WO2010044401A1 - モルホリノプリン誘導体 - Google Patents

モルホリノプリン誘導体 Download PDF

Info

Publication number
WO2010044401A1
WO2010044401A1 PCT/JP2009/067738 JP2009067738W WO2010044401A1 WO 2010044401 A1 WO2010044401 A1 WO 2010044401A1 JP 2009067738 W JP2009067738 W JP 2009067738W WO 2010044401 A1 WO2010044401 A1 WO 2010044401A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
alkylamino
substituents
substituents selected
compound
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.)
Ceased
Application number
PCT/JP2009/067738
Other languages
English (en)
French (fr)
Japanese (ja)
Inventor
清 中山
杉田　和幸
正樹 瀬戸口
裕一 冨永
正規 齋藤
高志 小田桐
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.)
Daiichi Sankyo Co Ltd
Original Assignee
Daiichi Sankyo Co Ltd
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
Priority to EP09820579.2A priority Critical patent/EP2336132B1/en
Priority to PL09820579T priority patent/PL2336132T3/pl
Priority to ES09820579.2T priority patent/ES2452541T3/es
Priority to BRPI0920199A priority patent/BRPI0920199A2/pt
Priority to DK09820579.2T priority patent/DK2336132T3/da
Priority to AU2009304789A priority patent/AU2009304789B2/en
Priority to NZ592761A priority patent/NZ592761A/en
Priority to MX2011003490A priority patent/MX2011003490A/es
Priority to RU2011119525/04A priority patent/RU2490269C2/ru
Application filed by Daiichi Sankyo Co Ltd filed Critical Daiichi Sankyo Co Ltd
Priority to CA2740471A priority patent/CA2740471C/en
Priority to HK11112477.4A priority patent/HK1158189B/en
Priority to CN200980151585.4A priority patent/CN102245607B/zh
Publication of WO2010044401A1 publication Critical patent/WO2010044401A1/ja
Priority to ZA2011/02449A priority patent/ZA201102449B/en
Priority to IL212278A priority patent/IL212278A/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
    • C07D473/32—Nitrogen atom
    • C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Definitions

  • a tumor in which overexpression of phosphatidylinositol 3-kinase (PI3K) is observed which comprises administering the compound according to any one of [1] to [18] or a salt thereof Method of treatment.
  • Treatment of a tumor in which a mutation of phosphatidylinositol 3-kinase (PI3K) is observed comprising administering the compound according to any one of [1] to [18] or a salt thereof Method.
  • a method for treating a tumor exhibiting enhanced phosphorylation of Akt comprising administering the compound according to any one of [1] to [18] or a salt thereof.
  • the “C 1 -C 6 alkylaminocarbonyl group” means a group in which the above C 1 -C 6 alkylamino group is substituted on the carbonyl group.
  • the “C 1 -C 6 alkylaminosulfonyl group” means a group in which the above C 1 -C 6 alkylamino is substituted on the sulfonyl group.
  • the “di-C 1 -C 6 alkylaminosulfonyl group” means a group in which the di-C 1 -C 6 alkylamino group is substituted on the sulfonyl group.
  • substituents of “aryl group which may be present” include one or more halogen atoms, hydroxy group, C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, amino group, C 1 -C 6.
  • Archi Amino group, di C 1 ⁇ C 6 alkylamino group, a cyano group, C 1 ⁇ C 6 alkylamino C 1 ⁇ C 6 alkyl group or a C 1 ⁇ C 6 alkylcarbonylamino group are preferred.
  • substituents may be on the same atom or different atoms.
  • X represents a 6-membered aromatic nitrogen-containing heterocyclic group containing one or two nitrogen atoms, which may have one or a plurality of substituents.
  • X includes a group derived from pyridine, pyridazine or pyrimidine. X may be bonded at any position to the imidazolopyrimidine ring in the general formula (1).
  • X is preferably a group derived from pyrimidine, particularly preferably bonded at the 2-position to the imidazolopyrimidine ring.
  • Rb and Rc each independently represent a C 1 -C 6 alkyl group which may have one or more substituents, or a hydrogen atom, or Rb and Rc are taken together This indicates that a 4- to 7-membered alicyclic nitrogen-containing heterocyclic group which may have one or more substituents together with the nitrogen atom to which Rb and Rc are bonded may be formed.
  • Conversion from compound 6 (when one or more of the substituents on the nitrogen atom bonded to X in the figure is hydrogen) to compound 7 is an excess mole of Boc 2 O, preferably 1 mole of compound 6.
  • a base such as 4-dimethylaminopyridine
  • N, N-dimethylformamide, tetrahydrofuran, 1,4-dioxane, N-methylpyrrolidone and the like are not adversely affected.
  • the reaction is carried out in a solvent at room temperature to 80 ° C. for about 1 to 10 hours.
  • Conversion from compound 7 to compound 8 is carried out by using a commonly used halogenating agent such as N-chlorosuccinimide, N-bromosuccinimide, N-iodosuccinimide, bromine, iodine, BrI and the like with respect to 1 mole of compound 7.
  • a commonly used halogenating agent such as N-chlorosuccinimide, N-bromosuccinimide, N-iodosuccinimide, bromine, iodine, BrI and the like with respect to 1 mole of compound 7.
  • Molar to excess molar, preferably 1 to 3 molar, in an appropriate solvent that does not adversely influence the reaction eg, N, N-dimethylformamide, acetonitrile, chloroform, methylene chloride
  • a radical initiator may be added.
  • reaction temperature 0. C. to 300.degree. C. is preferred, and room temperature to 200.degree. C. is more preferred.
  • the halogen reagent, mesylate reagent, and the like and the base are used in an amount of 1 to an excess mole, preferably 1 to 5 moles relative to 1 mole of Compound 13.
  • the reaction time is preferably 1 minute to 60 hours, more preferably 5 minutes to 24 hours.
  • the conversion from compound 15 to compound 8 can be carried out by using an organic base or an inorganic salt in a suitable solvent or a mixed solvent thereof that does not exert an adverse effect such as N, N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, or acetonitrile.
  • a base potassium carbonate, potassium t-butoxide, triethylamine, etc.
  • an appropriate additive for example, triethylbenzylammonium chloride, etc.
  • an alkyl halide compound or a methanesulfonyloxyalkyl compound is used. It is done by processing. It is preferable to use 1 to excess moles, preferably 1 to 5 moles of each of the alkyl halide or base, relative to 1 mole of Compound 15.
  • the reaction time is preferably 30 minutes to 72 hours, and more preferably 30 minutes to 24 hours.
  • optical isomer exists when the compound (1) of the present invention or the production intermediate has an asymmetric carbon.
  • These optical isomers can be isolated and purified by conventional methods such as fractional recrystallization (salt resolution) for recrystallization with an appropriate salt and column chromatography.
  • References for methods for resolution of optical isomers from racemates include: “Enantiomers, Racemates and Resolution, John Wiley And Sons, Inc.” by Jacques et al.
  • Antitumor antibiotics include, for example, anthracycline antibiotic antitumor agents such as mitomycin C, bleomycin, peplomycin, daunorubicin, aclarubicin, doxorubicin, pirarubicin, THP-adriamycin, 4'-epidoxorubicin or epirubicin, chromomycin A Examples include 3 or actinomycin D.
  • anthracycline antibiotic antitumor agents such as mitomycin C, bleomycin, peplomycin, daunorubicin, aclarubicin, doxorubicin, pirarubicin, THP-adriamycin, 4'-epidoxorubicin or epirubicin, chromomycin A
  • anthracycline antibiotic antitumor agents such as mitomycin C, bleomycin, peplomycin, daunorubicin, aclarubicin, doxorubicin, pir
  • Antitumor antibodies and molecular targeted drugs include trastuzumab, rituximab, cetuximab, nimotuzumab, denosumab, bevacizumab, infliximab, imatinib mesylate, gefitinib, erlotinib, sunitinib, lapatinib, sorafenib, etc.
  • 2,6-dichloropurine (21 g, 113 mmol), (tetrahydrofuran-3-yl) methanol (11.5 g, 113 mmol) was dissolved in tetrahydrofuran (250 ml), triphenylphosphine (33 g, 125 mmol), diisopropylazodicarboxyl.
  • a rate (24.5 ml, 125 mmol) / tetrahydrofuran (50 ml) solution was added dropwise under ice cooling, and the mixture was stirred at room temperature for 2 hours.
  • 2,2,6,6-tetramethylpiperidine (26.5 ml, 157 mmol) was dissolved in tetrahydrofuran (200 ml), and n-butyllithium (2.6 M hexane solution, 54 ml) was added dropwise at room temperature under an argon atmosphere. It stirred for 15 minutes after completion
  • Step 2 2- ⁇ 4- [2- (2-Aminopyrimidin-5-yl) -6-morpholin-4-yl-9- (2,2,2-trifluoroethyl) -9H-purine-8 -Yl] piperazin-1-yl ⁇ -N, N-dimethyl-2-oxoacetamide tert-butyl ⁇ 5- [8- ⁇ 4-[(dimethylamino) (oxo) acetyl] piperazin-1-yl ⁇ -6-morpholin-4-yl-9- (2,2,2-trifluoroethyl) Trifluoroacetic acid (5 ml) was added to -9H-purin-2-yl] pyrimidin-2-yl ⁇ carbamate (148 mg, 0.22 mmol) and stirred for 30 minutes.
  • Step 3 7-Benzyl-4,7-diazaspiro [2.5] octane Borane-tetrahydrofuran complex (0.93M tetrahydrofuran solution) (375 ml, 0.35 mol) was added to a tetrahydrofuran (200 ml) solution of the compound obtained in Step 2 above (20 g, 86.8 mmol) under ice-cooling, followed by heating for 19 hours.
  • Step 2 2-Chloro-6-[(3S) -3-methylmorpholin-4-yl] -9- (2,2,2-trifluoroethyl) -9H-purine
  • potassium carbonate 86 mg, 0.62 mmol
  • N, N-dimethylformamide 5 ml
  • 2,2,2-trifluoroethyl trifluoromethylsulfonate 83 ⁇ l, 0.57 mmol
  • Step 4 Di-tert-butyl (5- ⁇ 6-[(3S) -3-methylmorpholin-4-yl] -9- (2,2,2-trifluoroethyl) -9H-purine-2- Yl ⁇ pyrimidin-2-yl) imide dicarbonate 5- ⁇ 6-[(3S) -3-Methylmorpholin-4-yl] -9- (2,2,2-trifluoroethyl) -9H-purin-2-yl ⁇ pyrimidin-2-amine (423 mg, 1.07 mmol), 4-dimethylaminopyridine (26 mg, 0.21 mmol) in N, N-dimethylformamide (4 ml) in di-tert-butyl dicarbonate (1.17 g, 5.36 mmol) in N, N— Dimethylformamide (4 ml) solution was added.
  • Step 7 5- ⁇ 6-[(3S) -3-Methylmorpholin-4-yl] -8- [4- (methylsulfonyl) piperazin-1-yl] -9- (2,2,2-tri Fluoroethyl) -9H-purin-2-yl ⁇ pyrimidin-2-amine tert-butyl (5- ⁇ 6-[(3S) -3-methylmorpholin-4-yl] -8- [4- (methylsulfonyl) piperazin-1-yl] -9- (2,2,2-tri Fluoroethyl) -9H-purin-2-yl ⁇ pyrimidin-2-yl) carbamate (199 mg, 0.30 mmol) and trifluoroacetic acid (1 ml) in methylene chloride (5 ml) were stirred at room temperature for 1.5 hours.
  • Step 2 Di-tert-butyl (5- ⁇ 9- (cyclopropylmethyl) -6-[(3S) -3-methylmorpholin-4-yl] -9H-purin-2-yl ⁇ -4-methyl Pyrimidin-2-yl) imide dicarbonate 2-Chloro-9- (cyclopropylmethyl) -6-[(3S) -3-methylmorpholin-4-yl] -9H-purine (248 mg, 0.81 mmol), di-tert-butyl [4-methyl- 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrimidin-2-yl] imide dicarbonate (178 mg, 0.81 mmol), tetrakistriphenylphosphine palladium (93 mg , 0.08 mmol), a suspension of sodium carbonate (256 mg, 2.42 mmol) in 1,4-dioxane (5 ml) / water (1 ml)
  • Step 4 5- ⁇ 8- (4-acetylpiperazin-1-yl) -9- (cyclopropylmethyl) -6-[(3S) -3-methylmorpholin-4-yl] -9H-purine-2 -Yl ⁇ -4-methylpiperazin-2-amine
  • Di-tert-butyl (5- ⁇ 8-chloro-9- (cyclopropylmethyl) -6-[(3S) -3-methylmorpholin-4-yl] -9H-purin-2-yl ⁇ -4-methyl
  • a solution of pyrimidin-2-yl) imide dicarbonate (344 mg, 0.56 mmol) and trifluoroacetic acid (1 ml) in methylene chloride (3 ml) was stirred at room temperature for 2 hours and concentrated under reduced pressure.
  • reaction mixture was returned to room temperature.
  • a solution of the residue, acetic anhydride (56 ⁇ l, 0.59 mmol) and triethylamine (91 ⁇ l, 0.65 mmol) in methylene chloride (5 ml) was stirred at room temperature for 16 hours and concentrated under reduced pressure.
  • Ethyl acetate was added to the residue, and the mixture was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine.
  • the organic layer was dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure.
  • Formulation Example 1 Powder A powder can be obtained by mixing 5 g of the compound of an Example, 895 g of lactose, and 100 g of corn starch with a blender.
  • Formulation Example 2 Granule After mixing 5 g of the compound of Example, 895 g of lactose and 100 g of low-substituted hydroxypropylcellulose, 300 g of 10% hydroxypropylcellulose aqueous solution is added and kneaded. When this is granulated using an extrusion granulator and dried, granules can be obtained.
  • P Measured value of well containing PI3K ⁇ and test compound
  • an optimal curve was calculated with GraphPad Prism 4, and the concentration showing 50% inhibition was taken as the IC50 value of PI3K ⁇ inhibitory activity. Calculated.
  • Ratio 10000 ⁇ 665 nm fluorescence value / 620 nm fluorescence value (1)
  • the mTOR enzyme inhibitory activity (%) was calculated by the following formula (2).
  • Test Example 3 In Vitro Test of Test Compound: Cell Growth Inhibition Test The cell growth inhibition test was performed by treating a cultured cancer cell line with a test compound for a certain period of time and then treating MTT (3- (4,5-dimethylthiazol-2-yl). ) -2,5-diphenyltetrazole bromide) method was performed by measuring the number of viable cells.
  • MTT 3- (4,5-dimethylthiazol-2-yl).
  • MTT -2,5-diphenyltetrazole bromide
  • Human endometrial cancer cell line AN3CA, human ovarian cancer cell line IGROV1, and human colon cancer cell line HT29 were seeded at 5000, 1000, and 5000 cells per well of a 96-well plate, respectively.
  • a test compound having a predetermined concentration was added, and the culture at 37 ° C. and 5% CO 2 was continued for 3 days.
  • an MTT reaction solution was added and reacted for 4 hours to perform a formazan formation reaction with dehydrogenase held by living cells.
  • the culture solution was removed, DMSO was added to solubilize formazan, and the amount of formazan produced was measured by measuring the absorbance at 540 nm with a microplate reader.
  • the compounds of Examples 3, 8, 57, 60-65, 68-71, 75-77, 79-86, 90, 92-93, 96, 98, 100-116, 119, 130-134 are dosed 10 mg / kg.
  • S-6 phosphorylation after 6 hours was inhibited by 90% or more.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
PCT/JP2009/067738 2008-10-14 2009-10-13 モルホリノプリン誘導体 Ceased WO2010044401A1 (ja)

Priority Applications (14)

Application Number Priority Date Filing Date Title
RU2011119525/04A RU2490269C2 (ru) 2008-10-14 2009-10-13 ПРОИЗВОДНЫЕ МОРФОЛИНОПУРИНА, ОБЛАДАЮЩИЕ PI3K И/ИЛИ mTOR ИНГИБИРУЮЩЕЙ АКТИВНОСТЬЮ
ES09820579.2T ES2452541T3 (es) 2008-10-14 2009-10-13 Derivado de morfolinopurina
BRPI0920199A BRPI0920199A2 (pt) 2008-10-14 2009-10-13 composto ou um sal do mesmo, metanossulfonato do composto, sulfato do composto, composicao farm,aceutica, inibidores de fostatidilisitol 3-quinase, e do alvo mamifero da rapamicina, e, uso de um composto
DK09820579.2T DK2336132T3 (da) 2008-10-14 2009-10-13 Morpholinpurinderivat
AU2009304789A AU2009304789B2 (en) 2008-10-14 2009-10-13 Morpholinopurine derivatives
NZ592761A NZ592761A (en) 2008-10-14 2009-10-13 6-Morpholino-purine derivatives
MX2011003490A MX2011003490A (es) 2008-10-14 2009-10-13 Derivados de morfolinopurina.
EP09820579.2A EP2336132B1 (en) 2008-10-14 2009-10-13 Morpholinopurine derivative
CA2740471A CA2740471C (en) 2008-10-14 2009-10-13 Morpholinopurine derivatives
PL09820579T PL2336132T3 (pl) 2008-10-14 2009-10-13 Pochodne morfolinopuryny
HK11112477.4A HK1158189B (en) 2008-10-14 2009-10-13 Morpholinopurine derivative
CN200980151585.4A CN102245607B (zh) 2008-10-14 2009-10-13 吗啉代嘌呤衍生物
ZA2011/02449A ZA201102449B (en) 2008-10-14 2011-04-01 Morpholinopurine derivatives
IL212278A IL212278A (en) 2008-10-14 2011-04-12 Phosphatidylinositol suppressants 3-kinase (p13k) and mammalian rapamycin (mtor) suppressor derivatives morpholinophorin, preparations containing them and their uses

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP2008-264797 2008-10-14
JP2008264797 2008-10-14
JP2009121690 2009-05-20
JP2009-121690 2009-05-20

Publications (1)

Publication Number Publication Date
WO2010044401A1 true WO2010044401A1 (ja) 2010-04-22

Family

ID=42106564

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2009/067738 Ceased WO2010044401A1 (ja) 2008-10-14 2009-10-13 モルホリノプリン誘導体

Country Status (21)

Country Link
US (2) US8097622B2 (https=)
EP (1) EP2336132B1 (https=)
JP (1) JP5090423B2 (https=)
KR (1) KR101614976B1 (https=)
CN (1) CN102245607B (https=)
AU (1) AU2009304789B2 (https=)
BR (1) BRPI0920199A2 (https=)
CA (1) CA2740471C (https=)
CO (1) CO6362009A2 (https=)
DK (1) DK2336132T3 (https=)
ES (1) ES2452541T3 (https=)
IL (1) IL212278A (https=)
MX (1) MX2011003490A (https=)
MY (1) MY156456A (https=)
NZ (1) NZ592761A (https=)
PL (1) PL2336132T3 (https=)
PT (1) PT2336132E (https=)
RU (1) RU2490269C2 (https=)
TW (1) TWI378933B (https=)
WO (1) WO2010044401A1 (https=)
ZA (1) ZA201102449B (https=)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014185368A1 (ja) * 2013-05-13 2014-11-20 第一三共株式会社 ５－｛８－［（３ｒ）－４－アセチル－３－メチルピペラジン－１－イル］－６－モルホリン－４－イル－９－（２，２，２－トリフルオロエチル）－９ｈ－プリン－２－イル｝ピリミジン－２－アミン、およびその薬理上許容される塩の新規な結晶、およびその製造方法
WO2014185367A1 (ja) * 2013-05-13 2014-11-20 第一三共株式会社 モルホリノプリン誘導体の製造方法
WO2016157074A1 (en) 2015-03-30 2016-10-06 Daiichi Sankyo Company, Limited 6-morpholinyl-2-pyrazolyl-9h-purine derivatives and their use as pi3k inhibitors
WO2020111234A1 (ja) 2018-11-29 2020-06-04 第一三共株式会社 組み合わせ医薬として用いられるｅｚｈ１／２二重阻害剤を含有する医薬組成物
US11208442B2 (en) 2016-12-02 2021-12-28 Daiichi Sankyo Company, Limited Endo-beta-N-acetylglucosaminidase
WO2022197892A1 (en) * 2021-03-17 2022-09-22 Tango Therapeutics, Inc. Purine derivatives as anticancer agents

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2721851A1 (en) * 2008-05-30 2009-12-03 Genentech, Inc. Purine pi3k inhibitor compounds and methods of use
TWI378933B (en) * 2008-10-14 2012-12-11 Daiichi Sankyo Co Ltd Morpholinopurine derivatives
JP5579864B2 (ja) * 2009-11-12 2014-08-27 エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト Ｎ−９−置換プリン化合物、組成物及び使用の方法
CN102260263A (zh) * 2010-05-26 2011-11-30 四川大学 一类二苯胺基嘌呤衍生物及制备方法和医药用途
ES2536780T3 (es) 2010-07-14 2015-05-28 F. Hoffmann-La Roche Ag Compuestos de purina selectivos para I3 p110 delta, y métodos de uso
TW201500358A (zh) 2010-12-16 2015-01-01 赫夫門羅氏藥廠股份有限公司 三環ｐｉ３ｋ抑制劑化合物及其使用方法
PT2771342T (pt) 2011-10-28 2016-08-17 Novartis Ag Derivados de purina e o seu uso no tratamento de doença
CN103012284A (zh) * 2012-12-26 2013-04-03 无锡捷化医药科技有限公司 一种2-氨基-5-溴嘧啶类化合物的制备方法
CN112472699A (zh) 2013-07-26 2021-03-12 种族肿瘤学公司 改善比生群及衍生物的治疗益处的组合方法
MX364558B (es) * 2013-10-04 2019-04-29 Univ Basel INHIBIDORES DE PI3K Y mTOR CONFORMACIONALMENTE RESTRINGIDOS.
US10765681B2 (en) 2016-02-05 2020-09-08 Academia Sinica Purine compounds possessing anticancer activity
WO2017156350A1 (en) 2016-03-09 2017-09-14 K-Gen, Inc. Methods of cancer treatment
EP3360865A1 (en) 2017-02-13 2018-08-15 F.I.S.- Fabbrica Italiana Sintetici S.p.A. Process for the preparation of cyclopropyldiketopiperazines, and of a key intermediate of ds-5272
CN113368114B (zh) * 2020-03-10 2022-04-22 四川大学 一种吗啉嘧啶类化合物的抗肿瘤应用

Citations (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB864145A (en) * 1959-06-02 1961-03-29 Thomae Gmbh Dr K Novel purines and a process for their manufacture
JP2005120102A (ja) 2000-04-27 2005-05-12 Yamanouchi Pharmaceut Co Ltd 縮合ヘテロアリール誘導体
WO2006122806A2 (en) 2005-05-20 2006-11-23 Novartis Ag 1,3-dihydro-imidazo [4,5-c] quinolin-2-ones as lipid kinase inhibitors
GB2431156A (en) 2005-10-11 2007-04-18 Piramed Ltd 1-cyclyl-3-substituted- -benzenes and -azines as inhibitors of phosphatidylinositol 3-kinase
WO2007044698A1 (en) 2005-10-07 2007-04-19 Exelixis, Inc. PYRIDOPYRIMIDINONE INHIBITORS OF PI3Kα
WO2007044813A1 (en) 2005-10-07 2007-04-19 Exelixis, Inc. PYRIDOPYRIMIDINONE INHIBITORS OF PI3Kα
WO2007084786A1 (en) 2006-01-20 2007-07-26 Novartis Ag Pyrimidine derivatives used as pi-3 kinase inhibitors
WO2007122410A1 (en) 2006-04-26 2007-11-01 F.Hoffmann-La Roche Ag Pyrimidine derivatives as pi3k inhibitors
WO2007127183A1 (en) 2006-04-26 2007-11-08 Genentech, Inc. Phosphoinositide 3-kinase inhibitor compounds and pharmaceutical compositions containing them
WO2007129161A2 (en) 2006-04-26 2007-11-15 F. Hoffmann-La Roche Ag Thieno [3, 2-d] pyrimidine derivative useful as pi3k inhibitor
JP2007534687A (ja) * 2004-04-23 2007-11-29 エグゼリクシス， インコーポレイテッド キナーゼ調節因子および使用方法
WO2008023161A1 (en) 2006-08-23 2008-02-28 Kudos Pharmaceuticals Limited 2-methylmorpholine pyrido-, pyrazo- and pyrimido-pyrimidine derivatives as mtor inhibitors
WO2008032089A1 (en) 2006-09-14 2008-03-20 Astrazeneca Ab 4-benzimidaz0lyl-2-m0rph0lin0-6-piperidin-4-ylpyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders
WO2008032091A1 (en) 2006-09-14 2008-03-20 Astrazeneca Ab 4-benzimidaz0lyl-6-m0rph0lin0-2-piperidin-4-ylpyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders
WO2008032033A1 (en) 2006-09-14 2008-03-20 Astrazeneca Ab 4-benzimidazolyl-2-morpholino-6-piperazinylpyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders
WO2008032072A1 (en) 2006-09-14 2008-03-20 Astrazeneca Ab 2-benzimidaz0lyl-6-m0rph0lin0-4-piperidin-4-ylpyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders
WO2008032028A1 (en) 2006-09-14 2008-03-20 Astrazeneca Ab 2 -benzimidazolyl- 6 -morpholino-4- (azetidine, pyrrolidine, piperidine or azepine) pyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders
WO2008032086A1 (en) 2006-09-14 2008-03-20 Astrazeneca Ab 2-benzimidazolyl-6-morpholino-4-phenylpyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders
WO2008032036A1 (en) 2006-09-14 2008-03-20 Astrazeneca Ab 6-benzimidaz0lyl-2-m0rph0lin0-4- (azetidine, pyrrolidine, piperidine or azepine) pyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders
WO2008032060A1 (en) 2006-09-14 2008-03-20 Astrazeneca Ab 4-benzimidaz0lyl-6-m0rph0lin0-2-piperazinylpyrimidine derivatives as p13k and mtor inhibitors for the treatment of proliferative disorders
WO2008051493A2 (en) 2006-10-19 2008-05-02 Signal Pharmaceuticals, Llc Heteroaryl compounds, compositions thereof, and their use as protein kinase inhibitors
WO2008070740A1 (en) 2006-12-07 2008-06-12 F.Hoffmann-La Roche Ag Phosphoinositide 3-kinase inhibitor compounds and methods of use
WO2008098058A1 (en) 2007-02-06 2008-08-14 Novartis Ag Pi 3-kinase inhibitors and methods of their use
US20080233127A1 (en) 2007-03-21 2008-09-25 Wyeth Imidazolopyrimidine analogs and their use as pi3 kinase and mtor inhibitors
WO2009045175A1 (en) 2007-10-05 2009-04-09 S*Bio Pte Ltd Pyrimidine substituted purine derivatives
WO2009045174A1 (en) 2007-10-05 2009-04-09 S*Bio Pte Ltd 2-morpholinylpurines as inhibitors of pi3k
WO2009053716A1 (en) 2007-10-26 2009-04-30 F.Hoffmann-La Roche Ag Purine derivatives useful as pi3 kinase inhibitors

Family Cites Families (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100774855B1 (ko) 2000-04-27 2007-11-08 아스텔라스세이야쿠 가부시키가이샤 축합 헤테로아릴 유도체
US6608053B2 (en) * 2000-04-27 2003-08-19 Yamanouchi Pharmaceutical Co., Ltd. Fused heteroaryl derivatives
DE60217322T2 (de) * 2001-04-27 2007-10-04 Zenyaku Kogyo K.K. Heterocyclische verbindung und antitumormittel, das diese als wirkstoff enthält
JP4768265B2 (ja) 2002-10-15 2011-09-07 シンタ ファーマシューティカルズ コーポレーション 新規化合物
CA2503451C (en) * 2002-10-25 2011-07-12 Zenyaku Kogyo Kabushiki Kaisha Heterocyclic compounds and antitumor agent comprising the same as effective component
WO2004043913A2 (en) 2002-11-08 2004-05-27 Trimeris, Inc. Hetero-substituted benzimidazole compounds and antiviral uses thereof
EA013811B1 (ru) 2002-11-21 2010-08-30 Новартис Вэксинес Энд Дайэгностикс, Инк. 2,4,6-тризамещённые пиримидины, являющиеся ингибиторами фосфотидилинозитол(pi)-3-киназы, и их применение при лечении рака
GB0420719D0 (en) 2004-09-17 2004-10-20 Addex Pharmaceuticals Sa Novel allosteric modulators
GB0423653D0 (en) 2004-10-25 2004-11-24 Piramed Ltd Pharmaceutical compounds
WO2006128129A2 (en) 2005-05-26 2006-11-30 Synta Pharmaceuticals Corp. Method for treating cancer
GB0520657D0 (en) 2005-10-11 2005-11-16 Ludwig Inst Cancer Res Pharmaceutical compounds
GB0525081D0 (en) 2005-12-09 2006-01-18 Astrazeneca Ab Pyrimidine derivatives
EP1979325A1 (en) 2006-01-11 2008-10-15 AstraZeneca AB Morpholino pyrimidine derivatives and their use in therapy
TWI498332B (zh) 2006-04-26 2015-09-01 Hoffmann La Roche 作為pi3k抑制劑之嘧啶衍生物及相關製備方法、醫藥組合物、用途、套組及產物
GB0611152D0 (en) 2006-06-06 2006-07-19 Ucb Sa Therapeutic agents
EP2050749B1 (en) 2006-08-08 2017-11-22 Chugai Seiyaku Kabushiki Kaisha Pyrimidine derivative as pi3k inhibitor and use thereof
EP2057129A1 (en) 2006-08-24 2009-05-13 AstraZeneca AB Morpholino pyrimidine derivatives useful in the treatment of proliferative disorders
AU2007287428B2 (en) 2006-08-24 2011-08-11 Astrazeneca Ab Morpholino pyrimidine derivatives useful in the treatment of proliferative disorders
GB0620818D0 (en) 2006-10-19 2006-11-29 Ucb Sa Therapeutic agents
JP2010510245A (ja) 2006-11-21 2010-04-02 スミスクライン ビーチャム コーポレーション 抗ウイルス化合物
RU2470936C2 (ru) 2006-12-07 2012-12-27 Дженентек, Инк. Соединения-ингибиторы фосфоинозитид 3-киназы и способы применения
US20080234262A1 (en) 2007-03-21 2008-09-25 Wyeth Pyrazolopyrimidine analogs and their use as mtor kinase and pi3 kinase inhibitors
EP2146981A1 (en) 2007-04-12 2010-01-27 F. Hoffmann-Roche AG Pharmaceutical compounds
JP2010523639A (ja) 2007-04-12 2010-07-15 エフ．ホフマン−ラ ロシュ アーゲー 医薬化合物
GB0707087D0 (en) 2007-04-12 2007-05-23 Piramed Ltd Pharmaceutical compounds
US7893060B2 (en) 2007-06-12 2011-02-22 F. Hoffmann-La Roche Ag Thiazolopyrimidines and their use as inhibitors of phosphatidylinositol-3 kinase
WO2008152394A1 (en) 2007-06-12 2008-12-18 F.Hoffmann-La Roche Ag Pharmaceutical compounds
WO2008152387A1 (en) 2007-06-12 2008-12-18 F.Hoffmann-La Roche Ag Quinazoline derivatives as pi3 kinase inhibitors
AU2008273889B2 (en) 2007-07-09 2012-03-08 Astrazeneca Ab Trisubstituted pyrimidine derivatives for the treatment of proliferative diseases
TW200908984A (en) 2007-08-07 2009-03-01 Piramal Life Sciences Ltd Pyridyl derivatives, their preparation and use
EP2205242B1 (en) 2007-09-12 2015-04-15 Genentech, Inc. Combinations of phosphoinositide 3-kinase inhibitor compounds and chemotherapeutic agents, and methods of use
CA2704711C (en) 2007-09-24 2016-07-05 Genentech, Inc. Thiazolopyrimidine p13k inhibitor compounds and methods of use
JP5547637B2 (ja) 2007-10-05 2014-07-16 インデックス・ファーマシューティカルズ・アクチエボラーグ 浮腫を治療または軽減するための新規な化合物およびその使用方法
EA201000484A1 (ru) 2007-10-16 2010-12-30 ВАЙЕТ ЭлЭлСи Тиенопиримидиновые и пиразолопиримидиновые соединения и их применение в качестве ингибиторов киназы mtor и киназы pi3
JP5348725B2 (ja) 2007-10-25 2013-11-20 ジェネンテック， インコーポレイテッド チエノピリミジン化合物の製造方法
GB0721095D0 (en) 2007-10-26 2007-12-05 Piramed Ltd Pharmaceutical compounds
WO2009066084A1 (en) 2007-11-21 2009-05-28 F. Hoffmann-La Roche Ag 2 -morpholinopyrimidines and their use as pi3 kinase inhibitors
US20090149458A1 (en) 2007-11-27 2009-06-11 Wyeth PYRROLO[3,2-d]PYRIMIDINE COMPOUNDS AND THEIR USE AS PI3 KINASE AND mTOR KINASE INHIBITORS
WO2009071895A1 (en) 2007-12-04 2009-06-11 Ucb Pharma S.A. Fused thiazole and thiophene derivatives as kinase inhibitors
WO2009071890A1 (en) 2007-12-04 2009-06-11 Ucb Pharma S.A. Tricyclic kinase inhibitors
GB0723747D0 (en) 2007-12-04 2008-12-31 Ucb Pharma Sa Therapeutic agents
GB0723748D0 (en) 2007-12-04 2008-01-16 Ucb Pharma Sa Therapeutic agents
AU2008343813B2 (en) 2007-12-19 2012-04-12 Amgen Inc. Inhibitors of PI3 kinase
CA2712267A1 (en) 2008-01-15 2009-07-23 Wyeth Llc 3h-[1,2,3]triazolo[4,5-d]pyrimidine compounds, their use as mtor kinase and pi3 kinase inhibitors, and their syntheses
WO2009093981A1 (en) 2008-01-23 2009-07-30 S Bio Pte Ltd Triazine compounds as kinase inhibitors
WO2009094560A2 (en) 2008-01-24 2009-07-30 Semafore Pharmaceuticals, Inc. Thienopyranones as kinase inhibitors
RU2010133715A (ru) 2008-01-25 2012-02-27 Астразенека Аб (Se) ЭНАНТИОМЕРНО ЧИСТАЯ (-)2-[1-(7-МЕТИЛ-2-(МОРФОЛИН-4-ИЛ)-4-ОКСО-4Н-ПИРИДО[1,2-a]ПИРИМИДИН-9-ИЛ)БЕНЗОЙНАЯ КИСЛОТА, ЕЕ ПРИМЕНЕНИЕ В ФАРМАКОТЕРАПИИ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СОДЕРЖАЩАЯ ЕЕ
US9029411B2 (en) 2008-01-25 2015-05-12 Millennium Pharmaceuticals, Inc. Thiophenes and uses thereof
CL2009000241A1 (es) 2008-02-07 2010-09-03 Chugai Pharmaceutical Co Ltd Compuestos derivados de 5-(2-morfolin-4-il-7h-pirrolo[2,3-d]pirimidin-4-il)pirimidin-2-ilamina; proceso de preparacion; composicion farmaceutica; y uso de los compuestos para tratar o prevenir una enfermedad proliferativa tal como el cancer.
TWI378933B (en) * 2008-10-14 2012-12-11 Daiichi Sankyo Co Ltd Morpholinopurine derivatives

Patent Citations (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB864145A (en) * 1959-06-02 1961-03-29 Thomae Gmbh Dr K Novel purines and a process for their manufacture
JP2005120102A (ja) 2000-04-27 2005-05-12 Yamanouchi Pharmaceut Co Ltd 縮合ヘテロアリール誘導体
JP2007534687A (ja) * 2004-04-23 2007-11-29 エグゼリクシス， インコーポレイテッド キナーゼ調節因子および使用方法
WO2006122806A2 (en) 2005-05-20 2006-11-23 Novartis Ag 1,3-dihydro-imidazo [4,5-c] quinolin-2-ones as lipid kinase inhibitors
WO2007044698A1 (en) 2005-10-07 2007-04-19 Exelixis, Inc. PYRIDOPYRIMIDINONE INHIBITORS OF PI3Kα
WO2007044813A1 (en) 2005-10-07 2007-04-19 Exelixis, Inc. PYRIDOPYRIMIDINONE INHIBITORS OF PI3Kα
GB2431156A (en) 2005-10-11 2007-04-18 Piramed Ltd 1-cyclyl-3-substituted- -benzenes and -azines as inhibitors of phosphatidylinositol 3-kinase
WO2007084786A1 (en) 2006-01-20 2007-07-26 Novartis Ag Pyrimidine derivatives used as pi-3 kinase inhibitors
WO2007122410A1 (en) 2006-04-26 2007-11-01 F.Hoffmann-La Roche Ag Pyrimidine derivatives as pi3k inhibitors
WO2007127183A1 (en) 2006-04-26 2007-11-08 Genentech, Inc. Phosphoinositide 3-kinase inhibitor compounds and pharmaceutical compositions containing them
WO2007129161A2 (en) 2006-04-26 2007-11-15 F. Hoffmann-La Roche Ag Thieno [3, 2-d] pyrimidine derivative useful as pi3k inhibitor
WO2008023161A1 (en) 2006-08-23 2008-02-28 Kudos Pharmaceuticals Limited 2-methylmorpholine pyrido-, pyrazo- and pyrimido-pyrimidine derivatives as mtor inhibitors
WO2008032033A1 (en) 2006-09-14 2008-03-20 Astrazeneca Ab 4-benzimidazolyl-2-morpholino-6-piperazinylpyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders
WO2008032060A1 (en) 2006-09-14 2008-03-20 Astrazeneca Ab 4-benzimidaz0lyl-6-m0rph0lin0-2-piperazinylpyrimidine derivatives as p13k and mtor inhibitors for the treatment of proliferative disorders
WO2008032089A1 (en) 2006-09-14 2008-03-20 Astrazeneca Ab 4-benzimidaz0lyl-2-m0rph0lin0-6-piperidin-4-ylpyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders
WO2008032072A1 (en) 2006-09-14 2008-03-20 Astrazeneca Ab 2-benzimidaz0lyl-6-m0rph0lin0-4-piperidin-4-ylpyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders
WO2008032028A1 (en) 2006-09-14 2008-03-20 Astrazeneca Ab 2 -benzimidazolyl- 6 -morpholino-4- (azetidine, pyrrolidine, piperidine or azepine) pyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders
WO2008032086A1 (en) 2006-09-14 2008-03-20 Astrazeneca Ab 2-benzimidazolyl-6-morpholino-4-phenylpyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders
WO2008032036A1 (en) 2006-09-14 2008-03-20 Astrazeneca Ab 6-benzimidaz0lyl-2-m0rph0lin0-4- (azetidine, pyrrolidine, piperidine or azepine) pyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders
WO2008032091A1 (en) 2006-09-14 2008-03-20 Astrazeneca Ab 4-benzimidaz0lyl-6-m0rph0lin0-2-piperidin-4-ylpyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders
WO2008051493A2 (en) 2006-10-19 2008-05-02 Signal Pharmaceuticals, Llc Heteroaryl compounds, compositions thereof, and their use as protein kinase inhibitors
WO2008070740A1 (en) 2006-12-07 2008-06-12 F.Hoffmann-La Roche Ag Phosphoinositide 3-kinase inhibitor compounds and methods of use
WO2008098058A1 (en) 2007-02-06 2008-08-14 Novartis Ag Pi 3-kinase inhibitors and methods of their use
US20080233127A1 (en) 2007-03-21 2008-09-25 Wyeth Imidazolopyrimidine analogs and their use as pi3 kinase and mtor inhibitors
WO2008116129A2 (en) * 2007-03-21 2008-09-25 Wyeth Imidazolopyrimidine analogs and their use as pi3 kinase and mtor inhibitors
WO2009045175A1 (en) 2007-10-05 2009-04-09 S*Bio Pte Ltd Pyrimidine substituted purine derivatives
WO2009045174A1 (en) 2007-10-05 2009-04-09 S*Bio Pte Ltd 2-morpholinylpurines as inhibitors of pi3k
WO2009053716A1 (en) 2007-10-26 2009-04-30 F.Hoffmann-La Roche Ag Purine derivatives useful as pi3 kinase inhibitors

Non-Patent Citations (11)

* Cited by examiner, † Cited by third party
Title
"Bunshi Sekkei", vol. 7, 1990, HIROKAWA PUBLISHING CO, article "Iyakuhin no Kaihatsu", pages: 163 - 198
BRUN, VIRGINIE ET AL., TETRAHEDRON, vol. 58, 2002, pages 7911 - 7924
CANCER CELL, vol. 12, no. 1, 2007, pages 9 - 22
CELL, vol. 125, 2006, pages 733 - 747
J. JACQUES ET AL.: "Enantiomers, Racemates and Resolution", JOHN WILEY AND SONS, INC.
MOL. CANCER THER., vol. 7, no. 7, 2008, pages 1851 - 1863
NATURE REV. CANCER, vol. 5, 2005, pages 921 - 929
NATURE REV. GENET., vol. 7, 2006, pages 606 - 619
NATURE, vol. 441, 2006, pages 366 - 370
See also references of EP2336132A4
T.W. GREENE; P.G.M. WUTS: "Protective Groups in Organic Synthesis", 2006, JOHN WILEY & SONS, INC.

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014185368A1 (ja) * 2013-05-13 2014-11-20 第一三共株式会社 ５－｛８－［（３ｒ）－４－アセチル－３－メチルピペラジン－１－イル］－６－モルホリン－４－イル－９－（２，２，２－トリフルオロエチル）－９ｈ－プリン－２－イル｝ピリミジン－２－アミン、およびその薬理上許容される塩の新規な結晶、およびその製造方法
WO2014185367A1 (ja) * 2013-05-13 2014-11-20 第一三共株式会社 モルホリノプリン誘導体の製造方法
WO2016157074A1 (en) 2015-03-30 2016-10-06 Daiichi Sankyo Company, Limited 6-morpholinyl-2-pyrazolyl-9h-purine derivatives and their use as pi3k inhibitors
US11208442B2 (en) 2016-12-02 2021-12-28 Daiichi Sankyo Company, Limited Endo-beta-N-acetylglucosaminidase
WO2020111234A1 (ja) 2018-11-29 2020-06-04 第一三共株式会社 組み合わせ医薬として用いられるｅｚｈ１／２二重阻害剤を含有する医薬組成物
WO2022197892A1 (en) * 2021-03-17 2022-09-22 Tango Therapeutics, Inc. Purine derivatives as anticancer agents
JP2024511996A (ja) * 2021-03-17 2024-03-18 タンゴ セラピューティクス， インコーポレイテッド 抗がん剤としてのプリン誘導体

Also Published As

Publication number Publication date
AU2009304789B2 (en) 2012-04-05
KR101614976B1 (ko) 2016-04-22
BRPI0920199A2 (pt) 2019-09-24
MY156456A (en) 2016-02-26
CA2740471A1 (en) 2010-04-22
US20100130492A1 (en) 2010-05-27
NZ592761A (en) 2012-05-25
ZA201102449B (en) 2011-12-28
AU2009304789A1 (en) 2010-04-22
HK1158189A1 (en) 2012-07-13
EP2336132B1 (en) 2014-01-01
CN102245607A (zh) 2011-11-16
RU2011119525A (ru) 2012-11-27
TWI378933B (en) 2012-12-11
EP2336132A1 (en) 2011-06-22
US8309546B2 (en) 2012-11-13
CA2740471C (en) 2013-09-17
JP5090423B2 (ja) 2012-12-05
IL212278A (en) 2016-07-31
EP2336132A4 (en) 2012-03-21
US8097622B2 (en) 2012-01-17
US20120071476A1 (en) 2012-03-22
PL2336132T3 (pl) 2014-06-30
ES2452541T3 (es) 2014-04-01
CN102245607B (zh) 2014-07-02
CO6362009A2 (es) 2012-01-20
TW201018690A (en) 2010-05-16
RU2490269C2 (ru) 2013-08-20
PT2336132E (pt) 2014-04-02
IL212278A0 (en) 2011-06-30
KR20110067038A (ko) 2011-06-20
DK2336132T3 (da) 2014-04-07
JP2011001339A (ja) 2011-01-06
MX2011003490A (es) 2011-04-21

Similar Documents

Publication Publication Date Title
JP5090423B2 (ja) モルホリノプリン誘導体
EP3529241B1 (en) Piperidine derivatives as inhibitors of ubiquitin specific protease 7
EP4549439A1 (en) Substituted pyrimidine-fused ring inhibitor, method for preparing same, and use thereof
EP3733663B1 (en) 1-[6-[[4-(phenylamino)-6-quinazolinyl]oxy]-3-azabicyclo[3.1.1]hept-3-yl]-2-propen-1-one derivatives and related compounds as irreversible inhibitors of pan-her tyrosine kinase for the treatment of cancer
TW202334138A (zh) 癌症治療方法
EP3919491B1 (en) Akt inhibitor
WO2011146594A2 (en) Mtor selective kinase inhibitors
EP3556758B1 (en) 1,2-dihydro-1,6-naphthyridin-2-one derivatives as cdk4/6 inhibitors
JP2022529152A (ja) Ｃｄ７３阻害剤
EP3546458A1 (en) Pyrido[3, 4-d]pyrimidine derivative and pharmaceutically acceptable salt thereof
JP2011236198A (ja) モルホリノプリン誘導体
JP2025519493A (ja) Ｄｇｋ阻害剤としての三環式トリアゾロ化合物
RS59213B1 (sr) 6-morfolinil-2-pirazolil-9h-purinski derivati i njihova primena kao pi3k inhibitora
IL214541A (en) Tricyclic pyrazolopyrimidine history, preparations containing them and their uses
HK1158189B (en) Morpholinopurine derivative
HK40040029A (en) 1-[6-[[4-(phenylamino)-6-quinazolinyl]oxy]-3-azabicyclo[3.1.1]hept-3-yl]-2-propen-1-one derivatives and related compounds as irreversible inhibitors of pan-her tyrosine kinase for the treatment of cancer
HK40040029B (en) 1-[6-[[4-(phenylamino)-6-quinazolinyl]oxy]-3-azabicyclo[3.1.1]hept-3-yl]-2-propen-1-one derivatives and related compounds as irreversible inhibitors of pan-her tyrosine kinase for the treatment of cancer
HK1164308A (en) Tricyclic pyrazolopyrimidine derivative

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200980151585.4

Country of ref document: CN

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09820579

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2009820579

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: MX/A/2011/003490

Country of ref document: MX

WWE Wipo information: entry into national phase

Ref document number: 698/MUMNP/2011

Country of ref document: IN

WWE Wipo information: entry into national phase

Ref document number: 212278

Country of ref document: IL

Ref document number: 2740471

Country of ref document: CA

ENP Entry into the national phase

Ref document number: 20117008413

Country of ref document: KR

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 12011500746

Country of ref document: PH

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2009304789

Country of ref document: AU

Date of ref document: 20091013

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 11056552

Country of ref document: CO

WWE Wipo information: entry into national phase

Ref document number: 592761

Country of ref document: NZ

WWE Wipo information: entry into national phase

Ref document number: 2011119525

Country of ref document: RU

NENP Non-entry into the national phase

Ref country code: JP

ENP Entry into the national phase

Ref document number: PI0920199

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20110414