MX2012009613A - Compuestos de pirrolo-pirimidina como inhibidores de dk4/6. - Google Patents
Compuestos de pirrolo-pirimidina como inhibidores de dk4/6.Info
- Publication number
- MX2012009613A MX2012009613A MX2012009613A MX2012009613A MX2012009613A MX 2012009613 A MX2012009613 A MX 2012009613A MX 2012009613 A MX2012009613 A MX 2012009613A MX 2012009613 A MX2012009613 A MX 2012009613A MX 2012009613 A MX2012009613 A MX 2012009613A
- Authority
- MX
- Mexico
- Prior art keywords
- pyrrolo
- amino
- dimethyl
- pyridin
- cyclopentyl
- Prior art date
Links
- 150000004944 pyrrolopyrimidines Chemical class 0.000 title abstract description 5
- 239000003112 inhibitor Substances 0.000 title description 39
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- -1 5- (2,6-diazaspiro- [3,3] -heptan-2-carbonyl) -pyridin-2-yl-amino Chemical group 0.000 claims description 509
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- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims description 157
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- 229910052757 nitrogen Inorganic materials 0.000 claims description 106
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- 125000001424 substituent group Chemical group 0.000 claims description 30
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- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 8
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- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
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- 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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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
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| PCT/EP2011/052353 WO2011101409A1 (en) | 2010-02-19 | 2011-02-17 | Pyrrolopyrimidine compounds as inhibitors of cdk4/6 |
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| JP2015536933A (ja) | 2012-10-23 | 2015-12-24 | オンコメッド ファーマシューティカルズ インコーポレイテッド | Ｗｎｔ経路結合剤を用いて神経内分泌腫瘍を処置する方法 |
| CA2898861C (en) | 2013-01-29 | 2021-07-20 | Naurex, Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| CN105073195A (zh) | 2013-02-04 | 2015-11-18 | 昂科梅德制药有限公司 | 使用Wnt途径抑制剂进行治疗的方法及对该治疗的监测 |
| TW201444821A (zh) | 2013-03-13 | 2014-12-01 | Janssen Pharmaceutica Nv | 經取代之哌啶化合物及其作為食慾素受體調節劑之用途 |
| TW201444849A (zh) | 2013-03-13 | 2014-12-01 | Janssen Pharmaceutica Nv | 經取代的7-氮雜雙環類及其作為食慾激素受體調節劑之用途 |
| TWI621618B (zh) | 2013-03-13 | 2018-04-21 | 比利時商健生藥品公司 | 經取代２－氮雜雙環類及其作為食慾素受體調控劑之用途 |
| US9168300B2 (en) | 2013-03-14 | 2015-10-27 | Oncomed Pharmaceuticals, Inc. | MET-binding agents and uses thereof |
| JP6430483B2 (ja) | 2013-03-15 | 2018-11-28 | ジー１、セラピューティクス、インコーポレイテッドＧ１ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． | 化学療法の間の正常細胞の一時的な保護 |
| CA2906157C (en) | 2013-03-15 | 2022-05-17 | G1 Therapeutics, Inc. | Highly active anti-neoplastic and anti-proliferative agents |
| PH12015502383B1 (en) | 2013-04-19 | 2023-02-03 | Incyte Holdings Corp | Bicyclic heterocycles as fgfr inhibitors |
| EP4772247A2 (en) * | 2013-08-14 | 2026-07-08 | Novartis AG | Combination therapy comprising ribociclib and fulvestrant for the treatment of cancer |
| PT3395814T (pt) | 2013-10-25 | 2022-07-27 | Blueprint Medicines Corp | Inibidores do recetor do fator de crescimento de fibroblastos |
| WO2015108992A1 (en) | 2014-01-15 | 2015-07-23 | Blueprint Medicines Corporation | Heterobicyclic compounds and their use as fgfr4 receptor inhibitors |
| UA122479C2 (uk) | 2014-01-24 | 2020-11-25 | Дана-Фарбер Кенсер Інстітьют, Інк. | Виділена молекула антитіла, яка зв’язується з людським білком програмованої смерті-1 (pd-1) |
| PL3099717T3 (pl) | 2014-01-31 | 2019-10-31 | Novartis Ag | Cząsteczki przeciwciała dla TIM-3 i ich zastosowanie |
| EA201691765A1 (ru) | 2014-03-14 | 2016-12-30 | Новартис Аг | Молекулы антител против lag-3 и их применения |
| US20150320754A1 (en) | 2014-04-16 | 2015-11-12 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| WO2015161283A1 (en) | 2014-04-17 | 2015-10-22 | G1 Therapeutics, Inc. | Tricyclic lactams for use in hspc-sparing treatments for rb-positive abnormal cellular proliferation |
| RU2671494C2 (ru) * | 2014-05-28 | 2018-11-01 | Шанхай Фокон Фармасьютикал Ко., Лтд | Некоторые ингибиторы протеинкиназы |
| CN105294737B (zh) * | 2014-07-26 | 2019-02-12 | 广东东阳光药业有限公司 | Cdk类小分子抑制剂的化合物及其用途 |
| JP6715239B2 (ja) * | 2014-09-11 | 2020-07-01 | ヤンセン ファーマシューティカ エヌ．ベー． | 置換２−アザ二環式化合物及びオレキシン受容体調節因子としてのその使用 |
| WO2016040848A1 (en) | 2014-09-12 | 2016-03-17 | G1 Therapeutics, Inc. | Treatment of rb-negative tumors using topoisomerase inhibitors in combination with cyclin dependent kinase 4/6 inhibitors |
| EP3191098A4 (en) | 2014-09-12 | 2018-04-25 | G1 Therapeutics, Inc. | Combinations and dosing regimes to treat rb-positive tumors |
| MA41044A (fr) | 2014-10-08 | 2017-08-15 | Novartis Ag | Compositions et procédés d'utilisation pour une réponse immunitaire accrue et traitement contre le cancer |
| SG11201702401RA (en) | 2014-10-14 | 2017-04-27 | Novartis Ag | Antibody molecules to pd-l1 and uses thereof |
| CN105111201B (zh) * | 2014-10-16 | 2017-01-11 | 上海页岩科技有限公司 | 5-甲基-2-(吡啶-2-基氨基)-8H-吡啶并[2,3-d]嘧啶-7-酮化合物 |
| EP3233918A1 (en) | 2014-12-19 | 2017-10-25 | Novartis AG | Combination therapies |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| CA2976790C (en) | 2015-02-20 | 2024-02-27 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| TWI706958B (zh) | 2015-03-10 | 2020-10-11 | 美商艾杜諾生物科技公司 | 活化「干擾素基因刺激因子」依賴性訊息傳導之組合物及方法 |
| US9969719B2 (en) * | 2015-03-11 | 2018-05-15 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Substituted 2-hydrogen-pyrazole derivative serving as anticancer drug |
| US20180340025A1 (en) | 2015-07-29 | 2018-11-29 | Novartis Ag | Combination therapies comprising antibody molecules to lag-3 |
| EP3328418A1 (en) | 2015-07-29 | 2018-06-06 | Novartis AG | Combination therapies comprising antibody molecules to pd-1 |
| US20180207273A1 (en) | 2015-07-29 | 2018-07-26 | Novartis Ag | Combination therapies comprising antibody molecules to tim-3 |
| PT3370768T (pt) | 2015-11-03 | 2022-04-21 | Janssen Biotech Inc | Anticorpos que se ligam especificamente ao pd-1 e seus usos |
| CN106810536A (zh) | 2015-11-30 | 2017-06-09 | 甘李药业股份有限公司 | 一种蛋白激酶抑制剂及其制备方法和医药用途 |
| US10112924B2 (en) * | 2015-12-02 | 2018-10-30 | Astraea Therapeutics, Inc. | Piperdinyl nociceptin receptor compounds |
| CN122562777A (zh) * | 2015-12-02 | 2026-08-14 | 阿斯特来亚治疗有限责任公司 | 哌啶基痛敏肽受体化合物 |
| CN108495651A (zh) | 2015-12-17 | 2018-09-04 | 诺华股份有限公司 | 抗pd-1的抗体分子及其用途 |
| WO2017161253A1 (en) | 2016-03-18 | 2017-09-21 | Tufts Medical Center | Compositions and methods for treating and preventing metabolic disorders |
| CN105816437B (zh) | 2016-03-29 | 2018-08-03 | 深圳市药欣生物科技有限公司 | 一种帕布昔利布的药物制剂及其制备方法 |
| ES2954148T3 (es) | 2016-05-07 | 2023-11-20 | Fochon Pharmaceuticals Ltd | Ciertos inhibidores de proteína cinasa |
| WO2018005863A1 (en) | 2016-07-01 | 2018-01-04 | G1 Therapeutics, Inc. | Pyrimidine-based compounds for the treatment of cancer |
| WO2018005533A1 (en) | 2016-07-01 | 2018-01-04 | G1 Therapeutics, Inc. | Antiproliferative pyrimidine-based compounds |
| CN109789143A (zh) | 2016-07-01 | 2019-05-21 | G1治疗公司 | 基于嘧啶的抗增殖剂 |
| EP3507367A4 (en) | 2016-07-05 | 2020-03-25 | Aduro BioTech, Inc. | CYCLIC DINUCLEOTID COMPOUNDS WITH INCLUDED NUCLEIC ACIDS AND USES THEREOF |
| PE20190501A1 (es) | 2016-08-01 | 2019-04-10 | Aptinyx Inc | Moduladores nmda espiro-lactam y metodos de uso de los mismos |
| EP3490992B1 (en) * | 2016-08-01 | 2023-03-22 | Aptinyx Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| CA3031534C (en) | 2016-08-01 | 2023-10-17 | Aptinyx Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| CN110022900A (zh) | 2016-09-08 | 2019-07-16 | 蓝图药品公司 | 成纤维细胞生长因子受体4抑制剂与细胞周期蛋白依赖性激酶抑制剂的组合 |
| CN109843297A (zh) | 2016-10-20 | 2019-06-04 | 辉瑞大药厂 | 治疗pah的抗增殖剂 |
| WO2018081211A1 (en) * | 2016-10-26 | 2018-05-03 | Li George Y | Deuterated 7-cyclopentyl-n, n-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7h-pyrrolo[2,3-d]pyrimdine-6-carboxamide |
| US11865176B2 (en) | 2016-11-08 | 2024-01-09 | Dana-Farber Cancer Institute, Inc. | Compositions and methods of modulating anti-tumor immunity |
| US10676474B2 (en) | 2016-12-16 | 2020-06-09 | Cstone Pharmaceuticals | 1,6-naphthyridine derivatives as CDK4/6 inhibitor |
| JP7229162B2 (ja) | 2017-01-06 | 2023-02-27 | ジー１ セラピューティクス， インコーポレイテッド | 癌の治療に対する併用療法 |
| UY37695A (es) | 2017-04-28 | 2018-11-30 | Novartis Ag | Compuesto dinucleótido cíclico bis 2’-5’-rr-(3’f-a)(3’f-a) y usos del mismo |
| CN108794452B (zh) | 2017-05-05 | 2021-05-28 | 上海时莱生物技术有限公司 | 具有激酶抑制活性的化合物、其制备方法和用途 |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| US20200172628A1 (en) | 2017-06-22 | 2020-06-04 | Novartis Ag | Antibody molecules to cd73 and uses thereof |
| EP3645001B1 (en) | 2017-06-29 | 2024-07-03 | G1 Therapeutics, Inc. | Morphic forms of git38 and methods of manufacture thereof |
| WO2019126731A1 (en) | 2017-12-22 | 2019-06-27 | Petra Pharma Corporation | Aminopyridine derivatives as phosphatidylinositol phosphate kinase inhibitors |
| WO2019136451A1 (en) | 2018-01-08 | 2019-07-11 | G1 Therapeutics, Inc. | G1t38 superior dosage regimes |
| US12398209B2 (en) | 2018-01-22 | 2025-08-26 | Janssen Biotech, Inc. | Methods of treating cancers with antagonistic anti-PD-1 antibodies |
| PE20210455A1 (es) | 2018-01-31 | 2021-03-08 | Aptinyx Inc | Moduladores del receptor nmda espiro-lactama y usos de los mismos |
| WO2019161224A1 (en) | 2018-02-15 | 2019-08-22 | GiraFpharma LLC | Heterocyclic compounds as kinase inhibitors |
| AU2019227607C1 (en) | 2018-02-27 | 2023-07-20 | Incyte Corporation | Imidazopyrimidines and triazolopyrimidines as A2A / A2B inhibitors |
| CN111867586A (zh) * | 2018-03-13 | 2020-10-30 | 得克萨斯州大学系统董事会 | 用于治疗具有egfr激活突变的癌症的方法 |
| RS66310B1 (sr) | 2018-05-04 | 2025-01-31 | Incyte Corp | Čvrsti oblici inhibitora fgfr i procesi za njegovu pripremu |
| KR102956194B1 (ko) | 2018-05-04 | 2026-04-23 | 인사이트 코포레이션 | Fgfr 억제제의 염 |
| EP3810610A1 (en) | 2018-05-18 | 2021-04-28 | Incyte Corporation | Fused pyrimidine derivatives as a2a / a2b inhibitors |
| UY38247A (es) | 2018-05-30 | 2019-12-31 | Novartis Ag | Anticuerpos frente a entpd2, terapias de combinación y métodos de uso de los anticuerpos y las terapias de combinación |
| CN117304191A (zh) | 2018-07-05 | 2023-12-29 | 因赛特公司 | 作为a2a/a2b抑制剂的稠合吡嗪衍生物 |
| KR102962306B1 (ko) | 2018-08-24 | 2026-05-08 | 쥐원 쎄라퓨틱스, 인크. | 1,4-디아자스피로[5.5]운데칸-3-온의 개선된 합성 |
| US11066404B2 (en) | 2018-10-11 | 2021-07-20 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
| JP7598642B2 (ja) * | 2018-10-12 | 2024-12-12 | ボード オブ リージェンツ オブ ザ ユニヴァーシティー オブ ネブラスカ | ホスホジエステラーゼ阻害剤 |
| CN111100128B (zh) * | 2018-10-26 | 2022-09-06 | 广安凯特制药有限公司 | 一种瑞博西尼中间产品的合成方法及其中间体化合物 |
| EP3902805A4 (en) * | 2018-12-28 | 2023-03-01 | SPV Therapeutics Inc. | CYCLINE-DEPENDENT KINASE INHIBITORS |
| TWI829857B (zh) | 2019-01-29 | 2024-01-21 | 美商英塞特公司 | 作為a2a / a2b抑制劑之吡唑并吡啶及三唑并吡啶 |
| WO2020168197A1 (en) | 2019-02-15 | 2020-08-20 | Incyte Corporation | Pyrrolo[2,3-d]pyrimidinone compounds as cdk2 inhibitors |
| EA202192260A1 (ru) | 2019-02-15 | 2021-12-17 | Инсайт Корпорейшн | Биомаркеры циклин-зависимой киназы 2 и их применение |
| TW202100520A (zh) | 2019-03-05 | 2021-01-01 | 美商英塞特公司 | 作為cdk2 抑制劑之吡唑基嘧啶基胺化合物 |
| WO2020185532A1 (en) | 2019-03-08 | 2020-09-17 | Incyte Corporation | Methods of treating cancer with an fgfr inhibitor |
| US11919904B2 (en) | 2019-03-29 | 2024-03-05 | Incyte Corporation | Sulfonylamide compounds as CDK2 inhibitors |
| WO2020223558A1 (en) | 2019-05-01 | 2020-11-05 | Incyte Corporation | Tricyclic amine compounds as cdk2 inhibitors |
| WO2020223469A1 (en) | 2019-05-01 | 2020-11-05 | Incyte Corporation | N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-di hydro-1h-imidazo[4,5-h]quinazolin-8-amine derivatives and related compounds as cyclin-dependent kinase 2 (cdk2) inhibitors for treating cancer |
| TW202521536A (zh) | 2019-05-05 | 2025-06-01 | 美商基尼特奇公司 | Ｃｄｋ抑制劑 |
| TW202112767A (zh) | 2019-06-17 | 2021-04-01 | 美商佩特拉製藥公司 | 作為磷脂酸肌醇磷酸激酶抑制劑之胺基吡啶衍生物 |
| CN112094272A (zh) | 2019-06-18 | 2020-12-18 | 北京睿熙生物科技有限公司 | Cdk激酶抑制剂 |
| WO2021007269A1 (en) | 2019-07-09 | 2021-01-14 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| WO2021022172A1 (en) | 2019-08-01 | 2021-02-04 | Incyte Corporation | A dosing regimen for an ido inhibitor |
| WO2021030537A1 (en) | 2019-08-14 | 2021-02-18 | Incyte Corporation | Imidazolyl pyrimidinylamine compounds as cdk2 inhibitors |
| JP2022548881A (ja) | 2019-09-18 | 2022-11-22 | ノバルティス アーゲー | Ｅｎｔｐｄ２抗体、組合せ療法並びに抗体及び組合せ療法を使用する方法 |
| US12122767B2 (en) | 2019-10-01 | 2024-10-22 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| CR20220170A (es) | 2019-10-11 | 2022-10-10 | Incyte Corp | Aminas bicíclicas como inhibidoras de la cdk2 |
| GEP20247679B (en) | 2019-10-14 | 2024-10-10 | Incyte Corp | Bicyclic heterocycles as fgfr inhibitors |
| US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| MX2022006691A (es) | 2019-12-04 | 2022-09-19 | Incyte Corp | Derivados de un inhibidor de receptores del factor de crecimiento de fibroblastos (fgfr). |
| WO2021113479A1 (en) | 2019-12-04 | 2021-06-10 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| US12012409B2 (en) | 2020-01-15 | 2024-06-18 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| PH12022552347A1 (en) | 2020-03-06 | 2024-01-29 | Incyte Corp | Combination therapy comprising axl/mer and pd-1/pd-l1 inhibitors |
| CN121270550A (zh) | 2020-04-16 | 2026-01-06 | 因赛特公司 | 稠合三环kras抑制剂 |
| WO2021231526A1 (en) | 2020-05-13 | 2021-11-18 | Incyte Corporation | Fused pyrimidine compounds as kras inhibitors |
| JP7853532B2 (ja) | 2020-05-19 | 2026-04-30 | ファーマコスモス ホールディング エー／エス | 医学的障害を治療するためのサイクリン依存性キナーゼ阻害化合物 |
| US10988479B1 (en) | 2020-06-15 | 2021-04-27 | G1 Therapeutics, Inc. | Morphic forms of trilaciclib and methods of manufacture thereof |
| WO2022047093A1 (en) | 2020-08-28 | 2022-03-03 | Incyte Corporation | Vinyl imidazole compounds as inhibitors of kras |
| CN114306245A (zh) | 2020-09-29 | 2022-04-12 | 深圳市药欣生物科技有限公司 | 无定形固体分散体的药物组合物及其制备方法 |
| WO2022072783A1 (en) | 2020-10-02 | 2022-04-07 | Incyte Corporation | Bicyclic dione compounds as inhibitors of kras |
| CN112375081B (zh) * | 2020-11-23 | 2022-04-12 | 中国医学科学院医药生物技术研究所 | 具有抑制CDK4、6或9活性的吡咯[2,3-d]嘧啶衍生物及其制备方法和应用 |
| WO2022113003A1 (en) | 2020-11-27 | 2022-06-02 | Rhizen Pharmaceuticals Ag | Cdk inhibitors |
| WO2022149057A1 (en) | 2021-01-05 | 2022-07-14 | Rhizen Pharmaceuticals Ag | Cdk inhibitors |
| WO2022155941A1 (en) | 2021-01-25 | 2022-07-28 | Qilu Regor Therapeutics Inc. | Cdk2 inhibitors |
| WO2022206888A1 (en) | 2021-03-31 | 2022-10-06 | Qilu Regor Therapeutics Inc. | Cdk2 inhibitors and use thereof |
| EP4323405A1 (en) | 2021-04-12 | 2024-02-21 | Incyte Corporation | Combination therapy comprising an fgfr inhibitor and a nectin-4 targeting agent |
| TW202313610A (zh) | 2021-06-09 | 2023-04-01 | 美商英塞特公司 | 作為ｆｇｆｒ抑制劑之三環雜環 |
| CA3220274A1 (en) | 2021-06-09 | 2022-12-15 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| US11981671B2 (en) | 2021-06-21 | 2024-05-14 | Incyte Corporation | Bicyclic pyrazolyl amines as CDK2 inhibitors |
| WO2023283213A1 (en) | 2021-07-07 | 2023-01-12 | Incyte Corporation | Tricyclic compounds as inhibitors of kras |
| CA3224841A1 (en) | 2021-07-14 | 2023-01-19 | Zhenwu Li | Tricyclic compounds as inhibitors of kras |
| KR20240040768A (ko) | 2021-07-26 | 2024-03-28 | 셀퀴티 인크. | 암의 치료에 사용하기 위한 1-(4-｛[4-(디메틸아미노)피페리딘-1-일]카르보닐｝페닐)-3-[4-(4,6-디모르폴린-4-일-1,3,5-트리아진-2-일)페닐]우레아 (게다톨리십) 및 그의 조합물 |
| CA3229855A1 (en) | 2021-08-31 | 2023-03-09 | Incyte Corporation | Naphthyridine compounds as inhibitors of kras |
| WO2023036252A1 (zh) * | 2021-09-08 | 2023-03-16 | 希格生科（深圳）有限公司 | 吡咯并嘧啶类或吡咯并吡啶类衍生物及其医药用途 |
| US12030883B2 (en) | 2021-09-21 | 2024-07-09 | Incyte Corporation | Hetero-tricyclic compounds as inhibitors of KRAS |
| US12030884B2 (en) | 2021-10-01 | 2024-07-09 | Incyte Corporation | Pyrazoloquinoline KRAS inhibitors |
| KR20240101561A (ko) | 2021-10-14 | 2024-07-02 | 인사이트 코포레이션 | Kras의 저해제로서의 퀴놀린 화합물 |
| MX2024006113A (es) | 2021-11-22 | 2024-07-29 | Incyte Corp | Terapia de combinación que comprende un inhibidor del receptor del factor de crecimiento de fibroblastos (fgfr) y un inhibidor del sarcoma de rata de kirsten (kras). |
| TW202329937A (zh) | 2021-12-03 | 2023-08-01 | 美商英塞特公司 | 雙環胺ｃｋ１２抑制劑 |
| US11976073B2 (en) | 2021-12-10 | 2024-05-07 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
| US12084453B2 (en) | 2021-12-10 | 2024-09-10 | Incyte Corporation | Bicyclic amines as CDK12 inhibitors |
| CR20240297A (es) | 2021-12-22 | 2024-09-18 | Incyte Corp | Sales y formas sólidas de un inhibidor de fgfr y procesos para su preparación |
| TW202341982A (zh) | 2021-12-24 | 2023-11-01 | 大陸商上海齊魯銳格醫藥研發有限公司 | Ｃｄｋ２抑制劑及其用途 |
| WO2023168686A1 (en) | 2022-03-11 | 2023-09-14 | Qilu Regor Therapeutics Inc. | Substituted cyclopentanes as cdk2 inhibitors |
| JP2025512710A (ja) | 2022-03-07 | 2025-04-22 | インサイト・コーポレイション | Ｃｄｋ２阻害剤の固体形態、塩、ならびに調製プロセス |
| WO2023213271A1 (en) * | 2022-05-05 | 2023-11-09 | Beigene , Ltd. | Heterocyclic compounds, compositions thereof, and methods of treatment therewith |
| TW202413359A (zh) | 2022-06-22 | 2024-04-01 | 美商英塞特公司 | 雙環胺ｃｄｋ１２抑制劑 |
| US20240101557A1 (en) | 2022-07-11 | 2024-03-28 | Incyte Corporation | Fused tricyclic compounds as inhibitors of kras g12v mutants |
| US20260034111A1 (en) * | 2022-07-25 | 2026-02-05 | Cayman Chemical Company Incorporated | NOVEL HETEROCYCLES AS sPLA2-X INHIBITORS |
| EP4561552A4 (en) * | 2022-07-29 | 2026-07-15 | Cedilla Therapeutics Inc | CDK2 INHIBITORS AND THEIR METHODS OF USE |
| US20240390340A1 (en) | 2023-04-18 | 2024-11-28 | Incyte Corporation | Pyrrolidine kras inhibitors |
| KR20260011682A (ko) | 2023-04-18 | 2026-01-23 | 인사이트 코포레이션 | 2-아자비사이클로[2.2.1]헵탄 kras 억제제 |
| WO2024254245A1 (en) | 2023-06-09 | 2024-12-12 | Incyte Corporation | Bicyclic amines as cdk2 inhibitors |
| US20250163079A1 (en) | 2023-11-01 | 2025-05-22 | Incyte Corporation | Kras inhibitors |
| WO2025129002A1 (en) | 2023-12-13 | 2025-06-19 | Incyte Corporation | Bicyclooctane kras inhibitors |
| US20260053814A1 (en) | 2024-08-21 | 2026-02-26 | Celcuity Inc. | Treatment regimens for gedatolisib in hormonally-driven disorders |
| WO2026060143A1 (en) | 2024-09-11 | 2026-03-19 | Incyte Corporation | Kras inhibitors |
| WO2026076207A1 (en) | 2024-10-04 | 2026-04-09 | Incyte Corporation | Tricyclic heteroaryl compounds as inhibitors of tyk2 and/or jak1 |
| US20260116888A1 (en) | 2024-10-31 | 2026-04-30 | Novartis Ag | Cyclin-dependent kinase inhibitors |
| US20260125391A1 (en) | 2024-11-04 | 2026-05-07 | Incyte Corporation | Pyrimidine indoles as cdk4 inhibitors |
| WO2026107031A1 (en) | 2024-11-13 | 2026-05-21 | Incyte Corporation | Kras inhibitors |
| US20260209246A1 (en) | 2025-01-23 | 2026-07-23 | Incyte Corporation | Furanyl or thienyl pyrimidines as cdk4 inhibitors |
Family Cites Families (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT72878B (en) | 1980-04-24 | 1983-03-29 | Merck & Co Inc | Process for preparing mannich-base hydroxamic acid pro-drugs for the improved delivery of non-steroidal anti-inflammatory agents |
| KR100714519B1 (ko) | 2002-03-07 | 2007-05-07 | 에프. 호프만-라 로슈 아게 | 이환 피리딘 및 피리미딘 ｐ38 키나아제 억제제 |
| EP1590341B1 (en) | 2003-01-17 | 2009-06-17 | Warner-Lambert Company LLC | 2-aminopyridine substituted heterocycles as inhibitors of cellular proliferation |
| CA2755297A1 (en) | 2003-02-10 | 2004-08-26 | Vertex Pharmaceuticals Incorporated | Processes for the preparation of n-heteroaryl-n-aryl-amines by reacting an n-aryl carbamic acid ester with a halo-heteroaryl and analogous processes |
| EA200600372A1 (ru) | 2003-09-05 | 2006-08-25 | Ньюроджин Корпорейшн | Конденсированные с гетероарилом пиридины, пиразины и пиримидины в качестве лигандов рецептора кортикотропин-рилизинг-фактора (crf 1) |
| SG146624A1 (en) | 2003-09-11 | 2008-10-30 | Kemia Inc | Cytokine inhibitors |
| MXPA06005578A (es) | 2003-11-17 | 2006-08-11 | Pfizer Prod Inc | Compuestos de pirrolopirimidina utiles en el tratamiento del cancer. |
| US7319102B1 (en) | 2003-12-09 | 2008-01-15 | The Procter & Gamble Company | Pyrrolo[2,3-d]pyrimidine cytokine inhibitors |
| AR049769A1 (es) * | 2004-01-22 | 2006-09-06 | Novartis Ag | Derivados de pirazolo(1,5-a)pirimidin 7-il-amina para utilizarse en el tratamiento de enfermedades dependientes de la quinasa de proteina |
| PL1713806T3 (pl) | 2004-02-14 | 2013-09-30 | Irm Llc | Związki i kompozycje jako inhibitory kinaz białkowych |
| CN1926140A (zh) | 2004-03-05 | 2007-03-07 | 大正制药株式会社 | 吡咯并嘧啶衍生物 |
| PL2253614T3 (pl) | 2004-04-07 | 2013-03-29 | Novartis Ag | Inhibitory IAP |
| WO2005107760A1 (en) | 2004-04-30 | 2005-11-17 | Irm Llc | Compounds and compositions as inducers of keratinocyte differentiation |
| JP2008506761A (ja) | 2004-07-22 | 2008-03-06 | アステックス、セラピューティックス、リミテッド | プロテインキナーゼ阻害剤としてのチアゾールおよびイソチアゾール誘導体 |
| WO2006042102A2 (en) | 2004-10-05 | 2006-04-20 | Neurogen Corporation | Pyrrolo-pyridine, pyrrolo-pyrimidine and related heterocyclic compounds |
| BRPI0517272A (pt) | 2004-10-29 | 2008-10-07 | Tibotec Pharm Ltd | derivados de pirimidina bicìclicos de inibição de hiv |
| US7521446B2 (en) | 2005-01-13 | 2009-04-21 | Signal Pharmaceuticals, Llc | Haloaryl substituted aminopurines, compositions thereof, and methods of treatment therewith |
| US7723340B2 (en) | 2005-01-13 | 2010-05-25 | Signal Pharmaceuticals, Llc | Haloaryl substituted aminopurines, compositions thereof, and methods of treatment therewith |
| JP5190271B2 (ja) | 2005-01-14 | 2013-04-24 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | キナーゼ阻害剤としての５員の環付加複素環式ピリミジン |
| WO2006091737A1 (en) | 2005-02-24 | 2006-08-31 | Kemia, Inc. | Modulators of gsk-3 activity |
| JP2006241089A (ja) | 2005-03-04 | 2006-09-14 | Astellas Pharma Inc | ピロロピリミジン誘導体またはその塩 |
| AU2006259936B2 (en) | 2005-06-20 | 2010-08-12 | Astrazeneca Ab | Process for the preparation of 3,7-dihydroxy-1,5-diazacyclooctanes |
| DE102005030051A1 (de) | 2005-06-27 | 2006-12-28 | Grünenthal GmbH | Substituierte 1-Oxa-3,8-diazaspiro[4,5]-decan-2-on-Verbindungen und deren Verwendung zur Herstellung von Arzneimitteln |
| WO2007030438A2 (en) | 2005-09-06 | 2007-03-15 | Pharmacopeia, Inc. | Aminopurine derivatives for treating neurodegenerative diseases |
| GB0520164D0 (en) | 2005-10-04 | 2005-11-09 | Novartis Ag | Organic compounds |
| EP1932844B1 (en) | 2005-10-06 | 2015-09-02 | Nippon Soda Co., Ltd. | Cross-linked cyclic amine compounds and agents for pest control |
| WO2007058990A2 (en) | 2005-11-14 | 2007-05-24 | Kemia, Inc. | Therapy using cytokine inhibitors |
| GB0526246D0 (en) | 2005-12-22 | 2006-02-01 | Novartis Ag | Organic compounds |
| WO2007075783A2 (en) | 2005-12-22 | 2007-07-05 | Wyeth | Substituted isoquinoline-1,3(2h,4h)-diones, 1-thioxo-1,4-dihydro-2h-isoquinoline-3-ones and 1,4-dihydro-3(2h)-isoquinolones and use thereof as kinase inhibitor |
| EP1991547A2 (en) | 2006-03-09 | 2008-11-19 | Pharmacopeia, Inc. | 8-heteroarylpurine mnk2 inhibitors for treating metabolic disorders |
| WO2007125405A2 (en) | 2006-05-01 | 2007-11-08 | Pfizer Products Inc. | Substituted 2-amino-fused heterocyclic compounds |
| TWI398252B (zh) * | 2006-05-26 | 2013-06-11 | 諾華公司 | 吡咯并嘧啶化合物及其用途 |
| WO2008135232A1 (en) * | 2007-05-02 | 2008-11-13 | Riccardo Cortese | Use and compositions of purine derivatives for the treatment of proliferative disorders |
| WO2009049028A1 (en) | 2007-10-09 | 2009-04-16 | Targegen Inc. | Pyrrolopyrimidine compounds and their use as janus kinase modulators |
| EP2209789B1 (en) | 2007-11-20 | 2011-11-16 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine hcv ns5b inhibitors |
| AU2008343932B2 (en) | 2007-12-19 | 2013-08-15 | Amgen Inc. | Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors |
| UY31631A1 (es) | 2008-02-06 | 2009-09-30 | Nuevos derivados de 7-fenil-7h-pirrolo-[2,3d]-pirimidin-2-il-amino, sales de los mismos, procesos para su preparacion, composiciones farmacéuticas que los comprenden y aplicaciones | |
| WO2009115084A2 (de) | 2008-03-20 | 2009-09-24 | Schebo Biotech Ag | Neue pyrrolopyrimidin-derivate und deren verwendungen |
| AU2009284098B2 (en) | 2008-08-22 | 2012-03-29 | Astex Therapeutics Ltd. | Pyrrolopyrimidine compounds as CDK inhibitors |
| UY33226A (es) | 2010-02-19 | 2011-09-30 | Novartis Ag | Compuestos de pirrolopirimidina deuterada como inhibidores de la cdk4/6 |
| US20130035336A1 (en) | 2010-04-13 | 2013-02-07 | Novartis Ag | Combination comprising a cyclin dependent kinase 4 or cyclin dependent kinase (cdk4/6) inhibitor for treating cancer |
| AR083797A1 (es) | 2010-11-10 | 2013-03-20 | Novartis Ag | Succinato de dimetil-amida del acido 7-ciclopentil-2-(5-piperazin-1-il-piridin-2-il-amino)-7h-pirrolo-[2,3-d]pirimidin-6-carboxilico, proceso para prepararla, intermediarios de dicha sintesis y proceso de preparacion de los mismos |
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