ES2555982T3 - Inhibidores de la proteína quinasa C y usos de los mismos - Google Patents
Inhibidores de la proteína quinasa C y usos de los mismos Download PDFInfo
- Publication number
- ES2555982T3 ES2555982T3 ES10732030.1T ES10732030T ES2555982T3 ES 2555982 T3 ES2555982 T3 ES 2555982T3 ES 10732030 T ES10732030 T ES 10732030T ES 2555982 T3 ES2555982 T3 ES 2555982T3
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- alkyl
- hydrogen
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- fluoro
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- 229940123924 Protein kinase C inhibitor Drugs 0.000 title 1
- 239000003881 protein kinase C inhibitor Substances 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 abstract description 26
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 20
- 239000001257 hydrogen Substances 0.000 abstract description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 19
- 229910052736 halogen Inorganic materials 0.000 abstract description 16
- 150000002367 halogens Chemical group 0.000 abstract description 16
- 150000001875 compounds Chemical class 0.000 abstract description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 9
- 125000003545 alkoxy group Chemical group 0.000 abstract description 8
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 8
- 229910052799 carbon Inorganic materials 0.000 abstract description 6
- 229910052717 sulfur Inorganic materials 0.000 abstract description 4
- 125000004953 trihalomethyl group Chemical group 0.000 abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 abstract description 3
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 2
- 150000003839 salts Chemical class 0.000 abstract description 2
- 125000003342 alkenyl group Chemical group 0.000 abstract 1
- 125000000304 alkynyl group Chemical group 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 125000003884 phenylalkyl group Chemical group 0.000 abstract 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 23
- -1 amino, substituted amino Chemical group 0.000 description 10
- 125000000547 substituted alkyl group Chemical group 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 125000000623 heterocyclic group Chemical group 0.000 description 6
- 125000005309 thioalkoxy group Chemical group 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 125000005415 substituted alkoxy group Chemical group 0.000 description 5
- 125000002252 acyl group Chemical group 0.000 description 4
- 125000004442 acylamino group Chemical group 0.000 description 4
- 125000004423 acyloxy group Chemical group 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 125000004181 carboxyalkyl group Chemical group 0.000 description 4
- YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical compound NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 description 4
- 125000003627 8 membered carbocyclic group Chemical group 0.000 description 3
- 125000000266 alpha-aminoacyl group Chemical group 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 150000003573 thiols Chemical class 0.000 description 3
- RHCDVEMQOJHGDM-UHFFFAOYSA-N 2-n-(4,4-dimethyltetrazolo[5,1-c][1,4]benzoxazin-8-yl)-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C3N4N=NN=C4C(C)(C)OC3=CC=2)=NC=C1F RHCDVEMQOJHGDM-UHFFFAOYSA-N 0.000 description 2
- 102000003923 Protein Kinase C Human genes 0.000 description 2
- 108090000315 Protein Kinase C Proteins 0.000 description 2
- 125000000033 alkoxyamino group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- LTUVCCLUHBJWCT-UHFFFAOYSA-N 2-n-(4,4-difluorotetrazolo[5,1-c][1,4]benzoxazin-8-yl)-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C3N4N=NN=C4C(F)(F)OC3=CC=2)=NC=C1F LTUVCCLUHBJWCT-UHFFFAOYSA-N 0.000 description 1
- AJLYVTYOGIMHBE-UHFFFAOYSA-N 2-n-(4,4-dimethyltetrazolo[5,1-c][1,4]benzoxazin-8-yl)-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C3N4N=NN=C4C(C)(C)OC3=CC=2)=NC=C1F AJLYVTYOGIMHBE-UHFFFAOYSA-N 0.000 description 1
- RYRJESRMDKUMCP-UHFFFAOYSA-N 2-n-(4,4-dimethyltetrazolo[5,1-c][1,4]benzoxazin-8-yl)-5-fluoro-4-n-[(1,2,2,5,5-pentamethylpyrrolidin-3-yl)methyl]pyrimidine-2,4-diamine Chemical compound CC1(C)N(C)C(C)(C)CC1CNC1=NC(NC=2C=C3N4N=NN=C4C(C)(C)OC3=CC=2)=NC=C1F RYRJESRMDKUMCP-UHFFFAOYSA-N 0.000 description 1
- VZHILUJEISCFMV-UHFFFAOYSA-N 2-n-(4,4-dimethyltetrazolo[5,1-c][1,4]benzoxazin-8-yl)-5-fluoro-4-n-[(2,2,5,5-tetramethylpyrrolidin-3-yl)methyl]pyrimidine-2,4-diamine Chemical compound CC1(C)NC(C)(C)CC1CNC1=NC(NC=2C=C3N4N=NN=C4C(C)(C)OC3=CC=2)=NC=C1F VZHILUJEISCFMV-UHFFFAOYSA-N 0.000 description 1
- PSLAQLYMLSXBSN-UHFFFAOYSA-N 2-n-(5,5-dimethyltetrazolo[1,5-c][1,3]benzoxazin-9-yl)-5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C=C3C4=NN=NN4C(C)(C)OC3=CC=2)=NC=C1F PSLAQLYMLSXBSN-UHFFFAOYSA-N 0.000 description 1
- UUJVZPSLUNRRFW-UHFFFAOYSA-N 2-n-(5,5-dimethyltetrazolo[1,5-c][1,3]benzoxazin-9-yl)-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C3C4=NN=NN4C(C)(C)OC3=CC=2)=NC=C1F UUJVZPSLUNRRFW-UHFFFAOYSA-N 0.000 description 1
- KIWODJBCHRADND-UHFFFAOYSA-N 3-anilino-4-[1-[3-(1-imidazolyl)propyl]-3-indolyl]pyrrole-2,5-dione Chemical compound O=C1NC(=O)C(C=2C3=CC=CC=C3N(CCCN3C=NC=C3)C=2)=C1NC1=CC=CC=C1 KIWODJBCHRADND-UHFFFAOYSA-N 0.000 description 1
- 125000001845 4 membered carbocyclic group Chemical group 0.000 description 1
- 125000001054 5 membered carbocyclic group Chemical group 0.000 description 1
- HAVXZLJBBINFQG-UHFFFAOYSA-N 5-fluoro-2-n-(4-methyl-8,9-dihydro-4h-tetrazolo[5,1-c][1,4]benzoxazin-8-yl)-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound N12N=NN=C2C(C)OC(C=C2)=C1CC2NC(N=1)=NC=C(F)C=1NC1CC(C)(C)N(C)C(C)(C)C1 HAVXZLJBBINFQG-UHFFFAOYSA-N 0.000 description 1
- PVTQVFPZFZGQIT-UHFFFAOYSA-N 5-fluoro-2-n-(4-methyl-8,9-dihydro-4h-tetrazolo[5,1-c][1,4]benzoxazin-8-yl)-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound N12N=NN=C2C(C)OC(C=C2)=C1CC2NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 PVTQVFPZFZGQIT-UHFFFAOYSA-N 0.000 description 1
- PGRXJRINWODFNC-UHFFFAOYSA-N 5-fluoro-2-n-(4h-pyrrolo[2,1-c][1,4]benzoxazin-8-yl)-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C3N4C=CC=C4COC3=CC=2)=NC=C1F PGRXJRINWODFNC-UHFFFAOYSA-N 0.000 description 1
- YWICUEIGLYHVPU-UHFFFAOYSA-N 5-fluoro-2-n-spiro[8,9-dihydrotetrazolo[5,1-c][1,4]benzoxazine-4,1'-cyclobutane]-8-yl-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC2C=CC3=C(N4N=NN=C4C4(CCC4)O3)C2)=NC=C1F YWICUEIGLYHVPU-UHFFFAOYSA-N 0.000 description 1
- TUYVAPMHYIQKFZ-UHFFFAOYSA-N 5-fluoro-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2-n-spiro[8,9-dihydrotetrazolo[5,1-c][1,4]benzoxazine-4,1'-cyclobutane]-8-ylpyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC2C=CC3=C(N4N=NN=C4C4(CCC4)O3)C2)=NC=C1F TUYVAPMHYIQKFZ-UHFFFAOYSA-N 0.000 description 1
- ORWZEDUXBCRHIG-UHFFFAOYSA-N 5-fluoro-4-n-[(1,2,2,5,5-pentamethylpyrrolidin-3-yl)methyl]-2-n-(4h-tetrazolo[5,1-c][1,4]benzoxazin-8-yl)pyrimidine-2,4-diamine Chemical compound CC1(C)N(C)C(C)(C)CC1CNC1=NC(NC=2C=C3N4N=NN=C4COC3=CC=2)=NC=C1F ORWZEDUXBCRHIG-UHFFFAOYSA-N 0.000 description 1
- LIDVYEPHWJGKMQ-UHFFFAOYSA-N 5-fluoro-4-n-[(2,2,5,5-tetramethylpyrrolidin-3-yl)methyl]-2-n-(4h-tetrazolo[5,1-c][1,4]benzoxazin-8-yl)pyrimidine-2,4-diamine Chemical compound CC1(C)NC(C)(C)CC1CNC1=NC(NC=2C=C3N4N=NN=C4COC3=CC=2)=NC=C1F LIDVYEPHWJGKMQ-UHFFFAOYSA-N 0.000 description 1
- 125000004008 6 membered carbocyclic group Chemical group 0.000 description 1
- 125000001960 7 membered carbocyclic group Chemical group 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 125000000815 N-oxide group Chemical group 0.000 description 1
- 101000971435 Oryctolagus cuniculus Protein kinase C gamma type Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000014458 Protein Kinase C-epsilon Human genes 0.000 description 1
- 108010078137 Protein Kinase C-epsilon Proteins 0.000 description 1
- 102000001892 Protein Kinase C-theta Human genes 0.000 description 1
- 108010015499 Protein Kinase C-theta Proteins 0.000 description 1
- 102100024924 Protein kinase C alpha type Human genes 0.000 description 1
- 101710109947 Protein kinase C alpha type Proteins 0.000 description 1
- 102100024923 Protein kinase C beta type Human genes 0.000 description 1
- 101710094033 Protein kinase C beta type Proteins 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 125000005255 oxyaminoacyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
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- 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
- A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
-
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P5/00—Drugs for disorders of the endocrine system
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- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- 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
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- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- 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
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- 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
- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/14—Ortho-condensed systems
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
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| US14502109P | 2009-01-15 | 2009-01-15 | |
| US145021P | 2009-01-15 | ||
| US14735309P | 2009-01-26 | 2009-01-26 | |
| US147353P | 2009-01-26 | ||
| PCT/US2010/020888 WO2010083207A2 (en) | 2009-01-15 | 2010-01-13 | Protein kinase c inhibitors and uses thereof |
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| ES2555982T3 true ES2555982T3 (es) | 2016-01-12 |
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| ES10732030.1T Active ES2555982T3 (es) | 2009-01-15 | 2010-01-13 | Inhibidores de la proteína quinasa C y usos de los mismos |
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| CA (1) | CA2749195C (enExample) |
| ES (1) | ES2555982T3 (enExample) |
| WO (1) | WO2010083207A2 (enExample) |
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| JP6035238B2 (ja) | 2010-07-21 | 2016-11-30 | ライジェル ファーマシューティカルズ, インコーポレイテッド | プロテインキナーゼc阻害剤およびその使用 |
| AU2012357038B2 (en) | 2011-12-23 | 2016-05-12 | Cellzome Limited | Pyrimidine-2,4-diamine derivatives as kinase inhibitors |
| EP2833889B1 (en) | 2012-04-04 | 2017-11-01 | Rigel Pharmaceuticals, Inc. | Protein kinase c inhibitors and uses thereof |
| EP2928891B1 (en) | 2012-12-04 | 2019-02-20 | Rigel Pharmaceuticals, Inc. | Protein kinase c inhibitors and uses thereof |
| EP2970275B1 (en) | 2013-03-14 | 2018-05-09 | Rigel Pharmaceuticals, Inc. | Protein kinase c inhibitors and uses thereof |
| JP6998657B2 (ja) | 2013-09-18 | 2022-02-04 | エピアクシス セラピューティクス プロプライエタリー リミテッド | 幹細胞調節ii |
| EP3185858A4 (en) | 2014-08-25 | 2017-12-27 | University of Canberra | Compositions for modulating cancer stem cells and uses therefor |
| WO2017038552A1 (ja) * | 2015-09-04 | 2017-03-09 | Dic株式会社 | 安定剤化合物、液晶組成物および表示素子 |
| US10633590B2 (en) | 2015-09-04 | 2020-04-28 | Dic Corporation | Liquid crystal composition and liquid crystal display device including the same |
| CN108913655B (zh) * | 2018-07-16 | 2022-07-15 | 浙江大学 | 基于多能干细胞技术建立“人源性”心肌肥大模型的方法 |
| US11066404B2 (en) | 2018-10-11 | 2021-07-20 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
| WO2020168197A1 (en) | 2019-02-15 | 2020-08-20 | Incyte Corporation | Pyrrolo[2,3-d]pyrimidinone compounds as cdk2 inhibitors |
| WO2020180959A1 (en) | 2019-03-05 | 2020-09-10 | Incyte Corporation | Pyrazolyl pyrimidinylamine compounds as cdk2 inhibitors |
| WO2020205560A1 (en) | 2019-03-29 | 2020-10-08 | Incyte Corporation | Sulfonylamide compounds as cdk2 inhibitors |
| WO2020223469A1 (en) | 2019-05-01 | 2020-11-05 | Incyte Corporation | N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-di hydro-1h-imidazo[4,5-h]quinazolin-8-amine derivatives and related compounds as cyclin-dependent kinase 2 (cdk2) inhibitors for treating cancer |
| US11447494B2 (en) | 2019-05-01 | 2022-09-20 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
| PH12022550361A1 (en) | 2019-08-14 | 2023-02-27 | Incyte Corp | Imidazolyl pyrimidinylamine compounds as cdk2 inhibitors |
| PE20221905A1 (es) | 2019-10-11 | 2022-12-23 | Incyte Corp | Aminas biciclicas como inhibidoras de la cdk2 |
| CA3192563A1 (en) * | 2020-09-14 | 2022-03-17 | Gilles Ouvry | Novel jak inhibitor compounds, method for synthesizing same and use thereof |
| US11981671B2 (en) | 2021-06-21 | 2024-05-14 | Incyte Corporation | Bicyclic pyrazolyl amines as CDK2 inhibitors |
| US11976073B2 (en) | 2021-12-10 | 2024-05-07 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
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| GB9523675D0 (en) * | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| EP1242382B1 (en) * | 1999-12-29 | 2007-02-07 | Wyeth | Tricyclic protein kinase inhibitors |
| TWI329105B (en) * | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| WO2003095448A1 (en) * | 2002-05-06 | 2003-11-20 | Bayer Pharmaceuticals Corporation | Pyridinyl amino pyrimidine derivatives useful for treating hyper-proliferative disorders |
| CN1798748A (zh) * | 2003-04-07 | 2006-07-05 | Gpc生物科技公司 | 依赖细胞周期蛋白的激酶抑制剂及其组合物和相关用途 |
| US7122542B2 (en) * | 2003-07-30 | 2006-10-17 | Rigel Pharmaceuticals, Inc. | Methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds |
| DK1663242T3 (da) * | 2003-08-07 | 2011-08-01 | Rigel Pharmaceuticals Inc | 2,4-Pyrimidindiamin-forbindelser og anvendelse som antiproliferative midler |
| EP1765791A1 (en) * | 2004-07-08 | 2007-03-28 | Boehringer Ingelheim Pharmaceuticals Inc. | Pyrimidine derivatives useful as inhibitors of pkc-theta |
| EP1776826A1 (en) | 2004-08-03 | 2007-04-25 | Nokia Corporation | Mobile communication and/or gaming terminal |
| HRP20100715T1 (hr) * | 2004-10-21 | 2011-02-28 | Vertex Pharmaceuticals Incorporated | Triazoli korisni kao inhibitori protein kinaza |
| US8227455B2 (en) * | 2005-04-18 | 2012-07-24 | Rigel Pharmaceuticals, Inc. | Methods of treating cell proliferative disorders |
| WO2006129100A1 (en) * | 2005-06-03 | 2006-12-07 | Glaxo Group Limited | Novel compounds |
| RU2485106C2 (ru) | 2005-06-08 | 2013-06-20 | Райджел Фамэсьютикэлз, Инк. | Соединения, проявляющие активность в отношении jak-киназы (варианты), способ лечения заболеваний, опосредованных jak-киназой, способ ингибирования активности jak-киназы (варианты), фармацевтическая композиция на основе указанных соединений |
| WO2007002847A2 (en) | 2005-06-28 | 2007-01-04 | Community Power Corporation | Method and apparatus for a self-cleaning filter |
| WO2007028445A1 (en) * | 2005-07-15 | 2007-03-15 | Glaxo Group Limited | 6-indolyl-4-yl-amino-5-halogeno-2-pyrimidinyl-amino derivatives |
| WO2007146981A2 (en) | 2006-06-15 | 2007-12-21 | Boehringer Ingelheim International Gmbh | 2-anilino-4-(heterocyclic)amino-pyrimidines as inhibitors of protein kinase c-alpha |
| DE602007013399D1 (de) | 2006-06-28 | 2011-05-05 | Univ Alberta | Titanium-silicat-materialien, verfahren zu deren herstellung und verfahren zur verwendung der titanium-silicat-materialien für adsorptive flüssigkeitstrennungen |
| WO2008024634A1 (en) * | 2006-08-25 | 2008-02-28 | Smithkline Beecham Corporation | Pyrimdine compounds useful as kinase inhibitors |
| ITVI20070184A1 (it) | 2007-06-27 | 2008-12-28 | Simec Spa | Puleggia per macchine utensili multifilo. |
| CA2693594A1 (en) * | 2007-07-17 | 2009-01-22 | Rigel Pharmaceuticals, Inc. | Cyclic amine substituted pyrimidinediamines as pkc inhibitors |
| US8575165B2 (en) * | 2009-01-14 | 2013-11-05 | Rigel Pharmaceuticals, Inc. | Methods for treating inflammatory disorders using 2,4-pyrimidinediamine compounds |
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2010
- 2010-01-13 CN CN201080005581.8A patent/CN102292333B/zh not_active Expired - Fee Related
- 2010-01-13 CA CA2749195A patent/CA2749195C/en active Active
- 2010-01-13 JP JP2011546310A patent/JP5603881B2/ja not_active Expired - Fee Related
- 2010-01-13 ES ES10732030.1T patent/ES2555982T3/es active Active
- 2010-01-13 EP EP10732030.1A patent/EP2387572B1/en not_active Not-in-force
- 2010-01-13 US US12/687,054 patent/US8394951B2/en not_active Expired - Fee Related
- 2010-01-13 WO PCT/US2010/020888 patent/WO2010083207A2/en not_active Ceased
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2013
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2015
- 2015-06-29 US US14/754,415 patent/US9453028B2/en not_active Expired - Fee Related
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| CA2749195C (en) | 2017-03-07 |
| CN102292333B (zh) | 2015-05-13 |
| EP2387572A2 (en) | 2011-11-23 |
| CA2749195A1 (en) | 2010-07-22 |
| US20150376203A1 (en) | 2015-12-31 |
| EP2387572B1 (en) | 2015-09-16 |
| JP2012515206A (ja) | 2012-07-05 |
| US9453028B2 (en) | 2016-09-27 |
| US9095593B2 (en) | 2015-08-04 |
| CN102292333A (zh) | 2011-12-21 |
| EP2387572A4 (en) | 2012-07-25 |
| US8394951B2 (en) | 2013-03-12 |
| US20100184755A1 (en) | 2010-07-22 |
| US20130143875A1 (en) | 2013-06-06 |
| JP5603881B2 (ja) | 2014-10-08 |
| WO2010083207A3 (en) | 2010-11-04 |
| WO2010083207A2 (en) | 2010-07-22 |
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