EA035327B1 - Производные пирроло[3,2-d]пиримидина для лечения вирусных инфекций и других заболеваний - Google Patents
Производные пирроло[3,2-d]пиримидина для лечения вирусных инфекций и других заболеваний Download PDFInfo
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- EA035327B1 EA035327B1 EA201590663A EA201590663A EA035327B1 EA 035327 B1 EA035327 B1 EA 035327B1 EA 201590663 A EA201590663 A EA 201590663A EA 201590663 A EA201590663 A EA 201590663A EA 035327 B1 EA035327 B1 EA 035327B1
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- MWXBFHJQWUXYMG-UHFFFAOYSA-N n-methyl-1,2-oxazol-3-amine;hydrochloride Chemical compound Cl.CNC=1C=CON=1 MWXBFHJQWUXYMG-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- 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
- C07D487/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Virology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12187994 | 2012-10-10 | ||
| PCT/EP2013/070990 WO2014056953A1 (en) | 2012-10-10 | 2013-10-09 | Pyrrolo[3,2-d]pyrimidine derivatives for the treatment of viral infections and other diseases |
Publications (2)
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| EA201590663A1 EA201590663A1 (ru) | 2015-07-30 |
| EA035327B1 true EA035327B1 (ru) | 2020-05-28 |
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| EA201590663A EA035327B1 (ru) | 2012-10-10 | 2013-10-09 | Производные пирроло[3,2-d]пиримидина для лечения вирусных инфекций и других заболеваний |
| EA202090662A EA202090662A3 (ru) | 2012-10-10 | 2013-10-09 | ПРОИЗВОДНЫЕ ПИРРОЛО[3,2-d]ПИРИМИДИНА ДЛЯ ЛЕЧЕНИЯ ВИРУСНЫХ ИНФЕКЦИЙ И ДРУГИХ ЗАБОЛЕВАНИЙ |
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| EA202090662A EA202090662A3 (ru) | 2012-10-10 | 2013-10-09 | ПРОИЗВОДНЫЕ ПИРРОЛО[3,2-d]ПИРИМИДИНА ДЛЯ ЛЕЧЕНИЯ ВИРУСНЫХ ИНФЕКЦИЙ И ДРУГИХ ЗАБОЛЕВАНИЙ |
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Families Citing this family (179)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY170941A (en) | 2011-04-08 | 2019-09-19 | Janssen Sciences Ireland Uc | Pyrimidine derivatives for the treatment of viral infections |
| JP6349256B2 (ja) | 2011-11-09 | 2018-06-27 | ヤンセン・サイエンシズ・アイルランド・ユーシー | ウイルス感染の治療のためのプリン誘導体 |
| WO2014009509A1 (en) | 2012-07-13 | 2014-01-16 | Janssen R&D Ireland | Macrocyclic purines for the treatment of viral infections |
| NO2906563T3 (enExample) * | 2012-10-10 | 2018-07-28 | ||
| US9663474B2 (en) | 2012-11-16 | 2017-05-30 | Janssen Sciences Ireland Uc | Heterocyclic substituted 2-amino quinazoline derivatives for the treatment of viral infections |
| CN105189468B (zh) | 2013-02-21 | 2018-10-30 | 爱尔兰詹森科学公司 | 用于治疗病毒性感染的2-氨基嘧啶衍生物 |
| MX366481B (es) | 2013-03-29 | 2019-07-09 | Janssen Sciences Ireland Uc | Deaza-purinonas macrociclicas para el tratamiento de infecciones virales. |
| AU2014270418B2 (en) | 2013-05-24 | 2017-11-30 | Janssen Sciences Ireland Uc | Pyridone derivatives for the treatment of viral infections and further diseases |
| CN105473592B (zh) * | 2013-06-27 | 2018-10-26 | 爱尔兰詹森科学公司 | 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 |
| MY179503A (en) | 2013-07-30 | 2020-11-09 | Janssen Sciences Ireland Uc | Thieno[3,2-d]pyrimidines derivatives for the treatment of viral infections |
| EA032487B1 (ru) | 2014-05-01 | 2019-06-28 | Новартис Аг | Соединения и композиции в качестве агонистов toll-подобного рецептора 7 |
| US9902730B2 (en) * | 2014-05-01 | 2018-02-27 | Novartis Ag | Compounds and compositions as toll-like receptor 7 agonists |
| PT3190113T (pt) * | 2014-08-15 | 2021-06-17 | Chai Tai Tianqing Pharmaceutical Group Co Ltd | Compostos pirrolopirimidina utilizados como agonistas de tlr7 |
| WO2016048861A2 (en) | 2014-09-22 | 2016-03-31 | National Health Research Institutes | Heterocyclic compounds and use thereof |
| CN105732635A (zh) * | 2014-12-29 | 2016-07-06 | 南京明德新药研发股份有限公司 | 一类Toll样受体7激动剂 |
| SMT201800023T1 (it) | 2015-03-04 | 2018-03-08 | Gilead Sciences Inc | Composti 4,6-diamminopirido[3,2-d]pirimidinici modulanti i recettori di tipo toll |
| WO2017004133A1 (en) * | 2015-06-29 | 2017-01-05 | Nimbus Iris, Inc. | Irak inhibitors and uses thereof |
| EP3328859B1 (en) * | 2015-07-30 | 2020-06-03 | Boehringer Ingelheim International GmbH | 3-((4-isoquinolin-3-yl)methyl)-1h-imidazo[4,5-c]pyridin-2(3h)-one derivatives and related compounds as inhibitors of replication of the respiratory syncytial virus (rsv) |
| US20210292327A1 (en) | 2015-08-26 | 2021-09-23 | Gilead Sciences, Inc. | Deuterated toll-like receptor modulators |
| MA42818A (fr) | 2015-09-15 | 2018-07-25 | Gilead Sciences Inc | Modulateurs de récepteurs de type toll pour le traitement du vih |
| MA44334A (fr) * | 2015-10-29 | 2018-09-05 | Novartis Ag | Conjugués d'anticorps comprenant un agoniste du récepteur de type toll |
| MY196200A (en) | 2015-12-15 | 2023-03-22 | Gilead Sciences Inc | Human Immunodeficiency Virus Neutralizing Antibodies |
| CN107043378A (zh) * | 2016-02-05 | 2017-08-15 | 正大天晴药业集团股份有限公司 | 一种吡咯并[3,2-d]嘧啶类化合物的制备方法及其中间体 |
| CN107043380A (zh) * | 2016-02-05 | 2017-08-15 | 正大天晴药业集团股份有限公司 | 一种tlr7激动剂的马来酸盐、其晶型c、晶型d、晶型e、制备方法和用途 |
| CN107043377A (zh) * | 2016-02-05 | 2017-08-15 | 正大天晴药业集团股份有限公司 | 一种tlr7激动剂的三氟乙酸盐、晶型b及其制备方法、药物组合物和用途 |
| CN107043379A (zh) * | 2016-02-05 | 2017-08-15 | 正大天晴药业集团股份有限公司 | 一种tlr7激动剂的晶型a、其制备方法和医药用途 |
| BR102017010009A2 (pt) | 2016-05-27 | 2017-12-12 | Gilead Sciences, Inc. | Compounds for the treatment of hepatitis b virus infection |
| ES2969239T3 (es) | 2016-05-27 | 2024-05-17 | Gilead Sciences Inc | Combinación de ledipasvir y sofosbuvir para su uso en el tratamiento de infecciones por el virus de la hepatitis B en humanos |
| 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 |
| JOP20190024A1 (ar) | 2016-08-26 | 2019-02-19 | Gilead Sciences Inc | مركبات بيروليزين بها استبدال واستخداماتها |
| ES2826748T3 (es) | 2016-09-02 | 2021-05-19 | Gilead Sciences Inc | Derivados de 4,6-diamino-pirido[3,2-d]pirimidina como moduladores de receptores de tipo Toll |
| PT3507276T (pt) | 2016-09-02 | 2022-01-11 | Gilead Sciences Inc | Compostos moduladores do recetor de tipo toll |
| WO2018047081A1 (en) | 2016-09-09 | 2018-03-15 | Novartis Ag | Compounds and compositions as inhibitors of endosomal toll-like receptors |
| US10968184B2 (en) | 2016-09-29 | 2021-04-06 | Janssen Sciences Ireland Unlimited Company | Pyrimidine prodrugs for the treatment of viral infections and further diseases |
| FI3526323T3 (fi) | 2016-10-14 | 2023-06-06 | Prec Biosciences Inc | Hepatiitti B -viruksen genomissa oleville tunnistussekvensseille spesifisiä muokattuja meganukleaaseja |
| TWI784370B (zh) | 2017-01-31 | 2022-11-21 | 美商基利科學股份有限公司 | 替諾福韋埃拉酚胺(tenofovir alafenamide)之晶型 |
| JOP20180008A1 (ar) | 2017-02-02 | 2019-01-30 | Gilead Sciences Inc | مركبات لعلاج إصابة بعدوى فيروس الالتهاب الكبدي b |
| CN106727768A (zh) * | 2017-02-06 | 2017-05-31 | 灞卞嘲 | 一种治疗子宫内膜炎的药物组合物 |
| JOP20180040A1 (ar) | 2017-04-20 | 2019-01-30 | Gilead Sciences Inc | مثبطات pd-1/pd-l1 |
| AR112413A1 (es) * | 2017-08-17 | 2019-10-23 | Gilead Sciences Inc | Formas sólidas de un inhibidor de la cápside del vih |
| AR112412A1 (es) * | 2017-08-17 | 2019-10-23 | Gilead Sciences Inc | Formas de sal de colina de un inhibidor de la cápside del vih |
| JP6934562B2 (ja) | 2017-08-22 | 2021-09-15 | ギリアード サイエンシーズ, インコーポレイテッド | 治療用複素環式化合物 |
| WO2019084060A1 (en) | 2017-10-24 | 2019-05-02 | Silverback Therapeutics, Inc. | CONJUGATES AND METHODS OF USE FOR THE SELECTIVE DELIVERY OF IMMUNOMODULATORY AGENTS |
| CA3084667A1 (en) | 2017-12-15 | 2019-06-20 | Silverback Therapeutics, Inc. | Antibody construct-drug conjugate for the treatment of hepatitis |
| CA3084569A1 (en) | 2017-12-20 | 2019-06-27 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3' cyclic dinucleotides with phosphonate bond activating the sting adaptor protein |
| KR102492115B1 (ko) | 2017-12-20 | 2023-01-27 | 인스티튜트 오브 오가닉 케미스트리 앤드 바이오케미스트리 에이에스 씨알 브이.브이.아이. | Sting 어댑터 단백질을 활성화하는 포스포네이트 결합을 가진 2'3' 사이클릭 다이뉴클레오티드 |
| PL3752501T3 (pl) | 2018-02-13 | 2023-08-21 | Gilead Sciences, Inc. | Inhibitory pd-1/pd-l1 |
| CN111836805B (zh) | 2018-02-15 | 2023-07-14 | 吉利德科学公司 | 吡啶衍生物及其用于治疗hiv感染的用途 |
| WO2019161280A1 (en) | 2018-02-16 | 2019-08-22 | Gilead Sciences, Inc. | Methods and intermediates for preparing a therapeutic compound useful in the treatment of retroviridae viral infection |
| KR102526964B1 (ko) | 2018-02-26 | 2023-04-28 | 길리애드 사이언시즈, 인코포레이티드 | Hbv 복제 억제제로서의 치환된 피롤리진 화합물 |
| TW202415645A (zh) | 2018-03-01 | 2024-04-16 | 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 |
| US10870691B2 (en) | 2018-04-05 | 2020-12-22 | Gilead Sciences, Inc. | Antibodies and fragments thereof that bind hepatitis B virus protein X |
| TWI818007B (zh) | 2018-04-06 | 2023-10-11 | 捷克科學院有機化學與生物化學研究所 | 2'3'-環二核苷酸 |
| TW202005654A (zh) | 2018-04-06 | 2020-02-01 | 捷克科學院有機化學與生物化學研究所 | 2,2,─環二核苷酸 |
| TWI833744B (zh) | 2018-04-06 | 2024-03-01 | 捷克科學院有機化學與生物化學研究所 | 3'3'-環二核苷酸 |
| TW201945388A (zh) | 2018-04-12 | 2019-12-01 | 美商精密生物科學公司 | 對b型肝炎病毒基因體中之識別序列具有特異性之最佳化之經工程化巨核酸酶 |
| KR102591947B1 (ko) | 2018-04-19 | 2023-10-25 | 길리애드 사이언시즈, 인코포레이티드 | Pd-1/pd-l1 억제제 |
| WO2019209811A1 (en) | 2018-04-24 | 2019-10-31 | Bristol-Myers Squibb Company | Macrocyclic toll-like receptor 7 (tlr7) agonists |
| TW202014193A (zh) | 2018-05-03 | 2020-04-16 | 捷克科學院有機化學與生物化學研究所 | 包含碳環核苷酸之2’3’-環二核苷酸 |
| EP3817819B1 (en) | 2018-07-03 | 2025-06-11 | Gilead Sciences, Inc. | Antibodies that target hiv gp120 and methods of use |
| KR102629921B1 (ko) | 2018-07-06 | 2024-01-31 | 길리애드 사이언시즈, 인코포레이티드 | 치료 헤테로시클릭 화합물 |
| WO2020010200A1 (en) | 2018-07-06 | 2020-01-09 | Gilead Sciences, Inc. | Therapeutic heterocyclic compounds |
| TWI809427B (zh) | 2018-07-13 | 2023-07-21 | 美商基利科學股份有限公司 | Pd‐1/pd‐l1抑制劑 |
| TWI876477B (zh) | 2018-07-16 | 2025-03-11 | 美商基利科學股份有限公司 | 用於治療hiv之蛋白殼抑制劑 |
| WO2020028097A1 (en) | 2018-08-01 | 2020-02-06 | Gilead Sciences, Inc. | Solid forms of (r)-11-(methoxymethyl)-12-(3-methoxypropoxy)-3,3-dimethyl-8-0x0-2,3,8,13b-tetrahydro-1h-pyrido[2,1-a]pyrrolo[1,2-c] phthalazine-7-c arboxylic acid |
| 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 |
| WO2020056008A1 (en) | 2018-09-12 | 2020-03-19 | Silverback Therapeutics, Inc. | Compositions for the treatment of disease with immune stimulatory conjugates |
| WO2020072656A1 (en) | 2018-10-03 | 2020-04-09 | Gilead Sciences, Inc. | Imidozopyrimidine derivatives |
| WO2020086556A1 (en) | 2018-10-24 | 2020-04-30 | Gilead Sciences, Inc. | Pd-1/pd-l1 inhibitors |
| KR102658602B1 (ko) | 2018-10-31 | 2024-04-19 | 길리애드 사이언시즈, 인코포레이티드 | Hpk1 억제 활성을 갖는 치환된 6-아자벤즈이미다졸 화합물 |
| FI3873903T3 (fi) | 2018-10-31 | 2024-03-26 | Gilead Sciences Inc | Substituoituja 6-azabentsiimidatsoliyhdisteitä HPK1-inhibiittoreina |
| JP7637328B2 (ja) | 2019-02-07 | 2025-02-28 | ベイジーン リミテッド | Tlr7アゴニストとしてのイミダゾ[2,1-f][1,2,4]トリアジン-4-アミン誘導体 |
| WO2020176510A1 (en) | 2019-02-25 | 2020-09-03 | Gilead Sciences, Inc. | Protein kinase c agonists |
| WO2020176505A1 (en) | 2019-02-25 | 2020-09-03 | Gilead Sciences, Inc. | Protein kinase c agonists |
| US11766447B2 (en) | 2019-03-07 | 2023-09-26 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3′3′-cyclic dinucleotide analogue comprising a cyclopentanyl modified nucleotide as sting modulator |
| JP7350871B2 (ja) | 2019-03-07 | 2023-09-26 | インスティチュート オブ オーガニック ケミストリー アンド バイオケミストリー エーエスシーアール,ヴイ.ヴイ.アイ. | 2’3’-環状ジヌクレオチドおよびそのプロドラッグ |
| CA3129011C (en) | 2019-03-07 | 2023-12-19 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3'-cyclic dinucleotides and prodrugs thereof |
| CR20240238A (es) | 2019-03-22 | 2024-08-12 | Gilead Sciences Inc | Compuestos de carbamoyl piridona tricíclicos con puente y su uso farmacéutico (divisional 2021-0486) |
| TWI751516B (zh) | 2019-04-17 | 2022-01-01 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| TWI751517B (zh) | 2019-04-17 | 2022-01-01 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| TW202231277A (zh) | 2019-05-21 | 2022-08-16 | 美商基利科學股份有限公司 | 鑑別對使用gp120 v3聚醣導向之抗體的治療敏感之hiv病患的方法 |
| WO2020237025A1 (en) | 2019-05-23 | 2020-11-26 | Gilead Sciences, Inc. | Substituted exo-methylene-oxindoles which are hpk1/map4k1 inhibitors |
| CA3140708A1 (en) | 2019-06-18 | 2020-12-24 | Helen Horton | Combination of hepatitis b virus (hbv) vaccines and pyridopyrimidine derivatives |
| CA3141085A1 (en) | 2019-06-19 | 2020-12-24 | Brenda Stevens | Anti-mesothelin antibodies and immunoconjugates thereof |
| US20210009718A1 (en) | 2019-06-25 | 2021-01-14 | Gilead Sciences, Inc. | FLT3L-Fc FUSION PROTEINS AND METHODS OF USE |
| TWI879779B (zh) | 2019-06-28 | 2025-04-11 | 美商基利科學股份有限公司 | 類鐸受體調節劑化合物的製備方法 |
| CN120775062A (zh) | 2019-07-16 | 2025-10-14 | 吉利德科学公司 | Hiv疫苗及其制备和使用方法 |
| US20220257619A1 (en) | 2019-07-18 | 2022-08-18 | Gilead Sciences, Inc. | Long-acting formulations of tenofovir alafenamide |
| WO2021034804A1 (en) | 2019-08-19 | 2021-02-25 | Gilead Sciences, Inc. | Pharmaceutical formulations of tenofovir alafenamide |
| MY208114A (en) | 2019-09-30 | 2025-04-16 | Gilead Sciences Inc | Hbv vaccines and methods treating hbv |
| AU2020358726A1 (en) | 2019-10-01 | 2022-04-07 | Silverback Therapeutics, Inc. | Combination therapy with immune stimulatory conjugates |
| US11795223B2 (en) | 2019-10-18 | 2023-10-24 | Forty Seven, Inc. | Combination therapies for treating myelodysplastic syndromes and acute myeloid leukemia |
| MY209360A (en) | 2019-10-31 | 2025-07-03 | Forty Seven Llc | Anti-cd47 and anti-cd20 based treatment of blood cancer |
| TWI778443B (zh) | 2019-11-12 | 2022-09-21 | 美商基利科學股份有限公司 | Mcl1抑制劑 |
| TWI854067B (zh) | 2019-11-26 | 2024-09-01 | 美商基利科學股份有限公司 | 預防hiv之蛋白殼抑制劑 |
| EP4069729B1 (en) | 2019-12-06 | 2025-01-22 | Precision BioSciences, Inc. | Optimized engineered meganucleases having specificity for a recognition sequence in the hepatitis b virus genome |
| EP4445902A3 (en) | 2019-12-24 | 2024-12-18 | Carna Biosciences, Inc. | Diacylglycerol kinase modulating compounds |
| JP2023512207A (ja) | 2020-01-27 | 2023-03-24 | ブリストル-マイヤーズ スクイブ カンパニー | トール様受容体7(TLR7)アゴニストとしての1H-ピラゾロ[4,3-d]ピリミジン化合物 |
| US12485123B2 (en) | 2020-01-27 | 2025-12-02 | 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 |
| JP2023512208A (ja) | 2020-01-27 | 2023-03-24 | ブリストル-マイヤーズ スクイブ カンパニー | トール様受容体7(TLR7)アゴニストとしての1H-ピラゾロ[4,3-d]ピリミジン化合物 |
| 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 |
| 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 |
| KR20220132593A (ko) | 2020-01-27 | 2022-09-30 | 브리스톨-마이어스 스큅 컴퍼니 | 톨-유사 수용체 7 (TLR7) 효능제로서의 1H-피라졸로[4,3-d]피리미딘 화합물 |
| JP2023512230A (ja) | 2020-01-27 | 2023-03-24 | ブリストル-マイヤーズ スクイブ カンパニー | トール様受容体7(TLR7)アゴニストとしてのC3置換1H-ピラゾロ[4,3-d]ピリミジン化合物 |
| JP7712941B2 (ja) | 2020-01-27 | 2025-07-24 | ブリストル-マイヤーズ スクイブ カンパニー | トール様受容体7(TLR7)アゴニストとしての1H-ピラゾロ[4,3-d]ピリミジン化合物 |
| BR112022014623A2 (pt) | 2020-02-14 | 2022-09-13 | Jounce Therapeutics Inc | Anticorpos e proteínas de fusão que se ligam a ccr8 e usos dos mesmos |
| EP4106819A1 (en) | 2020-02-21 | 2022-12-28 | Silverback Therapeutics, Inc. | Nectin-4 antibody conjugates and uses thereof |
| JP2023518433A (ja) | 2020-03-20 | 2023-05-01 | ギリアード サイエンシーズ, インコーポレイテッド | 4’-c-置換-2-ハロ-2’-デオキシアデノシンヌクレオシドのプロドラッグ並びにその製造法及び使用法 |
| BR112022020769A2 (pt) | 2020-05-01 | 2022-12-20 | Gilead Sciences Inc | Compostos de 2,4-dioxopirimidina de inibição de cd73 |
| EP4153181A1 (en) | 2020-05-21 | 2023-03-29 | Gilead Sciences, Inc. | Pharmaceutical compositions comprising bictegravir |
| CN115996925A (zh) | 2020-06-25 | 2023-04-21 | 吉利德科学公司 | 用于治疗hiv的衣壳抑制剂 |
| IL299508A (en) | 2020-07-01 | 2023-02-01 | Ars Pharmaceuticals Inc | Anti-asgr1 antibody conjugates and uses thereof |
| PE20230779A1 (es) | 2020-08-07 | 2023-05-09 | Gilead Sciences Inc | Profarmacos de analogos de nucleotidos de fosfonamida y su uso farmaceutico |
| TW202406932A (zh) | 2020-10-22 | 2024-02-16 | 美商基利科學股份有限公司 | 介白素2-Fc融合蛋白及使用方法 |
| KR20230107288A (ko) | 2020-11-11 | 2023-07-14 | 길리애드 사이언시즈, 인코포레이티드 | gp120 CD4 결합 부위-지향 항체를 이용한 요법에 감수성인 HIV 환자를 식별하는 방법 |
| TW202304524A (zh) | 2021-04-10 | 2023-02-01 | 美商普方生物製藥美國公司 | Folr1結合劑、其結合物及使用方法 |
| TW202302145A (zh) | 2021-04-14 | 2023-01-16 | 美商基利科學股份有限公司 | CD47/SIRPα結合及NEDD8活化酶E1調節次單元之共抑制以用於治療癌症 |
| TW202308699A (zh) | 2021-04-23 | 2023-03-01 | 美商普方生物製藥美國公司 | Cd70結合劑、其結合物及其使用方法 |
| TW202348237A (zh) | 2021-05-13 | 2023-12-16 | 美商基利科學股份有限公司 | TLR8調節化合物及抗HBV siRNA療法之組合 |
| TW202313094A (zh) | 2021-05-18 | 2023-04-01 | 美商基利科學股份有限公司 | 使用FLT3L—Fc融合蛋白之方法 |
| EP4359413A1 (en) | 2021-06-23 | 2024-05-01 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| JP7654118B2 (ja) | 2021-06-23 | 2025-03-31 | ギリアード サイエンシーズ, インコーポレイテッド | ジアシルグリセロールキナーゼ調節化合物 |
| CA3222439A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| AU2022297373B2 (en) | 2021-06-23 | 2025-04-17 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| TW202320857A (zh) | 2021-07-06 | 2023-06-01 | 美商普方生物製藥美國公司 | 連接子、藥物連接子及其結合物及其使用方法 |
| US20230183216A1 (en) | 2021-10-28 | 2023-06-15 | Gilead Sciences, Inc. | Pyridizin-3(2h)-one derivatives |
| EP4422756A1 (en) | 2021-10-29 | 2024-09-04 | Gilead Sciences, Inc. | Cd73 compounds |
| CA3237155A1 (en) | 2021-12-03 | 2023-06-08 | Zhimin Du | Therapeutic compounds for hiv virus infection |
| US11787825B2 (en) | 2021-12-03 | 2023-10-17 | Gilead Sciences, Inc. | Therapeutic compounds for HIV virus infection |
| WO2023102523A1 (en) | 2021-12-03 | 2023-06-08 | Gilead Sciences, Inc. | Therapeutic compounds for hiv virus infection |
| WO2023107956A1 (en) | 2021-12-08 | 2023-06-15 | Dragonfly Therapeutics, Inc. | Proteins binding nkg2d, cd16 and 5t4 |
| WO2023107954A1 (en) | 2021-12-08 | 2023-06-15 | Dragonfly Therapeutics, Inc. | Antibodies targeting 5t4 and uses thereof |
| AU2022417491A1 (en) | 2021-12-22 | 2024-05-23 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
| KR20240123836A (ko) | 2021-12-22 | 2024-08-14 | 길리애드 사이언시즈, 인코포레이티드 | 이카로스 아연 핑거 패밀리 분해제 및 이의 용도 |
| TW202340168A (zh) | 2022-01-28 | 2023-10-16 | 美商基利科學股份有限公司 | Parp7抑制劑 |
| PT4245756T (pt) | 2022-03-17 | 2024-12-09 | Gilead Sciences Inc | Degradadores da família dos dedos de zinco ikaros e suas utilizações |
| CN119031937A (zh) | 2022-03-24 | 2024-11-26 | 吉利德科学公司 | 用于治疗表达Trop-2的癌症的联合疗法 |
| TWI876305B (zh) | 2022-04-05 | 2025-03-11 | 美商基利科學股份有限公司 | 用於治療結腸直腸癌之組合療法 |
| TW202446773A (zh) | 2022-04-06 | 2024-12-01 | 美商基利科學股份有限公司 | 橋聯三環胺甲醯基吡啶酮化合物及其用途 |
| PE20250157A1 (es) | 2022-04-21 | 2025-01-22 | Gilead Sciences Inc | Compuestos de modulacion de kras g12d |
| KR20250028371A (ko) | 2022-07-01 | 2025-02-28 | 길리애드 사이언시즈, 인코포레이티드 | Cd73 화합물 |
| US20240034724A1 (en) | 2022-07-01 | 2024-02-01 | Gilead Sciences, Inc. | Therapeutic compounds useful for the prophylactic or therapeutic treatment of an hiv virus infection |
| CA3259040A1 (en) | 2022-07-12 | 2024-01-18 | Gilead Sciences, Inc. | HIV Immunogenic Polypeptides and Vaccines and Their Uses |
| CA3265134A1 (en) | 2022-08-26 | 2024-02-29 | Gilead Sciences, Inc. | DOSING AND PLANNING REGIMEN FOR BROADLY NEUTRALIZING ANTIBODIES |
| US20240091351A1 (en) | 2022-09-21 | 2024-03-21 | Gilead Sciences, Inc. | FOCAL IONIZING RADIATION AND CD47/SIRPa DISRUPTION ANTICANCER COMBINATION THERAPY |
| WO2024076915A1 (en) | 2022-10-04 | 2024-04-11 | Gilead Sciences, Inc. | 4'-thionucleoside analogues and their pharmaceutical use |
| JP2025542338A (ja) | 2022-12-22 | 2025-12-25 | ギリアード サイエンシーズ, インコーポレイテッド | Prmt5阻害剤及びその使用 |
| CN120882725A (zh) | 2023-04-11 | 2025-10-31 | 吉利德科学公司 | Kras调节化合物 |
| AR132464A1 (es) | 2023-04-19 | 2025-07-02 | Gilead Sciences Inc | Régimen de dosificación de inhibidor de la cápside |
| AU2024259556A1 (en) | 2023-04-21 | 2025-10-23 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
| AU2024281548A1 (en) | 2023-05-31 | 2025-11-13 | Gilead Sciences, Inc. | Solid forms of compounds useful in the treatment of hiv |
| TW202448483A (zh) | 2023-05-31 | 2024-12-16 | 美商基利科學股份有限公司 | 用於hiv之治療性化合物 |
| US20250042922A1 (en) | 2023-06-30 | 2025-02-06 | Gilead Sciences, Inc. | Kras modulating compounds |
| TW202519517A (zh) | 2023-07-26 | 2025-05-16 | 美商基利科學股份有限公司 | Parp7抑制劑 |
| WO2025024663A1 (en) | 2023-07-26 | 2025-01-30 | Gilead Sciences, Inc. | Parp7 inhibitors |
| WO2025029247A1 (en) | 2023-07-28 | 2025-02-06 | Gilead Sciences, Inc. | Weekly regimen of lenacapavir for the treatment and prevention of hiv |
| WO2025042394A1 (en) | 2023-08-23 | 2025-02-27 | Gilead Sciences, Inc. | Dosing regimen of hiv capsid inhibitor |
| WO2025054347A1 (en) | 2023-09-08 | 2025-03-13 | Gilead Sciences, Inc. | Kras g12d modulating compounds |
| US20250109147A1 (en) | 2023-09-08 | 2025-04-03 | Gilead Sciences, Inc. | Kras g12d modulating compounds |
| WO2025072406A1 (en) | 2023-09-26 | 2025-04-03 | Profoundbio Us Co. | Ptk7 binding agents, conjugates thereof and methods of using the same |
| TW202530227A (zh) | 2023-10-11 | 2025-08-01 | 美商基利科學股份有限公司 | 橋聯三環胺甲醯基吡啶酮化合物及其用途 |
| WO2025080879A1 (en) | 2023-10-11 | 2025-04-17 | Gilead Sciences, Inc. | Bridged tricyclic carbamoylpyridone compounds and uses thereof |
| WO2025080850A1 (en) | 2023-10-11 | 2025-04-17 | Gilead Sciences, Inc. | Bridged tricyclic carbamoylpyridone compounds and uses thereof |
| US20250154172A1 (en) | 2023-11-03 | 2025-05-15 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
| CZ2023456A3 (cs) * | 2023-11-23 | 2025-04-23 | Univerzita Karlova | Substituovaný 5H-pyrrolo[3,2-d]pyrimidin a jeho použití a farmaceutický přípravek ho obsahující |
| US20250230163A1 (en) | 2023-12-22 | 2025-07-17 | Gilead Sciences, Inc. | Solid forms of hiv integrase inhibitors |
| US20250230168A1 (en) | 2023-12-22 | 2025-07-17 | Gilead Sciences, Inc. | Azaspiro wrn inhibitors |
| US20250296992A1 (en) | 2024-01-10 | 2025-09-25 | Genmab A/S | Slitrk6 binding agents, conjugates thereof and methods of using the same |
| WO2025181219A1 (en) | 2024-02-29 | 2025-09-04 | Genmab A/S | Egfr and c-met bispecific binding agents, conjugates thereof and methods of using the same |
| WO2025184609A1 (en) | 2024-03-01 | 2025-09-04 | Gilead Sciences, Inc. | Antiviral compounds |
| US20250296932A1 (en) | 2024-03-01 | 2025-09-25 | Gilead Sciences, Inc. | Pharmaceutical compositions comprising hiv integrase inhibitors |
| US20250289822A1 (en) | 2024-03-01 | 2025-09-18 | Gilead Sciences, Inc. | Solid forms of hiv integrase inhibitors |
| WO2025240242A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies with ribavirin |
| US20250345389A1 (en) | 2024-05-13 | 2025-11-13 | Gilead Sciences, Inc. | Combination therapies |
| US20250345390A1 (en) | 2024-05-13 | 2025-11-13 | Gilead Sciences, Inc. | Combination therapies |
| WO2025240246A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies with ribavirin |
| US20250376484A1 (en) | 2024-05-21 | 2025-12-11 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
| US20260007683A1 (en) | 2024-06-14 | 2026-01-08 | Gilead Sciences, Inc. | Pharmaceutical compositions comprising hiv integrase inhibitors |
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 |
| WO2009067081A1 (en) * | 2007-11-22 | 2009-05-28 | Astrazeneca Ab | Pyrimidine derivatives for the treatment of asthma, copd, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, cancer, hepatitis b, hepatitis c, hiv, hpv, bacterial infections and dermatosis |
| EP2133353A1 (en) * | 2007-03-20 | 2009-12-16 | Dainippon Sumitomo Pharma Co., Ltd. | Novel adenine compound |
Family Cites Families (81)
| 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 |
| CA2113639A1 (en) | 1991-07-25 | 1993-02-04 | Eui W. Choe | Copolyesters for high modulus fibers |
| DE69731823T2 (de) | 1996-07-03 | 2005-12-15 | Sumitomo Pharmaceuticals Co., Ltd. | Neue purinderivate |
| PL332040A1 (en) | 1996-08-28 | 1999-08-16 | Pfizer | Substitution 6,5-heterobicyclic derivatives |
| CN1083841C (zh) | 1996-10-04 | 2002-05-01 | 杏林制药株式会社 | 吡唑并吡啶基哒嗪酮衍生物及其制备方法 |
| 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 |
| ATE247654T1 (de) | 1997-11-28 | 2003-09-15 | Sumitomo Pharma | Neue heterozyklische verbindungen |
| 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 |
| AU748087B2 (en) | 1998-02-17 | 2002-05-30 | Tularik Inc. | Anti-viral pyrimidine derivatives |
| 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 |
| 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 |
| 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 |
| DE69917469T2 (de) | 1998-08-27 | 2005-05-12 | Sumitomo Pharmaceuticals Co., Ltd. | Pyrimidin derivate |
| US6583148B1 (en) | 1999-04-08 | 2003-06-24 | Krenitsky Pharmaceuticals, Inc. | Neurotrophic substituted pyrimidines |
| US6503908B1 (en) | 1999-10-11 | 2003-01-07 | 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 |
| AU2002364211A1 (en) | 2001-12-21 | 2003-07-15 | 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 |
| AU2003242252A1 (en) | 2002-06-07 | 2003-12-22 | Kyowa Hakko Kogyo Co., Ltd. | Bicyclic pyrimidine derivatives |
| BR0314761A (pt) | 2002-09-27 | 2005-07-26 | Sumitomo Pharma | Composto de adenina e seu uso |
| US8455458B2 (en) | 2002-10-16 | 2013-06-04 | Arthrodynamic Technologies, Animal Health Division, Inc. | Composition and method for treating connective tissue damage |
| KR20060016817A (ko) | 2003-06-20 | 2006-02-22 | 콜리 파마슈티칼 게엠베하 | 소분자 톨-유사 수용체 (tlr) 길항제 |
| KR20060096415A (ko) | 2003-09-05 | 2006-09-11 | 애나디스 파마슈티칼스, 인코포레이티드 | C형 간염 바이러스에 의한 감염증을 치료하기 위해투여하는 tlr7 리간드 및 이의 전구약물 |
| US20070225303A1 (en) | 2004-03-26 | 2007-09-27 | Haruhisa Ogita | 8-Oxoadenine Compound |
| EP1728793B1 (en) | 2004-03-26 | 2016-02-03 | Sumitomo Dainippon Pharma Co., Ltd. | 9-substituted 8-oxoadenine compound |
| WO2007084413A2 (en) | 2004-07-14 | 2007-07-26 | Ptc Therapeutics, Inc. | Methods for treating hepatitis c |
| RU2401833C2 (ru) | 2004-08-10 | 2010-10-20 | Янссен Фармацевтика Н.В. | Производные 1, 2, 4-триазин-6-она, ингибирующие вич |
| BRPI0517559A (pt) | 2004-11-09 | 2008-10-14 | Hoffmann La Roche | composto, processo para a sua preparação, método para o tratamento terapêutico e/ou profilático de enfermidades que são moduladas por inibidores de ptb-1b e utilização dos compostos |
| US7498409B2 (en) | 2005-03-24 | 2009-03-03 | Schering Corporation | Screening assay for TLR7, TLR8 and TLR9 agonists and antagonists |
| MX2007013780A (es) | 2005-05-04 | 2008-02-05 | Pfizer Ltd | Derivados 2 amido-6-amino-8-oxo purina como moduladores del receptor como tipo peaje (toll) para el tratamiento del cancer y las infecciones virales tal como la hepatitis c. |
| TW200716631A (en) | 2005-05-12 | 2007-05-01 | Tibotec Pharm Ltd | Pyrido[2,3-d]pyrimidines useful as HCV inhibitors, and methods for the preparation thereof |
| JP4850911B2 (ja) | 2005-09-01 | 2012-01-11 | エフ.ホフマン−ラ ロシュ アーゲー | P2x3およびp2x2/3モジュレーターとしてのジアミノピリミジン |
| WO2007034881A1 (ja) | 2005-09-22 | 2007-03-29 | Dainippon Sumitomo Pharma Co., Ltd. | 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 |
| BRPI0707945A2 (pt) | 2006-02-17 | 2011-05-17 | Pfizer Ltd | derivados de 3-deazapurina como modulares de tlr7 |
| US8673929B2 (en) | 2006-07-20 | 2014-03-18 | Gilead Sciences, Inc. | 4,6-di- 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 |
| TW200829594A (en) | 2006-12-07 | 2008-07-16 | Piramed Ltd | Phosphoinositide 3-kinase inhibitor compounds and methods of use |
| WO2008075103A1 (en) | 2006-12-20 | 2008-06-26 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa | Antiviral indoles |
| JP5425642B2 (ja) | 2007-02-07 | 2014-02-26 | 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 | 合成tlrアゴニストの結合体およびそのための使用 |
| 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 |
| US8067413B2 (en) | 2007-03-19 | 2011-11-29 | Astrazeneca Ab | 9-substituted-8-oxo-adenine compounds as toll-like receptor (TLR7 ) modulators |
| WO2008114819A1 (ja) | 2007-03-20 | 2008-09-25 | Dainippon Sumitomo Pharma Co., Ltd. | 新規アデニン化合物 |
| US9150556B2 (en) | 2007-05-22 | 2015-10-06 | Boehringer Ingelheim International Gmbh | Benzimidazolone chymase inhibitors |
| EP2170888B1 (en) | 2007-06-29 | 2015-04-22 | Gilead Sciences, Inc. | Purine derivatives and their use as modulators of toll-like receptor 7 |
| US20090176778A1 (en) | 2007-08-10 | 2009-07-09 | Franz Ulrich Schmitz | Certain nitrogen containing bicyclic chemical entities for treating viral infections |
| CA2696824A1 (en) | 2007-08-28 | 2009-03-12 | Irm Llc | Compounds and compositions as kinase inhibitors |
| WO2009030998A1 (en) | 2007-09-05 | 2009-03-12 | Coley Pharmaceutical Group, Inc. | Pyrimidine compounds as toll-like receptor (tlr) agonists |
| CA2710644C (en) | 2007-12-24 | 2016-03-29 | Tibotec Pharmaceuticals | Macrocyclic indoles as hepatitis c virus inhibitors |
| CN102088974A (zh) | 2008-02-07 | 2011-06-08 | 加利福尼亚大学校务委员会 | 用tlr7活化剂对膀胱疾病的治疗 |
| EP2271345B1 (en) | 2008-04-28 | 2015-05-20 | Merck Sharp & Dohme Corp. | Hcv ns3 protease inhibitors |
| 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 |
| EP2432768B1 (en) | 2009-05-21 | 2017-07-05 | Sumitomo Dainippon Pharma Co., Ltd. | Novel pyrimidine derivatives and their use in the treatment of cancer and further diseases |
| 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 |
| US8637525B2 (en) | 2009-07-31 | 2014-01-28 | Bristol-Myers Squibb Company | Compounds for the reduction of beta-amyloid production |
| WO2011049987A2 (en) | 2009-10-20 | 2011-04-28 | Eiger Biopharmaceuticals, Inc. | Azaindazoles to treat flaviviridae virus infection |
| AP3103A (en) | 2009-10-22 | 2015-01-31 | Gilead Sciences Inc | Derivatives of purine or deazapurine useful for the treatment of (inter alia)viral infections |
| 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 |
| WO2012066335A1 (en) | 2010-11-19 | 2012-05-24 | Astrazeneca Ab | Phenol compounds als toll -like receptor 7 agonists |
| WO2012067269A1 (en) | 2010-11-19 | 2012-05-24 | Dainippon Sumitomo Pharma Co., Ltd. | Aminoalkoxyphenyl compounds and their use in the treatment of disease |
| MY170941A (en) | 2011-04-08 | 2019-09-19 | Janssen Sciences Ireland Uc | Pyrimidine derivatives for the treatment of viral infections |
| RS57023B1 (sr) | 2011-05-18 | 2018-05-31 | Janssen Sciences Ireland Uc | Derivati hinazolina za tretman viralnih infekcija i drugih bolesti |
| JP6349256B2 (ja) | 2011-11-09 | 2018-06-27 | ヤンセン・サイエンシズ・アイルランド・ユーシー | ウイルス感染の治療のためのプリン誘導体 |
| CN104245695B (zh) | 2012-02-08 | 2017-06-06 | 爱尔兰詹森科学公司 | 用于治疗病毒性感染的哌啶基‑嘧啶衍生物 |
| SG10201704095UA (en) | 2012-04-24 | 2017-06-29 | Vertex Pharma | Dna-pk inhibitors |
| WO2014009509A1 (en) | 2012-07-13 | 2014-01-16 | Janssen R&D Ireland | Macrocyclic purines for the treatment of viral infections |
| WO2014023813A1 (en) | 2012-08-10 | 2014-02-13 | Janssen R&D Ireland | Alkylpyrimidine derivatives for the treatment of viral infections and further diseases |
| 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 |
| EP2903967B3 (en) | 2012-10-05 | 2020-04-15 | Janssen Sciences Ireland Unlimited Company | Acylaminopyrimidine derivatives for the treatment of viral infections and further diseases |
| NO2906563T3 (enExample) * | 2012-10-10 | 2018-07-28 | ||
| US9663474B2 (en) | 2012-11-16 | 2017-05-30 | Janssen Sciences Ireland Uc | Heterocyclic substituted 2-amino quinazoline derivatives for the treatment of viral infections |
| CN105189468B (zh) | 2013-02-21 | 2018-10-30 | 爱尔兰詹森科学公司 | 用于治疗病毒性感染的2-氨基嘧啶衍生物 |
| MX366481B (es) | 2013-03-29 | 2019-07-09 | Janssen Sciences Ireland Uc | Deaza-purinonas macrociclicas para el tratamiento de infecciones virales. |
| MY179503A (en) | 2013-07-30 | 2020-11-09 | Janssen Sciences Ireland Uc | Thieno[3,2-d]pyrimidines derivatives for the treatment of viral infections |
| 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 |
| EP2133353A1 (en) * | 2007-03-20 | 2009-12-16 | Dainippon Sumitomo Pharma Co., Ltd. | Novel adenine compound |
| WO2009067081A1 (en) * | 2007-11-22 | 2009-05-28 | Astrazeneca Ab | Pyrimidine derivatives for the treatment of asthma, copd, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, cancer, hepatitis b, hepatitis c, hiv, hpv, bacterial infections and dermatosis |
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