EP1254137A1 - PYRIDO 2,3-d]PYRIMIDINE-2,7-DIAMINE KINASE INHIBITORS - Google Patents

PYRIDO 2,3-d]PYRIMIDINE-2,7-DIAMINE KINASE INHIBITORS

Info

Publication number
EP1254137A1
EP1254137A1 EP01900591A EP01900591A EP1254137A1 EP 1254137 A1 EP1254137 A1 EP 1254137A1 EP 01900591 A EP01900591 A EP 01900591A EP 01900591 A EP01900591 A EP 01900591A EP 1254137 A1 EP1254137 A1 EP 1254137A1
Authority
EP
European Patent Office
Prior art keywords
pyrido
pyrimidin
urea
phenylamino
piperazin
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP01900591A
Other languages
German (de)
English (en)
French (fr)
Inventor
Richard John Booth
Ellen Myra Dobrusin
Vara Prasad Venkata Nagendra Josyula
Dennis Joseph Mcnamara
Peter Laurence Toogood
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Warner Lambert Co LLC
Original Assignee
Warner Lambert Co LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Warner Lambert Co LLC filed Critical Warner Lambert Co LLC
Publication of EP1254137A1 publication Critical patent/EP1254137A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings

Definitions

  • This invention relates to pyrido[2.3-d]pyrimidine-2.7-diamines that inhibit cyclin-dependent serine/threonine kinases and growth factor-mediated tyrosine kinase enzymes, and as such are useful to treat cell proliferation diseases and disorders.
  • flavopiridol is a flavonoid that has been shown to be a potent inhibitor of several types of breast and lung cancer cells (Kaur et al., J. Natl. Cancer Inst.. 1992:84: 1736-1740; Int. J. Oncol. 1996;9: 1143-1168). The compound has been shown to inhibit cdk2 and cdk4.
  • Olomoucine [2-(hydroxyethylamino)-6-benzylamine-9-methylpurine] is a potent inhibitor of cdk2 and cdk5 (Vesely et al.. Eur. J. Biochem.. 1994:224:771 -786). and has been shown to inhibit proliferation of approximately 60 different human tumor cell lines used by the National Cancer Institute (NCI) to screen for new cancer therapies (Abraham et al.. Biology of the Cell 1995:83: 105-120). More recently, the purvalanol class of cdk inhibitors has emerged as more potent derivatives of olomoucine (Gray N.S. et al.. Science. 1998:281 :533-538).
  • Tyrosine kinases are essential for the propagation of growth factor signal transduction leading to cell cycle progression, cellular proliferation. differentiation, and migration.
  • Tyrosine kinases include cell surface growth factor receptor tyrosine kinases such as FGFr and PDGFr. as well as nonreceptor tyrosine kinases. including c-Src and lck. Inhibition of these enzymes has been demonstrated to cause antitumor and antiangiogenesis activity (Hamby et al., Pharmacol Then. 1999:82(2-3): 169-193).
  • the present invention provides such compounds, their pharmaceutical formulations, and their use in treating proliferative disorders.
  • This invention provides novel pyrido[2.3-d]pyrimidine-2.7-diamine compounds which function as inhibitors of cell cycle regulatory' kinases such as the cyclin dependent kinases as well as the growth factor-mediated tyrosine kinases.
  • these compounds are useful to treat cell proliferative disorders such as atherosclerosis and restenosis; cancer: angiogenesis: viral infections including DNA viruses such as herpes and RNA viruses such as HIV; fungal infections; type 1 diabetes, diabetic neuropathy and retinopathy: multiple sclerosis; glomerulonephritis: neurodegenerative diseases including Alzheimer ' s disease; autoimmune diseases such as psoriasis, rheumatoid arthritis, and lupus; organ transplant rejection and host versus graft disease; gout; polycystic kidney disease; and inflammation including inflammatory bowel disease.
  • cancer angiogenesis: viral infections including DNA viruses such as herpes and RNA viruses such as HIV
  • fungal infections type 1 diabetes, diabetic neuropathy and retinopathy: multiple sclerosis
  • glomerulonephritis neurodegenerative diseases including Alzheimer ' s disease
  • autoimmune diseases such as psoriasis, rheumatoid arthritis, and lupus
  • R14 and R15 are independently hydrogen, or lower alkyl, lower alkenyl, or lower alkynyl. each of which is optionally substituted with up to 5 groups independently selected from halogen, cyano, nitro, -R 9 , -NR 9 R! °. -OR 9 . -(CH2) n CO 2 R 9 ,
  • -NR 9 SO 2 R 10 or a heterocycle optionally substituted with up to 3 groups independently selected from -R 9 . -NR 9 R 1 0 , -OR 9 . -NR 9 COR 1 0 . -COR 10 . -(CH2) n SO 2 R ⁇ . -(CH ⁇ R 1 1 , or -(CH 2 ) n R l - optionally substituted with up to 5 groups independently selected from halogen, cyano, nitro. -R 9 , -NR R 1 0 . -OR 9 , -(CH 2 ) n CO 2 R 9 . -(CH 2 ) n S0 2 R 1 1. -(CH ⁇ R 1 1. -COR 9 .
  • R 9 and R 10 are independently hydrogen, or lower alkyl. optionally substituted with up to 3 groups selected from the group consisting of halogen, amino. mono- or dialkylamino, hydroxy. lower alkoxy. phenyl or substituted phenyl, or when taken together with the nitrogen to which they are attached, R 9 and R 1 ° form a ring having from 3-7 members, up to four of which
  • R 1 ! is a heteroaryl or a heterocyclic group:
  • the present invention also provides methods for inhibiting cyclin- dependent kinase and growth factor-mediated kinase enzymes.
  • the present invention also provides a method of treating subjects suffering from diseases caused by cellular proliferation. The method comprises inhibiting proliferation of tumorigenic cells of epithelial origin and vascular smooth muscle proliferation, and/or cellular migration by administering a therapeutically effective amount of a compound of Formula I to a subject in need of treatment.
  • the present invention also provides a method of treating subjects suffering from diseases caused by DNA tumor viruses, such as herpes viruses comprising administering a compound of Formula I.
  • the compounds encompassed by the instant invention are those described by the general Formula I set forth above, and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof.
  • R 6 R! 7_ and R 1 8 are as defined above for the (CH 2 ) n R 1 - substituents. and preferably are independently hydrogen, halogen, amino. mono- or dialkylamino. hydroxy. lower alkyl. lower alkoxy. cyano. nitro, carboxy, carboxyalkyl. aminocarbonyl. mono- or dialkylaminocarbonyl, alkylcarbonyl. -S0 3 R 9 . -SO NR 9 R 10 , -SO 2 R 9 , -SR 9 . -PO 3 R 9 R 1 0, -POR 9 R 10 . -PO( R 9 R 10 ) 2 . -NR 9 COR 10 , -NR 9 CO 2 R 10 . -NR 9 CONR 9 R 1 0 . -NR 9 SO 2 R 1 0 ; or
  • R ⁇ is a carbocyclic group containing from 3-7 members, up to 2 of which members are heteroatoms selected from oxygen and nitrogen, wherein the carbocyclic group is unsubstituted or substituted with 1 , 2. or 3 groups as defined above, but preferably are independently selected from the group consisting of halogen, hydroxy. lower alkyl, trifluoromethyl. lower alkoxy. amino. mono- or dialkylamino. aryl. heteroaryl. arylalkyl. heteroarylalkyl. heteroarylsulfonyl. heteroarylsulfonylalkyl, heterocyclylalkyl. heterocyclylsulfonyl. or heterocyclylsulfonylalkyl.
  • R 3 is hydrogen or lower alkyl
  • R ⁇ is hydrogen, lower alkyl, cyano or halogen
  • R 1 ⁇ and R 18 are independently hydrogen, halogen, amino. mono- or dialkylamino. hydroxy, lower alkyl. lower alkoxy, aminocarbonyl. mono- or dialkylaminocarbonyl,
  • R 16 is optionally substituted N-piperidine.
  • '"Alkylaminoalkanoyl means an aminoalkanoyl group wherein the amine is substituted with a C] -C ⁇ Q alkyl group, and includes methylaminoacetyl and 4-(isobutylamino)-octanoyl.
  • "'Dialkylaminoalkanoyl' means an N.N-di-substituted aminoalkanoyl group such as diisopropylaminoacetyl.
  • a “"substituted heteroaryl “ group can be substituted with 1, 2, 3, or 4 of the groups mentioned above for “substituted aryl. " such as 2.3.4.6- tetrachloropyridyl and 2-methoxy-3-trifluoromethylthien-4-yl.
  • a “carbocyclic group " or "'cycloalkyr * is a nonaromatic cyclic ring or fused rings having from 3- to 7-ring carbon members. Examples include cyclopropyl, cvclobutyl. and cycloheptyl. These rings may be substituted with one or more of the substituent groups mentioned above for aryl, for example alkyl, halo, amino. hydroxy. and alkoxy. Typical substituted carbocyclic groups include 2-chlorocyclopropyl, 2.3-diethoxycyclopentyl, and 2.2.4,4-tetrafluorocyclohexyl. The carbocyclic group may contain 1 or 2 heteroatoms selected from oxygen, sulfur, and nitrogen, and such ring systems are referred to as "heterocyclyl " or
  • the compounds of Formulas I to VI can exist as pharmaceuticalK acceptable salts, esters, amides, and prodrugs.
  • pharmaceuticalK acceptable salts, esters, amides, and prodrugs refers to those carboxy late salts, amino acid addition salts, esters, amides, and prodrugs of the compounds of the present invention which are. within the scope of sound medical judgment, suitable for use in contact with the tissues of patients without undue toxicity. irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use. as well as the zwitterionic forms, where possible, of the compounds of the invention.
  • salts refers to the relatively nontoxic.
  • the compounds of the present invention are useful for treating cancer (for example, leukemia, and cancer of the lung, breast, prostate, and skin such as melanoma) and other proliferative diseases, including, but not limited to, psoriasis. HSV. HIV. restenosis. and atherosclerosis.
  • cancer for example, leukemia, and cancer of the lung, breast, prostate, and skin such as melanoma
  • other proliferative diseases including, but not limited to, psoriasis. HSV. HIV. restenosis. and atherosclerosis.
  • a patient having cancer is administered a therapeutically effective amount of a pharmaceutically acceptable composition comprising an invention compound.
  • the therapeutically effective dose of a compound of Formula I will generally be from about 1 to about 100 mg/kg of body weight per day. Typical adult doses will be about 50 to about 800 mg per day.
  • the quantity of active component in a unit dose preparation may be varied or adjusted from about 0.1 to about 500 mg, preferably about 0.5 to 100 mg according to the particular application and the potency of the active component.
  • the composition can. if desired, also contain other compatible therapeutic agents.
  • a subject in need of treatment with a compound of Formula I is administered a dosage of about 1 to about 500 mg per day. either singly or in multiple doses over a 24-hour period.
  • Typical hydroxy protecting groups include ether forming groups such as benzyl, and aryl groups such as tert-butoxycarbonyl (Boc). formyl. and acetyl.
  • Amino protecting groups include benzyl, aryl such as acetyl. and trialkylsilyl groups.
  • Carboxylic acid groups typically are protected by conversion to an ester that can be easily hydrolyzed. for example, trichloroethyl. tert-butyl. benzyl, and the like.
  • some of the invention compounds have one or more chiral centers, and thus can exist as individual optical isomers and geometric isomers. and mixtures thereof.
  • Compound 106 Some of the invention compounds have one or more chiral centers, and thus can exist as individual optical isomers and geometric isomers. and mixtures thereof.
  • Example 24 By substituting cis-3.5-dimethyl-l -(4-nitro-phenyl)-piperazine (Example 24) for l-(4-nitrophenyl)-piperazine in Example 11. 14.87 g (92.8%) of the product as a solid is obtained.
  • Example 28 By substituting cyclohexyl isocvanate for tert-butyl isocvanate in Example 28. 0.1156 g (60.8%) of the product is obtained as a solid.
  • Example 34 By substituting 1 -(4-amino-2-methylsulfanyl-pyrimidin-5-yl)-ethanol ( Example 34) for (4-amino-2-methylsulfanyl-pyrimidin-5-yl )-methanol in Example 3 and conducting the reaction at 80°C in toluene. 3.74 g (72%) of the product as a solid is obtained. MS (APCI) M+l : Calcd 184.0; Found 183.9.
  • EXAMPLE 84 4-[4-(7-Amino-6-bromo-pyrido[2,3-d]pyrimidin-2-ylamino)-phenyl]-cis-2,6- dimethyl-piperazine-1-carboxylic acid tert-butyl ester substituting the product of Example 76 in Example 27. 2.10 g (63.1%) of the product is obtained as a solid. MS (APCI) M-l : Calcd 528.2; Found 528.2.
  • Example 130 By substituting the product of Example 130 in Example 10. 0.05 g (48%) of the product as a solid is obtained.
  • a 20 ⁇ L sample of test agent (diluted in EDB) is then combined with 20 ⁇ L of the of the final cdk5/p25 enzyme preparation and allowed to stand for 5 minutes at room temperature. Twenty-five microliters of substrate solution containing 1 15 ⁇ L/mL Histone HI . 30 ⁇ M ATP (vanadate-free). and 30 ⁇ Ci/mL ⁇ -3->P ATP (Amersham) in EDB is then added to the test agent/enzyme preparation and shaken at 30°C for 45 minutes. A 50 ⁇ L sample of the final preparation is added to 100 mL of 150 mM phosphoric acid on ice for 30 minutes to facilitate precipitation.
  • reaction components 10 ⁇ L c-Src beads. 10 ⁇ L of 2.5 mg/mL poly GluTvr substrate, 5 ⁇ M ATP containing 0.2 ⁇ Ci labeled 2p_ATP. 5 ⁇ L DMSO containing inhibitors or as a solvent control, and buffer to make the final volume 125 ⁇ L.
  • the reaction is started at room temperature by addition of the ATP and quenched 10 minutes later by the addition of 125 ⁇ L of 30% TCA. 0.1 M sodium pyrophosphate for 5 minutes on ice.
  • the active ingredient, starch, and cellulose are passed through a No. 45 mesh US sieve and mixed thoroughly.
  • the solution of polyvinylpyrrolidone is mixed with the resultant powders and then passed through a No. 14 mesh US sieve.
  • the granules are dried at 50°C to 60°C and passed through a No. 18 mesh US sieve.
  • the sodium carboxymethyl starch, magnesium stearate. and talc. previously passed through a No. 60 mesh US sieve, are then added to the granules which, after mixing, are compressed on a tablet machine to yield tablets each weighing 150 mg.
  • R "7 , R . 13, R14_ anc j R1:> are independently hydrogen, or lower alkyl. lower alkenyl. or lower alkynyl. each of which is optionally substituted with up to 5 groups independently selected from halogen, cyano. nitro. -R 9 . -NR ⁇ R ⁇ O ⁇ -OR9 -(CH 2 ) n CO 2 R 9 . -(CH2) n SO2R n . -(CH 2 ) n R ⁇ - -COR 9 , -CONR 9 R 10 . -SO3R 9 . -SO 2 NR 9 R 10 . -SO R 9 . -SR 9 . -P0 R 9 R 10 . -POR 9 R 10 . -PO(NR 9 R 10 ) 2 . -NR 9 COR 10 ,

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Neurology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Cardiology (AREA)
  • Psychiatry (AREA)
  • Dermatology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Enzymes And Modification Thereof (AREA)
EP01900591A 2000-01-25 2001-01-23 PYRIDO 2,3-d]PYRIMIDINE-2,7-DIAMINE KINASE INHIBITORS Withdrawn EP1254137A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US17826100P 2000-01-25 2000-01-25
US178261P 2000-01-25
PCT/IB2001/000069 WO2001055147A1 (en) 2000-01-25 2001-01-23 PYRIDO[2,3-d]PYRIMIDINE-2,7-DIAMINE KINASE INHIBITORS

Publications (1)

Publication Number Publication Date
EP1254137A1 true EP1254137A1 (en) 2002-11-06

Family

ID=22651853

Family Applications (1)

Application Number Title Priority Date Filing Date
EP01900591A Withdrawn EP1254137A1 (en) 2000-01-25 2001-01-23 PYRIDO 2,3-d]PYRIMIDINE-2,7-DIAMINE KINASE INHIBITORS

Country Status (34)

Country Link
EP (1) EP1254137A1 (cs)
JP (1) JP4047010B2 (cs)
KR (1) KR20020065939A (cs)
CN (1) CN1395578A (cs)
AP (1) AP2002002586A0 (cs)
AR (1) AR030044A1 (cs)
AU (1) AU2542501A (cs)
BG (1) BG106850A (cs)
BR (1) BR0107751A (cs)
CA (1) CA2397961C (cs)
CO (1) CO5261549A1 (cs)
CR (1) CR6706A (cs)
CZ (1) CZ20022475A3 (cs)
DZ (1) DZ3266A1 (cs)
EA (1) EA200200643A1 (cs)
EE (1) EE200200405A (cs)
GT (1) GT200100016A (cs)
HN (1) HN2001000013A (cs)
HU (1) HUP0204141A3 (cs)
IL (1) IL150545A0 (cs)
IS (1) IS6443A (cs)
MA (1) MA26868A1 (cs)
MX (1) MXPA02007221A (cs)
NO (1) NO20023527L (cs)
OA (1) OA12161A (cs)
PA (1) PA8510701A1 (cs)
PE (1) PE20011066A1 (cs)
PL (1) PL356802A1 (cs)
SK (1) SK10632002A3 (cs)
SV (1) SV2002000294A (cs)
TN (1) TNSN01014A1 (cs)
WO (1) WO2001055147A1 (cs)
YU (1) YU50402A (cs)
ZA (1) ZA200205879B (cs)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7235551B2 (en) 2000-03-02 2007-06-26 Smithkline Beecham Corporation 1,5-disubstituted-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one compounds and their use in treating csbp/p38 kinase mediated diseases
ES2372028T3 (es) 2000-10-23 2012-01-13 Glaxosmithkline Llc Nuevo compuesto de 8h-pirido[2,3-d]pirimidin-7-ona trisustituida para el tratamiento de enfermedades mediadas por la csbp/p38 quinasa.
PE20030008A1 (es) * 2001-06-19 2003-01-22 Bristol Myers Squibb Co Inhibidores duales de pde 7 y pde 4
MXPA04010267A (es) 2002-04-19 2005-02-03 Smithkline Beecham Corp Compuestos novedosos.
KR20050084027A (ko) * 2002-11-28 2005-08-26 쉐링 악티엔게젤샤프트 Ｃｈｋ-, ｐｄｋ- 및 ａｋｔ-억제성 피리미딘, 그의제조방법 및 약제로서의 그의 용도
US7157455B2 (en) * 2003-02-10 2007-01-02 Hoffmann-La Roche Inc. 4-Aminopyrimidine-5-one derivatives
TW200502236A (en) 2003-03-28 2005-01-16 Hoffmann La Roche Novel pyrido[2,3-d]pyrimidin-7-carboxylic acid derivatives, their manufacture and use as pharmaceutical agents
FR2873118B1 (fr) 2004-07-15 2007-11-23 Sanofi Synthelabo Derives de pyrido-pyrimidine, leur application en therapeutique
CA2579406A1 (en) * 2004-09-21 2006-03-30 F.Hoffmann-La Roche Ag 6-(2-alkyl-phenyl) - pyrido[2,3-d] pyrimidines useful as protein kinase inhibitors
JP2008535822A (ja) 2005-03-25 2008-09-04 グラクソ グループ リミテッド 新規化合物
PE20100741A1 (es) 2005-03-25 2010-11-25 Glaxo Group Ltd COMPUESTOS DERIVADOS DE 3,4-DIHIDROPIRIMIDO[4,5-d]PIRIMIDIN-2(1H)-ONA COMO INHIBIDORES DE QUINASA p38
UY29440A1 (es) 2005-03-25 2006-10-02 Glaxo Group Ltd Nuevos compuestos
EP1865959A2 (en) 2005-03-25 2007-12-19 Glaxo Group Limited Process for preparing pyridoý2,3-d¨pyrimidin-7-one and 3,4-dihydropyrimidoý4,5-d¨pyrimidin-2(1h)-one derivatives
FR2887882B1 (fr) * 2005-07-01 2007-09-07 Sanofi Aventis Sa Derives de pyrido[2,3-d] pyrimidine, leur preparation, leur application en therapeutique
CN101243081A (zh) * 2005-07-21 2008-08-13 霍夫曼-拉罗奇有限公司 作为PTP1B抑制剂的吡啶并[2,3-d]嘧啶-2,4-二胺化合物
AU2006279992A1 (en) 2005-08-09 2007-02-22 Irm Llc Compounds and compositions as protein kinase inhibitors
FR2896246B1 (fr) 2006-01-13 2008-08-15 Sanofi Aventis Sa Derives de pyrido-pyrimidone, leur preparation, leur application en therapeutique.
EP1914234A1 (en) 2006-10-16 2008-04-23 GPC Biotech Inc. Pyrido[2,3-d]pyrimidines and their use as kinase inhibitors
JO2985B1 (ar) 2006-12-20 2016-09-05 Takeda Pharmaceuticals Co مثبطات كينازmapk/erk
FR2910813B1 (fr) 2006-12-28 2009-02-06 Sanofi Aventis Sa Nouvelle utilisation therapeutique pour le traitement des leucemies
EP2112150B1 (en) 2008-04-22 2013-10-16 Forma Therapeutics, Inc. Improved raf inhibitors
BRPI0922154A2 (pt) * 2008-12-01 2016-01-05 Merck Patent Gmbh pirido[4,3-d]pirimidinas 2,5-diamino-substituídas como inibidores de autotaxina contra o cãncer
GB201104267D0 (en) 2011-03-14 2011-04-27 Cancer Rec Tech Ltd Pyrrolopyridineamino derivatives
GB201216018D0 (en) 2012-09-07 2012-10-24 Cancer Rec Tech Ltd Pharmacologically active compounds
GB201216017D0 (en) 2012-09-07 2012-10-24 Cancer Rec Tech Ltd Inhibitor compounds
US9815847B2 (en) 2013-03-14 2017-11-14 Icahn School Of Medicine At Mount Sinai Pyrimidine compounds as kinase inhibitors
GB201403536D0 (en) 2014-02-28 2014-04-16 Cancer Rec Tech Ltd Inhibitor compounds
KR101671404B1 (ko) * 2014-09-02 2016-11-02 한국원자력의학원 항암 효과, 방사선 병용치료 효과 및 당뇨병 치료 효과를 갖는 피리미딘 유도체 및 이의 의학적 용도
CN107286180B (zh) * 2016-04-11 2019-07-02 上海勋和医药科技有限公司 杂代吡啶并嘧啶酮衍生物作为cdk抑制剂及其应用
GB201709840D0 (en) 2017-06-20 2017-08-02 Inst Of Cancer Research: Royal Cancer Hospital Methods and medical uses

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU711426B2 (en) * 1994-11-14 1999-10-14 Warner-Lambert Company 6-aryl pyrido(2,3-d)pyrimidines and naphthyridines for inhibiting protein tyrosine kinase mediated cellular proliferation
IL115256A0 (en) * 1994-11-14 1995-12-31 Warner Lambert Co 6-Aryl pyrido (2,3-d) pyrimidines and naphthyridines and their use
US5620981A (en) * 1995-05-03 1997-04-15 Warner-Lambert Company Pyrido [2,3-D]pyrimidines for inhibiting protein tyrosine kinase mediated cellular proliferation
BR9911590A (pt) * 1998-05-26 2001-02-13 Warner Lambert Co Pirimidinas bicìclicas e 3,4-diidropirimidinas bicìclicas como inibidores da proliferação celular

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0155147A1 *

Also Published As

Publication number Publication date
MA26868A1 (fr) 2004-12-20
CR6706A (es) 2005-04-04
DZ3266A1 (fr) 2001-08-02
NO20023527L (no) 2002-09-10
BG106850A (bg) 2003-02-28
PL356802A1 (en) 2004-07-12
PA8510701A1 (es) 2002-12-11
CZ20022475A3 (cs) 2003-03-12
ZA200205879B (en) 2003-09-29
PE20011066A1 (es) 2001-10-22
GT200100016A (es) 2001-10-19
IS6443A (is) 2002-06-25
EE200200405A (et) 2003-12-15
TNSN01014A1 (fr) 2005-11-10
JP4047010B2 (ja) 2008-02-13
CO5261549A1 (es) 2003-03-31
CA2397961A1 (en) 2001-08-02
EA200200643A1 (ru) 2002-12-26
KR20020065939A (ko) 2002-08-14
SK10632002A3 (sk) 2003-06-03
YU50402A (sh) 2005-11-28
AU2542501A (en) 2001-08-07
JP2003523357A (ja) 2003-08-05
AR030044A1 (es) 2003-08-13
NO20023527D0 (no) 2002-07-24
IL150545A0 (en) 2003-02-12
HUP0204141A2 (hu) 2003-04-28
SV2002000294A (es) 2002-07-16
OA12161A (en) 2006-05-08
MXPA02007221A (es) 2002-11-29
BR0107751A (pt) 2002-11-12
HN2001000013A (es) 2001-06-18
CA2397961C (en) 2008-08-26
CN1395578A (zh) 2003-02-05
HUP0204141A3 (en) 2005-03-29
AP2002002586A0 (en) 2002-09-30
WO2001055147A1 (en) 2001-08-02

Similar Documents

Publication Publication Date Title
WO2001055147A1 (en) PYRIDO[2,3-d]PYRIMIDINE-2,7-DIAMINE KINASE INHIBITORS
US7053070B2 (en) Pyrido[2,3-d]pyrimidine-2,7-diamine kinase inhibitors
AU777468B2 (en) Pteridinones as kinase inhibitors
CA2329703C (en) Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation
EP1751153B1 (de) Hetaryloxy-substituierte phenylaminopyrimidine als rho-kinasehemmer
US20090312321A1 (en) Compositions and methods for fgf receptor kinases inhibitors
SK141097A3 (en) Pyrido[2,3-d]pyrimidines for inhibiting protein tyrosine kinase mediated cellular proliferation
WO2008144253A1 (en) Protein kinase inhibitors and methods for using thereof
OA12227A (en) 5-AlkylpyridoÄ2,3-DÜpyrimidines tyrosine kinase inhibitors.
EP1651648A2 (en) Compounds and compositions as protein kinase inhibitors
WO2008112695A2 (en) Pyrazolo [3,4-d] pyrimidines and 1, 2, 5, 6-tetraaza- as- indacenes as protein kinase inhibitors for cancer treatment
JP2010508324A (ja) プロテインキナーゼモジュレーターとしての３−アミノカルボニル置換縮合ピラゾロ誘導体
WO2006002367A1 (en) Compounds and compositions as protein kinase inhibitors
US7323469B2 (en) 7H-pyrrolo[2,3-d]pyrimidine derivatives
OA11554A (en) Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation.

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20020708

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR

AX Request for extension of the european patent

Free format text: AL PAYMENT 20020708;LT PAYMENT 20020708;LV PAYMENT 20020708;MK PAYMENT 20020708;RO PAYMENT 20020708;SI PAYMENT 20020708

17Q First examination report despatched

Effective date: 20040308

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: WARNER-LAMBERT COMPANY LLC

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: WARNER-LAMBERT COMPANY LLC

17Q First examination report despatched

Effective date: 20040308

RTI1 Title (correction)

Free format text: PYRIDO 2,3-D PYRIMIDINE-2,7-DIAMINE KINASE INHIBITORS

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20100121