JP2010530885A - キナゾリノン化合物およびその使用方法 - Google Patents
キナゾリノン化合物およびその使用方法 Download PDFInfo
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- JP2010530885A JP2010530885A JP2010513424A JP2010513424A JP2010530885A JP 2010530885 A JP2010530885 A JP 2010530885A JP 2010513424 A JP2010513424 A JP 2010513424A JP 2010513424 A JP2010513424 A JP 2010513424A JP 2010530885 A JP2010530885 A JP 2010530885A
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- JP
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- Prior art keywords
- chloro
- oxo
- compound
- propyl
- phenylamino
- 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.)
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- 238000000034 method Methods 0.000 title claims abstract description 184
- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 title abstract description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 205
- -1 quinazolinone compound Chemical class 0.000 claims abstract description 115
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 84
- 201000011510 cancer Diseases 0.000 claims abstract description 52
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 38
- 230000002062 proliferating effect Effects 0.000 claims abstract description 31
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 22
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 11
- 229940127089 cytotoxic agent Drugs 0.000 claims abstract description 11
- 239000003937 drug carrier Substances 0.000 claims abstract description 11
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 66
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 60
- 125000003118 aryl group Chemical group 0.000 claims description 53
- 125000003342 alkenyl group Chemical group 0.000 claims description 49
- 125000000304 alkynyl group Chemical group 0.000 claims description 48
- 125000001072 heteroaryl group Chemical group 0.000 claims description 41
- 125000000623 heterocyclic group Chemical group 0.000 claims description 34
- 238000011282 treatment Methods 0.000 claims description 33
- 208000035475 disorder Diseases 0.000 claims description 31
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000003282 alkyl amino group Chemical group 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 19
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 18
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 125000004414 alkyl thio group Chemical group 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
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- 239000002207 metabolite Substances 0.000 claims description 10
- 229940002612 prodrug Drugs 0.000 claims description 10
- 239000000651 prodrug Substances 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 9
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- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 9
- 230000004614 tumor growth Effects 0.000 claims description 9
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 claims description 8
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 8
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- 125000003107 substituted aryl group Chemical group 0.000 claims description 8
- SPFPGSYLNIIQMG-UHFFFAOYSA-N (carboxyamino)carbamic acid Chemical compound OC(=O)NNC(O)=O SPFPGSYLNIIQMG-UHFFFAOYSA-N 0.000 claims description 7
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
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- 125000004438 haloalkoxy group Chemical group 0.000 claims description 7
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 6
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- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 claims description 6
- 229960000485 methotrexate Drugs 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 229930012538 Paclitaxel Natural products 0.000 claims description 5
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 5
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 5
- 229960001592 paclitaxel Drugs 0.000 claims description 5
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- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims description 4
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 4
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 claims description 4
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 claims description 4
- 108010069236 Goserelin Proteins 0.000 claims description 4
- 239000005517 L01XE01 - Imatinib Substances 0.000 claims description 4
- 239000005411 L01XE02 - Gefitinib Substances 0.000 claims description 4
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 4
- 208000006994 Precancerous Conditions Diseases 0.000 claims description 4
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims description 4
- 229940127093 camptothecin Drugs 0.000 claims description 4
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 claims description 4
- 229960001904 epirubicin Drugs 0.000 claims description 4
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims description 4
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- UPJSUQWHUVLLNW-XMMPIXPASA-N n-(3-aminopropyl)-n-[(1r)-1-(3-anilino-7-chloro-4-oxoquinazolin-2-yl)but-3-ynyl]-3-chloro-2-fluorobenzamide Chemical compound C1([C@@H](CC#C)N(CCCN)C(=O)C=2C(=C(Cl)C=CC=2)F)=NC2=CC(Cl)=CC=C2C(=O)N1NC1=CC=CC=C1 UPJSUQWHUVLLNW-XMMPIXPASA-N 0.000 claims description 4
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 3
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- 101100002068 Bacillus subtilis (strain 168) araR gene Proteins 0.000 claims description 3
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- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 3
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- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- 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
- C07D239/90—Oxygen atoms with acyclic radicals attached in position 2 or 3
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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| JP5469779B2 (ja) * | 2010-04-19 | 2014-04-16 | エスアールアイ インターナショナル | 多発性骨髄腫の治療のための組成物および方法 |
| US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| US9751888B2 (en) | 2013-10-04 | 2017-09-05 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| PT3052485T (pt) | 2013-10-04 | 2021-10-22 | Infinity Pharmaceuticals Inc | Compostos heterocíclicos e suas utilizações |
| US20150132575A1 (en) * | 2013-11-14 | 2015-05-14 | Honeywell International Inc. | Luminescent fibers, articles including the same, and methods of forming the same |
| MX382033B (es) | 2014-03-19 | 2025-03-13 | Infinity Pharmaceuticals Inc | Compuestos heterocíclicos para utilizarlos en el tratamiento de trastornos mediados por pi3k-gamma. |
| WO2016054491A1 (en) | 2014-10-03 | 2016-04-07 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| WO2017048702A1 (en) | 2015-09-14 | 2017-03-23 | Infinity Pharmaceuticals, Inc. | Solid forms of isoquinolinone derivatives, process of making, compositions comprising, and methods of using the same |
| WO2017161116A1 (en) | 2016-03-17 | 2017-09-21 | Infinity Pharmaceuticals, Inc. | Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as pi3k kinase inhibitors |
| WO2017214269A1 (en) | 2016-06-08 | 2017-12-14 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| 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 |
| 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 |
| 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 |
| EP3790878A1 (en) * | 2018-05-11 | 2021-03-17 | The United States of America, as represented by the Secretary, Department of Health and Human Services | Quinoline compounds and their preparation and use as antimalarial agents |
| CN113354590A (zh) * | 2020-03-05 | 2021-09-07 | 宁波康柏睿格医药科技有限公司 | 拮抗nod1/2受体信号通路的喹唑啉酮类化合物 |
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| BG16042A3 (bg) * | 1968-11-12 | 1972-05-20 | Nans Ott | Метод за получаване на нови 2(1н)-хиназолинони |
| AU543928B2 (en) | 1981-01-16 | 1985-05-09 | Masayuki Ishikawa | 4(311)-quinazolinone derivatives |
| US4522811A (en) * | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| US5187167A (en) * | 1986-03-27 | 1993-02-16 | Imperial Chemical Industries Plc | Pharmaceutical compositions comprising quinazolin-4-one derivatives |
| GB8707053D0 (en) * | 1987-03-25 | 1987-04-29 | Ici Plc | Anti-tumour agents |
| NZ227850A (en) * | 1988-02-10 | 1991-11-26 | Hoffmann La Roche | Indole substituted pyrrole derivatives; preparatory process and medicaments for use against inflammatory immunological, bronchopulmonary or vascular disorders |
| GB8827820D0 (en) * | 1988-11-29 | 1988-12-29 | Janssen Pharmaceutica Nv | (1h-azol-1-ylmethyl)substituted quinoline derivatives |
| GB8827988D0 (en) * | 1988-11-30 | 1989-01-05 | Smith Kline French Lab | Chemical compounds |
| USRE36736E (en) * | 1989-02-06 | 2000-06-13 | Hoffman-La Roche Inc. | Substituted pyrroles |
| MC2096A1 (fr) | 1989-02-23 | 1991-02-15 | Hoffmann La Roche | Pyrroles substitues |
| GB8904161D0 (en) * | 1989-02-23 | 1989-04-05 | Hoffmann La Roche | Substituted pyrroles |
| US5380746A (en) * | 1989-05-05 | 1995-01-10 | Goedecke Aktiengesellschaft | Bis-(1H-indol-3-YL)-maleinimide derivatives, processes for the preparation thereof and pharmaceutical compositions containing them |
| CA2015996C (en) | 1989-05-05 | 2001-08-28 | Hartmut Osswald | Bis-(1h-indol-3-yl)-maleinimide derivatives and their use as pharmaceuticals |
| DE4005970A1 (de) | 1990-02-26 | 1991-08-29 | Boehringer Mannheim Gmbh | Neue trisubstituierte maleinimide, verfahren zu ihrer herstellung sowie arzneimittel, die diese verbindungen enthalten |
| DE4005969A1 (de) | 1990-02-26 | 1991-08-29 | Boehringer Mannheim Gmbh | Neue trisubstituierte pyrrole, verfahren zu ihrer herstellung sowie arzneimittel, die diese verbindungen enthalten |
| ZA913730B (en) * | 1990-05-30 | 1992-02-26 | Ici Plc | Anti-tumor compounds |
| US5292747A (en) * | 1990-08-07 | 1994-03-08 | Hoffman-La Roche Inc. | Substituted pyrroles |
| US5591842A (en) * | 1991-11-29 | 1997-01-07 | Banyu Pharmaceutical Co., Ltd. | Indolopyrrolocarbazole derivatives |
| WO1993018036A1 (en) | 1992-03-12 | 1993-09-16 | Smithkline Beecham Plc | Condensed indole derivatives as 5ht4-receptor antagonists |
| AU3761393A (en) | 1992-03-20 | 1993-10-21 | Wellcome Foundation Limited, The | Indole derivatives with antiviral activity |
| US5721230A (en) * | 1993-05-10 | 1998-02-24 | Hoffmann-La Roche Inc. | Substituted pyrroles |
| CA2179650C (en) | 1993-12-23 | 2007-10-30 | William Francis Heath, Jr. | Bisindolemaleimides and their use as protein kinase c inhibitors |
| US5545636A (en) * | 1993-12-23 | 1996-08-13 | Eli Lilly And Company | Protein kinase C inhibitors |
| US6524832B1 (en) * | 1994-02-04 | 2003-02-25 | Arch Development Corporation | DNA damaging agents in combination with tyrosine kinase inhibitors |
| WO1995024190A2 (en) * | 1994-03-07 | 1995-09-14 | Sugen, Inc. | Receptor tyrosine kinase inhibitors for inhibiting cell proliferative disorders and compositions thereof |
| WO1995030682A1 (en) | 1994-05-09 | 1995-11-16 | Banyu Pharmaceutical Co., Ltd. | Antitumor indolopyprolocarbazole derivative |
| IL110831A (en) | 1994-08-31 | 1998-12-27 | Hadasit Med Res Service | Pharmaceutical compositions containing quinazolinone derivatives for preventing restenosis |
| US5591855A (en) * | 1994-10-14 | 1997-01-07 | Cephalon, Inc. | Fused pyrrolocarbazoles |
| IL112125A (en) | 1994-12-22 | 1998-02-08 | Hadasit Med Res Service | Quinazolinone-containing pharmaceutical compositions |
| US5559228A (en) * | 1995-03-30 | 1996-09-24 | Eli Lilly And Company | Synthesis of bisindolylmaleimides |
| US5747498A (en) * | 1996-05-28 | 1998-05-05 | Pfizer Inc. | Alkynyl and azido-substituted 4-anilinoquinazolines |
| US5919946A (en) | 1996-03-20 | 1999-07-06 | Eli Lilly And Company | Synthesis of indolylmaleimides |
| PE91598A1 (es) | 1996-07-29 | 1998-12-24 | Hoffmann La Roche | Pirroles sustituidos |
| PE91698A1 (es) * | 1996-07-29 | 1998-12-24 | Hoffmann La Roche | Pirroles sustituidos |
| US5990319A (en) | 1996-08-23 | 1999-11-23 | Eli Lilly And Company | Synthesis of bisindolylmaleimides |
| SE9603283D0 (sv) * | 1996-09-10 | 1996-09-10 | Astra Ab | New compounds |
| WO1998016528A1 (en) | 1996-10-11 | 1998-04-23 | Chiron Corporation | Purine inhibitors of glycogen synthase kinase 3 (gsk3) |
| US6028075A (en) | 1997-02-11 | 2000-02-22 | Pines; Mark | Quinazolinone containing pharmaceutical compositions for prevention of neovascularization and for treating malignancies |
| US5859261A (en) * | 1997-03-20 | 1999-01-12 | Eli Lilly And Company | Synthesis of indolylmaleimides |
| US6184377B1 (en) * | 1997-12-15 | 2001-02-06 | Sepracor Inc. | Compositions containing N-amino- and N-hydroxy-quinazolinones and methods for preparing libraries thereof |
| ID27510A (id) | 1998-07-30 | 2001-04-12 | Japan Tobacco Inc | Senyawa malimida tersubstitusi dan penggunaan farmasinya |
| EP1152002A4 (en) | 1999-02-09 | 2002-04-17 | Sagami Chem Res | PYRROL DERIVATIVES AND CELL DEATH INHIBITORS |
| CZ20021428A3 (cs) | 1999-10-27 | 2002-11-13 | Cytokinetics, Inc. | Způsoby a kompozice vyuľívající chinazoliny |
| US6545004B1 (en) * | 1999-10-27 | 2003-04-08 | Cytokinetics, Inc. | Methods and compositions utilizing quinazolinones |
| UA74803C2 (uk) * | 1999-11-11 | 2006-02-15 | Осі Фармасьютікалз, Інк. | Стійкий поліморф гідрохлориду n-(3-етинілфеніл)-6,7-біс(2-метоксіетокси)-4-хіназолінаміну, спосіб його одержання (варіанти) та фармацевтичне застосування |
| AU2576901A (en) | 1999-12-16 | 2001-06-25 | Eli Lilly And Company | Agents and methods for the treatment of proliferative diseases |
| EP1242420A2 (en) * | 1999-12-16 | 2002-09-25 | Eli Lilly And Company | Agents and methods for the treatment of proliferative diseases |
| EP1275646A4 (en) | 2000-03-30 | 2003-05-28 | Sagami Chem Res | INDOLYLPYRROL DERIVATIVES AND CELL DEATH INHIBITORS |
| AU783615B2 (en) | 2000-05-11 | 2005-11-17 | Consejo Superior De Investigaciones Cientificas | Heterocyclic inhibitors of glycogen synthase kinase GSK-3 |
| AU2001277854B2 (en) | 2000-06-29 | 2007-03-01 | North Shore-Long Island Jewish Health System | Modulators of cellular proliferation and angiogenesis, methods for use and identification thereof |
| US6962944B2 (en) | 2001-07-31 | 2005-11-08 | Arqule, Inc. | Pharmaceutical compositions containing beta-lapachone, or derivatives or analogs thereof, and methods of using same |
| US7074824B2 (en) | 2001-07-31 | 2006-07-11 | Arqule, Inc. | Pharmaceutical compositions containing beta-lapachone, or derivatives or analogs thereof, and methods of using same |
| JP2005511581A (ja) | 2001-11-07 | 2005-04-28 | メルク エンド カムパニー インコーポレーテッド | 有糸分裂キネシン阻害剤 |
| WO2003043995A1 (en) | 2001-11-20 | 2003-05-30 | Cytokinetics, Inc. | Process for the racemization of chiral quinazolinones |
| AU2003219679B2 (en) | 2002-01-23 | 2009-02-26 | Texas Tech University | Mammalian migration inducting gene and methods for detection and inhibition of migrating tumor cells |
| JP2005529076A (ja) | 2002-02-15 | 2005-09-29 | サイトキネティクス・インコーポレーテッド | キナゾリノンの合成 |
| WO2003076442A1 (en) | 2002-03-05 | 2003-09-18 | Eli Lilly And Company | Purine derivatives as kinase inhibitors |
| EP1553931A4 (en) | 2002-05-09 | 2006-08-30 | Cytokinetics Inc | COMPOUNDS, COMPOSITIONS AND METHODS |
| EP1517904A4 (en) * | 2002-05-23 | 2007-02-21 | Merck & Co Inc | INHIBITORS OF MITOTIC KINESINE |
| EP1513820A4 (en) * | 2002-05-23 | 2006-09-13 | Cytokinetics Inc | COMPOUNDS, COMPOSITIONS AND METHODS |
| EP1537089A4 (en) * | 2002-07-23 | 2008-04-16 | Cytokinetics Inc | CONNECTIONS, COMPOSITIONS AND PROCEDURES |
| JP2006523456A (ja) | 2003-04-15 | 2006-10-19 | アバロン ファーマシューティカルズ，インコーポレイテッド | 分子細胞遺伝学的方法を用いる癌連鎖遺伝子および治療標的の確認 |
| US20050043233A1 (en) | 2003-04-29 | 2005-02-24 | Boehringer Ingelheim International Gmbh | Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis |
| CA2526285A1 (en) | 2003-05-15 | 2004-12-23 | Arqule, Inc. | Inhibitors of p38 and methods of using the same |
| US7345046B2 (en) | 2003-05-30 | 2008-03-18 | Chiron Corporation | Heteroaryl-fused pyrimidinyl compounds as anticancer agents |
| WO2005001486A1 (en) | 2003-06-06 | 2005-01-06 | Genentech, Inc. | Modulating the interaction between hgf beta chain and c-met |
| WO2005007193A2 (en) | 2003-07-07 | 2005-01-27 | Vande Woude, George, F. | Inhibition of tumor angiogenesis by combination of thrombospondin-1 and inhibitors of vascular endothelial growth factor |
| CA2548282A1 (en) | 2003-12-11 | 2005-06-30 | Genentech, Inc. | Methods and compositions for inhibiting c-met dimerization and activation |
| EP2258704A1 (en) | 2004-10-19 | 2010-12-08 | ArQule, Inc. | Synthesis of imidazooxazole and imidazothiazole inhibitors of p38 map kinase |
| KR100941205B1 (ko) | 2005-02-09 | 2010-02-10 | 아르퀼 인코포레이티드 | 말레이미드 유도체, 약제학적 조성물 및 암을 치료하는방법 |
| EP1863519B1 (en) | 2005-03-31 | 2013-09-25 | The General Hospital Corporation | Modulating hgf/hgfr activity for treating lymphodema |
| WO2007123892A2 (en) * | 2006-04-17 | 2007-11-01 | Arqule Inc. | Raf inhibitors and their uses |
-
2008
- 2008-06-19 KR KR1020107001013A patent/KR20100024494A/ko not_active Withdrawn
- 2008-06-19 AU AU2008268613A patent/AU2008268613A1/en not_active Abandoned
- 2008-06-19 BR BRPI0813355-7A2A patent/BRPI0813355A2/pt not_active IP Right Cessation
- 2008-06-19 CA CA2704282A patent/CA2704282A1/en not_active Abandoned
- 2008-06-19 WO PCT/US2008/067571 patent/WO2009002808A2/en not_active Ceased
- 2008-06-19 EP EP08771527A patent/EP2173724B1/en active Active
- 2008-06-19 US US12/142,762 patent/US8232285B2/en active Active
- 2008-06-19 JP JP2010513424A patent/JP2010530885A/ja not_active Withdrawn
- 2008-06-19 CN CN200880104552A patent/CN101801937A/zh active Pending
- 2008-06-19 MX MX2009013815A patent/MX2009013815A/es not_active Application Discontinuation
- 2008-06-20 TW TW097123156A patent/TW200918069A/zh unknown
-
2009
- 2009-12-15 IL IL202740A patent/IL202740A0/en unknown
-
2010
- 2010-01-11 ZA ZA2010/00183A patent/ZA201000183B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20100024494A (ko) | 2010-03-05 |
| CN101801937A (zh) | 2010-08-11 |
| ZA201000183B (en) | 2011-03-30 |
| CA2704282A1 (en) | 2008-12-31 |
| BRPI0813355A2 (pt) | 2014-12-30 |
| AU2008268613A1 (en) | 2008-12-31 |
| MX2009013815A (es) | 2010-03-01 |
| TW200918069A (en) | 2009-05-01 |
| IL202740A0 (en) | 2010-06-30 |
| WO2009002808A2 (en) | 2008-12-31 |
| EP2173724B1 (en) | 2012-12-05 |
| US8232285B2 (en) | 2012-07-31 |
| US20090130097A1 (en) | 2009-05-21 |
| WO2009002808A3 (en) | 2009-07-23 |
| EP2173724A2 (en) | 2010-04-14 |
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