CN1259948A

CN1259948A - 6,7-disubstituted-4-aminopyrido [2,3-D] pyrimidine compounds

Info

Publication number: CN1259948A
Application number: CN98806072A
Authority: CN
Inventors: S·S·巴格瓦特; 李志宏; R·J·佩尔纳; 顾禹归
Original assignee: Abbott Laboratories
Current assignee: Abbott Laboratories
Priority date: 1997-04-16
Filing date: 1998-04-16
Publication date: 2000-07-12
Also published as: CO4940439A1; HUP0001402A3; SK142099A3; NO995033D0; AU744528B2; TW458977B; EP0979230A1; ZA982912B; HUP0001402A2; CA2287465A1; NZ337844A; AU7098198A; KR20010006453A; AR012435A1; BR9809088A; WO1998046603A1; TR199902456T2; IL131892A0; BG103861A; JP2001520649A

Abstract

A compound having formula (I), wherein R<1>, R<2>, R<3> and R<4> are defined variables selected from the groups as specified herein which include alkyl, aryl, heteroaryl and heterocyclic and substituted versions thereof, a method for inhibiting adenosine kinase by administering a compound thereof, a pharmaceutical composition comprising a therapeutically effective amount of a compound thereof above in combination with a pharmaceutically acceptable carrier, a method of treating cerebral ischemia, epilepsy, nociperception, pain, inflammation and sepsis in a mammal in need of such treatment, comprising administering to the mammal a therapeutically effective amount of a compound thereof, and methods of preparation thereof.

Description

6,7 - substituted-4 - amino-pyrido [2,3-D] pyrimidine compounds

Technology

The present invention relates to give 6,7 - substituted-4 - amino-pyrido [2,3-d] pyrimidine compounds The method of inhibiting adenosine kinase, relates to compositions containing these compounds and new pharmaceutical compositions 6,7 - substituted-4 - amino-pyrido [2,3-d] pyrimidine compound.

Background of the Invention

Adenosine kinase (ATP: adenosine 5'-phosphotransferase, EC2.7.1.20) is a commonly found In the enzyme, which preferentially use ATP as a source of phosphate catalyzed adenosine into AMP. Adenosine kinase with extensive tissue and species distribution, and has been from yeast, a lot of feeding Milk Animal Resources and certain microorganisms isolated. Has been found to exist in the real Determination including kidney, liver, brain, spleen, placenta and pancreas in each of the human tissue. Adenosine The control of intracellular adenosine kinase is a key enzyme concentration.

Adenosine is a purine nucleotide degradation and salvage pathway as an intermediate in purine Nucleosides. Adenosine also has many important physiologic effects, many of which are called P by₁Acceptor Activation of specific cell surface receptor mediated (Burnstock, Cell Membrane Receptors for Drugs and Hormones, 1978, (Bolis and Straub, eds.) Raven, New York, the first .107-118 page; Fredholm, etc., Pharmacol.Rev.1994, 46:143 - 156).

In the central nervous system inhibitory effect of certain neurotransmitters (Corradetti, etc., Eur.J. Pharmacol.1984 ,104:19-26) release, stable membrane potential (Rudolphi, etc. Cerebrovasc.Brain Metab.Rev.1992 ,4:346-360), as an endogenous anticonvulsant Drugs (Dragunow, Trends Pharmacol.Sci.1986 ,7:128-130) and having endogenous God The effect of the protective agent (Rudolphi, etc., Trends Pharmacol.Sci.1992, 13:439 - 445). Adenosine in several central nervous system disorders such as schizophrenia, anxiety, depression And play a role in Parkinson's disease (Williams, M., Psychopharmacology: The Fourth Generation of Progress; Bloom, Kupfer (editor), Raven Press, New York, 1995, pages 643-655).

Adenosine also adjust the spinal cord pain pathway conduction (Sawynok etc., Br.J. Pharmacol.1986 ,88:923-930) and mediated analgesic effect of morphine on (Sweeney, etc., J. Pharmacol.Exp.Ther.1987 ,243:657-665). In the immune system, adenosine inhibition Certain neutrophil function and exhibit anti-inflammatory effects (Cronstein, J.Appl. Physiol.1994 ,76:5-13). AK inhibitors have been reported in a rat adjuvant arthritis Model to reduce foot swelling (Firestein, etc., Arthritis and Rheumatism, 1993,36, S48).

Adenosine in the cardiovascular system can also display a variety of effects, including vasodilation, atrioventricular Damage and myocardial ischemia and reperfusion in the endogenous cardioprotective (Mullane and Williams, Adenosine and Adenosine Receptors, 1990 (Williams, editor) Human Press, New Jersey, the first .289-334 page). Broad effect of adenosine are also included in the kidney, respiratory Absorption, gastrointestinal and reproductive systems, and blood cells and the role of fat cells. After its Fat cells activation of the adenosine A1 receptor by inhibiting lipolysis effect for diabetes With [Londos, etc., Proc.Natl.Acad.Sci.USA, 1980,77,2551].

Endogenous adenosine release in many pathophysiological conditions, seems to act as a natural defense mechanism Function, these pathophysiological conditions including cerebral and myocardial ischemia, seizures, pain, Inflammation and sepsis. When low levels of adenosine to normal when present in the extracellular space, in the over- Cell activity, trauma or metabolic stress released parts of its local enhancement. Once the fine Extracellular gap, then the activation of specific extracellular adenosine receptors tend to excite many of the fine Cell function returned to normal response (Bruns, Nucleosides Nucleotides, 1991,10:931 - 943; Miller and Hsu, J.Neurotrauma, 1992,9: S563-S577). Adenosine in the cell Determination of extracellular fluid has a half-life of a few seconds (Moser, etc., Am.J.Physiol.1989, 25: C799-C806), so the effect of the height positioning of the endogenous. ...

Directly to the adenosine kinase inhibiting compound provides pharmacological site-specific adenosine and Event (event) of the disease-specific enhancement potential useful new and effective therapies. Such compounds May be useful include ischemic diseases such as cerebral ischemia, myocardial ischemia, angina pectoris, Coronary artery bypass graft surgery (CABG), percutaneous transluminal coronary angioplasty (PTCA), Stroke, thrombosis and embolism other neurological disorders such as epilepsy and anxiety, schizophrenia, Nociceptive sensory perception including pain, neuropathic pain, visceral pain, and inflammation, joint Inflammation, immunosuppression, sepsis, diabetes and gastrointestinal disorders such as abnormalities of the gastrointestinal Road initiative. ...

Adenosine kinase also caused many pharmacologically active nucleosides including killing tuberculin, a type of mold Su, ribavirin, topiramate furosemide streptozotocin and 6 - (methyl mercapto) activation of purine nucleosides (Miller Etc., J.Biol.Chem.1979 ,254:2339-2345). These purine nucleoside analogs on behalf of Table of an important group of cytotoxic, anti-cancer and anti-viral properties of anti-metabolites. They Useful as adenosine kinase substrate phosphorylated by the enzyme produced activated forms. Since Cells against these nucleoside analogues pharmacological mechanism of action of adenosine kinase activity was lost by the Effects (eg Bennett et al, Mol.Pharmacol. ,1966,2:432-443; Caldwell, etc. Can.J.Biochem. ,1967,45:735-744; Suttle, etc., Europ.J.Cancer, 1981, 17:43-51). Cellular adenosine kinase levels decreased also to resist toxicity of 2'-deoxyadenosine Effect on (Hershfield and Kredich, Proc.Natl.Acad.Sci.USA, 1980,77: 4292-4296). Tips from 2'-deoxyadenosine phosphorylation derived deoxyadenosine triphosphate (DATP) in connection with the accumulation of genetic lack of adenosine deaminase is an immune defect Kind of mechanism of toxicity (Kredich and Hershfield, in The Metabolic Basis of Inherited Diseases, 1989 (Scriver, etc., editor), McGraw-Hill, New York, p 1045-1075 Page). ...

BSHurlbert etc. (J.Med.Chem. ,11:711-717 (1968)) discloses as antibacterial Agents various 2,4 - diamino-pyrido [2,3-d] pyrimidine compound. RKRobins etc. (J.Amer. Chem.Soc. ,80:3449-3457 (1958)) discloses a number of anti-folate activity of 2,4 - Dihydroxy-, 2,4 - diamino-2 - amino - 4 - hydroxy-and 2 - mercapto-4 - hydroxy-pyrido [2,3-d] pyrimidine Preparation of pyridine. R.Sharma etc. (Indian.J.Chem., 31B :719-720 (1992)) male Having antibacterial activity on 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 of the Thereof. A.Gupta etc. (J.Indian.Chem.Soc. ,71:635-636 (1994)) discloses a Antibacterial active 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 compound. L.Prakash Etc. (Pharmazie ,48:221-222 (1993)) discloses a 4 antifungal activity - amino -5 - Phenyl-7 - (4 - aminophenyl) pyrido [2,3-d] pyrimidin-4 - amino-5 - phenyl-7 - (4 - bromophenyl) Pyrido [2,3-d] pyrimidin-4 - amino -5 - (4 - methoxyphenyl) -7 - (4 - aminophenyl) pyrido [2,3-d] pyrimidine and 4 - amino-5 - (4 - methoxyphenyl) -7 - (4 - bromophenyl) pyrido [2,3-d] pyrimidine Compounds. P.Victory etc., Tetrahedron ,51:10253-10258 (1995)) discloses a Acyclic precursor synthesis of 4 - amino-5, 7 - diphenyl-pyrido [2,3-d] pyrimidine compounds. Bridges and other (PCT application WO95/19774, 1995.7.27 Publication Date) discloses a Inhibit epidermal growth factor tyrosine kinase various utility bicyclic heteroaromatic compounds. ...............

The present invention provides a compound having adenosine kinase inhibitors utility 6,7 - substituted - 4 - amino pyridine Pyrido [2,3-d] pyrimidine compound.

One aspect, the invention provides a formula (I) are new compounds:Of which: R¹And R²Is independently H, lower alkyl, aryl or acyl group, or they are connected with the Then form together with the nitrogen atom optionally containing 1-3 heteroatoms selected from O, N or S heteroatom in addition A 5-7 membered ring; R³And R⁴Independently selected from lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl Group, a heteroaryl group, or a heterocyclic group, and the dotted line indicates a double bond is optionally present.

The present invention also includes compounds of formula I and pharmaceutically acceptable salts and amides Their uses are provided.

On the other hand, the present invention provides a given formula (I) compounds inhibit adenosine kinase Methods.

Specifically, the method of inhibiting adenosine kinase comprises adenosine kinase exposed to a Effective inhibiting amount of the compounds of formula (I) compound. When the adenosine kinase in vivo, may To convert said compound is administered to the organism.

On the other hand, the present invention provides a comprising a therapeutically effective amount of the formula (I) compounds and drugs Science acceptable carrier and pharmaceutical compositions comprising the combination of one of the above.

In another aspect, the present invention provides a therapeutic treatment of a mammal in need for such partial lack of Blood, neuropathy, nociception, inflammation, immune suppression, gastrointestinal dysfunction, diabetes Disease and sepsis, the method comprising administering to said mammal a therapeutically effective amount of Compounds of formula (I) compound.

In a preferred aspect, the present invention provides a treatment of a mammal in need such treatment Cerebral ischemia, myocardial ischemia, angina, coronary artery bypass graft surgery, percutaneous coronary Artery angioplasty, stroke, thrombosis and embolism disease, epilepsy, anxiety, schizophrenia Disorders, pain perception, neuropathic pain, visceral pain, arthritis, sepsis, diabetes, And abnormal motility of the gastrointestinal tract, the method comprising administering to said mammal a therapeutically An effective amount of the compounds of formula (I) compound.

On the other hand, the present invention also includes formula (I) compounds and pharmaceutically acceptable salts thereof Amides and their use in inhibiting adenosine kinase, in pharmaceutical compositions and administered to mammals in Purposes.

Furthermore, the present invention relates to formula (II) compound:Of which: R¹And R²Is independently H, lower alkyl, aryl or acyl group, or they are connected with the Then form together with the nitrogen atom optionally contain an additional oxygen or nitrogen atom a 5-7 membered ring; R³And R⁴Independently selected from lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl Group, a heteroaryl group, or a heterocyclic group.

On the other hand, the present invention provides a method for preparing compounds of formula II:

Of which: R¹And R²Is hydrogen; R³Is lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, heteroaryl Or a heterocyclic group; R⁴Is aryl, heteroaryl or heterocyclic group; Said method comprising: (a) The tetrakis (triphenylphosphine) palladium (O) and the presence of aqueous alkali metal base, the 4,6 - diamino-5 - Iodo-pyrimidine boronic acid having the vinyl derivative of formula:

Where R³Is lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, heteroaryl, Or heteroaryl ring or substituted forms, and separating the first intermediate with a compound of the formula:(b) under anhydrous conditions and the water generated in the reaction was removed, the first intermediate compound with Where R⁴Is aryl, heteroaryl or heterocyclic group of the formula R⁴-CHO aldehyde compound, And separated formula (II) compound.

On the other hand, the present invention provides a formula (II) the preparation of compounds:Of which: R¹And R²Is independently H, lower alkyl, aryl or acyl group, or they are connected with the Together with the nitrogen atom form an optionally containing one additional oxygen or nitrogen atom a 5 - to 7-membered ring, And R¹And R²Are not both hydrogen, R³Is lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, heteroaryl Or a heterocyclic group; R⁴Is aryl, heteroaryl or heterocyclic group; The method comprising:

(a) having formula (II) compound

Of which: R¹And R²Is hydrogen; R³Is lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, heteroaryl Or a heterocyclic group; R⁴Is aryl, heteroaryl or heterocyclic group; Respectively, and a compound selected from:

(i) alkylating reagent R¹-Y, wherein R¹Is a lower alkyl group, Y is selected from halide, methyl Sulfonate and toluenesulfonate;

(ii) an arylalkyl group of the reagent R¹- Lower alkyl-Y, wherein R¹Is an aryl group, Y selection Since halide, mesylate and tosylate;

(iii) an acyl compound R¹-Z, wherein R¹Is an acyl group, Z is selected from anhydride moieties, Halide or acyl activating group; and isolating the desired compound; and

(b) optionally, when asked R²Is other than hydrogen, a compound selected from the following process data from Step (a) the compound

(i) alkylating reagent R²-Y, wherein R²Is a lower alkyl group, Y is selected from halide, methyl Sulfonate and toluenesulfonate;

(ii) an arylalkyl group of the reagent R²- Lower alkyl-Y, wherein R²Is an aryl group, Y selection Since halide, mesylate and tosylate;

(iii) an acyl compound R²-Z, wherein R²Is an acyl group, Z is selected from anhydride moieties, Halide or acyl activating group; and separate the desired product.

Another aspect, the invention provides a formula (II) the preparation of compounds:Of which: R¹And R²Is independently H, lower alkyl, aryl or acyl group, or they are connected with the Then form together with the nitrogen atom optionally containing an additional oxygen or nitrogen atom a 5 - to 7-membered ring, Condition is R⁴And R⁵Are not both hydrogen; R³Is lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, heteroaryl Or a heterocyclic group; R⁴Is aryl, heteroaryl or heterocyclic group; Said method comprising:

(a) The tetrakis (triphenylphosphine) palladium (O) and the presence of aqueous alkali metal base, the 6 - amino - 4 - chloro-5 - iodo-pyrimidine having a vinyl boronic acid derivative of formula:

Where R³Is a lower alkyl, a lower alkenyl group, a lower alkynyl group, aryl group, arylalkyl group, Heterocycle or heteroaryl, and separating a first intermediate compound of the formula:

(b) under anhydrous conditions and removing water generated in the reaction, the first intermediate compound And where R⁴Is aryl, heteroaryl or heterocyclic group of the formula R⁴-CHO aldehyde compound, And separating a second intermediate compound of the formula:

(c) a wherein R¹And R²As described above formula R¹-NH-R ²Processing the first amino compounds Four intermediate compound and isolation of the desired product. Detailed Description of the invention

The present invention relates to inhibiting adenosine kinase 6,7 - substituted-4 - amino-pyrido [2,3-d] Pyrimidine compounds, a compound containing such pharmaceutical compositions, the use of such compounds inhibit The method of adenosine kinase and the new 6,7 - substituted-4 - amino-pyrido [2,3-d] pyrimidine compound Thereof.

One aspect, the invention provides for the adenosine kinase inhibitor 6,7 - substituted - 4 - amino Pyrido [2,3-d] pyrimidine compound. Adenosine kinase inhibitor of the present invention for the above compound of formula I or II compound.

In a preferred embodiment, the present invention is the above adenosine kinase inhibitors Formula (I) or (II) wherein R⁴Is aryl or heteroaryl, and their substituted forms.

In a more preferred embodiment, the present invention are adenosine kinase inhibitors for the above Formula (I) or (II) wherein R⁴Is aryl or heteroaryl, or substituted forms, and R³Is a lower alkyl group, an aryl group, an aryl group or a heteroaryl group or a substituted form.

In another embodiment, the present invention relates to a compound of formula as compounds I and II , Wherein R¹And R²Independently selected from hydrogen, lower alkyl, aryl C₁-C ₆Alkyl,-C (O) C₁-C ₆Alkyl group, -C (O) aryl,-C (O) heterocycle, or with the nitrogen atom to which they are attached form an optionally together with 1-2 heteroatoms selected from O, N or S, 5-7 additional hetero ring atom; R³And R⁴Independently selected from: C₁-C ₆Alkyl group, C₂-C ₆Alkenyl, C₂-C ₆Alkynyl group, C₃-C ₈Cycloalkyl group, Heteroaryl C₀-C ₆Alkyl, or substituted heteroaryl C₀-C ₆Alkyl group, Aryl C₀-C ₆Alkyl or substituted aryl C₀-C ₆Alkyl group, Heteroaryl C₂-C ₆Alkenyl group or a substituted heteroaryl C₂-C ₆Alkenyl, Aryl C₂-C ₆Alkenyl or substituted aryl C₂-C ₆Alkenyl, Heteroaryl C₂-C ₆Alkynyl group or a substituted heteroaryl C₂-C ₆Alkynyl group, Aryl C₂-C ₆Alkynyl group or a substituted aryl C₂-C ₆Alkynyl, wherein said aryl or heteroaryl 1-4 Substituents independently selected from Halogen, oxo, cyano, C₁-C ₆Alkyl, heteroaryl C₀-C ₆Alkyl, heterocyclyl C₀-C ₆Alkyl group, C₁-C ₆Alkoxy, C₁-C ₆Alkoxy C₁-C ₆Alkyl, aryl C₀-C ₆Alkyl, aryl C₁-C ₆Alkoxy group, R⁵R ⁶NC (O), cyano, C₂-C ₆Alkenyl, C₂-C ₆Alkynyl, C₁-C ₆Alkyl group, C₂-C ₆Dialkyl malonate alkenyl group, CF₃、HO-、C ₁-C ₆Alkoxy C₁-C ₆Alkoxy, C₁-C ₆Alkyl SO_nWhere n is 1-2, C₁-C ₆Alkylthio, C₁-C ₆Acryloyl group, CF₃O、 CF ₃、C ₁-C ₆Alkylenedioxy, C₁-C ₆Acrylic alkyl group, R⁵R ⁶N(CO)NR ⁵, N- Formyl (heterocyclic), NO₂、NR ⁵R ⁶C ₀-C ₆Alkyl group,

Where R⁵And R⁶Is independently selected from H, C₁-C ₆Alkyl, HC (O), C₁-C ₆Alkoxy C₁-C ₆

Alkyl, C₁-C ₆Alkoxy, C₁-C ₆Alkyl C (O), CF₃C(O)、NR ⁷R ⁸C ₁-

C ₆Alkyl, phthalimido group C₁-C ₆C(O)、C ₁-C ₆Alkyl SO_nWherein n

Is 1-2, CNC₁-C ₆Alkyl, R⁷R ⁸NC(O)NR ⁷-, Heteroaryl, NR⁷R ⁸C ₁-C ₆

Alkyl C (O), C₁-C ₆Ureido alkoxy C₁-C ₆Alkyl group,

Where R⁷And R⁸Independently selected from R⁵And R⁶Substituent group, or R⁵And R⁶Or R⁷

And R⁸With the nitrogen atom to which they are connected together to form an optionally containing 1-3

One another selected from O, N or S heteroatoms unsubstituted or 5-7

Generation of the ring, wherein said substituents are selected from C₁-C ₆Alkyl, and wherein in the formula

I the case, The dotted line --- indicates a double bond is optionally present. The invention also includes those in which R³And R⁴Independently selected from The following shows that 6 - and 7-substituted - substituted group-containing compound.

Typical of the invention and preferred compounds include: 4 - amino-6 - phenyl-7 - (p - dimethylaminophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - (dimethylamino) phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] Pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - phenyl-pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - bromophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - (dimethylamino) phenyl) -7 - (4 - pyridyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - (dimethylamino) phenyl) -7 - (4 - bromophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - (5 - pyrimidinyl) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - (2 - (2 - pyridyl) ethenyl) phenyl) pyrido [2,3-d] Pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (3 - pyridyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (thiophen-3 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (2 - pyridyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (3,4 - methylenedioxy-phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - butyl-7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - butyl-7 - (thiophen-3 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (5 - bromo-thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (5 - methyl-thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - (trifluoromethoxy) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (3 - phenoxy-phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (5 - nitro-thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - bromo-thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (3 - methyl-thiophene-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (furan-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (furan-3 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (5 - methyl - furan-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - (2 - propyl) phenyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - (2 - propyl) phenyl) -7 - (5 - nitro-thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (5 - nitro-thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - (dimethylamino) phenyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3,4 - dimethoxyphenyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3,4 - dimethoxyphenyl) -7 - (5 - nitro-thiophen-2 - yl) pyrido [2,3-d] pyrimidine Pyridine; 4 - amino-6 - hexyl-7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - amino-6 - hexyl-7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (2 - methyl - 2 - propyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - (2 - propyl) phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - (4 - propyl-phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3,4 - dimethoxyphenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - (3 - methoxy-phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - bromophenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - fluorophenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - (trifluoromethyl) phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - (3 - chlorophenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3,5 - dichlorophenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3,4 - methylenedioxyphenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] Pyrimidine; 4 - Amino-6 - (3,4 - methylenedioxyphenyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - methoxycarbonyl-phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - (3 - (2 - propyl) phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - (4 - (2 - methyl - 2 - propyl) phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3 - d] pyrimidine; 4 - Amino-6 - (4 - fluorophenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methoxyphenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - (phenylmethoxy) phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] Pyrimidine; 4 - Amino-6 - (4 - chlorophenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - fluoro-4 - methyl-phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - (3 - fluoro-4 - methyl-phenyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - phenyl-propyl) -7 - (4 - methoxyphenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - phenyl-propyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (2 - phenyl-ethyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - amino-6 - (phenylmethyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (cyclohexylmethyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - butyl-7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - amino-6 - pentyl -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (2 - methylpropyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - amino-6 - propyl -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - cyanopropyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - nitrophenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - amino-6 - pentyl-7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - (formylamino) propyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - ((4 - methoxyphenyl) methyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - ((3 - bromophenyl) methyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - ((4 - (2 - propyl) phenyl) methyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - ((4 - methoxyphenyl) methyl) -7 - (4 - (2 - propyl) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - ((4 - bromophenyl) methyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - ((3 - fluorophenyl) methyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - ((4 - bromophenyl) methyl) -7 - (thiazol-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - ((3 - methoxyphenyl) methyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (6 - methyl-phenyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - ((3 - methoxyphenyl) methyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] Pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - (trifluoromethyl) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - methylphenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - methoxyphenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - ethyl-phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - cyanophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - acetylamino-phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - phenoxy-phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - nitrophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - fluorophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - chlorophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - aminophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - (methylthio) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - ((4 - phenyl) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - ((4 - methoxy-phenyl)-phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - ((4-N, N-diethylamino) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - ((4-2 - phenyl) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - (2 - methyl - 2 - propoxy) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (3 - chlorophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (3,5 - dimethoxyphenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (thien-2 - yl) -7 - (4-N, N-dimethylaminophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (benzofuran-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (thien-2 - yl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (thien-2 - yl) -7 - (4 - methoxyphenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - bromophenyl) -7 - (4-N, N-dimethylaminophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - bromo-4 - methoxy-phenyl) -7 - (4-N, N-dimethylaminophenyl) pyrido [2,3 - d] pyrimidine; 4 - Amino-6 - (3 - bromo-4 - methoxy-phenyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - butoxyphenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (3 - methoxyphenyl) pyrido [2,3-d] pyrimidine; and 4 - Amino-6 - (4 - methyl-phenyl) -7 - (3,5 - dichlorophenyl) pyrido [2,3-d] pyrimidine. ...

Further, R³And R⁴Can be independently selected from phenyl, thiophene-2 - yl, 1 - methyl-2 - oxo-benzo Oxazol-5 - yl, 2 - (dimethylamino) -5 - pyrimidinyl, 2 - (N-formyl-N-methyl-amino) -3 - ethyl Piperidinyl, 2 - (N-(2 - methoxyethyl)-N-methyl-amino) -5 - pyrimidinyl, 2 - (N-methyl-amino) - 5 - pyrimidinyl, 2 - (1 - morpholinyl)-5 - pyrimidinyl, 2 - (1 - pyrrolidinyl) -5 - pyrimidinyl, 2 - dimethyl Yl-5 - pyrimidinyl, 2 - furyl, 2 - oxo-benzoxazol-5 - yl, 2 - pyridyl, 3 - (Dimethylamino) phenyl, 3 - amino - 4 - methoxy-phenyl, 3 - bromo-4 - (dimethylamino) phenyl, 3 - methoxy-phenyl, 3 - methyl -4 - (N-acetyl-N-methylamino) phenyl, 3 - methyl -4 - (N- Formyl-N-methyl-amino) phenyl, 3 - methyl--4 - (N-methyl-- (trifluoroacetyl) amino) phenyl, 3 - Methyl -4 - (N-methylamino) phenyl, 3 - methyl - 4 - alkyl pyrrolyl group, 3 - pyridyl, 3,4 - Dichlorophenyl, 3,4 - methylenedioxy-phenyl, 3,4,5 - trimethoxy-phenyl, 4 - (acetylamino) Phenyl, 4 - (dimethylamino) -3 - fluorophenyl, 4 - (dimethylamino) phenyl, 4 - (imidazol-1 - yl) Phenyl, 4 - (methylthio) phenyl, 4 - (morpholin-yl) phenyl, 4 - (N-(2 - (dimethylamino) ethyl) Amino) phenyl, 4 - (N-(2 - methoxyethyl) amino) phenyl, 4 - (N-acetyl-N-methyl-amino Yl) phenyl, 4 - (N-ethyl-N-formylamino) phenyl, 4 - (N-ethyl-amino) phenyl, 4 - (N- Formyl-N-(2 - methoxyethyl) amino) phenyl, 4 - (N-isopropylamino) phenyl, 4 - (N-methyl Yl-N-((2 - dimethylamino) ethyl) amino) phenyl, 4 - (N-methyl-N-(2 - (N-phthalimido Amino) 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-trifluoro-acetylamino) phenyl, 4 - (N-morpholinyl) phenyl, 4 - (thiophen-2 - yl) benzene Yl, 4 - (ureido) phenyl, 4 - (2 - (dimethylamino) acetylamino) phenyl, 4 - (2 - (2 - methoxy) Acetylamino) ethyl) amino) phenyl, 4 - (2 - methoxy) ethoxy phenyl, 4 - (2 - oxo - evil Oxazolidinyl) phenyl, 4 - (4 - methoxy-2 - butyl) phenyl, 4 - (4 - methyl-piperidinyl) phenyl, 4 - (5 - Pyrimidinyl) phenyl, 4 - amino-phenyl, 4 - bromophenyl group, a 4 - butoxy-phenyl, 4 - (formylamino) phenyl Group, a 4 - chlorophenyl, 4 - cyanophenyl, 4 - diethylamino group, a 4 - diethyl malonyl Allyl phenyl), 4 - dimethylamino-phenyl, 4 - ethoxy-phenyl, 4 - ethyl-phenyl, 4 - fluoro- Phenyl, 4 - hydroxyphenyl, 4 - imidazolyl group, a 4 - iodo-phenyl, 4 - isopropyl-phenyl, 4 - methyl Alkoxy phenyl, 4 - methyl-amino group, a 4 - methylsulfonyl group, a 4 - morpholinyl group, a 4 - N-(2 - (dimethylamino) ethyl)-N-formyl-amino)-phenyl ,4-N-(3 - methoxy-propionyl)-N-iso- Propyl - amino) phenyl ,4-N-ethyl-N-(2 - methoxyethyl) amino) phenyl ,4-N-formyl piperidine Piperidinyl phenyl, 4 - nitrophenyl, 4 - piperidyl group, 4 - pyridyl group, a 4 - pyrrolidinyl Phenyl, 4 - tert-butyl-acryloyl group, 5 - (dimethylamino) thiophene-2 - yl, 5 - amino-2 - Pyridyl group, a 5 - dimethylamino-2 - piperazinyl group, 3 - dimethylamino-pyridazin-6 - yl, 5 - dimethyl- Amino-2 - pyridyl group, a 5 - pyrimidinyl-phenyl, 6 - (N-methyl-N-formylamino) -3 - pyridyl, 6 - (N-methyl-N-(2 - methoxyethyl) amino) -3 - pyridyl, 6 - (2 - oxo - oxazolidin-morpholinyl) -3 - Pyridyl, 6 - dimethyl-3 - pyridyl, 6 - imidazol-3 - pyridyl, 6 - morpholin-3 - Pyridyl group, a 6 - pyrrolidinyl -, methyl group, (2 - propyl) -3 - pyridyl, and (4 - formylamino) Phenyl, (thiophen-2 - yl) methyl, (thiophen-3 - yl) methyl group, butyl group, cycloheptyl group, pentyl group, thiazolyl Thiophene -2 - yl, 1 - (3 - bromophenyl) ethyl, 2 - (N-phenyl-methoxycarbonyl) amino phenyl, 2 - (3 - Bromophenyl) ethyl, 2 - (3 - cyano-phenyl) methyl, 2 - (4 - bromophenyl) ethyl, 2 - (5 - chloro -2 - (thiophene Thiophene-3 - yl)) phenyl, 2 - bromophenyl group, a 2 - furyl, 2 - methylpropyl, 2 - phenylethyl, benzyl Ylmethyl, 2,3 - dimethoxyphenyl, 2,3 - methylenedioxy-phenyl, 3 - (furan-2 - yl) phenyl, 3 - (thiophen-2 - yl) phenyl, 3 - (2 - pyridyl) phenyl, 3 - (3 - methoxybenzyl) phenyl, 3 - (amino- Yl) propynyl group, a 3 - benzyloxy-phenyl, 3 - bromo-4 - fluorophenyl, 3 - bromo-5 - iodo-phenyl, 3 - bromo-5 - Methoxy-phenyl, 3 - bromophenyl, 3 - bromophenyl methyl 3 - methyl amido phenyl, 3 - chlorophenyl, 3 - Cyano group, a 3 - allyl diethyl malonyl phenyl, 3 - dimethylamino-phenyl, 3 - B Alkoxy group, a 3 - fluoro-5 - (trifluoromethyl) phenyl, 3 - fluorophenyl, 3 - hydroxyphenyl group, 3 - iodophenyl, 3 - methoxy-ethoxy group, a 3 - methoxy-phenyl, 3 - methylphenyl, 3 - methyl-phenyl-sulfonyl Group, 3 - (methylthio) phenyl, 3 - tert-butyl-acryloyl group, a 3 - (Trifluoromethoxy) phenyl, 3 - Trifluoromethyl-phenyl, 3 - vinyl pyridine group, a 3,4 - dichlorophenyl, 3,4 - dimethoxy- Phenyl, 3,4 - methylenedioxy-phenyl, 3,4,5 - trimethoxyphenyl, 3,5 - bis (trifluoromethyl) Phenyl, 3,5 - dibromo-phenyl, 3,5 - dichlorophenyl, 3,5 - dimethoxyphenyl, 3,5 - dimethyl- Phenyl, 4 - (2 - propyl) phenyl, 4 - (2 - propyl) oxy (oxy) phenyl, 4 - benzyloxy-phenyl, 4 - bromo- Phenyl, 4 - bromo-thiophen-2 - yl, 4 - butoxy group, a 4 - dimethylamino-phenyl, 4 - fluoro-3 - Three Fluoro-methylphenyl, 4 - methoxy-phenyl, 4 - neopentyl group, a 4 - phenoxy-phenyl, 5 - bromo-thiophene Thiophene -2 - yl, 5 - a cyclohexyl group, a 5 - cyclopropyl, 5 - hexyl group, a 5 - methyl-5 - phenyl, (2 - bromo-5 - chloro- Phenyl) methyl, (2 - bromophenyl) methyl and (5 - chloro -2 - (3 - methoxyphenyl) phenyl) methyl or It is here designated groups. ...

Can be independently selected from phenyl, thiophene-2 - yl, 1 - methyl-2 - oxo-benzo Oxazol-5 - yl, 2 - (dimethylamino) -5 - pyrimidinyl, 2 - (N-formyl-N-methyl-amino) -3 - ethyl Piperidinyl, 2 - (N-(2 - methoxyethyl)-N-methyl-amino) -5 - pyrimidinyl, 2 - (N-methyl-amino) - 5 - pyrimidinyl, 2 - (1 - morpholinyl)-5 - pyrimidinyl, 2 - (1 - pyrrolidinyl) -5 - pyrimidinyl, 2 - dimethyl Yl-5 - pyrimidinyl, 2 - furyl, 2 - oxo-benzoxazol-5 - yl, 2 - pyridyl, 3 - (Dimethylamino) phenyl, 3 - amino - 4 - methoxy-phenyl, 3 - bromo-4 - (dimethylamino) phenyl, 3 - methoxy-phenyl, 3 - methyl -4 - (N-acetyl-N-methylamino) phenyl, 3 - methyl -4 - (N- Formyl-N-methyl-amino) phenyl, 3 - methyl--4 - (N-methyl-- (trifluoroacetyl) amino) phenyl, 3 - Methyl -4 - (N-methylamino) phenyl, 3 - methyl - 4 - alkyl pyrrolyl group, 3 - pyridyl, 3,4 - Dichlorophenyl, 3,4 - methylenedioxy-phenyl, 3,4,5 - trimethoxy-phenyl, 4 - (acetylamino) Phenyl, 4 - (dimethylamino) -3 - fluorophenyl, 4 - (dimethylamino) phenyl, 4 - (imidazol-1 - yl) Phenyl, 4 - (methylthio) phenyl, 4 - (morpholin-yl) phenyl, 4 - (N-(2 - (dimethylamino) ethyl) Amino) phenyl, 4 - (N-(2 - methoxyethyl) amino) phenyl, 4 - (N-acetyl-N-methyl-amino Yl) phenyl, 4 - (N-ethyl-N-formylamino) phenyl, 4 - (N-ethyl-amino) phenyl, 4 - (N- Formyl-N-(2 - methoxyethyl) amino) phenyl, 4 - (N-isopropylamino) phenyl, 4 - (N-methyl Yl-N-((2 - dimethylamino) ethyl) amino) phenyl, 4 - (N-methyl-N-(2 - (N-phthalimido Amino) 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-trifluoro-acetylamino) phenyl, 4 - (N-morpholinyl) phenyl, 4 - (thiophen-2 - yl) benzene Yl, 4 - (ureido) phenyl, 4 - (2 - (dimethylamino) acetylamino) phenyl, 4 - (2 - (2 - methoxy) Acetylamino) ethyl) amino) phenyl, 4 - (2 - methoxy) ethoxy phenyl, 4 - (2 - oxo - evil Oxazolidinyl) phenyl, 4 - (4 - methoxy-2 - butyl) phenyl, 4 - (4 - methyl-piperidinyl) phenyl, 4 - (5 - Pyrimidinyl) phenyl, 4 - amino-phenyl, 4 - bromophenyl group, a 4 - butoxy-phenyl, 4 - (formylamino) phenyl Group, a 4 - chlorophenyl, 4 - cyanophenyl, 4 - diethylamino group, a 4 - diethyl malonyl Allyl phenyl), 4 - dimethylamino-phenyl, 4 - ethoxy-phenyl, 4 - ethyl-phenyl, 4 - fluoro- Phenyl, 4 - hydroxyphenyl, 4 - imidazolyl group, a 4 - iodo-phenyl, 4 - isopropyl-phenyl, 4 - methyl Alkoxy phenyl, 4 - methyl-amino group, a 4 - methylsulfonyl group, a 4 - morpholinyl group, a 4 - N-(2 - (dimethylamino) ethyl)-N-formyl-amino)-phenyl ,4-N-(3 - methoxy-propionyl)-N-iso- Propyl - amino) phenyl ,4-N-ethyl-N-(2 - methoxyethyl) amino) phenyl ,4-N-formyl piperidine Piperidinyl phenyl, 4 - nitrophenyl, 4 - piperidyl group, 4 - pyridyl group, a 4 - pyrrolidinyl Phenyl, 4 - tert-butyl-acryloyl group, 5 - (dimethylamino) thiophene-2 - yl, 5 - amino-2 - Pyridyl group, a 5 - dimethylamino-2 - piperazinyl group, 3 - dimethylamino-pyridazin-6 - yl, 5 - dimethyl- Amino-2 - pyridyl group, a 5 - pyrimidinyl-phenyl, 6 - (N-methyl-N-formylamino) -3 - pyridyl, 6 - (N-methyl-N-(2 - methoxyethyl) amino) -3 - pyridyl, 6 - (2 - oxo - oxazolidin-morpholinyl) -3 - Pyridyl, 6 - dimethyl-3 - pyridyl, 6 - imidazol-3 - pyridyl, 6 - morpholin-3 - Pyridyl group, a 6 - pyrrolidinyl -, methyl group, (2 - propyl) -3 - pyridyl, and (4 - formylamino) Phenyl, (thiophen-2 - yl) methyl, (thiophen-3 - yl) methyl group, butyl group, cycloheptyl group, pentyl group, thiazolyl Thiophene -2 - yl, 1 - (3 - bromophenyl) ethyl, 2 - (N-phenyl-methoxycarbonyl) amino phenyl, 2 - (3 - Bromophenyl) ethyl, 2 - (3 - cyano-phenyl) methyl, 2 - (4 - bromophenyl) ethyl, 2 - (5 - chloro -2 - (thiophene Thiophene-3 - yl)) phenyl, 2 - bromophenyl group, a 2 - furyl, 2 - methylpropyl, 2 - phenylethyl, benzyl Ylmethyl, 2,3 - dimethoxyphenyl, 2,3 - methylenedioxy-phenyl, 3 - (furan-2 - yl) phenyl, 3 - (thiophen-2 - yl) phenyl, 3 - (2 - pyridyl) phenyl, 3 - (3 - methoxybenzyl) phenyl, 3 - (amino- Yl) propynyl group, a 3 - benzyloxy-phenyl, 3 - bromo-4 - fluorophenyl, 3 - bromo-5 - iodo-phenyl, 3 - bromo-5 - Methoxy-phenyl, 3 - bromophenyl, 3 - bromophenyl methyl 3 - methyl amido phenyl, 3 - chlorophenyl, 3 - Cyano group, a 3 - allyl diethyl malonyl phenyl, 3 - dimethylamino-phenyl, 3 - B Alkoxy group, a 3 - fluoro-5 - (trifluoromethyl) phenyl, 3 - fluorophenyl, 3 - hydroxyphenyl group, 3 - iodophenyl, 3 - methoxy-ethoxy group, a 3 - methoxy-phenyl, 3 - methylphenyl, 3 - methyl-phenyl-sulfonyl Group, 3 - (methylthio) phenyl, 3 - tert-butyl-acryloyl group, a 3 - (Trifluoromethoxy) phenyl, 3 - Trifluoromethyl-phenyl, 3 - vinyl pyridine group, a 3,4 - dichlorophenyl, 3,4 - dimethoxy- Phenyl, 3,4 - methylenedioxy-phenyl, 3,4,5 - trimethoxyphenyl, 3,5 - bis (trifluoromethyl) Phenyl, 3,5 - dibromo-phenyl, 3,5 - dichlorophenyl, 3,5 - dimethoxyphenyl, 3,5 - dimethyl- Phenyl, 4 - (2 - propyl) phenyl, 4 - (2 - propyl) oxy (oxy) phenyl, 4 - benzyloxy-phenyl, 4 - bromo- Phenyl, 4 - bromo-thiophen-2 - yl, 4 - butoxy group, a 4 - dimethylamino-phenyl, 4 - fluoro-3 - Three Fluoro-methylphenyl, 4 - methoxy-phenyl, 4 - neopentyl group, a 4 - phenoxy-phenyl, 5 - bromo-thiophene Thiophene -2 - yl, 5 - a cyclohexyl group, a 5 - cyclopropyl, 5 - hexyl group, a 5 - methyl-5 - phenyl, (2 - bromo-5 - chloro- Phenyl) methyl, (2 - bromophenyl) methyl and (5 - chloro -2 - (3 - methoxyphenyl) phenyl) methyl or It is here designated groups. ...

As used herein, the term "aryl" or "substituted aryl" refers to a carbocyclic aryl group includes, for example Such as phenyl and 1 - or 2 - naphthyl group, which may be unsubstituted or substituted by Cl, Br, F, I, cyano, methyl Acylamino, hydroxy, lower alkoxy, lower alkyl, lower alkenyl, lower alkynyl group, Amino, lower alkylamino, di (lower alkylamino), N-lower alkyl-N-lower alkoxy Group, a trifluoromethyl group or a methoxy group is independently methyl group substitution on it 1, 2 Or 3 hydrogen atoms replaced. Further, the term "aryl" refers to the use a urea group, a Alkylsulfonyl group, a pyrimidinyl group, a pyridyl group, a pyridazinyl group, a morpholinyl group, a phenyl - lower alkoxy group, Phenyl - lower alkenyl group or a cycloalkyl - lower alkyl-substituted phenyl group. Examples of aromatic groups Including (but not limited) of 3 - bromophenyl, 3 - chlorophenyl, 4 - chlorophenyl, 3 - methoxy-phenyl, 3 - (2 - propyl) phenyl, 3,4 - dimethoxy-phenyl, 3 - (trifluoromethyl) phenyl, 3 - trifluoro-4 - fluorophenyl, 4 - (N-methyl-N-methoxy) ethyl group phenyl, 4 - dimethylamino-phenyl, 3 - fluoro-4 - methyl- Phenyl, 4 - methylphenyl, 4 - cyano-phenyl, 4 - methyl-propyl, 3,5 - dichlorophenyl, 3,4 - Methylenedioxy-phenyl, 3 - cyanopropyl group, 4 - ureido group, a 3 - methyl sulfonyl group, 3 - (formylamino) propyl group or the other groups shown here. ...

The term "aryloxy" refers to a bond via an ether (i.e., through an oxygen atom) connected to Aryl groups to the molecule, in terms of the examples is a phenoxy group, a naphthyl group, a 4 - chlorophenoxy, 4 - methylphenoxy group, 3,5 - dimethoxy phenyl group.

The term "cycloalkyl" refers to a ring having 3 to 7 atoms, a cyclic saturated hydrocarbon group. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. Ring Groups may also be described as C₃-C ₈Cycloalkyl.

The term "cycloalkyl - lower alkyl" refers to the practice with a ring as defined above Alkyl group to the replacement of a hydrogen atom as defined below substituted with a lower alkyl group. Ring Alkyl - Examples of lower alkyl groups include cyclopropyl group, cyclobutyl group, cyclopentyl group, a Cyclohexylmethyl and cycloheptyl and butyl.

The term "heteroaryl" refers to a five to seven ring atoms of which one ring atom Is nitrogen, oxygen or sulfur, monocyclic aryl, wherein 1 or 2 ring atoms independently selected for another From S, O or N heteroatom and the remaining ring atoms are carbon, the group through any The ring atom to other portions of the molecule. Heteroaryl groups may be unsubstituted or through Over a Cl, Br, F, I, cyano, carboxamido, hydroxy, lower alkoxy, lower alkoxy Group, a lower alkenyl group, a lower alkynyl group, an amino group, a lower alkylamino group, a di (lower alkyl amino Yl), N-lower alkyl-N-lower alkoxy group, a trifluoromethyl group or a methoxy group methyl group alone Are replaced at the site, two or three hydrogen atoms replaced. Further, the term "heteroaryl group" Refers to the use a urea group, a methylsulfonyl group, pyrimidinyl, pyridyl, pyridazinyl, morpholino Group, a phenyl - lower alkoxy group, a phenyl - lower alkenyl group or a cycloalkyl - lower alkyl group take Substituted heteroaryl group. Furthermore, heteroaryl groups can be replaced with a combination of atoms, Optionally two adjacent hydrogen atoms to form a fused and substituted benzene ring. Examples of heteroaryl groups include pyridine Piperidinyl, pyrazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, Yl, isoxazolyl, thiadiazolyl, oxadiazolyl, furanyl, thienyl, 5 - methyl-thiophene -2 - Yl, 5 - nitro-thiophen-2 - yl, 5 - methyl furyl, benzofuranyl, benzothienyl As shown here, etc. and other groups. ...

The term "heterocycle" refers to a saturated or unsaturated ring having four to seven atoms of One ring atom is nitrogen or oxygen group monocyclic ring system, 1 or 2 ring atoms are additional Is independently selected from S, O or N heteroatom and the remaining ring atoms are carbon, the group by Any of the ring atoms is connected to other parts of the molecule, and the nitrogen or carbon atom with another Outside of the substituted groups selected from: aryl-(lower alkyl), alkoxy carbonyl group, a lower alkyl group, Halo (lower alkyl), amino (lower alkyl), hydroxy-substituted lower alkyl, hydroxy, lower Alkoxy, halogen, amino, lower alkyl amino, and amino, (lower alkyl) amino group or Having 1 to 8 carbon atoms, alkanoylamino wherein said amino group may be further substituted by 1-8 Carbon alkanoyl, a α-amino acid or a polypeptide. Examples of heterocycles include pyridine Pyrrolidine, tetrahydrofuran, dihydropyrrole, isoxazolidine, oxazolidine, tetrahydropyridine, piperidine, Piperazine, morpholine, thiomorpholine, aziridine, azetidine, and those described herein in addition Said heterocycle. ...

In this use, the term "lower alkyl" refers to a containing 1 to 6 carbon atoms, saturated And the straight chain or branched chain hydrocarbon group, which may be unsubstituted or substituted by a group selected from the following set independently Exchanged for the 2 or 3 hydrogen atoms are replaced: Cl, Br, F, I, cyano, methyl amide , Hydroxy, lower alkoxy, amino, lower alkylamino, di (lower alkylamino) or N-lower alkyl-N-lower alkoxy-amino group. Examples of lower alkyl groups include (but are not Limited to) methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, neopentyl, n-hexyl Group, a hydroxy group, a methoxy group, trifluoromethyl 3 - cyano-propyl, 3 - formylaminopropionitrile Group. In some cases, the description of "C ...₁-C ₆In this use, the term "lower alkyl" refers to a containing 1 to 6 carbon atoms, saturated And the straight chain or branched chain hydrocarbon group, which may be unsubstituted or substituted by a group selected from the following set independently Exchanged for the 2 or 3 hydrogen atoms are replaced: Cl, Br, F, I, cyano, methyl amide , Hydroxy, lower alkoxy, amino, lower alkylamino, di (lower alkylamino) or N-lower alkyl-N-lower alkoxy-amino group. Examples of lower alkyl groups include (but are not Limited to) methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, neopentyl, n-hexyl Group, a hydroxy group, a methoxy group, trifluoromethyl 3 - cyano-propyl, 3 - formylaminopropionitrile Group. In some cases, the description of "C ...₀-C ₆Alkyl "indicates May be present in the carbon atoms in the alkyl chain including zero. These terms can also be used in a similar An aryl group or a heteroaryl group, or belong to the other group and represent or have as "aryl group" Or "heteroaryl group" meaning the same.

In this use, the term "lower alkenyl" refers to a containing from 2 to 6 carbon atoms, a single Branched unsaturated straight or branched chain hydrocarbon groups including (but not limited to) ethenyl, propenyl, n- Butenyl, isobutenyl, n-pentenyl and n-hexenyl. These variables can also be described as Like C₂-C ₆Alkenyl.

The term "lower alkoxy" refers to the ether by means of a key (i.e., through an oxygen atom) Connected to the molecule of the lower alkyl groups, such as methoxy, ethoxy, propoxy, 2 - propoxy Group, a 2 - methyl - 2 - propoxy, t-butoxy, pentyloxy, hexyloxy, and isomeric forms thereof And so on. The term is also described as C₁-C ₆Alkoxy.

In this use, the term "lower alkynyl group" refers to compounds having a triple bond and containing from 2 to 6 carbon atoms, a straight-chain or branched-chain hydrocarbon group, including (but not limited to) ethynyl, propynyl, N-butynyl, n-pentynyl and n-hexynyl. The term is also described as C₂-C ₆Alkynyl group.

The term "mammal" has its ordinary meaning and includes human.

In a further aspect of the invention, the present invention discloses a compound containing a pharmaceutically Pharmaceutically acceptable carrier composition.

As described above, the present invention comprises one or more compounds with one or more non-toxic Of physiologically tolerable or acceptable diluents, carriers, adjuvants or carriers (here Known diluent) formulated into compositions together for parenteral injection, in solid or liquid form Type for oral administration, for rectal or topical administration. As known in the art, the present invention is Compound may exist in various forms, including pharmaceutically acceptable salts, amides and so on.

Appropriate amount released can be prepared compounds of the invention compositions. We believe that the next Column can provide optimal therapeutic doses: intravenous infusion :0.1-250nmol / kg / min, preferably Is 1-50nmol/kg / min; oral :0.01-250μMol / kg / day, preferably about 0.1 to 50 μMol / kg / day; these oral molar dosage equivalent 0.005-125mg/kg / day, preferably 0.05-25mg/kg / day. For the treatment of acute illness, preferably intravenous route of administration; slow Preferably treatment of diseases of a tablet or sustained-release oral formulations.

"Pharmaceutically acceptable amide" refers to the compounds of the present invention, pharmaceutically acceptable Non-toxic amides, including the use of a suitable organic acid or amino acid amide in which the Amino acids include amino acids containing from 1 to 6 connected via an amide peptide bond, which may be of Branched or linear, wherein the amino acid is independently selected from the naturally occurring amino acids such as GAN Acid, alanine, leucine, valine, phenylalanine, proline, methionine, color Threonine, asparagine, aspartic acid, glutamic acid, glutamine, serine, threonine, Lysine, arginine, tyrosine, histidine, ornithine and the like. ...

The term "the substituted forms" refers to those groups in general, such as an aryl group or a heteroaryl group Or a heterocyclic group, and these groups are chemically suitable position on the aryl group, a heteroaryl group, a heterocyclic Or other generally around variable has a substituent, as in this designated or exemplified.

The compounds of the invention can be derived from inorganic or organic acids, pharmaceutically acceptable The salt form. Such salts include (but are not limited to): acetate, adipate, alginate Acid, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphor Brain acid, camphor sulfonate, citrate, cyclopentane-propionate, digluconate, ten Dialkyl sulfates, ethanesulfonate, Huang, fumarate, glucoheptonate, Glycerophosphate, hemisulfate, heptanoate, saccharinate, hydrochloride, hydrobromide, Hydroiodide 2 - hydroxy - ethanesulfonate, lactate, maleate, mesylate, nicotinate, Salt 2 - naphthalenesulfonate, oxalate, palmitate (palmoate), pectinate, persulfate Salt 3 - phenylpropionate, phosphate, picrate, pivalate, propionate, succinate, , Tartrate, thiocyanate, p-toluenesulfonate and undecanoate. ...

Suitable cationic salts can be easily prepared by a conventional method, such as with a suitable amount of A base such as an alkali or alkaline earth metal (e.g., sodium, potassium, lithium, calcium or magnesium) hydroxides, or organic bases Such as an amine (e.g., dibenzylethylenediamine, cyclohexylamine, dicyclohexylamine, triethylamine, piperidine, pyrrolidine Alkyl, benzyl amine, etc.) or quaternary ammonium hydroxide (such as tetramethyl ammonium hydroxide, etc.) treatment of the acid of formula I. Moreover, the nitrogen-containing basic group, such agents can also be used such as lower alkyl halides (such as methyl, Ethyl, propyl and butyl chlorides, bromides and iodides); dialkyl sulfates; long Chain halides (such as decyl, lauryl, myristyl and stearyl chloride, bromide Material and iodides; arylalkyl halide (such as benzyl and phenethyl bromides) quaternized Technology. Thus obtained water-soluble or oil-soluble or dispersible product. ...

Further included within the scope of the present invention containing one or more of such preparation and to Manner as described under one or more non-toxic pharmaceutically acceptable carriers, with A compound of formula I prepared pharmaceutical composition.

Further included within the scope of the present invention containing one or more of such preparation and to Manner as described under one or more non-toxic pharmaceutically acceptable carriers, with A compound of formula I prepared pharmaceutical composition....

These compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying and dispersing Agent. Prevention of the action of microorganisms can be a variety of antimicrobial and antifungal agents such as methyl p-hydroxybenzoate Esters, chlorobutanol, phenol, sorbic acid, etc. to ensure. May also need to include isotonic agents such as Sugars, and sodium chloride. Through the use of agents delaying absorption, such as aluminum monostearate and gelatin can cause Prolonged absorption of injectable pharmaceutical forms.

If requested and for more effective distribution, the compounds can be incorporated into slow release or targeted The transmission system such as a polymer backbone, liposomes, and microspheres. They may, for example by, for example thin Bacteria retaining filter filtration or by adding sterile solid compositions sterilization sterilizing agents, the use of Immediately before the composition is dissolved in sterile water or other sterile injectable matrix.

Solid dosage forms for oral administration may include capsules, tablets, pills, powders, and Granules. In such solid dosage forms, the active compound with said at least one inert customary With excipient (or carrier) such as sodium citrate or dicalcium phosphate and the further following substances mixed Together: (a) fillers or bulking agents such as starch, lactose, sucrose, glucose, mannitol and Silicic acid; (b) binders such as carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidine Ketones, 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 sodium carbonate; (e) was blocked Agents such as paraffin; (f) absorption accelerators such as quaternary ammonium compounds; (g) wetting agents such as cetyl alcohol monostearate Fatty acid glycerides; (h) adsorbents such as kaolin and bentonite high;, and (i) lubricants such as talc, Calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, or mixtures thereof. In capsules, tablets and pills, these formulations also include buffering agents. ...

Solid dosage forms such as tablets, dragees, capsules, pills and granules can be coated and Enteric coated capsule shell such as known in the art, and other prepared. They may contain opacifying agents (pacifying agent), but also for such compositions that are in a specific enteric delayed manner Parts of the release of active compound. The implant can be used Examples of compositions polymeric substances and waxes Classes.

If appropriate, the active compounds may also be with one or more of the above-mentioned In micro-encapsulated form excipients.

Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, Suspensions, syrups and elixirs. Addition to the active compounds, the liquid dosage forms may contain the ability Inert diluents commonly used in the domain (such as water or other solvents), solubilizing agents and emulsifiers (for example, Such as ethanol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene Diol, 1,3 - butylene glycol, dimethylformamide, oils, in particular cottonseed oil, peanut oil, corn Rice germ oil, olive oil, castor oil and sesame oil, glycerol, tetrahydrofurfuryl alcohol, polyethylene glycol, and Sorbitan fatty acid ester or a mixture of these substances. ...

Addition to the active compounds, suspending agents may include suspending agents such as ethoxylated isostearyl Alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum hydroxide side, Bentonite, agar and tragacanth, or mixtures of these substances.

For rectal and vaginal administration, the compositions preferably suppositories, which is obtained by the present invention. Compound with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository Prepared by mixing the wax and the like, which is solid at room temperature but liquid at body temperature, and therefore Melt in the rectum or vaginal cavity and release the active ingredient.

The compounds of the invention for topical or transdermal administration of a dosage form further comprises cream , Pastes, creams, lotions, gels, powders, solutions, sprays, inhalants Or transdermal posts agent. With transdermal delivery transdermal agent posts the present invention is particularly effective and preferred Forms. The active ingredient under sterile conditions with a pharmaceutically acceptable carrier and any of the Needed preservatives, buffers, or propellants mixed required. It is understood that agents in transdermal formulations posts Preparation of some medicines may need special treatment. For example, the nature of volatile compounds May require special preparation or with special packaging materials mixed with in order to ensure the proper dosage biography Delivery. Also, can very rapidly absorbed through the skin and absorption of the compound may require extension Late agents or barrier materials are formulated. Ophthalmic formulations, eye ointments, powders, solutions also In the scope of the invention. ...

The invention compounds may also be administered in the form of liposomes. As is known in the art, Liposomes are generally esters of phosphor or other materials derived from lipids. Dispersed in an aqueous medium through Quality of the single - or multi-chamber liquid crystal hydrate is formed liposomes. You can use any non-toxic, And physiologically acceptable metabolizable lipid capable of forming liposomes. In addition to the present compounds, In the form of liposome compositions may contain stabilizers, preservatives, excipients and the like. Preferred fat Quality is the natural and synthetic esters and phosphate esters of phosphorous acid choline (lecithin). Side forming liposomes Method known in the art. See, e.g., Prescott, Ed., Methods in Cell Biology, Volume 14, Academic Press, New York, NY, (1976), page 33 and the following and so on. Synthesis ...

The invention compounds may also be administered in the form of liposomes. As is known in the art, Liposomes are generally esters of phosphor or other materials derived from lipids. Dispersed in an aqueous medium through Quality of the single - or multi-chamber liquid crystal hydrate is formed liposomes. You can use any non-toxic, And physiologically acceptable metabolizable lipid capable of forming liposomes. In addition to the present compounds, In the form of liposome compositions may contain stabilizers, preservatives, excipients and the like. Preferred fat Quality is the natural and synthetic esters and phosphate esters of phosphorous acid choline (lecithin). Side forming liposomes Method known in the art. See, e.g., Prescott, Ed., Methods in Cell Biology, Volume 14, Academic Press, New York, NY, (1976), page 33 and the following and so on. Synthesis ...¹、R ²、 R ³And R⁴As defined above.

Process 1

Prepared in accordance with Scheme 1 where R¹And R²Is hydrogen, formula (II) compound. In four (three phenyl Lin) palladium (O) or other suitable palladium (O) complexes, and alkali metal bases such as sodium hydroxide or potassium Hydroxide aqueous solution (preferably aqueous sodium or potassium bicarbonate buffer) in the presence of the Materials 4,6 - diamino-5 - iodo-pyrimidine (1) wherein R³Is a lower alkyl, a lower alkenyl group, A lower alkynyl group, an aryl group, an arylalkyl group, a heterocyclic group or a substituted aryl or heteroaryl form ethylene Boronic acid derivative (2) under reflux for about 8 to about 24 hours, compound (3). In Presence of potassium carbonate in DMF at about 40 ℃ to about 50 ℃ under treatment with iodine 4,6 - Diaminopyridine about 24 hours to prepare the compound (1). In a solvent such as THF, by Such that R³- Substituted acetylene and catechol borane may be prepared by reaction of formula (2) compound. According to a variety of literature Methods such as Van Hijfte, Tetrahedron Letters, 1989,30:3655; Tao, etc., J.Org. Chem., 1990,55:63 and Rossi, etc., Gazz.Chim.Ital. ,1990,120:783-791 can be Preparation of R³- Replace acetylene.

Then the Suzuki reaction conditions, in a suitable anhydrous solvent such as diphenyl ether, 1,2,4 - Trichlorobenzene, toluene and the like, to absorb the water formed by the reaction of 4 presence of molecular sieves, Compound (3) and wherein R⁴Is aryl, heteroaryl or heterocyclic group aldehyde compound (4) in the return Flow for about 2 to about 24 hours, compound (5). Compound (5) wherein R¹And R²Is hydrogen, formula (II) compound. The compound was prepared according to Scheme 1 may be further treated with a suitable also The reducing agent in the presence of a catalyst such as hydrogen or other reducing agent to form a 5, 6 and / or 7, 8 also The original form of formula (II) compound. In addition, you can restore the formation of 5,6 - and 7,8-bit single- Between the key and the 6,7 double bond. In the former case, the formation of stereoisomers and package Included within the scope of the present invention. These isomers may be isolated by conventional methods after.

Process 2

In accordance with Scheme 2, wherein R¹And R²One or both of a lower alkyl group, an arylalkyl group Or acyl of the formula (II) can be prepared by treating the compound with an appropriate reagent (5) thereof. To The preparation of which R¹And R²Are not all hydrogen atoms of the formula (I) or (II) compound, from which R¹And R²Two hydrogen atoms are of the formula (I) required for preparing the derivatives of the compound are possible. When R¹Or R²Is lower alkyl, which can be in a suitable solvent such as dichloromethane or THF In the presence of a base such as triethylamine or potassium carbonate in the presence of the free amino group with the appropriate alkyl Based reagent such as an alkyl halide, alkyl mesylate or tosylate ester group to Complete. When R¹Or R²Is aryl alkyl, which can be in a suitable solvent such as dichloromethane Or THF in the presence of a base such as triethylamine or potassium carbonate in the presence of the free amino group with the appropriate When the aryl alkyl halide, alkyl mesylate or tosylate ester group can be finished Percent. When R¹Or R²An acyl group, which can be in a suitable solvent such as dichloromethane or THF In the presence of a base such as triethylamine or potassium carbonate in the presence of the free amino group with the appropriate acid anhydride, Acid halides such as acid chloride or an activated acyl group such as an acyl cyanide, azide or thiol Ester reaction to be completed. When R¹And R²With the nitrogen atom to which they are attached form optionally together Contain an additional oxygen or nitrogen atom a 5 - to 7-membered ring, the compounds may be used Having replaced the 4 - position of the amino group of a halogen atom and optionally containing precursor compound in addition An oxygen or nitrogen atom a 5 - to 7-membered ring compound was prepared. Such compounds Examples include (but are not limited to) morpholine, piperidine, pyrrolidine, piperazine, thiomorpholine, etc.. This An alternative method can also be used to prepare alkyl substituted amino compounds, for example, by reacting chlorine -Compound with mono-or di-substituted amines such as diethylamine, allyl amine, dibutyl amine anti- Should. The reaction example in a solvent such as dichloromethane, in the presence of tertiary amines such as occur easily. Having replaced the 4 - position of the amino group of a halogen atom by reacting the precursor compound 6 - amino-4 - Chloro-5 - iodo-pyrimidine substituted 4,6 - diamino-5 - iodo-pyrimidine (Scheme 1, compound (1)) to the system The product was prepared and to further reaction. ...

With the nitrogen atom to which they are attached form optionally together Contain an additional oxygen or nitrogen atom a 5 - to 7-membered ring, the compounds may be used Having replaced the 4 - position of the amino group of a halogen atom and optionally containing precursor compound in addition An oxygen or nitrogen atom a 5 - to 7-membered ring compound was prepared. Such compounds Examples include (but are not limited to) morpholine, piperidine, pyrrolidine, piperazine, thiomorpholine, etc.. This An alternative method can also be used to prepare alkyl substituted amino compounds, for example, by reacting chlorine -Compound with mono-or di-substituted amines such as diethylamine, allyl amine, dibutyl amine anti- Should. The reaction example in a solvent such as dichloromethane, in the presence of tertiary amines such as occur easily. Having replaced the 4 - position of the amino group of a halogen atom by reacting the precursor compound 6 - amino-4 - Chloro-5 - iodo-pyrimidine substituted 4,6 - diamino-5 - iodo-pyrimidine (Scheme 1, compound (1)) to the system The product was prepared and to further reaction. ...

In a further aspect of the present invention, discloses a method for inhibiting adenosine kinase. According to the party Method, the adenosine kinase exposed to an effective inhibiting amount of adenosine kinase inhibitor compounds of the present invention. The preferred compound used in the process the same as given above. Determination of an effective inhibitory amount Methods well known in the art.

The inhibition of adenosine kinase in vitro can be located, in situ or in vivo. Adenosine kinase in When in vitro, the adenosine kinase inhibitor compounds in contact, usually by adding the compound Contain enzymes into radiolabeled substrate adenosine, magnesium chloride and ATP solution. That Enzymes may be present in intact cells or present in the enzyme in isolated subcellular fractions. Then the presence of the enzyme inhibitor, and under physiological conditions in a suitable period of time. The method of measuring the holding time are well known in the art, and is particularly dependent on the concentration of enzyme and Physiological conditions. Suitable physiological conditions must be maintained for those conditions viability of adenosine kinase, Including temperature, acidity, tension. Inhibition of adenosine kinase can be in the art, for example, according Standard methods well known (Yamada, etc., Comp.Biochem.Physiol.1982, 71B: 367-372) implemented. ...

The compounds of the present invention, the so-called "therapeutically effective amount" means applicable to any medical treatment Therapy reasonable benefit / risk ratio, the treatment or alleviation of disease or related adenosine kinase that Some of adenosine by inhibiting adenosine kinase, and to improve the level of a disease or disorder can be improved compound A sufficient amount. However, be understood that the invention compounds and pharmaceutical compositions of the total daily dose Attending physician in the correct decisions within the scope of medical judgment. Any special treatment of patients with special Therapeutically effective dose will depend upon a variety of factors, including the disease being treated and the severity of the disease Level; the activity of the specific compound employed; the specific composition used; patients of Age, body weight, general health, sex and diet; administration time, administration route and the Excretion of the specific compound employed; duration of the treatment; the particular compound being used Joint or simultaneous use of drugs and medical fields and well-known ability to physician Within the scope of other factors. ...

The compounds of the present invention, the so-called "therapeutically effective amount" means applicable to any medical treatment Therapy reasonable benefit / risk ratio, the treatment or alleviation of disease or related adenosine kinase that Some of adenosine by inhibiting adenosine kinase, and to improve the level of a disease or disorder can be improved compound A sufficient amount. However, be understood that the invention compounds and pharmaceutical compositions of the total daily dose Attending physician in the correct decisions within the scope of medical judgment. Any special treatment of patients with special Therapeutically effective dose will depend upon a variety of factors, including the disease being treated and the severity of the disease Level; the activity of the specific compound employed; the specific composition used; patients of Age, body weight, general health, sex and diet; administration time, administration route and the Excretion of the specific compound employed; duration of the treatment; the particular compound being used Joint or simultaneous use of drugs and medical fields and well-known ability to physician Within the scope of other factors. ...¹⁴C-adenosine phosphorylation capacity measurement. These cells may be finished Whole or broken. The specificity of adenosine kinase inhibitory activity of inhibitors by And A2α adenosine A1 receptors, adenosine and adenosine deaminase activity to measure the role of transporters Fixed.

C-adenosine phosphorylation capacity measurement. These cells may be finished Whole or broken. The specificity of adenosine kinase inhibitory activity of inhibitors by And A2α adenosine A1 receptors, adenosine and adenosine deaminase activity to measure the role of transporters Fixed....

Pain in a mammal such as a mouse hot plate test compounds in the present invention in vivo Testing. In the following example, a method described in Example 55, 103 and 104, a compound Was pretreated (30μmol/kg ip) test for 30 minutes for the drug tested to 10 jump latency (in seconds). The longer the number of seconds, then the medication from the hot plate masking Feel pain more effectively. The solvent alone was (72.76 seconds ± 10.51), compound 55 is 132.86 Sec. Compound 103 was 103.29 seconds. When the test, the compound 104 was 62.44 seconds in Worthless score, so will the pain models in another test again. Therefore, as in this Animal models and the other tests described below demonstrated herein, the compounds of the invention Is effective pain relief agents and adenosine kinase inhibitors. ...

The weight is about 25-35g male CF1 mice (Charles River) with 10mg/kg Test compounds intraperitoneally or orally pretreated 8 animals per dose group. Place in the pre- Reasonable period ends, the mice were individually placed Omnitech Electronics Automated 16 Animal hot plate analgesia monitor (Columbus, OH; model AHP16AN) of warmed to 55 ℃ of 9.8 × 7.2 × 15.3cm (L × W × H) copper above the plastic limit of the inner zone. Located Each area within the limits of the infrared sensor near the top of the mouse jumped off the record when the hot surface Beam cross. Automatically record each jump latency time, and the first and tenth Both jumping latency times for data analysis. 180 seconds will not jump up to 10 times Standard mouse immediately removed from the hot plate in order to avoid tissue damage, and designated as 180 seconds For them to 10th jump preclinical maximum. ...

The present invention is determined in vitro inhibitor compounds of the invention and many of them can be found in To inhibit adenosine kinase activity. Some representative results shown in the following Table 1. This These data indicate that these compounds inhibit adenosine kinase.

Table 1 Representative compounds of the present invention for the inhibition of adenosine kinase

Compound of Example No.	IC ₅₀(nM)
Compound of Example No.	IC ₅₀(nM)	2	73
3	185	2	73
3	185	6	467
9	115	6	467
9	115	10	317
15	11	10	317
15	11	36	250
38	45	36	250
38	45	55	5
59	117	55	5
59	117	62	30
63	200	62	30
63	200	78	25
98	95	78	25
98	95	103	33
104	8	103	33

Treatment of cerebral ischemia, epilepsy, nociceptive perception (nociception) (pain), including as a result Sepsis, inflammatory diseases caused by infection such as septic shock method

In a further aspect of the present invention, discloses the treatment of human or lower mammal cerebral ischemia, Epilepsy, nociceptive sensory or nociceptive pain, including as a result of diseases caused by sepsis infection Inflammatory diseases such as septic shock, said method comprising administering to a mammal treated An effective amount of the compound.

In certain diseases cells has been observed to change adenosine kinase activity. Relative to normal Liver, rat liver cells in a variety of tumor cells found in adenosine kinase activity is reduced: the enzyme Activity in tumor growth rate showed a negative relationship (Jackson, etc., Br.J.Cancer, 1978,37:701-713). In experimental animals regenerating liver after partial hepatectomy in stimulated adenosine Activity is reduced (Jackson etc., Br.J.Cancer ,1978,37:701-713). In gout patients Erythrocyte adenosine kinase activity were found to decrease (Nishizawa, etc., Clin.Chim.Acta 1976, 67:15-20). Is infected with the human immunodeficiency virus (HIV) patients showing symptoms of AIDS Lymphocytes decreased adenosine kinase activity, and compared with the normal healthy control group in the absence of disease Like HIV-seropositive and HIV-seronegative high-risk subjects increased enzyme activity (Renouf, etc., Clin.Chem.1989 ,35:1478-1481). Tip measuring adenosine kinase activity Verifiable monitoring of patients infected with HIV is useful for clinical progression (Renouf, etc. Clin.Chem.1989 ,35:1478-1481). Sepsis infection may lead to system inflammatory syndrome (SIRS), which is characterized by increased production of cytokines, leukocyte neutrophil accumulation, hemodynamic Force effects and tissue damage or death. Due to a known anti-inflammatory effects of adenosine, adenosine kinase inhibitor Preparations in the organization's ability to raise levels of adenosine syndrome has been shown to improve symptoms (Firestein Etc., J.of Immunology, 1994, the first .5853-5859 page). Because adenosine has been confirmed Or an analogue thereof resulting antinociceptive perception or anti-nociceptive effect, so we expected to be adenosine Increased levels of adenosine kinase inhibitor's ability to relieve pain states (Swaynok etc. Neuroscience, 1989,32: No.3, page .557-569 page). ...

Example 1

4 - amino-6 - phenyl-7 - (p - dimethylaminophenyl) pyrido [2,3-d] pyrimidine

4,6 - diamino-5 - (2 - phenyl-vinyl) pyrimidine (150mg) was suspended in a sample containing 1.2eq 4 - (dimethylamino) benzaldehyde ("R⁴"Reagent) and 1.5g of 4 molecular sieves 10mL phenyl ether. The solution was heated to 170 ℃ for 4 hours, then cooled and addition Solvent. The residue was purified by column chromatography to give the title compound. IR (KBr) 3325, 1589,1555,1400,1340,1196,819 cm^-1；MS m/z 342(M+H) ⁺。

4,6 - Diamino-5 - (2 - phenyl-ethenyl) pyrimidine was prepared as follows:

1a.5-iodo-4, 6 - diaminopyrimidine

4,6 - diamino pyrimidine hemisulfate monohydrate (26.13g, 147.5mmol, Aldrich) and K₂CO ₃(30.58g, 221.3mmol) was suspended in water (400mL) in. To the suspension Solution was added iodine (41.19g, 162.3mmol) in DMF (100mL) was added. The mixture was stirred at 45 ℃ under heating for 23 hours. After cooling, Na₂S ₂O ₃(15mL) was quenched with an excess of 2M Of iodine. The white product was then collected, washed with water (3 × 20mL) and dried under high vacuum drying, To obtain the title compound 33.1g (90%).

1b.2-phenyl-vinyl boronic acid ("R³"Reagent)

Phenylacetylene (5mmol, Aldrich) was dissolved in 5mL of dry THF and at 0 ℃ Was added dropwise with borane (5mL, in THF, 1M, Aldrich). The solution was heated to Was refluxed for 1.5 hours and the solvent removed in vacuo. The solution was washed with a 1M HCl (10mL) step Cooling, and the solution was used directly in the next step.

1c.4, 6 - diamino-5 - (2 - phenyl-ethenyl) pyrimidine

A mixture of 2 - phenyl-vinyl boronic acid (5mmol), 5% of Pd (PPh₃) ₄And the 1M Na₂CO ₃(10mL) was added to 5 - iodo-4, 6 - diamino-pyrimidine (1mmol, from the above steps 1a) The dioxane solution of 50mL. The reaction mixture was heated for 12 hours. Except in vacuo The solvent and the residue was diluted with water and CH₂Cl ₂(3 × 30mL) extracted. Decompression The organic layer was concentrated and the residue was dried under high vacuum. Crude product was subjected to column chromatography (using 5% MeOH / CH₂Cl ₂As eluent) to give the title compound. MS m / z: 213 (M + H)⁺。

Example 2-107

The method as in Example 1, but using the following reagents given in Table 1 was used instead of Example 1 R³And R⁴Reagent to produce the compound of Example 2-107.

Table 1

Example 2-107

Example Number	Name	R ⁴Reagents - (7)	R3 reagent - (6 - bit)	Data
Example Number	Name	R ⁴Reagents - (7)	R3 reagent - (6 - bit)	Data	2	4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - (Dimethylamino) phenyl) pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR(KBr)3360， 1660，1600，1185， cm-1；MS m/z356 (M+H) ⁺。
3	4 - Amino-6 - (4 - (dimethylamino) benzene Yl) -7 - (4 - (dimethylamino) phenyl) Pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (4 - dimethylamino- Phenyl) - Vinyl - Boron Acid	IR (microscope) 3325,1608,1589, 1560,1520,1400, 1358,1340,1196, 818cm-1; MSm / z 385 (M + H)⁺。	2		4 - (dimethyl-amino Yl) - benzaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR(KBr)3360， 1660，1600，1185， cm-1；MS m/z356 (M+H) ⁺。
3		4 - (dimethyl-amino Yl) - benzaldehyde	2 - (4 - dimethylamino- Phenyl) - Vinyl - Boron Acid		4	4 - Amino-6 - (4 - methyl-phenyl) -7 - phenyl Yl pyrido [2,3-d] pyrimidine	Benzaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR (microscope) 3325,1659,1553, 1340,1340,821 cm- 1; MSm / z 313 (M + H)⁺。
5	4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - Bromophenyl) pyrido [2,3-d] pyrimidine	4 - Bromobenzaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR (microscope) 3325,1600,1553, 1340,1340,818 cm- 1; MSm / z 391 (M + H)⁺。	4		Benzaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid
5		4 - Bromobenzaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid		6	4 - Amino-6 - (4 - (dimethylamino) benzene Yl) -7 - (4 - pyridyl) pyrido [2,3 - d] pyrimidine	Pyridine-4 - formaldehyde	2 - (4 - dimethylamino- Phenyl) - Vinyl - Boron Acid	IR (microscope) 3320,1608,1560, 1521,1410,1344, 818cm-1; MS m / z 343 (M + H)⁺。
7	4 - Amino-6 - (4 - (dimethylamino) benzene Yl) -7 - (4 - bromophenyl) pyrido [2,3 -	4 - Bromobenzaldehyde	2 - (4 - dimethylamino- Phenyl) - Vinyl - Boron	IR (microscope) 3320,1606,1562, 1547,1520,1340,	6		Pyridine-4 - formaldehyde	2 - (4 - dimethylamino- Phenyl) - Vinyl - Boron Acid

	d] pyrimidine		Acid	1010，818cm-1； MS m/z 420 (M+H) ⁺。
	d] pyrimidine		Acid	1010，818cm-1； MS m/z 420 (M+H) ⁺。	8	4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - (5 - pyrimidinyl) phenyl) pyrido [2,3 - d] pyrimidine	4 - (5 - pyrimidinyl) Benzaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3360，3160， 1600，1555，1410， 1345，820；MS m/z 391(M+H) ⁺。
9	4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - (2 - (2 - pyridyl) ethenyl) phenyl) Pyrido [2,3-d] pyrimidine;	4 - (2 - (2 - pyridyl Yl) ethenyl) benzene Formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3400，3320， 3160，3040，1595， 1560，1340；MS m/z 416(M+H) ⁺。	8		4 - (5 - pyrimidinyl) Benzaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3360，3160， 1600，1555，1410， 1345，820；MS m/z 391(M+H) ⁺。
9		4 - (2 - (2 - pyridyl Yl) ethenyl) benzene Formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3400，3320， 3160，3040，1595， 1560，1340；MS m/z 416(M+H) ⁺。	10	4 - Amino-6 - (4 - methyl-phenyl) -7 - (3 - Pyridyl) pyrido [2,3-d] pyrimidine	3 - Pyridinecarboxaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3320，3360， 3040，1640，1550， 1340，815；MS m/z 314(M+H) ⁺。
11	4 - Amino-6 - (4 - methyl-phenyl) -7 - (thiophene Thiophene-3 - yl) (thiophen-3-y1) pyridine And [2,3-d] pyrimidine	3 - thiophenyl formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3440，3320， 3160，3100，1600， 1555，1335；MS m/z 319(M+H) ⁺。	10		3 - Pyridinecarboxaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3320，3360， 3040，1640，1550， 1340，815；MS m/z 314(M+H) ⁺。
11		3 - thiophenyl formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3440，3320， 3160，3100，1600， 1555，1335；MS m/z 319(M+H) ⁺。	12	4 - Amino-6 - (4 - methyl-phenyl) -7 - (thiophene Thiophene -2 - yl) pyrido [2,3-d] pyrimidine	Of 2 - thiophene formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3460，3360， 3310，3100，1600， 1555，1425；MS m/z 319(M+H) ⁺。
13	4 - Amino-6 - (4 - methyl-phenyl) -7 - (2 - Pyridyl) pyrido [2,3-d] pyrimidine	2 - Pyridinecarboxaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3440，3320， 3170，1640，1600， 1555，1340；MS m/z 314(M+H) ⁺。	12		Of 2 - thiophene formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3460，3360， 3310，3100，1600， 1555，1425；MS m/z 319(M+H) ⁺。
13		2 - Pyridinecarboxaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3440，3320， 3170，1640，1600， 1555，1340；MS m/z 314(M+H) ⁺。	14	4 - Amino-6 - (4 - methyl-phenyl) -7 - (3,4 - methylenedioxy-phenyl) pyridine And [2,3-d] pyrimidine	3,4 - methylenedioxy Benzaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3365，3120， 1600，1555，1440， 1250，1040；MS m/z 357(M+H) ⁺。
15	4 - Amino-6 - butyl-7 - (thiophen-2 - yl) Pyrido [2,3-d] pyrimidine	Of 2 - thiophene formaldehyde	1 - hexenyl - acid	IR 3320，3160， 2955，2860，1640， 1560，1335，；MS m/z 285(M+H) ⁺。	14		3,4 - methylenedioxy Benzaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3365，3120， 1600，1555，1440， 1250，1040；MS m/z 357(M+H) ⁺。
15		Of 2 - thiophene formaldehyde	1 - hexenyl - acid	IR 3320，3160， 2955，2860，1640， 1560，1335，；MS m/z 285(M+H) ⁺。	16	4 - Amino-6 - butyl-7 - (thiophen-3 - yl) Pyrido [2,3-d] pyrimidine	3 - thiophenyl formaldehyde	1 - hexenyl - acid	IR 3300，3070， 2950，2850，1600， 1565，1330，；MS m/z 285(M+H) ⁺。
17	4 - Amino-6 - (4 - methyl-phenyl) -7 - (5 -	5 - bromo-thiophene-2 -	2 - (4 - methylphenyl) -	IR 3450，3300， 3100，1640，1600，	16		3 - thiophenyl formaldehyde	1 - hexenyl - acid	IR 3300，3070， 2950，2850，1600， 1565，1330，；MS m/z 285(M+H) ⁺。

	Bromothiophene-2 - yl) pyrido [2,3-d] Pyrimidine	Formaldehyde	Vinyl - boric acid	1555，1425；MS m/z 397/399(M+H) ⁺。
	Bromothiophene-2 - yl) pyrido [2,3-d] Pyrimidine	Formaldehyde	Vinyl - boric acid	1555，1425；MS m/z 397/399(M+H) ⁺。	18	4 - Amino-6 - (4 - methyl-phenyl) -7 - (5 - Methyl-thiophen-2 - yl) pyrido [2,3 - d] pyrimidine	5 - methylthiophene - 2 - Formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3460，3380， 3300，3150，1640， 1555，1445；MS m/z 333(M+H) ⁺。
19	4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - (Trifluoromethoxy) phenyl) pyrido [2,3-d] pyrimidine	4 - (trifluoromethyl Yl) - benzaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3440，3320， 3180，1555，1490， 1340，820；MS m/z 397(M+H) ⁺。	18		5 - methylthiophene - 2 - Formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3460，3380， 3300，3150，1640， 1555，1445；MS m/z 333(M+H) ⁺。
19		4 - (trifluoromethyl Yl) - benzaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3440，3320， 3180，1555，1490， 1340，820；MS m/z 397(M+H) ⁺。	20	4 - Amino-6 - (4 - methyl-phenyl) -7 - (3 - Phenoxy-phenyl) pyrido [2,3-d] Pyrimidine	3 - phenoxybenzene Formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3400，3180， 3050，1555，1340， 1255，820；MS m/z 405(M+H) ⁺。
21	4 - Amino-6 - (4 - methyl-phenyl) -7 - (5 - Nitro-thiophen-2 - yl) pyrido [2,3 - d] pyrimidine	5 - nitro - thiophene - 2 - Formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3380，3100， 1595，1550，1330， 1260，815；MS m/z 364(M+H) ⁺。	20		3 - phenoxybenzene Formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3400，3180， 3050，1555，1340， 1255，820；MS m/z 405(M+H) ⁺。
21		5 - nitro - thiophene - 2 - Formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3380，3100， 1595，1550，1330， 1260，815；MS m/z 364(M+H) ⁺。	22	4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - Bromothiophene-2 - yl) pyrido [2,3-d] Pyrimidine	4 - bromo - thiophene-2 - Formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3320，3100， 1595，1555，1415， 1340，820；MS m/z 397，399(M+H) ⁺。
23	4 - Amino-6 - (4 - methyl-phenyl) -7 - (3 - Methyl-thiophen-2 - yl) pyrido [2,3 - d] pyrimidine	3 - methyl - thiophene - 2 - Formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3300，3060， 1600，1550，1450， 1355，820；MS m/z 333(M+H) ⁺。	22		4 - bromo - thiophene-2 - Formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid
23		3 - methyl - thiophene - 2 - Formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3300，3060， 1600，1550，1450， 1355，820；MS m/z 333(M+H) ⁺。	24	4 - Amino-6 - (4 - methyl-phenyl) -7 - (furosemide Furans -2 - yl) pyrido [2,3-d] pyrimidine	Furan-2 - formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3430，3300， 3170，1630，1560， 1450，1340；MS m/z 303(M+H) ⁺。
25	4 - Amino-6 - (4 - methyl-phenyl) -7 - (furosemide Furans -3 - yl) pyrido [2,3-d] pyrimidine	Furan-3 - formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3360，3140， 1655，1605，1555， 1340，1165；MS m/z 303(M+H) ⁺。	24		Furan-2 - formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3430，3300， 3170，1630，1560， 1450，1340；MS m/z 303(M+H) ⁺。
25		Furan-3 - formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3360，3140， 1655，1605，1555， 1340，1165；MS m/z 303(M+H) ⁺。	26	4 - Amino-6 - (4 - methyl-phenyl) -7 - (5 - Methyl - furan-2 - yl) pyrido [2,3 - d] pyrimidine	5 - methyl furan - 2 - Formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3440，3180， 1630，1600，1555， 1335，820；MS m/z 317(M+H) ⁺。
27	4 - Amino-6 - (4 - (2 - propyl) phenyl) - 7 - (thiophen-2 - yl) pyrido [2,3-d]	Thiophene-2 - formaldehyde	2 - (4 - (2 - propyl) benzene Yl) - vinyl - boric acid	IR 3460，3320， 3160，2960，1600，	26		5 - methyl furan - 2 - Formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3440，3180， 1630，1600，1555， 1335，820；MS m/z 317(M+H) ⁺。

	Pyrimidine			1555，1425；MS m/z 347(M+H) ⁺。
	Pyrimidine			1555，1425；MS m/z 347(M+H) ⁺。	28	4 - Amino-6 - (4 - (2 - propyl) phenyl) - 7 - (5 - nitro-thiophen-2 - yl) pyrido [2,3-d] pyrimidine	5 - nitro - thiophene - 2 - Formaldehyde	2 - (4 - (2 - propyl) benzene Yl) - vinyl - boric acid	IR 3380，3160， 2960，1635，1600， 1555，1330；MS m/z 392(M+H) ⁺。
29	4 - Amino-6 - (4 - methyl-phenyl) -7 - (5 - Nitro-thiophen-2 - yl) pyrido [2,3 - d] pyrimidine	5 - nitro - thiophene - 2 - Formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3330，3160， 1630，1600，1555， 1350，810；MS m/z 348(M+H) ⁺。	28		5 - nitro - thiophene - 2 - Formaldehyde	2 - (4 - (2 - propyl) benzene Yl) - vinyl - boric acid	IR 3380，3160， 2960，1635，1600， 1555，1330；MS m/z 392(M+H) ⁺。
29		5 - nitro - thiophene - 2 - Formaldehyde	2 - (4 - methylphenyl) - Vinyl - boric acid	IR 3330，3160， 1630，1600，1555， 1350，810；MS m/z 348(M+H) ⁺。	30	4 - Amino-6 - (4 - (dimethylamino) benzene Yl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine	Thiophene-2 - formaldehyde	2 - (4 - (dimethyl-amino Yl) phenyl) - vinyl - Boric acid	IR 3440，3160， 1610，1555，1525， 1340，820；MS m/z 348(M+H) ⁺。
31	4 - Amino-6 - (3,4 - dimethoxybenzene Yl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine	Thiophene-2 - formaldehyde	2 - (3,4 - dimethoxy- Phenyl) - Vinyl - Boron Acid	IR 3420，3080， 1600，1560，1515， 1425，1340；MS m/z 365(M+H) ⁺。	30		Thiophene-2 - formaldehyde	2 - (4 - (dimethyl-amino Yl) phenyl) - vinyl - Boric acid	IR 3440，3160， 1610，1555，1525， 1340，820；MS m/z 348(M+H) ⁺。
31		Thiophene-2 - formaldehyde	2 - (3,4 - dimethoxy- Phenyl) - Vinyl - Boron Acid	IR 3420，3080， 1600，1560，1515， 1425，1340；MS m/z 365(M+H) ⁺。	32	4 - Amino-6 - (3,4 - dimethoxybenzene Yl) -7 - (5 - nitro-thiophen-2 - yl) pyridine Pyrido [2,3-d] pyrimidine	5 - nitro - thiophene - 2 - Formaldehyde	2 - (3,4 - dimethoxy- Phenyl) - Vinyl - Boron Acid	IR 3420，2840， 1600，1555，1515， 1335，1255；MS m/z 410(M+H) ⁺。
33	4 - amino-6 - hexyl-7 - (4 - (dimethyl Amino) phenyl) pyrido [2,3-d] pyrimidine Pyridine	4 - (dimethyl-amino Yl) - benzaldehyde	1 - octenyl - acid	IR 3320，3100， 2920，2850，1600， 1560，1335；MS m/z 350(M+H) ⁺。	32		5 - nitro - thiophene - 2 - Formaldehyde	2 - (3,4 - dimethoxy- Phenyl) - Vinyl - Boron Acid	IR 3420，2840， 1600，1555，1515， 1335，1255；MS m/z 410(M+H) ⁺。
33		4 - (dimethyl-amino Yl) - benzaldehyde	1 - octenyl - acid	IR 3320，3100， 2920，2850，1600， 1560，1335；MS m/z 350(M+H) ⁺。	34	4 - amino-6 - hexyl-7 - (thiophen-2 - yl) Pyrido [2,3-d] pyrimidine	Thiophene-2 - formaldehyde	1 - octenyl - acid	IR 3320，3160， 2920，2840，1600， 1560，1425；MS m/z 313(M+H) ⁺。
35	4 - Amino-6 - (2 - methyl - 2 - propyl) -7 - (Thiophen-2 - yl) pyrido [2,3-d] pyrimidine Pyridine	Thiophene-2 - formaldehyde	3,3 - dimethyl-1 - D Enyl - boric acid	IR 3400，3320， 3180，IR 2960， 1640，1565，1335； MSm/z 285 (M+H) ⁺。	34		Thiophene-2 - formaldehyde	1 - octenyl - acid	IR 3320，3160， 2920，2840，1600， 1560，1425；MS m/z 313(M+H) ⁺。
35		Thiophene-2 - formaldehyde	3,3 - dimethyl-1 - D Enyl - boric acid		36	4 - Amino-6 - (4 - (2 - propyl) phenyl) - 7 - (4 - (dimethylamino) phenyl) pyridine And [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (4 - (2 - propyl) benzene Yl) - vinyl - boric acid	IR 3600-3250， 2955，1590，1555， 1400，1340，1195， 815； MS m/z 384 (M+H) ⁺。

37	4 - Amino-6 - (4 - propyl-phenyl) -7 - (4 - (Dimethylamino) phenyl) pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (4 - propyl-phenyl) - Vinyl - boric acid	IR 3520-3250， 2960，1590，1555， 1400，1340，1195， 815； MS m/z384 (M+H) ⁺。
37		4 - (dimethyl-amino Yl) - benzaldehyde	2 - (4 - propyl-phenyl) - Vinyl - boric acid		38	4 - Amino-6 - (3,4 - dimethoxybenzene Yl) -7 - (4 - (dimethylamino) phenyl) Pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3,4 - dimethoxy- Phenyl) - Vinyl - Boron Acid	IR 3320，3240- 2760，1590，1560， 1510，1515，1340， 820； MS m/z 384 (M+H) ⁺。
39	4 - Amino-6 - (3 - methoxy-phenyl) -7 - (4 - (dimethylamino) phenyl) pyridine And [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - methoxy-benzene Yl) - vinyl - boric acid	IR 3365，3320， 3250-2780，1660， 1590，1560，1460， 1400，1200，820； MS m/z 402 (M+H) ⁺。	38		4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3,4 - dimethoxy- Phenyl) - Vinyl - Boron Acid
39		4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - methoxy-benzene Yl) - vinyl - boric acid		40	4 - Amino-6 - (3 - bromophenyl) -7 - (4 - (Dimethylamino) phenyl) pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - bromophenyl) - B Enyl - boric acid	IR 3400-3250， 3250-2840，1660， 1590，1560，1340， 1200，820； MS m/z420 (M+H) ⁺。
41	4 - Amino-6 - (3 - fluorophenyl) -7 - (4 - (Dimethylamino) phenyl) pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - fluorophenyl) - B Enyl - boric acid	IR 3520-2800， 1645，1610，1590， 1560，1525，1400， 1340，1200，820； MSm/z 360 (M+H) ⁺。	40		4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - bromophenyl) - B Enyl - boric acid
41		4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - fluorophenyl) - B Enyl - boric acid		42	4 - Amino-6 - (3 - (trifluoromethyl) phenyl) - 7 - (4 - (dimethylamino) phenyl) pyridine And [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - (trifluoromethyl) phenyl Yl) - vinyl - boric acid	IR 3560，3520， 3240-2840，1660， 1590，1560，1400， 1340，1160，1120， 810，700； MS m/z 410 (M+H) ⁺。
43	4 - Amino-6 - (3 - chlorophenyl) -7 - (4 - (Dimethylamino) phenyl) pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - chlorophenyl) - B Enyl - boric acid	IR 3500-3280， 3200-2840，1660， 1590，1560，1395， 1370，1340，1200，	42		4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - (trifluoromethyl) phenyl Yl) - vinyl - boric acid

				820； MS m/z376 (M+H) ⁺。
				820； MS m/z376 (M+H) ⁺。	44	4 - Amino-6 - (3,5 - dichlorophenyl) -7 - (4 - (dimethylamino) phenyl) pyridine And [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3,5 - dichlorophenyl) - Vinyl - boric acid	IR 3560-3280， 3240-3300，1640， 1590，1560，1400， 1365，1340，1195， 820，800； MS m/z 411 (M+H) ⁺。
45	4 - amino-6 - (3,4 - methylenedioxybenzene Yl) -7 - (4 - (dimethylamino) phenyl) Pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3,4 - (methylenedioxy) Phenyl) - Vinyl - Boric acid	IR 3600-3280， 3240-3000，1595， 1560，1400，1195， 1040，815； MSm/z 386(M+H) ⁺。	44		4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3,5 - dichlorophenyl) - Vinyl - boric acid
45		4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3,4 - (methylenedioxy) Phenyl) - Vinyl - Boric acid		46	4 - amino-6 - (3,4 - methylenedioxybenzene Yl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine	Thiophene-2 - formaldehyde	2 - (3,4 - (methylenedioxy) Phenyl) - Vinyl - Boric acid	IR 3430，3300， 3170，1630，1595， 1575，1450，1425， 1035，820； MS m/z349 (M+H) ⁺。
47	4 - Amino-6 - (3 - Methoxycarbonylphenylboronic Yl) -7 - (4 - (dimethylamino) phenyl) Pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - methoxycarbonyl Phenyl) - Vinyl - Boron Acid	IR 3360，3320， 3200-3000，1720， 1660，1595，1560， 1400，1340，1200， 820； MS m/z 400 (M+H) ⁺。	46		Thiophene-2 - formaldehyde	2 - (3,4 - (methylenedioxy) Phenyl) - Vinyl - Boric acid
47		4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - methoxycarbonyl Phenyl) - Vinyl - Boron Acid		48	4 - Amino-6 - (3 - (2 - propyl) phenyl) - 7 - (4 - (dimethylamino) phenyl) pyridine And [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - (2 - propyl) benzene Yl) - vinyl - boric acid	IR 3500-3280， 3200-3000，2960， 1590，1555，1395， 1340，1195； MSm/z 384(M+H) ⁺。
49	4 - Amino-6 - (4 - (2 - methyl - 2 - propyl) Phenyl) -7 - (4 - (dimethylamino) benzene Yl) pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (4 - (2 - methyl - 2 - C Yl) phenyl) - vinyl - Boric acid	IR 3520-3280， 3180，2960，1590， 1555，1340，1195， 820； MS m/z 398 (M+H) ⁺。	48		4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - (2 - propyl) benzene Yl) - vinyl - boric acid

50	4 - Amino-6 - (4 - fluorophenyl) -7 - (4 - (Dimethylamino) phenyl) pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (4 - fluorophenyl) - B Enyl - boric acid	IR 3490，3320， 3200-3000，1590， 1555，1400，1340， 1195，820； MS m/z 360 (M+H) ⁺。
50		4 - (dimethyl-amino Yl) - benzaldehyde	2 - (4 - fluorophenyl) - B Enyl - boric acid		51	4 - Amino-6 - (4 - methoxyphenyl) -7 - (4 - (dimethylamino) phenyl) pyridine And [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (4 - Methoxyphenyl Yl) - vinyl - boric acid	IR 3370，3320， 3200-3000，1660， 1590，1555，1400， 1340，1250，1195， 815； MS m/z 372 (M+H) ⁺。
52	4 - Amino-6 - (3 - (phenylmethoxy) benzene Yl) -7 - (4 - (dimethylamino) phenyl) Pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - (phenyl-methoxy- Yl) phenyl) - vinyl - Boric acid	IR 3360，3320， 3200-3000，1655， 1590，1560，1400， 1195，820； MSm/z 448 (M+H) ⁺。	51		4 - (dimethyl-amino Yl) - benzaldehyde	2 - (4 - Methoxyphenyl Yl) - vinyl - boric acid
52		4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - (phenyl-methoxy- Yl) phenyl) - vinyl - Boric acid		53	4 - Amino-6 - (4 - chlorophenyl) -7 - (4 - (Dimethylamino) phenyl) pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (4 - chlorophenyl) - B Enyl - boric acid	IR 3480-3320， 3200-3020，1590， 1550，1410，1340， 1195，815； MS m/z 376 (M+H) ⁺。
54	4 - Amino-6 - (3 - fluoro-4 - methyl-phenyl) - 7 - (4 - (dimethylamino) phenyl) pyridine And [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - fluoro-4 - methyl-phenyl Yl) - vinyl - boric acid	IR 3360，3160- 3000，1660，1590， 1555，1340，1200， 820； MS m/z 374 (M+H) ⁺。	53		4 - (dimethyl-amino Yl) - benzaldehyde	2 - (4 - chlorophenyl) - B Enyl - boric acid
54		4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - fluoro-4 - methyl-phenyl Yl) - vinyl - boric acid		55	4 - Amino-6 - (3 - fluoro-4 - methyl-phenyl) - 7 - (thiophen-2 - yl) pyrido [2,3-d] Pyrimidine	Thiophene-2 - formaldehyde	2 - (3 - fluoro-4 - methyl-phenyl Yl) - vinyl - boric acid	IR 3600-3300， 3200，3020，1620， 1415； MS m/z 337 (M+H) ⁺。
56	4 - Amino-6 - (3 - phenyl-propyl) -7 - (4 - Methoxyphenyl) pyrido [2,3-d] Pyrimidine	4 - methoxy - phenyl Formaldehyde	5 - phenyl - 1 - pentenyl - Boric acid	NMR(CDCl3)δ 8.70(s，1H)，8.06(s， 1H)，7.53(d， J＝9Hz，2H)，7.22 (m，3H)，7.06(d，	55		Thiophene-2 - formaldehyde	2 - (3 - fluoro-4 - methyl-phenyl Yl) - vinyl - boric acid	IR 3600-3300， 3200，3020，1620， 1415； MS m/z 337 (M+H) ⁺。

				J＝8Hz，2H)，6.94 (d，J＝9Hz，2H)， 6.19(s，br，2H)， 3.88(s，3H)，2.88 (m，2H)，2.57(m， 2H)，1.88(m，2H)； MS m/z 371 (M+H) ⁺。
					57	4 - Amino-6 - (3 - phenyl-propyl) -7 - (4 - (Dimethylamino) phenyl) pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	5 - phenyl - 1 - pentenyl - Boric acid	NMR(CDCl3)δ 8.73(s，1H)，7.88(s， 1H)，7.58(d， J＝8Hz，2H)，7.22 (m，3H)，7.10(d， J＝8Hz，2H)，6.73 (d，J＝9Hz，2H)， 5.78(s，br，2H)， 3.04(s，6H)，2.96 (m，2H)，2.61(t， J＝8Hz，2H)，1.91 (m，2H)； MS m/z 384 (M+H) ⁺。
58	4 - Amino-6 - (2 - phenyl-ethyl) -7 - (4 - (Dimethylamino) phenyl) pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	4 - phenyl-1 - butenyl - Boric acid	NMR(CDCl3)δ 8.75(s，1H)，7.69(s， 1H)，7.65(m，2H)， 7.21(m，3H)，7.04 (m，2H)，6.79(m， 2H)，5.57(s，br， 2H)，3.25(m，2H)， 3.04(s，6H)，2.85 (m，2H)； MSm/z 370 (M+H) ⁺。	57		4 - (dimethyl-amino Yl) - benzaldehyde	5 - phenyl - 1 - pentenyl - Boric acid
58		4 - (dimethyl-amino Yl) - benzaldehyde	4 - phenyl-1 - butenyl - Boric acid		59	4 - amino-6 - (phenylmethyl) -7 - (4 - (Dimethylamino) phenyl) pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	3 - phenyl-1 - propenyl - Boric acid	NMR(CDCl3)δ 8.74(s，1H)，7.74(s， 1H)，7.65(d， J＝9Hz，2H)，7.30 (m，3H)，7.10(m， 2H)，6.74(d， J＝9Hz，2H)，5.64(s， br，2H)，4.29(s， 2H)，3.02(s，6H)；

				MS m/z 356 (M+H) ⁺。
				MS m/z 356 (M+H) ⁺。	60	4 - Amino-6 - (cyclohexylmethyl) -7 - (4 - (Dimethylamino) phenyl) pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	3 - cyclohexyl-1 - propene Base - boric acid	NMR(CDCl3)δ 8.75(s，1H)，7.90(s， 1H)，7.59(d， J＝9Hz，2H)，6.76 (d，J＝9Hz，2H)， 5.82(s，br，2H)， 3.03(s，6H)，2.83 (d，J＝7Hz，2H)， 1.70-1.40(m，6H)， 1.07(m，3H)，0.83 (m，2H)； MS m/z 362 (M+H) ⁺。
61	4 - Amino-6 - butyl-7 - (4 - (dimethyl Amino) phenyl) pyrido [2,3-d] pyrimidine Pyridine	4 - (dimethyl-amino Yl) - benzaldehyde	1 - hexenyl - acid	NMR (CDCl3) δ 8.74 (s, 1H), 7.96 (s, 1H), 7.62 (d, J = 9Hz, 2H), 6.77 (d, J = 9Hz, 2H), 5.86 (s, 2H), 3.04 (s, 6H), 2.91 (m, 2H), 1.57 (m, 2H), 1.32 (Sextet, J = 7Hz, 2H), 0.87 (t, J = 7Hz, 3H); MSm / z 322 (M H)⁺。	60		4 - (dimethyl-amino Yl) - benzaldehyde	3 - cyclohexyl-1 - propene Base - boric acid
61		4 - (dimethyl-amino Yl) - benzaldehyde	1 - hexenyl - acid		62	4 - amino-6 - pentyl -7 - (4 - (dimethyl Amino) phenyl) pyrido [2,3-d] pyrimidine Pyridine	4 - (dimethyl-amino Yl) - benzaldehyde	1 - heptenyl - acid	NMR(DMSO-d6) δ 8.53(s，1H)，8.45(s， 1H)，7.47(d， J＝8Hz，2H)，6.82 (d，J＝8Hz，2H)， 3.34(s，1H)，3.32 (s，1H)，2.99(s，6H)， 2.81(m，2H)，1.58 (m，2H)，1.23(m， 4H)，0.82(m，3H)； MSm/z 336 (M+H) ⁺。

63	4 - Amino-6 - (2 - methylpropyl) -7 - (4 - (Dimethylamino) phenyl) pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	4 - methyl-1 - pentenyl - Boric acid	NMR(CDCl3)δ 8.76(s，1H)，7.88(s， 1H)，7.61(d， J＝9Hz，2H)，6.77 (d，J＝9Hz，2H)， 5.76(s，br，2H)， 3.03(s，6H)，2.84 (d，J＝7Hz，2H)， 1.78(m，1H)，0.78 (d，J＝6Hz，6H)； MSm/z 322 (M+H) ⁺。
63		4 - (dimethyl-amino Yl) - benzaldehyde	4 - methyl-1 - pentenyl - Boric acid		64	4 - amino-6 - propyl -7 - (4 - (dimethyl Amino) phenyl) pyrido [2,3-d] pyrimidine Pyridine	4 - (dimethyl-amino Yl) - benzaldehyde	1 - pentenyl - acid	NMR (DMSO-d6) δ 8.52 (s, 1H), 8.45 (s, 1H), 7.90 (s, br, 2H), 7.48 (d, J = 8Hz, 2H), 6.82 (D, J = 8Hz, 2H), 2.99 (s, 6H), 2.80 (M, 2H), 1.60 (sextet Feng, J = 7Hz, 2H), 0.85 (t, J = 7Hz, 3H); MS m / z 308 (M + H) ...⁺。
65	NMR (DMSO-d6) δ 8.52 (s, 1H), 8.45 (s, 1H), 7.90 (s, br, 2H), 7.48 (d, J = 8Hz, 2H), 6.82 (D, J = 8Hz, 2H), 2.99 (s, 6H), 2.80 (M, 2H), 1.60 (sextet Feng, J = 7Hz, 2H), 0.85 (t, J = 7Hz, 3H); MS m / z 308 (M + H) ...	4 - (dimethyl-amino Yl) - benzaldehyde	5 - cyano-1 - pentenyl - Boric acid	NMR(DMSO-d6) δ 8.56(s，1H)，8.47(s， 1H)，7.94(s，br， 2H)，7.50(d， J＝9Hz，2H)，6.83 (d，J＝9Hz，2H)， 3.00(s，6H)，2.93 (m，2H)，2.50(m， 2H)，1.90(m，2H)； MS m/z 333 (M+H) ⁺。	64		4 - (dimethyl-amino Yl) - benzaldehyde	1 - pentenyl - acid
65		4 - (dimethyl-amino Yl) - benzaldehyde	5 - cyano-1 - pentenyl - Boric acid		66	4 - Amino-6 - (3 - nitrophenyl) -7 - (4 - (Dimethylamino) phenyl) pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - nitrophenyl) ethyl Alkenyl boronic acid	IR 3360，3100，1590， 1560

				MS m/z 387 (M+H) ⁺。
				MS m/z 387 (M+H) ⁺。	67	4 - amino-6 - pentyl-7 - (thiophen-2 - yl) Pyrido [2,3-d] pyrimidine	Thiophene-2 - formaldehyde	1 - heptenyl - acid	IR 3320，3100，1560， 1430 MS m/z 299 (M+H) ⁺。
68	4 - Amino-6 - (3 - (formylamino)-propyl) - 7 - (4 - (dimethylamino) phenyl) pyridine And [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	5 - cyano-1 - pentenyl - Boric acid	IR 3325，3120，1660， 1595 MS m/z351 (M+H) ⁺。	67		Thiophene-2 - formaldehyde	1 - heptenyl - acid	IR 3320，3100，1560， 1430 MS m/z 299 (M+H) ⁺。
68		4 - (dimethyl-amino Yl) - benzaldehyde	5 - cyano-1 - pentenyl - Boric acid	IR 3325，3120，1660， 1595 MS m/z351 (M+H) ⁺。	69	4 - amino-6 - ((4 - methoxyphenyl) A Yl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine	Thiophene-2 - formaldehyde	2 - (4 - Methoxyphenyl Yl) - propenyl boronic acid	IR 3360，3100，1605， 1565 MSm/z 349 (M+H) ⁺。
70	4 - Amino-6 - ((3 - bromophenyl) methyl) - 7 - (thiophen-2 - yl) pyrido [2,3-d] Pyrimidine	Thiophene-2 - formaldehyde	2 - (3 - bromophenyl) - C Alkenyl boronic acid	IR 3440，3120，1605， 1565 MS m/z 397/399 (M+H) ⁺。	69		Thiophene-2 - formaldehyde	2 - (4 - Methoxyphenyl Yl) - propenyl boronic acid	IR 3360，3100，1605， 1565 MSm/z 349 (M+H) ⁺。
70		Thiophene-2 - formaldehyde	2 - (3 - bromophenyl) - C Alkenyl boronic acid	IR 3440，3120，1605， 1565 MS m/z 397/399 (M+H) ⁺。	71	4 - Amino-6 - ((4 - (2 - propyl) phenyl) Methyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine	Thiophene-2 - formaldehyde	2 - (4 - (2 - propyl) benzene Yl) - propenyl boronic acid	IR 3440，3080，1600， 1560 MS m/z 361 (M+H) ⁺。
72	4 - amino-6 - ((4 - methoxyphenyl) A Yl) -7 - (4 - (2 - propyl) phenyl) pyridine And [2,3-d] pyrimidine	4 - iso-yl - benzene Formaldehyde	2 - (4 - Methoxyphenyl Yl) - propenyl boronic acid	IR 3360，3120，1565， 1510 MS m/z 385 (M+H) ⁺。	71		Thiophene-2 - formaldehyde	2 - (4 - (2 - propyl) benzene Yl) - propenyl boronic acid	IR 3440，3080，1600， 1560 MS m/z 361 (M+H) ⁺。
72		4 - iso-yl - benzene Formaldehyde	2 - (4 - Methoxyphenyl Yl) - propenyl boronic acid	IR 3360，3120，1565， 1510 MS m/z 385 (M+H) ⁺。	73	4 - Amino-6 - ((4 - bromophenyl) methyl) - 7 - (thiophen-2 - yl) pyrido [2,3-d] Pyrimidine	Thiophene-2 - formaldehyde	2 - (4 - bromophenyl) - C Alkenyl boronic acid	IR 3440，3160，1625， 1560 MS m/z 397/399 (M+H) ⁺。
74	4 - Amino-6 - ((3 - fluorophenyl) methyl) - 7 - (thiophen-2 - yl) pyrido [2,3-d] Pyrimidine	Thiophene-2 - formaldehyde	2 - (3 - fluorophenyl) - C Alkenyl boronic acid	IR 3320，3160，1600， 1560 MS m/z 337	73		Thiophene-2 - formaldehyde	2 - (4 - bromophenyl) - C Alkenyl boronic acid	IR 3440，3160，1625， 1560 MS m/z 397/399 (M+H) ⁺。

				(M+H) ⁺。
				(M+H) ⁺。	75	4 - Amino-6 - ((4 - bromophenyl) methyl) - 7 - (thiazol-2 - yl) pyrido [2,3-d] Pyrimidine	Thiazol-2 - formaldehyde	2 - (4 - bromophenyl) - C Alkenyl boronic acid	IR 3450，3100，1635， 1560 MS m/z 398/400 (M+H) ⁺。
76	4 - amino-6 - ((3 - methoxyphenyl) A Yl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine	Thiophene-2 - formaldehyde	2 - (3 - methoxy-benzene Yl) - propenyl boronic acid	IR 3450，3150，1600， 1560 MS m/z 349 (M+H) ⁺。	75		Thiazol-2 - formaldehyde	2 - (4 - bromophenyl) - C Alkenyl boronic acid	IR 3450，3100，1635， 1560 MS m/z 398/400 (M+H) ⁺。
76		Thiophene-2 - formaldehyde	2 - (3 - methoxy-benzene Yl) - propenyl boronic acid	IR 3450，3150，1600， 1560 MS m/z 349 (M+H) ⁺。	77	4 - Amino-6 - (6 - methyl-phenyl) -7 - (thiophene Thiophene -2 - yl) pyrido [2,3-d] pyrimidine	Thiophene-2 - formaldehyde	2 - phenyl-1 - propenyl Boric acid	IR 3390，3110，1605， 1565 MS m/z 319 (M+H) ⁺。
78	4 - amino-6 - ((3 - methoxyphenyl) A Yl) -7 - (4 - (dimethylamino) phenyl) Pyrido [2,3-d] pyrimidine	4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - methoxy-benzene Yl) - propenyl boronic acid	IR 3310，3080，1600， 1565 MS m/z 386 (M+H) ⁺。	77		Thiophene-2 - formaldehyde	2 - phenyl-1 - propenyl Boric acid	IR 3390，3110，1605， 1565 MS m/z 319 (M+H) ⁺。
78		4 - (dimethyl-amino Yl) - benzaldehyde	2 - (3 - methoxy-benzene Yl) - propenyl boronic acid	IR 3310，3080，1600， 1565 MS m/z 386 (M+H) ⁺。	79	2 - (3 - methoxy-benzene Yl) - propenyl boronic acid...	2 - (3 - methoxy-benzene Yl) - propenyl boronic acid...	2 - (4 - methylphenyl) - Vinyl borate	IR 3230，1325，820； MS m/z 381 (M+H) ⁺。
80	4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - Methylphenyl) pyrido [2,3-d] pyrimidine Pyridine	4 - methyl - benzoic Aldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3450，1449，1340， 820；MS m/z 327 (M+H) ⁺。	79	2 - (3 - methoxy-benzene Yl) - propenyl boronic acid...	2 - (3 - methoxy-benzene Yl) - propenyl boronic acid...	2 - (4 - methylphenyl) - Vinyl borate	IR 3230，1325，820； MS m/z 381 (M+H) ⁺。
80		4 - methyl - benzoic Aldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3450，1449，1340， 820；MS m/z 327 (M+H) ⁺。	81	4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - Methoxyphenyl) pyrido [2,3-d] Pyrimidine	4 - methoxy - phenyl Formaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3375，1600，820； MSm/z 343 (M+H) ⁺。
82	4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - Ethylphenyl) pyrido [2,3-d] pyrimidine Pyridine	4 - ethyl - benzoic Aldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3340，1558，1340， 820；MS m/z 341 (M+H) ⁺。	81		4 - methoxy - phenyl Formaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3375，1600，820； MSm/z 343 (M+H) ⁺。
82		4 - ethyl - benzoic Aldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3340，1558，1340， 820；MS m/z 341 (M+H) ⁺。	83	4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - Cyanophenyl) pyrido [2,3-d] pyrimidine Pyridine	4 - cyano - benzoic Aldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3320，1560，820； MS m/z 338 (M+H) ⁺。

84	4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - Acetylamino-phenyl) pyrido [2,3 - d] pyrimidine	4 - acetamido - Benzaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3325，1520，820； MSm/z 370 (M+H) ⁺。
84		4 - acetamido - Benzaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3325，1520，820； MSm/z 370 (M+H) ⁺。	85	4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - Phenoxy-phenyl) pyrido [2,3-d] Pyrimidine	4 - phenoxy - benzene Formaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3340，1550，1240， 750；MSm/z 405 (M+H) ⁺。
86	4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - Nitrophenyl) pyrido [2,3-d] pyrimidine Pyridine	4 - nitro - benzoic Aldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3390，1340，850； MS m/z 358 (M+H) ⁺。	85		4 - phenoxy - benzene Formaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3340，1550，1240， 750；MSm/z 405 (M+H) ⁺。
86		4 - nitro - benzoic Aldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3390，1340，850； MS m/z 358 (M+H) ⁺。	87	4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - Fluorophenyl) pyrido [2,3-d] pyrimidine	4 - fluoro - benzaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3320，1550，1340， 840；MSm/z 331 (M+H) ⁺。
88	4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - Chlorophenyl) pyrido [2,3-d] pyrimidine	4 - chloro - benzaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3340，1550，1340， 910；MS m/z 347 (M+H) ⁺。	87		4 - fluoro - benzaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3320，1550，1340， 840；MSm/z 331 (M+H) ⁺。
88		4 - chloro - benzaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3340，1550，1340， 910；MS m/z 347 (M+H) ⁺。	89	4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - Aminophenyl) pyrido [2,3-d] pyrimidine Pyridine	4 - amino - benzoic Aldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3325，1550，820； MS m/z 328 (M+H) ⁺。
90	4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - Methylthiophenyl) pyrido [2,3-d] Pyrimidine	4 - methylthio - benzene Formaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3310，1560，1340， 819；MSm/z 359 (M+H) ⁺。	89		4 - amino - benzoic Aldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3325，1550，820； MS m/z 328 (M+H) ⁺。
90		4 - methylthio - benzene Formaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3310，1560，1340， 819；MSm/z 359 (M+H) ⁺。	91	4 - Amino-6 - (4 - methyl-phenyl) -7 - ((4 - phenyl) phenyl) pyrido [2,3-d] Pyrimidine	4 - phenyl - benzoic Aldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3345，1560，820； MS m/z 389 (M+H) ⁺。
92	4 - Amino-6 - (4 - methyl-phenyl) -7 - ((4 - methoxy-phenyl)-phenyl) pyridine And [2,3-d] pyrimidine	4 - phenyl methoxy Base - benzaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3400，1340，1245， 700；MSm/z 419 (M+H) ⁺。	91		4 - phenyl - benzoic Aldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3345，1560，820； MS m/z 389 (M+H) ⁺。
92		4 - phenyl methoxy Base - benzaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3400，1340，1245， 700；MSm/z 419 (M+H) ⁺。	93	4 - Amino-6 - (4 - methyl-phenyl) -7 - ((4-N, N-diethylamino) phenyl) Pyrido [2,3-d] pyrimidine	4 - (N, N-diethyl Ylamino) - benzoic Aldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3330，1550，1200， 819；MS m/z 384 (M+H) ⁺。
94	4 - Amino-6 - (4 - methyl-phenyl) -7 -	4 - (2 - styrene	2 - (4 - methylphenyl) -	IR	93		4 - (N, N-diethyl Ylamino) - benzoic Aldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3330，1550，1200， 819；MS m/z 384 (M+H) ⁺。

	((4-2 - phenyl) phenyl) pyridine And [2,3-d] pyrimidine	Yl) - benzaldehyde	Vinyl borate	3460，1600，1340， 690；MS m/z 415 (M+H) ⁺。
	((4-2 - phenyl) phenyl) pyridine And [2,3-d] pyrimidine	Yl) - benzaldehyde	Vinyl borate	3460，1600，1340， 690；MS m/z 415 (M+H) ⁺。	95	4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - (2 - methyl - 2 - propoxy) phenyl) pyridine And [2,3-d] pyrimidine	4 - (2 - methyl - 2 - Propoxy) - benzoic Aldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3315，1550，1160， 900；MS m/z 385 (M+H) ⁺。
96	4 - Amino-6 - (4 - methyl-phenyl) -7 - (3 - Chlorophenyl) pyrido [2,3-d] pyrimidine	3 - chloro - benzaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3050，1555，1340， 825；MS m/z 347 (M+H) ⁺。	95		4 - (2 - methyl - 2 - Propoxy) - benzoic Aldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3315，1550，1160， 900；MS m/z 385 (M+H) ⁺。
96		3 - chloro - benzaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3050，1555，1340， 825；MS m/z 347 (M+H) ⁺。	97	4 - Amino-6 - (4 - methyl-phenyl) -7 - (3,5 - dimethoxyphenyl) pyrido [2,3-d] pyrimidine	3,5 - dimethoxy- Benzaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3430，1600， 1200，720；MS m/z 373(M+H) ⁺。
98	4 - Amino-6 - (thien-2 - yl) -7 - (4 - N, N-dimethyl-phenyl) pyrido [2,3-d] pyrimidine	4 - (N, N-dimethyl Ylamino) - benzoic Aldehyde	2 - (thien-2 - yl) - acetic Alkenyl boronic acid	IR 3320，1590，700； MS m/z 348 (M+H) ⁺。	97		3,5 - dimethoxy- Benzaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3430，1600， 1200，720；MS m/z 373(M+H) ⁺。
98		4 - (N, N-dimethyl Ylamino) - benzoic Aldehyde	2 - (thien-2 - yl) - acetic Alkenyl boronic acid	IR 3320，1590，700； MS m/z 348 (M+H) ⁺。	99	4 - Amino-6 - (4 - methyl-phenyl) -7 - (phenyl And furan-2 - yl) pyrido [2,3-d] Pyrimidine	Benzofuran-2 - Formaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3310，1640，750； MS m/z 353 (M+H) ⁺。
100	4 - Amino-6 - (thien-2 - yl) -7 - (thiophene Thiophene -2 - yl) pyrido [2,3-d] pyrimidine	Thiophene-2 - formaldehyde	2 - (thien-2 - yl) - acetic Alkenyl boronic acid	IR 3315，1560， 1420，700；MS m/z 311(M+H) ⁺。	99		Benzofuran-2 - Formaldehyde	2 - (4 - methylphenyl) - Vinyl borate	IR 3310，1640，750； MS m/z 353 (M+H) ⁺。
100		Thiophene-2 - formaldehyde	2 - (thien-2 - yl) - acetic Alkenyl boronic acid	IR 3315，1560， 1420，700；MS m/z 311(M+H) ⁺。	101	4 - Amino-6 - (thien-2 - yl) -7 - (4 - Methoxyphenyl) pyrido [2,3-d] Pyrimidine	4 - methoxy - phenyl Formaldehyde	2 - (thien-2 - yl) - acetic Alkenyl boronic acid	IR 3400，1560， 1250，835；MS m/z 335(M+H) ⁺。
102	4 - Amino-6 - (4 - bromophenyl) -7 - (4 - N, N-dimethyl-phenyl) pyrido [2,3-d] pyrimidine	4 - (N, N-dimethyl Ylamino) - benzoic Aldehyde	2 - (4 - bromophenyl) - B Alkenyl boronic acid	IR 3330，1545， 1190，810；MS m/z 420(M+H) ⁺。	101		4 - methoxy - phenyl Formaldehyde	2 - (thien-2 - yl) - acetic Alkenyl boronic acid	IR 3400，1560， 1250，835；MS m/z 335(M+H) ⁺。
102		4 - (N, N-dimethyl Ylamino) - benzoic Aldehyde	2 - (4 - bromophenyl) - B Alkenyl boronic acid	IR 3330，1545， 1190，810；MS m/z 420(M+H) ⁺。	103	4 - Amino-6 - (3 - bromo-4 - methoxybenzene Yl) -7 - (4-N, N-dimethyl-phenyl) pyridine Pyrido [2,3-d] pyrimidine	4 - (N, N-dimethyl Ylamino) - benzoic Aldehyde	2 - (3 - bromo-4 - methoxy- - Phenyl) - Vinyl boron Acid	IR 3380，1590， 1200，820；MS m/z 451.(M+H) ⁺。
104	4 - Amino-6 - (3 - bromo-4 - methoxybenzene Yl) -7 - ((thiophen-2 - yl) pyrido [2,3-d] pyrimidine	Thiophene-2 - formaldehyde 3 -	2 - (3 - bromo-4 - methoxy- - Phenyl) - Vinyl boron Acid	IR 3400，1550， 1280，715；MS m/z 414(M+H) ⁺。	103		4 - (N, N-dimethyl Ylamino) - benzoic Aldehyde	2 - (3 - bromo-4 - methoxy- - Phenyl) - Vinyl boron Acid	IR 3380，1590， 1200，820；MS m/z 451.(M+H) ⁺。
104		Thiophene-2 - formaldehyde 3 -	2 - (3 - bromo-4 - methoxy- - Phenyl) - Vinyl boron Acid	IR 3400，1550， 1280，715；MS m/z 414(M+H) ⁺。	105	4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - Butoxyphenyl) pyrido [2,3-d] Pyrimidine	4 - dibutoxybenzene Formaldehyde	2 - (4 - methylphenyl) - Vinyl borate	na

106	4 - Amino-6 - (4 - methyl-phenyl) -7 - (3 - Methoxyphenyl) pyrido [2,3-d] Pyrimidine;	3 - methoxy- Formaldehyde	2 - (4 - methylphenyl) - Vinyl borate	na
106		3 - methoxy- Formaldehyde	2 - (4 - methylphenyl) - Vinyl borate	na	107	4 - Amino-6 - (4 - methyl-phenyl) -7 - (3,5 - dichlorophenyl) pyrido [2,3-d] Pyrimidine	3,5 - dichloro-benzoic Aldehyde	2 - (4 - methylphenyl) - Vinyl borate	na

Claims

1 A compound having the formula and pharmaceutically acceptable salts and amides:Of which: R¹And R²Is independently H, lower alkyl, aryl or acyl group, or they are connected with the Then form together with the nitrogen atom optionally containing an additional oxygen or nitrogen atom a 5-7 membered ring; R³And R⁴Independently selected from lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl Group, a heteroaryl group, or a heterocyclic group, and the dotted line indicates a double bond is optionally present.

2 A compound according to claim 1, wherein: R³Selected from lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, heteroaryl, aryl Group or a heterocyclic group; and R⁴Group selected from aryl, arylalkyl, heteroaryl or a heterocyclic group.

3 A compound according to claim 1, wherein: R¹And R²Independently selected from hydrogen, lower alkyl, aryl C₁-C ₆Alkyl,-C (O) C₁-C ₆Alkyl group, -C (O) aryl,-C (O) heterocycle, or with the nitrogen atom to which they are attached form an optionally together with 1-2 another selected from O, N or S, 5-7 ring heteroatoms; R¹And R²Independently selected from: C₁-C ₆Alkyl group, C₂-C ₆Alkenyl, C₂-C ₆Alkynyl group, C₃-C ₈Cycloalkyl group, Heteroaryl C₀-C ₆Alkyl, or substituted heteroaryl C₀-C ₆Alkyl group, Aryl C₀-C ₆Alkyl or substituted aryl C₀-C ₆Alkyl group, Heteroaryl C₂-C ₆Alkenyl group or a substituted heteroaryl C₂-C ₆Alkenyl, Aryl C₂-C ₆Alkenyl or substituted aryl C₂-C ₆Alkenyl, Heteroaryl C₂-C ₆Alkynyl group or a substituted heteroaryl C₂-C ₆Alkynyl group, Aryl C₂-C ₆Alkynyl group or a substituted aryl C₂-C ₆Alkynyl, wherein said aryl or heteroaryl 1-4 Aryl substituents selected from:

Halogen, cyano, C₁-C ₆Alkyl, heteroaryl, heterocyclyl, C₁-C ₆Alkoxy, C₁-C ₆Alkyl

Alkoxy C₁-C ₆Alkyl, aryl C₁-C ₆Alkyl, H₂NC ₁-C ₆Alkyl, aryl C₁-

C ₆Alkoxy, H₂NC (O), cyano, C₂-C ₆Alkenyl, C₂-C ₆Alkynyl, C₁-

C ₆Alkyl, C₂-C ₆Dialkyl malonate alkenyl group, CF₃、HO-、C ₁-C ₆

Alkoxy C₁-C ₆Alkoxy, SO_nC ₁-C ₆Alkyl wherein n is 1-3, C₁-C ₆Alkyl

Alkylthio, C₁-C ₆Acryloyl group, CF₃O、CF ₃、C ₁-C ₄Alkylenedioxy,

C ₁-C ₆Acryloyl group, H₂NC (O) NH, N-formyl (heterocyclic), NO₂、

NR ⁵R ⁶C ₀-C ₆Alkyl group,

Where R⁵And R⁶Is independently selected from H, C₁-C ₆Alkyl, HC (O), C₁-C ₆Alkoxy

Group C₁-C ₆Alkyl, C₁-C ₆Alkoxy, C₁-C ₆Alkyl C (O), CF₃C(O)、

NR ⁷R ⁸C ₁-C ₆Alkyl, phthalimido group C₁-C ₆C(O)、CNC ₁-C ₆Alkyl

Group, H₃NC (O) NH-, heteroaryl, NR⁷R ⁸C ₁-C ₆Alkyl C (O), C₁-

C ₆Ureido alkoxy C₁-C ₆Alkyl group,

Where R⁷And R⁸Independently selected from R⁵And R⁶Group, Or R⁵And R⁶Or R⁷And R⁸With the nitrogen atom to which they are attached optionally form together containing 1 - 3 in addition, from O, N or S heteroatom unsubstituted or substituted 5-7 membered ring, wherein Said substituents selected from C₁-C ₆Group.

The process of claim 1 wherein R³And R⁴Independently selected from phenyl, thiophene-2 - yl, 1 - methyl-2 - oxo-benzoxazol-5 - yl, 2 - (dimethylamino) -5 - pyrimidinyl, 2 - (N-formyl-N-methyl-amino) -3 - pyrimidinyl, 2 - (N-(2 - Methoxyethyl)-N-methyl-amino) -5 - pyrimidinyl, 2 - (N-methylamino) 5 - pyrimidinyl, 2 - (1 - Morpholinyl) -5 - pyrimidinyl, 2 - (1 - pyrrolidinyl) -5 - pyrimidinyl, 2 - dimethyl-5 - pyrimidine Group, a 2 - furyl, 2 - oxo-benzoxazol-5 - yl, 2 - pyridyl, 3 - (dimethylamino) Phenyl, 3 - amino - 4 - methoxy-phenyl, 3 - bromo-4 - (dimethylamino) phenyl, 3 - methoxybenzene Group, a 3 - methyl--4 - (N-acetyl-N-methylamino) phenyl, 3 - methyl--4 - (N-formyl-N-methyl- Amino) phenyl, 3 - methyl--4 - (N-methyl-N-(trifluoroacetyl) amino) phenyl, 3 - methyl--4 - (N- Methylamino) phenyl, 3 - methyl - 4 - alkyl pyrrolyl group, 3 - pyridyl, 3,4 - dichlorophenyl, 3,4 - methylenedioxy-phenyl, 3,4,5 - trimethoxy-phenyl, 4 - (acetylamino) phenyl, 4 - (di- Methyl-amino) -3 - fluorophenyl, 4 - (dimethylamino) phenyl, 4 - (imidazol-1 - yl) phenyl, 4 - (methyl Thio) phenyl, 4 - (morpholin-yl) 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-ethyl-amino) phenyl, 4 - (N-formyl-N-(2 - methoxy- Yl-ethyl) amino) phenyl, 4 - (N-isopropylamino) phenyl, 4 - (N-methyl-N-((2 - dimethyl- Amino) ethyl) amino) phenyl, 4 - (N-methyl-N-(2 - (N-phthalimido) acetyl) amino Yl) phenyl, 4 - (N-methyl-N-(2 - cyano) ethylamino) phenyl, 4 - (N-methyl-N-(2 - methoxy- Yl-ethyl) amino) phenyl, 4 - (N-methyl-N-(3 - methoxy) propionylamino) phenyl, 4 - (N-methyl Yl-N-acetylamino) phenyl, 4 - (N-methyl-N-formylamino) phenyl, 4 - (N-methyl-N-three Fluoro-acetylamino) phenyl, 4 - (N-morpholinyl) phenyl, 4 - (thiophen-2 - yl) phenyl, 4 - (ureido) Phenyl, 4 - (2 - (dimethylamino) acetylamino) phenyl, 4 - (2 - (2 - methoxy) acetylamino) ethyl Yl) amino) phenyl, 4 - (2 - methoxy) ethoxy phenyl, 4 - (2 - oxo - oxazolidinyl) phenyl, 4 - (4 - methoxy-2 - butyl) phenyl, 4 - (4 - methyl-piperidinyl) phenyl, 4 - (5 - pyrimidinyl) phenyl, 4 - amino-phenyl, 4 - bromophenyl group, a 4 - butoxy-phenyl, 4 - (formylamino) phenyl, 4 - chlorophenyl, 4 - cyanophenyl, 4 - diethylamino group, a 4 - phenyl allyl diethyl malonyl), 4 - Dimethylamino-phenyl, 4 - ethoxy-phenyl, 4 - ethyl-phenyl, 4 - fluorophenyl, 4 - hydroxyphenyl Yl, 4 - imidazolyl group, a 4 - iodo-phenyl, 4 - isopropyl-phenyl, 4 - methoxyphenyl), 4 - methyl -Amino phenyl, 4 - methylsulfonyl phenyl, 4 - morpholinyl-phenyl ,4-N-(2 - (dimethylaminoethyl Yl) ethyl)-N-formyl-amino)-phenyl ,4-N-(3 - methoxy-propionyl)-N-isopropyl - amino) phenyl Yl ,4-N-ethyl-N-(2 - methoxyethyl) amino) phenyl ,4-N-formyl-piperidyl group, a 4 - Nitrophenyl, 4 - piperidyl group, 4 - pyridyl group, a 4 - pyrrolyl alkylphenyl group, a 4 - tert-butyl Acryloyl group phenyl, 5 - (dimethylamino) thiophene-2 - yl, 5 - amino-2 - pyridyl group, 5 - Methylamino-2 - piperazinyl group, 3 - dimethylamino-pyridazin-6 - yl, 5 - dimethyl-2 - pyridyl Group, a 5 - pyrimidinyl-phenyl, 6 - (N-methyl-N-formylamino) -3 - pyridyl, 6 - (N-methyl-N-(2 - Methoxyethyl) amino) -3 - pyridyl, 6 - (2 - oxo - oxazolidinyl) -3 - pyridyl, 6 - dimethyl Yl-3 - pyridyl, 6 - imidazol-3 - pyridyl, 6 - morpholin-3 - pyridyl, 6 - pyrrolidine -3 - pyridine, (2 - propyl) -3 - pyridyl, and (4 - formylamino) phenyl, (thien-2 - yl) methyl Group, (thiophen-3 - yl) methyl group, butyl group, cycloheptyl group, pentyl group, thiophene-2 - yl, 1 - (3 - bromophenyl Yl) ethyl, 2 - (N-phenyl-methoxycarbonyl) amino phenyl, 2 - (3 - bromophenyl) ethyl, 2 - (3 - Cyanophenyl) methyl, 2 - (4 - bromophenyl) ethyl, 2 - (5 - chloro -2 - (thiophen-3 - yl)) phenyl, 2 - bromo- Phenyl, 2 - furyl, 2 - methylpropyl, 2 - phenylethyl group, a phenyl group, 2,3 - dimethoxyphenyl -Phenyl, 2,3 - methylenedioxy-phenyl, 3 - (furan-2 - yl) phenyl, 3 - (thiophen-2 - yl) phenyl, 3 - (2 - pyridyl) phenyl, 3 - (3 - methoxybenzyl) phenyl, 3 - (amino) propynyl group, a 3 - benzyloxy Yl group, a 3 - bromo-4 - fluorophenyl, 3 - bromo-5 - iodo-phenyl, 3 - bromo-5 - methoxy-phenyl, 3 - bromophenyl Group, a 3 - bromophenyl methyl 3 - (formylamino) phenyl, 3 - chlorophenyl, 3 - cyanophenyl, 3 - Ethyl malonyl allyl phenyl, 3 - dimethylamino-phenyl, 3 - ethoxy group, a 3 - fluoro - 5 - (trifluoromethyl) phenyl, 3 - fluorophenyl, 3 - hydroxyphenyl group, 3 - iodo group, a 3 - methoxy-ethoxy Yl group, a 3 - methoxy-phenyl, 3 - methylphenyl, 3 - methyl-sulfonyl group, a 3 - (methylthio) Phenyl, 3 - tert-butyl-acryloyl group, a 3 - (Trifluoromethoxy) phenyl, 3 - trifluoromethylphenyl, 3 - vinyl pyridine group, a 3,4 - dichlorophenyl, 3,4 - dimethoxyphenyl, 3,4 - methylenedioxy , 3,4,5 - trimethoxyphenyl, 3,5 - bis (trifluoromethyl) phenyl, 3,5 - dibromobenzene , 3,5 - dichlorophenyl, 3,5 - dimethoxyphenyl, 3,5 - dimethylphenyl, 4 - (2 - propyl) Phenyl, 4 - (2 - propyl) oxy (oxy) phenyl, 4 - benzyloxy-phenyl, 4 - bromophenyl group, 4 - bromo-thiophene-2 - Yl, 4 - butoxy group, a 4 - dimethylamino-phenyl, 4 - fluoro-3 - (trifluoromethyl) phenyl, 4 - methyl Alkoxy phenyl, 4 - neopentyl group, a 4 - phenoxy-phenyl, 5 - bromo-thiophen-2 - yl, 5 - cyclohexyl, 5 - cyclopropyl, 5 - hexyl group, a 5 - methyl-5 - phenyl, (2 - bromo-5 - chlorophenyl) methyl, (2 - bromophenyl Yl) methyl and (5 - chloro -2 - (3 - methoxyphenyl) phenyl) methyl. ...

Independently selected from phenyl, thiophene-2 - yl, 1 - methyl-2 - oxo-benzoxazol-5 - yl, 2 - (dimethylamino) -5 - pyrimidinyl, 2 - (N-formyl-N-methyl-amino) -3 - pyrimidinyl, 2 - (N-(2 - Methoxyethyl)-N-methyl-amino) -5 - pyrimidinyl, 2 - (N-methylamino) 5 - pyrimidinyl, 2 - (1 - Morpholinyl) -5 - pyrimidinyl, 2 - (1 - pyrrolidinyl) -5 - pyrimidinyl, 2 - dimethyl-5 - pyrimidine Group, a 2 - furyl, 2 - oxo-benzoxazol-5 - yl, 2 - pyridyl, 3 - (dimethylamino) Phenyl, 3 - amino - 4 - methoxy-phenyl, 3 - bromo-4 - (dimethylamino) phenyl, 3 - methoxybenzene Group, a 3 - methyl--4 - (N-acetyl-N-methylamino) phenyl, 3 - methyl--4 - (N-formyl-N-methyl- Amino) phenyl, 3 - methyl--4 - (N-methyl-N-(trifluoroacetyl) amino) phenyl, 3 - methyl--4 - (N- Methylamino) phenyl, 3 - methyl - 4 - alkyl pyrrolyl group, 3 - pyridyl, 3,4 - dichlorophenyl, 3,4 - methylenedioxy-phenyl, 3,4,5 - trimethoxy-phenyl, 4 - (acetylamino) phenyl, 4 - (di- Methyl-amino) -3 - fluorophenyl, 4 - (dimethylamino) phenyl, 4 - (imidazol-1 - yl) phenyl, 4 - (methyl Thio) phenyl, 4 - (morpholin-yl) 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-ethyl-amino) phenyl, 4 - (N-formyl-N-(2 - methoxy- Yl-ethyl) amino) phenyl, 4 - (N-isopropylamino) phenyl, 4 - (N-methyl-N-((2 - dimethyl- Amino) ethyl) amino) phenyl, 4 - (N-methyl-N-(2 - (N-phthalimido) acetyl) amino Yl) phenyl, 4 - (N-methyl-N-(2 - cyano) ethylamino) phenyl, 4 - (N-methyl-N-(2 - methoxy- Yl-ethyl) amino) phenyl, 4 - (N-methyl-N-(3 - methoxy) propionylamino) phenyl, 4 - (N-methyl Yl-N-acetylamino) phenyl, 4 - (N-methyl-N-formylamino) phenyl, 4 - (N-methyl-N-three Fluoro-acetylamino) phenyl, 4 - (N-morpholinyl) phenyl, 4 - (thiophen-2 - yl) phenyl, 4 - (ureido) Phenyl, 4 - (2 - (dimethylamino) acetylamino) phenyl, 4 - (2 - (2 - methoxy) acetylamino) ethyl Yl) amino) phenyl, 4 - (2 - methoxy) ethoxy phenyl, 4 - (2 - oxo - oxazolidinyl) phenyl, 4 - (4 - methoxy-2 - butyl) phenyl, 4 - (4 - methyl-piperidinyl) phenyl, 4 - (5 - pyrimidinyl) phenyl, 4 - amino-phenyl, 4 - bromophenyl group, a 4 - butoxy-phenyl, 4 - (formylamino) phenyl, 4 - chlorophenyl, 4 - cyanophenyl, 4 - diethylamino group, a 4 - phenyl allyl diethyl malonyl), 4 - Dimethylamino-phenyl, 4 - ethoxy-phenyl, 4 - ethyl-phenyl, 4 - fluorophenyl, 4 - hydroxyphenyl Yl, 4 - imidazolyl group, a 4 - iodo-phenyl, 4 - isopropyl-phenyl, 4 - methoxyphenyl), 4 - methyl -Amino phenyl, 4 - methylsulfonyl phenyl, 4 - morpholinyl-phenyl ,4-N-(2 - (dimethylaminoethyl Yl) ethyl)-N-formyl-amino)-phenyl ,4-N-(3 - methoxy-propionyl)-N-isopropyl - amino) phenyl Yl ,4-N-ethyl-N-(2 - methoxyethyl) amino) phenyl ,4-N-formyl-piperidyl group, a 4 - Nitrophenyl, 4 - piperidyl group, 4 - pyridyl group, a 4 - pyrrolyl alkylphenyl group, a 4 - tert-butyl Acryloyl group phenyl, 5 - (dimethylamino) thiophene-2 - yl, 5 - amino-2 - pyridyl group, 5 - Methylamino-2 - piperazinyl group, 3 - dimethylamino-pyridazin-6 - yl, 5 - dimethyl-2 - pyridyl Group, a 5 - pyrimidinyl-phenyl, 6 - (N-methyl-N-formylamino) -3 - pyridyl, 6 - (N-methyl-N-(2 - Methoxyethyl) amino) -3 - pyridyl, 6 - (2 - oxo - oxazolidinyl) -3 - pyridyl, 6 - dimethyl Yl-3 - pyridyl, 6 - imidazol-3 - pyridyl, 6 - morpholin-3 - pyridyl, 6 - pyrrolidine -3 - pyridine, (2 - propyl) -3 - pyridyl, and (4 - formylamino) phenyl, (thien-2 - yl) methyl Group, (thiophen-3 - yl) methyl group, butyl group, cycloheptyl group, pentyl group, thiophene-2 - yl, 1 - (3 - bromophenyl Yl) ethyl, 2 - (N-phenyl-methoxycarbonyl) amino phenyl, 2 - (3 - bromophenyl) ethyl, 2 - (3 - Cyanophenyl) methyl, 2 - (4 - bromophenyl) ethyl, 2 - (5 - chloro -2 - (thiophen-3 - yl)) phenyl, 2 - bromo- Phenyl, 2 - furyl, 2 - methylpropyl, 2 - phenylethyl group, a phenyl group, 2,3 - dimethoxyphenyl -Phenyl, 2,3 - methylenedioxy-phenyl, 3 - (furan-2 - yl) phenyl, 3 - (thiophen-2 - yl) phenyl, 3 - (2 - pyridyl) phenyl, 3 - (3 - methoxybenzyl) phenyl, 3 - (amino) propynyl group, a 3 - benzyloxy Yl group, a 3 - bromo-4 - fluorophenyl, 3 - bromo-5 - iodo-phenyl, 3 - bromo-5 - methoxy-phenyl, 3 - bromophenyl Group, a 3 - bromophenyl methyl 3 - (formylamino) phenyl, 3 - chlorophenyl, 3 - cyanophenyl, 3 - Ethyl malonyl allyl phenyl, 3 - dimethylamino-phenyl, 3 - ethoxy group, a 3 - fluoro - 5 - (trifluoromethyl) phenyl, 3 - fluorophenyl, 3 - hydroxyphenyl group, 3 - iodo group, a 3 - methoxy-ethoxy Yl group, a 3 - methoxy-phenyl, 3 - methylphenyl, 3 - methyl-sulfonyl group, a 3 - (methylthio) Phenyl, 3 - tert-butyl-acryloyl group, a 3 - (Trifluoromethoxy) phenyl, 3 - trifluoromethylphenyl, 3 - vinyl pyridine group, a 3,4 - dichlorophenyl, 3,4 - dimethoxyphenyl, 3,4 - methylenedioxy , 3,4,5 - trimethoxyphenyl, 3,5 - bis (trifluoromethyl) phenyl, 3,5 - dibromobenzene , 3,5 - dichlorophenyl, 3,5 - dimethoxyphenyl, 3,5 - dimethylphenyl, 4 - (2 - propyl) Phenyl, 4 - (2 - propyl) oxy (oxy) phenyl, 4 - benzyloxy-phenyl, 4 - bromophenyl group, 4 - bromo-thiophene-2 - Yl, 4 - butoxy group, a 4 - dimethylamino-phenyl, 4 - fluoro-3 - (trifluoromethyl) phenyl, 4 - methyl Alkoxy phenyl, 4 - neopentyl group, a 4 - phenoxy-phenyl, 5 - bromo-thiophen-2 - yl, 5 - cyclohexyl, 5 - cyclopropyl, 5 - hexyl group, a 5 - methyl-5 - phenyl, (2 - bromo-5 - chlorophenyl) methyl, (2 - bromophenyl Yl) methyl and (5 - chloro -2 - (3 - methoxyphenyl) phenyl) methyl. ...

Of which: R¹And R²Is independently H, lower alkyl, aryl or acyl group, or they are connected with the Then form together with the nitrogen atom optionally containing an additional oxygen or nitrogen atom a 5-7 membered ring; R³And R⁴Independently selected from lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl Group, a heteroaryl group, or a heterocyclic group.

Claimed in claim 5 wherein R³Selected from lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, heteroaryl, aryl Group or a heterocyclic group; and R⁴Group selected from aryl, arylalkyl, heteroaryl or heterocyclic group.

Claimed in claim 5 wherein R¹And R²Is independently selected from H, lower alkyl, aryl C₁-C ₆Alkyl,-C (O) C₁-C ₆Alkyl group, -C (O) aryl,-C (O) heterocycle, or with the nitrogen atom to which they are attached form an optionally together with One another selected from 1-2 O, N or S, 5-7 ring heteroatoms; R³And R⁴Independently selected from: C₁-C ₆Alkyl group, C₂-C ₆Alkenyl, C₂-C ₆Alkynyl group, C₃-C ₈Cycloalkyl group, Heteroaryl C₀-C ₆Alkyl, or substituted heteroaryl C₀-C ₆Alkyl group, Aryl C₀-C ₆Alkyl or substituted aryl C₀-C ₆Alkyl group, Heteroaryl C₂-C ₆Alkenyl group or a substituted heteroaryl C₂-C ₆Alkenyl, Aryl C₂-C ₆Alkenyl or substituted aryl C₂-C ₆Alkenyl, Heteroaryl C₂-C ₆Alkynyl group or a substituted heteroaryl C₂-C ₆Alkynyl group, Aryl C₂-C ₆Alkynyl group or a substituted aryl C₂-C ₆Alkynyl, wherein said aryl or heteroaryl 1-4 Substituents independently selected from:

Halogen, oxo, cyano, C₁-C ₆Alkyl, heteroaryl C₀-C ₆Alkyl, heterocyclyl C₀-C ₆

Alkyl, C₁-C ₆Alkoxy, C₁-C ₆Alkoxy C₁-C ₆Alkyl, aryl C₀-C ₆

Alkyl, aryl C₁-C ₆Alkoxy group, R⁵R ⁶NC (O), cyano, C₂-C ₆Alkenyl,

C ₂-C ₆Alkynyl, C₁-C ₆Alkyl, C₂-C ₆Dialkyl malonate alkenyl group, CF₃、

HO-、C ₁-C ₆Alkoxy C₁-C ₆Alkoxy, C₁-C ₆Alkyl SO_nWherein n is 1-2,

C ₁-C ₆Alkylthio, C₁-C ₆Acryloyl group, CF₃O、CF ₃、C ₁-C ₄Alkylene

Dioxy, C₁-C ₆Acrylic alkyl group, R⁵R ⁶N(CO)NR ⁵, N-formyl (hetero

Ring), NO₂、NR ⁵R ⁶C ₀-C ₆Alkyl group,

Group C₁-C ₆Alkyl, C₁-C ₆Alkoxy, C₁-C ₆Alkyl C (O), CF₃C(O)、

NR ⁷R ⁸C ₁-C ₆Alkyl, phthalimido group C₁-C ₆C(O)、C ₁-C ₆Alkyl

SO _nWhere n is 1-2, CNC₁-C ₆Alkyl, R⁷R ⁸NC(O)NR ⁷-, Miscellaneous

Aryl, NR⁷R ⁸C ₁-C ₆Alkyl C (O), C₁-C ₆Ureido alkoxy C₁-C ₆Alkyl

Group,

Where R⁷And R⁸Independently selected from those for R⁵And R⁶Group, Or R⁵And R⁶Or R⁷And R⁸With the nitrogen atom to which they are attached optionally form together containing 1 - 3 in addition, from O, N or S heteroatom unsubstituted or substituted 5-7 membered ring, wherein Said substituents selected from C₁-C ₆Group.

The process of claim 5 wherein R³And R⁴Independently selected from phenyl, thiophene-2 - yl, 1 - methyl-2 - oxo-benzoxazol-5 - yl, 2 - (dimethylamino) -5 - pyrimidinyl, 2 - (N-formyl-N-methyl-amino) -3 - pyrimidinyl, 2 - (N-(2 - Methoxyethyl)-N-methyl-amino) -5 - pyrimidinyl, 2 - (N-methylamino) 5 - pyrimidinyl, 2 - (1 - Morpholinyl) -5 - pyrimidinyl, 2 - (1 - pyrrolidinyl) -5 - pyrimidinyl, 2 - dimethyl-5 - pyrimidine Group, a 2 - furyl, 2 - oxo-benzoxazol-5 - yl, 2 - pyridyl, 3 - (dimethylamino) Phenyl, 3 - amino - 4 - methoxy-phenyl, 3 - bromo-4 - (dimethylamino) phenyl, 3 - methoxybenzene Group, a 3 - methyl--4 - (N-acetyl-N-methylamino) phenyl, 3 - methyl--4 - (N-formyl-N-methyl- Amino) phenyl, 3 - methyl--4 - (N-methyl-N-(trifluoroacetyl) amino) phenyl, 3 - methyl--4 - (N- Methylamino) phenyl, 3 - methyl - 4 - alkyl pyrrolyl group, 3 - pyridyl, 3,4 - dichlorophenyl, 3,4 - methylenedioxy-phenyl, 3,4,5 - trimethoxy-phenyl, 4 - (acetylamino) phenyl, 4 - (di- Methyl-amino) -3 - fluorophenyl, 4 - (dimethylamino) phenyl, 4 - (imidazol-1 - yl) phenyl, 4 - (methyl Thio) phenyl, 4 - (morpholin-yl) 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-ethyl-amino) phenyl, 4 - (N-formyl-N-(2 - methoxy- Yl-ethyl) amino) phenyl, 4 - (N-isopropylamino) phenyl, 4 - (N-methyl-N-((2 - dimethyl- Amino) ethyl) amino) phenyl, 4 - (N-methyl-N-(2 - (N-phthalimido) acetyl) amino) Phenyl, 4 - (N-methyl-N-(2 - cyano) ethylamino) phenyl, 4 - (N-methyl-N-(2 - methoxy- Ethyl) 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-trifluoro-acetic Acylamino) 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 Yl) phenyl, 4 - (2 - methoxy) ethoxy phenyl, 4 - (2 - oxo - oxazolidinyl) phenyl, 4 - (4 - Methoxy-2 - butyl) phenyl, 4 - (4 - methyl-piperidinyl) phenyl, 4 - (5 - pyrimidinyl) phenyl, 4 - Amino-phenyl, 4 - bromophenyl group, a 4 - butoxy group, a 4 - (formylamino) phenyl, 4 - chlorophenyl, 4 - Cyano group, a 4 - diethylamino group, 4 - allyl diethyl malonyl-phenyl), 4 - Methylamino-phenyl, 4 - ethoxy-phenyl, 4 - ethyl-phenyl, 4 - fluorophenyl, 4 - hydroxyphenyl, 4 - imidazolyl group, a 4 - iodo-phenyl, 4 - isopropyl-phenyl, 4 - methoxy-phenyl, 4 - methyl-amino Yl group, a 4 - methylsulfonyl phenyl, 4 - morpholinyl-phenyl ,4-N-(2 - (dimethylamino) ethyl Yl)-N-formyl-amino)-phenyl ,4-N-(3 - methoxy-propionyl)-N-isopropyl - amino) phenyl, 4-N-ethyl-N-(2 - methoxyethyl) amino) phenyl ,4-N-formyl-piperidyl group, a 4 - nitro- Phenyl, 4 - piperidyl group, 4 - pyridyl group, a 4 - pyrrolyl alkylphenyl group, a 4 - tert-butyl-C Alkenoyl group, 5 - (dimethylamino) thiophene-2 - yl, 5 - amino-2 - pyridyl, 5 - dimethyl- Amino-2 - piperazinyl group, 3 - dimethylamino-pyridazin-6 - yl, 5 - dimethyl-2 - pyridyl group, a 5 - Phenyl pyrimidine, 6 - (N-methyl-N-formylamino) -3 - pyridyl, 6 - (N-methyl-N-(2 - methoxy- Ethyl) amino) -3 - pyridyl, 6 - (2 - oxo - oxazolidinyl) -3 - pyridyl, 6 - dimethylamino - 3 - pyridyl, 6 - imidazol-3 - pyridyl, 6 - morpholin-3 - pyridyl, 6 - pyrrolidinyl alkyl-3 - pyridine Piperidinyl, (2 - propyl) -3 - pyridyl, and (4 - formylamino) phenyl, (thien-2 - yl) methyl, (thiophene Thiophene-3 - yl) methyl group, butyl group, cycloheptyl group, pentyl group, thiophene-2 - yl, 1 - (3 - bromophenyl) ethyl, 2 - (N-phenyl-methoxycarbonyl) amino phenyl, 2 - (3 - bromophenyl) ethyl, 2 - (3 - cyanophenyl) Methyl 2 - (4 - bromophenyl) ethyl, 2 - (5 - chloro-2 - (thiophen-3 - yl) phenyl, 2 - bromophenyl group, a 2 - Furyl, 2 - methylpropyl, 2 - phenylethyl group, a phenyl group, 2,3 - dimethoxyphenyl, 2,3 - Methylenedioxy-phenyl, 3 - (furan-2 - yl) phenyl, 3 - (thiophen-2 - yl) phenyl, 3 - (2 - pyridyl Yl) phenyl, 3 - (3 - methoxybenzyl) phenyl, 3 - (amino) propynyl group, a 3 - benzyloxy-phenyl, 3 - Bromo-4 - fluorophenyl, 3 - bromo-5 - iodo-phenyl, 3 - bromo-5 - methoxy-phenyl, 3 - bromophenyl, 3 - bromophenyl Methyl 3 - (formylamino) phenyl, 3 - chlorophenyl, 3 - cyano group, a 3 - diethyl malonyl Allyl phenyl, 3 - dimethylamino-phenyl, 3 - ethoxy group, a 3 - fluoro-5 - (trifluoromethyl) Phenyl, 3 - fluorophenyl, 3 - hydroxyphenyl group, 3 - iodo group, a 3 - methoxy-ethoxy group, a 3 - Methoxy-phenyl, 3 - methylphenyl, 3 - methyl-sulfonyl group, a 3 - (methylthio) phenyl, 3 - t- Butyl-acryloyl group, a 3 - (Trifluoromethoxy) phenyl, 3 - (trifluoromethyl) phenyl, 3 - vinyl Pyridyl group, a 3,4 - dichlorophenyl, 3,4 - dimethoxyphenyl, 3,4 - methylenedioxy-phenyl, 3,4,5 - trimethoxyphenyl, 3,5 - bis (trifluoromethyl) phenyl, 3,5 - dibromo-phenyl, 3,5 - dichloro- Phenyl, 3,5 - dimethoxyphenyl, 3,5 - dimethylphenyl, 4 - (2 - propyl) phenyl, 4 - (2 - C Yl) oxy-phenyl, 4 - benzyloxy-phenyl, 4 - bromophenyl group, 4 - bromo-thiophen-2 - yl, 4 - butoxyphenyl, 4 - dimethylamino-phenyl, 4 - fluoro-3 - (trifluoromethyl) phenyl, 4 - methoxy-phenyl, 4 - neopentyl Phenyl, 4 - phenoxy-phenyl, 5 - bromo-thiophen-2 - yl, 5 - a cyclohexyl group, a 5 - cyclopropyl, 5 - hexyl group, 5 - methyl-5 - phenyl, (2 - bromo-5 - chlorophenyl) methyl, (2 - bromophenyl) methyl and (5 - chloro -2 - (3 - Methoxyphenyl) phenyl) methyl. ...

Independently selected from phenyl, thiophene-2 - yl, 1 - methyl-2 - oxo-benzoxazol-5 - yl, 2 - (dimethylamino) -5 - pyrimidinyl, 2 - (N-formyl-N-methyl-amino) -3 - pyrimidinyl, 2 - (N-(2 - Methoxyethyl)-N-methyl-amino) -5 - pyrimidinyl, 2 - (N-methylamino) 5 - pyrimidinyl, 2 - (1 - Morpholinyl) -5 - pyrimidinyl, 2 - (1 - pyrrolidinyl) -5 - pyrimidinyl, 2 - dimethyl-5 - pyrimidine Group, a 2 - furyl, 2 - oxo-benzoxazol-5 - yl, 2 - pyridyl, 3 - (dimethylamino) Phenyl, 3 - amino - 4 - methoxy-phenyl, 3 - bromo-4 - (dimethylamino) phenyl, 3 - methoxybenzene Group, a 3 - methyl--4 - (N-acetyl-N-methylamino) phenyl, 3 - methyl--4 - (N-formyl-N-methyl- Amino) phenyl, 3 - methyl--4 - (N-methyl-N-(trifluoroacetyl) amino) phenyl, 3 - methyl--4 - (N- Methylamino) phenyl, 3 - methyl - 4 - alkyl pyrrolyl group, 3 - pyridyl, 3,4 - dichlorophenyl, 3,4 - methylenedioxy-phenyl, 3,4,5 - trimethoxy-phenyl, 4 - (acetylamino) phenyl, 4 - (di- Methyl-amino) -3 - fluorophenyl, 4 - (dimethylamino) phenyl, 4 - (imidazol-1 - yl) phenyl, 4 - (methyl Thio) phenyl, 4 - (morpholin-yl) 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-ethyl-amino) phenyl, 4 - (N-formyl-N-(2 - methoxy- Yl-ethyl) amino) phenyl, 4 - (N-isopropylamino) phenyl, 4 - (N-methyl-N-((2 - dimethyl- Amino) ethyl) amino) phenyl, 4 - (N-methyl-N-(2 - (N-phthalimido) acetyl) amino) Phenyl, 4 - (N-methyl-N-(2 - cyano) ethylamino) phenyl, 4 - (N-methyl-N-(2 - methoxy- Ethyl) 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-trifluoro-acetic Acylamino) 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 Yl) phenyl, 4 - (2 - methoxy) ethoxy phenyl, 4 - (2 - oxo - oxazolidinyl) phenyl, 4 - (4 - Methoxy-2 - butyl) phenyl, 4 - (4 - methyl-piperidinyl) phenyl, 4 - (5 - pyrimidinyl) phenyl, 4 - Amino-phenyl, 4 - bromophenyl group, a 4 - butoxy group, a 4 - (formylamino) phenyl, 4 - chlorophenyl, 4 - Cyano group, a 4 - diethylamino group, 4 - allyl diethyl malonyl-phenyl), 4 - Methylamino-phenyl, 4 - ethoxy-phenyl, 4 - ethyl-phenyl, 4 - fluorophenyl, 4 - hydroxyphenyl, 4 - imidazolyl group, a 4 - iodo-phenyl, 4 - isopropyl-phenyl, 4 - methoxy-phenyl, 4 - methyl-amino Yl group, a 4 - methylsulfonyl phenyl, 4 - morpholinyl-phenyl ,4-N-(2 - (dimethylamino) ethyl Yl)-N-formyl-amino)-phenyl ,4-N-(3 - methoxy-propionyl)-N-isopropyl - amino) phenyl, 4-N-ethyl-N-(2 - methoxyethyl) amino) phenyl ,4-N-formyl-piperidyl group, a 4 - nitro- Phenyl, 4 - piperidyl group, 4 - pyridyl group, a 4 - pyrrolyl alkylphenyl group, a 4 - tert-butyl-C Alkenoyl group, 5 - (dimethylamino) thiophene-2 - yl, 5 - amino-2 - pyridyl, 5 - dimethyl- Amino-2 - piperazinyl group, 3 - dimethylamino-pyridazin-6 - yl, 5 - dimethyl-2 - pyridyl group, a 5 - Phenyl pyrimidine, 6 - (N-methyl-N-formylamino) -3 - pyridyl, 6 - (N-methyl-N-(2 - methoxy- Ethyl) amino) -3 - pyridyl, 6 - (2 - oxo - oxazolidinyl) -3 - pyridyl, 6 - dimethylamino - 3 - pyridyl, 6 - imidazol-3 - pyridyl, 6 - morpholin-3 - pyridyl, 6 - pyrrolidinyl alkyl-3 - pyridine Piperidinyl, (2 - propyl) -3 - pyridyl, and (4 - formylamino) phenyl, (thien-2 - yl) methyl, (thiophene Thiophene-3 - yl) methyl group, butyl group, cycloheptyl group, pentyl group, thiophene-2 - yl, 1 - (3 - bromophenyl) ethyl, 2 - (N-phenyl-methoxycarbonyl) amino phenyl, 2 - (3 - bromophenyl) ethyl, 2 - (3 - cyanophenyl) Methyl 2 - (4 - bromophenyl) ethyl, 2 - (5 - chloro-2 - (thiophen-3 - yl) phenyl, 2 - bromophenyl group, a 2 - Furyl, 2 - methylpropyl, 2 - phenylethyl group, a phenyl group, 2,3 - dimethoxyphenyl, 2,3 - Methylenedioxy-phenyl, 3 - (furan-2 - yl) phenyl, 3 - (thiophen-2 - yl) phenyl, 3 - (2 - pyridyl Yl) phenyl, 3 - (3 - methoxybenzyl) phenyl, 3 - (amino) propynyl group, a 3 - benzyloxy-phenyl, 3 - Bromo-4 - fluorophenyl, 3 - bromo-5 - iodo-phenyl, 3 - bromo-5 - methoxy-phenyl, 3 - bromophenyl, 3 - bromophenyl Methyl 3 - (formylamino) phenyl, 3 - chlorophenyl, 3 - cyano group, a 3 - diethyl malonyl Allyl phenyl, 3 - dimethylamino-phenyl, 3 - ethoxy group, a 3 - fluoro-5 - (trifluoromethyl) Phenyl, 3 - fluorophenyl, 3 - hydroxyphenyl group, 3 - iodo group, a 3 - methoxy-ethoxy group, a 3 - Methoxy-phenyl, 3 - methylphenyl, 3 - methyl-sulfonyl group, a 3 - (methylthio) phenyl, 3 - t- Butyl-acryloyl group, a 3 - (Trifluoromethoxy) phenyl, 3 - (trifluoromethyl) phenyl, 3 - vinyl Pyridyl group, a 3,4 - dichlorophenyl, 3,4 - dimethoxyphenyl, 3,4 - methylenedioxy-phenyl, 3,4,5 - trimethoxyphenyl, 3,5 - bis (trifluoromethyl) phenyl, 3,5 - dibromo-phenyl, 3,5 - dichloro- Phenyl, 3,5 - dimethoxyphenyl, 3,5 - dimethylphenyl, 4 - (2 - propyl) phenyl, 4 - (2 - C Yl) oxy-phenyl, 4 - benzyloxy-phenyl, 4 - bromophenyl group, 4 - bromo-thiophen-2 - yl, 4 - butoxyphenyl, 4 - dimethylamino-phenyl, 4 - fluoro-3 - (trifluoromethyl) phenyl, 4 - methoxy-phenyl, 4 - neopentyl Phenyl, 4 - phenoxy-phenyl, 5 - bromo-thiophen-2 - yl, 5 - a cyclohexyl group, a 5 - cyclopropyl, 5 - hexyl group, 5 - methyl-5 - phenyl, (2 - bromo-5 - chlorophenyl) methyl, (2 - bromophenyl) methyl and (5 - chloro -2 - (3 - Methoxyphenyl) phenyl) methyl. ...³And R⁴Independently selected from: phenyl, 4 - dimethyl -Amino phenyl, 4 - methylphenyl, 4 - bromophenyl group, 4 - pyridyl, (5 - pyrimidinyl) phenyl, 2 - (2 - pyridyl) vinyl phenyl, 3 - pyridyl, thiophene-3 - yl, 2 - pyridyl, 3,4 - methylenedioxy Phenyl, butyl, 5 - bromo-thiophen-2 - yl, 5 - methyl-thiophen-2 - yl, 4 - (trifluoromethoxy) Phenyl, 3 - phenoxy-phenyl, 5 - nitro-thiophen-2 - yl, 4 - bromo-thiophen-2 - yl, 3 - methylthiophene -2 - Yl, furan-2 - yl, furan-3 - yl, 5 - methyl - furan-2 - yl, 4 - (2 - propyl) phenyl, 3,4 - Dimethoxyphenyl, hexyl, 2 - methyl - 2 - propyl, 4 - (2 - propyl) phenyl, 4 - propyl group, 3 - methoxy-phenyl, 3 - bromophenyl, 3 - fluorophenyl, 3 - (trifluoromethyl) phenyl, 3 - chlorophenyl, 3,5 - Dichloro-phenyl, 3 - methoxycarbonyl-phenyl, 3 - (2 - propyl) phenyl, 4 - (2 - methyl - 2 - propyl) benzene Group, 4 - fluorophenyl, 4 - methoxyphenyl, 3 - (phenylmethoxy) phenyl, 4 - chlorophenyl, 3 - fluoro- -4 - Methylphenyl, 3 - phenylpropyl, 4-- methoxy-phenyl, 3 - phenyl-propyl, 2 - phenylethyl, Phenylmethyl, cyclohexylmethyl, pentyl, 2 - methyl-propyl, propyl, 3 - cyano-propyl, 3 - Nitrophenyl group, a 3 - (formylamino) propyl, (4 - methoxyphenyl) methyl, (3 - bromophenyl) methyl, (4 - (2 - propyl) phenyl) methyl), (4 - methoxyphenyl) methyl, (4 - bromophenyl) methyl), (3 - Fluorophenyl) methyl, (4 - bromophenyl) methyl, thiazol-2 - yl, (3 - methoxyphenyl) methyl, phenyl Methyl group, (3 - methoxyphenyl) methyl 4 - methylphenyl, 4 - (trifluoromethyl) phenyl, 4 - B Yl group, a 4 - acetylamino phenyl, 4 - phenoxy-phenyl, 4 - nitrophenyl, 4 - fluorophenyl, 4 - Chlorophenyl, 4 - amino-phenyl, 4 - (methylthio) phenyl, (4 - phenyl) phenyl, (4 - methoxy-phenyl) Phenyl, (4-N, N-diethylamino) phenyl, (4-2 - phenyl) phenyl, (2 - methyl -2 - Propoxy) phenyl, 3 - chlorophenyl, 3,5 - dimethoxyphenyl ,4-N, N-dimethyl-phenyl, And furan-2 - yl, 3 - bromo-4 - methoxy-phenyl, 4 - butoxy-phenyl, 3 - methoxy-phenyl and 3,5 - Dichlorophenyl. ...

10 compound as claimed in claim 5: 4 - amino-6 - phenyl-7 - (4 - dimethylaminophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - (dimethylamino) phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] Pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - phenyl-pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - bromophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - (dimethylamino) phenyl) -7 - (4 - pyridyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - (dimethylamino) phenyl) -7 - (4 - bromophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - (5 - pyrimidinyl) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - (2 - (2 - pyridyl) ethenyl) phenyl) pyrido [2,3-d] Pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (3 - pyridyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (thiophen-3 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (2 - pyridyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (3,4 - methylenedioxy-phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - butyl-7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - butyl-7 - (thiophen-3 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (5 - bromo-thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (5 - methyl-thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - (trifluoromethoxy) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (3 - phenoxy-phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (5 - nitro-thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - bromo-thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (3 - methyl-thiophene-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (furan-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (furan-3 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (5 - methyl - furan-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - (2 - propyl) phenyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - (2 - propyl) phenyl) -7 - (5 - nitro-thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (5 - nitro-thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - (dimethylamino) phenyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3,4 - dimethoxyphenyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3,4 - dimethoxyphenyl) -7 - (5 - nitro-thiophen-2 - yl) pyrido [2,3-d] pyrimidine Pyridine; 4 - amino-6 - hexyl-7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - amino-6 - hexyl-7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (2 - methyl - 2 - propyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - (2 - propyl) phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - (4 - propyl-phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3,4 - dimethoxyphenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - (3 - methoxy-phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - bromophenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - fluorophenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - (trifluoromethyl) phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - (3 - chlorophenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3,5 - difluorophenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3,4 - methylenedioxyphenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] Pyrimidine; 4 - Amino-6 - (3,4 - methylenedioxyphenyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - methoxycarbonyl-phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - (3 - (2 - propyl) phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - (4 - (2 - methyl - 2 - propyl) phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3 - d] pyrimidine; 4 - Amino-6 - (4 - fluorophenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methoxyphenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - (phenylmethoxy) phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] Pyrimidine; 4 - Amino-6 - (4 - chlorophenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - fluoro-4 - methyl-phenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - (3 - fluoro-4 - methyl-phenyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - phenyl-propyl) -7 - (4 - methoxyphenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - phenyl-propyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (2 - phenyl-ethyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - amino-6 - (phenylmethyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (cyclohexylmethyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - butyl-7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - amino-6 - pentyl -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (2 - methylpropyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - amino-6 - propyl -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - cyanopropyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - nitrophenyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine; 4 - amino-6 - pentyl-7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - (formylamino) propyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - ((4 - methoxyphenyl) methyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - ((3 - bromophenyl) methyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - ((4 - (2 - propyl) phenyl) methyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - ((4 - methoxyphenyl) methyl) -7 - (4 - (2 - propyl) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - ((4 - bromophenyl) methyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - ((3 - fluorophenyl) methyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - ((4 - bromophenyl) methyl) -7 - (thiazol-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - ((3 - methoxyphenyl) methyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - amino-6 - (phenylmethyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - ((3 - methoxyphenyl) methyl) -7 - (4 - (dimethylamino) phenyl) pyrido [2,3-d] Pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - (trifluoromethyl) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - methylphenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - methoxyphenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - ethyl-phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - cyanophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - acetylamino-phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - phenoxy-phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - nitrophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - fluorophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - chlorophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - aminophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - (methylthio) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - ((4 - phenyl) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - ((4 - methoxy-phenyl)-phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - ((4-N, N-diethylamino) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - ((4-2 - phenyl) phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - (2 - methyl - 2 - propoxy) phenyl) pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (3 - chlorophenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (3,5 - dimethoxyphenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (thien-2 - yl) -7 - (4-N, N-dimethyl-phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (benzofuran-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (thien-2 - yl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (thien-2 - yl) -7 - (4 - methoxyphenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - bromophenyl) -7 - (4-N, N-dimethyl-phenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (3 - bromo-4 - methoxy-phenyl) -7 - (4-N, N-dimethyl-phenyl) - pyrido [2,3-d] pyrimidine Pyridine; 4 - Amino-6 - (3 - bromo-4 - methoxy-phenyl) -7 - (thiophen-2 - yl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (4 - butoxyphenyl) pyrido [2,3-d] pyrimidine; 4 - Amino-6 - (4 - methyl-phenyl) -7 - (3 - methoxyphenyl) pyrido [2,3-d] pyrimidine; or 4 - Amino-6 - (4 - methyl-phenyl) -7 - (3,5 - dichlorophenyl) pyrido [2,3-d] pyrimidine. ...

12 A pharmaceutical composition comprising a therapeutically effective amount of a claimed compound of claim 1 or 5, Substance and a pharmaceutically acceptable carrier.

13. Treatment needs of such treatment a mammal ischemia, neurological diseases, injury Harm-grouping, inflammation, immune suppression, gastrointestinal disorders, diabetes and sepsis , The method comprising administering to said mammal a therapeutically effective amount of a claimed in claim 1 or 3, Compounds.

14 The method of claim 12, wherein said method comprises the treatment of cerebral ischemia, cardiac Myocardial ischemia, angina, coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty Surgery, stroke, thrombosis and embolism disease, epilepsy, anxiety, schizophrenia, pain perception, Neuropathic pain, visceral pain, arthritis, sepsis, diabetes and abnormal gastrointestinal Initiative.

15 having the preparation of the compound of formula:

Of which: R¹And R²Is hydrogen, R³Is lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, heteroaryl Or a heterocyclic group or substituted forms; R⁴Is aryl, heteroaryl or heterocyclic group or substituted forms; The method comprising: (a) The tetrakis (triphenylphosphine) palladium (O) and the presence of aqueous alkali metal base, the 4,6 - diamino-5 - Iodo-pyrimidine boronic acid having the formula of a vinyl derivative:

Of which: R³Is a lower alkyl, a lower alkenyl group, a lower alkynyl group, an aryl group, an aryl group or a heteroaryl group Or a heterocyclic group or substituted forms, and separating the first intermediate with a compound of the formula:(b) under anhydrous conditions and removing water formed by the reaction of the first intermediate compound with a There formula R⁴-CHO aldehyde compound, wherein R⁴Is aryl, heteroaryl or heterocyclic group Or a substituted form, and isolated compound of formula II.

16 with the preparation of compounds of the formula:Of which: R¹And R²Is independently H, lower alkyl, aryl or acyl group, or they are connected with the Then form together with the nitrogen atom optionally containing an additional oxygen or nitrogen atom 5-7 ring before Mention is R¹And R²Are not both hydrogen; R³Is lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, heteroaryl Or a heterocyclic group or substituted forms; R⁴Is aryl, heteroaryl or heterocyclic group or substituted forms; Said method comprising: (a) reacting a compound of the formula:Of which: R¹And R²Is hydrogen; R³Is lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, heteroaryl Or a heterocyclic group or substituted forms; R⁴Is aryl, heteroaryl or heterocyclic group or substituted forms; A compound selected from the following: (i) alkylating reagent R¹-Y, wherein R¹Is a lower alkyl group, Y is selected from halide, mesylate Esters and toluenesulfonate; (ii) an arylalkyl group of the reagent R¹- Lower alkyl-Y, wherein R¹Is an aryl group, Y is selected from a halogen Compounds, mesylate and tosylate; (iii) an acyl compound R¹-Z, wherein R¹Is an acyl group, Z is selected from anhydride moieties, halogenated Objects or acyl activating group; and isolating the desired compound; and (b) optionally, when needed R²Is not hydrogen, with a compound selected from process data from step Step (a) is a compound: (i) alkylating reagent R²-Y, wherein R²Is a lower alkyl group, Y is selected from halide, mesylate Esters and toluenesulfonate; (ii) an arylalkyl group of the reagent R²- Lower alkyl-Y, wherein R²Is an aryl group and Y is selected from Halide, mesylate and tosylate; (iii) an acyl compound R²-Z, wherein R²Is an acyl group, Z is selected from anhydride moieties, halogenated Objects or acyl activating group; and separate the compound of formula II.

17 having the preparation of the compound of formula:Of which: R¹And R²Is independently H, lower alkyl, aryl or acyl group, or with which they are Together with the nitrogen atom to form an optionally containing one additional oxygen or nitrogen atom 5-7 ring, Condition is R⁴And R⁵Are not both hydrogen; R³Is lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, heteroaryl Or a heterocyclic group or substituted forms; R⁴Is aryl, heteroaryl or heterocyclic group or substituted forms; The method comprising: (a) The tetrakis (triphenylphosphine) palladium (O) and the presence of aqueous alkali metal base, the 6 - amino-4 - chloro-5 - Iodo-pyrimidine boronic acid having the vinyl derivative of formula:

Where R³Is a lower alkyl, a lower alkenyl group, a lower alkynyl group, an aryl group, an aryl group or a heteroaryl group An aryl group or a heterocyclic ring or a substituted form, and separating the first intermediate with a compound of the formula(b) removed from the reaction under anhydrous conditions and in the water, the first intermediate compound of the formula R⁴-CHO aldehyde compound, wherein R⁴Is aryl, heteroaryl or heterocyclic group or Substituted forms, and separating the second intermediate with a compound of the formula:(c) the formula R¹-NH-R ²The amine compound treatment fourth intermediate compound, wherein R¹And R²As described above, and the isolated compound of formula II.

18 compound of the formulaWherein X is selected from halogen or OH, R³And R⁴As defined above.