EA029473B1 - Применение ингибиторов pi3k для лечения острой и церебральной малярии - Google Patents
Применение ингибиторов pi3k для лечения острой и церебральной малярии Download PDFInfo
- Publication number
- EA029473B1 EA029473B1 EA201491182A EA201491182A EA029473B1 EA 029473 B1 EA029473 B1 EA 029473B1 EA 201491182 A EA201491182 A EA 201491182A EA 201491182 A EA201491182 A EA 201491182A EA 029473 B1 EA029473 B1 EA 029473B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- tetrahydropyrido
- pyrrolidin
- methoxy
- yloxy
- methanone
- Prior art date
Links
- 206010063094 Cerebral malaria Diseases 0.000 title claims description 13
- 230000001154 acute effect Effects 0.000 title claims description 11
- 239000012828 PI3K inhibitor Substances 0.000 title abstract 2
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 title abstract 2
- 239000003112 inhibitor Substances 0.000 claims abstract description 111
- 150000003839 salts Chemical class 0.000 claims abstract description 74
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 59
- 102000001708 Protein Isoforms Human genes 0.000 claims abstract description 56
- 108010029485 Protein Isoforms Proteins 0.000 claims abstract description 56
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 43
- 201000010099 disease Diseases 0.000 claims abstract description 27
- 208000035475 disorder Diseases 0.000 claims abstract description 16
- 230000009454 functional inhibition Effects 0.000 claims abstract description 5
- -1 tetrahydropyridopyrimidine compound Chemical class 0.000 claims description 928
- 238000000034 method Methods 0.000 claims description 349
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 335
- 150000001875 compounds Chemical class 0.000 claims description 179
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 70
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims description 65
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 60
- 125000001424 substituent group Chemical group 0.000 claims description 32
- CXLGNJCMPWUZKM-UHFFFAOYSA-N oxane-4-carbaldehyde Chemical compound O=CC1CCOCC1 CXLGNJCMPWUZKM-UHFFFAOYSA-N 0.000 claims description 31
- 229910052736 halogen Inorganic materials 0.000 claims description 29
- 125000005842 heteroatom Chemical group 0.000 claims description 28
- 125000000623 heterocyclic group Chemical group 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 25
- 125000003282 alkyl amino group Chemical group 0.000 claims description 24
- 150000002367 halogens Chemical group 0.000 claims description 24
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 claims description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 14
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- 230000003647 oxidation Effects 0.000 claims description 14
- 238000007254 oxidation reaction Methods 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 claims description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 12
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 12
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 11
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical group [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 10
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
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- ZXRLWHGLEJGMNO-UHFFFAOYSA-N 1,3-thiazole-5-carbaldehyde Chemical compound O=CC1=CN=CS1 ZXRLWHGLEJGMNO-UHFFFAOYSA-N 0.000 claims description 4
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
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- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 239000010452 phosphate Substances 0.000 claims description 4
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- 239000001294 propane Substances 0.000 claims description 4
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 claims description 4
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 claims description 3
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- 239000012453 solvate Substances 0.000 claims 2
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- VBXBTOGGSZJEEI-UHFFFAOYSA-M sodium;[2-(pyridine-4-carbonyl)hydrazinyl]methanesulfonate;hydrate Chemical compound O.[Na+].[O-]S(=O)(=O)CNNC(=O)C1=CC=NC=C1 VBXBTOGGSZJEEI-UHFFFAOYSA-M 0.000 description 1
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- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
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- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 230000000475 sunscreen effect Effects 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
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- UQJLSMYQBOJUGG-UHFFFAOYSA-N tert-butyl 2,2,2-trifluoroacetate Chemical compound CC(C)(C)OC(=O)C(F)(F)F UQJLSMYQBOJUGG-UHFFFAOYSA-N 0.000 description 1
- UXAWXZDXVOYLII-UHFFFAOYSA-N tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1C2N(C(=O)OC(C)(C)C)CC1NC2 UXAWXZDXVOYLII-UHFFFAOYSA-N 0.000 description 1
- CMIBWIAICVBURI-UHFFFAOYSA-N tert-butyl 3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)C1 CMIBWIAICVBURI-UHFFFAOYSA-N 0.000 description 1
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- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 125000001583 thiepanyl group Chemical group 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 239000012443 tonicity enhancing agent Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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- 238000002604 ultrasonography Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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- 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
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- A61K31/54—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 sulfur as the ring hetero atoms, e.g. sulthiame
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- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/74—Quinazolines; Hydrogenated quinazolines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
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- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Steroid Compounds (AREA)
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| PT2994465T (pt) | 2013-05-10 | 2018-10-25 | Karus Therapeutics Ltd | Novos inibidores de histona desacetilase |
| EP3054953B1 (en) * | 2013-10-10 | 2020-07-01 | Acetylon Pharmaceuticals, Inc. | Hdac inhibitors in combination with pi3k inhibitors, for treating non-hodgkin's lymphoma |
| AU2014361800B2 (en) | 2013-12-13 | 2020-05-07 | Dana-Farber Cancer Institute, Inc. | Methods to treat lymphoplasmacytic lymphoma |
| AU2014361798B2 (en) | 2013-12-13 | 2020-06-11 | Dana-Farber Cancer Institute, Inc. | Methods to treat lymphoplasmacytic lymphoma |
| WO2015162584A1 (en) | 2014-04-24 | 2015-10-29 | Novartis Ag | Crystalline forms of the sulfate salt of n-[5-(3-imidazol-1-yl-4-methanesulfonyl-phenyl)-4-methyl-thiazol-2-yl]-acetamide |
| EP3209648B1 (en) | 2014-10-22 | 2020-03-11 | Dana-Farber Cancer Institute, Inc. | Thiazolyl-containing compounds for treating proliferative diseases |
| GB201419264D0 (en) | 2014-10-29 | 2014-12-10 | Karus Therapeutics Ltd | Compounds |
| GB201419228D0 (en) | 2014-10-29 | 2014-12-10 | Karus Therapeutics Ltd | Compounds |
| CN112074505B (zh) | 2018-03-08 | 2024-04-05 | 因赛特公司 | 作为PI3K-γ抑制剂的氨基吡嗪二醇化合物 |
| US20220106296A1 (en) * | 2018-06-19 | 2022-04-07 | Novartis Ag | Cyanotriazole compounds and uses thereof |
| US11046658B2 (en) | 2018-07-02 | 2021-06-29 | Incyte Corporation | Aminopyrazine derivatives as PI3K-γ inhibitors |
| EP3825303A4 (en) | 2018-07-17 | 2022-07-06 | Nippon Chemiphar Co., Ltd. | T-type calcium channel blocker |
| US20220226299A1 (en) | 2019-03-29 | 2022-07-21 | Nippon Chemiphar Co., Ltd. | Use of t-type calcium channel blocker for treating pruritus |
| JP2025509154A (ja) | 2022-03-08 | 2025-04-11 | エクアシールド メディカル リミテッド | ロボット医薬品調製システムにおける流体移送ステーション |
| CN114957676B (zh) * | 2022-06-22 | 2023-05-16 | 安徽工程大学 | 一种利用反溶剂沉积快速调控水分活度制备美拉德反应产物的方法 |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005086814A2 (en) * | 2004-03-09 | 2005-09-22 | The Uab Research Foundation | Methods and compositions related to regulation of cytokine production by glycogen synthase kinase 3 (gsk-3) |
| WO2008012326A1 (en) * | 2006-07-28 | 2008-01-31 | Novartis Ag | 2,4-substituted quinazolines as lipid kinase inhibitors |
| WO2008157191A2 (en) * | 2007-06-14 | 2008-12-24 | Smithkline Beecham Corporation | Quinazoline derivatives as pi3 kinase inhibitors |
| WO2009058361A1 (en) * | 2007-10-31 | 2009-05-07 | Dynavax Technologies Corp. | Inhibition of type i ifn production |
| WO2010036908A1 (en) * | 2008-09-26 | 2010-04-01 | Eisai R & D Management Co., Ltd. | Use of benzoxazole compounds in the treatment of malaria |
| WO2010120991A1 (en) * | 2009-04-17 | 2010-10-21 | Wyeth Llc | 5, 6, 7, 8-tetrahydropyrido[4,3-d]pyrimidine compounds, their use as mtor, pi3, and hsmg-1 kinase inhibitors, and their syntheses |
| WO2010129816A2 (en) * | 2009-05-07 | 2010-11-11 | Intellikine, Inc. | Heterocyclic compounds and uses thereof |
| WO2012004299A1 (en) * | 2010-07-06 | 2012-01-12 | Novartis Ag | Tetrahydro-pyrido-pyrimidine derivatives |
Family Cites Families (109)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5300645A (en) | 1993-04-14 | 1994-04-05 | Eli Lilly And Company | Tetrahydro-pyrido-indole |
| US5858753A (en) | 1996-11-25 | 1999-01-12 | Icos Corporation | Lipid kinase |
| US5939421A (en) | 1997-07-01 | 1999-08-17 | Signal Pharmaceuticals, Inc. | Quinazoline analogs and related compounds and methods for treating inflammatory conditions |
| US6667300B2 (en) | 2000-04-25 | 2003-12-23 | Icos Corporation | Inhibitors of human phosphatidylinositol 3-kinase delta |
| WO2001085986A2 (en) | 2000-05-10 | 2001-11-15 | Icos Corporation | Phosphatidyl inositol 3-kinase delta binding partner |
| DE10043667A1 (de) | 2000-09-05 | 2002-03-14 | Merck Patent Gmbh | 2-Guanidino-4-aryl-chinazoline |
| BRPI0115193B1 (pt) | 2000-11-07 | 2016-08-09 | Novartis Ag | derivados de indolilmaleimida, processo para preparação dos mesmos, bem como composição farmacêutica que os compreende |
| EP1389617B1 (en) | 2001-04-27 | 2007-01-03 | Zenyaku Kogyo Kabushiki Kaisha | Heterocyclic compound and antitumor agent containing the same as active ingredient |
| AR039209A1 (es) | 2002-04-03 | 2005-02-09 | Novartis Ag | Derivados de indolilmaleimida |
| BR0317099A (pt) | 2002-12-09 | 2005-10-25 | Boardd Of Regents Of The Unive | Método in vitro para inibir a função e/ou proliferação de uma janus tirosina quinase 3, método de teste in vitro para auxiliar na identificação de substâncias que são úteis como imunossupressores terapêuticos, método in vitro para auxiliar na identificação de um novo medicamento imunossupressor, método in vitro para inibir a função e/ou proliferação de uma célula expressando a janus tirosina quinase 3, uso de pelo menos um composto, composto quìmico isolado ou purificado e composição farmacêutica |
| AU2003292436B2 (en) | 2002-12-27 | 2009-07-30 | Msd Italia S.R.L. | Tetrahydro-4H-pyrido[1,2-A]pyrimidines and related compounds useful as HIV integrase inhibitors |
| US20050054614A1 (en) | 2003-08-14 | 2005-03-10 | Diacovo Thomas G. | Methods of inhibiting leukocyte accumulation |
| US20050043239A1 (en) | 2003-08-14 | 2005-02-24 | Jason Douangpanya | Methods of inhibiting immune responses stimulated by an endogenous factor |
| KR101164541B1 (ko) | 2004-01-12 | 2012-07-10 | 와이엠 바이오사이언시즈 오스트레일리아 피티와이 엘티디 | 선택적 키나제 저해제 |
| EP1713807A1 (en) | 2004-01-23 | 2006-10-25 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
| RS55546B1 (sr) | 2004-05-13 | 2017-05-31 | Icos Corp | Hinazolinoni kao inhibitori humane fosfatidilonozitol 3-delta kinaze |
| CA2566436C (en) | 2004-05-13 | 2011-05-10 | Vanderbilt University | Phosphoinositide 3-kinase delta selective inhibitors for inhibiting angiogenesis |
| MXPA06014478A (es) | 2004-06-11 | 2007-03-21 | Japan Tobacco Inc | Derivados de 5-amino-2, 4, 7-trioxo-3, 4, 7, 8-tetrahidro -2h-pirido[2, 3-d]pirimidina y compuestos relacionados para el tratamiento del cancer. |
| GB0423653D0 (en) | 2004-10-25 | 2004-11-24 | Piramed Ltd | Pharmaceutical compounds |
| US20060128710A1 (en) | 2004-12-09 | 2006-06-15 | Chih-Hung Lee | Antagonists to the vanilloid receptor subtype 1 (VR1) and uses thereof |
| WO2006071095A1 (en) | 2004-12-31 | 2006-07-06 | Sk Chemicals Co., Ltd. | Quinazoline derivatives for the treatment and prevention of diabetes and obesity |
| WO2006119504A2 (en) | 2005-05-04 | 2006-11-09 | Renovis, Inc. | Fused heterocyclic compounds, and compositions and uses thereof |
| GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| WO2007023186A1 (en) | 2005-08-26 | 2007-03-01 | Laboratoires Serono S.A. | Pyrazine derivatives and use as pi3k inhibitors |
| GB0520657D0 (en) | 2005-10-11 | 2005-11-16 | Ludwig Inst Cancer Res | Pharmaceutical compounds |
| US20070197509A1 (en) | 2005-12-21 | 2007-08-23 | Painceptor Pharma Corporation | Compositions and methods for modulating gated ion channels |
| GB0612630D0 (en) | 2006-06-26 | 2006-08-02 | Novartis Ag | Organic compounds |
| US8673929B2 (en) | 2006-07-20 | 2014-03-18 | Gilead Sciences, Inc. | 4,6-di- and 2,4,6-trisubstituted quinazoline derivatives and pharmaceutical compositions useful for treating viral infections |
| EP1891958A1 (en) * | 2006-08-03 | 2008-02-27 | Universite Pierre Et Marie Curie (Paris Vi) | Rho/Rock/PI3/Akt kinase inhibitors for the treatment of diseases associated with protozoan parasites. |
| CA2669399A1 (en) | 2006-11-13 | 2008-05-29 | Eli Lilly & Co. | Thienopyrimidinones for treatment of inflammatory disorders and cancers |
| HRP20140147T1 (hr) | 2007-03-23 | 2014-03-28 | Amgen Inc. | 3-supstituirani derivati hinolina ili hinoksalina i njihova uporaba kao inhibitora fosfatidilinozitol 3-kinaze (pi3k) |
| EP2132207A2 (en) | 2007-03-23 | 2009-12-16 | Amgen Inc. | Heterocyclic compounds and their uses |
| PL2137186T3 (pl) | 2007-03-23 | 2016-09-30 | Związki heterocykliczne i ich zastosowania | |
| CA2682162C (en) | 2007-04-02 | 2016-05-10 | Renovis, Inc. | Pyrid-2-yl fused heterocyclic compounds, and compositions and uses thereof |
| GB0707087D0 (en) | 2007-04-12 | 2007-05-23 | Piramed Ltd | Pharmaceutical compounds |
| WO2008125839A2 (en) | 2007-04-12 | 2008-10-23 | Piramed Limited | Pyrimidine derivatives as inhibitors of phosphatidylinositol-3-kinase |
| EP2146981A1 (en) | 2007-04-12 | 2010-01-27 | F. Hoffmann-Roche AG | Pharmaceutical compounds |
| PL2139334T3 (pl) | 2007-04-17 | 2013-11-29 | Evotec Ag | Skondensowane związki heterocykliczne 2-cyjanofenylu i ich kompozycje i zastosowania |
| PE20090717A1 (es) | 2007-05-18 | 2009-07-18 | Smithkline Beecham Corp | Derivados de quinolina como inhibidores de la pi3 quinasa |
| WO2008150827A1 (en) | 2007-05-29 | 2008-12-11 | Smithkline Beecham Corporation | Naphthyridine, derivatives as p13 kinase inhibitors |
| 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 |
| JP5539190B2 (ja) | 2007-06-12 | 2014-07-02 | エフ.ホフマン−ラ ロシュ アーゲー | チアゾロピリミジン類及びホスファチジルイノシトール−3キナーゼのインヒビターとしてのそれらの使用 |
| RU2341527C1 (ru) | 2007-07-17 | 2008-12-20 | Общество С Ограниченной Ответственностью "Исследовательский Институт Химического Разнообразия" | Аннелированные азагетероциклы, включающие пиримидиновый фрагмент, способ их получения и ингибиторы pi3k киназ |
| TW200908984A (en) | 2007-08-07 | 2009-03-01 | Piramal Life Sciences Ltd | Pyridyl derivatives, their preparation and use |
| WO2009036768A2 (en) | 2007-09-19 | 2009-03-26 | H. Lundbeck A/S | Diagnosing potential weight gain in a subject |
| GB2467670B (en) | 2007-10-04 | 2012-08-01 | Intellikine Inc | Chemical entities and therapeutic uses thereof |
| EP2209775A1 (en) | 2007-10-09 | 2010-07-28 | UCB Pharma, S.A. | Heterobicyclic compounds as histamine h4-receptor antagonists |
| GEP20125635B (en) | 2007-11-13 | 2012-09-10 | Icos Corp | Inhibitors of human phosphatidyl-inositol 3-kinase delta |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| DK2240451T3 (da) | 2008-01-04 | 2017-11-20 | Intellikine Llc | Isoquinolinonderivater substitueret med en purin, der er anvendelig som pi3k-inhibitorer |
| US20110053907A1 (en) | 2008-03-27 | 2011-03-03 | Auckland Uniservices Limited | Substituted pyrimidines and triazines and their use in cancer therapy |
| US8436005B2 (en) | 2008-04-03 | 2013-05-07 | Abbott Laboratories | Macrocyclic pyrimidine derivatives |
| EP2280705B1 (en) | 2008-06-05 | 2014-10-08 | Glaxo Group Limited | Novel compounds |
| ES2445199T3 (es) | 2008-06-05 | 2014-02-28 | Glaxo Group Limited | Derivados de benzpirazol como inhibidores de PI3-quinasas |
| JP5502077B2 (ja) | 2008-06-05 | 2014-05-28 | グラクソ グループ リミテッド | 新規な化合物 |
| AU2009260782B2 (en) | 2008-06-19 | 2014-12-11 | Millennium Pharmaceuticals, Inc. | Thiophene or thiazole derivatives and their use as PI3K inhibitors |
| EP2307414A4 (en) | 2008-07-07 | 2011-10-26 | Xcovery Holding Co Llc | SELECTIVE INHIBITORS OF PI3 KINASE ISOFORMS |
| BRPI0915231A2 (pt) | 2008-07-08 | 2018-06-12 | Intellikine Inc | compostos inibidores de quinase e métodos de uso |
| CA2738429C (en) | 2008-09-26 | 2016-10-25 | Intellikine, Inc. | Heterocyclic kinase inhibitors |
| ES2674719T3 (es) | 2008-11-13 | 2018-07-03 | Gilead Calistoga Llc | Terapias para neoplasias hematológicas |
| WO2010059593A1 (en) | 2008-11-18 | 2010-05-27 | Intellikine, Inc. | Methods and compositions for treatment of ophthalmic conditions |
| EP2365810A2 (en) | 2008-12-04 | 2011-09-21 | The U.S.A. As Represented By The Secretary, Department Of Health And Human Services | Phosphatidylinositol-3-kinase p110 delta-targeted drugs in the treatment of cns disorders |
| US8524751B2 (en) | 2009-03-09 | 2013-09-03 | GlaxoSmithKline Intellecutual Property Development | 4-oxadiazol-2-YL-indazoles as inhibitors of P13 kinases |
| EP2411003A4 (en) | 2009-03-24 | 2012-10-17 | Univ Singapore | USE OF ARTEMISININE DERIVATIVES IN THE TREATMENT OF ASTHMA AND CHRONIC OBSTRUCTIVE BRONCHO-PNEUMOPATHY (COPD) |
| CA2756347A1 (en) | 2009-03-24 | 2010-09-30 | Gilead Calistoga Llc | Atropisomers of 2-purinyl-3-tolyl-quinazolinone derivatives and methods of use |
| MX2011011036A (es) | 2009-04-20 | 2012-01-20 | Gilead Calistoga Llc | Metodos de tratamiento para tumores solidos. |
| ES2644724T3 (es) | 2009-04-30 | 2017-11-30 | Glaxo Group Limited | Indazoles sustituidos con oxazol como inhibidores de PI3-cinasas |
| SG175708A1 (en) | 2009-05-27 | 2011-12-29 | Genentech Inc | Bicyclic pyrimidine pi3k inhibitor compounds selective for p110 delta, and methods of use |
| SG182247A1 (en) | 2009-05-27 | 2012-08-30 | Hoffmann La Roche | Bicyclic indole-pyrimidine pi3k inhibitor compounds selective for p110 delta, and methods of use |
| AU2010266064A1 (en) | 2009-06-25 | 2012-01-19 | Amgen Inc. | 4H - pyrido [1, 2 - a] pyrimidin - 4 - one derivatives as PI3 K inhibitors |
| AU2010265971B2 (en) | 2009-06-25 | 2014-08-14 | Amgen Inc. | Heterocyclic compounds and their uses as inhibitors of PI3 K activity |
| EA201270051A1 (ru) | 2009-06-25 | 2012-05-30 | Амген Инк. | Гетероциклические соединения и их применения |
| EA201270013A1 (ru) | 2009-06-25 | 2012-06-29 | Амген Инк. | Гетероциклические соединения и их применение |
| EP2448938B9 (en) | 2009-06-29 | 2015-06-10 | Incyte Corporation | Pyrimidinones as pi3k inhibitors |
| AU2010267815B2 (en) | 2009-07-02 | 2015-07-16 | Sanofi | Novel 1,2,3,4-tetrahydro-pyrimido(1,2-a)pyrimidin-6-one derivatives, preparation thereof, and pharmaceutical use thereof |
| ES2627428T3 (es) | 2009-07-02 | 2017-07-28 | Sanofi | Nuevos derivados de 2,3-dihidro-1H-imidazo{1,2-a}pirimidin-5-ona, su preparación y su utilización farmacéutica |
| KR20120049281A (ko) | 2009-07-21 | 2012-05-16 | 길리아드 칼리스토가 엘엘씨 | Pi3k 억제제를 이용한 간 장애의 치료 |
| CN102498115B (zh) | 2009-08-20 | 2016-12-07 | 卡鲁斯治疗有限公司 | 作为磷酸肌醇3-激酶抑制剂的三环杂环化合物 |
| CN102741253A (zh) | 2009-09-29 | 2012-10-17 | 艾科睿控股公司 | PI3K(δ)选择性抑制剂 |
| GB0918249D0 (en) | 2009-10-19 | 2009-12-02 | Respivert Ltd | Compounds |
| AP2012006294A0 (en) | 2009-11-05 | 2012-06-30 | Rhizen Pharmaceuticals Sa | Novel kinase modulators. |
| CA2779951A1 (en) | 2009-11-06 | 2011-05-12 | Piramal Life Sciences Limited | Imidazopyridine derivatives |
| JP5735526B2 (ja) | 2009-11-13 | 2015-06-17 | メルク セローノ ソシエテ アノニム | 三環式ピラゾールアミン誘導体 |
| JP2013512879A (ja) | 2009-12-03 | 2013-04-18 | グラクソ グループ リミテッド | Pi3キナーゼの阻害剤としてのベンズピラゾール誘導体 |
| EP2507226A1 (en) | 2009-12-03 | 2012-10-10 | Glaxo Group Limited | Novel compounds |
| US20120238571A1 (en) | 2009-12-03 | 2012-09-20 | Glaxo Group Limited | Indazole derivatives as pi 3-kinase |
| US8759359B2 (en) | 2009-12-18 | 2014-06-24 | Incyte Corporation | Substituted heteroaryl fused derivatives as PI3K inhibitors |
| AU2010330875B2 (en) | 2009-12-18 | 2013-08-01 | Amgen Inc. | Heterocyclic compounds and their uses |
| TW201130842A (en) | 2009-12-18 | 2011-09-16 | Incyte Corp | Substituted fused aryl and heteroaryl derivatives as PI3K inhibitors |
| WO2011101429A1 (en) | 2010-02-22 | 2011-08-25 | F. Hoffmann-La Roche Ag | Pyrido[3,2-d]pyrimidine pi3k delta inhibitor compounds and methods of use |
| UY33304A (es) | 2010-04-02 | 2011-10-31 | Amgen Inc | Compuestos heterocíclicos y sus usos |
| AR081823A1 (es) | 2010-04-14 | 2012-10-24 | Incyte Corp | DERIVADOS FUSIONADOS COMO INHIBIDORES DE PI3Kd |
| GB201007347D0 (en) | 2010-04-30 | 2010-06-16 | Karus Therapeutics Ltd | Compounds |
| AU2011255218B2 (en) | 2010-05-21 | 2015-03-12 | Infinity Pharmaceuticals, Inc. | Chemical compounds, compositions and methods for kinase modulation |
| US9062055B2 (en) | 2010-06-21 | 2015-06-23 | Incyte Corporation | Fused pyrrole derivatives as PI3K inhibitors |
| US8293736B2 (en) | 2010-07-14 | 2012-10-23 | F. Hoffmann La Roche Ag | Purine compounds selective for PI3K P110 delta, and methods of use |
| AU2011302124B2 (en) | 2010-09-14 | 2016-03-17 | Exelixis, Inc. | Inhibitors of PI3K-delta and methods of their use and manufacture |
| AU2011302196B2 (en) | 2010-09-14 | 2016-04-28 | Exelixis, Inc. | Inhibitors of PI3K-delta and methods of their use and manufacture |
| PE20180318A1 (es) | 2011-01-10 | 2018-02-09 | Infinity Pharmaceuticals Inc | Procedimiento para preparar isoquinolinonas y formas solidas de isoquinolinonas |
| US9108984B2 (en) | 2011-03-14 | 2015-08-18 | Incyte Corporation | Substituted diamino-pyrimidine and diamino-pyridine derivatives as PI3K inhibitors |
| CA2825966A1 (en) | 2011-03-21 | 2012-09-27 | F. Hoffmann-La Roche Ag | Benzoxazepin compounds selective for pi3k p110 delta and methods of use |
| US9126948B2 (en) | 2011-03-25 | 2015-09-08 | Incyte Holdings Corporation | Pyrimidine-4,6-diamine derivatives as PI3K inhibitors |
| BR112013024909A2 (pt) | 2011-03-28 | 2019-09-24 | Mei Pharma Inc | composto, composição farmacêutica, método para o tratamento, prevenção ou melhoria de um ou mais sintomas de desordem, doença, ou condição mediada por pi3k, e método para modular a atividade enzimática de pi3k |
| UY34013A (es) | 2011-04-13 | 2012-11-30 | Astrazeneca Ab | ?compuestos de cromenona con actividad anti-tumoral?. |
| EP2518071A1 (en) | 2011-04-29 | 2012-10-31 | Almirall, S.A. | Imidazopyridine derivatives as PI3K inhibitors |
| EP2518070A1 (en) | 2011-04-29 | 2012-10-31 | Almirall, S.A. | Pyrrolotriazinone derivatives as PI3K inhibitors |
| JP2014530851A (ja) | 2011-10-21 | 2014-11-20 | ノバルティスアーゲー | Pi3kモジュレータとしてのキナゾリン誘導体 |
| DK2790705T3 (en) | 2011-12-15 | 2018-03-12 | Novartis Ag | Use of inhibitors of the activity or function of PI3K |
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Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005086814A2 (en) * | 2004-03-09 | 2005-09-22 | The Uab Research Foundation | Methods and compositions related to regulation of cytokine production by glycogen synthase kinase 3 (gsk-3) |
| WO2008012326A1 (en) * | 2006-07-28 | 2008-01-31 | Novartis Ag | 2,4-substituted quinazolines as lipid kinase inhibitors |
| WO2008157191A2 (en) * | 2007-06-14 | 2008-12-24 | Smithkline Beecham Corporation | Quinazoline derivatives as pi3 kinase inhibitors |
| WO2009058361A1 (en) * | 2007-10-31 | 2009-05-07 | Dynavax Technologies Corp. | Inhibition of type i ifn production |
| WO2010036908A1 (en) * | 2008-09-26 | 2010-04-01 | Eisai R & D Management Co., Ltd. | Use of benzoxazole compounds in the treatment of malaria |
| WO2010120991A1 (en) * | 2009-04-17 | 2010-10-21 | Wyeth Llc | 5, 6, 7, 8-tetrahydropyrido[4,3-d]pyrimidine compounds, their use as mtor, pi3, and hsmg-1 kinase inhibitors, and their syntheses |
| WO2010129816A2 (en) * | 2009-05-07 | 2010-11-11 | Intellikine, Inc. | Heterocyclic compounds and uses thereof |
| WO2012004299A1 (en) * | 2010-07-06 | 2012-01-12 | Novartis Ag | Tetrahydro-pyrido-pyrimidine derivatives |
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