EA201270505A1 - Производные иминотиадиазиндиоксида в качестве ингибиторов bace, композиции на их основе, и их применение - Google Patents

Производные иминотиадиазиндиоксида в качестве ингибиторов bace, композиции на их основе, и их применение

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Publication number
EA201270505A1
EA201270505A1 EA201270505A EA201270505A EA201270505A1 EA 201270505 A1 EA201270505 A1 EA 201270505A1 EA 201270505 A EA201270505 A EA 201270505A EA 201270505 A EA201270505 A EA 201270505A EA 201270505 A1 EA201270505 A1 EA 201270505A1
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Eurasian Patent Office
Prior art keywords
compounds
derivatives
bace inhibitors
iminothiadiazindioxide
compositions
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EA201270505A
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English (en)
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EA025120B1 (ru
Inventor
Джек Д. Скотт
Эндрю В. Стэмфорд
Эрик Дж. Гилберт
Джаред Н. Камминг
Ульрих Изерло
Джеффри А. Мисяшек
Гоцин Ли
Original Assignee
Мерк Шарп Энд Домэ Корп.
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Application filed by Мерк Шарп Энд Домэ Корп. filed Critical Мерк Шарп Энд Домэ Корп.
Publication of EA201270505A1 publication Critical patent/EA201270505A1/ru
Publication of EA025120B1 publication Critical patent/EA025120B1/ru

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Abstract

В большом разнообразии вариантов осуществления изобретение предлагает некоторые производные иминотиадиазиндиоксида, включая соединения формулы (I), его стереоизомеры и фармацевтически приемлемые соли указанных соединений, указанных стереоизомеров, где каждый из R, R, R, R, R, R, цикла А, цикла В, m, n, р, -L-, -L- и -L- выбраны независимо и являются такими, как определены в настоящем описании. Неожиданно было установлено, что новые производные иминотиадиазиндиоксида по изобретению проявляют свойства, которые, как предполагают, делают их применимыми в качестве ингибиторов ВАСЕ и/или для лечения и профилактики различных патологий, связанных с продуцированием β-амилоида (Аβ). Раскрываются также фармацевтические композиции, содержащие одно или несколько таких соединений (в одиночку и в комбинации с одним или несколькими другими активными средствами), и способы их получения и применения для лечения патологий, связанных с β-амилоидным (Аβ) белком, включая болезнь Альцгеймера.
EA201270505A 2009-10-08 2010-10-06 Производные иминотиадиазиндиоксида в качестве ингибиторов bace, композиции на их основе и их применение EA025120B1 (ru)

Applications Claiming Priority (2)

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Families Citing this family (126)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7763609B2 (en) 2003-12-15 2010-07-27 Schering Corporation Heterocyclic aspartyl protease inhibitors
ES2476027T3 (es) 2005-10-25 2014-07-11 Shionogi & Co., Ltd. Derivados de aminodihidrotriazina
ES2476605T3 (es) 2007-04-24 2014-07-15 Shionogi & Co., Ltd. Derivados de aminohidrotiazina sustituidos con grupos cíclicos
WO2008133273A1 (ja) 2007-04-24 2008-11-06 Shionogi & Co., Ltd. アルツハイマー症治療用医薬組成物
AU2009258496B8 (en) 2008-06-13 2014-06-26 Shionogi & Co., Ltd. Sulfur-containing heterocyclic derivative having beta-secretase-inhibiting activity
JPWO2010047372A1 (ja) 2008-10-22 2012-03-22 塩野義製薬株式会社 Ｂａｃｅ１阻害活性を有する２−アミノピリミジン−４−オンおよび２−アミノピリジン誘導体
TW201020244A (en) 2008-11-14 2010-06-01 Astrazeneca Ab New compounds
US8563543B2 (en) * 2009-10-08 2013-10-22 Merck Sharp & Dohme Corp. Iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use
US8557826B2 (en) 2009-10-08 2013-10-15 Merck Sharp & Dohme Corp. Pentafluorosulfur imino heterocyclic compounds as BACE-1 inhibitors, compositions, and their use
UA108363C2 (uk) 2009-10-08 2015-04-27 Похідні імінотіадіазиндіоксиду як інгібітори bace, композиція на їх основі і їх застосування
WO2011044185A2 (en) 2009-10-08 2011-04-14 Schering Corporation Pentafluorosulfur imino heterocyclic compounds as bace-1 inhibitors, compositions, and their use
US8999980B2 (en) 2009-12-11 2015-04-07 Shionogi & Co., Ltd. Oxazine derivatives
EP2634188A4 (en) 2010-10-29 2014-05-07 Shionogi & Co FUSIONED AMINODIHYDROPYRIMIDINE DERIVATIVE
EP2634186A4 (en) 2010-10-29 2014-03-26 Shionogi & Co naphthyridine
US8404680B2 (en) 2011-02-08 2013-03-26 Hoffmann-La Roche Inc. N-[3-(5-amino-3,3a,7,7a-tetrahydro-1H-2,4-dioxa-6-aza-inden-7-yl)-phenyl]-amides as BACE1 and/or BACE2 inhibitors
WO2012138590A1 (en) 2011-04-07 2012-10-11 Merck Sharp & Dohme Corp. Pyrrolidine-fused thiadiazine dioxide compounds as bace inhibitors, compositions, and their use
WO2012138734A1 (en) 2011-04-07 2012-10-11 Merck Sharp & Dohme Corp. C5-c6 oxacyclic-fused thiadiazine dioxide compounds as bace inhibitors, compositions, and their use
JP2014514302A (ja) * 2011-04-13 2014-06-19 メルク・シャープ・アンド・ドーム・コーポレーション Ｂａｃｅ阻害薬としての５−置換されたイミノチアジン類およびそれのモノおよびジオキシド、組成物およびそれらの使用
JPWO2012147762A1 (ja) 2011-04-26 2014-07-28 塩野義製薬株式会社 ピリジン誘導体およびそれを含有するｂａｃｅ１阻害剤
TW201247635A (en) 2011-04-26 2012-12-01 Shionogi & Co Oxazine derivatives and a pharmaceutical composition for inhibiting BAC1 containing them
EP2747769B1 (en) 2011-08-22 2017-08-02 Merck Sharp & Dohme Corp. 2-spiro-substituted iminothiazines and their mono-and dioxides as bace inhibitors, compositions and their use
UY34278A (es) 2011-08-25 2013-04-05 Novartis Ag Derivados novedosos de oxazina y su uso en el tratamiento de enfermedades
JP6124015B2 (ja) * 2011-12-06 2017-05-10 宇部興産株式会社 ペンタフルオロスルファニル安息香酸の製造方法
UA113538C2 (xx) 2012-01-26 2017-02-10 Фторметил-5,6-дигідро-4h-$1,3]оксазини
CN104271566B (zh) * 2012-05-22 2017-05-31 霍夫曼-拉罗奇有限公司 取代的联吡啶胺及其用途
US9416129B2 (en) 2012-10-17 2016-08-16 Merck Sharp & Dohme Corp. Tricyclic substituted thiadiazine dioxide compounds as BACE inhibitors, compositions and their use
WO2014062549A1 (en) 2012-10-17 2014-04-24 Merck Sharp & Dohme Corp. Tricyclic substituted thiadiazine dioxide compounds as bace inhibitors, compositions, and their use
WO2014065434A1 (en) 2012-10-24 2014-05-01 Shionogi & Co., Ltd. Dihydrooxazine or oxazepine derivatives having bace1 inhibitory activity
US8865723B2 (en) 2012-10-25 2014-10-21 Tetra Discovery Partners Llc Selective PDE4 B inhibition and improvement in cognition in subjects with brain injury
US9447085B2 (en) 2012-12-14 2016-09-20 Merck Sharp & Dohme Corp. Iminothiadiazine dioxides containing a thioamide, amidine, or amide oxime group as BACE inhibitors, compositions, and their use
WO2014099794A1 (en) * 2012-12-20 2014-06-26 Merck Sharp & Dohme Corp. C5, c6 oxacyclic-fused iminothiazine dioxide compounds as bace inhibitors
US9489013B2 (en) 2012-12-20 2016-11-08 Merck Sharp & Dohme Corp. C6-azaspiro iminothiadiazine dioxides as bace inhibitors, compositions, and their use
EP2934149B1 (en) * 2012-12-20 2019-02-06 Merck Sharp & Dohme Corp. C6-azaspiro iminothiadiazine dioxides as bace inhibitors
JP5422782B1 (ja) 2012-12-21 2014-02-19 独立行政法人放射線医学総合研究所 脳内に蓄積したタウタンパク質をイメージングするための新規化合物
US9580396B2 (en) 2012-12-21 2017-02-28 Merck Sharp & Dohme Corp. C6-spiro iminothiadiazine dioxides as BACE inhibitors, compositions, and their use
US10202355B2 (en) 2013-02-12 2019-02-12 Buck Institute For Research On Aging Hydantoins that modulate bace-mediated app processing
US9296734B2 (en) 2013-03-01 2016-03-29 Amgen Inc. Perfluorinated 5,6-dihydro-4H-1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use
SG11201507196WA (en) 2013-03-08 2015-10-29 Amgen Inc Perfluorinated cyclopropyl fused 1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use
US9422255B2 (en) 2013-03-15 2016-08-23 Merck Sharp & Dohme Corp. S-imino-S-oxo-iminothiazine compounds as BACE inhibitors, compositions, and their use
EP2968353B1 (en) 2013-03-15 2018-12-19 Merck Sharp & Dohme Corp. C2-azaspiro iminothiazine dioxides as bace inhibitors
US9428476B2 (en) 2013-03-15 2016-08-30 Merck Sharp & Dohme Corp. S-imino-S-oxo-iminothiadiazine compounds as BACE inhibitors, compositions, and their use
CN103214413B (zh) * 2013-03-22 2015-05-13 郑州泰基鸿诺药物科技有限公司 一种含杂环的三氟甲基酮化合物及其制备方法
BR112015027381A8 (pt) 2013-05-01 2018-01-30 Hoffmann La Roche pirimidinas substituídas por heterocicloalquila ligadas ao c e seus usos
HUE042111T2 (hu) * 2013-07-31 2019-06-28 Merck Patent Gmbh Piridinek, pirimidinek és pirazinok mint BTK inhibitorok, továbbá ezek alkalmazása
WO2015095104A1 (en) 2013-12-18 2015-06-25 Merck Sharp & Dohme Corp. Iminothiadiazepane dioxide compounds as bace inhibitors, compositions, and their use
WO2015094930A1 (en) 2013-12-18 2015-06-25 Merck Sharp & Dohme Corp. C-6 spirocarbocyclic iminothiadiazine dioxides as bace inhibitors, compositions, and their use
ES2813875T3 (es) * 2014-01-01 2021-03-25 Medivation Tech Llc Compuestos y procedimientos de uso
CN103910781B (zh) * 2014-03-18 2016-02-17 重庆大学 一种Aβ聚集抑制剂
KR20180078347A (ko) 2014-04-10 2018-07-09 화이자 인코포레이티드 2-아미노-6-메틸-4,4a,5,6-테트라히드로피라노[3,4-d][1,3]티아진-8a(8H)-일-1,3-티아졸-4-일 아미드
CN103880757B (zh) * 2014-04-15 2016-02-24 上海毕得医药科技有限公司 一种5-羟基嘧啶-2-羧酸的合成方法
WO2016022724A1 (en) 2014-08-08 2016-02-11 Amgen Inc. Cyclopropyl fused thiazin-2-amine compounds as beta-secretase inhibitors and methods of use
WO2016025364A1 (en) * 2014-08-14 2016-02-18 Merck Sharp & Dohme Corp. Novel crystalline forms of a bace inhibitor, compositions, and their use
US20170233382A1 (en) * 2014-08-14 2017-08-17 Merck Sharp & Dohme Corp. Processes for the preparation of a bace inhibitor
CN106459006B (zh) * 2014-08-15 2020-02-11 豪夫迈·罗氏有限公司 2,2,2-三氟乙基-噻二嗪
EP3191447B1 (en) * 2014-09-12 2019-05-01 Merck Sharp & Dohme Corp. S-imino-s-oxo iminothiazine compounds as bace inhibitors, compositions, and their use
US9868738B2 (en) 2014-09-19 2018-01-16 Merck Sharp & Dohme Corp. Diazine-fused amidines as BACE inhibitors, compositions, and their use
WO2016053767A1 (en) * 2014-09-30 2016-04-07 Merck Sharp & Dohme Corp. Novel crystalline forms of a bace inhibitor, compositions, and their use
EP3201204B1 (en) 2014-10-03 2021-02-24 Merck Sharp & Dohme Corp. C5-c6-fused tricyclic iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use
WO2016085780A1 (en) 2014-11-25 2016-06-02 Merck Sharp & Dohme Corp. C5-c6-oxacyclic fused iminopyrimidinone compounds as bace inhibitors, compositions, and their use
US10071998B2 (en) 2015-01-20 2018-09-11 Merck Sharp & Dohme Corp. Iminothiadiazine dioxides bearing an amine-linked substituent as BACE inhibitors, compositions, and their use
JP6765681B2 (ja) * 2015-04-21 2020-10-07 オールジェネシス バイオセラピューティクス インコーポレイテッド Ｂａｃｅ１阻害剤としての化合物およびそれらの使用
WO2017051303A1 (en) 2015-09-24 2017-03-30 Pfizer Inc. Tetrahydropyrano[3,4-d][1,3]oxazin derivatives and their use as bace inhibitors
BR112018003489A2 (pt) 2015-09-24 2018-09-25 Pfizer n-[2-(2-amino-6,6-dissubstituído-4,4a,5,6-tetra-hidropirano[3,4-d][1,3]tiazin-8a(8h)-il)-1,3-tiazol-4-il]amidas
WO2017051294A1 (en) 2015-09-24 2017-03-30 Pfizer Inc. N-[2-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2h-1,2,4-thiadiazin-5-yl)-1,3-thiazol-4-yl] amides useful as bace inhibitors
ES2928164T3 (es) 2015-10-19 2022-11-15 Incyte Corp Compuestos heterocíclicos como inmunomoduladores
CN105218425A (zh) * 2015-10-31 2016-01-06 丁玉琴 一种3,5-二甲氧基吡咯-2-甲酸的合成方法
CA3005727A1 (en) 2015-11-19 2017-05-26 Incyte Corporation Substituted 2-methylbiphenyl-3-yl heterocyclic compounds and pharmaceutical compositions thereof useful as immunomodulators
US10329291B2 (en) 2015-12-04 2019-06-25 Merck Sharp & Dohme Corp. C5-C6-carbocyclic fused iminothiadiazine dioxides as BACE inhibitors, compositions, and their use
WO2017106634A1 (en) * 2015-12-17 2017-06-22 Incyte Corporation N-phenyl-pyridine-2-carboxamide derivatives and their use as pd-1/pd-l1 protein/protein interaction modulators
PE20230731A1 (es) 2015-12-22 2023-05-03 Incyte Corp Compuestos heterociclicos como inmunomoduladores
US10604534B2 (en) 2016-02-11 2020-03-31 Merck Sharp & Dohme Corp. C5-C6-oxacyclic fused iminothiadiazine dioxide compounds bearing an ether linker as BACE inhibitors, compositions, and their use
US10618892B2 (en) * 2016-02-17 2020-04-14 Merck Sharp & Dohme Corp. Processes for the preparation of a BACE inhibitor
GB201603104D0 (en) * 2016-02-23 2016-04-06 Ucb Biopharma Sprl Therapeutic agents
AR108396A1 (es) 2016-05-06 2018-08-15 Incyte Corp Compuestos heterocíclicos como inmunomoduladores
ES2905980T3 (es) 2016-05-26 2022-04-12 Incyte Corp Compuestos heterocíclicos como inmunomoduladores
PE20190731A1 (es) 2016-06-20 2019-05-23 Incyte Corp Compuestos heterociclicos como inmunomoduladores
TWI798751B (zh) 2016-07-01 2023-04-11 美商美國禮來大藥廠 抗－N3pGlu類澱粉β肽抗體及其用途
ES2930092T3 (es) 2016-07-14 2022-12-07 Incyte Corp Compuestos heterocíclicos como inmunomoduladores
MA46045A (fr) 2016-08-29 2021-04-28 Incyte Corp Composés hétérocycliques utilisés comme immunomodulateurs
JP7149271B2 (ja) * 2016-12-15 2022-10-06 アムジエン・インコーポレーテツド β－セクレターゼ阻害剤としての１，４－チアジンジオキシドおよび１，２，４－チアジアジンジオキシド誘導体ならびに使用方法
MA54101A (fr) 2016-12-15 2021-10-27 Amgen Inc Dérivés de thiazine et d'oxazine bicycliques en tant qu'inhibiteurs de bêta-sécrétase et procédés d'utilisation
AU2017378316B2 (en) 2016-12-15 2021-04-01 Amgen Inc. Cyclopropyl fused thiazine derivatives as beta-secretase inhibitors and methods of use
MX2019007101A (es) 2016-12-15 2019-12-16 Amgen Inc Derivados de oxazina como inhibidores de beta secretasa y metodos de uso.
JP7149272B2 (ja) 2016-12-15 2022-10-06 アムジエン・インコーポレーテツド β－セクレターゼ阻害剤としてのチアジン誘導体および使用方法
MY197635A (en) 2016-12-22 2023-06-29 Incyte Corp Benzooxazole derivatives as immunomodulators
BR112019012957A2 (pt) 2016-12-22 2019-11-26 Incyte Corp derivados de tetra-hidroimidazo[4,5-c]piridina como indutores de internalização de pd-l1
ES2899402T3 (es) 2016-12-22 2022-03-11 Incyte Corp Derivados de piridina como inmunomoduladores
EP3558989B1 (en) 2016-12-22 2021-04-14 Incyte Corporation Triazolo[1,5-a]pyridine derivatives as immunomodulators
EP3372599A1 (en) 2017-03-07 2018-09-12 Sandoz AG Crystalline form of verubecestat
WO2018204408A1 (en) * 2017-05-02 2018-11-08 Sanford Burnham Prebys Medical Discovery Institute Methods of diagnosing and treating alzheimer's disease
EP3619196B1 (de) 2017-05-04 2022-03-30 Bayer CropScience Aktiengesellschaft 2-{[2-(phenyloxymethyl)pyridin-5-yl]oxy}-ethanamin-derivate und verwandte verbindungen als schädlingsbekämpfungsmittel z.b. für den pflanzenschutz
WO2018231634A1 (en) 2017-06-13 2018-12-20 Merck Sharp & Dohme Corp. A novel crystalline form of a bace inhibitor, compositions, and use
HRP20230090T1 (hr) 2018-03-30 2023-03-17 Incyte Corporation Heterociklički spojevi kao imunomodulatori
GB201805816D0 (en) 2018-04-06 2018-05-23 Ucb Biopharma Sprl Therapeutic agents
JP2022511167A (ja) * 2018-04-23 2022-01-31 塩野義製薬株式会社 選択的ｂａｃｅ１阻害活性を有する二環式複素環誘導体
BR112020021728A2 (pt) 2018-04-27 2021-01-26 Shionogi & Co., Ltd. derivados de tetra-hidropiranooxazina tendo atividade inibitória de bace1 seletiva
CA3099318C (en) * 2018-05-09 2024-02-13 Aprinoia Therapeutics Inc. Heteroaryl compounds and uses thereof
CN112752756A (zh) 2018-05-11 2021-05-04 因赛特公司 作为PD-L1免疫调节剂的四氢-咪唑并[4,5-c]吡啶衍生物
CN110467611B (zh) * 2018-05-11 2022-09-27 广东东阳光药业有限公司 亚氨基噻二嗪二氧化物衍生物及其用途
CN108863983B (zh) * 2018-08-03 2020-01-21 广东东阳光药业有限公司 亚氨基噻二嗪二氧化物衍生物及其用途
CN108997328B (zh) * 2018-09-06 2021-06-08 广东东阳光药业有限公司 亚氨基噻二嗪二氧化物衍生物及其用途
CN109180669B (zh) * 2018-09-06 2022-05-27 广东东阳光药业有限公司 亚氨基噻二嗪二氧化物衍生物及其用途
CN109180670A (zh) * 2018-09-17 2019-01-11 广东东阳光药业有限公司 亚氨基噻二嗪二氧化物衍生物及其用途
CN109180671A (zh) * 2018-09-21 2019-01-11 广东东阳光药业有限公司 亚氨基噻二嗪二氧化物衍生物及其用途
CN109180672A (zh) * 2018-09-29 2019-01-11 广东东阳光药业有限公司 亚氨基噻二嗪二氧化物衍生物及其用途
CN109796447B (zh) * 2019-01-07 2020-03-13 广东东阳光药业有限公司 亚氨基噻二嗪二氧化物衍生物及其用途
GB201906804D0 (en) 2019-05-14 2019-06-26 Ucb Biopharma Sprl Therapeutic agents
US11753406B2 (en) 2019-08-09 2023-09-12 Incyte Corporation Salts of a PD-1/PD-L1 inhibitor
WO2021026884A1 (en) * 2019-08-15 2021-02-18 Merck Sharp & Dohme Corp. Antimalarial agents
CN114206856A (zh) * 2019-08-19 2022-03-18 Ucb生物制药有限责任公司 抗疟疾的六氢嘧啶类似物
AR120109A1 (es) 2019-09-30 2022-02-02 Incyte Corp Compuestos de pirido[3,2-d]pirimidina como inmunomoduladores
PE20230407A1 (es) 2019-11-11 2023-03-07 Incyte Corp Sales y formas cristalinas de un inhibidor de pd-1/pd-l1
TWI759962B (zh) 2019-11-13 2022-04-01 香港商新旭生技股份有限公司 用於降解tau蛋白聚集體的化合物及其用途
WO2021117759A1 (ja) 2019-12-10 2021-06-17 塩野義製薬株式会社 含窒素芳香族複素環式基を有するヒストン脱アセチル化酵素阻害剤
CN113087669B (zh) * 2019-12-23 2023-11-17 南京药石科技股份有限公司 一种4-氰基-5-溴嘧啶的制备方法
WO2021155612A1 (en) * 2020-02-09 2021-08-12 Merck Sharp & Dohme Corp. Antimalarial agents
WO2021195403A1 (en) 2020-03-26 2021-09-30 Cyclerion Therapeutics, Inc. Deuterated sgc stimulators
JP2023532331A (ja) * 2020-07-02 2023-07-27 リミックス セラピューティクス インコーポレイテッド 核酸をスプライシングするため及び増殖性疾患を処置するための修飾因子としての５－［５－（ピペリジン－４－イル）チエノ［３，２－ｃ］ピラゾール－２－イル］インダゾール誘導体及び関連する化合物並びにスプライシングを調節するための化合物及び方法
GB202010606D0 (en) 2020-07-10 2020-08-26 Ucb Biopharma Sprl Therapeutic agents
WO2023102747A1 (en) * 2021-12-07 2023-06-15 Merck Sharp & Dohme Llc Antimalarial agents
US11780836B2 (en) 2020-11-06 2023-10-10 Incyte Corporation Process of preparing a PD-1/PD-L1 inhibitor
WO2022099075A1 (en) 2020-11-06 2022-05-12 Incyte Corporation Crystalline form of a pd-1/pd-l1 inhibitor
MX2023005362A (es) 2020-11-06 2023-06-22 Incyte Corp Proceso para hacer un inhibidor de proteina de muerte programada 1 (pd-1)/ligando de muerte programada 1 (pd-l1) y sales y formas cristalinas del mismo.
WO2022175508A1 (en) 2021-02-22 2022-08-25 Solvay Sa Catalytic method for the preparation of perfluoroalkoxy-substituted arenes and heteroarenes
CN113880755A (zh) * 2021-08-27 2022-01-04 成都药明康德新药开发有限公司 2-溴-5-(三氟甲氧基)吡啶的制备方法
WO2023133229A2 (en) * 2022-01-05 2023-07-13 Remix Therapeutics Inc. Compounds and methods for modulating splicing

Family Cites Families (170)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4863936A (en) * 1982-12-14 1989-09-05 Smith Kline & French Laboratories Limited 3,5-Substituted-2-pyridyl-alkylaminocyclobutenediones having histamine h1 -antagonist activity
IL92011A0 (en) 1988-10-19 1990-07-12 Abbott Lab Heterocyclic peptide renin inhibitors
US5534520A (en) 1990-04-10 1996-07-09 Fisher; Abraham Spiro compounds containing five-membered rings
WO1993004047A1 (en) 1991-08-16 1993-03-04 Merck & Co., Inc. Quinazoline derivatives as inhibitors of hiv reverse transcriptase
US5629322A (en) 1994-11-15 1997-05-13 Merck & Co., Inc. Cyclic amidine analogs as inhibitors of nitric oxide synthase
BR9811544A (pt) 1997-07-28 2000-08-22 Ober Utensili Pneumatici Srl Pistola de rebitar pneumática-hidráulica
WO2000051992A1 (en) 1999-03-04 2000-09-08 E.I. Du Pont De Nemours And Company Fused bicyclic oxazinone and thiazinone fungicides
US7161962B1 (en) 1999-05-27 2007-01-09 Nuera Communications, Inc. Method and apparatus for coding modem signals for transmission over voice networks
WO2003014075A2 (en) 2001-08-03 2003-02-20 Schering Corporation Novel gamma secretase inhibitors
US6673821B2 (en) 2001-10-22 2004-01-06 Enanta Pharmaceuticals, Inc. Nitrogen heterocycle inhibitors of aspartyl protease
GB0211649D0 (en) 2002-05-21 2002-07-03 Novartis Ag Organic compounds
AU2004204692B2 (en) 2003-01-07 2009-07-09 Merck & Co., Inc. Macrocyclic beta-secretase inhibitors for treatment of Alzheimer's disease
US7244764B2 (en) 2003-06-23 2007-07-17 Neurochem (International) Limited Methods and compositions for treating amyloid-related diseases
CA2529994A1 (en) 2003-06-30 2005-01-20 Merck & Co., Inc. N-alkyl phenylcarboxamide beta-secretase inhibitors for the treatment of alzheimer's disease
CA2530006A1 (en) 2003-07-01 2005-01-20 Merck & Co., Inc. Phenylcarboxylate beta-secretase inhibitors for the treatment of alzheimer's disease
US7598250B2 (en) 2003-08-08 2009-10-06 Schering Corporation Cyclic amine BACE-1 inhibitors having a heterocyclic substituent
JP4448134B2 (ja) 2003-08-08 2010-04-07 シェーリング コーポレイション ベンズアミド置換基を有する環状アミンｂａｓｅ−１阻害剤
WO2005032471A2 (en) 2003-10-03 2005-04-14 Merck & Co., Inc. Benzylether and benzylamino beta-secretase inhibitors for the treatment of alzheimer's disease
US20060034848A1 (en) 2003-11-07 2006-02-16 Ayae Kinoshita Methods and compositions for treating Alzheimer's disease
AU2004293416B2 (en) 2003-11-24 2009-09-24 Merck & Co., Inc. Benzylether and benzylamino beta-secretase inhibitors for the treatment of Alzheimer's disease
US7763609B2 (en) * 2003-12-15 2010-07-27 Schering Corporation Heterocyclic aspartyl protease inhibitors
PL1699455T3 (pl) 2003-12-15 2013-10-31 Merck Sharp & Dohme Heterocykliczne inhibitory proteaz aspartylowych
US7592348B2 (en) 2003-12-15 2009-09-22 Schering Corporation Heterocyclic aspartyl protease inhibitors
TW200619203A (en) * 2003-12-15 2006-06-16 Schering Corp Heterocyclic aspartyl protease inhibitors
CA2548849A1 (en) 2003-12-19 2005-07-21 Merck & Co., Inc. Phenylamide and pyridylamide beta-secretase inhibitors for the treatment of alzheimer's disease
AU2005236020A1 (en) 2004-04-20 2005-11-03 Merck & Co., Inc. 1,3,5-substituted phenyl derivative compounds useful as beta-secretase inhibitors for the treatment of Alzheimer's disease
CA2563639A1 (en) 2004-04-20 2005-11-03 Merck & Co., Inc. 2, 4, 6-substituted pyridyl derivative compounds useful as beta-secretase inhibitors for the treatment of alzheimer's disease
JP2007533740A (ja) 2004-04-22 2007-11-22 イーライ リリー アンド カンパニー Ｂａｃｅ阻害剤としてのアミド
CN1968924B (zh) 2004-06-15 2011-08-03 默沙东公司 作为β-分泌酶抑制剂用于治疗阿尔茨海默氏病的吡咯烷-3-基化合物
AU2005264917A1 (en) 2004-06-16 2006-01-26 Wyeth Diphenylimidazopyrimidine and -imidazole amines as inhibitors of B-secretase
PE20060459A1 (es) 2004-06-16 2006-05-30 Wyeth Corp DERIVADOS DE AMINO-5,5-DIFENILIMIDAZOLONA COMO INHIBIDORES DE LA ß-SECRETASA
DE602005025363D1 (de) 2004-07-22 2011-01-27 Schering Corp Substituierte amide als inhibitoren der beta-sekretase
WO2006014944A1 (en) 2004-07-28 2006-02-09 Schering Corporation Macrocyclic beta-secretase inhibitors
CN101068545A (zh) 2004-10-13 2007-11-07 默克公司 作为β－分泌酶抑制剂用于治疗阿尔茨海默病的螺哌啶化合物
US20090221579A1 (en) 2004-10-15 2009-09-03 Jeffrey Scott Albert Substituted Amino-Compounds and Uses Thereof
US20090062282A1 (en) 2004-10-15 2009-03-05 Astrazeneca Ab Substituted Amino-Pyrimidones and Uses Thereof
JP2008518969A (ja) 2004-10-29 2008-06-05 メルク エンド カムパニー インコーポレーテッド アルツハイマー病を治療するためのβ−セクレターゼ阻害薬として有用な２−アミノピリジン化合物
WO2006057983A1 (en) 2004-11-23 2006-06-01 Merck & Co., Inc. Macrocyclic aminopyridyl beta-secretase inhibitors for the treatment of alzheimer's disease
SG123624A1 (en) * 2004-12-17 2006-07-26 Singapore Tech Dynamics Pte An apparatus for altering the course of travellingof a moving article and a method thereof
CN101103034A (zh) 2005-01-14 2008-01-09 惠氏公司 抑制β-分泌酶的氨基-咪唑酮
EP1855679B1 (en) 2005-01-19 2016-06-29 Merck Sharp & Dohme Corp. Aminomethyl beta-secretase inhibitors for the treatment of alzheimer's disease
EP1841426B1 (en) 2005-01-19 2011-04-27 Merck Sharp & Dohme Corp. Tertiary carbinamines having substituted heterocycles, which are active as inhibitors of beta-secretase, for the treatment of alzheimer's disease
DE102005023943A1 (de) 2005-05-20 2006-11-23 Grünenthal GmbH Pentafluorsulfanyl-substituierte Verbindung und deren Verwendung zur Herstellung von Arzneimitteln
KR20080028881A (ko) 2005-06-14 2008-04-02 쉐링 코포레이션 헤테로사이클릭 아스파르틸 프로테아제 억제제, 이의제조방법 및 용도
EP1896430B1 (en) 2005-06-14 2010-11-24 Schering Corporation The preparation and use of compounds as aspartyl protease inhibitors
WO2006138217A1 (en) 2005-06-14 2006-12-28 Schering Corporation Aspartyl protease inhibitors
TWI332005B (en) 2005-06-14 2010-10-21 Schering Corp Aspartyl protease inhibitors
MX2007016185A (es) 2005-06-14 2008-03-07 Schering Corp Inhibidores de aspartil proteasa heterociclicos macrociclicos.
WO2006138230A2 (en) 2005-06-14 2006-12-28 Schering Corporation The preparation and use of protease inhibitors
CA2610812A1 (en) 2005-06-14 2006-12-28 Schering Corporation Aspartyl protease inhibitors
WO2007005404A1 (en) 2005-06-30 2007-01-11 Wyeth AMINO-5-(6-MEMBERED)HETEROARYLIMIDAZOLONE COMPOUNDS AND THE USE THEREOF FOR ß-SECRETASE MODULATION
TW200738683A (en) 2005-06-30 2007-10-16 Wyeth Corp Amino-5-(5-membered)heteroarylimidazolone compounds and the use thereof for β-secretase modulation
WO2007011833A2 (en) 2005-07-18 2007-01-25 Merck & Co., Inc. Spiropiperidine beta-secretase inhibitors for the treatment of alzheimer's disease
TW200730523A (en) 2005-07-29 2007-08-16 Wyeth Corp Cycloalkyl amino-hydantoin compounds and use thereof for β-secretase modulation
WO2007019078A2 (en) 2005-08-03 2007-02-15 Merck & Co., Inc. Tricyclic beta-secretase inhibitors for the treatment of alzheimer's disease
US7816378B2 (en) 2005-08-03 2010-10-19 Merck Sharp & Dohme Corp. Cyclic ketal beta-secretase inhibitors for the treatment of alzheimer's disease
EP2256107A1 (en) 2005-09-26 2010-12-01 Wyeth LLC Amino-5-[4-(difluoromethoxy)phenyl]-5-phenylimidazolone compounds as inhibitors of the beta-secretase (BACE)
ES2476027T3 (es) 2005-10-25 2014-07-11 Shionogi & Co., Ltd. Derivados de aminodihidrotriazina
ATE478070T1 (de) 2005-10-27 2010-09-15 Schering Corp Heterozyklische aspartyl-proteasehemmer
US7560451B2 (en) 2005-10-31 2009-07-14 Schering Corporation Aspartyl protease inhibitors
TW200804290A (en) 2005-11-15 2008-01-16 Astrazeneca Ab Compounds and uses thereof
EP1951680A4 (en) 2005-11-15 2011-08-10 Astrazeneca Ab NOVEL 2-AMINOPYRIMIDINONE DERIVATIVES AND THEIR USE
US20080255167A1 (en) 2005-11-15 2008-10-16 Jeffrey Albert Novel 2-Aminopyrimidine or 2-Aminiopyridinone Derivatives and Their Use
CA2629317A1 (en) 2005-11-16 2007-05-24 Merck & Co., Inc. Imidazolidinone compounds useful as beta-secretase inhibitors for the treatment of alzheimer's disease
TW200734311A (en) 2005-11-21 2007-09-16 Astrazeneca Ab New compounds
US20090176850A1 (en) 2005-11-21 2009-07-09 Astrazeneca Ab Novel 2-Amino-Imidazole-4-One Compounds And Their Use In The Manufacture Of A Medicament To Be Used In The Treatment Of Cognitive Impairment, Alzheimer's Disease, Neurodegeneration And Dementia
CN101360737A (zh) 2005-12-19 2009-02-04 惠氏公司 2-氨基-5-哌啶咪唑酮化合物和其用于β分泌酶调节的用途
AR058381A1 (es) 2005-12-19 2008-01-30 Astrazeneca Ab Compuestos derivados de 2-aminopiridin-4-onas y una composicion farmaceutica
GB0602951D0 (en) 2006-02-14 2006-03-29 Novartis Ag Organic Compounds
WO2007100536A1 (en) 2006-02-24 2007-09-07 Wyeth DIHYDROSPIRO[DIBENZO[A,D][7]ANNULENE-5,4'-IMIDAZOL] COMPOUNDS FOR THE INHIBITION OF β-SECRETASE
WO2007114771A1 (en) 2006-04-05 2007-10-11 Astrazeneca Ab 2-AMINOPYRIMIDIN-4-ONES AND THEIR USE FOR TREATING OR PREVENTING Aβ-RELATED PATHOLOGIES
EP2032542A2 (en) 2006-06-12 2009-03-11 Schering Corporation Heterocyclic aspartyl protease inhibitors
TW200808796A (en) 2006-06-14 2008-02-16 Astrazeneca Ab New compounds III
TW200815447A (en) 2006-06-14 2008-04-01 Astrazeneca Ab Novel compounds IV
TW200815449A (en) 2006-06-14 2008-04-01 Astrazeneca Ab Novel compounds II
TW200815443A (en) 2006-06-14 2008-04-01 Astrazeneca Ab Novel compounds I
TW200815349A (en) 2006-06-22 2008-04-01 Astrazeneca Ab New compounds
TW200817406A (en) 2006-08-17 2008-04-16 Wyeth Corp Imidazole amines as inhibitors of β-secretase
EP2063889A4 (en) 2006-09-07 2009-09-16 Merck & Co Inc SPIROPIPERIDINE BETA SEKRETASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER DISEASE
US8143405B2 (en) 2006-09-21 2012-03-27 Merck, Sharp & Dohme Corp Piperidine and pyrrolidine beta-secretase inhibitors for the treatment of alzheimer's disease
AU2007307170A1 (en) 2006-10-06 2008-04-17 Merck & Co., Inc. Macrocyclic spiropiperidine beta-secretase inhibitors for the treatment of Alzheimer's disease
EP2091328B1 (en) 2006-10-30 2011-12-28 Merck Sharp & Dohme Corp. Spiropiperidine beta-secretase inhibitors for the treatment of alzheimer's disease
WO2008063114A1 (en) 2006-11-20 2008-05-29 Astrazeneca Ab Amino- imidazolones and their use as medicament for treating cognitive impairment alzheimer disease, neurodegeneration and dementia
EP2061771A1 (en) 2006-12-12 2009-05-27 Schering Corporation Aspartyl protease inhibitors containing a tricyclic ring system
KR20090087487A (ko) 2006-12-12 2009-08-17 쉐링 코포레이션 아스파르틸 프로테아제 억제제
TW200831484A (en) 2006-12-20 2008-08-01 Astrazeneca Ab New compounds
TW200831091A (en) 2006-12-20 2008-08-01 Astrazeneca Ab New compounds
WO2008076043A1 (en) 2006-12-20 2008-06-26 Astrazeneca Ab Novel 2-amino-5,5-diaryl-imidazol-4-ones
PE20090160A1 (es) 2007-03-20 2009-02-11 Wyeth Corp COMPUESTOS AMINO-5-[4-(DIFLUOROMETOXI)FENIL SUSTITUIDO]-5-FENILIMIDAZOLONA COMO INHIBIDORES DE ß-SECRETASA
PE20090617A1 (es) 2007-03-23 2009-05-08 Wyeth Corp Compuestos amino-5-[-4-(difluorometoxi)fenil]-5-fenilimidazolona para la inhibicion de -secretasa
WO2008133273A1 (ja) 2007-04-24 2008-11-06 Shionogi & Co., Ltd. アルツハイマー症治療用医薬組成物
ES2476605T3 (es) 2007-04-24 2014-07-15 Shionogi & Co., Ltd. Derivados de aminohidrotiazina sustituidos con grupos cíclicos
WO2009015917A2 (en) 2007-05-14 2009-02-05 F. Hoffmann-La Roche Ag Dihydroquinone and dihydronaphthridine inhibitors of jnk
TW200902499A (en) 2007-05-15 2009-01-16 Astrazeneca Ab New compounds
WO2009005470A1 (en) 2007-07-05 2009-01-08 Astrazeneca Ab Aryl and heteroaryl substituted isoindole derivatives as bace inhibitors
WO2009005471A1 (en) 2007-07-05 2009-01-08 Astrazeneca Ab Aryl and heteroaryl substituted isoindole derivatives as bace inhibitors
EP2185522A1 (en) 2007-08-06 2010-05-19 Schering Corporation Gamma secretase modulators
US20090041201A1 (en) 2007-08-06 2009-02-12 Carestream Health, Inc. Alignment apparatus for imaging system
PE20091438A1 (es) 2008-01-18 2009-09-26 Eisai Randd Man Co Ltd Derivados fusionados de aminodihidrotiazina
CN101952260B (zh) 2008-02-18 2013-02-13 弗·哈夫曼-拉罗切有限公司 4,5-二氢-*唑-2-基胺衍生物
AU2009217518A1 (en) 2008-02-28 2009-09-03 Merck Sharp & Dohme Corp. 2-aminoimidazole beta-secretase inhibitors for the treatment of Alzheimer's disease
TW200948364A (en) 2008-04-22 2009-12-01 Schering Corp Thiophenyl-substituted 2-imino-3-methyl pyrrolo pyrimidinone compounds as BACE-1 inhibitors, compositions, and their use
TWI431004B (zh) 2008-05-02 2014-03-21 Lilly Co Eli Ｂａｃｅ抑制劑
EA201001566A1 (ru) 2008-05-05 2011-04-29 Пфайзер Инк. Новый класс спиропиперидинов для лечения нейродегенеративных заболеваний
AU2009258496B8 (en) 2008-06-13 2014-06-26 Shionogi & Co., Ltd. Sulfur-containing heterocyclic derivative having beta-secretase-inhibiting activity
EP2318416B1 (en) 2008-07-28 2013-09-04 Eisai R&D Management Co., Ltd. Spiroaminodihydrothiazine derivatives
WO2010013302A1 (ja) 2008-07-28 2010-02-04 エーザイ・アール・アンド・ディー・マネジメント株式会社 スピロアミノジヒドロチアジン誘導体
WO2010021680A2 (en) 2008-08-19 2010-02-25 Vitae Pharmaceuticals, Inc. Inhibitors of beta-secretase
BRPI0918449A2 (pt) 2008-09-11 2019-09-24 Amgen Inc compostos de anel espiro-tricíclico como moduladores de beta-secretas e métodos de uso
US20110207723A1 (en) 2008-09-30 2011-08-25 Eisai R&D Management Co., Ltd. Novel fused aminodihydrothiazine derivative
WO2010048149A2 (en) 2008-10-20 2010-04-29 Kalypsys, Inc. Heterocyclic modulators of gpr119 for treatment of disease
JPWO2010047372A1 (ja) 2008-10-22 2012-03-22 塩野義製薬株式会社 Ｂａｃｅ１阻害活性を有する２−アミノピリミジン−４−オンおよび２−アミノピリジン誘導体
WO2010056195A1 (en) 2008-11-14 2010-05-20 Astrazeneca Ab New compounds 575
WO2010056194A1 (en) 2008-11-14 2010-05-20 Astrazeneca Ab 5h-pyrrolo [ 3, 4-b] pyridin derivatives and their use
TW201020244A (en) 2008-11-14 2010-06-01 Astrazeneca Ab New compounds
WO2010063718A1 (en) 2008-12-02 2010-06-10 ETH Zürich Screening assay for metabolic disease therapeuticals
US8865701B2 (en) 2009-02-20 2014-10-21 Merck Sharp & Dohme Corp. Spiropyrrolidine beta-secretase inhibitors for the treatment of alzheimer'S disease
NZ594230A (en) 2009-03-13 2013-11-29 Vitae Pharmaceuticals Inc Inhibitors of beta-secretase
WO2010113848A1 (ja) 2009-03-31 2010-10-07 塩野義製薬株式会社 Ｂａｃｅ１阻害作用を有するイソチオウレア誘導体またはイソウレア誘導体
US8461160B2 (en) 2009-05-08 2013-06-11 Hoffmann-La Roche, Inc. Dihydropyrimidinones
TW201105650A (en) 2009-07-02 2011-02-16 Astrazeneca Ab New compounds
WO2011002409A1 (en) 2009-07-02 2011-01-06 Astrazeneca Ab 5h-pyrrolo[3,4-£>]pyrazin-7-amine derivatives inhibitors of beta-secretase
UY32750A (es) 2009-07-02 2011-01-31 Astrazeneca Ab Imidazoles sustituidos y uso de los mismos
AR077277A1 (es) 2009-07-09 2011-08-17 Lilly Co Eli Compuestos de biciclo (1,3)tiazin-2-amina formulacion farmaceutica que lo comprende y su uso para la manufactura de un medicamento util para el tratamiento de la enfermedad de alzheimer
GB0912778D0 (en) 2009-07-22 2009-08-26 Eisai London Res Lab Ltd Fused aminodihydro-oxazine derivatives
GB0912777D0 (en) 2009-07-22 2009-08-26 Eisai London Res Lab Ltd Fused aminodihydropyrimidone derivatives
UY32799A (es) 2009-07-24 2011-02-28 Novartis Ag Derivados de oxazina y su uso en el tratamiento de trastornos neurológicos
US8188079B2 (en) 2009-08-19 2012-05-29 Hoffman-La Roche Inc. 3-amino-5-phenyl-5,6-dihydro-2H-[1,4]oxazines
US20110065695A1 (en) 2009-09-11 2011-03-17 Jeremy Beauchamp Use of aminodihydrothiazines for the treatment or prevention of diabetes
US8563543B2 (en) 2009-10-08 2013-10-22 Merck Sharp & Dohme Corp. Iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use
UA108363C2 (uk) * 2009-10-08 2015-04-27 Похідні імінотіадіазиндіоксиду як інгібітори bace, композиція на їх основі і їх застосування
WO2011044185A2 (en) 2009-10-08 2011-04-14 Schering Corporation Pentafluorosulfur imino heterocyclic compounds as bace-1 inhibitors, compositions, and their use
US8557826B2 (en) * 2009-10-08 2013-10-15 Merck Sharp & Dohme Corp. Pentafluorosulfur imino heterocyclic compounds as BACE-1 inhibitors, compositions, and their use
CN102686584A (zh) 2009-11-13 2012-09-19 盐野义制药株式会社 具有氨基连接基的氨基噻嗪或氨基噁嗪衍生物
WO2011072064A1 (en) 2009-12-08 2011-06-16 Array Biopharma Inc. S piro [chroman - 4, 4 ' - imidazol] ones as beta - secretase inhibitors
WO2011071057A1 (ja) 2009-12-09 2011-06-16 塩野義製薬株式会社 含硫黄複素環誘導体を含有するアルツハイマー症の治療用または予防用医薬組成物
JPWO2011070781A1 (ja) 2009-12-09 2013-04-22 塩野義製薬株式会社 置換アミノチアジン誘導体
US7964594B1 (en) 2009-12-10 2011-06-21 Hoffmann-La Roche Inc. Amino oxazine derivatives
EP2511269A4 (en) 2009-12-11 2013-04-24 Shionogi & Co FUSED HETEROCYCLIC COMPOUND HAVING AN AMINO GROUP
UA103272C2 (ru) 2009-12-11 2013-09-25 Ф. Хоффманн-Ля Рош Аг 2-амино-5,5-дифтор-5,6-дигидро-4h-оксазины как ингибиторы bace1 и/или bace2
US8999980B2 (en) 2009-12-11 2015-04-07 Shionogi & Co., Ltd. Oxazine derivatives
EP2518059A4 (en) 2009-12-24 2013-05-29 Shionogi & Co 4-AMINO-1,3-THIAZINE OR OXAZINE DERIVATIVE
US20120277244A1 (en) 2009-12-31 2012-11-01 Novartis Ag Pyrazine derivatives and their use in the treatment of neurological disorders
US8735384B2 (en) 2010-01-19 2014-05-27 Amgen Inc. Amino heteroaryl compounds as beta-secretase modulators and methods of use
EP2539322B1 (en) 2010-02-24 2014-01-01 Vitae Pharmaceuticals, Inc. Inhibitors of beta-secretase
AU2011227511B2 (en) 2010-03-15 2014-02-20 Amgen Inc. Spiro-tetracyclic ring compounds as Beta - secretase modulators
JP5584352B2 (ja) 2010-03-15 2014-09-03 アムジエン・インコーポレーテツド β−セクレターゼ調節剤としてのアミノ−ジヒドロオキサジン系およびアミノ−ジヒドロチアジン系スピロ化合物ならびにそれらの医学的用途
WO2011123674A1 (en) 2010-03-31 2011-10-06 Array Biopharma Inc. Compounds for treating neurodegenerative diseases
US20130108645A1 (en) 2010-04-13 2013-05-02 The Johns Hopkins University Methods for enhancing axonal regeneration
WO2011130741A1 (en) 2010-04-16 2011-10-20 Array Biopharma Inc. Compounds for treating neurodegenerative diseases
US8673894B2 (en) 2010-05-07 2014-03-18 Hoffmann-La Roche Inc. 2,5,6,7-tetrahydro-[1,4]oxazepin-3-ylamine or 2,3,6,7-tetrahydro-[1,4]oxazepin-5-ylamine compounds
WO2011142716A1 (en) 2010-05-12 2011-11-17 Astrazeneca Ab Novel hemifumarate salt of isoindole compound acting as bace inhibitor
WO2011154431A1 (en) 2010-06-09 2011-12-15 Janssen Pharmaceutica Nv 5,6-dihydro-2h-[1,4]oxazin-3-yl-amine derivatives useful as inhibitors of beta-secretase (bace)
JP2013531644A (ja) 2010-06-09 2013-08-08 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 βセクレターゼ（ＢＡＣＥ）の阻害剤として有用な５−アミノ−３，６−ジヒドロ−１Ｈ−ピラジン−２−オン誘導体
TWI421250B (zh) 2010-07-13 2014-01-01 Novartis Ag 衍生物及其用於治療神經性疾病之用途
US8815881B2 (en) 2010-08-09 2014-08-26 Hoffmann-La Roche Inc. 1,4,5,6-tetrahydro-pyrimidin-2-ylamine compounds
AR083169A1 (es) 2010-09-24 2013-02-06 Array Biopharma Inc Compuestos para tratar enfermedades neurodegenerativas
EP2634188A4 (en) 2010-10-29 2014-05-07 Shionogi & Co FUSIONED AMINODIHYDROPYRIMIDINE DERIVATIVE
EP2634186A4 (en) 2010-10-29 2014-03-26 Shionogi & Co naphthyridine
AR083953A1 (es) 2010-11-22 2013-04-10 Array Biopharma Inc Compuestos para tratar enfermedades neurodegenerativas
EP2643325A1 (en) 2010-11-23 2013-10-02 Amgen Inc. Spiro-amino-imidazolone and spiro-amino-dihydro-pyrimidinone compounds as beta-secretase modulators and methods of use
US9242943B2 (en) 2011-01-18 2016-01-26 Siena Biotech S.P.A. 1,4 oxazines as BACE1 and/or BACE2 inhibitors
US8399459B2 (en) 2011-02-02 2013-03-19 Hoffmann-La Roche Inc. 1,4 oxazines as BACE1 and/or BACE2 inhibitors
US8404680B2 (en) 2011-02-08 2013-03-26 Hoffmann-La Roche Inc. N-[3-(5-amino-3,3a,7,7a-tetrahydro-1H-2,4-dioxa-6-aza-inden-7-yl)-phenyl]-amides as BACE1 and/or BACE2 inhibitors
WO2012138590A1 (en) * 2011-04-07 2012-10-11 Merck Sharp & Dohme Corp. Pyrrolidine-fused thiadiazine dioxide compounds as bace inhibitors, compositions, and their use
US8754075B2 (en) 2011-04-11 2014-06-17 Hoffmann-La Roche Inc. 1,3-oxazines as BACE1 and/or BACE2 inhibitors
US9079919B2 (en) 2011-05-27 2015-07-14 Hoffmann-La Roche Inc. Spiro-[1,3]-oxazines and spiro-[1,4]-oxazepines as BACE1 and/or BACE2 inhibitors
JP2012250933A (ja) 2011-06-03 2012-12-20 Shionogi & Co Ltd オキサジン誘導体を含有するアルツハイマー症治療用または予防用医薬組成物
EP2747769B1 (en) * 2011-08-22 2017-08-02 Merck Sharp & Dohme Corp. 2-spiro-substituted iminothiazines and their mono-and dioxides as bace inhibitors, compositions and their use
US8338413B1 (en) 2012-03-07 2012-12-25 Novartis Ag Oxazine derivatives and their use in the treatment of neurological disorders

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