoxy) propionylamino) phenyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (N-formyl-N-methylamino) phenyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (N-methylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (4-methoxy-2-butyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (2- (N-phthalimidyl) acetyl) amino) phenyl) pyrido [2,3-pyrimidine;

4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (N-methyl-N- (trifluoroacetyl) amino) phenyl) pyrido [2,3-pyrimidine;

4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (N-acetyl-N-methylamino) phenyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (6-dimethylamino-3-pyridinyl) pyrido [2,3-pyrimidine,

4-amino-5- (3-cyanophenyl) -7- (4-methylsulfonylphenyl) pyrido [2,3-d] pyrimidine,

4-Amino-5- (3-cyanophenyl) -7- (4- (N-methyl-N-formylamino) phenyl) pyrido [2,3-d] pyrimidine ₁

4-amino-5- (3-bromophenyl) -7- (6- (N-methyl-N-formylamino) -3-pyridinyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (6-morpholinyl-3-pyridinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6- (N-methyl-N-methoxy-ethylamino) -3-pyridinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6-pyrrolidinyl-3-pyridinyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (2- (dimethylamino) -5-pyrimidinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (2- (N-rnetoxyetyl-N-methylamino) -5-pyrimidinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (2- (N-formyl-N-methylamino) -5-pyrimidinyl) pyrido [2,3djpyrimidín,

4-amino-5- (3-bromophenyl) -7- (2- (N-methylamino) 5-pyrimidinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (2- (l-pyrrolidinyl) -5-pyrimidinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (2- (l-morpholinyl) -5-pyrimidinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6- (2-oxo-3-oxazolidinyl) -3-pyridinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (2-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3- (thiophen-2-yl) phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3- (furan-2-yl) phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3- (3-methoxyphenyl) phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5-phenyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-chlorophenyl) -7- (4- (morpholinyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromo-4-fluorophenyl) -7- (4- (morpholinyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-chlorophenyl) -7- (4-iodo-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-chlorophenyl) -7- (4- (thiophen-2-yl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-chlorophenyl) -7- (4- (5-pyrimidinyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromo-4-fluorophenyl) -7- (4-iodo-phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (4-bromo-thiophen-2-yl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) methyl-7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (2-phenylethyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (2-methylpropyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (butyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (2- (4-bromophenyl) ethyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (butyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (2- (3-cyanophenyl) methyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (2- (N-phenylmethoxycarbonyl) aminoethyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (cycloheptyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (2- (5-chloro-2- (thiophen-3-yl) phenylmethyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (pentyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5-hexyl-7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (2- (3-bromophenyl) ethyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5 - ((2-bromophenyl) methyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5-cyclopropyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5 - ((2-bromo-5-chlorophenyl) methyl) -7- (4diethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5-methyl-7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (2,3-methylenedioxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-fluoro-5-trifluoromethylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (2-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dimethyl-phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3,4-dichlorophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyritnidín;

4-amino-5- (4-fluoro-3-trifluoromethylphenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromo-5-methoxyphenyl) -7- (4-morfblinylfenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromo-5-methoxyphenyl) -7- (4-pyrrolidinylphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromo-5-methoxyphenyl) -7- (4-piperidinyIfenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromo-5-methoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-methylthiophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromo-5-methoxyphenyl) -7- (thiophen-2-yl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (2,3-dimethoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-methylsulfonylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-acetylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-formylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4- (methoxyacetyl) amino-5- (3-bromophenyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-trifluoro-acetylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-pentanoylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4-benzoylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4- (YV-BOC-glycyl) amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4- (N-phthalimidylglycyl) amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3djpyrimidín,

4- (ethoxycarbonyl) amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine,

4- (ethylaminocarbonyl) amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3djpyrimidín;

4-Allylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine; 4- (2- (N, N-dimethylamino) ethylamino) -5- (4-bromophenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine;

4- (4- (N, N-dimethylamino) butylamino) -5- (3-bromophenyl) -7- (4dimetylaminofenyl) -pyrido [2,3-d] pyrimidine;

4- (N-allyl-N-formylamino) -5- (4-dimethylaminophenyl) -7- (4-bromophenyl) pyrido [2,3djpyrimidín;

4-diacetylamino-5- (p-dimethylaminophenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (5-amino-2-pyridyl) pyrido [2,3-pyrimidine;

4-amino-5- (3-bromophenyl) -7- (5-dimethylamino-2-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (5-dimethylamino-2-pyrazinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (2-oxobenzoxazolin-6-yl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (l-methyl-2-oxobenzoxazolin-6-yl) pyrido [2,3-pyrimidine,

4-amino-5 - ((5-chloro-2- (3-methoxyphenyl) phenyl) methyl) -7- (4-dimethylaminophenyl) -pyrido [2,3djpyrimidín,

4-amino-5 - ((thiophen-2-yl) methyl) -7- (4diethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5 - ((thiophen-3-yl) methyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5 - ((2-bromophenyl) methyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (N-formyl-N- (2-methoxyethyl) amino) phenyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (4- (N- (2-methoxyethyl) amino) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N - ((2-dimethylamino) ethyl) amino) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (2-methoxy) acetylamino) ethyl) amino) phenyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7 - ((4-formylamino) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (2- (dimethylamino) acetylamino) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (2-oxo-3-oxazolidinyl) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6- (2-propyl) -3-pyridinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (3-methyl-4pyrrolidinylphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6-imidazolyl-3-pyridinyl) pyrido [2,3-d] pyrimidine,

4-amino-5-phenylmethyl-7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (2- (3-aminopropinyI) phenylmethyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (l- (3-bromophenyl) ethyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (4-dimethylaminophenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (2-furanyl) -7- (4- (N-morpholinyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (2-dimethylamino-5-pyrimidinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (ureido) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (l-phenylmethyl-3-piperidinyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidin;

4-amino-5- (3-bromophenyl) -7- (6- (3-methyl-5-isoxazolyl)) - 3-pyridinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6-chloro-3-pyridinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6-methoxy-3-pyridinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6- (l, 2,4-triazol-4-yl) -3-pyridinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (2-morpholinyl-5-pyrimidinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (2-thiazolyl) -7- (4-pyrrolidinylphenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6-pyrazolyl-3-pyridinyl)) - pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (l-methyl-ureido) phenyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (2-pyrimidinyl) amino) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (3-fluoro-4- (N-formyl-N-methylamino) phenyl) -pyrido [2,3djpyrimidín;

4-formylamino-5- (3-bromophenyl) -7- (3-fluoro-4- (N-formyl-N-methylamino) phenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N-metylsulfbnylamino) phenyl) -pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (6- (N-methyl-N-metylsulfbnylamino) -3-pyridinyl) pyrido [2,3djpyrimidín,

4-amino-5- (3-bromophenyl) -7- (l-methyl-5-indolinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (l-methyl-5-benzimidazolyl) pyrido [2,3-pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6-dimethylamino-3-pyridazinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6-morpholinyl-3-pyridazinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6-pyrrolidinyl-3-pyridazinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (5-morpholinyl-2-pyrazinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (5- (N- (2-methoxyethyl) -N-methylamino) -2-pyrazinyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (morpholinylmethyl) -phenyl) pyrido [2,3-pyrimidine;

4-amino-5- (3-bromophenyl) -7- (5- (N, N-bis (2-methoxyethyl) amino) -2-pyridinyl) pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (4- (imidazolylmethyl) -phenyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5- (l-morpholinyl) -2-pyridinyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4 - ((dimethylamino) methyl) phenyl) -pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5- (4-hydroxy-1-piperidinyl) -2-pyridinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (5- (N-formyl-N-methylamino) -2-pyridinyl) pyrido [2,3djpyrimidín,

4-amino-5- (3-bromophenyl) -7- (5- (2-propenyl) -2-pyridinyl) pyrido [2,3-pyrimidine;

4-amino-5- (3-bromophenyl) -7- (3- (2-methoxy-ethyl) -2-oxo-6-benzoxazolyl) pyrido [2,3djpyrimidín,

4-amino-5- (3-bromophenyl) -7- (4- (l- (N-formylamino) ethyl) phenyl) pyrido [2,3-d] pyrimidine,

4- (methylamino) -5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-dJpyrimidínhydrochlorid;

4- (2-methoxy-ethylamino) -5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-dJpyrimidínhydrochlorid,

4-amino-5- (3-bromophenyl) -7- (4- (l-methyl-2-imidazolyl) phenyl) pyrido [2,3-dJpyrimidintrihydrochlórid;

4-amino-5- (3-bromophenyl) -7- (4- (aminomethyl) phenyl) pyrido [2,3-pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (2-bromo-4- (dimethylamino) phenyl) pyrido [2,3-pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (dimethylaminoethyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (3- (dimethylamino) propynyl) phenyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (4- (3-amino-3-methylbutynyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-dimethylphosphonatophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (3- (metoxypropinyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-carboxyphenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-methyl-3-oxo-2H-4H-pyrido [3,2-b] -l, 4-oxazin-7-yl) -pyrido [2, 3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (2- (dimethylamino) ethyl) -3-oxo-2H-4H-pyrido [3,2-b] -l, 4oxazin-7-yl ) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (2,3-dihydro-3- (dimethylaminoethyl) -2- oxobenzoxazol-6-yl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-methyl-3-oxo-2H-4H-benzo-l, 4-oxazin-7-yl) -pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (2,2,4-trimethyl-3-oxo-2H-4H-benzo-l, 4-oxazin-7-yl) -pyrido [2,3-d] pyrimidine ;

4-amino-5-cyclohexyl-7- (4- (2-dimethylamino) ethyl) -2-4 H -benzo-3-oxo-4-oxazin-7-yl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (5- (l-methylethyl) -2-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5-piperidin-l-yl-pyridin-2-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (l- (4-bromophenyl) ethyl) -7- (6-morfolinylpyrid-3-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4 - ((N-formylamino) methyl) phenyl) -pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (1-methyl-1- (N-methylamino) ethyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4- (1-dimethylamino) -1-methylethyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (N-acetyl-5-indolinyl) pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (6-chloro-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (l- (2-bromophenyl) ethyl) -7- (6-diethylamino-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (l- (2-bromophenyl) ethyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (l- (2-bromophenyl) ethyl-7- (4- (N-methyl-N-formyl) amino) phenyl) pyrido [2,3djpyrimidín,

4-amino-5-cyclohexyl-7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5 - ((2-bromophenyl) methyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (4-tetrahydropyranyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-pyrimidine,

4-amino-5-cyclohexyl-7- (6-dimethylamino-3-pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (l-ethyl-propyl) -7- (6-dimethylamino-3-pyridyl) pyrido [2,3-d] pyrimidine,

4-Amino-5-cyclopentyl-7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (2-chloro-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3,5-dimethylcyclohexyl) -7- (6-dimethylamino-3-pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5 - ((N- (benzyloxycarbonyl) -4-piperidinyl) methyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (6-bromo-3-pyridyl) pyrido [2,3-pyrimidine;

4-amino-5-cyclohexyl-7- (3-cyanophenyl) pyrido [2,3-pyrimidine;

4-amino-5- (l- (2-bromophenyl) ethyl) -7- (6-dimethylamino-3-pyridazinyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6-imidazolyl-3-pyridazinyl) pyrido [2,3-d] pyrimidine;

Of 4-amino-5- (3-bromophenyl) -7- (6- (azacycloheptanyl) -3-pyridazinyl) pyrido [2,3-pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6-N-methyl-N- (l-methylethyl) amino) -3-pyridazinyl) pyrido [2,3djpyrimidín;

4-amino-5- (l- (2-bromophenyl) -7- (6-morpholinyl-3-pyridazinyl) pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (6- (4-acetylpiperazinyl) -3-pyridyl) pyrido _[2} 3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (6- (4-acetyl-l, 4-diazacycloheptanyl) -3-pyridyl) pyrido [2,3djpyrimidín;

4-amino-5-cyclohexyl-7- (6- (4-methyl-l, 4-diazacycloheptanyl) -3-pyridyl) pyrido [2,3djpyrimidín;

4-amino-5-cyclohexyl-7- (6- (N-methyl-N- (2- (2-pyridyl) ethyl) amino) -3-pyridyl) pyrido [2,3djpyrimidín,

4-amino-5-cyclohexyl-7- (6-2- (N- (N ', N'-dimethylaminoethyl) -N-methyl-amino) -3pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5-cyclohexyl-7- (6-azetidinyl-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (6- (3- (N-methylacetamido) pyrrolidinyl) pyridyl) pyrido [2,3djpyrimidín,

4-amino-5-cyclohexyl-7- (6- (3-formamido) pyrrolidinyl) pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (4-oxo-l-phenyl-l, 3,8-triazaspiro [4,5Jdekan-8-yl) -pyrido [2,3djpyrimidín;

4-amino-5-cyclohexyl-7- (6- (2-methoxymethyl) pyrrolidin-l-yl) pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5-cyclohexyl-7- (6- (N-methoxyethyl-N-propylamino) pyridyl) pyrido [2,3djpyrimidín;

4-amino-5-cyclohexyl-7- (N-methyl-N- (2,2-dimethoxyethyl) amino) pyrido [2,3-d] pyrimidine,

4-amino-5-cyclohexyl-7- (6- (4-dimethylamino) piperidinyl) pyridyl) pyrido [2,3-pyrimidine;

4-amino-5-cyclohexyl-7- (6- (4-aminocarbonyl) piperidinyl) pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (N-methyl-N- (3- (diethylamino) propyl) aminopyridin-3-yl) -pyrido [2,3djpyrimidin,

4-amino-5-cyclohexyl-7- (6- (N-methyl-N- (4-pyridyl) ethylamino) pyrid-3-yl) -pyrido [2,3djpyrimidin,

4-amino-5-cyclohexyl-7- (6- (N-methyl-N- (3-pyridylmethylamino) pyrid-3-yl) -pyrido [2,3djpyrimidin;

4-amino-5- (l- (2-bromophenyl) ethyl) -7- (l-methyl-5-indolyl) -pyrido [2,3-pyrimidine;

4-amino-5- (l- (2-bromophenyl) ethyl) -7- (l-methyl-2,3-dioxo-5-indolyl) -pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (3-fluoro-4- (l-morpholinyl) phenyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-hydroxy-3-nitrophenyl) -pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6- (4,4-etyléndioxypiperidinyl-3-pyridyl) pyrido [2,3djpyrimidín,

4-amino-5- (3-bromophenyl) -7- (6- (4-oxopiperidinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6- (4-formyIpiperazinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6- (4 "methyl piperidinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6-thiomorpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6- (4,4-dioxo-thiomorpholinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (2-bromophenyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromo-4-methoxyphenyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (4-bromophenyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-chlorophenyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (5-chloro-6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6- (N-oxidomorfolinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine,

4-amino-5- (3-bromophenyl) -7- (6- (N- (2-hydroxyethoxyethyl) amino) -3-pyridyl) pyrido [2,3djpyrimidin.

4-amino-5- (3-bromophenyl) -7- (6- (N- (2-hydroxyetoxyetyI) -N-formylamino) -3pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6- (N- (2-hydroxyethoxyethyl) -3-pyridyl N-oxide) -pyrido [2,3djpyrimidín;

4-amino-5- (3-bromophenyl) -7- (6- (3-hydroxy) morpholinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine, 1- (5- (4-amino) disodium salt 5- (3-bromophenyl) pyrido [2,3-d] pyrimidin-7-yl) -2-pyridyl) piperidine-4-phosphate;

4-amino-5- (3-bromophenyl) -7- (4-methylenylpiperidinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (4-hydroxy-4- (hydroxymethyl) piperidinyl) -3pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5- (3-bromophenyl) -7- (6- (4,4-etyléndioxypiperidinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (6- (4-oxopiperidinyI) -3-pyridyl) pyrido [2,3-d] pyrimidine;

4-amino-5-cyclohexyl-7- (6- (4-methylenylpiperidinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine;

4-N- (iminomethyl) amino-5-cyclohexyl-7- (6-dimethylamino-3-pyridyl) pyrido [2,3d] pyrimidine;

and pharmaceutically acceptable salts and amides thereof. Also included within the scope of the invention are partially hydrogenated or fully hydrogenated versions of the above compounds wherein the double bonds are 5,6 and / or 7,8 hydrogenated. A preferred substitution scheme on the Rp group when selected from, for example, a substituted aryl group is at least one meta substituent. A preferred substitution scheme at the R ⁴ position when selected from, for example, a substituted heteroaryl group is at least one substituent at the para position. Thus, the invention is directed to compounds of formula I or II with the above variables wherein, when R 1 is selected from the group consisting of substituted aryl or heteroaryl and R ⁴ is selected from the group consisting of substituted aryl or heteroaryl, they are substituents on the group

R @ 4 and the substituents on R @ ⁴ are para. Further, the invention encompasses prodrugs of the aforementioned compounds, which may be effective in themselves or are metabolized or converted to the non-precursor form of the above examples. The invention is not limited to the synthetic versions of the claimed compounds and includes the compounds as such or their precursors or metabolites, regardless of the method for their manufacture or recovery.

The term acyl, as used herein, refers to a group attached by a carbonyl bond, such as lower alkyl-carbonyl or aryl-carbonyl, wherein lower alkyl and aryl are as defined herein. Examples include, for example, acetyl, propionyl, hexanoyl, trifluoroacetyl, benzoyl, 4-methylbenzoyl, methoxyacetyl, pentanoyl, N-Boc-glycylimidazoyl, N-phthalimidylglycyl and the like or the others mentioned herein.

The term aryl or substituted aryl as used herein refers to a carbocyclic aromatic moiety, including, for example, phenyl and 1- or 2-naphthyl, which may be unsubstituted or substituted by independent replacement of one, two or two, respectively. three of its hydrogen atoms with Cl, Br, F, I, cyano, carboxamido, hydroxy, lower alkoxy, lower alkyl, lower alkenyl, lower alkynyl, amino, lower alkylamino, di (lower alkylamino), lower alkyl-N-lower alkoxyamino, trifluoromethyl or methoxymethyl. Further, the term aryl refers to a phenyl group substituted with one ureido, methylsulfonyl, pyrimidinyl, pyridinyl, pyridazinyl, morpholinyl, phenyl-lower alkoxy, phenyl-lower alkenyl or cycloalkyl-lower alkyl group. Examples of aryl residues include, but are not limited to, 3-bromophenyl, 3-chlorophenyl, 4-chlorophenyl, 3-methoxyphenyl, 3- (2-propyl) phenyl, 3,4-dimethoxyphenyl, 3-trifluoromethylphenyl, 3-trifluoro-4-fluorophenyl, 4 - (N-methyl-N-methoxy) ethylaminophenyl, 4-dimethylaminophenyl, 3-fluoro-4-methylphenyl, 4-methylphenyl, 4-cyanophenyl, 4-propylmethyl, 3,5-dichlorophenyl, 3,4-methylenedioxyphenyl, 3-cyanopropylphenyl, 4-ureidophenyl, 3-methylsulfonylphenyl, 3-carboxamidopropylphenyl

The term arylalkyl refers to a lower alkyl radical to which the above aryl group is attached, such as benzyl and phenylethyl

The term aryloxy refers to an aryl moiety that is attached to the molecule by an ether bond (i.e., through an oxygen atom) such as phenoxy, naphthyloxy, 4-chlorophenoxy, 4-methylphenoxy,

3,5-dimethoxyphenoxy, and the like.

The term cycloalkyl refers to a cyclic saturated hydrocarbon radical having 3 to 7 ring atoms. Examples of cycloalkyl are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. Cycloalkyl is also described as C 3 -C 8 cycloalkyl.

The term cycloalkyl-lower alkyl refers to a lower alkyl radical as defined below, substituted with a cycloalkyl group as defined above by replacing one hydrogen atom.

Examples of cycloalkyl-lower alkyl groups include cyclopropylmethyl, cyclobutylethyl, cyclopentylmethyl, cyclohexylmethyl and cycloheptylbutyl, and the like

The term heteroaryl or substituted heteroaryl refers to a monocyclic aromatic radical having 5 to 7 ring atoms, of which one ring atom is nitrogen, oxygen or sulfur, none, one or two ring atoms being other heteroatoms independently selected from the group consisting of S, O and N; and the remaining ring atoms are carbons, the remainder being attached to the rest of the molecule via any ring atom. The heteroaryl group may be unsubstituted or substituted by independent replacement of one, two or three of its hydrogen atoms with Cl, Br, F, I, cyano, carboxamido, hydroxy, lower alkoxy, lower alkyl, lower alkenyl, lower alkynyl, amino, lower alkylamino, di (lower alkylamino), N-lower alkyl-N-lower alkoxyamino, trifluoromethyl or methoxymethyl. Further, the term heteroaryl refers to a heteroaryl group substituted with one ureido, methylsulfonyl, pyrimidinyl, pyridinyl, pyridazinyl, morpholinyl, phenyl-lower alkoxy, phenyl-lower alkenyl or cycloalkyl-lower alkyl group. In addition, the heteroaryl group may be substituted by substituting any of the adjacent hydrogen atoms for grouping the atoms to form a fused benzene ring, for example, benz derivatives such as indole, benzoxazole and the like. Examples of heteroaryls are pyridinyl, pyrazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, thiadiazolyl, oxadiazolyl, furanyl, thiophenyl, 5-methylthiophen-2-yl, 5-nitrothiophen-2-yl, 5-methylthiofuranyl, benzofuranyl , etc. and others described herein.

The term heterocycle refers to a saturated or unsaturated monocyclic radical having 4 to 7 ring atoms, one of which is nitrogen or oxygen; none, one or two ring atoms are other heteroatoms independently selected from the group consisting of S, O and N; and the residue is carbons, the residue being attached to the rest of the molecule through any of the ring atoms and optionally substituted on either the nitrogen or carbon atom with another residue selected from the group consisting of aryl (lower alkyl), alkoxycarbonyl, lower alkyl, halo (lower alkyl), amino (lower alkyl), hydroxy-substituted lower alkyl, hydroxy, lower alkoxy, halogen, amino, lower alkylamino and amino, (lower alkyl) amino or alkanoylamino of 1 to 8 carbon atoms, wherein the amino group may be further substituted with 1 to 8 alkanoyl Examples of heterocycles include pyrrolidine, tetrahydrofuran, dihydropyrole, isoxazolidine, oxazolidine, tetrahydropyridine, piperidine, piperazine, morpholine, thiomorpholine, aziridine and azetidine or others described herein.

The term heterocycle-lower alkyl refers to the below-defined lower alkyl radical substituted with the above-defined heterocyclic group by replacement of one hydrogen atom. Examples of cycloalkyl-lower alkyl groups include pyrrolidinylmethyl, piperidinylethyl and the like

The term lower alkyl, as used herein, refers to straight or branched chain saturated hydrocarbon radicals containing from 1 to 6 carbon atoms inclusive, which may be unsubstituted or substituted independently by substituting one, two or three of its hydrogen atoms with Cl, Br, F, I, cyano, carboxamido, hydroxy, lower alkoxy, amino, lower alkylamino, imino-lower alkylamino, di (lower alkylamino) or N-lower alkylN-lower alkoxyamino. Examples of lower alkyl include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, neopentyl, n-hexyl, hydroxyethyl, methoxymethyl, trifluoromethyl, 3-cyanopropyl, 3-carboxamidopropyl, and the like. In some instances, a C 1 -C 6 alkyl group is mentioned which has a similar meaning to the aforementioned lower alkyl, but more specifically. Similarly, the term C 0 -C 6 alkyl indicates how many carbon atoms may be present in the alkyl chain, including zero. These terms are also indicated in the neighborhood of aryl or heteroaryl or other general groups and represent, respectively. have the same meaning as, for example, arylalkyl or heteroarylalkyl.

The term lower alkenyl as used herein refers to straight or branched chain mono-unsaturated hydrocarbon radicals having 2 to 6 carbon atoms, including, but not limited to, vinyl, propenyl, "-butenyl, z-butenyl," -pentenyl and n-hexenyl. These variables are also referred to, for example, as C2-C6alkenyl.

The term lower alkoxy refers to a lower alkyl moiety that is attached to the molecule by an ether bond (ie, through an oxygen atom) such as methoxy, ethoxy, propoxy, 2-propoxy, 2-methyl-2-propoxy, tert-butoxy, pentyloxy, hexyloxy, their isomeric forms and the like. This term is also described as C 1 -C 6 alkyloxy.

The term lower alkynyl as used herein refers to straight or branched chain single or branched chain hydrocarbon radicals containing from two to six carbon atoms including, but not limited to, ethynyl, propynyl, z-butynyl, zz-pentynyl and n. -hexinyl. This term is also described as C2-C6alkynyl.

The term mammal has its usual meaning and includes human beings as well

In another aspect, the invention includes pharmaceutical compositions comprising a compound of the invention in combination with a pharmaceutically acceptable carrier.

The invention includes one or more of the aforementioned compounds formulated with one or more non-toxic physiologically tolerable or acceptable diluents, carriers, adjuvants or vehicles collectively referred to herein as diluents, for parenteral injection, oral administration in solid or liquid form, for rectal or topical application. As is known in the art, the compound of the invention may exist in various forms including pharmaceutically acceptable salts, amides, and the like.

Preparations can be prepared to deliver the correct amount of the compound or compounds of the invention. The following iv dose infusions are believed to provide optimal therapy: 0.1 to 250 nmol / kg / min, preferably 1 to 50 nmol / kg / min; orally: 0.01 to 250 gmol / kg / day, preferably about 0.1 to 50 µmηοΐ / kg / day; these molar ranges of oral dosage correspond to 0.005 to 125 mg / kg / day, preferably 0.05 to 25 mg / kg / day. For the treatment of acute conditions, the preferred route of administration is intravenous; a preferred method of treating chronic conditions is the oral route using tablets or sustained release formulations.

"Pharmaceutically acceptable amide" refers to pharmaceutically acceptable, non-toxic amides of the compounds of the invention, which include amides formed with suitable organic acids or amino acids, including short peptides of 1 to 6 amino acids linked by amide bonds, which may be branched or linear, wherein amino acids are independently selected from naturally occurring amino acids such as glycine, alanine, leucine, valine, phenylalanine, proline, methionine, tryptophan, asparagine, aspartic acid, glutamic acid, glutamine, serine, threonine, lysine, arginine, tyrosine, histidine, ornithine and the like.

"Pharmaceutically acceptable salts" refers to the pharmaceutically acceptable, non-toxic addition salts of the compounds of the invention with inorganic or organic acids, which are described in more detail below.

The compounds of the invention may be used in the form of pharmaceutically acceptable salts derived from inorganic or organic acids. Such salts include, but are not limited to. acetate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentane propionate, digluconate, dodecylsulfate, ethanesulfonate, flavianate, fumarate, glucoheptonate, glycerophosphate, glycerophosphate, glycerophosphate, glycerophosphate, 2-hydroxyethanesulfonate, lactate, maleate, methanesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, palmoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, tosylate and tosylate, tozylate

The corresponding cationic salts are also readily prepared by conventional methods such as reacting an acid of formula I with an appropriate amount of a base such as an alkali or alkaline earth metal hydroxide, for example sodium, potassium, lithium, calcium or magnesium, or an organic base such as an amine, for example, dibenzylethylenediamine, cyclohexylamine, dicyclohexylamine, triethylamine, piperidine, pyrrolidine, benzylamine and the like, or a quaternary ammonium hydroxide such as tetramethylammonium hydroxide and the like. The basic nitrogen-containing groups may be further quaternized with agents such as lower alkyl halides, for example methyl, ethyl, propyl and butyl chloride, bromide and iodide; dialkyl; long chain halides such as decyl, lauryl, myristyl and stearyl chloride, bromide and iodide; arylalkyl halides such as benzyl and phenethyl bromide and others. Water or oil-soluble or dispersible products are thus obtained

Salts of the invention may be synthesized from compounds of formula I that contain a basic or acidic moiety by conventional methods, for example by reacting the free base or acid with a stoichiometric amount or an excess of the appropriate inorganic acid or base in a suitable solvent or various solvent combinations.

The invention further provides pharmaceutical compositions comprising one or more compounds of Formula I, prepared and formulated in combination with one or more non-toxic pharmaceutically acceptable carrier compositions as described below.

Formulations suitable for parenteral injection may contain pharmaceutically acceptable sterile aqueous or non-aqueous solutions, dispersions, suspensions or emulsions and sterile powders for reconstitution into sterile injectable solutions or dispersions. Examples of suitable aqueous and non-aqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (propylene glycol, polyethylene glycol, glycerol and the like), suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants

These compositions may further comprise adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms can be ensured by various antibacterial and antifungal agents such as parabens, chlorobutanol, phenol, sorbic acid and the like. It may also be desirable to add isotonic agents such as sugars, sodium chloride, and the like. Prolonged absorption of the injectable pharmaceutical form may be brought about by the use of agents delaying absorption, such as aluminum monostearate and gelatin.

If desired, they may be incorporated into slow release or targeted delivery systems such as polymer matrices, liposomes and microspheres for more efficient distribution. They may be sterilized, for example, by filtration through a bacteria-retaining filter or by the addition of sterilizing agents in the form of sterile solid preparations. be dissolved in sterile water or other sterile injection medium immediately prior to use.

Solid dosage forms for oral administration may include capsules, tablets, pills, powders, and granules. In these solid dosage forms, the active compound is admixed with at least one conventional inert excipient (or carrier) such as sodium citrate or calcium phosphate, and (a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol and silicic acid; (b) binders such as carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and acacia; (c) humectants, such as glycerol; (d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain complex silicates, and calcium carbonate; (e) retardants such as paraffin; (f) absorption accelerators such as quaternary ammonium compounds; (g) wetting agents such as cetyl alcohol and glycerol monostearate; (h) adsorbents, such as kaolin and bentonite; and (i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate or mixtures thereof. In the case of capsules, tablets and pills, the dosage forms may further comprise buffering agents

Solid compositions of a similar type may 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 polyethylene glycols and the like.

Solid dosage forms such as tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells, such as enteric coatings and other coatings known in the art. They may contain opacifiers and may also be of a composition such that they release the active compound or compounds delayed in a certain part of the digestive tract. Examples of suitable carrier compositions are polymeric substances and waxes.

The active ingredients may also optionally be in microencapsulated form with one or more of the above-mentioned excipients.

Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs. In addition to the active ingredients, the liquid dosage forms may contain inert diluents commonly used in the art, such as water or other solvents, solubilizers and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol , dimethylformamide, oils, especially cottonseed oil, peanut oil, germ oil, olive oil, castor oil and sesame oil, glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and esters of fatty acids and sorbitan or mixtures thereof and the like.

In addition to these inert diluents, these liquid dosage forms may also contain adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring and perfuming agents.

The suspensions may contain, in addition to the active compounds, suspending agents such as ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, or mixtures thereof and the like.

Formulations for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the compounds of the invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or suppository wax, which are solid at ordinary temperatures but liquid at body temperature and therefore they melt in the rectum or vaginal cavity and release the active ingredient.

Dosage forms for topical or transdermal administration of a compound of the invention further include ointments, pastes, creams, emulsions, gels, powders, solutions, sprays, inhalants or transdermal patches. Transdermal patch delivery is a particularly effective and preferred dosage form of the invention. The active ingredient is admixed under sterile conditions with a pharmaceutically acceptable carrier and appropriate preservative, buffer or propellant as desired. It is known that some formulations may require special handling when preparing formulations for transdermal patches. For example, compounds that are volatile in nature may require mixing with special formulations or special packaging to ensure the correct dosage. Compounds that are very rapidly absorbed through the skin may further require formulation with absorption retardants or barriers. Ophthalmic formulations, eye ointments, powders and solutions are also included within the scope of the invention

The compounds of the invention may also be administered in the form of liposomes. As is known in the art, liposomes are usually derived from phospholipids or other lipid substances. Liposomes are formed by mono- or multilamellar hydrated liquid crystals which are dispersed in an aqueous medium. Any physiologically acceptable and metabolizable lipid capable of forming liposomes can be used. Liposome formulations of the invention may contain, in addition to the compounds of the invention, stabilizers, preservatives, excipients and the like. Preferred lipids are phospholipids and phosphatidylcholines (lecithins), both natural and synthetic. Methods for obtaining lipids are known; see, for example, Proscott, Ed., Methods in Cell Biology. Volume XIV, Academic Press, New York, N.Y., (1976), p 33 elseq.

Synthetic methods

The compounds and methods of the invention are illustrated in the following synthetic schemes which illustrate the methods by which the compounds of the invention may be prepared. The R groups are as defined above unless otherwise stated below.

Scheme 1

Compounds of the invention can be synthesized according to the methods depicted in Schemes 1 and 2. Scheme 1 can be used to prepare 5,7-disubstituted compounds wherein R ⁴ and R ³ are aryl, heteroaryl or heterocyclic groups by modifying the method of Kambe et al., Synthesis, 1980, 366-368. The appropriately substituted acetophenone (1, R ⁴ component) wherein R ⁴ is aryl, heteroaryl or heterocyclic group, the appropriately substituted aldehyde (2, R ³ component), R ³ is aryl, heteroaryl or heterocyclic group, and the malononitrile are heated in an aprotic solvent in the presence of ammonium acetate or other suitable ammonium salt, such as ammonium propionate, ammonium iodide and the like, to give compound (3). The reaction water may be removed using a Dean-Stork apparatus or other suitable means, such as molecular sieves. Suitable aprotic solvents include benzene, toluene, methylene chloride, DMF, THF, dioxane and the like. The reaction may be carried out at about 40 ° C to about 200 ° C, preferably at the reflux temperature of the solvent, for about 1 hour to about 24 hours, preferably about 4 hours to 8 hours. The item (3), after isolation from the reaction mixture is preferably purified by chromatography The reaction may take place such that the aldehyde (2) is contacted with malononitrile and isolating the resulting dicyano ^R3 substituted alkene which is then reacted with the ketone (1) and yields compound (3) upon addition of ammonium and cyclization. This method is not effective for aliphatic aldehydes. However, ketone (1) may include R ⁴ as alkyl groups.

The starting acetophenones (1) can be obtained commercially or readily prepared by Friedel-Crafts acylation of, for example, a suitable aromatic substrate. The corresponding starting aldehydes (2) can also be obtained commercially or are readily prepared, for example, by reduction of esters or acids by treatment with DIBAL or another suitable hydride reducing agent, or by oxidation of alcohols, for example under Swern conditions.

Compound (3) is then treated with excess formamide while heating to reflux. Product formation is monitored by TLC, and when the reaction is complete (after about 1 to about 8 hours), the reaction mixture is cooled to room temperature. The product, 5,7-disubstituted pyrido [2,3-d] pyrimidine (I) is then filtered off and purified by column chromatography. This compound can then be partially or fully reduced by catalytic hydrogenation to a partially or fully saturated version (s) (on the right side of the molecule) of the compounds shown in Scheme 1 or Formula I. The stereoisomers formed during these reduction steps are included within the scope of the invention. The invention also encompasses reductions that result in double bonds between positions 5,6 and 7,8 and a double bond between carbon 6,7. The stereoisomers may be isolated and purified in conventional manner.

According to Scheme 2, compounds of formula (I) are prepared wherein R ** is preferably an aryl, heteroaryl or heterocyclic group and R 6 is lower alkyl, lower alkenyl, lower alkynyl or arylalkyl. R 6 may further be selected from the group consisting of other groups listed for R 6

Compound (4, component R- *) can be obtained commercially or prepared by suitable reactions from the ester or alcohol precursor (5). Compound (5) can be reduced with a suitable reducing agent, such as diisobutylaluminum hydride, or other similar alkyl aluminum hydride, under conditions known in the art. Compound (6) can be oxidized to the aldehyde (4) under Swern oxidation conditions or other reactions known to those skilled in the art. The desired compound (4) is prepared freshly before use in the reactions described below.

Compound (9), component R1) may be prepared by a two-step process from the alphabrom ketone precursor (7). Compound (7) is treated with triphenylphosphine in the presence of a base such as triethylamine to give compound (8). Compound (8) is then treated with an alkali metal base such as NaOH and the like to give compound (9). The procedure normally proceeds with vigorous stirring of a solution of compound (8) in an organic solvent with an aqueous base solution.

Compounds (4) and (9) are combined and the mixture is maintained at ambient temperature until completion of the reaction (TLC monitoring) and the product (10) is purified by chromatography. The mixture of cis and trans isomers is obtained and used in the next step without further separation. Compound (10) is condensed with malononitrile by heating in the presence of ammonium acetate as defined above for Scheme 1 to give compound (11).

Scheme 2 .O

OR ⁶ red.

-► R ³ - R ³ .0 oxide _-CH2 -OH

(Ph) ₃ ⁺ Br '

Compound (11) is then treated with excess formamide with heating to reflux. The formation of the product is monitored by TLC and after completion of the reaction (routinely after about 1 to about 8 hours, the reaction mixture is cooled to room temperature. The product, 5,7-disubstituted pyrido [2,3-d] pyrimidine (I), is then filtered off and Purified by Column Chromatography Alternatively, compound (11) is treated with formamidine acetate heating in ethoxyethanol, then purified by flash chromatography In another alternative, compound (11) and ammonium sulfate are heated at reflux for about 1 to about 8 hours, preferably about The reaction mixture was cooled and added to a mixture of ammonia in ethanol, stirred for about 12-24 hours at 25 ° C, then for 1-4 hours under reflux, then the solvent was removed in vacuo. chloroform / ethyl acetate and the product can be converted to the hydrochloride by suspending in 3M HCl followed by lyophilization

Scheme 3

Scheme 3 illustrates an alternative process for preparing compounds (I) of the invention. Compounds (1) prepared as described above are reacted with dicyanoalkene (12) with heating to reflux in an alcoholic or aprotic solvent to give compound (I) Suitable solvents for the reaction are readily determined by one skilled in the art without undue trial and error and may include, for example, ethanol , propanol, isopropanol, t-butanol, n-butanol, 1,2-dichloroethane, benzene, chloroform, carbon tetrachloride, toluene, dioxane, dimethoxyethane and the like. A preferred solvent is 1,2-dichloroethane. The dicyano compounds (12) can be prepared from the aldehyde precursor (4) by treating malononitrile in 1: 1 H 2 O: EtOH in the presence of a catalytic amount of glycine according to the method described by Bastus (Tetrahedron Leti., 1963: 955). an aprotic solvent (see Broekhuis et al., Recl. J. R. Neth. Chem. Soc. 99: 6-12 (1980); Moison et al., Tetrahedron (1987), 43.537-542).

For the preparation of compounds of formula (I) wherein R ¹ and R ² are both hydrogen atoms, a desired derivative can be prepared from a compound of formula (1) wherein R 1 and R ² are hydrogen atoms When R 1 or R ^{2 is} lower alkyl, this can be accomplished by reacting the free amino group with an appropriate alkylating agent, such as an alkyl halide, alkyl mesylate or alkyl tosylate, in the presence of a base such as triethylamine or potassium carbonate in a suitable solvent such as methylene chloride or THF. When R 1 or R 1 is arylalkyl, this may be accomplished by reacting the free amino group with, for example, an appropriate arylalkyl halide, alkyl mesylate or alkyl tosylate, in the presence of a base such as triethylamine or potassium carbonate in a suitable solvent such as methylene chloride or THF. When R 6 or R 6 is acyl, this may be accomplished by reacting the free amino group with the appropriate acid anhydride, acyl chloride or activated acyl group in the presence of a base such as triethylamine or potassium carbonate in a suitable solvent such as methylene chloride or THF. When R 5 and R 4 together with the nitrogen atom to which they are attached form a 5-7 membered ring, optionally containing an additional oxygen or nitrogen atom, this compound can be prepared by reacting a precursor having a halogen atom at the 4-position of the amino group, a 5-7 membered ring compound optionally containing an additional oxygen or nitrogen atom. Examples of such compounds include, but are not limited to, morpholine, piperidine, pyrrolidine, piperazine, thiomorpholine, and the like. This alternative process can also be used to prepare alkyl-substituted amino compounds, for example by reacting a chlorinated compound with a mono- or disubstituted amine such as diethylamine, allylamine, dibutylamine. This reaction proceeds readily in a solvent such as methylene chloride in the presence of a tertiary amine. The halogen precursor instead of the amino group at the 4-position can be prepared by replacing the formamide with triethyl orthoformate followed by ring chlorination with phosphorus oxychloride or thionyl chloride in the presence of DMF in Scheme 1, where compound (3) is converted to compound (1).

Method for inhibiting kinase

In another aspect, the invention includes a method of inhibiting adenosine kinase. According to this method, the adenosine kinase enzyme is exposed to an effective inhibiting amount of an adenosine kinase inhibiting compound of the invention. Preferred compounds for use in this method are as described above. Methods for determining an effective inhibitory amount are known in the art.

The adenosine kinase to be inhibited can be located in vitro, in situ or in vivo. When placed in vitro, adenosine kinase is contacted with the inhibitory compound, typically by adding the compound to an aqueous solution containing the enzyme, radiolabeled substrate adenosine, magnesium chloride, and ATP. The enzyme may exist in intact cells or even isolated subcellular fractions containing the enzyme. The enzyme is then maintained for a period of time and under suitable physiological conditions in the presence of an inhibitor. Methods for determining the maintenance period are known in the art and depend, inter alia, on enzyme concentration and physiological conditions. Suitable physiological conditions are those necessary to maintain the viability of adenosine kinase and include temperature, acidity, tonicity, and the like. Inhibition of adenosine kinase can be accomplished, for example, by known standard procedures (Yamada, et al., Comp. Biochem. Physiol. 1982, 71B: 367 -372).

When adenosine kinase is placed in situ or in vivo, it is typically administered to a fluid flowing through tissue containing the enzyme. The fluid may be a naturally occurring fluid such as blood or plasma or an artificial fluid such as saline, Ringer's solution and the like. A method of inhibiting adenosine kinase in vivo is particularly useful in mammals such as man. Administration of the inhibitory compound is typically accomplished by parenteral (e.g., intravenous injection or oral) administration of the compound. The amount administered is an effective inhibitory or therapeutic amount.

By "therapeutically effective amount" of a compound of the invention is meant a sufficient amount of the compound to treat adenosine kinase-related disorders or conditions or diseases that ameliorate or modify by local enzyme inhibition that results in an increase in adenosine concentration. It will be understood, however, that the total daily application of the compounds and compositions of the invention must be determined by the attending physician within the scope of sound medical judgment. The particular therapeutically effective dose size for a particular patient depends on various factors, including the conditions to be treated and the severity of the condition, the efficacy of the particular compound employed; the particular preparation used; the patient's age, body weight, health, sex, and diet; the time of administration, the mode of administration and the rate of excretion of the particular compound employed; duration of treatment; drugs used in combination or concurrently with the particular compound used and similar factors known in the medical art and within the skill of the attending physician.

The compounds of the invention inhibit adenosine kinase activity in vitro and in vivo. In vitro adenosine kinase activity can be measured using any of the standard procedures known in the art. For example, cells containing adenosine kinase, such as human neuroblastoma cells IMR-32, can be cultured in the presence or absence of an inhibitor. Inhibition is measured as the ability to inhibit the phosphorylation of endogenous or externally administered ¹⁴ Cadenosine by these cells. Cells may be intact or disrupted. The specificity of the adenosine kinase inhibitory activity is determined by studying the effects of inhibitors on the binding of adenosine A1 and A2a receptors, adenosine deaminase activity, and adenosine transport.

Compounds of the invention are effective in inhibiting adenosine kinase activity in vivo Various animal models are known in the art for studying adenosine kinase activity and the effects of inhibiting this activity. For example, it has been reported that adenosine kinase inhibitors protect rodents (e.g., mice and rats) from seizures induced by subcutaneous administration of pentylenetetrazole (PTZ). Typically, rodents are injected with different doses of a given inhibitor, followed by subcutaneous administration of about 10 to about 500 mg / kg PTZ at different times. Treated animals are then monitored for seizure onset.

The compounds of the invention were tested in vivo in a hot plate analgesia assay in mammals such as mice. For example, the compounds of Examples 6, 79, 104, 130, 133, 134, 137, 205, 246, and 256 in the procedure immediately below were tested 30 min after drug pretreatment (30 mmol / kg ip) for time to tenth jump (in seconds). The higher the number of seconds, the more effective the drug was in masking the pain felt from the plate. Compound 6 reached 152 s versus vehicle alone of 72.8 ± 10.5 s (mean ± standard deviation); compound 79 reached 143 s; compound 104 reached 180 s; Compound 130 reached 158 s; Compound 133 reached 131 s; Compound 134 reached 137 s; Compound 137 reached 159 s; Compound 205 reached 158 s, Compound 246 reached 160 s, and Compound 256 reached 143 s. Thus, this animal model demonstrates that the compounds of the invention effectively relieve pain.

Mouse test with hot plate

Male CF1 mice (Charles River) weighing approximately 25-30 g are pretreated with 10 ml / kg test compound, i.p. or p.o, in groups of 8 animals per dose. At the end of the pre-treatment period, mice were individually housed in an Omnitech Electronics Automated 16 Animal Hot Plate Analgesia Monitor (Columbus, OH, Model AHP16AN), with plastic covers 9.8 x 7.2 x 15.3 cm (L x W x H) for copper plate heated to 55 ° C. Infrared sensors located near each enclosure detect beam crossings that occur when the mouse bounces off the heated surface The time for each jump is automatically recorded and the time for the first and tenth leaps is used for data analysis. are immediately removed from the plate to prevent tissue damage and a maximum value of 180 s is recorded as time to the tenth jump.

Numerous other animal models of adenosine kinase activity have been described [see Davies, et al., Biochem. Pharmacol., 33, 347-355 (1984), Kuil, et al., Eur. J. Pharmacol., 27137-46 (1994); Murray, et al., Drug Development Res., 28: 410-415 (1993)].

The compounds of the invention were also tested in vitro. The results of some representative studies are shown below in Table 1. The following examples all relate to adenosine kinase inhibitors. The data show that the compounds inhibit adenosine kinase and are useful as adenosine kinase inhibitors. The compounds of the invention, including the compounds of formula I and Π with the variables listed herein, are also useful as screening agents or as comparative indicators of adenosine kinase inhibitory activity against unknown inhibitors or potential inhibitors.

Table 1

Inhibition of adenosine kinase by representative compounds of the invention

Example compound no. IC50 (nM) 6 200 15 7 44 50 53 3 56 35 57 1 64 8 79 5 81 3 100 2 104 2 130 1 133 2 137 5 147 150 150 150 170 1 175 300 177 25 201 3 205 3

208 4 246 5 247 3 256 1 270 20 272 > 100 274 2 283 8 288 0.3 290 1 291 0.6 292 10 303 1 304 1 306 0.3 308 2 309 0.1 315 0.3 319 1 327 1 330 5 333 2 336 8 337 4 338 4.5 347 3

Method for the treatment of cerebral ischemia, epilepsy, nociperception (nociception) (pain), conditions including conditions such as septic shock due to infection

In another aspect, the invention includes a method of treating cerebral ischemia, epilepsy, nociperception or nociception, conditions including inflammation such as septic shock due to infection in a human or lower mammal, comprising administering to the mammal a therapeutically effective amount of a compound of formula 1 R8 is as defined herein. Preferred are compounds of formula 11 with the radicals R as defined above. In particular, the invention relates to a method of treating the above disorders comprising administering a compound of formula II wherein R 1 is substituted aryl or heteroaryl, wherein the substituent (preferably halogen) is in the meta position relative to the ring attachment and R ⁴ is substituted heteroaryl or aryl, wherein the substituent is in the para position relative to the ring attachment. Most preferred use is for the treatment of pain

Changes in adenosine kinase activity in cells have been observed in some disorders. In various rat hepatomas, adenosine kinase activity has been found to be reduced relative to normal liver, thus giving a negative correlation with tumor growth rate (Jackson, et al. Br. J. Cancer, 1978, 37; 701-713). Adenosine kinase activity was also reduced in liver regeneration after partial hepatectomy in experimental animals (Jackson, et al. Br. J. Cancer, 1978, 37: 701-713). Reduced erythrocyte adenosine kinase activity has been found in gout patients (Nishizawa, et al., Clin. Chim. Acta 1976, 67: 15-20). Lymphocyte adenosine kinase activity was reduced in AIDS-infected patients infected with human immunodeficiency virus (HIV) compared to normal healthy controls, and decreased in asymptomatic HIV-seropositive and HIV-seronegative high-risk individuals (Renouf et al., 1989, Cbn. 35: 1478-1481). It has been suggested that measuring adenosine kinase activity may be useful in monitoring the clinical progress of HIV infection (Renouf et al., Clin. Chem. 1989, 35: 1478-1481). Septic infection may lead to systemic inflammatory syndrome (SIRS), characterized by an increase in cytokine production, neutrophil accumulation, hemodynamic effects, and tissue damage or death. The ability of an adenosine kinase inhibitor to increase the level of adenosine in tissues has been shown to improve the symptoms of the syndrome due to the known anti-inflammatory effects of adenosine. (Firestein, et al., J. of Immunology, 1994: 5853-5859). It is believed that the ability of adenosine kinase inhibitors to increase adenosine levels will alleviate pain conditions since administration of adenosine or analogues thereof has been shown to lead to antinociception or antinociperception. (Swaynok, et al., Neuroscience, 1989, 32,557,569).

The following examples illustrate preferred embodiments of the invention and do not limit the description or claims in any way.

Example 1

4-amino-5- (p-dimethylaminophenyl) -7- (p-bromophenyl) pyridoí2.3-dlpyrimidín

A sample of 4- (4-bromophenyl) -3-cyano-6- (4- (dimethylamino) phenyl) pyridin-2-amine (1 g) was suspended in formamide (20 mL) and the reaction mixture was heated to reflux. h, the reaction was complete by TLC and cooled to room temperature. The product was allowed to precipitate, then was filtered and washed with water. Additional product was obtained from the filtrate The product was purified by column chromatography eluting with 10% MeOH / CH 2 Cl 2 to give the pure title compound. IR (KBr) 3503, 3398, 1731, 1658, 1510, 1467, 1278 cm ^-1 ; MS m / z 421 (M + H) &lt; ^{+ &gt};.

4- (4-Bromophenyl) -3-cyano-6- (4- (dimethylamino) phenyl) pyridin-2-amine was prepared as follows:

The reagents, ie 4-bromoacetophenone (10 mmol, component R ⁴ ), 4-dimethylaminobenzaldehyde (10 mmol, component R ³ ), malononitrile (10 mmol) and ammonium acetate (1.4 g) were added to 25 mL of benzene. The reaction mixture was heated to reflux in a flask equipped with a DeanStork apparatus. After 3.5 h the mixture was cooled and the solvent removed. The residue was purified by flash chromatography eluting with methylene chloride, optionally adding 5% ethyl acetate to the eluent. MS m / z 394 (M + H) &lt; ^{+ &gt};.

Examples 2 to 156

Following the procedure of Example 1, but substituting R ⁴ and R ^{3 for the} respective components listed in Table 2 below, the compounds of Examples 2 to 156 were prepared.

Table 2

Examples 2 to 156

Pr. no. Title Component R ⁴ (for position 7) Component R ³ (for position 5) Analytical data 2 4-amino-5- (4- dimethylaminophenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine, l- (4- dimethylamino- phenyl) -ethanone 4 dimethylamino- benzaldehyde IR (KBr) 3440, 1615, 1760, 1210 cm -1, MS m / z 385 (M + H) ⁺ . 3 4-amino-5- (4-methoxyphenyl) -7- (4-dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 4-metoxybenz- aldehyde IR (KBr) 3330, 1600, 1640, 1780, 1200 cm -1; MS m / z 372 (M + H) &lt; ^{+ &gt};.

4 4-amino-5- (4- dimethylaminophenyl) -7- (4- methoxyphenyl) -pyrido [2,3- djpynmidín; l- (4- methoxyphenyl) - ethanone 4 dimethylamino- benzaldehyde IR (KBr) 3660, 1600, 1620, 1510, 1360, 1240 cm &^lt; -1 ^&gt;, MS m / z 372 (M + H) &lt; ^{+ &gt;} 5 4-amino-5- (4-isopropylphenyl) - 7- (4-methoxyphenyl) -pyrido [2,3- pyrimidine; l- (4- methoxyphenyl) - ethanone 4-isopropyl- benzaldehyde IR (KBr) 3430, 3360, 1580, 1540 cm ^-1 ; MS m / z 371 (M + H) &lt; + &gt;. 6 4-amino-5- (4-neopentylphenyl) 7- (4-methoxyphenyl) pyrido [2,3-d] pyrimidine; l- (4- methoxyphenyl) - ethanone 4-neopentyl benzaldehyde IR (KBr) 3480, 2960, 1580, 1510, 1240 cm &lt; ^{-1 &gt};; MS m / z 399 (M + H) &lt; ^{+ &gt};. 7 4-amino-5- (4-butoxy-phenyl) -7- (4-methoxyphenyl) -pyrido [2,3- pyrimidine; l- (4- methoxyphenyl) - ethanone 4-butoxybenz- aldehyde IR (KBr) 3480, 1600, 1580, 1510, 1240, 1180 cm ^-1 ; MS m / z 401 (M + H) &lt; ^{+ &gt};. 8 4-amino-5- (4-methoxyphenyl) -7- (4-bromophenyl) pyrido [2,3- pyrimidine; l- (4- bromophenyl) - ethanone 4-metoxybenz- aldehyde IR (KBr) 3660, 1600, 1680, 1520, 1240 cm ^-1 ; MS m / z 407 (M + H) &lt; ^{+ &gt};. 9 4-amino-5- (4-isopropoxyphenyl) -7- (4-methoxyphenyl) pyrido [2,3-d] pyrimidine; l- (4- methoxyphenyl) - ethanone 4-isopropoxy benzaldehyde IR (KBr) 3480, 2940, 1600, 1580, 1504 cm ^-1 ; MS m / z 386 (M + H) &lt; ⁺ &gt; ^. 10 4-amino-5- (4-butoxy-phenyl) -7- (4-N-formylpiperazinylphenyl) - pyrido [2,3-d] pyrimidine; l- (4-N- formylpipera- zinylfenyl) - ethanone 4-butoxy benzaldehyde IR (KBr) 3480, 2940, 1660, 1600, 1580, 1510 cm &^lt; -1 ^&gt;, MS m / z 483 (M + H) &lt; ^{+ &gt;} 11 4-amino-5- (4-benzyloxy-phenyl) - 7- (4-methoxyphenyl) -pyrido [2,3- pyrimidine; l- (4- methoxyphenyl) - ethanone 4-benzyloxy benzaldehyde IR (KBr) 3480, 3040, 1600, 1580, 1560 cm ^-1 ; MS m / z 435 (M + H) &lt; ⁺ &gt; ^. 12 4-Amino-5- (4-phenoxyphenyl) -7- (4-methoxyphenyl) -pyrido [2,3- pyrimidine; l- (4- methoxyphenyl) - ethanone 4-phenoxy benzaldehyde IR (KBr) 3456, 3053, 1580, 1558, 1247 cm ^-1 ; MS m / z 421 (M + H) &lt; ^{+ &gt};.

13 4-amino-5- (4-isopropyl-phenyl) - 7- (4-dietylmalonylalylfe- phenyl) -pyrido [2,3-d] pyrimidine; 1- (4- (3 (diethylmalonyl) allyl) phenyl) ethanone 4-isopropyl- benzaldehyde IR (KBr) 3480, 2980, 1735, 1580, 1555 cm &lt; -1 &gt; MS MS m / z 539 (M + H) &lt; ^{+ &gt;} 14 4-amino-5- (4-isopropyl-phenyl) -7- (4-t-butylacrylphenyl) pyrido [2,3-pyrimidine, l- (4-t- butylakrylfe- phenyl) -ethanone 4-isopropyl- benzaldehyde IR (KBr) 3471, 2957, 1708, 1584, 1556, 1149 cm ^-1 ; MS m / z 467 (M + H) &lt; ⁺ &gt; ^. 15 4-Amino-5- (3-bromophenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3480, 1610, 1580, 1560, 1360, 1200 cm ^-1 ; MS m / z 421 (M + H) &lt; ^{+ &gt};. 16 4-amino-5- (3,4- dimethoxyphenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3,4-dimethoxy- benzaldehyde IR (KBr) 3450, 1610, 1580, 1560, 1510 cm &lt; -1 &gt; MS MS m / z 402 (M + H) &lt; ^{+ &gt};. 17 4-amino-5- (3-t butylacrylphenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine, l- (4- dimethylamino- phenyl) -ethanone 3- (3-Formyl-phenyl) -acrylic acid t-butyl ester IR (KBr) 3480, 3400, 1700, 1610, 1580, 1560 cm ^-1 ; MS m / z 468 (M + H) &lt; ⁺ &gt; ^. 18 4-amino-5- (3-methoxyphenyl-7 (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3-methoxy- benzaldehyde IR (KBr) 3475, 1610, 1580, 1560, 1200 cm -1; MS m / z 372 (M + H) &lt; ⁺ &gt; ^. 19 4-amino-5- (3,5-dimetoxyfenyl7- (4-dimethylaminophenyl) -pyrido [2,3-pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3,5-dimethoxy- benzaldehyde IR (KBr) 3419, 1637, 1600, 1572, 1371, 1202 cm ^-1 ; MS m / z 402 (M + H) &lt; ⁺ &gt; ^. 20 4-amino-5- (3- diethylmalonylallylphenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone [2- (3-Formylphenyl) -vinyl] malonic acid diethyl ester IR (KBr) 3480, 1720, 1610, 1580, 1558, 1524, 1360 cm -1; MS / m / z 540 (M + H) ⁺ .

21 4-amino-5- (3- vinylpyridinylphenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3 vinylpyridinyl- benzaldehyde IR (KBr) 3480, 1610, 1580, 1560, 1513, 1360 cm &^lt; -1 & gt ^; , MS m / z 385 (M + H) &lt; + &gt; 22 4-amino-5- (3-trifluoromethylphenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine, l- (4- dimethylamino- phenyl) -ethanone 3-trifluoromethyl benzaldehyde IR (KBr) 3480, 1610, 1580, 1560, 1360, 1200 cm ^-1 ; MS m / z 410 (M + H) &lt; ⁺ &gt; ^. 23 4-amino-5- (3- carboxamidophenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; 1- (4- dimethylamino- phenyl) -ethanone 3-amido benzaldehyde IR (KBr) 3480, 1610, 1580, 1380, 1200 cm ^-1 ; MS m / z 446 (M + H) &lt; ⁺ &gt; ^. 24 4-amino-5- (3-cyanophenyl) -7- (4-dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3-cyano- benzaldehyde IR (KBr) 3460, 3400, 2210, 1610, 1580, 1554, 1360 cm &lt; -1 &gt; MS / w / z 367 (M + H) &lt; ^{+ &gt};. 25 4-Amino-5- (3-benzyloxyphenyl) - 7- (4-dimethylaminophenyl) - pyrido [2,3-pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3-benzyloxy- benzaldehyde IR (KBr) 3470, 1640, 1580, 1550, 1515, 1357, 1250 cm &lt; ^{-1 &gt};; MS m / z 448 (M + H) &lt; ⁺ &gt; ^. 26 4-amino-5- (3-methoxyphenyl) -7- (4-methoxy-phenyl) -pyrido [2,3- pyrimidine; l- (4- methoxyphenyl) - ethanone 3-methoxy- benzaldehyde IR (KBr) 3470, 1640, 1580, 1550, 1515, 1357, 1250, 1240, 1180 cm &^lt; -1 ^&gt;; MS m / z 359 (M + H) &lt; ^{+ &gt};. 27 4-amino-5- (3-bromophenyl) -7- (4- butoxy-phenyl) -pyrido [2,3- pyrimidine, l- (4- butoxy-phenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3478, 1610, 1580, 1560, 1515, 1355, 1255, 1240, 1180 cm &^lt; -1 & gt ^; , MS m / z 449 (M + H) &lt; + &gt; 28 4-amino-5- (3- (2- pyridyl) phenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine, l- (4- dimethylamino- phenyl) -ethanone 3- (2-pyridyl) - benzaldehyde IR (microscope) 3476, 1609, 1580, 1560, 1358 cm ^-1 ; MS m / z 419 (M + H) &lt; ⁺ &gt; ^.

29 4-amino-5- (3-methylphenyl) -7- (4-dimethylaminophenyl) - pyrido [2,3-d] pyrimidine, l- (4- dimethylamino- -phenyl-ethanone 3-methyl benzaldehyde IR (microscope) 3400, 1640, 1600, 1580, 1540 cm @ -1, MS m / z 356 (M + H) ^{@ +} 30 4-amino-5- (3-chlorophenyl) -7- (4dimetylaminofenyl) -pyrido [2,3-pyrimidine, l- (4- dimethylamino- phenyl) -ethanone 3-chloro- benzaldehyde IR (microscope) 3400, 1600, 1580, 1540 cm ^- 7 MS m / z 376 (M + H) &lt; ^{+ &gt;} 31 4-amino-5- (3-fluorophenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3-fluoro- benzaldehyde IR (microscope) 3480, 1640, 1580, 1560 cm ^-1 ; MS m / z 360 (M + H) &lt; ⁺ &gt; ^. 32 4-amino-5- (3-bromophenyl) -7- (4-methoxyphenyl) pyrido [2,3d] pyrimidine; l- (4- methoxyphenyl) - ethanone 3-bromo- benzaldehyde IR (microscope) 3485, 1607, 1575, 1550, 1515, 1350, 1255, 1240, 1180, 1030 cm ^-1 ; MS m / z 407 (M + H) &lt; ^{+ &gt};. 33 4-amino-5- (3-methoxyphenyl) -7 (4-bromophenyl) pyrido [2,3-d] pyrimidine; l- (4- bromophenyl) - ethanone 3-methoxy- benzaldehyde IR (microscope) 3450, 1640, 1573, 1555, 1496, 1350, 1260 cm ^-1 ; MS m / z 407 (M + H) &lt; ^{+ &gt};. 34 4-amino-5- (3-bromophenyl) -7-phenyl pyrido [2,3-d] pyrimidine; 1-phenyl-ethanone 3-bromo- benzaldehyde IR (KBr) 3480, 1640, 1580, 1560, 1480, 1350, 700 cm @ ^-1 ; MSw / z377 (M + H) ^{@ +} 35 4-amino-5- (3-bromophenyl) -7- (4-ethylphenyl) pyrido [2,3-d] pyrimidine; 1- (4-Ethylphenyl) ethanone 3-bromo- benzaldehyde IR (microscope) 3480, 1645, 1580 (br), 1490, 1380 cm @ -1 ^. 36 4-amino-5- (3-bromophenyl) -7- (4- bromophenyl) pyrido [2,3- pyrimidine; l- (4- bromophenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3480, 1610, 1575, 1540, 1350 cm ^-1 ; MS m / z 455 (M + H) &lt; ^{+ &gt};.

37 4-amino-5- (3-bromophenyl) -7- (4- cyanophenyl) pyrido [2,3- d] pyrimidine; l- (4- cyanophenyl) - ethanone 3-bromo- benzaldehyde IR (microscope) 3480, 2230, 1618, 1580, 1555, 1545, 1350 cm -1; MS m / z 402 (M + H) &lt; ⁺ &gt; ^. 38 4-amino-5- (3-bromophenyl) -7- (4- hydroxy-phenyl) -pyrido [2,3- d] pyrimidine; l- (4- hydroxyphenyl) - ethanone 3-bromo- benzaldehyde IR (microscope) 3481, 3060 (br), 1645, 1580, 1560, 1544, 1360, 1240 1155 cm-1 MS MS m / z 393 (M + H) + 39 4-amino-5- (3-iodophenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3-iodo benzaldehyde IR (microscope) 3500, 3040, 1640, 1600, 1580, 1560 cm -1; MS m / z 468 (M + H) ⁺ 40 4-Amino-5- (3-ethoxyphenyl) -7- (4-dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3-ethoxy benzaldehyde IR (microscope) 3460, 3250, 1640, 1600, 1580, 1560 cm -1; MS m / z 386 (M + H) ⁺ . 41 4-amino-5- (3- trifluórmetyoxyfenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; μ ⁽ 4-dimethylamino-phenyl) -ethanone 3 trifluoromethoxy benzaldehyde IR (microscope) 3480, 1710, 1610, 1580, 1560, 1540 cm -1, MS / w / z 426 (M + H) ⁺ . 42 4-amino-5- (3,5-dichlorophenyl) 7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3,5-dichloro- benzaldehyde IR (microscope) 3500, 3040, 1640, 1600, 1580, 1560 cm -1; MS m / z 411 (M + H) &lt; ⁺ &gt; ^. 43 4-amino-5- (3-bromo-4- fluorophenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine, l- (4- dimethylamino- phenyl) -ethanone 3-bromo-4- fluoro benzaldehyde IR (microscope) 3440, 3015, 1633, 1607, 1583 cm ^-1 ; MS m / z 438 (M + H) &lt; ⁺ &gt; ^. 44 4-amino-5- (3-hydroxyphenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3-hydroxy- benzaldehyde IR (microscope) 3450, 1640, 1610, 1580, 1560 cm ^-1 , MS m / z 358 (M + H) ⁺

45 4-amino-5- (3-bromophenyl) -7- (4- morpholinylphenyl) pyrido [2,3- d] pyrimidine; l- (4-morpholinyl linylfenyl) - ethanone 3-bromo- benzaldehyde IR (microscope) 3483, 1607, 1578, 1561, 1518, 1355, 1228, 1120 cm ^{@ -1} , MS m / z 462 (M + H) ^{@ +} 46 4-amino-5- (3-bromophenyl) -7- (4-piperidinylphenyl) pyrido [2,3d] pyrimidine; 1- (4-piperidino- cyanophenyl) - ethanone 3-bromo- benzaldehyde IR (microscope) 3486, 1606, 1561, 1540, 1519, 1353, 1231, 1199, 1128 cm ^_ l; MS / M / z 460 (M + H) ⁺ 47 4-amino-5- (3-bromophenyl) -7- (4 (imidazol-1-yl) phenyl) pyrido [2,3d] pyrimidine; 1- (4- (imidazol yl) phenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3481, 1580, 1555, 1525, 1482, 1352, 1303, 1053 cm -1; MS m / z 443 (M + H) &lt; ^{+ &gt};. 48 4-amino-5- (3-bromophenyl) -7- (4- chloro-phenyl) -pyrido [2,3- d] pyrimidine; l- (4- chlorophenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3470, 1635, 1580, 1560, 1500, 1350, 1090 cm ^- l; MS m / z 411 (M + H) &lt; ⁺ &gt; ^. 49 4-amino-5- (3-bromophenyl) -7- (4-isopropylphenyl) pyrido [2,3d] pyrimidine; l- (4- isopropylphenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3484, 1610, 1579, 1560, 1550, 1483, 1357 cm &lt; -1 &gt;; MSz / z 419 (M + H) &lt; ^{+ &gt};. 50 4-amino-5- (3-bromophenyl) -7- (4- trifluorophenyl) -pyrido [2,3- d] pyrimidine; l- (4- trifluorophenyl) - ethanone 3-bromo- benzaldehyde IR (microscope) 3481,3289, 1616, 1579, 1547, 1324, 1312,1122, 1070 cm ^-1 ; MS m / z 445 (M + H) &lt; ⁺ &gt; ^. 51 4-amino-5- (3-bromophenyl) -7- (4- diethylaminophenyl) pyrido [2,3- d] pyrimidine; 1- (4-diethyl- minofenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3481, 1607, 1578, 1561, 1533, 1353, 1200, 1155 cm ^- b MS m / z 448 (M + H) ⁺

52 4-amino-5- (3-bromophenyl) -7- (3,4,5 trimethoxyphenyl) pyrido [2,3- pyrimidine; 1- (3,4,5- trimethoxyphenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3485, 1579, 1548, 1507, 1340, 1129 cm &^lt; -1 & gt ^; , MS m / z 467 (M + H) &lt; ^{+ &gt;} 53 4-amino-5- (3- (3- methoxybenzyl) phenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3- (3- benzyl) - benzaldehyde IR (KBr) 3425, 1613, 1580, 1558, 1537 cm &lt; -1 ^& gt ;; MS m / z 478 (M + H) &lt; + &gt;. 54 4-amino-5- (3- methoxyethyoxyphenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3 methoxyethoxy- benzaldehyde IR (KBr) 3469, 1610, 1580, 1560, 1357 cm -1; MS m / z 416 (M + H) &lt; + &gt;. 55 4-amino-5- (3,4-methylenedioxyphenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3,4- methylenedioxy benzaldehyde IR (KBr) 3466, 16245, 1579, 1560 cm ^_1, MS / m / z 386 (M + H) ^+. 56 4-amino-5- (3-bromophenyl) -7- (4-ethoxyphenyl) pyrido [2,3d] pyrimidine; l- (4- ethoxyphenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3480, 1607, 1579, 1560, 1517, 1360, 1238, 1180 cm &lt; ^{-1 &gt};; MS m / z 421 (M + H) &lt; ⁺ &gt; ^. 57 4-amino-5- (3-bromophenyl) -7- (2'-thiophene) pyrido [2,3- pyrimidine; 1-phenyl-ethanone 3-bromo- benzaldehyde IR (KBr) 3470, 1579, 1560, 1547, 1429, 1361 cm &^lt; -1 & gt ^; , MS m / z 383 (M + H) &lt; ^{+ &gt};. 58 4-amino-5- (3-bromophenyl) -7- (4-fluorophenyl) pyrido [2,3-d] pyrimidine; l- (4- fluorophenyl) - ethanone 3-bromo- benzaldehyde IR (microscope) 3476, 1600, 1580, 1555, 1515, 1350, 1230 cm ^-1 ; MS m / z 395 (M + H) &lt; ⁺ &gt; ^. 59 4-amino-5- (3- dimethylaminophenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3 dimethylamino- benzaldehyde IR (KBr) 3436, 1601, 1580, 1563, 1534, 1200 cm ^-1 , MS m / z 385 (M + H) ⁺ .

60 4-amino-5-phenyl-7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone benzaldehyde IR (KBr) 3400, 1600, 1580, 1560, 1530, 1200 cm ^-1 ; MS m / z 342 (M + H) &lt; ⁺ &gt; ^. 61 4-amino-5- (3,4,5- trimethoxyphenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3,4,5 trimethoxy- benzaldehyde IR (KBr) 33460, 1607, 1578, 1127 cm ^-1 , MS m / z 432 (M + H) ⁺ . 62 4-amino-5- (3-bromophenyl) -7- (4- nitrophenyl) pyrido [2,3- pyrimidine; l- (4-nitro- phenyl) -ethanone 3-bromo- benzaldehyde IR (microscope) 3485, 1618, 1580, 1550, 1520, 1340, 860 cm ^{@ -1} , MS m / z 422 (M + H) ^{@ +} 63 4-amino-5- (3-bromophenyl) -7- (4- iodo-phenyl) -pyrido [2,3- pyrimidine; l- (4-iodophenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3480, 1610, 1575, 1570, 1540, 1350, 1000 cm &lt; ^{-1 &gt};; MS / m / z 503 (M + H) &lt; ^{+ &gt};. 64 4-amino-5- (3-bromophenyl) -7- (3,4-methylenedioxyphenyl) -pyrido [2,3-d] pyrimidine; 1- (3,4- methylenedioxy phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3485, 1607, 1575, 1545, 1500, 1440, 1350, 1255, 1038 cm ^-1 ; MS m / z 421 (M + H) &lt; ⁺ &gt; ^. 65 4-amino-5- (thiophen-2-yl) -7- (4-morpholinylphenyl) pyrido [2,3d] pyrimidine; l- (4-morpholinyl linylfenyl) - ethanone thiophene-2- carboxaldehyde IR (KBr) 3480, 1607, 1580, 1560, 1226 cm ^-1 ; MS m / z 390 (M + H) &lt; ⁺ &gt; ^. 66 4-amino-5- (3,5-dimethoxyphenyl) -7- (thiophen-2-yl) pyrido [2,3-d] pyrimidine; 1- (Thiophen-2-yl) ethanone 3,5-dimethoxy- benzaldehyde IR (KBr) 3450, 1640, 1600, 1580, 1560 cm ^-1 ; MS m / z 365 (M + H) &lt; ⁺ &gt; ^. 67 4-amino-5- (3-bromophenyl) -7- (4- carboxamidophenyl) pyrido [2,3- d] pyrimidine; l- (4- carboxamido phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3481, 1674, 1611, 1577, 1558, 1352 cm &^lt; -1 &gt;; MS (m / z) 420 (M + H) ⁺

68 4-amino-5- (3-bromophenyl) -7- (4- (2-methoxy) ethoxy-phenyl) - pyrido [2,3-d] pyrimidine, 1- (4- (2- methoxy) ethoxy phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3478, 1607, 1580, 1560, 1515, 1357, 1260, 1235, 1180, 1113 cm ^-1 ; MS m / z 451 (M + H) &lt; ^{+ &gt};. 69 4-amino-5- (3,5-dimethoxyphenyl) -7- (4-morpholinylphenyl) pyrido [2,3d] pyrimidine; l- (4-morpholinyl linylfenyl) - ethanone 3,5-dimethoxy- benzaldehyde IR (KBr) 3450, 1608, 1580, 1555, 1541, 1230, 1210, 1160 cm &lt; ^{-1 &gt};; MS m / z 444 (M + H) &lt; ⁺ &gt; ^. 70 4-amino-5- (3- trifluoromethylphenyl) -7- (thiophen-2-yl) pyrido [2,3-d] pyrimidine, 1- (Thiophen-2-yl) ethanone 3-trifluoromethyl benzaldehyde IR (KBr) 3486, 1620, 1580, 1560, 1325, 1123 cm -1; MS m / z 373 (M + H) ⁺ 71 4-amino-5- (3-bromophenyl) -7- (4-aminophenyl) pyrido [2,3-d] pyrimidine; l- (4- aminophenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3450, 1632, 1605, 1580, 1365 cm -1; MS m / z 393 (M + H) &lt; ^{+ &gt};. 72 4-amino-5- (3-bromo-4-fluorophenyl) -7- (thiophen-2-yl) pyrido [2,3-d] pyrimidine; l- (thiophen-2-yl) - ethanone 3-bromo-4- fluoro benzaldehyde IR (KBr) 3480, 1640, 1580, 1560, 1500 cm &lt; ^{-1 &gt};; MS m / z 401 (M + H) &lt; ⁺ &gt; ^. 73 4-amino-5- (3-bromo-4-fluorophenyl) -7- (2-furanyl) pyrido [2,3-d] pyrimidine; l- (2-furanyl) - ethanone 3-bromo-4- fluoro benzaldehyde IR (KBr) 3460, 1600, 1580, 1560, 1500 cm ^-1 ; MS m / z 385 (M + H) &lt; ⁺ &gt; ^. 74 4-amino-5- (3,5- dimethoxyphenyl) -7- (4- iodo-phenyl) -pyrido [2,3- d] pyrimidine; l- (4-iodophenyl) - ethanone 3,5-dimethoxy- benzaldehyde IR (KBr) 3460, 1604, 1575, 1556, 1541, 1207, 1160 cm -1; MS m / z 485 (M + H) +. 75 4-amino-5- (3,5-dimethoxyphenyl) -7- (4imidazolylphenyl) pyrido [2,3d] pyrimidine, 1- (4-imidazo- ylphenyl) - ethanone 3,5-dimethoxy- benzaldehyde IR (KBr) 3459, 1604, 1580, 1556, 1524, 1484, 1304, 1159, 1056 cm &lt; -1 ^&gt;, MS m / z 425 (M + H) &lt; ^{+ &gt;}

76 4-amino-5- (3,5- dimethoxyphenyl) -7- (4- (thiophen-2- yl) phenyl) pyrido [2,3- pyrimidine, l- (4- (thiophen-2- yl) phenyl) - ethanone 3,5-dimethoxy- benzaldehyde IR (KBr) 3457, 1602, 1579, 1557, 1207, 1159 cm ^-1 , MS m / z 441 (M + H) ⁺ . 77 4-amino-5- (3,5- dimethoxyphenyl) -7- (4- (3- pyridyl) phenyl) pyrido [2,3- d] pyrimidine; 1- (4- (3- pyridyl) phenyl) - ethanone 3,5-dimethoxy- benzaldehyde IR (KBr) 3452, 1604, 1578, 1558, 1287, 1206, 1159 cm &lt; -1 &gt;; MS / w / z 436 (M + H) &lt; ^{+ &gt};. 78 4-amino-5- (3-bromophenyl) -7- (4- (4-methylpiperidinyl) phenyl) pyrido [2,3-d] pyrimidine; 1- (4- (4- methylpiperidin yl) phenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3475, 1607, 1577, 1558, 1540, 1356, 1232 cm ^_1, MS? M / z 475 (M + H) ^+. 79 4-amino-5- (3-bromophenyl) -7- (4-pyrrolidinylphenyl) pyrido [2,3d] pyrimidine; l- (4- pyrrolidinyl phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3486, 1608, 1577, 1560, 1533, 1353, 1196 cm &lt; -1 &gt;. MS / w / z 446 (M + H) &lt; ^{+ &gt};. 80 4-amino-5- (4-bromothiophen-2-yl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 4-brómtiofen- 2-karbox- aldehyde IR (KBr) 3327, 1604, 1578, 1548, 1521, 1367, 1350, 1202, 820 cm &^lt; -1 ^&gt;; MS m / z 426 (M + H) &lt; ⁺ &gt; ^. 81 4-amino-5- (4-bromo-thiophen-2- yl) -7- (4- morpholinylphenyl) pyrido [2,3d] pyrimidine; 1- (4-morpho- linylfenyl) - ethanone 4-brómtiofén- 2-karbox- aldehyde IR (KBr) 3460, 1606, 1578, 1558, 1541, 1517, 1232, 824 cm &lt; ^{-1 &gt};; MS m / z 468 (M + H) &lt; ^{+ &gt};. 82 4-morpholinyl-5- (3-bromophenyl) - 7- (4-dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3-bromophenyl benzaldehyde IR (microscope) 3340, 1603, 1580, 1540 cm ^-1 ; MS m / z 490 (M + H) &lt; ⁺ &gt; ^. 83 4-amino-5- (5-bromo-thiophen-2- yl) -7- (4- morpholinylphenyl) pyrido [2,3- pyrimidine, 1- (4-morpho- linylfenyl) - ethanone 5-brómtiofen- 2-yl benzaldehyde IR (KBr) 3460, 1606, 1580, 1558, 1541, 1517, 1233 cm &lt; ^{-1 &gt};; MS / w / z 468 (M + H) &lt; ^{+ &gt;}

84 4-amino-5- (4-bromophenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 4-bromo- benzaldehyde IR (microscope) 3480, 3320, 1603, 1580, 1540, 820 cm ^{@ -1} , MS m / z 420 (M + H) @ + 85 4-amino-5- (3-bromophenyl) -7- (4 (acetylamino) phenyl) pyrido [2,3-d] pyrimidine; l- (4- (Acetylamino) - phenyl) -ethanone 3-bromo- benzaldehyde IR (microscope) 3480 1600, 1580, 1520cm *; MS m / z 434 (M + H) &lt; ⁺ &gt; ^. 86 4-amino-5- (3-bromophenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3-bromo- benzaldehyde IR (microscope) 3300, 1606, 1600, 1580, 1560 cm ^-1 ; MS m / z 421 (M + H) &lt; ^{+ &gt};. 87 4-amino-5- (3,5- dimethoxyphenyl) -7- (5- pyrimidinylphenyl) pyrido [2,3- pyrimidine; l- (5- pyrimidinyl phenyl) -ethanone 3,5-dimethoxy- benzaldehyde IR (microscope) 3458, 1602, 1579, 1558, 1460, 1414, 1364, 1196, 1058 cm ^{@ -1} ; MS / m / z 437 (M + H) &lt; ⁺ &gt; ^. 88 4- (4-fluorophenyl) amino) -5- (3- bromophenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-pyrimidine; μ (4- dimethylamino- phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3410, 1605, 1570, 1525, 1503 cm ^-1 ; MS m / z 514 (M + H) &lt; ⁺ &gt; ^. 89 4-amino-5- (4-bromo-thiophen-2- yl) -7- (4- pyrolidinyIfenyl) pyrido [2,3- pyrimidine; l- (4- pyrrolidinyl phenyl) -ethanone 4-brómtiofén- 2-karbox- aldehyde IR (KBr) 3470, 1609, 1577, 1555, 1520, 1409, 1386, 1350, 1196, 821 cm ^-1 ; MS m / z 452 (M + H) &lt; ⁺ &gt; ^. 90 4-amino-5- (4-bromo-thiophen-2- yl) -7- (thiophen-2-yl) pyrido [2,3- pyrimidine; 1- (Thiophen-2-yl) ethanone 4-brómtiofén- 2-karbox- aldehyde IR (KBr) 3308, 1606, 1578, 1543, 1526, 1427, 1359 cm &lt; -1 &gt; m / z 389 (M + H) ⁺ 91 4-amino-5- (3-bromophenyl) -7- (5- (Dimethylamino) thiophen-2- yl) pyrido [2,3-d] pyrimidine, l- (5- (Dimethylamino) thiophen-2-yl) - ethanone 3-bromo- benzaldehyde IR (microscope) 3490, 1581, 1556, 1501, 1481, 1407, 1373, 1072 cm ^-1 ; MS m / z 426 (M + H) &lt; ^{+ &gt};.

92 4-amino-5- (3-bromo-5-iodophenyl) -7- (4 (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; l- (4- (Dimethylamino) phenyl) -ethanone 3-bromo-5-iodo- benzaldehyde IR (KBr) 3493, 1608, 1562, 1533, 1364, 1350, 1200 cm &lt; -1 &gt;, MS m / z 546 (M + H) &lt; ^{+ &gt;} 93 4-amino-5- (3,5- di (trifluoromethyl) phenyl) -7- (4- (Dimethylamino) phenyl) - pyrido [2,3-d] pyrimidine; 1- (4- (Dimethylamino) phenyl) -ethanone 3,5- di (trifluoromethyl benzaldehyde IR (KBr) 3484, 1607, 1580, 1554, 1386, 1280 cm &^lt; -1 & gt ^; , MS m / z 478 (M + H) &lt; ^{+ &gt};. 94 4-amino-5- (3,5di (trifluoromethyl) phenyl) -7- (4-morpholinylphenyl) pyrido [2,3-d] pyrimidine; 1- (4-morpho- linylfenyl) - ethanone 3,5- di (trifluoromethyl benzaldehyde IR (KBr) 3500, 1643, 1602, 1578, 1554, 1280 cm &^lt; -1 ^&gt;; MS m / z 520 (M + H) &lt; + &gt;. 95 4-amino-5- (3,5-dibromophenyl) -7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; l- (4- (Dimethylamino) phenyl) -ethanone 3,5-dibromo- benzaldehyde IR (KBr) 3440, 1608, 1570, 1559, 1536 cm ^-1 ; MS m / z 475 (M + H) &lt; ⁺ &gt; ^. 96 4-Amino-5- (3,5-dibromophenyl) 7- (4- morpholinylphenyl) pyrido [2,3-d] pyrimidine; l- (4-morpholinyl linylfenyl) - ethanone 3,5-dibromo- benzaldehyde IR (KBr) 3480, 1607, 1560, 1540, 1225 cm &lt; ^{-1 &gt};; MS m / z 540 (M + H) &lt; ⁺ &gt; ^. 97 4-amino-5- (4-bromo-thiophen-2- yl) -7- (4- (4- methylpiperidinyl) phenyl) - pyrido [2,3-d] pyrimidine; 1- (4- (4- methylpiperidin yl) phenyl) - ethanone 4-brómtiofén- 2-karbox- aldehyde IR (KBr) 3460, 1608, 1576, 1557, 1540, 1513, 1384, 1353, 1240, 823 cm -1, MS m / z 481 (M + H) ⁺ . 98 4-amino-5- (3,5-dibromophenyl) - 7- (4- (dimethylamino) phenyl) - pyrido [2,3-d] pyrimidine; l- (4- (Dimethylamino) phenyl) -ethanone 3,5-dibromo- benzaldehyde IR (KBr) 3486, 1608, 1570, 1559, 1536, 1360, 1350, 1200, 823 cm ^-1 ; MS m / z 498 (M + H) &lt; ⁺ &gt; ^. 99 4-amino-5- (3-bromophenyl) -7- (3- (Dimethylamino) phenyl) - pyrido [2,3-d] pyrimidine; ? - (4- (Dimethylamino) phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3480, 1601, 1579, 1548, 1483, 1357 cm &^lt; -1 & gt ^; , MS m / z 420 (M + H) &lt; ^{+ &gt;}

100 4-Amino-5- (3-bromophenyl) -7- (4- methylsulfonylphenyl) - pyrido [2,3-d] pyrimidine; l- (4- methylsulfonyl phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3486, 1600, 1580, 1550, 1490 cm -1; MS m / z 455 (M + H) + 101 4-amino-5- (3-bromophenyl) -7- (3-methoxyphenyl) pyrido [2,3-d] pyrimidine. l- (3- methoxyphenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3486, 1605, 1578, 1550, 1492, 1346, 1263 cm -1; MS m / z 407 (M + H) ⁺ . 102 4-amino-5- (3-bromophenyl) -7- (4- (Methylthio) phenyl) pyrido [2,3- pyrimidine; l- (4- (Methylthio) - phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3485, 1607, 1578, 1566, 1538, 1350, 1094, 795 cm ^- *; MS m / z 423 (M + H) &lt; ^{+ &gt};. 103 4-amino-5- (3-bromophenyl) -7 (3,4-dichlorophenyl) pyrido [2,3-d] pyrimidine; 1- (3,4- dichlorophenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3482, 1634, 1576, 1545, 1488, 1342 cm ^-1 ; MS m / z 445 (M + H) &lt; ^{+ &gt};. 104 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- formylamino) phenyl) pyrido [2,3- pyrimidine; L- (4- (N-methyl- N- formylamino) - phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3478, 1672, 1639, 1603, 1579, 1547.841 cm -1 hMS2 / z 434 (M + H) ⁺ . 105 4-amino-5- (3-bromophenyl) -7- (4- methylaminophenyl) pyrido [2,3- pyrimidine; l- (4- methylamino- phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3488, 1637, 1607, 1587, 1360 cm ^- l; MS m / z 480 (M + H) &lt; ⁺ &gt; ^. 106 4-amino-5- (3-bromo-4- fluorophenyl) -7- (4- methylsulfonylphenyl) - pyrido [2,3-d] pyrimidine; l- (4- methylsulfonyl phenyl) -ethanone 3-bromo-4- fluoro benzaldehyde IR (KBr) 3489, 1578, 1560, 1496, 1311, 1151, 775 cm &lt; -1 &gt; MS m / z 473 (M + H) &lt; ^{+ &gt};. 107 4-Amino-5- (3-bromophenyl) -7- (3-amino-4- methoxyphenyl) -pyrido [2,3- pyrimidine. l- (3-amino-4- methoxyphenyl) - ethanone 3-bromo- benzaldehyde IR (microscope) 3431, 1629, 1606, 1583, 1274 cm ^-1 ; MS m / z 422 (M + H) &lt; ^{+ &gt};.

108 4-amino-5- (3-bromophenyl) -7- (3- bromo-4- (dimethylamino) phenyl) - pyrido [2,3-d] pyrimidine; l- (3-bromo-4- (Dimethylamino) phenyl) -ethanone 3-bromo- benzaldehyde IR (microscope) 3470, 1638, 1570, 1560, 1538, 1480, 1345 cm -1; MS m / z 498 (M + H) &lt; ⁺ &gt; ^. 109 4-amino-5- (3-bromophenyl) -7- (3- methyl-4- (dimethylamino) phenyl) - pyrido [2,3-d] pyrimidine; l- (3-bromo-4- (Dimethylamino) phenyl) -ethanone 3-bromo- benzaldehyde IR (microscope) 3438, 1640, 1605, 1580, 1555, 1368 cm @ -1, MS / w / z 434 (M + H) ^{@ +} 110 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- amino) -phenyl) pyrimido [2,3-d] pyrimidine; l- (4- (N-methyl- N- trifluoroacetyl- amino) phenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3443, 1699, 1635, 1606, 1201 cm &lt; -1 &gt;. MS m / z 502 (M + H) &lt; ^{+ &gt};. 111 4-amino-5- (3-bromophenyl) -7- (4- (dimethylamino) -3-fluorophenyl) pyrido [2,3-d] pyrimidine; l- (4- (Dimethylamino) -3-fluorophenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3438, 1638, 1592, 1365 cm-1; MS m / z 438 (M + H) &lt; ⁺ &gt; ^. 112 4-amino-5- (3-bromophenyl) -7- (4 (N-ethyl-N-formylamino) phenyl) pyrido [2,3-d] pyrimidine; l- (4- (N-ethyl- N- formylamino) - phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3477, 1672, 1604, 1580, 1562, 1353 cm &^lt; -1 ^&gt;; MS m / z 448 (M + H) &lt; ⁺ &gt; ^. 113 4,4-bis (acetylamino) -5- (3-bromophenyl) -7- (4- (N-methyl-Nacetylamino) phenyl) pyrido [2,3-d] pyrimidine; 1- (4- (N-methyl-N-) acetylamino) - phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3434, 1667, 1635, 1600, 1200 cm -1; MS m / z 532 (M + H) &lt; ⁺ &gt; ^. 114 4-amino-5- (3-bromophenyl) -7- (4- (N-acetyl-N- amino) phenyl) pyrido [2,3- pyrimidine; l- (4- (N-acetyl- N- methylamino) - phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3443, 1667, 1635, 1600, 1200 cm &lt; -1 &gt;; MS m / z 532 (M + H) &lt; ^{+ &gt};. 115 4-amino-5- (3-bromophenyl) -7- (4- (N-ethylamino) phenyl) pyrido [2,3-d] pyrimidine, l- (4- (N- ethylamino) - phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3441, 1633, 1603, 1572, 1368 cm &lt; -1 &gt; MS m / z 420 (M + H) &lt; ^{+ &gt;} 116 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (2- methoxyethyl) amino) - phenyl) pyrido [2,3-d] pyrimidine; l - (- (N-methyl- N- (2- methoxyethyl) - amino) phenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3439, 1636, 1601, 1529, 1361 cm -1, MS m / z 464 (M + H) ⁺ .

117 4-Amino-5- (3-bromophenyl) -7- (4- (N-isopropylamino) phenyl) - pyrido [2,3-d] pyrimidine, l - (- (N- isopropylamino amino) phenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3430, 1632, 1600, 1578, 1530, 1357 cm &lt; -1 &gt;; MS m / z 434 (M + H) ⁺ 118 4-amino-5- (3-bromophenyl) -7- (4- N-ethyl-N- (2- methoxyethyl) amino) - phenyl) pyrido [2,3-d] pyrimidine; l- (4-N-ethyl-N- (2- methoxyethyl) - amino) phenyl) - ethanone 3-bromo- benzaldehyde IR (microscope) 3488, 1657, 1604, 1579, 1552, 1118 cm -1; MS m / z 506 (M + H) &lt; + &gt;. 119 4-Amino-5- (3-bromophenyl) -7- (4- N- (3-methoxy-propionyl) -N isopropyl amino) phenyl) pyrido [2,3-d] pyrimidine; l- (4-N- (3- metoxypropio- phenyl) -N- isopropyl amino) phenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3201, 1679, 1617, 1597, 1576, 1539, 1177, 1117 cm &lt; -1 &gt;; MS m / z 521 (M + H) &lt; ^{+ &gt};. 120 4-amino-5- (3-bromophenyl) -7- (4N- (2- (dimethylamino) ethyl) -Nformylamino) phenyl) pyrido [2,3d] pyrimidine; l- (4-N- (2- (Dimethylamino) ethyl) -N- formylamino) - phenyl) -ethanone 3-bromo- benzaldehyde ER (KBr) 3475, 1681, 1579, 1351, cm -1, MSw / z 491 (M + H) ⁺ . 121 4-amino-5- (3-bromophenyl) -7- (4- (N- (2- (dimethylamino) ethyl) amino) phenyl) pyrido [2,3djpyrimidín; l- (4- (N- (2- (Dimethylamino) ethyl) amino) - phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3431, 1634, 1601, 1573, 1359 cm &lt; -1 &gt;, [delta] m / z 463 (M + H) &lt; ^{+ &gt;} 122 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (2- cyano) ethylamino) phenyl) - pyrido [2,3-d] pyrimidine; 1- (4- (N-methyl-N- (2-cyano) ethylamino) phenyl) ethanone 3-bromo- benzaldehyde IR (KBr) 3475, 2220, 1660, 1604, 1580.1560, 1352 cm ^_ l MS / m / z 459 (M + H) ⁺ 123 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (3- methoxy) propionylamino) phenyl) pyrido [2,3-d] pyrimidine; 1- (4- (N-methyl-) N- (3-methoxy) - propionylamino- amino) phenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3475, 1663, 1604, 1578.1559, 1352 1114 cm ^- 1; MS m / z 478 (M + H) &lt; ^{+ &gt};. 124 4-amino-5- (3-bromophenyl) -7- (3- methyl-4- (N-formyl-N- amino) phenyl) pyrido [2,3- d] pyrimidine; l- (3-methyl-4- (N-formyl-N- methylamino) - phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3486, 1677, 1607, 1579, 1549, 1351 cm &lt; -1 &gt;; MS m / z 448 (M + H) &lt; ⁺ &gt; ^.

125 4-amino-5- (3-bromophenyl) -7- (3- methyl-4- (N-methylamino) phenyl) - pyrido [2,3-d] pyrimidine; l- (3-methyl-4- (N methylamino) - phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3433, 1635, 1605, 1585, 1359 cm @ ^-1 , MS m / z 420 (M + H) ⁺ 126 4-amino-5- (3-bromophenyl) -7- (4- (4-methoxy-2- butyl) phenyl) pyrido [2,3- pyrimidine; 1- (4- (4- methoxy-2 butyl) phenyl) - ethanone 3-bromo- benzaldehyde IR (microscope) 3473, 3063, 1710, 1671, 1582, 1564, 1352 cm ^-1 ; MS m / z 593 (M + H) &lt; ⁺ &gt; ^. 127 4-amino-5- (3-bromophenyl) -7- (4 (N-methyl-N- (2- (N-phthalimidyl) acetyl) amino) phenyl) pyrido [2,3-d] pyrimidine; l- (4- (N-methyl- N- (2- (N- phthalimidyl) - acetyl) amino) - phenyl) -ethanone 3-bromo- benzaldehyde IR (microscope) 3443, 1638, 1606, 1582, 1359cm ^-1 ; MS m / z 463 (M + H) &lt; ⁺ &gt; ^. 128 4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (N-methyl-N (trifluoroacetyl) amino) phenyl) pyrido [2,3-d] pyrimidine; l- (3-methyl-4- (N-methyl-N- (Trifluoroacetyl) - amino) phenyl) - ethanone 3-bromo- benzaldehyde IR (microscope) 3484, 1701, 1610, 1579, 1559, 1221, 1205, 1151 cm ^-1 ; MS m / z 516 (M + H) &lt; ⁺ &gt; ^. 129 4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (N-acetyl-N-methylamino) phenyl) pyrido [2,3-d] pyrimidine; l- (3-methyl-4- (N-acetyl-N- methylamino) - phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3484, 1663, 1607, 1574, 1547, 1354 cm ^-1 ; MS m / z 462 (M + H) &lt; ^{+ &gt};. 130 4-amino-5- (3-bromophenyl) -7- (6- dimethylamino-3- pyridinyl) pyrido [2,3- d] pyrimidine; l- (6- dimethylamino- 3-pyridinyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3428, 1652, 1635, 1606, 1585, 1365 cm &^lt; -1 & gt ^; , MS m / z 421 (M + H) &lt; ^{+ &gt};. 131 4-amino-5- (3-cyanophenyl) -7- (4-methylsulfonylphenyl) - pyrido [2,3-d] pyrimidine, l- (4- methylsulfonyl phenyl) -ethanone 3-cyano- benzaldehyde IR (KBr) 3479, 1638, 1576, 1559, 1303, 1147 cm ^-1 , MS m / z 402 (M + H) ⁺ 132 4-amino-5- (3-cyanophenyl) -7- (4- (N-methyl-N-formylamino) - phenyl) pyrido [2,3-d] pyrimidine, L- (4- (N-methyl- N-formyl- amino) phenyl) - ethanone 3-kyánobenz- aldehyde IR (KBr) 3418, 2230, 1688, 1674, 1584, 1554, 1114 cm &lt; ^{-1 &gt};; MS / w / z 381 (M + H) &lt; ^{+ &gt};.

133 4-amino-5- (3-bromophenyl) -7- (6- (N-methyl-N-formylamino) -3 pyridinyl) pyrido [2,3- pyrimidine; l- (6- (N-methyl- N- formylamino) - 3-pyridinyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3474, 1676, 1577, 1561, 1353, 1130 cm ^-1 , MS m / z 435 (M + H) ⁺ . 134 4-amino-5- (3-bromophenyl) -7- (6-morpholinyl-3-pyridinyl) pyrido [2,3-d] pyrimidine; l- (6- morpholinyl-3 pyridinyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3487, 3396, 1601, 1580, 1558, 1234 cm ^_1; MS m / z 463 (M + H) &lt; ⁺ &gt; ^. 135 4-amino-5- (3-bromophenyl) -7- (6- (N-methyl-N-methoxyethylamino) -3 pyridinyl) pyrido [2,3-d] pyrimidine; l- (6- (N-methyl- N-methoxy- ethylamino) -3- pyridinyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3476, 3307, 1702, 1683, 1605, 1560, 1116 cm ^_1; MS m / z 465 (M + H) &lt; ^{+ &gt};. 136 4-amino-5- (3-bromophenyl) -7- (6-pyrrolidinyl-3-pyridinyl) pyrido [2,3-d] pyrimidine; l- (6- pyrrolidinyl-3 pyridinyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3487, 3396, 1601, 1580, 1558, 1234 cm &^lt; -1 ^&gt;; MS m / z 447 (M + H) &lt; ⁺ &gt; ^. 137 4-amino-5- (3-bromophenyl) -7- (2- (Dimethylamino) -5- pyrimidinyl) pyrido [2,3- pyrimidine; 1- (2- (Dimethylamino) -5- pyrimidinyl) - ethanone 3-bromo- benzaldehyde IR (microscope) 3442 1640, 1604, 1577, 1536, 1408, 1367, 1348 cm ^-1 , MS m / z 422 (M + H) ⁺ . 138 4-amino-5- (3-bromophenyl) -7- (2 (N-methoxyethyl-N-methylamino) -5-pyrimidinyl) pyrido [2,3-d] pyrimidine; l- (2- (N- methoxyethyl-N methylamino) -5- pyrimidinyl) - ethanone 3-bromo- benzaldehyde IR (microscope) 3439, 1640, 1606, 1587, 1556, 1537, 1374, 1347 cm ^-1 ; MS m / z 466 (M + H) &lt; ^{+ &gt};. 139 4-amino-5- (3-bromophenyl) -7- (2- (N-formyl-N-methylamino) -5- pyrimidinyl) pyrido [2,3- pyrimidine, l- (2- (N- formyl-N- methylamino) -5- pyrimidinyl) - ethanone 3-bromo- benzaldehyde IR (microscope) 3472, 1687, 1583, 1565, 1459, 1353, 1142, 988 cm ^{@ -1} ; MS m / z 436 (M + H) &lt; + &gt;. 140 4-amino-5- (3-bromophenyl) -7- (2- (N-methylamino) -5- pyrimidinyl) pyrido [2,3- pyrimidine. l- (2- (N- methylamino) -5- pyrimidinyl) - ethanone 3-bromo- benzaldehyde IR (microscope) 3483, 1605, 1550, 1346 cm ^-1 ; MS m / z 408 (M + H) &lt; ⁺ &gt; ^.

141 4-amino-5- (3-bromophenyl) -7- (2 (1-pyrrolidinyl) -5-pyrimidinyl) pyrido [2,3d] pyrimidine, '- (2- pyrrolidinyl-5- pyrimidinyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3468, 1600, 1581, 1552, 1527, 1482, 1330 cm &lt; -1 &gt;; MS m / z 448 (M + H) ⁺ 142 4-amino-5- (3-bromophenyl) -7- (2 (1-morpholinyl) -5-pyrimidinyl) pyrido [2,3d] pyrimidine, l- (2- morpholinyl-5- pyrimidinyl) - ethanone 3-bromo- benzaldehyde IR (microscope) ⁷ cm 1; MS m / z 463 (M + H) &lt; ⁺ &gt; ^. 143 4-amino-5- (3-bromophenyl) -7- (6- (2-oxo-3-oxazolidinyl) -3 pyridinyl) pyrido [2,3-d] pyrimidine; l- (6- (2-oxo-3- oxazolidinyl) - 3-pyridinyl) - ethanone 3-bromo- benzaldehyde IR (microscope) 3473, 1762, 1583, 1571, 1562, 1491, 1477, 1402, 1348, 1217 cm @ -1; MS m / z 463 (M + H) &lt; ⁺ &gt; ^. 144 4-amino-5- (3-bromophenyl) -7- (2-pyridyl) pyrido [2,3-d] pyrimidine; 1- (2-pyridyl) ethanone 3-bromo- benzaldehyde IR (microscope) 3427, 3017, 1601, 783 cm -1; MS m / z 351/353 (M + H) &lt; ⁺ &gt; ^. 145 4-amino-5- (3-bromophenyl) -7- (3- pyridyl) pyrido [2,3- d] pyrimidine; l- (3-pyridyl) - ethanone 3-bromo- benzaldehyde IR (microscope) 3434, 3042, 1634, 1372 cm ^-1 ; MS m / z 351/353 (M + H) &lt; + &gt; 146 4-amino-5- (3- (thiophen-2-yl) phenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine; and, (4 dimethylamino- phenyl) -ethanone 3- (thiophen-2-yl) - benzaldehyde IR (microscope) 3482, 2922, 1578, 1356 cm -1; MS m / z 420/422 (M + H) &lt; ⁺ &gt; ^. 147 4-amino-5- (3- (furan-2-yl) phenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3- (furan-2-yl) - benzaldehyde IR (microscope) 3479, 3104, 1559, 1356 cm -1; MS m / z 420/422 (M + H) &lt; ⁺ &gt; ^. 148 4-amino-5- (3- (3- methoxyphenyl) phenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone 3- (3- methoxyphenyl) - benzaldehyde IR (microscope) 3477, 2924, 1579, 1356 cm -1; MS m / z 420/422 (M + H) &lt; ^{+ &gt};. 149 4-amino-5-phenyl-7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine; l- (4- dimethylamino- phenyl) -ethanone benzaldehyde IR (microscope) 3477, 3298, 1580, 1355 cm -1; MS m / z 315 (M + H) &lt; ⁺ &gt; ^.

150 4-amino-5- (3-chlorophenyl) -7- (4- (Morpholinyl) phenyl) pyrido [2,3- d] pyrimidine; l- (4- (Morpholinyl) - phenyl) -ethanone 3-chloro- benzaldehyde IR (microscope) 3480, 3056, 1579, 1356 cm -1; MS m / z 391 (M + H) &lt; ⁺ &gt; ^. 151 4-amino-5- (3-bromo-4- fluorophenyl) -7- (4- (Morpholinyl) phenyl) pyrido [2,3- d] pyrimidine; l- (4- (Morpholinyl) - phenyl) -ethanone 3-bromo-4- fluoro benzaldehyde IR (microscope) 3491.3044, 1560, 1230 cm ^- l; MS m / z 453 (M + H) &lt; ⁺ &gt; ^. 152 4-amino-5- (3-chlorophenyl) -7- (4- iodo-phenyl) -pyrido [2,3- pyrimidine; l- (4-iodophenyl) - ethanone 3-chloro- benzaldehyde IR (microscope) 3478, 3280, 1539, 1350 cm ^_ l; MS m / z 432 (M + H) &lt; ^{+ &gt};. 153 4-amino-5- (3-chlorophenyl) -7- (4- (Thiophen-2-yl) phenyl) pyrido [2,3- d] pyrimidine; l- (4- (thiophen-2- yl) phenyl) - ethanone 3-chloro- benzaldehyde IR (microscope) 3484, 3055, 1560, 1354 cm -1; MS m / z 459 (M + H) &lt; ^{+ &gt};. 154 4-amino-5- (3-chlorophenyl) -7- (4- (5-pyrimidinyl) phenyl) pyrido [2,3-d] pyrimidine; 1- (4- (5- pyrimidinyl) - phenyl) -ethanone 3-chloro- benzaldehyde IR (microscope) 3477, 3040, 1578, 1351 cm -1; MS m / z 459 (M + H) &lt; ^{+ &gt};. 155 4-amino-5- (3-bromo-4-fluorophenyl) -7- (4-iodophenyl) pyrido [2,3d] pyrimidine, l- (4-iodophenyl) - ethanone 3-bromo-4- fluoro benzaldehyde IR (microscope) 3444, 3048, 1607, 1356 cm ^- h MS m / z 494/496 (M + H) ^+. 156 4-amino-5- (4-bromo-thiophen-2- yl) -7- (4- methoxyphenyl) pyrido [2,3-d] pyrimidine; l- (4- methoxyphenyl) - ethanone 4-brómtiofen- 2 carboxaldehyde IR (microscope) 3460, 3300, 29003100, 1700, 1580, 1510 cm -1; MS m / z 413 (M + H) &lt; ^{+ &gt};.

Example 157

4-Amino-5- (3-bromophenyl) methyl-7- (4- (dimethylamino) phenylpyrido [2,3-d] pyrimidine hydrochloride

A mixture of 3-cyano-4- (3-bromophenyl) methyl-6- (4- (dimethyl) aminophenyl) pyridin-2-amine (1.58 g) and ammonium sulfate (40 mg) in triethyl orthoformate was heated at reflux for 2 h. The reaction mixture was cooled and added to a mixture of 8 g of ammonia in 150 ml of ethanol. After 16 h at 25 ° C, the reaction mixture was heated at reflux for 2 h and the solvent was evaporated in vacuo. The residue was purified by chromatography, then converted to the hydrochloride with ether / HCl and dried to give the title compound.

3-Cyano-4- (3-bromophenyl) methyl-6- (4- (dimethyl) aminophenyl) pyridin-2-amine was prepared by the following four step procedure:

step 157a: preparation of 3-bromophenylacetaldehyde (component R ³ )

To a solution of ethyl 3-bromophenylacetate (10.2 g, US Patent 2,624,731 (1950)) in 230 mL dichloromethane at -78 ° C was added with stirring 42 mL IM Dibal-H in toluene After 40 min at -78 ° C was added 10 ml of methanol, the reaction mixture was allowed to warm to room temperature and was partitioned between 50 ml of dichloromethane and 1200 ml of saturated aqueous sodium potassium tartrate solution. The organic layer was dried over sodium sulfate and the aldehyde was used immediately in the next step without purification.

step 157b: preparation of α- (triphenylphosphonium) -4- (dimethylamino) phenylethan-1-one chloride

Following the procedure of Fukui et al. {J. Org. Chem. 33: 3594-3507 (1968)), α-bromo (4-dimethylaminophenyl) ethan-1-one (component R ⁴ , CAS # 37904-72-6; Chem. Abst. (1956), 864) was treated with triphenylphosphine in triethylamine and acetonitrile. α-Bromo- (4-dimethylaminophenyl) ethan-1-one was prepared by bromination with bromine in hydrobromic acid as described by Suzuki et al. (J. Pharm. Soc. Japan, (1955), 75:54) Removal of the solvent and recrystallization from methanol / ethyl acetate / toluene gave the title product as a white powder.

step 157c: preparation of 1- (4- (dimethylamino) phenyl) -4- (3-bromophenyl) -but-2-en-1-one g of α- (triphenylphosphonium) -4- (dimethylamino) phenylethan-1-one chloride ( from step b) was partitioned between dichloromethane and 50 mL 2N NaOH. The organic phase was dried over sodium sulfate and concentrated in vacuo. The residue was stirred with 3-bromophenylacetaldehyde (from step a) at 25 ° C for 24 h. The mixture was purified by chromatography to give 8.35

7Κg (61%) of the cis / trans mixture of the title compound The cis / trans mixture was used in the next step without separation of the isomers.

step 157d: preparation of 3-cyano-4- (3-bromophenyl) methyl-6- (4- (dimethyl) aminophenyl) pyridin-2-amine

A mixture of 1- (4- (dimethylamino) phenyl) -4- (3-bromophenyl) -but-2-en-1-one chloride (3.85 g, from step c), ammonium acetate (2.6 g) and malononitrile (739 mg) in 3 mL of dimethoxyethane and 22 mL of ethanol was heated at 115 ° C for 5 h, then cooled and worked up by partitioning between dichloromethane and water. The residue obtained by concentration of the organic phase was purified by flash chromatography to give the title compound.

Examples 158-174

Following the procedure of Example 157 but substituting the components of R and R · ¹ of Example 157 the corresponding components indicated in Table 3, were prepared compounds of Examples 158-174. Treatment with HCl was omitted and free bases were obtained unless otherwise noted.

In Examples 167-174, the action of formamide or formamidine acetate (periodically added to complete the reaction) was replaced by treatment with triethyl orthoformate under reflux in the presence of a catalytic amount of ammonium sulfate followed by cooling to 25 ° C and addition of excess ammonia in ethanol. After 24 h, the precipitated amidine compound was filtered off and washed with hexanes and then dried in vacuo. The amidine compound was then heated for 1 to 8 hours at 120 to 180 ° C in 1,2-dichlorobenzene. The reaction mixture was cooled to room temperature, purified by chromatography and the product recrystallized as necessary (chloroform in methanol).

Table 3

Examples 158-187

Pr. w c. Title Component R ⁴ (for position 7) Component R ³ (for position 5) Analytical data 158 4-amino-5- (2-phenylethyl) - 7- (4-diethylamino) - pyrido [2,3-d] pyrimidine l- (4- diethylamino phenyl) -ethanone 3-phenyl propionaldehyde IR (KBr) 3340, 32402800, 1600, 1580, 1540, H. Res. MS m / z 398.2343 (M + H) &lt; ⁺ &gt; ^. 159 4-amino-5- (2- methylpropyl) -7- (4- diethylamino) - pyrido [2,3-d] pyrimidine l- (4- diethylamino phenyl) -ethanone 3-methyl -butanoaldehyde IR (KBr) 3550, 3410, 3320, 32402800, 1605, 1580, 1560 Res. MS m / z 350.2357 (M + H) &lt; ^{+ &gt};. 160 4-amino-5- (butyl) -7- (4- diethylamino) - pyrido [2,3-d] pyrimidine l- (4- diethylamino phenyl) -ethanone pentánaldehyd IR (KBr) 3450,3300,32002800,1660,1610,1580,15 40 H. Res. MS m / z 350.2354 (M + H) &lt; ^{+ &gt};. 161 4-Amino-5- (2- (4-bromophenyl) ethyl) -7- (4-diethylamino-phenyl) pyrido [2,3-d] pyrimidine l- (4- diethylamino phenyl) -ethanone 4- (4- bromophenyl) - propionaldehyde IR (KBr) 3500, 300, 300, 3000, 3000, 1650, 1615, 1580 H. Res. MS m / z 478.1429 (M + H) &lt; ⁺ &gt; ^. 162 4-Amino-5- (butyl) -7- (4-dimethylaminophenyl) pyrido [2,3d] pyrimidine * IR (KBr) 3400.3350.32002900.1650.1620.1580.15 70 H. Res MS m / z 322.2032 (M + H) +. 163 4-amino-5- (2- (3- cyanophenyl) methyl) -7- (4- dimethylaminophenyl) pyridylmethyl [2,3-d] pyrimidine l- (4- dimethylamino- phenyl) -ethanone 3-Cyanophenyl acetaldehyde IR (KBr) 28503550, 2220, 1610, 1580, 15, 60.1540 MS / w / z 381 (M + H) ⁺ . 164 4-amino-5- (2- (N- carbobenzyloxy) - aminoethyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine H4 dimethylamino- phenyl) -ethanone 3- (N- karbobenzyl- oxy) - aminopropión- aldehyde IR (KBr) 30003500, 1710, 1690, 1650, 1590 H. Res. MS m / z 443.2184 (M + H) &lt; ⁺ &gt; ^.

165 4-amino-5- (Cycloheptyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine l- (4- dimethylamino- phenyl) -ethanone cykloheptän- carboxaldehyde IR (KBr) 3500.3250.3100.2950.28 50.1620.1575 H Res MS m / z 362.2349 (M + H) ⁺ . 166 4-amino-5- (2- (5-chloro- 2- (thiophen-3 yl) phenylmethyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine ** IR (KBr) 3200- 3450, 2950- 3100, 1605, 1580, 1550 H. Res. MS m / z 472.1363 (M + H) &lt; ^{+ &gt};. 167 4-amino-5- (pentyl) -7- (4- diethylamino) - pyrido [2,3-d] pyrimidine l- (4- diethylamino phenyl) -ethanone hexanal IR (KBr) 3430, 3320, 32402800, 1580, 1560, 1540, 1350; mp. 211-214; MS m / z 364 (M + H) ^&lt; ^{+ &gt};; H. Res. MS m / z 364.2506 (M + H) &lt; ^{+ &gt};. 168 4-amino-5-hexyl-7- (4- diethylamino) - pyrido [2,3-d] pyrimidine 1- (4- diethylamino phenyl) -ethanone heptanal IR (KBr) 3440, 3310, 32402800, 1580, 1560, 1540, 1350; mp. 215-217; MS m / z 378 (M + H) ^&lt; ^{+ &gt};; H. Res. MS m / z (M + H) &lt; ^{+ &gt};. 169 4-amino-5- (2- (3- bromophenyl) ethyl) -7- (4- diethylamino) - pyrido [2,3-d] pyrimidine l- (4- diethylamino phenyl) -ethanone 3- (3- bromophenyl) - propionaldehyde IR (KBr) 36403240,3200- 2800,1580,1555,1535,13 45; mp. 201-202; MS m / z 476/478 (M + H) ^&lt; ^{+ &gt};; H. Res. MS m / z 476-1448 (M + H) &lt; ^{+ &gt};. 170 4-amino-5 - ((2- bromophenyl) methyl) -7- (4- diethylamino) - pyrido [2,3-d] pyrimidine l- (4- diethylamino phenyl) -ethanone 2- (2- bromophenyl) - acetaldehyde IR (KBr) 36403240,3240- 2800,1580,1555,1540,13 50; mp. 130-133; MS m / z 462/464 (M + H) ^&lt; ^{+ &gt};; H Res. MS m / z 462.1297 (M + H) &lt; + &gt;. 171 4-amino-5-cyclopropyl- 7- (4-dimethylaminophenyl) - pyrido [2,3-d] pyrimidine l- (4- dimethylamino- phenyl) -ethanone cyclopropane carboxaldehyde IR (KBr) 3490,3290,32402760,1610,1580,1540,13 75; mp. 235-237; MS m / z 462/464 (M + H) &lt; ^{+ &gt};,

172 4-amino-5-cyclohexyl-7- (4-dimethylaminophenyl) - pyrido [2,3-d] pyrimidine l- (4- dimethylamino- phenyl) -ethanone cyclohexane carboxaldehyde IR (KBr) 36403000, 2980, 2760, 1610, 1580, 1540, 1345; mp 231-234; MS m / z 462/464 (M + H) ^&lt; ^{+ &gt};; 173 4-amino-5 - ((2-bromo-5- chlorophenyl) methyl) -7- (4- diethylamino) - pyrido [2,3-d] pyrimidine l- (4- dimethylamino- phenyl) -ethanone 2- (2-bromo-5- chlorophenyl) - acetaldehyde IR (KBr) 3460, 32202760, 1610, 1575, 1535.13 65, mp. 185-187, MS m / z 462/464 (M + H) ^&lt; ^{+ &gt};; 174 4-amino-5-methyl-7- (4-Diethylaminophenyl) -pyrido [2,3-pyrimidine l- (4- dimethylamino- phenyl) -ethanone acetaldehyde IR (KBr) 36403250, 3250- 2760, 1610, 1585, 1560, 1350; mp. 238-246; MS m / z 462/464 (M + H) &lt; ^{+ &gt};, * prepared from the compound of Ex Example 157 by reaction with Pd (PPh 3) 4 and zinc cyanide in DMF

under Suzuki reaction conditions.

** prepared from Example 173 by reaction with 2-thiopheneboronic acid, Pd (PPh 3) 4 and aqueous sodium carbonate under Suzuki reaction conditions.

Examples 175-188

As in Example 1, but substituting the components of R ⁴ and Example 1, the respective components listed in Table 4, were prepared compounds of Examples 175-188. Treatment with HCl was omitted and free bases were obtained unless otherwise noted.

Table 4

Examples 175-188

Pr. w c. Title Component R ⁴ (for position 7) Component R ³ (for position S) Analytical data 175 4-amino-5- (2,3- methylenedioxyphenyl) -7- (4-dimethylaminophenyl) - pyrido [2,3-d] pyrimidine l- (4- dimethylamino- phenyl) -ethanone 2,3 methylenedioxy benzaldehyde IR (KBr) 35002500, 1595, 1580, 1375, mp. 290-305;

176 4-amino-5- (3-fluoro-5- phenyl) -7- (4-dimethylaminophenyl) - pyrido [2,3-d] pyrimidine l- (4- dimethylamino- phenyl) -ethanone 3-fluoro-5- trifluoromethyl- benzaldehyde IR (KBr) 3500.34403240.3200- 2800.1610.1580.1560.154 0.1370; mp 293-296, MS m / z 428 (M + H) &lt; ^{+ &gt};, H Res. MS m / z 428, 1509 (M + H) &lt; ^{+ &gt};. 177 4-Amino-5- (2-bromophenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine l- (4- dimethylamino- phenyl) -ethanone 2-bromo- benzaldehyde IR (KBr) 3480,34403240,3200- 2800,1610,1575,1555,153 5,1355; mp. 261-263; MS m / z 420/422 (M + H) &lt; ^{+ &gt};, H. Res. MS m / z 420.0823 (M + H) + 178 4-amino-5- (3,5-dimethylphenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine l- (4- dimethylamino- phenyl) -ethanone 3,5-dimethyl- benzaldehyde IR (KBr) 3480,34403240,3200- 2800,1610,1575,1555,153 5,1360; mp. 284-286; MS m / z 370 (M + H) ^&lt; ^{+ &gt};; H. Res. MS m / z 370.2036 (M + H) &lt; ^{+ &gt};. 179 4-amino-5- (3,4- dichlorophenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine l- (4- dimethylamino- phenyl) -ethanone 3,4-dichloro- benzaldehyde IR (KBr) 3490,34403240,3200- 2800,1610,1575,1560,153 5,1355; mp. 288-291; MS m / z 410/412 (M + H) ⁺ ; H. Res. MS m / z 410.0948 (M + H) &lt; + &gt;. 180 4-amino-5- (4-fluoro-3- phenyl) -7- (4-dimethylaminophenyl) - pyrido [2,3-d] pyrimidine l- (4- dimethylamino- phenyl) -ethanone 4-fluoro-3- trifluoromethyl- benzaldehyde IR (KBr) 3500.54403240.3200- 2800.1610.1580.1560.154 0.1505.1360, mp 254257; MS m / z 428 (M + H) ^&lt; ^{+ &gt};; H Res MS m / z 428.1487 (M + H) &lt; ⁺ &gt; ^.

181 4-amino-5- (3-bromo-5- methoxyphenyl) -7- (4- morpholinylphenyl) - pyrido [2,3-d] pyrimidine l- (4- morpholinylphenyl) -ethanone 3-bromo-5- methoxy benzaldehyde IR (KBr) 3470.34403240.32002800, 1605.1580.1560, mp 257-260, MS m / z 492/494 (M + H) &lt; ^{+ &gt;} 182 4-Amino-5- (3-bromo-5-methoxyphenyl) -7- (4-pyrrolidinylphenyl) pyrido [2,3-d] pyrimidine l- (4- pyrrolidinylphenyl) -ethanone 3-bromo-5- methoxy benzaldehyde IR (KBr) 3470,34403240,3200- 2800,1610,1580,1560,154 0,1355; mp d 250; MS m / z 476/478 (M + H) &lt; ⁺ &gt; ^. 183 4-amino-5- (3-bromo-5- methoxyphenyl) -7- (4- piperidinylphenyl) - pyrido [2,3-pyrimidine 1, (4- piperidinylphenyl) -ethanone 3-bromo-5- methoxy benzaldehyde IR (KBr) 3470.34403240.3200-2800.1565; mp. 224-244; MS m / z 490/492 (M + H) &lt; ^{+ &gt};, 184 4-amino-5- (3-bromo-5- methoxyphenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-pyrimidine l- (4- dimethylamino- phenyl) -ethanone 3-bromo-5- methoxy benzaldehyde IR (KBr) 3470,34203240,3200- 2800,1610,1575,1555,153 5,1355; mp. 262-266; MS m / z 450/452 (M + H) &lt; ^{+ &gt};, H Res. MS m / z 450.0944 (M + H) &lt; ⁺ &gt; ^. 185 4-amino-5- (3metyltiofenyl) -7- (4dimetylaminofenyl) -pyrido [2,3-pyrimidine l- (4- dimethylamino- -phenyl-ethanone 3-methylthio benzaldehyde IR (KBr) 3460.34203240.3200- 2800.1605.1575.1560.153 5.1355, mp 184-220; MS m / z 388 (M + H) ^&lt; ^{+ &gt};; H. Res. MS m / z 388.1586 (M + H) &lt; ^{+ &gt};. 186 4-Amino-5- (3-bromo-5-methoxyphenyl) -7- (thiophen-2-yl) -pyrido [2,3-d] pyrimidine 1- (Thiophen-2-yl) ethanone 3-bromo-5- methoxy benzaldehyde IR (KBr) 3470, 33502200, 1700, 1640, 1580, 143, 5.1365, 1270, mp. 246249, MS m / z 413/415 (M + H) &lt; ^{+ &gt};, H. Res MS m / z 413.0069 (M + H) &lt; ^{+ &gt};.

187 4-amino-5- (2,3- dimethoxyphenyl) -7- (4- dimethylaminophenyl) - pyrido [2,3-d] pyrimidine *** l- (4- dimethylamino- phenyl) -ethanone 2,3-dimethoxy- benzaldehyde IR (KBr) 3480,34403240,3200- 2800,1610,1580,1550,153 0,1360; mp. 222-225; MS m / z 402 (M + H) ^&lt; ^{+ &gt};; H. Res. MS m / z 402.1922 (M + H) &lt; ^{+ &gt};. 188 4-Amino-5- (3-methylsulfonylphenyl) -7 (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine l- (4- dimethylamino- phenyl) -ethanone 3 methylsulfonyl benzaldehyde IR (KBr) 3490,34002800,1610,1580,1555,153 5,1355; mp. 245-270; MS m / z 420 (M + H) ^&lt; ^{+ &gt};; H. Res. MS m / z 420.1493 (M + H) &lt; ^{+ &gt};.

Example 189

4-acetylamino-5- (3-bromophenyl) -7- (4-dimetylaminofenynpyridor2.3-d1pyrimidín

To a suspension of 4-amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine (from Example 15, 0.28 g, 0.67 mol) in pyridine (3 mL) Acetic anhydride (0.10 g, 1.0 mmol) was added and the reaction mixture was stirred at 25 ° C for 4 h. The volatiles were removed under reduced pressure and the residue was purified by flash chromatography (SiO 2, EtOAc / hexanes) to give the title compound (0.23 g, 73% of theory): IR (KBr) 3368, 3048, 1695, 1567; MS m / z 462/464 (M + H) &lt; ^{+ &gt};.

Examples 190-198

Using the procedures of Example 189, but substituting the acetic anhydride of Example 189 with the appropriate acylating agent listed in Table 5 below, the compounds of Examples 190198 were prepared.

Table 5

Examples 190-198

Pr. no. Title Acylating agent Analytical data 190 4-formylamino-5- (3-bromophenyl) 7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine-190 acetic anhydride and formic acid IR (KBr) 3382, 3047, 1704, 1570; MS m / z 448/450 (M + H) &lt; ⁺ &gt; ^. 191 4- (methoxyacetyl) amino-5- (3- bromophenyl) -7- (4- diethylaminophenyl) pyrido [2,3- d] pyrimidine methoxyacetyl chloride IR (KBr) 3344, 3044, 1731, 1561; MS m / z 492/494 (M + H) &lt; ⁺ &gt; ^. 192 4-trifluoro-acetylamino-5- (3- bromophenyl) -7- (4- dimethylaminophenyl) pyrido [2,3- pyrimidine trifluoroacetic IR (KBr) 3426, 3072, 1610, 1578; MS m / z 516/518 (M + H) &lt; ⁺ &gt; ^. 193 4-Pentanoylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine pentanoyl IR (KBr) 3408, 2954, 1699, 1569; MS m / z 504/506 (M + H) &lt; ^{+ &gt};. 194 4-benzoylamino-5- (3- bromophenyl) -7- (4- dimethylaminophenyl) pyrido [2,3- pyrimidine benzoic anhydride IR (KBr) 3420, 3056, 1606, 1583; MS m / z 524/526 (M + H) &lt; ⁺ &gt; ^. 195 4- (N-B OC-glycyl) amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine / V-Boc-glycyl imidazole IR (KBr) 3362, 2975, 1719, 1570; MS m / z 577/579 (M + H) &lt; ⁺ &gt; ^. 196 4 - (/ V-phthalimidylglycyl) amino-5- (3-bromophenyl) -7- (4- dimethylaminophenyl) pyrido [2,3- pyrimidine N-phthalimidyl-glycyl chloride IR (KBr) 3408, 2927, 1719, 1570; MS m / z 607/609 (M + H) &lt; + &gt;. 197 4- (ethoxycarbonyl) amino-5- (3- bromophenyl) -7- (4- dimethylaminophenyl) pyrido [2,3- pyrimidine dietyldikarbonát IR (KBr) 3405, 2987, 1738, 1569; MS m / z 492/494 (M + H) &lt; ⁺ &gt; ^. 198 4- (ethylaminocarbonyl) amino-5- (3-bromophenyl) -7- (4- dimethylaminophenyl) pyrido [2,3- pyrimidine ethyl isocyanate IR (KBr) 3405, 3053, 1701, 1548; MS m / z 491/493 (M + H) &lt; ⁺ &gt; ^.

Example 199

4-Allylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine

The product was prepared by mixing a solution of 4-chloro-5- (p-dimethylaminophenyl) -7- (bromophenyl) pyrido [2,3-d] pyrimidine in CH 2 Cl 2 -TEA with allylamine and heating the resulting mixture for 1 h at reflux temperature. The volatiles were removed under reduced pressure and the residue was purified by flash chromatography (SiO 2, EtOAc / hexanes) to give the title compound IR (KBr) 3437, 1564, 1355, 1195; MS m / z 460/462 (M + H) &lt; ^{+ &gt};.

4-Chloro-5- (p-dimethylaminophenyl) -7- (p-bromophenyl) pyrido [2,3-d] pyrimidine was prepared as follows:

A sample of 4- (4-bromophenyl) -3-cyano-6- (4- (dimethylamino) phenyl) pyridin-2-amine (from Example 1, 5.0 g, 12.7 mmol) in 20 mL H 2 SO 4 was 30 min heated at 80 ° C. Ice was added and the reaction mixture was neutralized with aqueous NaOH. The resulting crude 3-carboxamide was filtered off, triturated with EtOAc-hexanes and then dried under reduced pressure (4.95 g, 95% of theory). To a solution of this carboxamide (4.25 g, 10.3 mmol) in triethyl orthoformate (20 mL) was added p-toluenesulfonic acid (catalytic amount) and the reaction mixture was heated at 80 ° C for 4 h. The volatiles were removed and the crude bicyclic 4-hydroxyl-5- (p-dimethylaminophenyl) -7- (p-bromophenyl) pyrido [2,3-d] pyrimidine was suspended in POCl 3 (15 mL) and then heated at 100 ° C for 2 h. . POCl 3 was removed under reduced pressure to give crude 4-chloro-5- (p-dimethylaminophenyl) -7- (p-bromophenyl) pyrido [2,3-d] pyrimidine. The invention therefore relates to intermediates of formula III wherein X is selected from the group consisting of hydroxyl or halogen and the remaining variables are the same as in formula I or II.

Example 200

4- (2- (N, N-dimethylamino) ethylamino) -5- (4-bromophenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine trihydrochloride

The product was prepared by mixing a solution of 4-chloro-5- (p-dimethylaminophenyl) -7- (bromophenyl) pyrido [2,3-d] pyrimidine in CH 2 Cl 2 -TEA with 2- (dimethylamino) ethylamine and heating the resulting mixture for 1 h. The volatiles were removed under reduced pressure and the residue was purified by flash chromatography (SiO 2, EtOAc / hexanes) to give the title compound. Excess 2M HCl (aq) was then added to the product followed by lyophilization to give the product as trihydrochloride; IR (KBr) 3385, 1561, 1356, 1197; MS m / z 491/493 (M + H) &lt; ⁺ &gt; ^.

Example 201

4- (4- (N, N-dimethylamino) butylamino) -5- (3-bromophenyl-7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine tetrahydrochloride

The product was prepared by mixing a solution of 4-amino-5- (p-dimethylaminophenyl) -7- (bromophenyl) pyrido [2,3-d] pyrimidine in CH 2 Cl 2 -TEA with 4- (dimethylamino) butylamine and heating the resulting mixture for 1 hk reflux. The volatiles were removed under reduced pressure and the residue was purified by flash chromatography (SiO 2, EtOAc / hexanes). Excess 2M HCl (aq) was added to the product followed by lyophilization to give the product as tetrahydrochloride; IR (KBr) 3439, 1567, 1356, 1196; MS m / z 519/521 (M + H) &lt; ^{+ &gt};.

Example 202

4-f N-allyl-N-formylamino) -5- (4-dimethylaminophenyl) -7- (p-bromophenyl) pyrido [2,3-dlpyrímidín

To a sample of the compound of Example 190, 4-formylamino-5- (2-phenylethyl) -7- (4-diethylaminophenyl) -pyrido [2,3-d] pyrimidine (0.27 g, 0.6 mmol) in 3 mL of mixture 4 : 1 THF and DMF at 0 ° C was added NaH (60% dispersion, 36 mg, 0.9 mmol) and the solution was stirred for 0.5 h. Allyl bromide (0.29 g, 2.4 mmol) was added and the reaction the mixture was stirred for an additional 0.5 h. Workup with water followed by flash chromatography gave the title compound ^- LRMS m / z 488/490. IR (cm ^-1 ) 3428, 2910, 1696, 1551, 1362, 1193.

Example 203

4-diacetylamino-5- (4-dimethylaminophenyl) -7- (p-bromophenyl) -pyridof2.3-d] pyrimidine

This compound was isolated from the minor product of the reaction mixture of Example 190 LRMS m / z 504/506 IR (cm ^-1 ) 2922, 1726, 1550, 1360, 1197.

Example 204

4-amino-5- (3-bromophenyl) -7- (5-amino-2-pyridyl) pyridoí2.3-dlpyrimidín

A solution of 5-aminopyridine-2-ethanone (1.15 g, 8.45 mmol), 3-bromobenzaldehyde (1.70 g, 9.2 mmol), malononitrile (0.61 g, 9.2 mmol) and ammonium acetate (1.15 g, 15 mmol) in 25 mL benzene was heated to reflux with azootropic removal of water. After 6 h, the reaction mixture was concentrated and the desired intermediate (1.82 g, 49%) was isolated after flash chromatography (SiO 2, EtOAc-CH 2 Cl 2). LRMS m / z 366/368. The intermediate was suspended in 15 ml of formamide and the reaction mixture was heated at 180 ° C for 4 h. The solution was cooled to 25 ° C, 10 mL of 4M HCl (aq) was added and stirred for 1 h. The aqueous solution was neutralized with NaOH (aq) and the precipitate was filtered off. The title compound (1.3 g, 68%) was isolated after flash chromatography of the precipitate: LRMS m / z 393/395; ER (cm -1) 3481, 3161, 1620, 1573, 1483, 1359

The starting 5-aminopyridine-2-carboxaldehyde was prepared as follows:

204a. 5-amino-2-bromopyridine

To a solution of 2-bromo-5-nitropyridine (5.1 g, 25 mmol) in 50 mL of 10: 1 acetic acid and water was added powdered iron (7.8 g, 140 mmol) in many portions over 20 min. After an additional 30 min the volatiles were removed under reduced pressure and the residue diluted with 5% aqueous sodium carbonate solution. The aqueous solution was extracted with methylene chloride and the combined organic layer was dried (sodium sulfate), concentrated in vacuo to give the desired product as a white solid (4). , 25 g, 98%).

204b 5-Aminopyridine-2-carboxaldehyde

Sample of 5-amino-2-bromopyridine (4.25 g, 24 mmol), PdCl 2 (PPh 3) 2 (0.34 g, 2 mol%), CuI (0.09 g, 2 mol%) and trimethylsilylacetylene ( 3.0 g (31 mmol) were dissolved in 100 mL of 4: 1 triethylamine / acetonitrile and the reaction mixture was stirred at 25 ° C for 24 h. The reaction mixture was concentrated and the residue was dissolved in 100 mL of 10: 1 acetone / water. To the reaction mixture was added Hg (O2CCF3) 2 (11.1 g, 26 mmol) and H 2 SO 4 (72 mmol), and the solution was heated to reflux. The reaction mixture was cooled to 25 ° C and neutralized with saturated aqueous sodium carbonate. The aqueous layer was extracted with methylene chloride then combined, the organic layer was dried (Na 2 SO 4) and concentrated in vacuo. Flash chromatography (SiO 2, EtOAc-hexanes) gave the title compound: LRMS m / z 137 (M = H +); IR (cm ^-1 ) 3428, 1668, 1646, 1582, 1358, 1274.

Example 205

4-Amino-5- (3-bromophenyl-7- (5-dimethylamino-2-pyridyl) pyrido [2,3-d] pyrimidine trihydrochloride

Following the procedure of Example 204, 5-dimethylaminopyridin-2-ethanone was reacted with bromobenzaldehyde, malononitrile and ammonium acetate to give the title compound. The residue was triturated with excess HCl / ether, the volatiles removed under reduced pressure, and the title compound was dried under high vacuum. LRMS m / z 421/423. IR (cm -1) 3245, 1664, 1545, 1395.

The starting 5-dimethylaminopyridine-2-carboxaldehyde was prepared as follows.

205a..3-jV.V-dimethylaminopyridine

A solution of 3-aminopyridine (9.4 g, 0.10 mol) in a mixture of 1.1 formic acid (96%) and formaldehyde (37% aqueous solution) was heated at reflux for 18 h. The volatiles were removed under reduced pressure and the residue was neutralized with saturated aqueous NaHCO 3. The aqueous layer was extracted with CH 2 Cl 2, then the combined organic layer was dried (Na 2 SO 4) and concentrated under reduced pressure. Flash chromatography (SiO 2, EtOAc-hexanes) gave the title compound ^- (11.1 g, 91%), LRMS m / z 123 ( M + H +).

205b. 2-bromo-5-7V. / V-dimethylaminopyridine

To a solution of 3- N, N -dimethylaminopyridine (5.88 g, 48.1 mmol) in 150 mL of CH 2 Cl 2 at 0 ° C was added 2,4,4,6-tetra-bromo-2,5 in many portions over 30 min. -cyclohexadienone (20.7 g, 50 mmol). After 2 h at 0 ° C, the reaction mixture was concentrated and the desired 2-bromo-5- N, N, dimethylaminopyridine was isolated after flash chromatography (16.5 g, 82%): LRMS m / z 201/203.

205c. MJV-5-dimethylaminopyridine-2-ethanone

Following the procedure of Example 203b, 2-bromo-5-N, N -dimethylaminopyridine was converted to the title compound, except for conversion to trihydrochloride by treatment with HCl / ether: LRMS m / z 165; IR (cm -1) 3480, 1666, 1581, 1368, 1272.

Example 206

4-amino-5- (3-bromophenyl) -7- (5-dimethylamino-2-pyrazinyl) -pyrido-2,3-dlpyrimidine hydrochloride

Following the procedure of Example 204, 5-dimethylaminopyrazine-2-ethanone was treated with bromobenzaldehyde, malononitrile and sodium acetate to give the title compound. The residue was triturated with excess HCl / ether, the volatiles were removed under reduced pressure and the title compound was dried under high vacuum. : LRMS m / z 422/424. IR (cm ^-1 ) 3310, 1630, 1525, 1444, 1375.

The starting 5-dimethylaminopyrazine-2-carboxaldehyde was prepared as follows.

206a. 5-dimethylamino-pyrazin-2-ethanone

A solution of 5-hydroxypyrazine-2-carboxylic acid (4.0 g, 28.5 mmol) in 50 mL thionyl chloride and 0.1 mL DMF was heated to reflux for 8 h. The volatiles were removed under reduced pressure and the residue was dissolved in 20 mL of toluene. This solution was added to a solution of dimethyl malonate (4.75 g, 36 mmol), MgCl 2 (2.09 g, 22 mmol) and triethylamine (7.08 g, 70 mmol) in 100 ml toluene. The reaction mixture was stirred for 1 h at 25 ° C, diluted with water and the product was extracted with methylene chloride. The solvent was removed, the crude intermediate was dissolved in 25 mL of 25: 1 DMSO / water and heated at 150 ° C for 2 h. The reaction mixture was diluted with water and the product extracted with methylene chloride gave 2-acetyl-5-chloropyrazine (LRMS m / z 156). This intermediate was treated with dimethylamine for 30 min at room temperature to give 5-dimethylaminopyrazine-2-ethanone (LRMS m / z 166): LRMS m / z 422/424; IR (cm ^-1 ) 3310, 1630, 1525, 1444, 1375.

Example 207

4-amino-5- (3-bromophenyl) -7- (2-oxobenzoxazolin-6-yl) pyridor2.3-dlpyrimidín

Following the procedure of Example 204, 2-oxobenzoxazoline-6-ethanone was reacted with bromobenzaldehyde, malononitrile and ammonium acetate to give the title compound: LRMS m / z 434/436; IR (cm ^-1 ) 3095, 1760, 1579, 1481, 1350.

The starting 2-oxobenzoxazoline-5-ethanone was prepared as follows:

207a. 2-oxobenzoxazolin-6-ethanone

DMF (9 mL) was added dropwise to AlCl 3 (58.7 g, 440 mmol) over 20 min and the resulting suspension was stirred at 25 ° C for 15 min. Acetic anhydride (7.14 g, 70 mmol) and 2-benzoxazolinone (6.0 g, 44 mmol) were added, the reaction mixture was heated to 80 ° C and stirred for 4 h. The mixture was cooled to 25 ° C and poured into ice / H 2 O. The resulting precipitate was filtered, dried in vacuo to give the title compound (6.4 g, 81%, LRMS m / z Υ1Ί).

Example 208

4-amino-5- (3-bromophenyl) -7- (l-methyl-2-oxobenzoxazolin-6-yl) -pyridor2.3-dlpyrimidin

Following the procedure of Example 204, 1-methyl-2-oxobenzoxazoline-5-ethanone was treated with bromobenzaldehyde, malononitrile and ammonium acetate to give the title compound. LRMS m / z 448/450; IR (cm ^-1 ) 3440, 1782, 1605, 1458, 1350

The starting 1-methyl-2-oxobenzoxazoline-5-ethanone was prepared as follows

208a. 1-Methyl-2-oxobenzoxazolin-5-ethanone

To a solution of 2-oxobenzoxazoline-5-ethanone (from Example 206a, 2.50 g, 14.1 mmol) in 20 mL of 4: 1 THF and DMF was added NaH (60% dispersion, 0.8 g) at 0 ° C. , 20 mmol) and the mixture was stirred at 0 ° C for 20 min. Methyl iodide (3.97 g, 28 mmol) was added, the reaction mixture was warmed to 25 ° C and stirred for 15 min. Saturated aqueous NaHCO 3 was added and the aqueous layer was extracted with CH 2 Cl 2. The desired product (2.55 g, 94%, LRMS m / z 191) was isolated after flash chromatography (SiO 2, EtOAc-CH 2 Cl 2).

Example 209

4-amino-5 - ((5-chloro-2- (3-methoxyphenyl) fenyBmetyn-7- (4-dimetylaminofenyn -pyrido [2,3dlpyrimidín

The title compound was prepared from Example 173 by treatment with 3-methoxyphenylboronic acid, Pd (PPh ₃ ) _4, and aqueous sodium carbonate under Suzuki IR (KBr) conditions 3550-3250, 3240-2760, 1580, 1560, 1540, 1350, H Res MS m / z 946.1902 (M + H) &lt; ^{+ &gt};.

Example 210

4-amino-5 - ((2-bromophenyl) methyl) -7- (4-dimethylaminophenyl) pyridoí2.3-d1pyrimidín

Using the procedures of Example 157, but substituting R ^{4 for} 1- (4-dimethylaminophenyl) ethanone and R ^{3 for} 2- (2-bromophenyl) acetaldehyde, the title compound was prepared as shown in Table 6.

Table 6

Pr. no. Title Component R ⁴ (for position 7) Component R ³ (for position 5) Analytical data 210 4-amino-5 - ((2- bromophenyl) methyl) -7- (4- dimethylamino- phenyl) pyrido [2,3- pyrimidine l- (4- dimethylamino- phenyl) -ethanone 2- (2- bromophenyl) - acetaldehyde IR (KBr); MS m / z 434.436 (M + H) &lt; + &gt;.

Example 211

4-amino-5- (2 - ((thiophen-2-yl) phenyl) mety0-7- (4-dimethylaminophenyl) -pyridoí2.3-d1pyrimidín

The title compound was prepared from Example 173 by treatment with 2-thiopheneboronic acid, Pd (PPh ₃ ) ₄ and aqueous sodium carbonate under Suzuki reaction conditions. IR (KBr) 3640-3240, 3240-2800, 1580, 1560, 1540, 1350; h. Res. MS m / z 466.2070 (M + H) &lt; ^{+ &gt};.

Example 212

4-amino-5- (2 - ((thiophen-3-yl) phenyl) methyl) -7- (4-dimethylaminophenyl) -pyridoí2.3-d1pyrimidín

The title compound was prepared from Example 173 by treatment with 3-thiopheneboronic acid, Pd (PPh ₃ ) ₄ and aqueous sodium carbonate under Suzuki reaction conditions. IR (KBr) 3640-3240, 3240-2800, 1580, 1560, 1540, 1350; h. Res. MS m / z 466.2057 (M + H) &lt; ^{+ &gt};.

Examples 213-222

Using the procedures of Example 1, but substituting the reagents R ⁴ and R ^{3 with the} appropriate reagents listed in Table 7 below, the compounds of Examples 212-222 were prepared.

Table 7

Examples 213-222

Pr. no. Title Component R ⁴ (for position 7) Component R ³ (for position 5) Analytical data 213 4-amino-5- (3-bromophenyl) - 7- (4- (N-formyl-N- (2- methoxyethyl) amino) - phenyl) pyrido [2,3- pyrimidine; 1- (4- (N-formyl) - (2- methoxy) ethyl amino) phenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3490, 1689, 1120, 800 cm &lt; -1 &gt; hMS / n / z 478/480 (M + H) &lt; ^{+ &gt;}

214 4-Amino-5- (3-bromophenyl) - 7- (4- (N- (2- methoxyethyl) amino) - phenyl) pyrido [2,3- pyrimidine; * IR (KBr) 3330, 2925, 1675, 800 cm @ -1 MS m / z 451/453 (M + H) ⁺ . 215 4-Amino-5- (3-bromophenyl) - 7- (4- (N-methyl-N - ((2- dimethylamino) ethyl) amino) phenyl) pyrido [2,3- pyrimidine; 1- (4- (N-methyl-N - ((2- dimethylamino) - ethyl) amino) phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3440, 1600, 1160, 810 cm &lt; -1 &gt;; MSr 477/479 (M + H) ⁺ 216 4-amino-5- (3-bromophenyl) - 7- (4- (2- methoxy) acetylamino) ethyl) amino) phenyl) pyrido [2,3- pyrimidine; ** IR (KBr) 3480, 1520, 710 cm ^-1 ; MS m / z 464.466 (M + H) &lt; ⁺ &gt; ^. 217 4-amino-5- (3-bromophenyl) - 7 - ((4-formylamino) phenyl) - pyrido [2,3-d] pyrimidine; *** IR (KBr) 3475, 1690, 1355, 800 cm &lt; -1 &gt; MS / n / z 420/422 (M + H) ⁺ 218 4-amino-5- (3-bromophenyl) 7- (4- (2- (dimethylamino) acetylamino) phenyl) pyrido [2,3-d] pyrimidine; **** IR (KBr) 3452,1605,1250,590 cm ^J , MS m / z 477/479 (M + H) &lt; ^{+ &gt;} 219 4-Amino-5- (3-bromophenyl) - 7- (4- (2-oxo-3- oxazolidinyl) - phenyl) pyrido [2,3- pyrimidine; l- (4- (2-oxo-3- oxazolidinyl) - phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3480, 1750, 1400, 700 cm ^{@ -1} , MS m / z 462/464 (M + H) ^{@ +} 220 4-Amino-5- (3-bromophenyl) 7- (6- (2-propyl) -3-pyridinyl) pyrido [2,3-d] pyrimidine trihydrochloride l- (6- (2-propyl) - 3-pyridinyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3474, 3098, 1636, 1566, 1499, 1352, 1282 cm &lt; ^{-1 &gt};; MSw / z 393 (M + H) &lt; ^{+ &gt;} 221 4-amino-5- (3-bromophenyl) - 7- (3-methyl-4- pyrrolidinylphenyl) - pyrido [2,3-d] pyrimidine dihydrochloride 1- (3-methyl-4- pyrrolidinylphenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3440, 1640, 1607, 1586, 1370 cm ^-1 ; MS m / z 433 (M + H) &lt; ⁺ &gt; ^. 222 4-Amino-5- (3-bromophenyl) 7- (6-imidazolyl-3-pyridinyl) pyrido [2,3-d] pyrimidine trihydrochloride 1- (6-imidazolyl- 3-pyridinyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3028, 1641, 1607, 1595, 1375 cm &^lt; ^{-1 &gt};; MS m / z 417 (M + H) &lt; ⁺ &gt; ^.

* prepared by deformylating the component of Example 213 with dilute HCl in methanol.

** prepared by acylating the component of Example 213 with 2-methoxyacetyl chloride / pyridine.

*** Prepared by formylation of 7- (3-bromophenyl) -2-cyano-5- (4-aminophenyl) pyridin-2-amine intermediate.

**** prepared by acylating the component of Example 213 with 2- (dimethylamino) acetyl chloride.

Examples 223-225

Using the procedures of Example 157, but substituting the appropriate reagents listed in Table 8 below for components R 4 and R 6, Examples 223-225 were prepared.

Table 8

Examples 223-225

Pr. w c. Title Component R ⁴ (for position 7) Component R ³ (for position 5) Analytical data 223 4-amino-5-phenylmethyl-7- (4-diethylamino) - pyrido [2,3-d] pyrimidine l- (4- diethylamino phenyl) -ethanone 2-phenyl- acetaldehyde IR (KBr) 3450,3380,28503200,1605,1580,1560,15 40; H Res MS m / z 384.2176 (M + H) &lt; ⁺ &gt; ^. 224 4-amino-5- (2- (3- aminopropinyl) phenyl methyl) -7- (4- diethylamino) - pyrido [2,3-d] pyrimidine * IR (KBr) 24003450, 2050, 2120, 1650, 16, 0540; MS m / z 437 (M + H) + 225 4-amino-5- (l- (2- bromophenyl) ethyl) -7- (4- dimethylamino- phenyl) pyrido [2,3- pyrimidine l- (4- dimethylamino- phenyl) -ethanone 2- (2- bromophenyl) - ) propionaldehyde IR (KBr) 3 520.32503500.2850-3150.1605.1580.1560.15 40; H. Res. MS m / z 448.1137 (M + H) &lt; ^{+ &gt};.

* prepared from the compound of Example 170 by reaction with propargylamine, CuI and Pd (PPh 3) 4 under Suzuki reaction conditions.

Examples 226-228

Using the procedures of Example 1, but substituting the components and R @ 8 with the appropriate reagents listed in Table 9 below, the compounds of Examples 226-228 were prepared.

Table 9

Examples 226-228

Pr. w c. Title Component R ⁴ (for position 7) Component R ³ (for position 5) Analytical data 226 4-Amino-5- (4-dimethylaminophenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine l- (4-bromophenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3456, 3053, 16600, 1556 cm -1; MS m / z 420 (M + H) ⁺ 227 4-amino-5- (2-furanyl) -7- (4- (N-morpholinyl) phenyl) - pyrido [2,3-d] pyrimidine l- (4- (N- morpholinyl) phenyl) -ethanone furan-2 carboxaldehyde IR (KBr) 3460, 1600, 1580, 1457 cm -1; MS m / z 374 (M + H) ⁺ 228 4-Amino-5- (3-bromophenyl) 7- (2-dimethylamino-5-pyrimidinyl) pyrido [2,3-d] pyrimidine 1- (5- (2- (Dimethylamino) - pyrimidinyl) - ) ethanone 3-bromo- benzaldehyde IR (KBr) 3442 1640, 1604, 1577, 1536, 1408, 1367, 1348 cm &lt; ^{-1 &gt};; MS m / z 422 (M + H) &lt; ^{+ &gt};.

Example 229

4-amino-5- (3-bromophenyl) -7- (4-Fureidis) phenyl) pyridor2.3-dlpyrimidín

To a solution of 4-amino-5- (3-bromophenyl) -7- (4-aminophenyl) pyrido [2,3-d] pyrimidine (Example 71, 310 mg, 0.79 mmol) in 2 mL acetic acid was added cyanate sodium (56 mg, 0.87 mmol) was added and the reaction mixture was stirred at 25 ° C for 30 min. The solution was concentrated and the residue was suspended in aqueous NaHCO 3 solution. The crude product was filtered off and then purified by flash chromatography. The product was dissolved in methanol and an excess of 2M aqueous was added

HCl to give the hydrochloride-LRMS m / z 435/437. IR (cm ^-1 ) 3442, 2212, 3186, 3059, 1681, 1582, 1525, 1358

Example 230

4-Amino-5- (1-phenylmethyl-3-piperidinyl) -7- (4-diethylaminophenyl) pyrido [2,3-d] pyrimidine

Using the procedures of Example 157, but substituting R ^{4 for} 1- (4-diethylaminophenyl) ethanone and R ^{3 for} 1-phenylmethylpiperidine-3-carboxaldehyde (prepared as described by Gilligan et al., J. Med. Chem., 35: 4344 -4361 (1992)), the title compound was prepared by treatment with aqueous HCl was omitted, and the free base IR (KBr) 3440, 3100-28001640, 1605, 1595, 1535 cm ^-1; MS m / z 467 (M + H) +, 112. 218-220 ° C.

Examples 231-243

Using the procedures of Example 1, but substituting the reagents R ²¹ and R 16 with the appropriate reagents listed in Table 10 below, the compounds of Examples 231-243 were prepared. In some cases, aqueous HCl treatment was omitted and free bases were obtained.

Table 10

Examples 231-243

Pr. in c. Title Component R ⁴ (for position 7) Component R ³ (for position S) Analytical data 231 4-amino-5- (3-bromophenyl) -7 (6- (3-methyl-5-isoxazolyl)) - 3-pyridinyl) pyrido [2,3-d] pyrimidine; l- (6- (3-methyl- 5-isoxazolyl)) - 3-pyridinyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3484, 1635, 1574, 1562, 1352 cm &lt; ^{-1 &gt};; MS m / z 459 (M + H) &lt; ⁺ &gt; ^. 232 4-amino-5- (3-bromophenyl) -7- (6-chloro-3- pyridinyl) pyrido [2,3- pyrimidine; l- (6-chloro-3- pyridinyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3478, 1608, 1574, 1542 cm ^-1 ; MS m / z 414 (M + H) &lt; ^{+ &gt};. 233 4-amino-5- (3-bromophenyl) -7- (6-methoxy-3- pyridinyl) pyrido [2,3- pyrimidine; l- (6-methoxy-3- pyridinyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3484, 1635, 1560, 1348 cm &lt; ^{-1 &gt};; MS m / z 409 (M + H) &lt; ^{+ &gt};.

234 4-amino-5- (3-bromophenyl) -7 (6- (1,2,4-triazol-4-yl) -3-pyridinyl) pyrido [2,3-d] pyrimidine; 1- (6- (1,2,4- triazol-4-yl) -3- pyridinyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3494, 1612, 1579, 1467, 1359, 1271, 1233 cm ^-1 ; MS m / z 445 (M + H) &lt; ^{+ &gt};. 235 4-amino-5- (3-bromophenyl) -7- (2-morpholinyl-5 pyrimidinyl) pyrido [2,3- pyrimidine, l- (2- morpholinyl-5- pyrimidinyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3434, 1637, 1608, 1585, 1335, cm ^-1 ; MS m / z 463 (M + H) ⁺ 236 4-amino-5- (2-thiazolyl) -7- (4- pyrrolidinylphenyl) pyrido [2,3- pyrimidine; H4 pyrrolidinyl phenyl) -ethanone Thiazol-2 carboxaldehyde IR (KBr) 3400, 1637, 1608, 1532, cm &lt; ^{-1 &gt}; MS / w / z 376 (M + H) &lt; + &gt; 237 4-amino-5- (3-bromophenyl) -7- (6-pyrazolyl-3-pyridinyl) pyrido [2,3-d] pyrimidine; l- (6-pyrazolyl 3-pyridinyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3474, 1580, 1562, 1492, 1395, cm ^-1 ; MS m / z 444 (M + H) &lt; + &gt;. 238 4-amino-5- (3-bromophenyl) -7- (4- (1-methyl-ureido) phenyl) pyrido [2,3-d] pyrimidine; 1- (4- (1-methylureido) phenyl) ethanone 3-bromo- benzaldehyde IR (KBr) 3400, 1665, 1350 cm ^-1 ; MS m / z 450 (M + H) &lt; ⁺ &gt; ^. 239 4-amino-5- (3-bromophenyl) -7 (4- (N-methyl-N- (2-pyrimidinyl) amino) phenyl) pyrido [2,3-d] pyrimidine; L- (4- (N-methyl- N- (2- pyrimidinyl) - amino) phenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3475, 1578, 1553, 1482, 1396, cm ^-1 ; MS m / z 484 (M + H) &lt; ⁺ &gt; ^. 240 4-amino-5- (3-bromophenyl) -7- (3-fluoro-4- (N-formyl-N-methylamino) phenyl) pyrido [2,3-d] pyrimidine; * l- (3-fluoro-4- (N methylamino) - phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3448, 1600, 1525, 1476, cm &lt; ^{-1 &gt};; MSw / z 484 (M + H) ⁺ . 241 4-formylamino-5- (3-bromophenyl) -7- (3-fluoro-4- (N-formyl-N-methylamino) phenyl) pyrido [2,3-d] pyrimidine; * l- (3-fluoro-4- (N methylamino) - phenyl) -ethanone 3-bromo- benzaldehyde IR (KBr) 3465, 1607, 1546, 1350, cm ^-1 ; MS m / z 481 (M + H) &lt; ^{+ &gt};. 242 4-amino-5- (3-bromophenyl) -7- (4- (N -methyl- N methylsulfonylamino) - phenyl) pyrido [2,3- pyrimidine; 1- (4- (N-methyl-N-) methylsulfonyl amino) phenyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3470, 1650, 1570, 1338, cm &^lt; -1 & gt ^; , MS m / z 484 (M + H) &lt; ^{+ &gt;}

243 4-amino-5- (3-bromophenyl) -7 (6- (N-methyl-N-methylsulfonylamino) -3 pyridinyl) pyrido [2,3-d] pyrimidine; l- (6- (N-methyl- N-methyl- sulfonyl amino) -3- pyridinyl) - ethanone 3-bromo- benzaldehyde IR (KBr) 3460, 1680, 1580, 1330 cm &^lt; -1 & gt ^; , MS m / z 485 (M + H) &lt; ^{+ &gt;} divides chromatographically the reaction mixture; formylation for ) during cyclization-

him degree

Example 244

4-Amino-5- (3-bromophenyl-7- (1-methyl-5-indolinyl) pyrido [2,3-d] pyrimidine dihydrochloride)

A sample of 4- (3-bromophenyl) -3-cyano-6- (1-methyl-5-indolinyl) pyridin-2-amine was maintained at reflux temperature in formamide. The reaction was monitored by TLC and once complete, the mixture was cooled to room temperature. The product was allowed to precipitate, then was filtered and washed with water. Additional product was extracted from the filtrate. The product was purified by column chromatography eluting with 10% MeOH / CH 2 Cl 2 and converted to the hydrochloride with ether / HCl. The salt was isolated and dried in vacuo to give the title compound. LRMS m / z 432/434; IR (cm ^-1 ) 3500, 3400, 3300, 3200-2800, 1610, 1580, 1560, 1540

The starting 4- (3-bromophenyl) -3-cyano-6- (1-methyl-5-indolyl) pyridin-2-amine was prepared as follows:

244a. 5-bromo-l-methylindolin

Acetic acid (60 mL) was added to a mixture of 5-bromo-1-methylindole (10 g, 47.6 mmol) and sodium cyanoborohydride (8 g). After 1 h at 15 ° C, the reaction mixture was basified with aqueous NaOH and extracted with toluene. The organic phase was dried over MgSO 4 and concentrated in vacuo to a powder. This material was purified by flash chromatography to give the title compound, 8.62 g (82%): MS 212, 214 [M + H] ⁺ .

100

244b 5-Acetyl-1-methylindoline

A mixture of 5-bromo-1-methylindoline (8.6 g, 40.7 mmol), trimethylsilylacetylene (12 mL), palladium bis-triphenylphosphine dichloride (600 mg), CuI (620 mg) and triethylamine (16 mL) in acetonitrile (20 mL) ) was maintained at 75 ° C for three days, then cooled and concentrated in vacuo. The residue was dissolved in 120 mL of 1: 1 ethyl acetate / hexane and the solid was filtered off. The solvent was removed and a sample of the residue (5 g) was dissolved in 90% aqueous acetone (44 mL). To this solution was added sulfuric acid (2.2 g) and Hg (OCOCF 3) 2 (9 g). The reaction mixture was refluxed for 20 min, cooled, basified with aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic layer was dried over MgSO 4 and concentrated to an oil which purified by flash chromatography to give 850 mg of the title compound: MS 176 [M + H] ⁺ .

244c, 4- (3-Bromophenyl) -3-cyano-6- (1-methyl-5-indolinyl) pyridin-2-amine

Prepared by condensation of ((3-bromophenyl) methylene) propanedinitrile (prepared as described by Moison et al., Tetrahedron, (1987), 43: 537-542) and 5-acetyl-1-methylindoline (component R ⁴ ) with ammonium acetate in ethanol. The reaction mixture was heated to reflux in a flask equipped with a Dean-Stark apparatus. After 3.5 h the mixture was cooled and the solvent removed. The residue was purified by flash chromatography eluting with methylene chloride to give the title compound (588 mg, yield 30%; MS m / z 394 (M + H) ⁺ ).

Example 245

4-Amino-5- (3-bromophenyl) -7- (1-methyl-5-benzimidazolyl) pyridine-2,3-d1-pyrimidine tetrachloride

The title compound was prepared according to the procedure of Example 1, but substituting 4-dimethylaminobenzaldehyde (component R ³ ) with 1-methyl-5-acetylbenzimidazole (prepared as described by DJ Evans et al., J Chem Soc. Perkin Trans. II, 1978, 865) IR (KBr) 3650-3230, 32302000, 1635, 1605, 1590, 1555, 1365 cm ^-1 ; MS m / z 431/433, 431 0605 (M + H) &lt; - &gt;

ΙΟΙ

Example 246

40-Amino-5- (3-bromophenyl-7- (6-dimethylamino-3-pyridazines) -pyrido [2,3-d] pyrimidine tetrachloride

246a 6- (1-butoxyethoxy-B-3-chloropyridazine)

To a solution of 20 g (200 mmol) of butyl vinyl ether in 80 ml of THF at -78 ° C was added 130 ml of a 1.7 M solution of tert-butyllithium in pentane over about 20 min. The yellow suspension was allowed to warm to 0 ° C with stirring. THF (150 mL) was added, then the mixture was cooled to -78 ° C and a solution of 23 mL (200 mmol) of trimethylborate in 50 mL of THF was added. The reaction mixture was warmed to 20 ° C, 20 mL of methanol was added and the solution was concentrated in vacuo. The residue was diluted with 400 mL of dioxane and 20.9 g (140 mmol) of 3,6-dichloropyridazine, 2.31 g of Pd (PPh ₃ ) 4 and 200 mL of 2M aqueous sodium carbonate were added. The reaction mixture was heated at reflux for 1 h, then cooled and the solid was filtered off. The filtrate was concentrated in vacuo and partitioned between ethyl acetate and 1M sodium hydroxide. The organic phase was dried over Na ₂ SO ₄ , concentrated in vacuo and purified by flash chromatography to give 6.3 g (21%) of the title compound. MS [M + 1] 213, 215.

246b. 1- (6-Chloropyridazin-3-ylethanone)

A mixture of 6.3 g of the compound from Step 246a in 40 mL of dimethoxyethane, 10 ml of water and 4 mL of 12 M HCl was stirred for 20 minutes, then add 125 ml water and the reaction mixture was neutralized with 12 g NaHCO _third The reaction mixture was extracted with ethyl acetate, dried over Na ₂ SO ₄ and concentrated in vacuo to a yellow solid, 4.7 g.

246c. 1- (3- (6- (dimethylamino) pyridazin-3-yl) ethanone (component R ⁴ )

To a solution of 1.57 g (10 mmol) of 1- (6-chloropyridazin-3-yl) ethanone (from step 246b) in 15 ml of dimethoxyethane was added 50 mmol of a 40% aqueous dimethylamine solution After 1 h, the reaction mixture was partitioned between CH ₂ Cl ₂ and water. The organic phase was dried over CH ₂ Cl ₂ and concentrated in vacuo to give the title compound

102

246d 3-Acetyl-6- (dimethylamino) pyridazine

The title compound was prepared by condensing 1,1-dicyano- (3- (3-bromophenyl) propene (component R ³ ) with the compound of step 246c (component R ⁴ ) and ammonium acetate in ethanol according to the procedure of Example 157d.

246e. 4-Amino-5- (3-bromophenyl-7- (6-dimethylamino-3-pyridazinyl) pyridine-2,3-d] pyrimidine tetrahydrochloride

The title compound was prepared from the compound of step 246d following the procedure of Example 157, but substituting formamide for ammonium sulfate and triethyl orthoformate.

Examples 247-248

Using the procedures of Example 246 but substituting methylamine in step (c) with the appropriate reagents listed in Table 11A below, the compounds of Examples 247-248 were prepared.

Table 11A

Examples 247-248

Pr. no. Title Ingredient of step c Analytical data 247 4-Amino-5- (3-bromophenyl) -7- (6-morpholinyl-3-pyridazinyl) -pyrido [2,3-d] pyrimidine dihydrochloride morpholino IR (KBr) 3600-3200, 3000, 1630, 1605, 1590, 1550 cm -1; MS m / z 464/466, 464.0829 (M + H) ⁺ ; 248 4-Amino-5- (3-bromophenyl) -7- (6-pyrrolidinyl-3-pyridazinyl) -pyrido [2,3-d] pyrimidine dihydrochloride pyrrolidine IR (KBr) 3600-3250, 31002800, 1640, 1605, 1560 cm -1; MS m / z 448/450 (M + H) ^&lt; ^{+ &gt};;

103

Examples 249-251

Using the procedures of Example 244 but substituting R ⁴ in Example 244, step c with the corresponding R ⁴ in step c, shown in Table 11B below, and conducting the condensation with ammonium acetate to replace ethanol in Example 244, step c with dichloroethane as the solvent Examples 249-251 were prepared. In some cases, hydrochlorides were not prepared.

Table 11B

Examples 249-260

Pr. in c. Title Component R ⁴ (for position 7) Analytical data 249 4-Amino-5- (3-bromophenyl) -7 (5-morpholinyl-2-pyrazinyl) pyrido [2,3d] pyrimidine dihydrochloride 2-Acetyl-5 morpholinyl-pyrazine IR (KBr) 3478, 3058, 1562, 1542, 1378, 1306 cm &lt; ^{-1 &gt};; MS m / z 464/466 (M + H) ^&lt; ^{+ &gt};; 250 4-Amino-5- (3-bromophenyl) -7 (5- (N- (2-methoxyethyl) -N-methylamino) -2-pyrazinyl) pyrido [2,3-d] pyrimidine dihydrochloride 2-acetyl-5- (N- (2- methoxyethyl) -N- methylamino) - pyrazine IR (KBr) 3482, 3299, 3053, 1612, 1540, 1310 cm &^lt; -1 &gt;; MS m / z 466/468 (M + H) &lt; ^{+ &gt};, 251 4-amino-5- (3-bromophenyl) -7 (4- (morpholinylmethyl) phenyl) pyrido [2,3-d] pyrimidine hydrochloride l - ((4-acetylphenyl) - methyl) -morpholine IR (KBr) 3040, 1680, 1640, 1605, 1580, 1400 cm &^lt; -1 &gt;; MS m / z 466/468 (M + H) ^&lt; ^{+ &gt};;

Example 252

4-amino-5- (3-bromophenyl) -7- (5-N, N-bis (2-methoxyethylamino) -2-pyridinylpyridor-2,3-pyrimidine trihydrochloride

Step 252a. 1- (5-Bromo-2-pyridyl) ethanone. one ethylene

104

A solution of dibromopyridine (5.2 g, 21.95 mmol), tributyl (1-ethoxyvinyl) tin (9.11 g, 25.24 mmol), Pd ₂ (dba) ₃ (0.7 g, 0.8 mmol) and (2-furyl) ₃ P (0.37 g, 1.6 mmol) in 50 mL toluene / THF (5.1) was kept at reflux for 10 h. The reaction mixture was concentrated and the crude product was purified by elution through a short silica gel column. The resulting enol-ether compound was dissolved in 50 mL of toluene together with ethylene glycol (2.79 g, 45 mmol) and p-toluenesulfonic acid (0.1 g) and the solution was heated to reflux for 10 h. The reaction mixture was diluted by addition of saturated aqueous NaHCO 3 and the aqueous layer was extracted with CH 2 Cl 2 The combined organic layer was dried (Na ₂ SO 4), concentrated under reduced pressure, and the resulting crude product purified by flash chromatography to give the title compound (3.68 g, 79%) .

Step 252b. l- (5- (bis (2-metoxyetyDamino) -2-pyridyl) ethanone

According to the literature (J. Org. Chem. 1996, 61, 720), a suspension of the compound of step 252a, bis (2-methoxyethyl) amine, t-BuONa, Pd ₂ (dba) ₃ and BINAP in toluene was maintained at temperature 80 ° C. The reaction mixture was diluted by addition of saturated aqueous NaHCO 3 and the aqueous layer was extracted with CH 2 Cl 2. The combined organic layer was concentrated and the resulting residue was dissolved in 20 mL of THF / 3M HCl (4: 1) and stirred for 4 h. The reaction mixture was neutralized by addition of 2M NaOH (aq) and the aqueous layer was extracted with CH 2 Cl 2. The combined organic layer was dried, concentrated under reduced pressure, and the crude product was purified by flash chromatography to give the title compound.

Step 252c. 4-amino-5- (3-bromophenyl) -7- (5-N, N-bis (2-methoxyethyl) amino) -2-pyridinylpyrido [2,3-d] pyrimidine trihydrochloride

Following the procedures of Example 244, but first substituting component R ⁴ in step c of Example 244 compound from step 252b in step CA, first performing the condensation with ammonium acetate substituting ethanol in Step C of Example 244 with dichloroethane as a solvent, was prepared by the free base of the title compound. The title compound was prepared by treatment with HCl in ether IR (KBr) 3440, 1635, 1605, 1580, 1360 cm ^-1 , MS m / z 466/468, (M + H) ⁺ .

105

Examples 253-260

The procedures of Example 244 but substituting the reagent R ⁴ in step 244 of Example 244 with the appropriate reagent listed in Table 11B below, and c and condensing ammonium acetate with the replacement of ethanol in step 244 of Example 244 with dichloroethane as solvent were prepared. the compounds in Examples 253-260. In some cases, hydrochlorides were not prepared

Pr. no. Title Component R ⁴ (for position 7) Analytical data 253 4-Amino-5- (3-bromophenyl) -7- (4 (imidazolylmethyl) phenyl) pyrido [2,3-d] pyrimidine trihydrochloride l - ((4-acetylphenyl) - methyl) imidazole IR (KBr) 3105, 1645, 1620, 1570, 1350 cm ^-1 ; MS m / z 466/468 (M + H) ^&lt; ^{+ &gt};; 254 4-amino-5- (3-bromophenyl) -7- (5- (L-morpholinyl) -2- pyridinyl) pyrido [2,3-d] pyrimidine trihydrochloride 1- (5-Morpholinyl-2-pyridyl) -ethanone * IR (KBr) 3297, 3081, 1646, 1564, 1494, 1362 cm ^-1 , MS m / z 463/465, (M + H) ⁺ , 255 4-Amino-5- (3-bromophenyl) -7- (4 ((dimethylamino) methyl) phenyl) pyrido [2,3-d] pyrimidine dihydrochloride l- (4 - ((dimethyl- amino) methyl) - phenyl) -ethanone IR (KBr) 3308, 1645, 1590, 1560, 1375 cm ^-1 ; MS m / z 509/511 (M + H) ^&lt; ^{+ &gt};; 256 4-Amino-5- (3-bromophenyl) -7- (5- (4-hydroxy-1-piperidinyl) -2-pyridinyl) pyrido [2,3-d] pyrimidine dihydrochloride l- (5- (4-hydroxy- piperidinyl) -2- pyridyl) ethanone ** IR (KBr) 3000, 1650, 1600, 1580, 1550, 1400 cm ^-1 ; MS m / z 477/479, (M + H) &lt; ^{+ &gt};, 257 4-Amino-5- (3-bromophenyl) -7- (5 (N-formyl-N-methylamino) -2-pyridinyl) pyrido [2,3-d] pyrimidine dihydrochloride 5-acetyl-2- pyridínmetán- amine IR (KBr) 3477, 3060, 1678, 1638, 1566, 1495, 1319 cm &lt; ^{-1 &gt};; MS m / z 435/437 (M + H) ^&lt; ^{+ &gt};; 258 4-amino-5- (3-bromophenyl) -7- (5- (2-propenyl) -2- pyridinyl) pyrido [2,3-d] pyrimidine 2-acetyl-5- (2- propenyl) pyridine IR (KBr) 3085, 1562, 1485, 1357 cm ^-1 , MS m / z 418/420, (M + H) ⁺ ; 259 4-Amino-5- (3-bromophenyl) -7- (3 (2-methoxyethyl) -2-oxo-6-benzoxazolyl) pyrido [2,3-d] pyrimidine hydrochloride 6-acetyl-3- (2- methoxyethyl) - benzoxazol-2-one IR (KBr) 3440, 1770, 1625, 1605, 1580, 1360 cm ^-1 ; MS m / z 492/494, (M + H) &lt; ^{+ &gt};,

106

260 4-Amino-5- (3-bromophenyl) -7- (4- (1- (N-formylamino) ethyl) phenyl) pyrido [2,3d] pyrimidine N- (l- (4-acetyl- phenyl) ethyl) - formamide IR (KBr) 3283, 3054, 1678, 1631, 1547, 1352 cm ^-1 , MS m / z 448/450, (M + H) ⁺ ;

* Prepared as in Example 252b, but with the substitution of bis (2-methoxyethyl) amine with morpholine ** Prepared as in Example 252b, but with the substitution of bis (2-methoxyethyl) amine with 4-hydroxypiperidine.

Example 261

4-amino-5- (3-pyridyl) -7- (4-dimethylamino) fenylpyridor2.3-dlpyrimidin

This compound was prepared using the procedure generally outlined above in Scheme 3 and the accompanying examples, using 1- (4-dimethylaminophenyl) ethanone as component R ⁴ (position 7) and nicotinaldehyde as component (position 5). IR (cm ^-1 ) 3305.8, 2922, 1606, 1578, 1535, 1360. MS (M + H) 342.

Example 262

4- ('Methylamino') -5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido-2,3-dlpyrimidine hydrochloride

The title compound was prepared using the procedure described in Example 200 but substituting methylamine for 2- (dimethylamino) ethylamine. MS (M + H), 478 (1Br); IR (cm ^-1 ) 3455, 3047, 2959, 1580, 1351, 1234.

Example 263

4- (2-Methoxyethylamino) -5- (3-bromophenyl) -7- (4-dimethylaminophenyl) pyridine-2,3-di-pyrimidine hydrochloride

107

The title compound was prepared using the procedure described in Example 200, but substituting 2- (dimethylamino) ethylamine for 2-methoxyethylamine. MS (M + H), 522 (IBr), IR (cm ^-1 ) 3415, 2920, 1569, 1321, 1234

Example 264

4-amino-5- (3-bromophenyl) -7- (4- (l-methyl-2-imidazolyl) phenyl) pyridor2.3-d1pyrimidíntrihydrochlorid

Step 264a. 1- (4- (1-Methylimidazol-2-yl) phenyl) ethanone

A solution of N-methylimidazole (0.90 g, 11.0 mmol) in 12 mL of THF at -78 ° C was treated with n-BuLi (7.5 mL, 1 mL) at -78 ° C for 0.5 h. 6M solution in hexanes, 12.0 mmol). ZnCl ₂ (20 mL of a 1.0 M solution in Et ₂ O, 20 mmol) was then added and the solution was warmed to 25 ° C. To this solution was added Pd (PPh 3) 4 (70 mg, 0.06 mmol) followed by 4-iodoacetophenone ethylene acetal (prepared from iodoacetophenone and ethylene glycol in the presence of an acid catalyst by standard procedures) and the reaction mixture was refluxed for 4 h. The solution was then cooled to 25 ° C and diluted with the addition of saturated aqueous NaHCO 3 (10 mL). The aqueous layer was extracted with CH ₂ Cl ₂ and the combined organic layer was concentrated under reduced pressure. The residue was dissolved in 30 mL of THF, 15 mL of 3M aqueous HCl solution was added, and the mixture was stirred at 25 ° C for 2 h. The solution was neutralized by the addition of saturated aqueous NaHCO 3 and the aqueous layer was extracted with CH ₂ Cl ₂ . The combined organic layer was dried (MgSO 4) then concentrated under reduced pressure. The crude product was purified by flash chromatography to give the title compound (0.89 g, 64%).

Stage 264b. 4-Amino-5- (3-bromophenyl) -7- (4- (1-methyl-2-imidazolyl) phenyl) pyridine-2,3-di-pyrimidine trihydrochloride

Using the procedures of Example 244 but substituting component R ⁴ of step 244c with component R ⁴ of step 264a and second carrying out condensation with ammonium acetate to replace the solvent of ethanol in step 244c with dichloroethane, the title compound was prepared. MS (M + H) 458 (IBr); IR (cm ^-1 ) 3051, 2948, 1577, 1474, 1354.

108

Examples 265-267

Following the procedures of Example 244 but substituting the reagent R ⁴ in step 244 of Example 244 with the appropriate reagent listed in the table below, and performing the condensation with ammonium acetate substituting ethanol in step 244 of Example 244 with dichloroethane as solvent, the compounds were prepared. in Examples 264-285 In Example 266, the hydrochloride was not prepared.

Pr. no. Title Component R ⁴ (for position 7) Analytical data 265 4-Amino-5- (3-bromophenyl) -7 (4- (aminomethyl) phenyl) pyrido [2,3-d] pyrimidine trihydrochloride l- (4- (aminomethyl) - phenyl) -ethanone MS (M + H), 460; IR (cm ^-1 ) 3024, 2933, 1550, 1493, 1328 266 4-Amino-5- (3-bromophenyl) -7 (2-bromo-4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine trihydrochloride l- (2-bromo-4- (Dimethylamino) Fe- phenyl) -ethanone MS (M + H), 500 (2 Br.); IR (cm ^-1 ) 3049, 2949, 1536, 1468, 1320 267 4-Amino-5- (3-bromophenyl) -7 (4- (dimethylaminomethyl) phenyl) pyrido [2,3-d] pyrimidine dihydrochloride l- (4- (dimethyl- aminoethyl) phenyl) - ethanone MS (M + H), 488 (1H); IR (cm ^-1 ) 3420, 3000, 2980, 1635, 1610, 1590, 1435, 1415

Example 268

4-amino-5- (3-brómfeny0-7- (4- (3- (dimethylamino) propiny0fenyBpyridoí2.3-d] pyrimidine

A suspension of Example 63 (0.80 g, 1.59 mmol), PdCl 2 (PPh ₃ ) ₂ , CuI and 3dimethylaminoprop-1-yne in 20 mL DMF / TEA (4: 1) was heated at 50 ° C for 3 h. . The volatiles were removed under reduced pressure and the residue was purified by flash chromatography to give the title compound (0.50 g, 68%). MS (M + H), 459 (1H); IR (cm ^-1 ) 3027, 2964, 1513, 1470, 1360.

Examples 269-271

Using the procedures of Example 268, but substituting 3-dimethylaminoprop-1-yne for Example 268 with the appropriate reagent in the table below, the compounds shown in Table 2 were prepared.

109

Pr. no. Title agent Analytical data 269 4-Amino-5- (3-bromophenyl) -7- (4- (3 amino-3-methylbutinyl) phenyl) pyrido [2,3-d] pyrimidine trihydrochloride 1,1-dimethylpropargylamine MS (M + H), 459 (1H); IR (cm ^-1 ) 3041, 2967, 1562, 1484, 1319 270 4-Amino-5- (3-bromophenyl) -7- (4-dimethylphosphonato-phenyl) pyrido [2,3-d] pyrimidine trihydrochloride dimethyl phosphite MS (M + H), 486 (1H); IR (cm ^-1 ) 3105, 2912, 1625, 1437, 1350 271 4-Amino-5- (3-bromophenyl) -7- (4- (3 (methoxy-propynyl) pyrido [2,3-d] pyrimidine dihydrochloride) metylpropargyl- ether MS (M + H), 466 (1H); IR (cm ^-1 ) 3053, 2929, 1560, 1484, 1352

Example 272

4-atnino-5- (3-bromophenyl) -7- (4-carboxyphenyl) pyridor2.3-d1pyrimidín

A solution of 4-amino-5- (3-bromophenyl) -7- (4-cyanophenyl) pyrido [2,3-d] pyrimidine (Example 37, 0.47 g, 1.17 mmol) in 15 mL 6M HCl (aqueous solution) was heated at 60 ° C for 8 h. The mixture was lyophilized and the crude product was purified by flash chromatography to give the title compound (0.14 g, 28%), MS (M + H), 422 (1 Br), IR (cm ^-1 ) 3064, 2628, 1692, 1403 , 1273.

Example 273

4-amino-5- (3-bromophenyl) -7- (4-methyl-3-oxo-2H-4H-pyrídoí3.2-b1-1.4-oxazinyl) pyrido [ '2.3dlpyrimidín

Stage 273a. 7-acetyl-pyridof3.2-b1-1.4-oxazin-3 (4H) -one

To a solution of 2H-pyrido [3,2-b] -1,4-oxazin-3 (4H) -one (93.8 g, 65.27 mmol, Aldrich) in 120 mL THF / MeOH (5.1) was added 0 4 mL of concentrated HCl (aq) and then portionwise over 10 min N-bromosuccinimide (17.8 g, 100 mmol). After 12 h at 25 ° C, the reaction mixture was neutralized by addition of saturated aqueous NaHCO ₃ solution. The aqueous layer was extracted with CH 2 Cl 2 and the combined organic layer was dried (Na 2 SO 4, concentrated under reduced pressure and purified by flash chromatography to give 7-bromo-2H-pyrido). [3,2-b] -1,4-oxazin-3 (4H) -one (8.4 g, 56%) 7-Bromo-2H-pyrido [3,2-b] -1,4-oxazine- 3 (4H) -one (3.2 g, 14 mmol), tributyl (1-ethoxyvinyl) tin (6.1 g, 17 mmol), Pd ₂ (dba) ₃ (0.5 g, 0.56 mmol) and (2-furyl) ₃ P (0.3 g, 1.2 mmol) in 30 mL of toluene / THF (5: 1) was kept at reflux for 10 h, the reaction mixture was concentrated under reduced pressure and the residue was dissolved in 50 mL THF, was added 15 ml 4 M HC1 (aqueous) and the mixture was stirred for 4 h at 25 ° C. the solution was neutralized by addition of _NaHCO3 (aq) and the aqueous layer was extracted with CH2Cl2. the combined organic layer was dried (Na ₂ SO ₄ ), concentrated and the crude product was purified by digging flash chromatography to give 7-acetyl-2H-pyrido [3,2-b] -1,4-oxazin-3 (4H) -one (2.37 g, 88%) MS (M + H), 463 (1). br); IR (cm ^-1 ) 3400, 3200-2800, 1700, 1640, 1605, 1590, 1395, 1380, 1345

Stage 273b. 7-acetyl-4-methyl-2 H-pyridoľ3.2 b1-1.4-oxazin-3 (4H) -one

Methyl iodide and NaH in THF / DMF 1: 1 were added to the compound of step 273a over 6 h at 0 to 25 ° C. The reaction mixture was diluted with aqueous sodium bicarbonate solution, extracted with dichloromethane and the residue purified by chromatography to give the title compound. MS (M + H) 407

Step 273c, 4-Amino-5- (3-bromophenyl) -7- (4-methyl-3-oxo-2H-4H-pyrido [3,2-b] -1,4-oxazinyl) pyrido [2,3-dlpyrimidine]

Following the procedure of Example 244c, but substituting, for the first step, component R ⁴ in step 244c, 7-acetyl-4-methyl-2H-pyrido [3,2-b] -1,4-oxazin-3 (4H) -one from step 273b (Component R) ⁴ ) and, secondly, by condensation with ammonium acetate to replace ethanol as the solvent in step 244c with dichloroethane, the title compound MS (M + H), 463 (1 Br) was prepared; IR (cm ^-1 ) 3400, 3200-2800, 1700, 1640, 1605, 1590, 1395, 1380, 1345.

111

Example 274

4-amino-5- (3-brómfenyn-7- (4- (2-dimethylamino) ethyl) -3-oxo-2H-4H-pyridoí3.2-bl-1.4-oxazin-7ynpyridoí2.3-d1pyrimidín

Step 274a 7-Acetyl-4-dimethylaminoethyl-2H-pyrido [3,2-b] -1,4-oxazin-3 (4H) -one

To compound of step 273a was added 2-chloro (N, N-dimethyl) ethylamine.HCl and K ₂ CO ₃ under reflux in aqueous acetone. The mixture was diluted with water and extracted with dichloromethane and the residue was purified by chromatography to give the title compound.

Step 274b. 4-amino-5- (3-bromophenyl) -7- (4- (2- (dimethylamino) etyD-3-oxo-2H-4H-pyridor3.2b1-1.4-oxazin-7-yl) pyridor2.3-dlpyrimidín

Using the procedures of Example 244c but substituting component R ⁴ for step 244c

7-acetyl-4-dimethylaminoethyl-2H-pyrido [3,2-b] -1,4-oxazin-3 (4H) -one (component R ⁴ of step 273b) and, secondly, condensation with ammonium acetate with a replacement ethanol as solvent in step 244c with dichloroethane, the title compound was prepared. MS (M + H), 519 (1H); IR (cm ^-1 ) 3440, 1685, 1630, 1605, 1580, 1395.

Example 275

4-amino-5- (3-brómfeny0-7- (2,3-dihydro-3- (2-dimetylaminoetyD-oxobenzoxazol-6-yl) -pyrido [2,3-d1pvrimidín

Step 275a, 6-acetyl-2-benzoxazolinone

Using the procedures of Example 273a but substituting 2H-pyrido [3,2-b] -1,4-oxazin-3 (4H) -one for 2-benzoxazolinone (Aldrich), the title compound was prepared.

112

Step 275b. 6-acetyl-3- (dimethylaminoethyl) -2-benzoxazolinone

To the compound of step 275a was added 2-chloro- (N, N-dimethyl) ethylamine.HCl and K 2 CO 3 at reflux in aqueous acetone. The mixture was diluted with water and extracted with dichloromethane, and the residue was purified by chromatography to give the title compound.

Grade 275c. 4-amino-5- (3-bromophenyl) -7- (2,3-dihydro-3- (dimethylaminoethyl) -2-oxobenzoxazol6-yl) pyridor2.3-d1pyrimidín

Following the procedure of Example 244c but substituting the compound of step 275b for the component of R ⁴ in step 244c and the second condensation with ammonium acetate to replace ethanol as the solvent in step 244c with dichloroethane, the title compound was prepared. MS (M + H), 506 (1H); IR (cm ^-1 ) 3400, 3050, 1630, 1610, 1360.

Example 276

4-amino-5- (3-bromophenyl) -7- (4-methyl-3-oxo-2H-4 H -benzo-1.4-oxazin-7-yl) pyridor2.3dlpyrimidín

Step 276a, 6-Acetyl-3-methyl-2-benzoxazolinone

To the compound of Example 275a was added methyl iodide and NaH in THF / DMF 1: 1 over 6 h at 0 to 25 ° C. The reaction mixture was diluted with aqueous sodium bicarbonate solution, extracted with dichloromethane, and the residue purified by chromatography to give the title compound.

Step 276b, 1- (3-hydroxy-4-methylaminophenyl) ethanone

The compound of step 276a (1.60 g, 8.37 mmol) was dissolved in acetone (70 mL) and treated with 1M K 2 CO 3 aqueous solution while heating at reflux overnight.

113 (25 mL). The mixture was neutralized with acid, then extracted with diethyl ether. The solvent was dried (MgSO ₄ ) and removed in vacuo to give the title compound (2.01 g).

Step 276c 7-Acetyl-4-methyl-2H-4H-benzo-1,4-oxazin-3-one

The compound of step 276b (2.01 g, 8.37 mmol) was dissolved in DMSO and treated with sodium ethoxide (8.4 mmol) with heating at room temperature overnight. The mixture was diluted with water and ether and the title compound was isolated by filtration (0.48 g). MS (m + H) 206;

Step 276d, 4-Amino-5- (3-bromophenyl) -7- (4-methyl-3-oxo-2H-H-benzo-1,4-oxazin-7-yl) pyrido [2,3-dlpyrimidine

As in Example 244C but substituting, first component R ⁴ in step 244c the compound of step 276c (component R ^4), and secondly performing the condensation with ammonium acetate substituting ethanol as solvent in Example 244 step c, the title compound was prepared. MS (M + H), 462 (1H), IR (cm ^-1 ) 3500, 2800-3200, 1690, 1645, 1610, 1590, 1385, 1355.

Example 277

4-amino-5- (3-bromophenyl) -7- (2.2.4-trimethyl-3-oxo-2H-4 H -benzo-1.4-oxazin-7-yl) pyridoí2,3dlpyrimidin

Grade ΠΊ &. 7-acetyl-2.2.4-trimethyl-2H-benzo-4H-1,4-oxazin-3-one

The compound from step 276b (2.25 g, 9 mmol) was dissolved in DMSO and treated with sodium ethoxide (9 mmol) and 2-bromo-2-methylpentanoic acid (1.76 g, 9 mmol) overnight at room temperature. Dilute with water and extract with ether-ethyl acetate Ex114 tract dried (MgSO 4, solvent removed in vacuo and residue purified by chromatography (silica gel) to give the title compound (1.33 g) MS (M + H), 234

Step 277b. 4-amino-5- (3-bromophenyl) -7- (2.2.4-trimethyl-3-oxo-2H-4 H -benzo-1.4-oxazin-7-yl) pyridoí2.3-d1pyrimidín

Following the procedure of Example 244c but substituting the compound of step 277a for component R ⁴ in step 244c and the second condensation with ammonium acetate to replace ethanol as the solvent in step 244c with dichloroethane, the title compound was prepared. MS (M + H), 490 (1H); IR (cm ^-1 ) 3450, 2900-3100, 1680, 1645, 1610, 1515, 1385, 1365, 1165.

Example 278

4-amino-5-cyclohexyl-7- (4- (2-dimethylamino) ethyl) -2-4 H -benzo-3-oxo-1,4-oxazin-7-yl) pyridor2.3-dlpyrimidín

Step 278a, 1- (3-hydroxy-4- (2-dimethylamino) ethyl) phenyl) ethanone

A sample of 6-acetyl-3- (dimethylaminoethyl) -2-benzoxazolinone (from Example 275b) was dissolved in acetone and treated with 1M K 2 CO 3 aqueous solution overnight at reflux. The mixture was neutralized with acid, then extracted with diethyl ether. The solvent was dried (MgSO 4) and removed in vacuo to give the title compound

Step 278b. 7-acetyl-4- (dimethylamino) ethyl) -2H-4H-benzo-1.4-oxazin-3-one

A sample of the compound from step 278a (8.94 g, 32 mmol) was dissolved in DMSO and treated at room temperature with sodium ethoxide (32 mmol) and bromoacetic acid (5.34 g, 32 mmol) at room temperature for 2 days. then extracted with ether. extract

115 was dried (MgSO 4) and the solvent was removed in vacuo and the residue purified by chromatography (silica gel) to give the title compound (1.94 g, MS (M + H), 263

Step 278c, 4-Amino-5-cyclohexyl-7- (4- (dimethylamino) ethyl) -2H-4H-benzo-3-oxo-1,4-oxazin-7-yl) pyridine 2,3-pyrimidine

Following the procedure of Example 244c but substituting 1,1dicyano-3-cyclohexylethylene (prepared by the method of Moison et al., Tetrahedron (1987), 43: 537-542) for R ³ in step 244c by reacting cyclohexanecarboxyaldehyde with malononitrile in the presence of finely powdered magnesium chloride in dichloromethane) and replacing the component R ⁴ in Example 244c with the compound of step 278b and also condensing with ammonium acetate to replace ethanol as the solvent in step 244c with dichloroethane, the title compound MS (M + H), 447 (1 Br) was prepared. ); IR (cm ^-1 ) 3400, 2900, 1690, 1610, 1590, 1395.

Example 279

4-amino-5- (3-bromophenyl) -7- (5- (l-metyletyB-2-pyridyl) pyridor2.3-dlpvrimidín

Step 279a. l- (5-ethyl-2-pyridyl) ethanone

A solution of 2-acetyl-5-bromopyridine (1.45 g, 7.9 mmol), 2-propenyltrimethyltin (1.77 g, 8.7 mmol), Pd ₂ (dba) ₃ (0.33 g, 0.36) mmol) and tri-2-furylphosphine (0.47 g, 0.72 mmol) in 25 mL benzene were heated at 60 ° C for 4 h. The reaction mixture was concentrated and the condensed product was purified by flash chromatography (1.22 g, 96%). The product was dissolved in 25 mL of EtOH and purged with H ₂ stream. 10% Palladium on carbon (50 mg) in 0.5 mL EtOH was added and the reaction mixture was stirred under an atmosphere of H ₂ for 12 h. The reaction mixture was filtered and the resulting solution was concentrated under reduced pressure. The title compound 2 (1.04 g, 84%) was isolated after flash chromatography.

116

Stage 279b. 4-amino-5- (3-bromophenyl) -7- (5- (l-methylethyl) -2-pyridyl) pyrido [2.3-dlpyrimidín

Following the procedure of Example 244c but substituting the compound of step 279a for component R ⁴ in step 244c and the second condensation with ammonium acetate to replace ethanol as the solvent in step 244c with dichloroethane, the title compound MS (M + H), 421 was prepared. (1 Br); IR (cm ^-1 ) 3489, 2940, 1545, 1482, 1357.

Examples 280-281

Following the procedures of Example 244c but substituting the compound of Example ⁴ for Example 244 in step c with the following compound and condensing with ammonium acetate to replace ethanol in Example 244 for step 244 with dichloroethane as the solvent, the compounds shown in the table below were prepared.

EX Title Component R ⁴ (for position 7) Analytical data 280 4-Amino-5- (3-bromophenyl) -7 (5-piperidin-1-ylpyrid-2-yl) pyrido [2,3-d] pyrimidine 1- (5-piperidinyl-2-pyridyl) -ethanone * MS (M + H), 460 (Br); IR (cm ^-1 ) 3064, 2937, 1556, 1493, 1358 281 4-Amino-5- (1- (4-bromophenyl) ethyl-7- (6-morpholinylpyrid-3-yl) pyrido [2,3-d] pyrimidine 1- (2-Morpholinyl-5-pyridyl) -ethanone ** MS (M + H), 491 (1H); IR (cm ^-1 ) 1585, 1555, 1505, 1240, 1110, 940

Prepared as in Example 252b but substituting morpholine for bis (2-methoxyethyl) amine.

** Prepared by reacting 5-acetyl-2-chloropyridine with morpholine in refluxing ethanol.

Example 282

4-amino-5- (3-brómfenyB-7- (4- (f N-formvlamino) methyl) phenyl) pyridoí2.3-dlpyrimidin

Step 282a 4-Quanoacetophenone. acetal with 2,2-dimethylpropylene glycol

117

A sample of 4-cyanoacetophenone (4.35 g, 30 mmol) was dissolved in 150 mL of hexanes and to this was added 2,2-dimethylpropylene glycol (3.44 g, 33 mmol) and a catalytic amount (10 mg) of p-toluenesulfonic acid. The reaction mixture was heated under reflux conditions with a Dean-Stark condenser overnight and an additional portion of glycol (33 mmol) was added. The reaction was continued for 3 h, then the reaction mixture was cooled and the solvent removed. The residue was dissolved in ethyl acetate and this solution was washed with aqueous NaHCO 3, water, and brine and dried over MgSO _{4. The} solvent was evaporated in vacuo to give the title compound (7.46 g).

Step 282b, 4- (aminomethyl) acetophenone. acetal with 2,2-dimethylpropylene glycol

The compound of step 282a (2.31 g, 10 mmol) was dissolved in ether (50 mL) and stirred overnight at room temperature with lithium aluminum hydride (0.76 g, 20 mmol). The mixture was neutralized with MgSO ₄ .10H ₂ O and then diluted with ether. The mixture was filtered and the filtrate was removed to give the title compound.

Step 282c, 1- (4- (BOC-aminomethyl) phenyl) ethanone

The compound of step 282b (1.18 g, 5 mmol) was dissolved in THF (20 mL), 1 N HCl (20 mL) was added, and the mixture was stirred for 2 days. The volatiles were removed in vacuo, the residue was dissolved in THF (20 mL) and tert-dibutyl dicarbonate (2.18 g, 10 mmol) was added. The mixture was stirred at room temperature over the weekend. The solution was diluted with water and the mixture was extracted with ether and ethyl acetate. The organic extracts were dried (MgSO ₄ ) and the solvent removed in vacuo to give the title compound.

Step 282d 4-Amino-5- (3-bromophenyl) -7- (4- (N-formvlamino) methyl) phenyl) pyridine-2,3-dlpyrimidine

As in Example 244C but substituting, first component R ⁴ in step 244c the compound of step 282c (component R ^4), and secondly performing the condensation with acetate amón118 nym substituting ethanol as solvent in Example 244 step c, the title compound was prepared. MS (MH +). 434 (1H); IR (cm -1) 3440, 2700-3150, 1635, 1580, 1380

Example 283

4-Amino-5- (3-bromophenyl) -7- (4- (1-N-methylamino) -1-methylethyl) phenyl) pyrido [2,3-d] pyrimidine

Step 283a. 4- (l-amino-1-metyletyBacetofenón

CeCl 2 (10 g, 34.9 mmol) was suspended in THF (60 mL) and the mixture was cooled to -78 ° C. Methyl lithium (1.4 M, 2 mL) was added and the mixture was stirred for 20 min. The compound of Example 282a (acetal of 4-cyanoacetophenone with 2,2-dimethylpropylene glycol, (2.31 g, 10 mmol) in 2 mL of THF was then added. After stirring for 4 h, the mixture was allowed to warm to room temperature with stirring for 16 h. The reaction was quenched with water and ammonium hydroxide, filtered, the filtrate was extracted with dichloromethane, dried (MgSO ₄ ) and the solvent was evaporated to give the title compound.

Step 283b. 4- (l- (N-BOC-amino) -l-metyletvBacetofenón

Step 283a (2.32 g, 8.77 mmol) was treated sequentially with HCl and di-tert-butyl dicarbonate by the procedures of Example 282c to give the title compound (1.60 g). MS (M + H) 278.

Step 283c. 4-Amino-5- (3-bromophenyl-7- (4- (1- (N-formylamino) -1-methylethyl) phenyl) pyrido [2,3-d] pyrimidine

Following the procedure of Example 244c but substituting the component of stage 283b (component R ⁴ ) for component R ⁴ in step 244c and secondly condensing with ammonium acetate to replace ethanol as the solvent in stage 244c with dichloroethane, the title compound MS (M) was prepared. + H), 462 (1H); IR (cm ^-1 ) 3440, 1640, 1605, 1580, 1380.

119

Example 284

4-amino-5- (3-bromophenyl) -7- (4- (l- (N, N-dimethylamino) methyl-ethyl) fenyBpyridoí2.3-d1pyrimidín

Step 284a. 4- (l- (dimethylamino) -1-metyletvBacetofenón

The compound of step 283a (1.18 g, 5 mmol) was dissolved in 5 mL formic acid and 5 mL formalin (37%) was added. The mixture was heated to reflux for 4 h, then cooled and neutralized with 2N Na 2 CO ₃ . The mixture was extracted with dichloromethane. The solution was dried (MgSO ₄ ) and the solvent removed to give the title compound (0.94 g). MS (M + H), 462 (1H), ER (cm -1) 3520, 1640, 1610, 1580, 1375.

Examples 285-286

Using the procedures of Example 157, but substituting the components of R ³ and R ⁴ in Example 157 as shown in the table below, the compounds of Examples 285-286 were prepared. In Example 286, treatment with aqueous HCl was omitted and the free base was obtained.

Examples 285-286

Pr. in c. Title Component R3 (for position S) Component R ^ (for position 7) Analytical data 285 4-amino-5- (3-bromophenyl) - 7- (N-acetyl-5-indolinyl) - pyrido [2,3-d] pyrimidine l, l-dicyano (3- (3-bromophenyl) - propene l- (N-acetyl-5 indolinyl) -ethanone mp (hydrochloride)> 270 ° C. IR (cm ^-1 ) 3445, 3100-2500, 1640, 1605, 1445, 1395, 1325 LRMS [M + H] ⁺ m / z 460, 462; 286 4-amino-5-cyclohexyl-7- (6-chloro-3-pyridyl) - pyrido [2,3-d] pyrimidine, l, l-dicyano-3- cyclohexyl-ethene I- (6-chloro-3- pyridyl) ethanone mp 240-242 ° C. IR (cm ^-1 ) 3528, 3300, 3086, 2936, 1646, 1590, 1575, 1565, 1350. LRMS [M + H] ⁺ m / z 340.

120

Examples 287-300

Using the procedures of Example 157, but replacing the components R ³ and R ⁴ as shown in the table below, and replacing the formamide or formamidine with triethylorthoformate under reflux in the presence of a catalytic amount of ammonium sulfate followed by cooling to 25 ° C and addition of excess ammonia in ethanol, the compounds of Examples 287-300 were prepared. After 24 h, the precipitated amidine compound was filtered off and washed with hexanes and then dried in vacuo. The amidine compound was then heated to reflux with 1,2-dichloroethane for 1 to 8 h. The reaction mixture was cooled to room temperature and purified by chromatography, and the product was recrystallized if necessary. In some cases, treatment with aqueous HCl was omitted and the free bases were obtained.

Examples 287-300

Pr. in c. Title Component (for position 5) Component R ⁴ (for position 7) Analytical data 287 4-Amino-5- (1- (2-bromophenyl) ethyl-7- (6-dimethylamino-3-pyridyl) pyrido [2,3-d] pyrimidine l, l-dicyano-2- methyl (3- (2- bromophenyl) - propene l- (6- dimethylamino-3- pyridyl) ethanone IR (cm ^-1 ) 2600-3500, 1650, 1602, 1596, 1520. LRMS [M + H] ⁺ m / z 449, 451; 288 4-amino-5- (l- (2-bromophenyl) ethyl-7- (6morfolinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; l, l-dicyano-2- methyl (3- (2- bromophenyl) - propene l- (6-morpholinyl 3-pyridyl) - ethanone mp (dihydrochloride) 213-216 ° C IR (cm -1) 2400-3500, 1660, 1600. LRMS [M + H] ⁺ m / z 491 & 493. 289 4-amino-5- (l- (2- bromophenyl) ethyl) -7- (6- (N- methyl-N-formyl) amino) - 3-phenyl) -pyrido [2,3- pyrimidine l, l-dicyano-2- methyl (3- (2- bromophenyl) - propene l- (6- (N-methyl- N-formyl) - amino) -3- pyridyl) ethanone mp 252-253 ° C. IR (cm ^-1 ) 3515, 3310, 3200-2800, 1675, 1585, 1560, 1545, 1340 LRMS [M + H] ⁺ m / z 462.464 290 4-amino-5-cyclohexyl-7- (6-morpholinyl-3-pyridyl) - pyrido [2,3-d] pyrimidine l, l-dicyano-3- cyklehexyletén l- (6-morpholinyl 3-pyridyl) - ethanone 11 (dihydrochloride) 208-210 ° C IR (cm -1) 3490, 3300, 30503250, 1620, 1580, 1550, 1490. LRMS [M + H] ⁺ m / z 391.

121

291 4-amino-5 - ((2- bromophenyl) methyl) -7- (6- morpholinyl-3 pyridyl) pyrido [2,3-DJ- pyrimidine 1,1-dicyano- (3- (2-bromophenyl) - propene 1- (6-morpholinyl- 3-pyridyl) - ethanone mp (dihydrochloride) 201-204 ° C IR (cm -1) 3601, 3500, 3310, 2960, 2850, 1585, 1561, 1502, 1345 LRMS [M + H] + m / z 477, 479. 292 4-amino-5- (4- tetrahydropyranyl) -7- (6- morpholinyl-3 pyridyl) pyrido [2,3- pyrimidine 1,1-dicyano-3- (4-tetrahydropyranyl) ethene * l- (6-morpholinyl 3-pyridyl) - ethanone mp (dihydrochloride) 213-216 ° C. IR (cm ^-1 ) 3310, 3060, 2955, 1587, 1559, 1506, 1350. LRMS [M + H] + m / z 393. 293 4-Amino-5-cyclohexyl-7 (6-dimethylamino-3-pyridyl) -pyrido [2,3-d] pyrimidine l, l-dicyano-3- cyclohexyl- ethylene l- (6-dimethyl- amino-3- pyridyl) ethanone mp (dihydrochloride) 272-274 ° C. IR (cm ^-1 ) 3532, 3294, 3100, 2930, 2853, 1606, 1586, 1560, 1522, 1387. LRMS [M + H] + m / z 349. 294 4-amino-5- (l-ethyl- propyl) -7- (6-dimethyl- amino-3- pyridyl) pyrido [2,3-d] pyrimidine l, l-dicyano-3- etylpentén l- (6-dimethyl- amino-3- pyridyl) ethanone mp (free base) 223.5-225 ° C. IR (cm ^-1 ) 3480, 30003470, 2800-3000, 1630, 1610, 1580, 1565, 1520 LRMS [M + H] + m / z 337. 295 4-Amino-5-cyclopentyl-7 (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine l, l-dicyano-3- cyclopentyl-ethene 1- (6-morpholinyl) 3-pyridyl) - ethanone IR (cm ^-1 ) 3495, 3320, 3080, 2950, 1645, 1600, 1500, 1400, 1350, 1240. LRMS [M + H] + m / z 377. 296 4-Amino-5-cyclohexyl-7 (2-chloro-3-pyridyl) pyrido [2,3-d] pyrimidine l, l-dicyano-3- cyklohexyletén l- (2-chloro-3- pyridyl) ethanone IR (cm ^-1 ) 3305, 3155, 2930, 2855, 1590, 1610, 1590, 1545, 1345. LRMS [M + H] + m / z 340, 342. 297 4-Amino-5- (3,5-dimethyl-cyclohexyl) -7- (6-dimethylamino-3-pyridyl) -pyrido [2,3-d] pyrimidine l, l-dicyano-3- (3,5-dimethyl- cyclohexyl) ethene 1- (6-Dimethyl- amino-3- pyridyl) ethanone IR (cm ^-1 ) 3310, 3100, 2950, 1605, 1590, 1555, 1390, 1350 LRMS [M + H] + m / z 377

122

298 4-amino-5 - ((N- (Benzyloxycarbonyl) -4- piperidinyl) methyl) -7- (6- morpholinyl-3 pyridyl) pyrido [2,3-d] - pyrimidine 1,1-dicyano- (3- (4- (benzyloxy carbonyl) - piperidin-I-yl) - propene 1- (6-morpholinyl- 3-pyridyl) - ethanone IR (cm ^-1 ) 3538, 3311, 3032, 2925, 2852, 1696, 1585, 1560. LRMS [M + H] ⁺ m / z 540 299 4-amino-5-cyclohexyl-7- (6-bromo-3- pyridyl) pyrido [2,3-d] - pyrimidine l, l-dicyano-3- cyklohexyletén l- (6-bromo-3- pyridyl) ethanone mp 250-252 ° C, IR (cm ^-1 ) 3530, 3298, 3093, 2932, 2856, 1645, 1583, 1569, 1543, 1461, 1346 LRMS [M + H] ⁺ m / z 384, 386; 300 4-amino-5-cyclohexyl-7- (3- cyanophenyl) pyrido [2,3- pyrimidine l, l-dicyano-3- cyklohexyletén l- (3- cyanophenyl) - ethanone mp 223-224 ° C, IR (cm ^-1 ) 3528, 3298, 3075, 2937, 2235, 1645, 1586, 1548, 1567, 1463. LRMS [M + H] ⁺ m / z 332.

* 1,1-dicyano-3-cyclohexylethene was prepared according to the method of Moison, et al. (Tetrahedron, (1987), 43: 537-542) by treating cyclohexanecarboxaldehyde with malononitrile in the presence of finely powdered magnesium oxide in dichloromethane.

The reactants for the following examples were prepared in this way by replacing the cylohexanecarboxaldehyde used to prepare the component in Example 290 with the following compound:

Example 292: tetrahydropyran-4-carboxaldehyde.

Example 294: 2-Ethylbutanaldehyde.

Example 295: Cyclopentanecarboxaldehyde.

Example 297: 3,5-dimethylcyclohexanecarboxaldehyde.

Example 298: N- (phenylmethoxycarbonyl) piperidine-4-carboxaldehyde (prepared from N- (carbobenzyloxy) -4- (2-hydroxyethyl) piperidine (Brehm et al., Helv. Chim Acta 70; (1987), 1981) -1987 by treatment with TEMPO (2,2,6,6-tetramethylpiperidinyloxy) and potassium bromide in dichloromethane at 0 ° C with the addition of a commercial bleach (Clorox) containing sodium bicarbonate).

Examples 301-305

123

Using the procedures of Example 246 but substituting the methylamine in step (c) with the substances listed in the table below to obtain the correct R ⁴ component, and replacing the R ³ component in step (d) of Example 246 with the R ³ component below, Examples 301-305. Only in Example 302 was the solvent for the condensation of DMSO instead of ethanol and dimethoxyethane

Examples 301-305

Pr. in c. Title Component R ³ The component in step c Analytical data 301 4-amino-5- (l- (2- bromophenyl) ethyl-7- (6- dimethylamino-3- pyridazinyl) pyrido [2,3- pyrimidine l, l-dicyano (3- (2-bromophenyl) - propene dimethylamine mp (dihydrochloride)> 220 ° C. IR (cm ^-1 ) 3500-2400, 1640, 1610, 1580, 1370. LRMS [M + H] ⁺ m / z 450, 452; 302 4-amino-5- (3-bromophenyl) - 7- (6-imidazolyl-3 pyridazinyl) pyrido [2,3- d] pyrimidine Γ, Γ-dicyano (3-bromostyrene imidazole sodium mp (tetrahydrochloride) > 240 ° C. IR (cm ^-1 ) 3600-2400, 1640, 1610, 1590, 1560, 1415, 1370. LRMS [M + H] ⁺ m / z 445.447. 303 4-Amino-5- (3-bromophenyl) 7- (6- (azacycloheptanyl) 3-pyridazinyl) pyrido [2,3-d] pyrimidine Γ, Γ-dicyano (3-bromostyrene azacycloheptan 11, (dihydrochloride) > 190 ° C. IR (cm -1) 3455, 3100-2400, 1635, 1610, 1590, 1550, 1440, 1370. LRMS [M + H] ⁺ m / z 476, 478; 304 4-Amino-5- (3-bromophenyl) 7- (6- (N-methyl-N- (1-methylethyl) amino) -3 pyridazinyl) pyrido [2,3d] pyrimidine Γ, Γ-dicyano (3-bromostyrene N-methyl-N- (l- methyl-ethyl)) - amine 11, (dihydrochloride) > 210 ° C. IR (cm ^-1 ) 3455, 3100-2400, 1635, 1610, 1590, 1550, 1410, 1370 LRMS [M + H] ⁺ m / z 450, 452; 305 4-amino-5- (l- (2- bromophenyl) ethyl) -7- (6- morpholinyl-3 pyridazinyl) pyrido [2,3- d] pyrimidine l, l-dicyano (3- (2-bromophenyl) - propene morpholino IR (cm ^-1 ) 2475, 3113, 3100, 1650, 1620, 1580, 1555. LRMS [M + H] ⁺ m / z 492.494.

124

Example 306

4-amino-5-cyclohexyl-7- (6- (4-acetylpiperazinyl) -3-pyridyl) pyridoí2.3-d1pyrimidín

A mixture of 679 mg (2 mmol) of the compound of Example 298 and 1.28 g (10 mmol) of N-acetylpiperazine in 5 mL of DMSO was heated at 110 ° C for 5 h. On cooling a precipitate settled and was collected and washed with 20% methanol. and dried to give 647 mg of the product as orange flakes IR (cm ^-1 ) 3522, 3306, 3110, 2925, 2854, 1670, 1650, 1586, 1506. LRMS [M + H] + m / z 432.

Examples 307-322

Following the procedure of Example 306, but substituting the compound shown in the table below for the N-acetylpiperazine used in Example 306, the compounds shown in the table were prepared. The compounds were purified by HPLC chromatography.

EX Title component Analytical data 307 4-amino-5-cyclohexyl-7- (6- (4-acetyl-1,4-diazacycloheptanyl) -3pyridyl) pyrido [2,3-d] pyrimidine 1-Acetyl-heptane 1,4diazacyklo mp 169-171 ° C. IR (cm ^-1 ) 3535, 3309, 3093, 2930, 2854, 1638, 1605, 1587, 1558, 1513. LRMS [M + H] ⁺ 446; 308 4-amino-5-cyclohexyl-7- (6- (4-methyl-1,4-diazacycloheptanyl) -3pyridyl) pyrido [2,3-d] pyrimidine 1-methyl-heptan-1,4diazacyklo LRMS [M + H] + 419. 309 4-amino-5-cyclohexyl-7- (6- (N- methyl-N- (2- (2-pyridyl) ethyl) amino) - 3-pyridyl) pyrido [2,3-d] pyrimidine N-methyl-N- (2- (2- pyridyl) ethyl) amine LRMS [M + H] &lt; ⁺ &gt; 441. 310 4-amino-5-cyclohexyl-7- (6-2- (N- (N ', N'-dimethylaminoethyl) -N- methylamino) -3-pyridyl) pyrido [2,3- pyrimidine Ν, Ν-dimethyl, N‘- methyl-1,2- ethylene LRMS [M + H] &lt; ⁺ &gt; 421. 311 4-Amino-5-cyclohexyl-7- (6-azetidinyl-3-pyridyl) pyrido [2,3-d] pyrimidine azetidin LRMS [M + H] &lt; ⁺ &gt; 361

125

312 4-amino-5-cyclohexyl-7- (6- (3- (N- methylacetamido) - pyrrolidinyl) pyridyl) pyrido [2,3- d] pyrimidine N-methyl-N- (3- pyrrolidinyl) - acetamide LRMS [M + H] + 447 313 4-amino-5-cyclohexyl-7- (6- (3- (Formamido) pyrrolidinyl) pyridyl) - pyrido [2,3-d] pyrimidine pyrrolidine-2- formamide LRMS [M + H] + 419. 314 4-Amino-5-cyclohexyl-7- (4-oxo-1-phenyl-1,3,8-triazaspiro [4.5] (decan-8-yl) pyrido [2,3-d] pyrimidine 1-phenyl-1,3,8- triazaspiro [4.5J- decan-4-one LRMS [M + H] + 536 315 4-Amino-5-cyclohexyl-7- (6- (2 (methoxymethyl) pyrrolidin-1-yl) pyridyl-pyrido [2,3-d] pyrimidine) Of 2- (methoxy methyl) -pyrrolidine LRMS [M + H] + 420. 316 4-amino-5-cyclohexyl-7- (6- (N- methoxyethyl-N propylamino) pyridyl) pyrido [2,3- pyrimidine N- (methoxy-ethyl) - propylamine LRMS [M + H] + 421. 317 4-amino-5-cyclohexyl-7- (N-methyl- N- (2,2-dimethoxyethyl) amino) - pyrido [2,3-d] pyrimidine 2- (methyl amino) dimethyl acetaldehyde LRMS [M + H] + 429. 318 4-amino-5-cyclohexyl-7- (6- (4- (Dimethylamino) - piperidinyl) pyridyl) pyrido [2,3- pyrimidine N- (4-piperidinyl) - dimethylamine LRMS [M + H] + 433. 319 4-amino-5-cyclohexyl-7- (6- (4- (Aminocarbonyl) - piperidinyl) pyridyl) pyrido [2,3- pyrimidine piperidin-4 formamide LRMS [M + H] + 433. 320 4-Amino-5-cyclohexyl-7- (N-methyl-N- (3- (diethylamino) propyl) aminopyrid-3-yl) pyrido [2,3-d] pyrimidine N'.N'-diethyl-N ³ -methyl-1,3-propanediamine LRMS [M + H] + 449 321 4-amino-5-cyclohexyl-7- (6- (N- methyl-N- (4-pyridyl) ethylamino) - pyridin-3-yl) -pyrido [2,3-d-pyrimidine N-methyl (4- pyridyl) -ethylamine LRMS [M + H] + 441 322 4-amino-5-cyclohexyl-7- (6- (N- methyl-N- (3-pyridylmethyl) amino) - pyridin-3-yl) -pyrido [2,3-d] pyrimidine N-methyl- (3- pyridyl) - methylamine LRMS [M + H] + 427.

126

Example 323

4-Amino-5- (1- (2-bromophenyl) ethyl) -7- (1-methyl-5-indolypyridine-2,3-dlpyrimidine)

The procedure of Example 157 was followed, but substituting R ³ 'with 1', 1'-dicyano-3-bromostyrene and R ^{4 with} 1- (1-methyl-5-indolyl) ethanone. After 24 h, the precipitated amidine was filtered off and washed with hexanes and then dried under vacuum. The amidine was then heated to reflux in 1,2-dichloroethane for 1-8 h. The reaction mixture was cooled to room temperature and purified by chromatography, and then the product was recrystallized as necessary. Aqueous HCl treatment was omitted and free bases were obtained. IR (KBr) cm ^-1 3500, 1578, 1500; MS m / z 431 (M + H) &lt; + &gt;.

Example 324

4-Amino-5- (1- (2-bromophenyl) ethyl) 7- (1-methyl-2,3-dioxo-5-indolopyrido [2,3-d] pyrimidine)

The title compound was prepared from Example 323 by oxidation with CrO ₃ in sulfuric acid. IR (microscope) 3471, 1765, 1500 cm ^-1 ; MS m / z 461 (M + H) &lt; ^{+ &gt};.

Examples 325-326

Following the procedure of Example 157, but substituting the compounds R ³ and R ^{4 with the} appropriate compounds listed in the table below, the compounds of Examples 325-326 were prepared. After 24 h, the precipitated amidine was filtered off and washed with hexanes and then dried under vacuum. The amidine was then heated at reflux in 1,2-dichloroethane for 1-8 h. The reaction mixture was cooled to room temperature and purified by chromatography, and then the product was recrystallized as necessary. In some cases, aqueous HCl treatment was omitted and free bases were obtained.

127

Examples 325-326

Pr. w c. Title Ingredient (for position 5 Component R ⁴ (for position 7) Analytical data 325 4-amino-5- (3-bromophenyl) 7- (3-fluoro-4- (1-morpholinyl) phenyl) pyrido [2,3d] pyrimidine l ', l'-dicyano-3- bromostyrene l- (3-fluoro-4- (l- morpholinyl) - phenyl) -ethanone IR (microscope) 3443, 3044, 1639, 1606, 1584, 1520, 1362, 1245 cm ^-1 MS m / z 480 (M + H) ⁺ 326 4-Amino-5- (3-bromophenyl) 7- (4-hydroxy-3-nitrophenyl) pyrido [2,3-d] pyrimidine L, L-dicyano-3- bromostyrene l- (4-hydroxy-3- nitro-phenyl) - ethanone IR (KBr) 3461, 1623, 1579, 1548, 1523, 1353 cm ^-1 . MS m / z 438 (M + H) &lt; ^{+ &gt};.

Example 327

Following the procedure of Example 244, step c, but substituting R ^{4 for the} compound formed by reacting 2-acetyl-5-chloropyridine in refluxing ethanol with the following precursor (4-piperidinone methylene ketal) and replacing ethanol as solvent with dichloroethane, the following table was prepared.

Pr. no. Title precursor Analytical data 327 4-Amino-5- (3-bromophenyl) -7- (6- (4,4-ethylenedioxypiperidinyl) -3 pyridyl) pyrido [2,3-d] pyrimidine 4-piperidinón- one ethylene IR (microscope) 3091, 1602, 1580, 1558, 1512, 1353, 1236, 1103 cm ^-1 ; MS m / z 519 (M + H) &lt; ^{+ &gt};.

Example 328

4-amino-5- (3-brómfenyB-7- (6- (4-oxopiperidinyl) -3pyridyľ) pyridor2.3-pyrimidine

Treatment of Example 327 with dilute HCl afforded the title compound. IR (microscope) 3428, 3051, 1645, 1605, 1558, 1450, 1371, 1240 cm &^lt; -1 & gt ^; , MS m / z 475 (M + H) &lt; + &gt;

128

Examples 329-33 I

Following the procedure of Example 244, step c, but substituting the compound of R ^{4 with a} compound formed by reacting 2-acetyl-5-chloropyridine in refluxing ethanol with the following precursor and replacing ethanol as solvent with dichloroethane, the following compounds were prepared.

Examples 329-331

Pr. no. Title precursor Analytical data 329 4-amino-5- (3-bromophenyl) -7- (6- (4-formylpiperazinyl) -3- pyridyl) pyrido [2,3-d] pyrimidine piperazine IR (KBr) 3489, 1674, 1602, 1581, 1559, 1503, 1233, 1004 cm ^-1 ; MS m / z 491 (M + H) &lt; ⁺ &gt; ^. 330 4-Amino-5- (3-bromophenyl) -7 (6- (4-methylpiperazinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine methylpiperazine ER. (microscope) 3438, 3051, 1540 cm ^-1 ; MS m / z 477 (M + H) &lt; ^{+ &gt};. 331 4-Amino-5- (3-bromophenyl) -7 (6-thiomorpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine thiomorpholine IR (KBr) 3486, 1602, 1581, 1560, 1502, 1228 cm &^lt; -1 &gt;; MS m / z 479 (M + H) &lt; ^{+ &gt};.

Example 332

4-amino-5- (3-bromophenyl) -7- (6- (4,4-dioxothiomorpholinyl) -3-pyridyl) pyridor-2,3-dlpyrimidine

Treatment of Example 331 with 4-chloroperbenzoic acid in methanol and dichloromethane afforded the title compound. IR (microscope) 3471, 1601, 1581, 1562, 1510, 1353, 1316, 1285, 1122 cm ^-1 ; MS m / z 511 (M + H) &lt; ^{+ &gt};.

Example 333

4-amino-5- (2-bromophenyl) -7- (6-morpholinyl) -3-pyridyl) pyridof2.3-dlpyrímidin

Stage 333a l. 1-Dicyano-2-bromostyrene

129

The title compound was prepared by condensation of 2-bromobenzaldehyde with malononitrile and MgO in dichloromethane by a standard procedure of Broekhuis et al (Red. J. R. Neth. Chem. Soc., 99 6-12 (1980)).

Step 333b. 5-acetyl-2-morfoliny1pyridin

The title compound was prepared by reacting 5-acetyl-2-chloropyridine with morpholine in refluxing ethanol.

Grade 333c. 4- (2-bromophenyl) -3-cyano-6-morfolinylpyridín-2-amine

The title compound was prepared by condensation of r, r-dicyano-2-bromostyrene with 5-acetyl-2-morpholinylpyridine and ammonium acetate at reflux in dichloroethane. After completion of the reaction (TLC), the mixture was cooled and the solvent removed. The residue was triturated with methanol to give the product.

Stage 333d. 4-amino-5- (2-brómfeny0-7- (6-morpholinyl-3-pyridyl) pyridor2.3-d1pyrimidín

A sample of 4- (2-bromophenyl) -3-cyano-6-morpholinylpyridin-2-amine was heated in formamide at 180-190 ° C. The reaction was monitored by TLC and once complete, the mixture was cooled to room temperature. The product was allowed to precipitate, then was filtered and washed with water. Additional product was extracted from the filtrate. The product was purified by column chromatography eluting with 10% MeOH / CH 2 Cl 2. IR (microscope) 3493, 1547, 1109 cm ^-1 . MS m / z 464 (M + H) &lt; ^{+ &gt};.

Examples 334-336

Following the procedure of Example 333, but substituting 2-bromobenzaldehyde in step (a) with the following aldehyde precursor and treating the product as in steps 333b-d, the compounds listed in the table below were prepared.

130

Examples 334-336

Pr. no. Title aldehyde prodrug Analytical data 334 4-amino-5- (3-bromo-4- methoxyphenyl) -7- (6-morpholinyl-3 pyridyl) pyrido [2,3-d] pyrimidine 3-bromo-4- metoxybenz- aldehyde IR (microscope) 3486, 1600, 1575, 1562, 1500, 1260, 1237 cm ^-1 ; MS m / z 493 (M + H) &lt; ⁺ &gt; ^. 335 4-Amino-5- (4-bromophenyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine 4-bromo- benzaldehyde CR (microscope) 3497, 1532, 1098 cm ^-1 , MS m / z 464 (M + H) ⁺ . 336 4-Amino-5- (3-chlorophenyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine 3-chloro- benzaldehyde IR (microscope) 3484, 1500, 1034 cm ^-1 ; MS m / z 587 (M + H) &lt; + &gt;.

Example 337

4-amino-5- (3-bromophenyl) -7- (5-chloro-6-morfolinyn-3-pyridyDpyridor2.3-d1pyrimidín

Using the procedures of Example 333 but substituting 2-bromobenzaldehyde in step (a) with 3-bromobenzaldehyde, replacing 5-acetyl-2-chloropyridine in step (b) with 5-acetyl-2,3-dichloropyridine to give 5-acetyl-3-chloro-2 morpholinylpyridine, and replacing 5-acetyl-2-morpholinylpyridine in step (c) with 5-acetyl-3-chloro-2-morpholinylpyridine and treating the product as in step 333d, to give the title compound. IR (microscope) 3493, 1635, 1585, 1555, 1492, 1340, 1241, 1113 cm ^-1 ; MS / m / z 497 (M + H) ⁺ .

Example 338

4-amino-5- (3-bromophenyl) -7- (6-f N-oxidomorfolinyl) -3-pyridyl) pvridoí2.3-d1pyrimidín

The title compound was prepared by reacting the compound of Example 134 with hydrogen peroxide in acetic acid according to standard procedures. IR (microscope) 3486, 1579, 1552, 1353, 1121, 1020 cm &^lt; -1 & gt ^; , MS m / z 479 (M + H) &lt; - &gt;

131

Example 339

4-amino-5- (3-brómfenyn-7- (6- (N- (2-hydroxyetoxyetvl) amino) -3-pyridyl) pyrido [2.3-dlpyrimidín

Step 339a. l, l-dicyano-3-bromostyrene

The title compound was prepared by condensation of 3-bromobenzaldehyde with malononitrile and MgO in dichloromethane by a standard procedure of Broekhuis et al. {Recl. J. Neth. Chem. Soc., 99: 6-12 (1980)).

Step 339b. 5-acetyl-2- (N- (2-ethoxyethyl) amino) pyridine

The title compound was prepared by reacting 5-acetyl-2-chloropyridine with 2-ethoxyethylamine in refluxing ethanol.

Step 339c. 4- (3-bromophenyl) -3-cyano-6- (N- (2-ethoxyethyl) amino) pyridin-2-amine

The title compound was prepared by condensation of r, r-dicyano-2-bromostyrene with 5-acetyl-2-morpholinylpyridine and ammonium acetate in dichloroethane at reflux. Upon completion of the reaction (TLC), the mixture was cooled and the solvent removed. The residue was triturated with methanol to give the product.

Step 339d. 4-amino-5- (2-bromophenyl) -7- (6- (N- (2-ethoxyethyl) amino) -3-pyridyl) pyrido [2,3-d] pyrimidine

A sample of the compound from step 239d was treated as in step 233d to give the title compound. IR (microscope) 3301, 1610, 1579, 1543, 1346, 1304, 1120 cm ^-1 ; MS m / z 481 (M + H) &lt; + &gt; ^.

Example 340

132

4-amino-5- (3-bromophenyl-7- (6-FN- (2-hydroxyethoxyethyl) -N-formylamino) -3-pyridyl) pyrido [2.3djpyrimidín

This compound was isolated by chromatography as the product of the reaction described in Example 239d IR (microscope) 3306, 1679, 1596, 1577, 1548, 1493, 1352, 1125 cm ^-1 ; MS m / z 509 (M + H) &lt; - &gt;

Example 341

4-amino-5- (3-brómfenyD-7- (6- (N- (2-hydroxvetoxyetyl) -3-pyridyl N-oxide) pyridor2,3dlpyrimidín

The title compound was prepared by reacting the compound of Example 341 with hydrogen peroxide in acetic acid according to standard procedures. IR (microscope) 3296, 1628, 1560, 1411, 1353 cm ^-1 ; MS m / z 497 (M + H) &lt; ^{+ &gt};.

Example 342

4-amino-5- (3-brómfenyD-7- (6- (3-hydroxy) morfolinyD-3-pyridyl) pyridof2.3-d1pyrimidín

The title compound was prepared by reacting the compound of Example 328 with lithium aluminum hydride reduction followed by work-up according to standard procedures. IR (microscope) 3349, 1510, 1116 cm ^-1 ; MS m / z 478 (M + H) &lt; ⁺ &gt; ^.

Example 343 1- (5- (4-Amino-5- (3-bromo-phenyl) -pyrido-2,3-dl-pyrimidin-7-yl) -2-pyridyl) -piperidine-4-phosphate. disodium salt

The title compound was prepared from Example 342 by POCl ₃ followed by standard procedures. IR (microscope) 3498, 1500, 1444 cm ^-1 ; MS m / z 556 (M + H) &lt; ^{+ &gt};.

133

Example 344

4-amino-5- (3-brómfenyB-7- (6- (2-hydroxy) rnorfolinyn-3-pyridynpyridoí2.3-d] pyrimidine

The title compound was prepared from Example 339 by oxidation of the free hydroxy group to the aldehyde by TEMPO. During processing of the mixture, the compound itself condensed to give the title compound. IR (microscope) cm ^-1 ; MS m / z 492 (M + CH ₃ OH-H ₂ O) ⁴ .

Example 345

4-amino-5- (3-brómfenyD-7- (4-methylenylpiperidinyl) -3-pyridyl) pyridor2.3-dlpyrimidin

The title compound was prepared from Example 328 by treatment with methyltriphenylphosphine bromide in DMSO at -78 ° C. After diluting and warming the mixture to room temperature, the title compound was extracted and then chromatographed. IR (microscope) 3055, 1602, 1559, 1508, 1440, 1344, 1174 cm @ -1; MS n / z 473 (M + H) ⁺ .

Example 346

4-amino-5- (3-bromophenyl) -7- (4-hydroxy-4- (hydroxymetyBpiperidinyl) -3-pyridyDpyridoí2.3dlpyrimidin

The title compound was prepared from Example 345 by treatment with OsO ₄ in DMSO at room temperature. After dilution, the title compound was extracted and then chromatographed. IR (microscope) 3304, 1603, 1580, 1557, 1509, 1352, 1241 cm ^-1 ; MS m / z 507 (M + H) &lt; - &gt;

Example 347

4-amino-5- (3-bromophenyl) -7- (6- (4,4-etyléndioxypiperidinyľ) -3-pyridyl) pyridof2.3-dlpyrimidin

134

Step 347a of 1,1-dicyano-3-cyclohexylethene

1,1-Dicyano-3-cyclohexylethene was prepared according to the method of Moison et al. (Tetrahedron (1987), 43 537-542), by reacting cyclohexanecarboxaldehyde with malononitrile in the presence of finely powdered magnesium oxide in dichloromethane

Step 347b. 2-acetyl-5- (4,4-etyléndioxypiperidinyl) pyridine

A sample of 2-acetyl-5-chloropyridine in refluxing ethanol was treated with 4-piperidinone methylene ketal to give the title compound.

Step 347c. 4-Amino-5-cyclohexyl-7- (6- (4,4-ethylenedioxypiperidinyl-3-pyridylpyrido-2,3-d) pyrimidine

Using the procedure of Example 339 Step (c), but substituting the 337a and 339b for the compounds of 339a and 339b, and treating the product according to the 339d step, the title compound was prepared. IR (microscope) 2929, 1604, 1585, 1557, 1514, 1426, 1344, 1238, 1106 cm ^-1 ; MS m / z 447 (M + H) &lt; ^{+ &gt};.

Example 348

4-amino-5-cyclohexyl-7- (6- (4-oxopiperidinyD-3-pyridyDpyridor2.3-d1pyrimidín

The title compound was prepared from Example 347 by treatment with dilute HCl in ethanol. The title compound was purified by chromatography. IR (microscope) 2928, 1715, 1603, 1585, 1559, 1507, 1344, 1226 cm ^-1 ; MS m / z 403 (M + H) &lt; ^{+ &gt};.

Example 349

4-amino-5-cyclohexyl-7- (6- (4-methylenylpiperidinyl) -3-pyridyl) pyrido [2.3-d1pyrimidín

135

The title compound was prepared from Example 348 by treatment with methyltriphenylphosphine bromide in DMSO at -78 ° C. After dilution and warming to room temperature, the title compound was extracted and then chromatographed. IR (microscope) 2929, 1604, 1584, 1557, 1506, 1342, 1239 cm ^-1 ; MS m / z 401 (M + H) &lt; ^{+ &gt};.

Example 350

4-N- (iminometynamino-5-cyclohexyl-7- (6-dimethylamino-3-pyridyl) pyridor2.3-d1pyrimidin

The title compound was isolated from the reaction mixture of Example 293 as a by-product. IR ⁽ cm ^-1 ) 3289, 3089, 2930, 2841, 1674, 1606, 1559, 1531. LRMS [M + H] ⁺ m / z 376;

Claims (20)

PATENT CLAIMS Use of a compound of formula I (I) wherein R ¹ and R ² are independently selected from the group consisting of H, lower alkyl, C 1 -C 6 alkoxyC 1 -C 6 alkyl, arylC 1 -C 6 alkyl, -C (O) C 1 -C 6 alkyl, -C (O) aryl, -C (O) heterocycle or may be joined with the nitrogen to which they are attached, to a 5- to 7-membered ring, optionally containing 1 to 2 additional heteroatoms selected from the group consisting of O, N or S; r 3 is selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heterocyclic, heteroarylalkyl or heterocycloalkyl, wherein the heteroaryl and heterocyclic groups are attached directly or indirectly by a ring carbon; R 6 is selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heterocyclic, heteroarylalkyl or heterocycloalkyl and a dotted line - indicates that a double bond is optionally present as long as the correct valencies are maintained, or a pharmaceutically acceptable salt or amide thereof, for the manufacture of a medicament for inhibiting adenosine kinase in a mammal. 137 Use of a compound of formula I according to claim 1, wherein R ¹ and R ² are independently selected from the group consisting of H, lower alkyl, arylC 1 -C 6 alkyl, C (O) C 1 -C 6 alkyl, -C (O) aryl, -C (O) heterocycle or may be together with the nitrogen to which are bonded to a 5-7 membered ring optionally containing 1 to 2 additional heteroatoms selected from O, N, or S; R ³ and R 4 are independently selected from the group consisting of: C-COalkyl, C 2 -C 6 alkenyl, C2-C6 alkynyl, C 3 -C 8 cycloalkyl, heteroarylC 0 -C 6 alkyl or substituted heteroaryl C 0 -C 6 alkyl, optionally substituted cycloalkyl, arylC 0 -C 6 alkyl or substituted arylC 0 -C 6 alkyl, heteroarylC 2 -C 6 alkenyl or substituted heteroaryl C 2 -C 6 alkenyl, arylC 2 -C 6 alkenyl or substituted heteroC 2 -C 6 alkenyl, -C 6 alkynyl, arylC 2 -C 6 alkynyl or substituted arylC 2 -C (alkynyl) wherein 1-4 heteroaryl or aryl substituents are independently selected from the group consisting of halogen, oxo, CO 2 R ⁵ , cyanoC 1 -C 6 alkyl, heteroarylC 0 -C 6 alkyl, heterocycle C 0 -C 6 alkyl, C 1 -C 6 alkyloxy, C 1 -C 6 alkyloxyC 1 -C 6 alkyl, arylC 0 -C 6 alkyl, arylC 1 -C 6 alkykyloxy, R ⁵ R ⁶ NC (O), cyano, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyldialkylmalonyl, CF 3, HO-, C 1 -C 6 C 6 alkylSOn wherein n is 1-2, C 1 -C 6 alkylthio, C 1 -C 6 alkylacryl, CF 3 O, CF 3, C 1 -C 4 alkylenedioxy, C 1 -C 6 alkylacryl, R 6 R 6 N (CO) NR 5, N-formyl (heterocycle), NO 2, NR 6 R 6 COalkyl , (R ⁵ O) (R ⁶ O) -P (O) -C ₀ -C ₆ alkyl, wherein R 5 and R 6 are independently selected from the group consisting of H, C 1 -C 6 alkyl, HC (O), C 1 -C 6 alkyloxyC 1 - C 6 alkyl, C 1 -C 6 alkyloxy, C 1 -C 6 alkylC (O), CF 3 C (O), 138 NR ⁷ R ⁸ C 1 -C 6 alkyl, phthalimidoC 1 -C 6 C (O), C 1 -C 6 alkylSOn where n is 1 to 2, CNC 1 C 6 alkyl, R ⁷ R ⁸ NC (O) NR ⁷ -, heteroaryl, NR ⁷ R ⁸ C 1 -C 6 alkylC ( O), C 1 -C 6 alkyloxycarbamidoC 1 -C 6 alkyl, wherein R ⁷ and R ⁸ are independently selected from the group consisting of R ⁵ and R ^6, or R 5 and R ⁶ or R ⁷ and R ⁸ may be taken together with the nitrogen to which they are attached to a 5-7 membered unsubstituted or substituted ring, optionally containing 1 to 3 additional heteroatoms selected from the group consisting of O, N or S wherein the substituents are selected from the group consisting of C 1 -C 6 alkyl and dashed line - indicates that a double bond is optionally present. Use according to claim 2, wherein the compound has the formula II _σΐ) wherein R ¹ to R ⁸ and n are as defined in claim 2. The use of claim 3, wherein R 1 is selected from the group consisting of: phenyl; thiophen-2-yl; 3-methyl-2-oxobenzoxazolin-6-yl; 2- (dimethylamino) -5-pyrimidinyl; 2- (N-formyl-N-methylamino) -5-pyrimidinyl; 2- (N-methoxyethyl-N-methylamino) -5-pyrimidinyl; 2- (N-methylamino) 5-pyrimidinyl; 2- (1-morpholinyl) -5-pyrimidinyl; 2- (1-pyrrolidinyl) -5-pyrimidinyl; 2-dimethylamino-5-pyrimidinyl; 2-furanyl; 2-oxobenzoxazolin-6-yl; 2-pyridyl; 3 (dimethylamino) phenyl; 3-amino-4-methoxy-phenyl; 3-bromo-4- (dimethylamino) phenyl; 3-methoxyphenyl; 3-methyl-4- (N-acetyl-N-methylamino) phenyl; 3-methyl-4- (N-formyl-N-methyl-139min) phenyl; 3-methyl-4- (N-methyl-N- (trifluoroacetyl) amino) phenyl; 3-methyl-4- (N-methylamino) phenyl, 3-methyl-4-pyrrolidinylphenyl; 3-pyridyl; 3,4-dichlorophenyl; 3,4-methylenedioxyphenyl; 3,4,5-trimethoxyphenyl; 4- (acetylamino) phenyl; 4- (dimethylamino) -3-fluorophenyl; 4- (dimethylamino) phenyl; 4- (imidazol-l-yl) phenyl; 4- (methylthio) phenyl; 4- (morpholinyl) phenyl; 4- (N- (2 (dimethylamino) ethyl) amino) phenyl; 4- (N- (2-methoxyethyl) amino) phenyl; 4- (N-acetyl-N-methylamino) phenyl; 4- (N-ethyl-N-formylamino) phenyl; 4- (N-ethylamino) phenyl; 4- (N-formyl-N- (2-methoxyethyl) amino) phenyl; 4- (N-isopropylamino) phenyl; 4- (N-methyl-N - ((2-dimethylamino) ethyl) amino) phenyl; 4- (N-methyl-N- (2- (N-phthalimidyl) acetyl) amino) phenyl; 4- (N-methyl-N- (2-cyano) ethylamino) phenyl; 4- (N-methyl-N- (2-methoxyethyl) amino) phenyl; 4- (N-methyl-N- (3-methoxy) propionylamino) phenyl; 4- (N-methyl-N-acetylamino) phenyl; 4- (N-methyl-Nformylamino) phenyl; 4- (N-methyl-N-amino) -phenyl; 4- (N-morpholinyl) phenyl; 4 (thiophen-2-yl) phenyl; 4- (ureido) phenyl; 4- (2- (dimethylamino) acetylamino) phenyl; 4- (2-methoxy) acetylamino) ethyl) amino) phenyl; 4- (2-methoxy) ethoxyphenyl; 4- (2-oxo-3-oxazolidinyl) phenyl; 4- (4-methoxy-2-butyl) phenyl; 4- (4-methylpiperidinyl) phenyl; 4- (5-pyrimidinyl) phenyl; 4-amino-phenyl; 4-bromo-phenyl; 4-butoxy-phenyl; 4-carboxamidophenyl; 4-chlorophenyl; 4-cyanophenyl; 4diethylaminophenyl; 4-diethylmalonylallylphenyl; 4-dimethylaminophenyl; 4-ethoxyphenyl; 4-ethylphenyl; 4-fluorophenyl; 4-hydroxyphenyl; 4-imidazolylphenyl; 4-iodophenyl; 4-isopropyl-phenyl; 4-methoxyphenyl; 4-methylaminophenyl; 4-methylsulfonylphenyl; 4-morpholinyl-phenyl; 4-N- (2- (dimethylamino) ethyl) -N-formylamino) phenyl; 4-N- (3-methoxypropionyl) -N-isopropylamino) phenyl; 4-N-ethyl-N- (2-methoxyethyl) amino) phenyl; 4-N-formylpiperazinyl-phenyl), 4-nitrophenyl; 4piperidinylphenyl; 4- (3-pyridyl) phenyl; 4pyrolidinylfenyl; 4-t-butylacrylphenyl; 5- (dimethylamino) thiophen-2-yl; 5-amino-2-pyridyl; 5dimetylamino-2-pyrazinyl; 3-dimetylaminopyridazin-6-yl; 5-dimethylamino-2-pyridyl; 5pyrimidinylfenyl; 6- (N-methyl-N-formylamino) -3-pyridinyl; 6- (N-methyl-N-methoxy-ethylamino) -3-pyridinyl; 6- (2-oxo-3-oxazolidinyl) -3-pyridinyl; 6-dimethylamino-3-pyridinyl; 6imidazolyl-3-pyridinyl; 6-morpholinyl-3-pyridinyl; 6-pyrrolidinyl-3-pyridinyl; 6- (2-propyl) -3-pyridinyl and (4-formyl-amino) phenyl. The use of claim 3, wherein R ³ is selected from the group consisting of (thiophen-2-yl) methyl; (Thiophen-3-yl) methyl; butyl; cycloheptyl; pentyl; thiophen-2-yl; l- (3-bromophenyl) ethyl; 2- (Nfenylmetoxykarbonyl) aminophenyl; 2- (3-bromophenyl) ethyl; 2- (3-cyanophenyl) methyl; 2- (4140 bromophenyl) ethyl; 2- (5-chloro-2- (thiophen-3-yl) phenyl; 2-bromophenyl; 2-furanyl; 2-methylpropyl; 2-phenylethyl; phenylmethyl; 2,3-dimethoxyphenyl; 2,3-methylenedioxyphenyl; 3- (furan) 2-yl) phenyl; 3 (thiophen-2-yl) phenyl; 3- (2-pyridyl) phenyl; 3- (3-methoxybenzyl) phenyl; 2- (3-aminopropinyl) phenylmethyl; 3-benzyloxyphenyl; 3- bromo-4-fluorophenyl; 3-bromo-5-iodophenyl; 3-bromo-5-methoxyphenyl; 3-bromophenyl; 3-bromophenyl) methyl; 3carboxamidophenyl; 3-chlorophenyl; 3-cyanophenyl; 3-diethylmalonylallylphenyl; 3-dimethylamino-phenyl; 3-ethoxyphenyl; 3-fluoro-5trifluórmetylfenyl; 3-fluorophenyl; 3-hydroxyphenyl; 3-iodophenyl; 3-methoxyethyoxyphenyl; 3-methoxyphenyl; 3-methylphenyl; 3-methylsulfonylphenyl; 3-methylthiophenyl; 3-t-butylacrylphenyl; 3trifluórmetoxyfenyl; 3-trifluoromethylphenyl; 3-vinylpyridinylphenyl; 3,4-dichlorophenyl; 3,4-dimethoxyphenyl; 3,4-methylenedioxyphenyl; 3,4,5-trimethoxyphenyl; 3,5-di (trifluoromethyl) phenyl; 3,5-dibromophenyl; 3,5-dichlorophenyl; 3,5-dimethoxyphenyl; 3,5-dimethyl-phenyl; 4- (2-propyl) phenyl; 4- (2-propyl) oxyphenyl; 4-benzyloxyphenyl; 4-bromophenyl; 4-bromo-thiophen-2-yl; 4-butoxy-phenyl; 4dímetylaminofenyl; 4-fluoro-3-trifluoromethylphenyl; 4-methoxyphenyl; 4-neopentylphenyl; 4-phenoxyphenyl; 5-bromo-thiophen-2-yl; 5-cyclohexyl; 5-cyclopropyl; 5-hexyl; 5-methyl; 5-phenyl; (2-bromo-5-chlorophenyl) methyl; (2-bromophenyl) methyl and (5-chloro-2- (3-methoxyphenyl) phenyl) methyl. The use of claim 1, wherein the compound is selected from the group consisting of: 4-amino-5- (4-dimethylaminophenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (4-dimethylaminophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-methoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-dimethylaminophenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4- (2-propyl) phenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-neopentylphenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-butyloxyphenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-methoxyphenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (4- (2-propyl) phenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-butoxy-phenyl) -7- (4-N-formylpiperazinylphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-benzyloxyphenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 141 4-amino-5- (4-phenoxyphenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4- (2-propyl) phenyl) -7- (4-diethylmalonylallylphenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (4- (2-propyl) phenyl) -7- (4-t-butylacrylphenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3,4-dimethoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-t-butylacrylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-methoxyphenyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dimethoxyphenyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-diethylmalonylallylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-vinylpyridinylfenyI) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-trifluoromethylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-carboxamidophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-cyanophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-benzyloxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-methoxyphenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-butoxy-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3- (2-pyridyl) phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-methylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-chlorophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-fluorophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-methoxyphenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7-phenyl-pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-ethyl-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-cyanophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-hydroxyphenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-iodophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-ethoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-trifluórmetyloxyfenyl) 7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 142 4-amino-5- (3,5-dichlorophenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-4-fluorophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-hydroxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-piperidinylphenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (imidazol-l-yl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-chloro-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-isopropyl-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-trifluorophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-dietyIaminofenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3,4,5-trimethoxy-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3- (3-methoxybenzyl) phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-methoxyethyloxyphenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3,4-methylenedioxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-ethoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- ^(2, thiophene) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-fluoro-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-dimethylaminophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5-phenyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3,4,5-trimethoxyphenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-nitrophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-iodo-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3,4-methylenedioxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (thiophen-2-yl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dimethoxyphenyl) -7- (thiophen-2-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-carboxamidophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (2-methoxy) ethoxyphenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dimethoxyphenyl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-trifluoromethylphenyl) -7- (thiophen-2-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-amino-phenyl) -pyrido [2,3-d] pyrimidine; 143 4-amino-5- (3-bromo-4-fluorophenyl) -7- (thiophen-2-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-4-fluorophenyl) -7- (2-furanyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dimethoxyphenyl) -7- (4-iodo-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dimethoxyphenyl) -7- (4-imidazolylphenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dimethoxyphenyl) -7- (4- (thiophen-2-yl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dimethoxyphenyl) -7- (4- (3-pyridyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (4-methylpiperidinyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-pyrrolidinylphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-bromothiophene -) - 7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-bromo-thiophen-2-yl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine; 4-morpholinyl-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (5-bromo-thiophen-2-yl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (acetylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dimethoxyphenyl) -7- (5-pyrimidinylphenyl) pyrido [2,3-d] pyrimidine; 4- (4-fluorophenyl) amino) -5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-bromo-thiophen-2-yl) -7- (4-pyrolidinyIfenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-bromo-thiophen-2-yl) -7- (thiophen-2-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5- (dimethylamino) thiophen-2-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-5-iodophenyl) -7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-di (trifluoromethyl) phenyl) -7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-di (trifluoromethyl) phenyl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dibromophenyl) -7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dibromophenyl) -7- (4-morfolmylfenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-bromo-thiophen-2-yl) -7- (4- (4-methylpiperidinyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dibromophenyl) -7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-methylsulfonylphenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 144 4-amino-5- (3-bromophenyl) -7- (4- (methylthio) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3,4-dichlorophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N-formylamino) phenyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-4-fluorophenyl) -7- (4-metylsuIfbnylfenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3-amino-4-methoxy-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3-bromo-4- (dimethylamino) phenyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N-trifluoro-acetylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (dimethylamino) -3-fluorophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N-ethyl-N-formylamino) phenyl) pyrido [2,3-d] pyrimidine; 4,4-bis (acetylamino) -5- (3-bromophenyl) -7- (4- (N-methyl-N-acetylamino) phenyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (4- (N-acetyl-N-methylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N-ethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (2-methoxyethyl) amino) phenyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (4- (N-isopropylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-N-ethyl-N- (2-methoxyethyl) amino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-N- (3-methoxypropionyl) -N-isopropylamino) phenyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-N- (2- (dimethylamino) ethyl) -N-formylamino) phenyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (4- (N- (2- (dimethylamino) ethyl) amino) phenyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (2-cyano) ethylamino) phenyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (3-methoxy) propionylamino) phenyl) pyrido [2,3djpyrimidín; 145 4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (N-formyl-N-methylamino) phenyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (N-methylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (4-methoxy-2-butyl) phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (2- (N-phthalimidyl) acetyl) amino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (N-methyl-N- (trifluoroacetyl) amino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (N-acetyl-N-methylamino) phenyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (6-dimethylamino-3-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-cyanophenyl) -7- (4-methylsulfonylphenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-cyanophenyl) -7- (4- (N-methyl-N-formylamino) phenyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (N-methyl-N-formylamino) -3-pyridinyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (6-morpholinyl-3-pyridinyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (N-methyl-N-methoxy-ethylamino) -3-pyridinyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (6-pyrrolidinyl-3-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (2- (dimethylamino) -5-pyrimidinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (2- (N-methoxyethyl-N-methylamino) -5-pyrimidinyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (2- (N-formyl-N-methylamino) -5-pyrimidinyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (2- (N-methylamino) 5-pyrimidinyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (2- (l-pyrrolidinyl) -5-pyrimidinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (2- (l-morpholinyl) -5-pyrimidinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (2-oxo-3-oxazolidinyl) -3-pyridinyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (2-pyridyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3-pyridyl) pyrido [2,3-pyrimidine; 146 4-amino-5- (3- (thiophen-2-yl) phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3- (furan-2-yl) phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3- (3-methoxyphenyl) phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine, 4-amino-5-phenyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-chlorophenyl) -7- (4- (rnorfolinyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-4-fluorophenyl) -7- (4- (morpholinyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-chlorophenyl) -7- (4-iodo-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-chlorophenyl) -7- (4- (thiophen-2-yl) phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-chlorophenyl) -7- (4- (5-pyrimidinyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-4-fluorophenyl) -7- (4-iodophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (4-bromo-thiophen-2-yl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) methyl-7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (2-phenylethyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (2-methylpropyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (butyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (2- (4-bromophenyl) ethyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (butyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (2- (3-cyanophenyl) methyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (2- (N-phenylmethoxycarbonyl) aminoethyl) -7- (4-dimethylaminophenyl) -pyrido [2,3djpyrimidín; 4-amino-5- (cycloheptyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (2- (5-chloro-2- (thiophen-3-yl) phenylmethyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (pentyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5-hexyl-7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (2- (3-bromophenyl) ethyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5 - ((2-bromophenyl) methyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5-cyclopropyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5 - ((2-bromo-5-chlorophenyl) methyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 147 4-amino-5-methyl-7- (4diethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (2,3-methylenedioxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d} pyrimidine; 4-amino-5- (3-fluoro-5-trifluoromethylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-pyrimidine; 4-amino-5- (2-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-pyrimidine; 4-amino-5- (3,5-dimethylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3,4-dichlorophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-fluoro-3-trifluoromethyl-phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-5-methoxyphenyl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-5-methoxyphenyl) -7- (4-pyrrolidinylphenyl) -pyrido [2,3-pyrimidine; 4-amino-5- (3-bromo-5-methoxyphenyl) -7- (4-piperidinylphenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-5-methoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-methylthiophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-5-methoxyphenyl) -7- (thiophen-2-yl) -pyrido [2,3-pyrimidine; 4-amino-5- (2,3-dimethoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-methylsulfonylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-pyrimidine; 4-acetylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-formylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4- (methoxyacetyl) amino-5- (3-bromophenyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-trifluoro-acetylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-pyrimidine; 4-pentanoylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-benzoylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-pyrimidine; 4- (N-BOC-glycyl) amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4 - (/ V-phthalimidylglycyl) amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3djpyrimidín; 4- (ethoxycarbonyl) amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-pyrimidine; 4- (ethylaminocarbonyl) amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3djpyrimidín; 4-allylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4- (2- (N, N-dimethylamino) ethylamino) -5- (4-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3djpyrimidín; 148 4- (4- (N, N-dimethylamino) butylamino) -5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3djpyrimidín; 4- (N-allyl-N-formylamino) -5- (4-dimethylaminophenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine; 4-diacetyIamino-5- (p-dimethylaminophenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5-amino-2-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5-dimethylamino-2-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5-dimethylamino-2-pyrazinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (2-oxobenzoxazolin-6-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (l-methyl-2-oxobenzoxazolin-6-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5 - ((5-chloro-2- (3-methoxyphenyl) phenyl) methyl) -7- (4-dimethylaminophenyl) -pyrido [2,3djpyrimidín; 4-amino-5 - ((thiophen-2-yl) methyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-pyrimidine; 4-amino-5 - ((thiophen-3-yl) methyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5 - ((2-bromophenyl) methyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N-formyl-N- (2-methoxyethyl) amino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N- (2-methoxyethyl) amino) phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N - ((2-dimethylamino) ethyl) amino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (2-methoxy) acetylamino) ethyl) amino) phenyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7 - ((4-formylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (2- (dimethylamino) acetylamino) phenyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (2-oxo-3-oxazolidinyl) phenyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (2-propyl) -3-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3-methyl-4pyrrolidinylphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-imidazolyl-3-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5-phenylmethyl-7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (2- (3aminopropynyl) phenylmethyl) -7- (4-dietyIaminofenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (l- (3-bromophenyl) ethyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-pyrimidine; 149 4-amino-5- (4-dimethylaminophenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (2-furanyl) -7- (4- (N-morpholinyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (2-dimethylamino-5-pyrimidinyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (ureido) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (l-phenylmethyl-3-piperidinyl) -7- (4diethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (3-methyl-5-izoxazoIyl)) - 3-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-chloro-3-pyridinyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-methoxy-3-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (l, 2,4-triazol-4-yl) -3-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (2-morpholinyl-5-pyrimidinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (2-thiazolyl) -7- (4-pyrrolidinylphenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-pyrazolyl-3-pyridinyl)) - pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (l-methyl-ureido) phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (2-pyrimidinyl) amino) phenyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (3-fluoro-4- (N-formyl-N-methylamino) phenyl) -pyrido [2,3djpyrimidín; 4-formylamino-5- (3-bromophenyl) -7- (3-fluoro-4- (N-formyl-N-methylamino) phenyl) -pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N-methylsulfonylamino) phenyl) -pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (6- (N-methyl-N-methylsulfonylamino) -3- pyridinyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (l-methyl-5-indolinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (l-methyl-5-benzimidazolyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-dimethylamino-3-pyridazinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-morpholinyl-3-pyridazinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-pyrrolidinyl-3-pyridazinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5-morpholinyl-2-pyrazinyl) pyrido [2,3-d] pyrimidine; 150 4-amino-5- (3-bromophenyl) -7- (5- (N- (2-methoxyethyl) -N-methylamino) -2-pyrazinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (morfolmylmetyl) phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5- (N, N-bis (2-methoxyethyl) amino) -2-pyridinyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (4- (imidazolyImetyl) phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5- (l-morpholinyl) -2-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4 - ((dimethylamino) methyl) phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5- (4-hydroxy-l-piperidinyl) -2-pyridinyl) pyrido [2,3djpyrimidín, 4-amino-5- (3-bromophenyl) -7- (5- (N-formyl-N-methylamino) -2-pyridinyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (5- (2-propenyl) -2-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3- (2-methoxy-ethyl) -2-oxo-6-benzoxazolyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (4- (l- (N-formylamino) ethyl) phenyl) pyrido [2,3-d] pyrimidine; 4- (methylamino) -5- (3-bromophenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine hydrochloride; 4- (2-methoxyethylamino) -5- (3-bromophenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine hydrochloride; 4-amino-5- (3-bromophenyl) -7- (4- (1-methyl-2-imidazolyl) phenyl) pyrido [2,3-d] pyrimidine trihydrochloride; 4-amino-5- (3-bromophenyl) -7- (4- (aminomethyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (2-bromo-4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (dimethylaminoethyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (3- (dimethylamino) propynyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (3-amino-3-methylbutynyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-dimethylphosphonatophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (3- (metoxypropinyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-carboxyphenyl) -pyrido [2,3-d] pyrimidine; 151 4-amino-5- (3-bromophenyl) -7- (4-methyl-3-oxo-2H-4H-pyrido [3,2-b] -l, 4-oxazin-7-yl) -pyrido [2, 3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (2- (dimethylamino) ethyl) -3-oxo-2H-4H-pyrido [3,2-b-l 4oxazin-7-yl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (2,3-dihydro-3- (dimethylaminoethyl) -2-oxobenzoxazol-6-yl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-methyl-3-oxo-2H-4H-benzo-l, 4-oxazin-7-yl) -pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (2,2,4-trimethyl-3-oxo-2H-4H-benzo-l, 4-oxazin-7-yl) -pyrido [2,3-pyrimidine; 4-amino-5-cyclohexyl-7- (4- (2-dimethylamino) ethyl) -2-4 H -benzo-3-oxo-4-oxazin-7-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5- (l-methylethyl) -2-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5-piperidin-l-yl-pyridin-2-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (1- (4-bromophenyl) ethyl) -7- (6-morpholinylpyrid-3-yl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4 - ((N-formylamino) methyl) phenyl) -pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (l-methyl-l- (N-methylamino) ethyl) phenyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (l-dimethylamino) -l-methylethyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (N-acetyl-5-indolinyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6-chloro-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (l- (2-bromophenyl) ethyl) -7- (6-diethylamino-3-pyridyl) pyrido [2,3-pyrimidine; 4-amino-5- (l- (2-bromophenyl) ethyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-pyrimidine; 4-amino-5- (l- (2-bromophenyl) ethyl-7- (4- (N-methyl-N-formyl) amino) phenyl) -pyrido [2,3djpyrimidín; 4-amino-5-cyclohexyl-7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5 - ((2-bromophenyl) methyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (4-tetrahydropyranyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-pyrimidine; 4-amino-5-cyclohexyl-7- (6-dimethylamino-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (l-ethyl-propyl) -7- (6-dimethylamino-3-pyridyl) pyrido [2,3-pyrimidine; 4-Amino-5-cyclopentyl-7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 152 4-amino-5-cyclohexyl-7- (2-chloro-3-pyridyl) pyrido [2,3-pyrimidine; 4-amino-5- (3,5-dimetyIcyklohexyl) -7- (6-dimethylamino-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5 - ((N- (benzyloxycarbonyl) -4-piperidinyl) methyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6-bromo-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (3-cyano-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (l- (2-bromophenyl) ethyl) -7- (6-dimethylamino-3-pyridazinyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-imidazolyl-3-pyridazinyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (azacycloheptanyl) -3-pyridazinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-N-methyl-N- (l-methylethyl) amino) -3-pyridazinyl) pyrido [2,3djpyrimidín; 4-amino-5- (l- (2-bromophenyl) -7- (6-morpholinyl-3-pyridazinyl) pyrido [2,3-pyrimidine; 4-amino-5-cyclohexyl-7- (6- (4-acetylpiperazinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6- (4-acetyl-l, 4-diazacycloheptanyl) -3-pyridyl) pyrido [2,3djpyrimidín, 4-amino-5-cyclohexyl-7- (6- (4-methyl-l, 4-diazacycloheptanyl) -3-pyridyl) pyrido [2,3djpyrimidín; 4-amino-5-cyclohexyl-7- (6- (N-methyl-N- (2- (2-pyridyl) ethyl) amino) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6-2- (N- (N ', N' -dimethylaminoethyl) -N-methylamino) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6-azetidinyl-3-pyridyl) pyrido [2,3-pyrimidine; 4-amino-5-cyclohexyl-7- (6- (3- (N-methylacetamido) pyrrolidinyl) pyridyl) pyrido [2,3djpyrimidín; 4-amino-5-cyclohexyl-7- (6- (3-formamido) pyrrolidinyl) pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (4-oxo-1-phenyl-1,3,8-triazaspiro [4.5] decan-8-yl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6- (2-methoxymethyl) pyrrolidin-l-yl) pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6- (N-methoxyethyl-N-propylamino) pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (N-methyl-N- (2,2-dimethoxyethyl) amino) pyrido [2,3-d] pyrimidine; 153 4-amino-5-cyclohexyl-7- (6- (4-dimethylamino) piperidinyl) pyridyl) pyrido [2,3-d] pyrimidine, 4-amino-5-cyclohexyl-7- (6- (4-aminocarbonyl) piperidinyl) pyridyl) pyrido [2,3-d] pyrimidine, 4-amino-5-cyclohexyl-7- (N-methyl-N- (3- (diethylamino) propyl) aminopyridin-3-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6- (N-methyl-N- (4-pyridyl) ethylamino) pyrid-3-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6- (N-methyl-N- (3-pyridylmethylamino) pyrid-3-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (1- (2-bromophenyl) ethyl) -7- (1-methyl-5-indolyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (1- (2-bromophenyl) ethyl) -7- (1-methyl-2,3-dioxo-5-indolyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3-fluoro-4- (1-morpholinyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-hydroxy-3-nitrophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (4,4-etyléndioxypiperidinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (4-oxopiperidinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (4-formylpiperazinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (4-methyl piperidinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-thiomorpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (4,4-dioxo-thiomorpholinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (2-bromophenyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-4-methoxyphenyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (4-bromophenyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-chlorophenyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5-chloro-6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (N-oxidomorfolinyI) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (N- (2-hydroxyethoxyethyl) amino) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (N- (2-hydroxyethoxyethyl) -N-formylamino) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (N- (2-hydroxyethoxyethyl) -3-pyridyl N-oxide) pyrido [2,3-d] pyrimidine; 154 4-amino-5- (3-bromophenyl) -7- (6- (3-hydroxy) morpholinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine; 1- (5- (4-amino-5- (3-bromophenyl) pyrido [2,3-d] pyrimidin-7-yl) -2-pyridyl) piperidine-4-phosphate disodium salt; 4-amino-5- (3-bromophenyl) -7- (4-methylenylpiperidinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-hydroxy-4- (hydroxymethyl) piperidinyl) -3-pyridyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (6- (4,4-etyléndioxypiperidinyl) -3-pyridyl) pyrido [2,3djpyrimidín; 4-amino-5-cyclohexyl-7- (6- (4-oxopiperidinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6- (4-methylenylpiperidinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-N- (iminomethyl) amino-5-cyclohexyl-7- (6-dimethylamino-3pyridyl) pyrido [2,3-d] pyrimidine. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically acceptable carrier. Use of a compound of formula I or Π according to claim 1 or 3 for the preparation of a medicament for the treatment of ischemia, neurological disorders, nociperception, inflammation, immunosuppression, gastrointestinal dysfunction, diabetes and sepsis in a mammal. Use of a compound of formula I or II according to claim 1 or 3 for the preparation of a medicament for the treatment of cerebral ischemia, myocardial ischemia, angina, graft surgery in coronary bypass, percutaneous transluminal angioplasty, stroke, thrombotic and embolic states, epilepsy, anxiety, schizophrenia pain, neuropathic pain, visceral pain, arthritis, sepsis, diabetes and abnormal gastrointestinal motility. 10. A method of inhibiting adenosine kinase comprising administering a compound of formula I 155 (d) where R 1 and R 2 are independently selected from the group consisting of H, lower alkyl, C 1 -C 6 alkoxyC 1 -C 6 alkyl, arylC 1 -C 6 alkyl, -C (O) C 1 -C 6 alkyl, -C (O) aryl, -C (O) heterocycle or may be linked to the nitrogen to which they are attached to a 5-7 membered ring optionally containing 1 to 2 additional heteroatoms selected from the group consisting of O, N or S; r 3 is selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heterocyclic, heteroarylalkyl or heterocycloalkyl, wherein the heteroaryl and heterocyclic groups are attached directly or indirectly by a ring carbon; R 6 is selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heterocyclic, heteroarylalkyl or heterocycloalkyl and a dotted line - indicates that a double bond is optionally present if the correct valences are maintained, or a pharmaceutically acceptable salt or amide thereof, in vitro. A compound of formula I wherein (I) 156 R ¹ and R ² are independently selected from the group consisting of H, lower alkyl, C 1 -C 6 alkoxyC 1 -C 6 alkyl, arylC 1 -C 6 alkyl, -C (O) C 1 -C 6 alkyl, -C (O) aryl, -C (O) heterocycle or may be bonded to the nitrogen to which they are attached to form a 5-7 membered ring, optionally containing 1 to 2 additional heteroatoms selected from O, N, or S; R ³ is selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heterocyclic, heteroarylalkyl or heterocycloalkyl, wherein the heteroaryl and heterocyclic group are attached directly or indirectly by a ring carbon; R ⁴¹ is selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heterocyclic, heteroarylalkyl or heterocycloalkyl, and a dotted line - indicates that a double bond is optionally present as long as proper valencies are maintained; or a pharmaceutically acceptable salt or amide thereof, with the proviso that the compound may not be selected from the group consisting of: (a) 4-amino-5- (4-chlorophenyl) -7- (4-nitrophenyl) pyrido [2,3-d] pyrimidine; (b) 4-amino-5- (4-methoxyphenyl) -7- (4-nitrophenyl) pyrido [2,3-d] pyrimidine; (c) 4-amino-5- (4-fluorophenyl) -7- (4-fluorophenyl) pyrido [2,3-d] pyrimidine; (d) 4-amino-5- (4-chlorophenyl) -7- (4-fluorophenyl) pyrido [2,3-d] pyrimidine; (e) 4-amino-5-phenyl-7- (4-aminophenyl) pyrido [2,3-d] pyrimidine; (f) 4-amino-5-phenyl-7- (4-bromophenyl) pyrido [2,3-d] pyrimidine; (g) 4-amino-5- (4-methoxyphenyl) -7- (4-aminophenyl) pyrido [2,3-d] pyrimidine; (h) 4-amino-5- (4-methoxyphenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyriniidine; and (i) 4-amino-5,7-diphenylpyrido [2,3-d] pyrimidine . A compound according to claim 11 of formula II (II), wherein 157 R 1 and R 2 are independently selected from the group consisting of H, lower alkyl, arylC 1 -C 6 alkyl, C (O) C 1 -C 6 alkyl, -C (O) aryl, -C (O) heterocycle, or may be joined together with nitrogen to which they are attached and form a 5 to 7 membered ring, optionally containing 1 to 2 additional heteroatoms selected from the group consisting of O, N or S; R 3 and R 4 are independently selected from the group consisting of: C-COalkyl, C 2 -C 6 alkenyl, C2-C6 alkynyl, C 3 -C 8 cycloalkyl, heteroarylC 0 -C 6 alkyl or substituted heteroaryl C 0 -C 6 alkyl, optionally substituted cycloalkyl, arylC 0 -C 6 alkyl or substituted arylC 0 -C 6 alkyl, heteroaryl C 2 -C 6 alkenyl or substituted heteroaryl C 2 -C 6 alkenyl, arylC 2 -C 6 alkenyl or substituted heteroC 2 -C 6 alkenyl, -C 6 alkynyl, arylC 2 -C 6 alkynyl or substituted arylC 2 -C 6 alkynyl wherein 1-4 heteroaryl or aryl substituents are independently selected from the group consisting of halogen, oxo, CO ₂ R ⁵ , cyanoC 1 -C 6 alkyl, heteroarylC 0 -C 6 alkyl, heterocycle C 0 -C 6 alkyl, C 1 -C 6 alkykyloxy, C 1 -C 6 alkynyl -C 6 alkyloxyC 1 -C 6 alkyl, arylC 0 -C 6 alkyl, arylC 1 -C 6 alkykyloxy, R 6 R ⁶ NC (O), cyano, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyldialkylmalonyl, CF 3, HO- n is 1-2, C 1 -C 6 alkylthio, C 1 -C 6 alkylacryl, CF 3 O, CF 3, C 1 -C 4 alkylenedioxy, C 1 -C 6 alkylacryl, R 6 R ⁶ N (CO) NR ⁵ , N-formyl (heterocycle), NO 2, NR ⁵ R ⁶ Co- C6 alkyl, (R ⁵ O) (R ⁶ O) -P (O) -C ₀ -C ₆ alkyl, wherein r 5 and R 6 are independently selected from the group consisting of H, C 1 -C 6 alkyl, HC (O), C 1 -C 6 alkyloxyCi -C 6 alkyl, C 1 -C 6 alkyloxy, C 1 -C 6 alkylC (O), CF ³ C (O), NR ⁷ R ⁸ C ¹ -C 6 alkyl, phthalimidoC ¹ -C ⁶ C (O), C 1 -C 6 alkylSO _n where n is 1-2, CNCi158 C 6 alkyl, R ⁷ R ⁸ NC (O) NR ⁷ -, heteroaryl, NR ⁷ R ⁸ C ¹ -C 6 alkylC (O), C ¹ -C 6 alkyloxycarbamidoC 1 -C 6 alkyl, wherein R ⁷ and R ⁸ are independently selected from the group consisting of R 6 and R 6 ^ or R 5 _and R 6 or R ⁷ and R ⁸ may be combined with the nitrogen atom to which they are attached form a 5 to 7 membered unsubstituted or substituted ring optionally containing 1-3 additional heteroatoms selected from O, N or s, wherein the substituents are selected from the group consisting of C 1 -C 6 alkyl; and with the proviso that the compound may not be selected from the group consisting of: (a) 4-amino-5- (4-chlorophenyl) -7- (4-nitrophenyl) pyrido [2,3-d] pyrimidine; (b) 4-amino-5- (4-methoxyphenyl) -7- (4-nitrophenyl) pyrido [2,3-d] pyrimidine; (c) 4-amino-5- (4-fluorophenyl) -7- (4-fluorophenyl) pyrido [2,3-d] pyrimidine; (d) 4-amino-5- (4-chlorophenyl) -7- (4-fluorophenyl) pyrido [2,3-d] pyrimidine; (e) 4-amino-5-phenyl-7- (4-aminophenyl) pyrido [2,3-d] pyrimidine; (f) 4-amino-5-phenyl-7- (4-bromophenyl) pyrido [2,3-d] pyrimidine; (g) 4-amino-5- (4-methoxyphenyl) -7- (4-aminophenyl) pyrido [2,3-d] pyrimidine; (h) 4-amino-5- (4-methoxyphenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine; and (i) 4-amino-5,7-diphenylpyrido [2,3-d] ] pyrimidine. The compound of claim 11, wherein R ⁴ is selected from the group consisting of: phenyl; thiophen-2-yl; 3-Methyl-2-oxobenzoxazolin-6-yl; 2- (dimethylamino) -5-pyrimidinyl; 2- (N-formyl-N-methylamino) -5-pyrimidinyl; 2- (N-methoxyethyl-N-methylamino) -5-pyrimidinyl; 2- (N-methylamino) 5-pyrimidinyl; 2- (l-morpholinyl) -5-pyrimidinyl; 2- (l-pyrrolidinyl) -5-pyrimidinyl; 2-dimethylamino-5-pyrimidinyl; 2-furanyl; 2-oxobenzoxazolin-6-yl; 2-pyridyl; 3- (dimethylamino) phenyl; 3-amino-4-methoxy-phenyl; 3-bromo-4- (dimethylamino) phenyl; 3-methoxyphenyl; 3-methyl-4- (N-acetyl-N-methylamino) phenyl; 3-methyl-4- (N-formyl-N-methylamino) phenyl; 3-methyl-4- (N-methyl-N- (trifluoroacetyl) amino) phenyl; 3-methyl-4- (N-methylamino) phenyl; 3-methyl-4pyrolidinylfenyl; 3-pyridyl; 3,4-dichlorophenyl; 3,4-methylenedioxyphenyl; 3,4,5-trimethoxyphenyl; 4- (acetylamino) phenyl; 4- (dimethylamino) -3-fluorophenyl; 4- (dimethylamino) phenyl; 4- (imidazol-159-yl) phenyl; 4- (methylthio) phenyl; 4- (morpholinyl) phenyl; 4- (N- (2- (dimethylamino) ethyl) amino) phenyl; 4- (N- (2-methoxyethyl) amino) phenyl; 4- (N-acetyl-N-methylamino) phenyl; 4- (N-ethyl-N-formylamino) phenyl; 4- (N-ethylamino) phenyl; 4- (N-formyl-N- (2-methoxyethyl) amino) phenyl; 4- (N-isopropylamino) phenyl; 4- (N-methyl-N - ((2dimetylamino) ethyl) amino) phenyl; 4- (N-methyl-N- (2- (N-phthalimidyl) acetyl) amino) phenyl; 4- (NmetyI-N- (2-cyano) ethylamino) phenyl; 4- (N-methyl-N- (2-methoxyethyl) amino) phenyl; 4- (N-methyl-N- (3-methoxy) propionylamino) phenyl; 4- (N-methyl-N-acetylamino) phenyl; 4- (N-methyl-Nformylamino) phenyl; 4- (N-methyl-N-amino) -phenyl; 4- (N-morpholinyl) phenyl; 4 (thiophen-2-yl) phenyl; 4- (ureido) phenyl; 4- (2- (dimethylamino) acetylamino) phenyl; 4- (2-methoxy) acetylamino) ethyl) amino) phenyl; 4- (2-methoxy) ethoxyphenyl; 4- (2-oxo-3 oxazolidinyl) phenyl; 4- (4-methoxy-2-butyl) phenyl; 4- (4-methylpiperidinyl) phenyl; 4- (5pyrimidinyl) phenyl; 4-aminophenyl; 4-bromophenyl) 4-butoxyphenyl; 4-carboxamidophenyl; 4-chlorophenyl; 4-cyanophenyl; 4diethylaminophenyl; 4-diethylmalonylalylphenyl, 4-dimethylaminophenyl, 4-ethoxyphenyl; 4-ethylphenyl; 4-fluorophenyl; 4-hydroxyphenyl; 4imidazolylfenyl; 4-iodophenyl; 4-isopropyl-phenyl; 4-methoxyphenyl, 4-methylaminophenyl; 4-methylsulfonylphenyl; 4morpholinylphenyl; 4-N- (2- (dimethylamino) ethyl) -N-formylamino) phenyl; 4N- (3-methoxypropionyl) -N-isopropylamino) phenyl; 4-N-ethyl-N- (2-methoxyethyl) amino) phenyl; 4-N-formylpiperazinylphenyl, 4-nitrophenyl; 4piperidinylphenyl; 4- (3-pyridyl) phenyl; 4pyrolidinylfenyl; 4-t-butylacrylphenyl; 5- (dimethylamino) thiophen-2-yl; 5-amino-2-pyridyl; 5dimetylamino-2-pyrazinyl; 5-dimethylamino-2-pyridyl; 5-pyrimidinyl-phenyl; 6- (N-methyl-Nformylamino) -3-pyridinyl; 6- (N-methyl-N-methoxy-ethylamino) -3-pyridinyl; 6- (2-oxo 3-oxazolidinyl) -3-pyridinyl; 6-dimethylamino-3-pyridinyl; 6-imidazolyl-3-pyridinyl; 6morfolinyl-3-pyridinyl; 6-pyrrolidinyl-3-pyridinyl; 6- (2-propyl) -3-pyridinyl and (4-formylamino) phenyl. The compound of claim 11, wherein R ³ is selected from the group consisting of: (thiophen-2-yl) methyl; (Thiophen-3-yl) methyl; butyl; cycloheptyl; pentyl; thiophen-2-yl; l- (3-bromophenyl) ethyl; 2- (Nfenylmetoxykarbonyl) aminophenyl; 2- (3-bromophenyl) ethyl; 2- (3-cyanophenyl) methyl; 2- (4-bromophenyl) ethyl; 2- (5-chloro-2- (thiophen-3-yl) phenyl; 2-bromophenyl; 2-furanyl; 2-methylpropyl; 2-phenylethyl; phenylmethyl; 2,3-dimethoxyphenyl; 2,3-methylenedioxyphenyl; 3- (furan) 2-yl) phenyl; 3 (thiophen-2-yl) phenyl; 3- (2-pyridyl) phenyl; 3- (3-methoxybenzyl) phenyl; 2- (3-aminopropienyl) phenylmethyl; 3-benzyloxyphenyl; 3 -bromo-4-fluorophenyl; 3-bromo-5-iodophenyl; 3-bromo-5-methoxyphenyl; 3-bromophenyl; 3-bromophenyl) methyl; 3carboxamidophenyl; 3-chlorophenyl; 3-cyanophenyl; 3-diethylmalonylallylphenyl; 3-dimethylamino-phenyl; 3-ethoxyphenyl; 3-fluoro-5trifluórmetylfenyl; 3-fluorophenyl; 3-hydroxyphenyl; 3-iodophenyl; 3-methoxyethyoxyphenyl; 3-methoxyphenyl; 3-methylphenyl; 3-methylsulfonylphenyl; 3-methylthiophenyl; 3-t-butylacrylphenyl; 3trifluórmetyloxyfenyl; 3-trifIuórmetylfenyl; 3-vinylpyridinylphenyl; 3,4-dichlorophenyl; 3,4-dimethoxyphenyl; 3,4-methylenedioxyphenyl; 3,4,5-trimethoxyphenyl; 3,5-di (trifluoromethyl) phenyl; 3,5dibrómfenyl; 3,5-dichlorophenyl; 3,5-dimethoxyphenyl; 3,5-dimethyl-phenyl; 4- (2-propyl) phenyl; 4- (2-propyl) oxyphenyl; 4-benzyloxyphenyl; 4-bromophenyl; 4-bromo-thiophen-2-yl; 4-butoxy-phenyl; 4dimetylaminofenyl; 4-fluoro-3-trifluoromethylphenyl; 4-methoxyphenyl; 4-neopentylphenyl; 4-phenoxyphenyl; 5-bromo-thiophen-2-yl; 5-cyclohexyl; 5-cyclopropyl; 5-hexyl; 5-methyl; 5-phenyl; (2-bromo-5-chlorophenyl) methyl; (2-bromophenyl) methyl and (5-chloro-2- (3-methoxyphenyl) phenyl) methyl. The compound of claim 11 which is 4-amino-5- (4-dimethylaminophenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (4-dimethylaminophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-methoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-dimethylaminophenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4- (2-propyl) phenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-neopentylphenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-butyloxyphenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-methoxyphenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (4- (2-propyl) phenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-butoxy-phenyl) -7- (4-N-formylpiperazinylphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-benzyloxyfenyI) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-phenoxyphenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4- (2-propyl) phenyl) -7- (4-diethylmalonylallylphenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (4- (2-propyl) phenyl) -7- (4-t-butyIakrylfenyl) -pyrido [2,3-d] pyrimidine; 161 4-amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3,4-dimethoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-t-butylacrylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-methoxyphenyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dimethoxyphenyl-7- (4-dimetylam'mofenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-diethylmalonylallylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-vinyIpyridinylfenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-trifluoromethylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-carboxamidophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-cyanophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-benzyloxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-methoxyphenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-butoxy-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3- (2-pyridyl) phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-methylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-chlorophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-fluorophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-methoxyphenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7-phenyl-pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-ethyl-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-cyanophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-hydroxyphenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-iodophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-ethoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-trifluórmetyIoxyfenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dichlorophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-4 'fluoro-phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-hydroxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 162 4-amino-5- (3-bromophenyl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-piperidinylphenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (imidazol-l-yl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-chloro-phenyl) -pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-Isopropylphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-trifluorophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3,4,5-trimethoxy-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3- (3-methoxybenzyl) phenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-methoxyethyoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3,4-methylenedioxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-ethoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (2'-thiophene) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-fluoro-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-dimethylaminophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5-phenyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3,4,5-trimethoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-nitrophenyl) -pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-iodo-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3,4-methylenedioxyphenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (thiophen-2-yl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dimethoxyphenyl) -7- (thiophen-2-yl) -pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-carboxamidophenyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (2-methoxy) ethoxyphenyl) pyrido [2,3-pyrimidine; 4-amino-5- (3,5-dimethoxyphenyl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-trifluoromethylphenyl) -7- (thiophen-2-yl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-amino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-4-fluorophenyl) -7- (thiophen-2-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-4-fluorophenyl) -7- (2-furanyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dimethoxyphenyl) -7- (4-iodo-phenyl) -pyrido [2,3-pyrimidine; 163 4-amino-5- (3,5-dimethoxyphenyl) -7- (4-imidazolylphenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dimethoxyphenyl) -7- (4- (thiophen-2-yl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dimethoxyphenyl) -7- (4- (3-pyridyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (4-methylpiperidinyl) phenyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-pyrrolidinylphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-bromothiophene -) - 7- (4-dimethylaminophenyl) -pyrido [2,3-pyrimidine; 4-amino-5- (4-bromo-thiophen-2-yl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine; 4-morpholinyl-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (5-bromo-thiophen-2-yl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (acetylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-pyrimidine; 4-amino-5- (3,5-dimethoxyphenyl) -7- (5-pyrimidinylphenyl) pyrido [2,3-d] pyrimidine; 4- (4-fluorophenyl) amino) -5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-bromo-thiophen-2-yl) -7- (4-pyrrolidinylphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-bromo-thiophen-2-yl) -7- (thiophen-2-yl) -pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5- (dimethylamino) thiophen-2-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-5-iodophenyl) -7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-di (trifluoromethyl) phenyl) -7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-di (trifluoromethyl) phenyl) -7- (4-morpholinylphenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dibromophenyl) -7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dibromophenyl) -7- (4-morfolinylfenyI) -pyrido [2,3-d) pyrimidine; 4-amino-5- (4-bromo-thiophen-2-yl) -7- (4- (4-methylpiperidinyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dibromophenyl) -7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-methylsulfonylphenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (methylthio) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3,4-dichlorophenyl) -pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N-formylamino) phenyl) pyrido [2,3-d] pyrimidine; 164 4-amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-4-fluorophenyl) -7- (4-methylsulfonylphenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3-amino-4-methoxy-phenyl) -pyrido [2,3-d] pyrimidine, 4-amino-5- (3-bromophenyl) -7- (3-bromo-4- (dimethylamino) phenyl) pyrido _[2> 3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N-trifluoro-acetylamino) phenyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (dimethylamino) -3-fluorophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N-ethyl-N-formylamino) phenyl) pyrido [2,3-d] pyrimidine; 4,4-bis (acetylamino) -5- (3-bromophenyl) -7- (4- (N-methyl-N-acetylamino) phenyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (4- (N-acetyl-N-methylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N-ethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (2-methoxyethyl) amino) phenyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (4- (N-isopropylamino) phenyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-N-ethyl-N- (2-methoxyethyl) amino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-N- (3-methoxypropionyl) -N-isopropyl-amino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-N- (2- (dimethylamino) ethyl) -N-formylamino) phenyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (4- (N- (2- (dimethylamino) ethyl) amino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (2-cyano) ethylamino) phenyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (3-methoxy) propionylamino) phenyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (N-formyl-N-methylamino) phenyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (N-methylamino) phenyl) pyrido [2,3-pyrimidine; 165 4-amino-5- (3-bromophenyl) -7- (4- (4-methoxy-2-butyl) phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (2- (N-phthalimidyl) acetyl) amino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (N-methyl-N- (trifluoroacetyl) amino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3-methyl-4- (N-acetyl-N-methylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-dimethylamino-3-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-cyanophenyl) -7- (4-metyIsulfonylfenyI) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-cyanophenyl) -7- (4- (N-methyl-N-formylamino) phenyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (N-methyl-N-formylamino) -3-pyridinyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-morpholinyl-3-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (N-methyl-N-methoxy-ethylamino) -3-pyridinyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (6-pyrrolidinyl-3-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (2- (dimethylamino) -5-pyrimidinyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (2- (N-methoxyethyl-N-methylamino) -5-pyrimidinyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (2- (N-formyl-N-methylamino) -5-pyrimidinyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (2- (N-methylamino) 5-pyrimidinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (2- (l-pyrrolidinyl) -5-pyrimidinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (2- (l-morpholinyl) -5-pyrimidinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (2-oxo-3-oxazolidinyl) -3-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (2-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3- (thiophen-2-yl) phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-pyrimidine; 4-amino-5- (3- (furan-2-yl) phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-pyrimidine; 4-amino-5- (3- (3-methoxyphenyl) phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 166 4-amino-5-phenyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-chlorophenyl) -7- (4- (morpholinyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-4-fluorophenyl) -7- (4- (morpholinyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-chlorophenyl) -7- (4-iodo-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-chlorophenyl) -7- (4- (thiophen-2-yl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-chlorophenyl) -7- (4- (5-pyrimidinyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-4-fluorophenyl) -7- (4-iodo-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-bromo-thiophen-2-yl) -7- (4-methoxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) methyl-7- (4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (2-phenylethyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (2-methylpropyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (butyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (2- (4-bromophenyl) ethyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (butyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (2- (3-cyanophenyl) methyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (2- (N-phenylmethoxycarbonyl) aminoethyl) -7- (4-dimethylaminophenyl) -pyrido [2,3djpyrimidín; 4-amino-5- (cycloheptyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (2- (5-chloro-2- (thiophen-3-yl) phenylmethyl) -7- (4-dimethylaminophenyl) -pyrido [2,3djpyrimidín; 4-amino-5- (pentyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5-hexyl-7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (2- (3-bromophenyl) ethyl) -7- (4-dietyIaminofenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5 - ((2-bromophenyl) methyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5-cyclopropyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5 - ((2-bromo-5-chlorophenyl) methyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5-methyl-7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (2,3-methylenedioxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-fluoro-5-trifluoromethylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 167 4-amino-5- (2-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dimethyl-phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-pyrimidine; 4-amino-5- (3,4-dichlorophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-fluoro-3-trifluoromethyl-phenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-pyrimidine; 4-amino-5- (3-brótn-5-methoxyphenyl) -7- (4-morpholinyl-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-5-methoxyphenyl) -7- (4-pyrrolidinylphenyl) -pyrido [2,3-pyrimidine; 4-amino-5- (3-bromo-5-methoxyphenyl) -7- (4-piperidinylphenyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromo-5-methoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-methylthiophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-5-methoxyphenyl) -7- (thiophen-2-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (2,3-dimethoxyphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-methylsulfonylphenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-acetylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-formylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4- (methoxyacetyl) amino-5- (3-bromophenyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-trifluoro-acetylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-pentanoylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-benzoylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4 - (/ \ / - BOC-glycyl) amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4- (7V-phthalimidylglycyl) amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3djpyrimidín; 4- (ethoxycarbonyl) amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine; 4- (ethylaminocarbonyl) amino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3djpyrimidín, 4-allylamino-5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-pyrimidine; Of 4- (2- (N, N-dimethylamino) ethylamino) -5- (4-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3djpyrimidín; 4- (4- (N, N-dimethylamino) butylamino) -5- (3-bromophenyl) -7- (4-dimethylaminophenyl) -pyrido [2,3djpyrimidín; 4- (N-allyl-N-formylamino) -5- (4-dimethylaminophenyl) -7- (4-bromophenyl) pyrido [2,3-pyrimidine; 168 4-diacetylamino-5- (p-dimethylaminophenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5-amino-2-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5-dimethylamino-2-pyridyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5-dimethylamino-2-pyrazinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (2-oxobenzoxazolin-6-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (l-methyl-2-oxobenzoxazolin-6-yl) pyrido [2,3-pyrimidine; 4-amino-5 - ((5-chloro-2- (3-methoxyphenyl) phenyl) methyl) -7- (4-dimethylaminophenyl) -pyrido [2,3djpyrimidín; 4-amino-5 - ((thiophen-2-yl) methyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5 - ((thiophen-3-yl) methyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5 - ((2-bromophenyl) methyl) -7- (4-dimethylaminophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N-formyl-N- (2-methoxyethyl) amino) phenyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (4- (N- (2-methoxyethyl) amino) phenyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N - ((2-dimethylamino) ethyl) amino) phenyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (4- (2-methoxy) acetylamino) ethyl) amino) phenyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7 - ((4-Nformylamino) phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (2- (dimethylamino) acetylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (2-oxo-3-oxazolidinyl) phenyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (2-propyl) -3-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3-methyl-4pyrrolidinylphenyl) -pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-imidazolyl-3-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5-phenylmethyl-7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (2- (3aminopropynyl) phenylmethyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-pyrimidine; 4-amino-5- (l- (3-bromophenyl) ethyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (4-dimethylaminophenyl) -7- (4-bromophenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (2-furanyl) -7- (4- (N-morpholinyl) phenyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (2-dimethylamino-5-pyrimidinyl) pyrido [2,3-d] pyrimidine; 169 4-amino-5- (3-bromophenyl) -7- (4- (ureido) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (l-phenylmethyl-3-piperidinyl) -7- (4-diethylamino-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (3-methyl-5-isoxazolyl)) - 3-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-chloro-3-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-methoxy-3-pyridinyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (l, 2,4-triazol-4-yl) -3-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (2-morpholinyl-5-pyrimidinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (2-tiazoIyl) -7- (4-pyrrolidinylphenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-pyrazolyl-3-pyridinyl)) - pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (l-methyl-ureido) phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N- (2-pyrimidinyl) amino) phenyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (3-fluoro-4- (N-formyl-N-methylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-Nformylamino-5- (3-bromophenyl) -7- (3-fluoro-4- (N-formyl-N-methylamino) phenyl) -pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (4- (N-methyl-N-methylsulfonylamino) phenyl) -pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (6- (N-methyl-N-methylsulfonylamino) -3- pyridinyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (l-methyl-5-indolinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (l-methyl-5-benzimidazolyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-dimethylamino-3-pyridazinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-morpholinyl-3-pyridazinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-pyrrolidinyl-3-pyridazinyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5-morpholinyl-2-pyrazinyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5- (N- (2-methoxyethyl) -N-methylamino) -2- pyrazinyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (4- (morpholinylmethyl) -phenyl) pyrido [2,3-d] pyrimidine; 170 4-amino-5- (3-bromophenyl) -7- (5- (N, N-bis (2-methoxyethyl) amino) -2-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (imidazolylmethyl) -phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5- (l-morpholinyl) -2-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4 - ((dimethylamino) methyl) phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5- (4-hydroxy-l-piperidinyl) -2-pyridinyl) pyrido [2,3-d] pyrimidine, 4-amino-5- (3-bromophenyl) -7- (5- (N-formyl-N-methylamino) -2-pyridinyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (5- (2-propenyl) -2-pyridinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3- (2-methoxyethyl) -2-oxo-6-benzoxazolyl) pyrido [2,3d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (l- (N-formylamino) ethyl) phenyl) pyrido [2,3-d] pyrimidine; 4- (methylamino) -5- (3-bromophenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine hydrochloride; 4- (2-Methoxyethylamino) -5- (3-bromophenyl) -7- (4-dimethylaminophenyl) pyrido [2,3-d] pyrimidine hydrochloride; 4-amino-5- (3-bromophenyl) -7- (4- (1-methyl-2-imidazolyl) phenyl) pyrido [2,3-d] pyrimidine trihydrochloride; 4-amino-5- (3-bromophenyl) -7- (4- (aminomethyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (2-bromo-4- (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (dimethylaminoethyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (3- (dimethylamino) propynyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (3-amino-3-methylbutynyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-dimethylphosphonatophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (3- (metoxypropinyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-carboxyphenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-methyl-3-oxo-2H-4H-pyrido [3,2-b] -l, 4-oxazin-7-yl) -pyrido [2, 3-d] pyrimidine; 171 4-amino-5- (3-bromophenyl) -7- (4- (2- (dimethylamino) ethyl) -3-oxo-2H-4H-pyrido [3,2-b] -l, 4oxazin-7-yl ) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (2,3-dihydro-3- (dimethylaminoethyl) -2- oxobenzoxazol-6-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-methyl-3-oxo-2H-4H-benzo-l, 4-oxazin-7-yl) -pyrido [2,3dlpyrimidín; 4-amino-5- (3-bromophenyl) -7- (2,2,4-trimethyl-3-oxo-2H-4H-benzo-l, 4-oxazin-7-yl) -pyrido [2,3-d ] pyrimidine; 4-amino-5-cyclohexyl-7- (4- (2-dimethylamino) ethyl) -2-4 H -benzo-3-oxo-4-oxazin-7-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5- (l-methylethyl) -2-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5-piperidin-l-yl-pyridin-2-yl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (l- (4-bromophenyl) ethyl) -7- (6-morfolinylpyrid-3-yl) -pyrido [2,3-dlpyrimidín; 4-amino-5- (3-bromophenyl) -7- (4 - ((N-formylamino) methyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (1-methyl-1- (N-methylamino) ethyl) phenyl) pyrido [2,3-dlpyrimidine; 4-amino-5- (3-bromophenyl) -7- (4- (1-dimethylamino) -1-methylethyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (N-acetyl-5-indolinyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6-chloro-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (l- (2-bromophenyl) ethyl) -7- (6-diethylamino-3-pyridyl) pyrido [2,3-dlpyrimidín; 4-amino-5- (l- (2-bromophenyl) ethyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (l- (2-bromophenyl) ethyl-7- (4- (N-methyl-N-formyl) amino) phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5 - ((2-bromophenyl) methyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (4-tetrahydropyranyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6-dimethylamino-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (l-ethyl-propyl) -7- (6-dimethylamino-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-Amino-5-cyclopentyl-7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (2-chloro-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3,5-dimethylcyclohexyl) -7- (6-dimethylamino-3-pyridyl) pyrido [2,3-d] pyrimidine; 172 4-amino-5 - ((N- (benzyloxycarbonyl) -4-piperidinyl) methyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6-bromo-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (3-cyano-phenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (l- (2-bromophenyl) ethyl) -7- (6-dimethylamino-3-pyridazinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-imidazolyl-3-pyridazinyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (azacycloheptanyl) -3-pyridazinyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-N-methyl-N- (l-methylethyl) amino) -3-pyridazinyl) pyrido [2,3djpyrimidín; 4-amino-5- (1- (2-bromophenyl) -7- (6-morpholinyl-3-pyridazinyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6- ( 4-acetylpiperazinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6- (4-acetyl-1,4-diazacycloheptanyl) -3-pyridyl) pyrido [2, 3djpyrimidín; 4-Amino-5-cyclohexyl-7- (6- (4-methyl-1,4-diazacycloheptanyl) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6- (N-methyl-N- (2- (2-pyridyl) ethyl) amino) -3-pyridyl) pyrido [2,3djpyrimidín; 4-amino-5-cyclohexyl-7- (6-2- (N- (N ', N'-dimethylaminoethyl) -N-methylamino) -3-pyridyl) pyrido [2,3-pyrimidine; 4-amino-5-cyclohexyl-7- (6-azetidinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6- (3- (N-methylacetamido) pyrrolidinyl) pyridyl) pyrido [2,3djpyrimidín; 4-amino-5-cyclohexyl-7- (6- (3-formamido) pyrrolidinyl) pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (4-oxo-l-phenyl-l, 3,8-triazaspiro [4,5Jdekan-8-yl) -pyrido [2,3djpyrimidín; 4-amino-5-cyclohexyl-7- (6- (2-methoxymethyl) pyrrolidin-l-yl) pyridyl) pyrido [2,3-pyrimidine; 4-amino-5-cyclohexyl-7- (6- (N-methoxyethyl-N-propylamino) pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (N-methyl-N- (2,2-dimethoxyethyl) amino) pyrido [2,3-d] pyrimidine; 4-amino-5-cyclohexyl-7- (6- (4-dimethylamino) piperidinyl) pyridyl) pyrido [2,3-pyrimidine; 4-amino-5-cyclohexyl-7- (6- (4-aminocarbonyl) piperidinyl) pyridyl) pyrido [2,3-d] pyrimidine; 173 4-amino-5-cyclohexyl-7- (N-methyl-N- (3- (diethylamino) propyl) aminopyridin-3-yl) -pyrido [2,3djpyrimidín; 4-amino-5-cyclohexyl-7- (6- (N-methyl-N- (4-pyridyl) ethylamino) pyrid-3-yl) -pyrido [2,3djpyrimidín; 4-amino-5-cyclohexyl-7- (6- (N-methyl-N- (3-pyridylmethylamino) pyrid-3-yl) -pyrido [2,3djpyrimidín; 4-amino-5- (1- (2-bromophenyl) ethyl) -7- (1-methyl-5-indolyl) pyrido [2,3-d] pyrimidine; 4-Amino-5- (1- (2-bromophenyl) ethyl) -7- (1-methyl-2,3-dioxo-5-indolyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (3-fluoro-4- (l-morpholinyl) phenyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-hydroxy-3-nitrophenyl) -pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (4,4-etyléndioxypiperidinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (4-oxopiperidinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (4-formylpiperazinyl) -3-pyridyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (4-methyl piperidinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6-thiomorpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (4,4-dioxotiomorfblinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (2-bromophenyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromo-4-methoxyphenyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (4-bromophenyl) -7- (6-morfblinyI-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-chlorophenyl) -7- (6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (5-chloro-6-morpholinyl-3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (N-oxidomorfolinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (N- (2-hydroxyethoxyethyl) amino) -3-pyridyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (6- (N- (2-hydroxyethoxyethyl) -N-formylamino) -3-pyridyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (6- (N- (2-hydroxyethoxyethyl) -3-pyridyl N-oxide) -pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (6- (3-hydroxy) morpholinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine; 174 1- (5- (4-Amino-5- (3-bromophenyl) pyrido [2,3-d] pyrimidin-7-yl) -2-pyridyl) piperidine-4-phosphate disodium salt; 4-amino-5- (3-bromophenyl) -7- (4-methylenylpiperidinyl) -3-pyridyl) pyrido [2,3-pyrimidine; 4-amino-5- (3-bromophenyl) -7- (4-hydroxy-4- (hydroxymethyl) piperidinyl) -3-pyridyl) pyrido [2,3djpyrimidín; 4-amino-5- (3-bromophenyl) -7- (6- (4,4-etyléndioxypiperidinyl) -3-pyridyl) pyrido [2,3djpyrimidín; 4-amino-5-cyclohexyl-7- (6- (4-oxopiperidinyl) -3-pyridyl) pyrido [2,3-pyrimidine; 4-amino-5-cyclohexyl-7- (6- (4-metylenyIpiperidinyl) -3-pyridyl) pyrido [2,3-d] pyrimidine; 4-N- (iminomethyl) amino-5-cyclohexyl-7- (6-dimethylamino-3-pyridyl) pyrido [2,3-pyrimidine; or a pharmaceutically acceptable salt or amide thereof. 16. A pharmaceutical composition comprising a compound of claim 11 and a pharmaceutically acceptable carrier. A compound of formula III (III) wherein X is selected from the group consisting of -OH or halogen, and R ³ and R 6 are as hereinbefore defined and broken line - indicates that a double bond is optionally present. The compound of claim 17, wherein the compound is an intermediate for the manufacture of the compound of claim 11 or 12 175 19th A process for the preparation of an adenosine kinase inhibitor compound of formula (I) wherein R ¹ and R 4 are hydrogen, characterized in that (a) a ketone of formula R 4 -CO-CH 3, wherein R 4 is as defined above, is reacted under anhydrous conditions with an aldehyde of formula R 1 -CHO, wherein R 1 is as defined above, and malononitrile in the presence of an ammonium salt, and the first intermediate of formula (b) is isolated and the first intermediate is reacted under reflux with formamide for about 1 to about 8 h. and (c) optionally, the compound of step (b) is reduced by catalytic hydrogenation to form a partially reduced or fully reduced right side of Formula I. A process for the preparation of an adenosine kinase inhibitor compound of the formula 176 ^R 1 ^{R 2} R 1 ^{NN 7 R 4} , (I) wherein R ¹ and R ² are hydrogen, characterized in that (a) the ketone of formula R ⁴ -CO-CH 3, wherein R ⁴ is as defined above, is allowed to heat react at reflux with a dicyanoalkene of formula R 1 -CH = C (CN) 2, wherein R 1 is as defined above, and isolate the first intermediate of formula (b) the first intermediate is reacted with formamide at reflux for about 1 to about 8 ha isolating a compound of formula (I) having a carbon-to-carbon double bond of 5.6 and a carbon-to-nitrogen double bond of 8 and (c) optionally reducing the compound of step (b) by catalytic hydrogenation to form a partially reduced or fully reduced right side Formula I.