SK287498B6 - Vybrané kondenzované pyrolokarbazoly, farmaceutické kompozície s ich obsahom a ich použitie - Google Patents
Vybrané kondenzované pyrolokarbazoly, farmaceutické kompozície s ich obsahom a ich použitie Download PDFInfo
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| US27845501P | 2001-03-23 | 2001-03-23 | |
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| PCT/US2001/026266 WO2002017914A2 (en) | 2000-08-25 | 2001-08-23 | Fused pyrrolocarbazoles against inflammation |
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Families Citing this family (82)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6811992B1 (en) * | 1998-05-14 | 2004-11-02 | Ya Fang Liu | Method for identifying MLK inhibitors for the treatment of neurological conditions |
| UA80447C2 (en) | 2002-10-08 | 2007-09-25 | Methods for treating pain by administering nerve growth factor antagonist and opioid analgesic | |
| PL211654B1 (pl) | 2002-10-08 | 2012-06-29 | Rinat Neuroscience Corp | Przeciwciało skierowane przeciwko NGF do zastosowania w leczeniu bólu pooperacyjnego, zastosowanie tego przeciwciała do wytwarzania leku do leczenia bólu pooperacyjnego i kompozycja farmaceutyczna zawierająca przeciwciało skierowane przeciwko NGF do zastosowania w leczeniu bólu pooperacyjnego |
| US7569364B2 (en) | 2002-12-24 | 2009-08-04 | Pfizer Inc. | Anti-NGF antibodies and methods using same |
| US9498530B2 (en) | 2002-12-24 | 2016-11-22 | Rinat Neuroscience Corp. | Methods for treating osteoarthritis pain by administering a nerve growth factor antagonist and compositions containing the same |
| SI2263692T1 (sl) | 2002-12-24 | 2020-10-30 | Rinat Neuroscience Corp. | Anti-NGF protitelesa in postopki, v katerih se le-ta uporabljajo |
| AU2004213044A1 (en) | 2003-02-19 | 2004-09-02 | Rinat Neuroscience Corp. | Methods for treating pain by administering a nerve growth factor antagonist and an NSAID and compositions containing the same |
| MEP31408A (en) | 2003-07-18 | 2010-10-10 | Abgenix Inc | Specific binding agents to hepatocyte growth factor |
| US7169802B2 (en) * | 2003-12-23 | 2007-01-30 | Cephalon, Inc. | Fused pyrrolocarbazoles |
| US7241779B2 (en) * | 2003-12-23 | 2007-07-10 | Cephalon, Inc. | Fused pyrrolocarbazoles |
| DK2206728T3 (en) | 2004-04-07 | 2018-04-23 | Rinat Neuroscience Corp | METHODS OF TREATING BONE CANCER PAIN BY SUBMITTING A NERVOUS FACTOR-ANTAGONISTIC ANTIBODY |
| EP1827434B1 (en) | 2004-11-30 | 2014-01-15 | Amgen Inc. | Quinolines and quinazoline analogs and their use as medicaments for treating cancer |
| US20060134175A1 (en) * | 2004-12-22 | 2006-06-22 | Stephen Bartels | Drug eluting pharmaceutical delivery system for treatment of ocular disease and method of use |
| US20060134176A1 (en) * | 2004-12-22 | 2006-06-22 | Bausch & Lomb Incorporated | Pharmaceutical delivery system and method of use |
| US20060134174A1 (en) * | 2004-12-22 | 2006-06-22 | Bausch & Lomb Incorporated | Pharmaceutical delivery system and method of use |
| US20060216288A1 (en) * | 2005-03-22 | 2006-09-28 | Amgen Inc | Combinations for the treatment of cancer |
| WO2007002670A2 (en) * | 2005-06-28 | 2007-01-04 | Bausch & Lomb Incorporated | Method of lowering intraocular pressure |
| AR059066A1 (es) | 2006-01-27 | 2008-03-12 | Amgen Inc | Combinaciones del inhibidor de la angiopoyetina -2 (ang2) y el inhibidor del factor de crecimiento endotelial vascular (vegf) |
| US8217177B2 (en) | 2006-07-14 | 2012-07-10 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| PE20121506A1 (es) | 2006-07-14 | 2012-11-26 | Amgen Inc | Compuestos triazolopiridinas como inhibidores de c-met |
| US20080021013A1 (en) * | 2006-07-21 | 2008-01-24 | Cephalon, Inc. | JAK inhibitors for treatment of myeloproliferative disorders |
| CA2672438A1 (en) | 2006-12-20 | 2008-07-03 | Amgen Inc. | Substituted heterocycles and methods of use |
| US7759344B2 (en) | 2007-01-09 | 2010-07-20 | Amgen Inc. | Bis-aryl amide derivatives and methods of use |
| MX2009008531A (es) | 2007-02-16 | 2009-08-26 | Amgen Inc | Cetonas de heterociclilo que contienen nitrogeno y su uso como inhibidores de c-met. |
| US9061009B2 (en) * | 2007-06-08 | 2015-06-23 | University Of Massachusetts | Mixed lineage kinases and metabolic disorders |
| TWI595005B (zh) | 2007-08-21 | 2017-08-11 | 安健股份有限公司 | 人類ｃ－ｆｍｓ抗原結合蛋白質 |
| AU2009316600B2 (en) * | 2008-11-19 | 2015-09-24 | Cephalon, Inc. | Novel forms of an indazolo [5,4-a] pyrrolo [3,4-c] carbazole compound |
| EP2192121A1 (en) | 2008-11-27 | 2010-06-02 | Cephalon France | Regioselective reduction of fused pyrrolocarbazoles-5,7-diones |
| KR101038055B1 (ko) * | 2010-06-10 | 2011-06-01 | 송광섭 | 수중 마사지장치 |
| WO2011161217A2 (en) | 2010-06-23 | 2011-12-29 | Palacký University in Olomouc | Targeting of vegfr2 |
| ES2543569T3 (es) | 2011-03-23 | 2015-08-20 | Amgen Inc. | Inhibidores duales tricíclicos condensados de CDK 4/6 y FLT3 |
| US9745288B2 (en) | 2011-08-16 | 2017-08-29 | Indiana University Research And Technology Corporation | Compounds and methods for treating cancer by inhibiting the urokinase receptor |
| AR090263A1 (es) | 2012-03-08 | 2014-10-29 | Hoffmann La Roche | Terapia combinada de anticuerpos contra el csf-1r humano y las utilizaciones de la misma |
| WO2014036022A1 (en) | 2012-08-29 | 2014-03-06 | Amgen Inc. | Quinazolinone compounds and derivatives thereof |
| ES2887474T3 (es) | 2015-01-08 | 2021-12-22 | Univ Leland Stanford Junior | Factores y células que proporcionan inducción de hueso, médula ósea y cartílago |
| MX2019007643A (es) | 2016-12-22 | 2019-09-09 | Amgen Inc | Benzoisotiazol, isotiazolo[3,4-b]piridina, quinazolina, ftalazina, pirido[2,3-d]piridazina y derivados de pirido[2,3-d]pirimidina como inhibirores de kras g12c para tratar el cancer de pulmon, pancreatico o colorrectal. |
| JOP20190272A1 (ar) | 2017-05-22 | 2019-11-21 | Amgen Inc | مثبطات kras g12c وطرق لاستخدامها |
| CN111051306B (zh) | 2017-09-08 | 2023-01-03 | 美国安进公司 | Kras g12c的抑制剂及其使用方法 |
| WO2019213516A1 (en) | 2018-05-04 | 2019-11-07 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
| MA52496A (fr) | 2018-05-04 | 2021-03-10 | Amgen Inc | Inhibiteurs de kras g12c et leurs procédés d'utilisation |
| US10988485B2 (en) | 2018-05-10 | 2021-04-27 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
| MX2020012731A (es) | 2018-06-01 | 2021-02-22 | Amgen Inc | Inhibidores de kras g12c y metodos para su uso. |
| MX2020012204A (es) | 2018-06-11 | 2021-03-31 | Amgen Inc | Inhibidores de kras g12c para tratar el cáncer. |
| US11285156B2 (en) | 2018-06-12 | 2022-03-29 | Amgen Inc. | Substituted piperazines as KRAS G12C inhibitors |
| JP7516029B2 (ja) | 2018-11-16 | 2024-07-16 | アムジエン・インコーポレーテツド | Ｋｒａｓ ｇ１２ｃ阻害剤化合物の重要な中間体の改良合成法 |
| JP7377679B2 (ja) | 2018-11-19 | 2023-11-10 | アムジエン・インコーポレーテツド | がん治療のためのｋｒａｓｇ１２ｃ阻害剤及び１種以上の薬学的に活性な追加の薬剤を含む併用療法 |
| CA3117222A1 (en) | 2018-11-19 | 2020-05-28 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
| EP3898592A1 (en) | 2018-12-20 | 2021-10-27 | Amgen Inc. | Heteroaryl amides useful as kif18a inhibitors |
| AU2019403486A1 (en) | 2018-12-20 | 2021-06-24 | Amgen Inc. | KIF18A inhibitors |
| JP2022513967A (ja) | 2018-12-20 | 2022-02-09 | アムジエン・インコーポレーテツド | Ｋｉｆ１８ａ阻害剤として有用なヘテロアリールアミド |
| AU2019403488A1 (en) | 2018-12-20 | 2021-06-24 | Amgen Inc. | KIF18A inhibitors |
| US20230148450A9 (en) | 2019-03-01 | 2023-05-11 | Revolution Medicines, Inc. | Bicyclic heteroaryl compounds and uses thereof |
| AU2020232616A1 (en) | 2019-03-01 | 2021-09-09 | Revolution Medicines, Inc. | Bicyclic heterocyclyl compounds and uses thereof |
| EP3738593A1 (en) | 2019-05-14 | 2020-11-18 | Amgen, Inc | Dosing of kras inhibitor for treatment of cancers |
| CR20210665A (es) | 2019-05-21 | 2022-01-25 | Amgen Inc | Formas en estado sólido |
| AU2020325115A1 (en) | 2019-08-02 | 2022-03-17 | Amgen Inc. | Pyridine derivatives as KIF18A inhibitors |
| WO2021026099A1 (en) | 2019-08-02 | 2021-02-11 | Amgen Inc. | Kif18a inhibitors |
| EP4007756A1 (en) | 2019-08-02 | 2022-06-08 | Amgen Inc. | Kif18a inhibitors |
| CA3146693A1 (en) | 2019-08-02 | 2021-02-11 | Amgen Inc. | Kif18a inhibitors |
| MX2022004656A (es) | 2019-10-24 | 2022-05-25 | Amgen Inc | Derivados de piridopirimidina utiles como inhibidores de kras g12c y kras g12d en el tratamiento del cancer. |
| US11566007B2 (en) | 2019-11-04 | 2023-01-31 | Revolution Medicines, Inc. | Ras inhibitors |
| CN115873020A (zh) | 2019-11-04 | 2023-03-31 | 锐新医药公司 | Ras抑制剂 |
| KR20220109407A (ko) | 2019-11-04 | 2022-08-04 | 레볼루션 메디슨즈, 인크. | Ras 억제제 |
| CN116425742A (zh) | 2019-11-08 | 2023-07-14 | 锐新医药公司 | 双环杂芳基化合物及其用途 |
| AU2020381492A1 (en) | 2019-11-14 | 2022-05-26 | Amgen Inc. | Improved synthesis of KRAS G12C inhibitor compound |
| TW202132271A (zh) | 2019-11-14 | 2021-09-01 | 美商安進公司 | Ｋｒａｓ ｇ１２ｃ抑制劑化合物之改善的合成 |
| JP2023505100A (ja) | 2019-11-27 | 2023-02-08 | レボリューション メディシンズ インコーポレイテッド | 共有ｒａｓ阻害剤及びその使用 |
| AU2021206217A1 (en) | 2020-01-07 | 2022-09-01 | Revolution Medicines, Inc. | SHP2 inhibitor dosing and methods of treating cancer |
| IL299131A (en) | 2020-06-18 | 2023-02-01 | Revolution Medicines Inc | Methods for delaying, preventing and treating acquired resistance to RAS inhibitors |
| AU2021344830A1 (en) | 2020-09-03 | 2023-04-06 | Revolution Medicines, Inc. | Use of SOS1 inhibitors to treat malignancies with SHP2 mutations |
| CR20230165A (es) | 2020-09-15 | 2023-06-02 | Revolution Medicines Inc | Derivados indólicos como inhibidores de ras en el tratamiento del cáncer |
| JP2024501280A (ja) | 2020-12-22 | 2024-01-11 | キル・レガー・セラピューティクス・インコーポレーテッド | Ｓｏｓ１阻害剤およびその使用 |
| BR112023022819A2 (pt) | 2021-05-05 | 2024-01-16 | Revolution Medicines Inc | Compostos, composição farmacêutica, conjugados e métodos para tratar câncer em um sujeito, para tratar um distúrbio e para inibir uma proteína ras em uma célula |
| CA3217920A1 (en) | 2021-05-05 | 2022-11-10 | Andreas BUCKL | Ras inhibitors for the treatment of cancer |
| CN117500811A (zh) | 2021-05-05 | 2024-02-02 | 锐新医药公司 | 共价ras抑制剂及其用途 |
| AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
| TW202340214A (zh) | 2021-12-17 | 2023-10-16 | 美商健臻公司 | 做為shp2抑制劑之吡唑并吡𠯤化合物 |
| EP4227307A1 (en) | 2022-02-11 | 2023-08-16 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
| WO2023172940A1 (en) | 2022-03-08 | 2023-09-14 | Revolution Medicines, Inc. | Methods for treating immune refractory lung cancer |
| WO2023212596A1 (en) | 2022-04-27 | 2023-11-02 | Regeneron Pharmaceuticals, Inc. | Treatment of arthropathy based upon stratification of osteoarthritis polygenic risk score |
| WO2023240263A1 (en) | 2022-06-10 | 2023-12-14 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
| WO2024081916A1 (en) | 2022-10-14 | 2024-04-18 | Black Diamond Therapeutics, Inc. | Methods of treating cancers using isoquinoline or 6-aza-quinoline derivatives |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4552842A (en) | 1983-01-28 | 1985-11-12 | Bristol-Myers Company | Process for producing rebeccamycin |
| US5438050A (en) | 1988-02-06 | 1995-08-01 | Godecke Aktiengesellschaft | Indolocarbazole derivatives, processes for their preparation and compositions containing them |
| US5185260A (en) | 1991-08-29 | 1993-02-09 | The United States Of America As Represented By The United States Department Of Energy | Method for distinguishing normal and transformed cells using G1 kinase inhibitors |
| US5705511A (en) * | 1994-10-14 | 1998-01-06 | Cephalon, Inc. | Fused pyrrolocarbazoles |
| US5591855A (en) | 1994-10-14 | 1997-01-07 | Cephalon, Inc. | Fused pyrrolocarbazoles |
| US5475110A (en) | 1994-10-14 | 1995-12-12 | Cephalon, Inc. | Fused Pyrrolocarbazoles |
| US5594009A (en) | 1994-10-14 | 1997-01-14 | Cephalon, Inc. | Fused pyrrolocarbazoles |
| US5705711A (en) * | 1995-08-17 | 1998-01-06 | Huntsman Specialty Chemicals Corporation | Manufacture of methyl tertiary butyl ether in reactive distillation column |
| US5808060A (en) | 1995-12-11 | 1998-09-15 | Cephalon, Inc. | Fused isoindolones |
| US5616724A (en) | 1996-02-21 | 1997-04-01 | Cephalon, Inc. | Fused pyrrolo[2,3-c]carbazole-6-ones |
| PL187205B1 (pl) | 1996-08-22 | 2004-06-30 | Bristol Myers Squibb Co | Cytotoksyczne aminocukrowe i pokrewne cukrowe pochodne indolopirolokarbazoli |
| US6127401A (en) | 1998-06-05 | 2000-10-03 | Cephalon, Inc. | Bridged indenopyrrolocarbazoles |
| WO2000018407A1 (en) | 1998-09-25 | 2000-04-06 | Cephalon, Inc. | Methods for preventing/treating damage to sensory hair cells and cochlear neurons |
| US6841567B1 (en) | 1999-02-12 | 2005-01-11 | Cephalon, Inc. | Cyclic substituted fused pyrrolocarbazoles and isoindolones |
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