CN109369643B - 用于治疗病毒感染和其他疾病的吡咯并[3,2-d]嘧啶衍生物 - Google Patents
用于治疗病毒感染和其他疾病的吡咯并[3,2-d]嘧啶衍生物 Download PDFInfo
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- CN109369643B CN109369643B CN201811093750.2A CN201811093750A CN109369643B CN 109369643 B CN109369643 B CN 109369643B CN 201811093750 A CN201811093750 A CN 201811093750A CN 109369643 B CN109369643 B CN 109369643B
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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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- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TR201815062T4 (tr) | 2011-04-08 | 2018-11-21 | Janssen Sciences Ireland Uc | Viral enfeksiyonların tedavisine yönelik pirimidin deriveleri. |
| HRP20171720T1 (hr) * | 2013-06-27 | 2017-12-29 | Janssen Sciences Ireland Uc | Derivati pirolo [3,2-d] pirimidina za liječenje virusnih infekcija i drugih bolesti |
| JOP20150177B1 (ar) | 2014-08-01 | 2021-08-17 | Janssen Pharmaceutica Nv | مركبات 6 ، 7 ثاني هيدرو بيرازولو [ 1، 5 الفا ] بيرازين – 4 (5 يد) – اون واستخدامها كمنظمات الوسترية سلبية لمستقبلات ملجور 2 |
| MA44334A (fr) | 2015-10-29 | 2018-09-05 | Novartis Ag | Conjugués d'anticorps comprenant un agoniste du récepteur de type toll |
| AU2016374568B2 (en) | 2015-12-18 | 2020-08-27 | Janssen Pharmaceutica Nv | Radiolabelled mGluR2/3 PET ligands |
| HRP20201372T1 (hr) | 2015-12-18 | 2020-11-27 | Janssen Pharmaceutica Nv | Radioaktivno označeni pet mglur2/3 ligandi |
| CN109476675B (zh) * | 2016-07-01 | 2022-12-09 | 爱尔兰詹森科学公司 | 用于治疗病毒性感染的二氢吡喃并嘧啶衍生物 |
| EP3519406B1 (en) | 2016-09-29 | 2022-02-23 | Janssen Sciences Ireland Unlimited Company | Pyrimidine prodrugs for the treatment of viral infections and further diseases |
| TW201945003A (zh) * | 2018-03-01 | 2019-12-01 | 愛爾蘭商健生科學愛爾蘭無限公司 | ２，４－二胺基喹唑啉衍生物及其醫學用途 |
| US11485741B2 (en) | 2018-04-24 | 2022-11-01 | Bristol-Myers Squibb Company | Macrocyclic toll-like receptor 7 (TLR7) agonists |
| US11554120B2 (en) | 2018-08-03 | 2023-01-17 | Bristol-Myers Squibb Company | 1H-pyrazolo[4,3-d]pyrimidine compounds as toll-like receptor 7 (TLR7) agonists and methods and uses therefor |
| WO2020162705A1 (ko) | 2019-02-08 | 2020-08-13 | 성균관대학교산학협력단 | 톨-유사 수용체 7 또는 8 작용자와 콜레스테롤의 결합체 및 그 용도 |
| WO2021154666A1 (en) | 2020-01-27 | 2021-08-05 | Bristol-Myers Squibb Company | 1H-PYRAZOLO[4,3-d]PYRIMIDINE COMPOUNDS AS TOLL-LIKE RECEPTOR 7 (TLR7) AGONISTS |
| EP4097102A1 (en) | 2020-01-27 | 2022-12-07 | Bristol-Myers Squibb Company | 1h-pyrazolo[4,3-d]pyrimidine compounds as toll-like receptor 7 (tlr7) agonists |
| WO2021154664A1 (en) | 2020-01-27 | 2021-08-05 | Bristol-Myers Squibb Company | 1H-PYRAZOLO[4,3-d]PYRIMIDINE COMPOUNDS AS TOLL-LIKE RECEPTOR 7 (TLR7) AGONISTS |
| WO2021154663A1 (en) | 2020-01-27 | 2021-08-05 | Bristol-Myers Squibb Company | 1H-PYRAZOLO[4,3-d]PYRIMIDINE COMPOUNDS AS TOLL-LIKE RECEPTOR 7 (TLR7) AGONISTS |
| KR20220132602A (ko) | 2020-01-27 | 2022-09-30 | 브리스톨-마이어스 스큅 컴퍼니 | 톨-유사 수용체 7 (TLR7) 효능제로서의 1H-피라졸로[4,3-d]피리미딘 화합물 |
| EP4097103A1 (en) | 2020-01-27 | 2022-12-07 | Bristol-Myers Squibb Company | 1h-pyrazolo[4,3-d]pyrimidine compounds as toll-like receptor 7 (tlr7) agonists |
| CN115135655B (zh) | 2020-01-27 | 2024-07-02 | 百时美施贵宝公司 | 作为Toll样受体7(TLR7)激动剂的1H-吡唑并[4,3-d]嘧啶化合物 |
| CN115151546A (zh) | 2020-01-27 | 2022-10-04 | 百时美施贵宝公司 | 作为Toll样受体7(TLR7)激动剂的C3-取代的1H-吡唑并[4,3-d]嘧啶化合物 |
| WO2021154668A1 (en) | 2020-01-27 | 2021-08-05 | Bristol-Myers Squibb Company | 1H-PYRAZOLO[4,3-d]PYRIMIDINE COMPOUNDS AS TOLL-LIKE RECEPTOR 7 (TLR7) AGONISTS |
| US20230100429A1 (en) | 2020-03-02 | 2023-03-30 | Progeneer Inc. | Live-pathogen-mimetic nanoparticles based on pathogen cell wall skeleton, and production method thereof |
| CN116056725A (zh) | 2020-08-04 | 2023-05-02 | 蛋白科技先鋒 | 活性位点暂时灭活的功能性药物与Toll样受体7或8激动剂的缀合物及其用途 |
| JP7690222B2 (ja) | 2020-08-04 | 2025-06-10 | プロジェニア インコーポレイテッド | 動力学的制御が可能なアジュバントを含むｍＲＮＡワクチン |
| EP4194008A4 (en) | 2020-08-04 | 2025-01-08 | Progeneer Inc. | Kinetically acting adjuvant ensemble |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1970373A1 (en) * | 2005-12-02 | 2008-09-17 | Mitsubishi Tanabe Pharma Corporation | Alicyclic heterocyclic compound |
| JP2008222557A (ja) * | 2007-03-08 | 2008-09-25 | Kotobuki Seiyaku Kk | ピロロ［３，２−ｄ］ピリミジン誘導体及びこれを有効成分とする医薬組成物 |
| CN103342682A (zh) * | 2007-11-22 | 2013-10-09 | 阿斯利康(瑞典)有限公司 | 用于制备嘧啶衍生物的中间体 |
Family Cites Families (84)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2610889B2 (ja) | 1987-09-03 | 1997-05-14 | 日本臓器製薬株式会社 | 新規架橋アデニン誘導体 |
| DE69731823T2 (de) | 1996-07-03 | 2005-12-15 | Sumitomo Pharmaceuticals Co., Ltd. | Neue purinderivate |
| JP3621706B2 (ja) | 1996-08-28 | 2005-02-16 | ファイザー・インク | 置換された６，５―ヘテロ―二環式誘導体 |
| EP0989129B1 (en) | 1996-10-04 | 2002-12-11 | Kyorin Pharmaceutical Co., Ltd. | Pyrazolopyridylpyridazinone derivatives and process for the preparation thereof |
| AR012634A1 (es) | 1997-05-02 | 2000-11-08 | Sugen Inc | Compuesto basado en quinazolina, composicion famaceutica que lo comprende, metodo para sintetizarlo, su uso, metodos de modulacion de la funcion deserina/treonina proteinaquinasa con dicho compuesto y metodo in vitro para identificar compuestos que modulan dicha funcion |
| US6339089B2 (en) | 1997-08-13 | 2002-01-15 | Fujirebio Inc. | Pyrimidine nucleus-containing compound and a medicament containing the same for a blood oxygen partial pressure amelioration, and a method for preparing the same |
| AU732361B2 (en) | 1997-11-28 | 2001-04-26 | Dainippon Sumitomo Pharma Co., Ltd. | Novel heterocyclic compounds |
| TW572758B (en) | 1997-12-22 | 2004-01-21 | Sumitomo Pharma | Type 2 helper T cell-selective immune response inhibitors comprising purine derivatives |
| US6187777B1 (en) * | 1998-02-06 | 2001-02-13 | Amgen Inc. | Compounds and methods which modulate feeding behavior and related diseases |
| EA200000840A1 (ru) | 1998-02-17 | 2001-02-26 | Туларик, Инк. | Антивирусные производные пиримидина |
| US6110929A (en) | 1998-07-28 | 2000-08-29 | 3M Innovative Properties Company | Oxazolo, thiazolo and selenazolo [4,5-c]-quinolin-4-amines and analogs thereof |
| JP4315300B2 (ja) | 1998-08-10 | 2009-08-19 | 大日本住友製薬株式会社 | 新規なキナゾリン誘導体 |
| JP4342007B2 (ja) | 1998-08-10 | 2009-10-14 | 大日本住友製薬株式会社 | キナゾリン誘導体 |
| JP4497340B2 (ja) | 1998-08-27 | 2010-07-07 | 大日本住友製薬株式会社 | ピリミジン誘導体 |
| US6583148B1 (en) | 1999-04-08 | 2003-06-24 | Krenitsky Pharmaceuticals, Inc. | Neurotrophic substituted pyrimidines |
| CA2323008C (en) | 1999-10-11 | 2005-07-12 | Pfizer Inc. | Pharmaceutically active compounds |
| WO2002088079A2 (en) | 2001-05-01 | 2002-11-07 | Bristol-Myers Squibb Company | Dual inhibitors of pde 7 and pde 4 |
| WO2003055890A1 (en) | 2001-12-21 | 2003-07-10 | Bayer Pharmaceuticals Corporation | Thienopyrimidine derivative compounds as inhibitors of prolylpeptidase, inducers of apoptosis and cancer treatment agents |
| US7091232B2 (en) | 2002-05-21 | 2006-08-15 | Allergan, Inc. | 4-(substituted cycloalkylmethyl) imidazole-2-thiones, 4-(substituted cycloalkenylmethyl) imidazole-2-thiones, 4-(substituted cycloalkylmethyl) imidazol-2-ones and 4-(substituted cycloalkenylmethyl) imidazol-2-ones and related compounds |
| TW200407143A (en) | 2002-05-21 | 2004-05-16 | Bristol Myers Squibb Co | Pyrrolotriazinone compounds and their use to treat diseases |
| EP1552842A1 (en) | 2002-06-07 | 2005-07-13 | Kyowa Hakko Kogyo Co., Ltd. | Bicyclic pyrimidine derivatives |
| AU2003271064B2 (en) | 2002-09-27 | 2010-06-17 | Dainippon Sumitomo Pharma Co., Ltd. | Novel adenine compound and use thereof |
| US8455458B2 (en) | 2002-10-16 | 2013-06-04 | Arthrodynamic Technologies, Animal Health Division, Inc. | Composition and method for treating connective tissue damage |
| MXPA05013922A (es) | 2003-06-20 | 2006-02-24 | Coley Pharm Group Inc | Antagonistas de receptor tipo toll de molecula pequena. |
| OA13310A (en) | 2003-09-05 | 2007-04-13 | Anadys Pharmaceuticals Inc | TLR7 ligands for the treatment of hepatitis C. |
| EP1728792A4 (en) | 2004-03-26 | 2010-12-15 | Dainippon Sumitomo Pharma Co | 8-OXOADENINE COMPOUND |
| MXPA06011080A (es) | 2004-03-26 | 2007-04-16 | Astrazeneca Ab | Compuesto de 8-oxoadenina 9-sustituido. |
| WO2007084413A2 (en) | 2004-07-14 | 2007-07-26 | Ptc Therapeutics, Inc. | Methods for treating hepatitis c |
| ES2442857T3 (es) | 2004-08-10 | 2014-02-13 | Janssen Pharmaceutica Nv | Derivados de 1,2,4-triazin-6-ona inhibidores de VIH |
| KR100915481B1 (ko) | 2004-11-09 | 2009-09-03 | 에프. 호프만-라 로슈 아게 | 아미노퀴나졸린 화합물 |
| US7498409B2 (en) | 2005-03-24 | 2009-03-03 | Schering Corporation | Screening assay for TLR7, TLR8 and TLR9 agonists and antagonists |
| CN101203519A (zh) | 2005-05-04 | 2008-06-18 | 辉瑞有限公司 | 用于治疗癌症和病毒感染如丙型肝炎的用作Toll样受体调节剂的2－酰氨基－6－氨基－8－氧代嘌呤衍生物 |
| WO2006122003A2 (en) * | 2005-05-05 | 2006-11-16 | Ardea Biosciences, Inc. | Diaryl-purine, azapurines and -deazapurines as non-nucleoside reverse transcriptase inhibitors for treatment of hiv |
| AR054122A1 (es) | 2005-05-12 | 2007-06-06 | Tibotec Pharm Ltd | Pirido[2,3-d]pirimidas utiles como inhibidores de hcv, y metodos para la preparacion de las mismas |
| US7994360B2 (en) | 2005-05-16 | 2011-08-09 | Xtl Biopharmaceuticals Ltd. | Benzofuran compounds |
| ES2612890T3 (es) | 2005-09-01 | 2017-05-19 | F. Hoffmann-La Roche Ag | Diaminopirimidinas como moduladores de P2X3 y P2X2/3 |
| JPWO2007034881A1 (ja) | 2005-09-22 | 2009-03-26 | 大日本住友製薬株式会社 | 新規アデニン化合物 |
| WO2007056208A2 (en) | 2005-11-02 | 2007-05-18 | Cytovia, Inc. | N-arylalkyl-thienopyrimidin-4-amines and analogs as activators of caspases and inducers of apoptosis and the use thereof |
| CA2640672A1 (en) | 2006-02-17 | 2007-08-23 | Pfizer Limited | 3 -deazapurine derivatives as tlr7 modulators |
| WO2008009077A2 (en) | 2006-07-20 | 2008-01-24 | Gilead Sciences, Inc. | 4,6-dl- and 2,4,6-trisubstituted quinazoline derivatives and pharmaceutical compositions useful for treating viral infections |
| WO2008009078A2 (en) | 2006-07-20 | 2008-01-24 | Gilead Sciences, Inc. | 4,6-dl- and 2,4,6-trisubstituted quinazoline derivatives useful for treating viral infections |
| WO2008073785A2 (en) | 2006-12-07 | 2008-06-19 | Genentech, Inc. | Phosphoinositide 3-kinase inhibitor compounds and methods of use |
| EP2121707B1 (en) | 2006-12-20 | 2012-12-05 | Istituto di Ricerche di Biologia Molecolare P. Angeletti S.R.L. | Antiviral indoles |
| EA019151B1 (ru) | 2007-02-07 | 2014-01-30 | Дзе Регентс Оф Дзе Юниверсити Оф Калифорния | Конъюгаты синтетических агонистов tlr и их применение |
| DK2132209T3 (da) | 2007-03-19 | 2014-04-14 | Astrazeneca Ab | 9-substituerede 8-oxo-adeninforbindelser som modulatorer af tlr7 (toll-like receptor 7) |
| EP2138497A4 (en) | 2007-03-20 | 2012-01-04 | Dainippon Sumitomo Pharma Co | NEW ADENINE CONNECTION |
| AR065784A1 (es) * | 2007-03-20 | 2009-07-01 | Dainippon Sumitomo Pharma Co | Derivados de 8-oxo adenina,medicamentos que los contienen y usos como agentes terapeuticos para enfermedades alergicas, antivirales o antibacterianas. |
| CA2687821C (en) | 2007-05-22 | 2015-04-14 | Boehringer Ingelheim International Gmbh | Benzimidazolone chymase inhibitors |
| JP5395068B2 (ja) | 2007-06-29 | 2014-01-22 | ギリアード サイエンシーズ， インコーポレイテッド | トール様受容体７の調節物質としてのプリン誘導体およびその使用 |
| CN101842098A (zh) | 2007-08-10 | 2010-09-22 | 基因实验室技术有限公司 | 用于治疗病毒感染的含氮的二环化学实体 |
| BRPI0815979A2 (pt) | 2007-08-28 | 2017-06-13 | Irm Llc | compostos e composições com inibidores de quinase, bem como uso dos mesmos |
| WO2009030998A1 (en) | 2007-09-05 | 2009-03-12 | Coley Pharmaceutical Group, Inc. | Pyrimidine compounds as toll-like receptor (tlr) agonists |
| PL2238142T3 (pl) | 2007-12-24 | 2012-11-30 | Janssen R&D Ireland | Makrocykliczne indole jako inhibitory wirusa zapalenia wątroby typu C |
| JP2011511073A (ja) | 2008-02-07 | 2011-04-07 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Ｔｌｒ７活性化物質による膀胱の疾患の治療 |
| EP2271345B1 (en) | 2008-04-28 | 2015-05-20 | Merck Sharp & Dohme Corp. | Hcv ns3 protease inhibitors |
| WO2009157560A1 (ja) | 2008-06-27 | 2009-12-30 | 京セラ株式会社 | ユーザインタフェース生成装置 |
| US8946239B2 (en) | 2008-07-10 | 2015-02-03 | Duquesne University Of The Holy Spirit | Substituted pyrrolo, -furano, and cyclopentylpyrimidines having antimitotic and/or antitumor activity and methods of use thereof |
| UY31982A (es) | 2008-07-16 | 2010-02-26 | Boehringer Ingelheim Int | Derivados de 1,2-dihidropiridin-3-carboxamidas n-sustituidas |
| JP5913093B2 (ja) | 2009-05-21 | 2016-04-27 | アストラゼネカ アクチボラグ | 新規ピリミジン誘導体と、癌とさらなる疾患の治療におけるそれらの使用 |
| US8637525B2 (en) | 2009-07-31 | 2014-01-28 | Bristol-Myers Squibb Company | Compounds for the reduction of beta-amyloid production |
| TWI468402B (zh) | 2009-07-31 | 2015-01-11 | 必治妥美雅史谷比公司 | 降低β－類澱粉生成之化合物 |
| CN102666537A (zh) | 2009-10-20 | 2012-09-12 | 艾格尔生物制药股份有限公司 | 治疗黄病毒科病毒感染的氮杂吲唑 |
| SI2491035T1 (sl) | 2009-10-22 | 2017-10-30 | Gilead Sciences, Inc. | Derivati purina ali deazapurina uporabni za zdravljenje (med drugimi) virusnih okužb |
| KR101094446B1 (ko) | 2009-11-19 | 2011-12-15 | 한국과학기술연구원 | 단백질 키나아제 저해활성을 가지는 2,4,7-치환된 티에노［3,2-ｄ］피리미딘 화합물 |
| JP2013032290A (ja) | 2009-11-20 | 2013-02-14 | Dainippon Sumitomo Pharma Co Ltd | 新規縮合ピリミジン誘導体 |
| DE102010040233A1 (de) | 2010-09-03 | 2012-03-08 | Bayer Schering Pharma Aktiengesellschaft | Bicyclische Aza-Heterocyclen und ihre Verwendung |
| WO2012067269A1 (en) | 2010-11-19 | 2012-05-24 | Dainippon Sumitomo Pharma Co., Ltd. | Aminoalkoxyphenyl compounds and their use in the treatment of disease |
| WO2012066335A1 (en) | 2010-11-19 | 2012-05-24 | Astrazeneca Ab | Phenol compounds als toll -like receptor 7 agonists |
| TR201815062T4 (tr) | 2011-04-08 | 2018-11-21 | Janssen Sciences Ireland Uc | Viral enfeksiyonların tedavisine yönelik pirimidin deriveleri. |
| SMT201800152T1 (it) | 2011-05-18 | 2018-05-02 | Janssen Sciences Ireland Uc | Derivati della chinazolina per il trattamento di infezioni virali e ulteriori malattie |
| KR102025276B1 (ko) | 2011-11-09 | 2019-09-25 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | 바이러스 감염 치료를 위한 퓨린 유도체 |
| EP2812331B1 (en) | 2012-02-08 | 2019-01-02 | Janssen Sciences Ireland Unlimited Company | Piperidino-pyrimidine derivatives for the treatment of viral infections |
| LT2841428T (lt) | 2012-04-24 | 2018-12-10 | Vertex Pharmaceuticals Incorporated | Dnr-pk inhibitoriai |
| PL2872515T3 (pl) | 2012-07-13 | 2017-05-31 | Janssen Sciences Ireland Uc | Puryny makrocykliczne do leczenia infekcji wirusowych |
| UA115558C2 (uk) | 2012-08-10 | 2017-11-27 | ЯНССЕН САЙЄНСЕС АЙРЛЕНД ЮСі | Алкілпіримідинові похідні для лікування вірусних інфекцій та подальших захворювань |
| EP2712866A1 (en) | 2012-10-01 | 2014-04-02 | Centre National de la Recherche Scientifique (CNRS) | 1,2,4-triazine derivatives for the treatment of viral infections |
| CA2882786C (en) | 2012-10-05 | 2020-10-20 | Janssen Sciences Ireland Uc | Acylaminopyrimidine derivatives for the treatment of viral infections and further diseases. |
| MX386924B (es) * | 2012-10-10 | 2025-03-19 | Janssen Sciences Ireland Uc | Derivados pirrolo[3,2-d]pirimidínicos para el tratamiento de infecciones víricas y otras enfermedades. |
| EA035431B1 (ru) | 2012-11-16 | 2020-06-15 | Янссен Сайенсиз Айрлэнд Юси | Гетероциклические замещенные производные 2-амино-хиназолина в качестве модуляторов tlr7 и/или tlr8 для лечения вирусных инфекций |
| SG11201506639XA (en) | 2013-02-21 | 2015-09-29 | Janssen Sciences Ireland Uc | 2-aminopyrimidine derivatives for the treatment of viral infections |
| AU2014242954B2 (en) | 2013-03-29 | 2018-03-15 | Janssen Sciences Ireland Uc | Macrocyclic deaza-purinones for the treatment of viral infections |
| HRP20171720T1 (hr) * | 2013-06-27 | 2017-12-29 | Janssen Sciences Ireland Uc | Derivati pirolo [3,2-d] pirimidina za liječenje virusnih infekcija i drugih bolesti |
| CN105492446B (zh) | 2013-07-30 | 2018-08-03 | 爱尔兰詹森科学公司 | 用于治疗病毒性感染的噻吩并[3,2-d]嘧啶衍生物 |
| WO2016007966A2 (en) | 2014-07-11 | 2016-01-14 | Northwestern University | 2-imidazolyl-pyrimidine scaffolds as potent and selective inhibitors of neuronal nitric oxide synthase |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1970373A1 (en) * | 2005-12-02 | 2008-09-17 | Mitsubishi Tanabe Pharma Corporation | Alicyclic heterocyclic compound |
| JP2008222557A (ja) * | 2007-03-08 | 2008-09-25 | Kotobuki Seiyaku Kk | ピロロ［３，２−ｄ］ピリミジン誘導体及びこれを有効成分とする医薬組成物 |
| CN103342682A (zh) * | 2007-11-22 | 2013-10-09 | 阿斯利康(瑞典)有限公司 | 用于制备嘧啶衍生物的中间体 |
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