NO322825B1 - Kinazolinoner, syntese av slike, anvendelse av slike for fremstilling av medikamenter for behandling av proliferative sykdommer, farmasoytiske preparater inneholdende slike forbindelser samt anvendelse in vitro for a hemme KSP-kinase. - Google Patents
Kinazolinoner, syntese av slike, anvendelse av slike for fremstilling av medikamenter for behandling av proliferative sykdommer, farmasoytiske preparater inneholdende slike forbindelser samt anvendelse in vitro for a hemme KSP-kinase. Download PDFInfo
- Publication number
- NO322825B1 NO322825B1 NO20021907A NO20021907A NO322825B1 NO 322825 B1 NO322825 B1 NO 322825B1 NO 20021907 A NO20021907 A NO 20021907A NO 20021907 A NO20021907 A NO 20021907A NO 322825 B1 NO322825 B1 NO 322825B1
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- Prior art keywords
- hydrogen
- benzyl
- ksp
- compounds
- ethyl
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Classifications
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- 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
- A61K31/495—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
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen atoms
- C07D239/91—Oxygen atoms with aryl or aralkyl radicals attached in position 2 or 3
-
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- 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
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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
- A61P9/08—Vasodilators for multiple indications
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Paints Or Removers (AREA)
- Medicines Containing Plant Substances (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US19825399P | 1999-10-27 | 1999-10-27 | |
US21310400P | 2000-06-21 | 2000-06-21 | |
PCT/US2000/029585 WO2001030768A1 (fr) | 1999-10-27 | 2000-10-26 | Procedes et compositions utilisant des quinazolinones |
Publications (3)
Publication Number | Publication Date |
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NO20021907D0 NO20021907D0 (no) | 2002-04-23 |
NO20021907L NO20021907L (no) | 2002-06-07 |
NO322825B1 true NO322825B1 (no) | 2006-12-11 |
Family
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Application Number | Title | Priority Date | Filing Date |
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NO20021907A NO322825B1 (no) | 1999-10-27 | 2002-04-23 | Kinazolinoner, syntese av slike, anvendelse av slike for fremstilling av medikamenter for behandling av proliferative sykdommer, farmasoytiske preparater inneholdende slike forbindelser samt anvendelse in vitro for a hemme KSP-kinase. |
Country Status (19)
Country | Link |
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EP (2) | EP1686120A3 (fr) |
JP (2) | JP2003512461A (fr) |
KR (2) | KR20050049562A (fr) |
CN (1) | CN100381428C (fr) |
AT (1) | ATE327224T1 (fr) |
AU (2) | AU774748B2 (fr) |
BR (1) | BR0015110A (fr) |
CA (1) | CA2388646C (fr) |
CZ (1) | CZ20021428A3 (fr) |
DE (1) | DE60028227T2 (fr) |
ES (1) | ES2263501T3 (fr) |
HK (1) | HK1045994A1 (fr) |
HU (1) | HUP0203430A3 (fr) |
IL (2) | IL149164A0 (fr) |
MX (1) | MXPA02004162A (fr) |
NO (1) | NO322825B1 (fr) |
NZ (2) | NZ518480A (fr) |
PL (1) | PL203998B1 (fr) |
WO (1) | WO2001030768A1 (fr) |
Families Citing this family (95)
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---|---|---|---|---|
ATE342257T1 (de) | 1999-08-27 | 2006-11-15 | Chemocentryx Inc | Heterozyclische verbindungen und verfahren zur modulierung von cxcr3 funktion |
US20070021493A1 (en) | 1999-09-16 | 2007-01-25 | Curis, Inc. | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
US7230000B1 (en) | 1999-10-27 | 2007-06-12 | Cytokinetics, Incorporated | Methods and compositions utilizing quinazolinones |
US7671200B2 (en) | 1999-10-27 | 2010-03-02 | Cytokinetics, Inc. | Quinazolinone KSP inhibitors |
US6545004B1 (en) * | 1999-10-27 | 2003-04-08 | Cytokinetics, Inc. | Methods and compositions utilizing quinazolinones |
US8852937B2 (en) | 2000-03-30 | 2014-10-07 | Curis, Inc. | Small organic molecule regulators of cell proliferation |
US7115653B2 (en) | 2000-03-30 | 2006-10-03 | Curis, Inc. | Small organic molecule regulators of cell proliferation |
US6667300B2 (en) | 2000-04-25 | 2003-12-23 | Icos Corporation | Inhibitors of human phosphatidylinositol 3-kinase delta |
JP4259877B2 (ja) * | 2000-12-11 | 2009-04-30 | アムジエン・インコーポレーテツド | Cxcr3アンタゴニスト |
US6992082B2 (en) | 2001-01-19 | 2006-01-31 | Cytokinetics, Inc. | Phenothiazine kinesin inhibitors |
US6809102B2 (en) | 2001-03-29 | 2004-10-26 | Bristol-Myers Squibb Company | Cyano-substituted dihydropyrimidine compounds and their use to treat diseases |
US6900214B2 (en) | 2001-03-29 | 2005-05-31 | Bristol-Myers Squibb Company | Cyano-substituted dihydropyrimidine compounds and their use to treat diseases |
US6794379B2 (en) | 2001-06-06 | 2004-09-21 | Tularik Inc. | CXCR3 antagonists |
OA12624A (en) | 2001-06-22 | 2006-06-12 | Pfizer Prod Inc | Pharmaceutical compositions comprising low-solubility and/or acid-sensitive drugs and neutralized acidic polymers. |
US8349853B2 (en) * | 2001-09-05 | 2013-01-08 | Minerva Biotechnologies Corporation | Compositions and methods of treatment of cancer |
US7060705B2 (en) | 2001-11-07 | 2006-06-13 | Merck & Co., Inc. | Mitotic kinesin inhibitors |
AU2002366103A1 (en) | 2001-11-19 | 2003-06-10 | Iconix Pharmaceuticals, Inc. | Modulators of rho c activity |
WO2003043995A1 (fr) * | 2001-11-20 | 2003-05-30 | Cytokinetics, Inc. | Procede de racemisation de quinazolinones chirales |
CA2468156A1 (fr) | 2001-12-06 | 2003-06-19 | Merck & Co., Inc. | Inhibiteurs mitotiques de la kinesine |
EP1458726B1 (fr) * | 2001-12-06 | 2009-07-15 | Merck & Co., Inc. | Inhibiteurs miotitiques de la kinesine |
US7244723B2 (en) | 2001-12-06 | 2007-07-17 | Merck & Co., Inc. | Substituted furopyrimidinones as a mitotic kinesin inhibitors |
ES2291543T3 (es) | 2001-12-06 | 2008-03-01 | MERCK & CO., INC. | Inhibicion de kinesina mitotica. |
EP1551812B1 (fr) * | 2001-12-06 | 2009-03-04 | Merck & Co., Inc. | Inhibiteurs mitotiques de la kinesine |
US7425636B2 (en) | 2001-12-11 | 2008-09-16 | Kyowa Hakko Kogyo Co., Ltd. | Thiadiazoline derivative |
WO2003094839A2 (fr) * | 2002-05-09 | 2003-11-20 | Cytokinetics, Inc. | Composes, compositions et procedes |
ATE356804T1 (de) * | 2002-06-14 | 2007-04-15 | Merck & Co Inc | Inhibitoren von mitotischem kinesin |
US6949538B2 (en) * | 2002-07-17 | 2005-09-27 | Cytokinetics, Inc. | Compounds, compositions, and methods |
US7208487B2 (en) * | 2002-12-13 | 2007-04-24 | Cytokinetics, Incorporated | Compounds, compositions and methods |
EP1608317B1 (fr) * | 2003-03-25 | 2012-09-26 | Takeda Pharmaceutical Company Limited | Inhibiteurs de dipeptidyle peptidase |
WO2004092123A2 (fr) * | 2003-04-10 | 2004-10-28 | Microbia, Inc. | Inhibiteurs d'invasion fongique |
WO2004092147A1 (fr) | 2003-04-18 | 2004-10-28 | Kyowa Hakko Kogyo Co., Ltd. | Inihibiteur de kinesine de stade m |
EP1636225B1 (fr) | 2003-06-20 | 2010-02-24 | Novartis Vaccines and Diagnostics, Inc. | Composes de pyridino 1,2-a pyrimidin-4-one servant d'agents anticancereux |
AU2004266629B2 (en) * | 2003-08-15 | 2009-11-26 | Merck Sharp & Dohme Corp. | Mitotic kinesin inhibitors |
WO2005051922A1 (fr) | 2003-11-25 | 2005-06-09 | Chiron Corporation | Composes quinazolinone utilises en tant qu'agents anticancereux |
JP2007513154A (ja) * | 2003-12-08 | 2007-05-24 | サイトキネティクス・インコーポレーテッド | 化合物、組成物及び方法 |
US7662581B1 (en) | 2003-12-18 | 2010-02-16 | Novartis Vaccines And Diagnostics, Inc. | Eg5 co-crystals |
WO2005060654A2 (fr) | 2003-12-19 | 2005-07-07 | Merck & Co., Inc. | Inhibiteurs de kinesines mitotiques |
JPWO2005061707A1 (ja) * | 2003-12-24 | 2007-07-12 | 協和醗酵工業株式会社 | 癌細胞のEg5阻害剤に対する感受性を判定する方法 |
US7608739B2 (en) * | 2004-03-22 | 2009-10-27 | Merck & Co. Inc. | Mitotic kinesin inhibitors |
DK1737831T3 (da) | 2004-04-02 | 2013-08-19 | Prana Biotechnology Ltd | Neurologisk aktive forbindelser |
LT2612862T (lt) | 2004-05-13 | 2017-01-25 | Icos Corporation | Chinazolinonai kaip žmogaus fosfatidilinozitol-3-kinazės delta inhibitoriai |
ATE404536T1 (de) | 2004-05-21 | 2008-08-15 | Novartis Vaccines & Diagnostic | Substituierte chinolinderivate als inhibitoren von mitotischem kinesin |
WO2005117889A1 (fr) * | 2004-05-25 | 2005-12-15 | Icos Corporation | Methodes de traitement et/ou de prevention de la proliferation aberrante des cellules hematopoietiques |
NZ552510A (en) | 2004-06-18 | 2010-12-24 | Novartis Vaccines & Diagnostic | N-(1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dimethylpropyl) benzamide derivatives and related compounds as kinesin spindle protein (KSP) inhibitors for the treatment of cancer |
US7939538B2 (en) | 2004-06-28 | 2011-05-10 | Amgen Inc. | Compounds, compositions and methods for prevention and treatment of inflammatory and immunoregulatory disorders and diseases |
US7375102B2 (en) | 2004-06-28 | 2008-05-20 | Amgen Sf, Llc | Tetrahydroquinazolin-4(3H)-one-related and tetrahydropyrido[2,3-D]pyrimidin-4(3H)-one-related compounds, compositions and methods for their use |
US7271271B2 (en) | 2004-06-28 | 2007-09-18 | Amgen Sf, Llc | Imidazolo-related compounds, compositions and methods for their use |
CA2575188A1 (fr) | 2004-08-18 | 2006-02-23 | Astrazeneca Ab | Enantiomeres de pyrimidones fusionnes selectionnes et utilisations dans le traitement et la prevention du cancer |
EP1811844A4 (fr) * | 2004-09-14 | 2009-12-02 | Minerva Biotechnologies Corp | Méthodes de diagnostic et de traitement du cancer |
AU2005301133A1 (en) | 2004-10-19 | 2006-05-11 | Novartis Vaccines And Diagnostics Inc. | Indole and benzimidazole derivatives |
CA2595127A1 (fr) * | 2005-01-19 | 2006-07-27 | Paul J. Coleman | Inhibiteurs mitotiques de la kinesine |
DE102005011822A1 (de) * | 2005-03-15 | 2006-09-21 | Merck Patent Gmbh | Phthalazinone |
EP1908755A4 (fr) | 2005-06-24 | 2009-06-24 | Kyowa Hakko Kirin Co Ltd | Agent thérapeutique contre la resténose |
MY147188A (en) * | 2005-08-09 | 2012-11-14 | Novartis Ag | Substituted imidazole compounds as ksp inhibitors |
GB0603041D0 (en) | 2006-02-15 | 2006-03-29 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
JP5489333B2 (ja) | 2006-09-22 | 2014-05-14 | メルク・シャープ・アンド・ドーム・コーポレーション | 脂肪酸合成阻害剤を用いた治療の方法 |
US8916552B2 (en) | 2006-10-12 | 2014-12-23 | Astex Therapeutics Limited | Pharmaceutical combinations |
JP5528807B2 (ja) | 2006-10-12 | 2014-06-25 | アステックス、セラピューティックス、リミテッド | 複合薬剤 |
US20110218176A1 (en) | 2006-11-01 | 2011-09-08 | Barbara Brooke Jennings-Spring | Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development |
US8273747B2 (en) | 2006-11-02 | 2012-09-25 | Curis, Inc. | Small organic molecule regulators of cell proliferation |
AU2007323998B2 (en) | 2006-11-13 | 2011-09-22 | Novartis Ag | Substituted pyrazole and triazole compounds as KSP inhibitors |
US7820646B2 (en) | 2007-01-05 | 2010-10-26 | Novartis Vaccines And Diagnostics, Inc. | Cyclized derivatives as Eg-5 inhibitors |
PL2336120T3 (pl) | 2007-01-10 | 2014-12-31 | Msd Italia Srl | Kombinacje zawierające indazole podstawione grupą amidową jako inhibitory polimerazy poli(ADP-rybozy) (PARP) |
MX2009009304A (es) | 2007-03-01 | 2009-11-18 | Novartis Ag | Inhibidores de cinasa pim y metodos para su uso. |
KR20100017866A (ko) | 2007-05-21 | 2010-02-16 | 노파르티스 아게 | Csf-1r 억제제, 조성물 및 사용 방법 |
AU2008268613A1 (en) | 2007-06-22 | 2008-12-31 | Arqule, Inc. | Quinazolinone compounds and methods of use thereof |
AU2008269154B2 (en) | 2007-06-27 | 2014-06-12 | Merck Sharp & Dohme Llc | 4-carboxybenzylamino derivatives as histone deacetylase inhibitors |
JP5794919B2 (ja) | 2008-11-13 | 2015-10-14 | ギリアード カリストガ エルエルシー | 血液学的な悪性疾患のための療法 |
US9492449B2 (en) | 2008-11-13 | 2016-11-15 | Gilead Calistoga Llc | Therapies for hematologic malignancies |
JP2013500257A (ja) | 2009-07-21 | 2013-01-07 | ギリアード カリストガ エルエルシー | Pi3kインヒビターでの肝障害の処置 |
CA2805265A1 (fr) | 2010-08-02 | 2012-02-09 | Merck Sharp & Dohme Corp. | Inhibition a mediation par interference arn de catenine (proteine associee a cadherine), expression du gene beta 1 (ctnnb1) a l'aide de petit acide nucleique interferent (sian) |
CA2807307C (fr) | 2010-08-17 | 2021-02-09 | Merck Sharp & Dohme Corp. | Inhibition mediee par des arn interferents de l'expression genique du virus de l'hepatite b (vhb) a l'aide de petits acides nucleiques interferents (pani) |
EP2608669B1 (fr) | 2010-08-23 | 2016-06-22 | Merck Sharp & Dohme Corp. | Nouveaux dérivés de pyrazolo[1,5-a]pyrimidine utilisés comme inhibiteurs de mtor |
EP2615916B1 (fr) | 2010-09-16 | 2017-01-04 | Merck Sharp & Dohme Corp. | Dérivés condensés de pyrazole utilisés comme nouveaux inhibiteurs erk |
ES2663009T3 (es) | 2010-10-29 | 2018-04-10 | Sirna Therapeutics, Inc. | Inhibición de la expresión génica mediada por interferencia por ARN utilizando ácidos nucleicos de interferencia cortos (ANic) |
JP2014514321A (ja) | 2011-04-21 | 2014-06-19 | メルク・シャープ・アンド・ドーム・コーポレーション | インスリン様増殖因子1受容体阻害剤 |
CA2864305C (fr) | 2012-03-05 | 2021-02-16 | Gilead Calistoga Llc | Formes polymorphes de l'acide -2-(1-(9h-purine-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3h)-one |
EP3358013B1 (fr) | 2012-05-02 | 2020-06-24 | Sirna Therapeutics, Inc. | Compositions d'acide nucléique interférent court (sina) |
TW201437203A (zh) | 2012-12-21 | 2014-10-01 | Gilead Calistoga Llc | 磷脂醯肌醇3-激酶之抑制劑 |
ES2677919T3 (es) | 2012-12-21 | 2018-08-07 | Gilead Calistoga Llc | Aminoalquil-quinazolonas sustituidas con pirimidina como inhibidores de la fosfatidilinositol 3-quinasa |
EP3008053B1 (fr) | 2013-06-14 | 2018-03-21 | Gilead Calistoga LLC | Inhibiteurs de phosphatidylinositol 3-kinase |
EP3041938A1 (fr) | 2013-09-03 | 2016-07-13 | Moderna Therapeutics, Inc. | Polynucléotides circulaires |
US9567337B2 (en) | 2013-12-20 | 2017-02-14 | Gilead Calistoga Llc | Process methods for phosphatidylinositol 3-kinase inhibitors |
WO2015095605A1 (fr) | 2013-12-20 | 2015-06-25 | Gilead Calistoga Llc | Formes polymorphes d'un sel chlorhydrate de la (s)-2-(9h-purine-6-ylamino)propyl)-5-fluoro-3-phénylquinazolin-4(3h)-one |
KR20170015508A (ko) | 2014-06-13 | 2017-02-08 | 길리애드 사이언시즈, 인코포레이티드 | 포스파티딜이노시톨 3-키나제 억제제로서의 퀴나졸리논 유도체 |
WO2015191726A1 (fr) | 2014-06-13 | 2015-12-17 | Gilead Sciences, Inc. | Inhibiteurs de la phosphatidylinositol 3-kinase |
SG11201609540TA (en) | 2014-06-13 | 2016-12-29 | Gilead Sciences Inc | Phosphatidylinositol 3-kinase inhibitors |
US10092563B2 (en) | 2014-06-13 | 2018-10-09 | Gilead Sciences, Inc. | Phosphatidylinositol 3-kinase inhibitors |
JO3589B1 (ar) | 2014-08-06 | 2020-07-05 | Novartis Ag | مثبطات كيناز البروتين c وطرق استخداماتها |
WO2017003723A1 (fr) | 2015-07-01 | 2017-01-05 | Crinetics Pharmaceuticals, Inc. | Modulateurs de la somatostatine et leurs utilisations |
TW201825465A (zh) | 2016-09-23 | 2018-07-16 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
TW201813963A (zh) | 2016-09-23 | 2018-04-16 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
TW201815787A (zh) | 2016-09-23 | 2018-05-01 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
WO2019023278A1 (fr) | 2017-07-25 | 2019-01-31 | Crinetics Pharmaceuticals, Inc. | Modulateurs de la somatostatine et utilisations de ces derniers |
CN111189935A (zh) * | 2019-12-30 | 2020-05-22 | 卓和药业集团有限公司 | 盐酸右美托咪定的高效液相色谱分析方法 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU543928B2 (en) * | 1981-01-16 | 1985-05-09 | Masayuki Ishikawa | 4(311)-quinazolinone derivatives |
ES2245015T3 (es) * | 1997-06-09 | 2005-12-16 | Pfizer Products Inc. | Quinazolin-4-onas como antagonistas de ampa. |
US6545004B1 (en) * | 1999-10-27 | 2003-04-08 | Cytokinetics, Inc. | Methods and compositions utilizing quinazolinones |
-
2000
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