HUE026912T2 - Substituted 5-fluoro-1h-pyrazolopyridines and use thereof - Google Patents
Substituted 5-fluoro-1h-pyrazolopyridines and use thereof Download PDFInfo
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- HUE026912T2 HUE026912T2 HUE11720806A HUE11720806A HUE026912T2 HU E026912 T2 HUE026912 T2 HU E026912T2 HU E11720806 A HUE11720806 A HU E11720806A HU E11720806 A HUE11720806 A HU E11720806A HU E026912 T2 HUE026912 T2 HU E026912T2
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- LTYNYHHABUSSHS-UHFFFAOYSA-N 5-fluoro-1h-pyrazolo[4,3-b]pyridine Chemical class FC1=CC=C2NN=CC2=N1 LTYNYHHABUSSHS-UHFFFAOYSA-N 0.000 title 1
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- -1 pyrrolidin-5-yl Chemical group 0.000 claims description 18
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102010021637A DE102010021637A1 (de) | 2010-05-26 | 2010-05-26 | Substituierte 5-Fluor-1H-Pyrazolopyridine und ihre Verwendung |
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| HUE026912T2 true HUE026912T2 (en) | 2016-07-28 |
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| HUE11720806A HUE026912T2 (en) | 2010-05-26 | 2011-05-24 | Substituted 5-fluoro-1h-pyrazolopyridines and use thereof |
| HUS2100032C HUS2100032I1 (hu) | 2010-05-26 | 2021-08-27 | Helyettesített 5-fluor-1H-pirazolopiridin-származékok és alkalmazásuk |
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| HUS2100032C HUS2100032I1 (hu) | 2010-05-26 | 2021-08-27 | Helyettesített 5-fluor-1H-pirazolopiridin-származékok és alkalmazásuk |
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|---|---|---|---|---|
| DE102008063992A1 (de) * | 2008-12-19 | 2010-09-02 | Lerner, Zinoviy, Dipl.-Ing. | Neue aliphatisch substituierte Pyrazolopyridine und ihre Verwendung |
| EP3699180A1 (de) | 2009-11-27 | 2020-08-26 | Adverio Pharma GmbH | Verfahren zur herstellung von methyl-{4,6-diamino-2-[1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}methylcarbamat und dessen aufreinigung für die verwendung als pharmazeutischer wirkstoff |
| WO2011119518A1 (en) | 2010-03-25 | 2011-09-29 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
| DE102010021637A1 (de) | 2010-05-26 | 2011-12-01 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 5-Fluor-1H-Pyrazolopyridine und ihre Verwendung |
| PE20130222A1 (es) | 2010-05-27 | 2013-03-14 | Merck Sharp & Dohme | Activadores de guanilato ciclasa soluble |
| MX2013000198A (es) | 2010-07-09 | 2013-01-28 | Bayer Ip Gmbh | Pirimidinadas y triazinas condensadas y su uso. |
| WO2012058132A1 (en) | 2010-10-28 | 2012-05-03 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
| DE102010043379A1 (de) | 2010-11-04 | 2012-05-10 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 6-Fluor-1H-Pyrazolo[4,3-b]pyridine und ihre Verwendung |
| DE102010043380A1 (de) | 2010-11-04 | 2012-05-10 | Bayer Schering Pharma Aktiengesellschaft | Benzyl-substituierte Carbamate und ihre Verwendung |
| DE102011007272A1 (de) | 2011-04-13 | 2012-10-18 | Bayer Pharma Aktiengesellschaft | Verzweigte 3-Phenylpropionsäure-Derivate und ihre Verwendung |
| JP6005134B2 (ja) | 2011-04-21 | 2016-10-12 | バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＢａｙｅｒ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ ＧｍｂＨ | フルオロアルキル置換ピラゾロピリジンおよびその使用 |
| EP2594270A3 (en) * | 2011-11-18 | 2013-07-31 | BIP Patents | The use of sGC stimulators, sGC activators, alone and combinations with PDE5 inhibitors for the treatment of systemic sclerosis (SSc) |
| BR112014012414B1 (pt) * | 2011-11-25 | 2022-01-11 | Adverio Pharma Gmbh | Processos para preparar 5-flúor-1h-pirazolopiridinas substituídas |
| CN102491974B (zh) | 2011-12-12 | 2013-08-07 | 南京药石药物研发有限公司 | 1-（2-氟苄基）-1H-吡唑并[3，4-b]吡啶-3-甲脒盐酸盐的合成方法 |
| DE102012200352A1 (de) * | 2012-01-11 | 2013-07-11 | Bayer Intellectual Property Gmbh | Substituierte, annellierte Imidazole und Pyrazole und ihre Verwendung |
| DE102012200360A1 (de) | 2012-01-11 | 2013-07-11 | Bayer Intellectual Property Gmbh | Substituierte Triazine und ihre Verwendung |
| DE102012200349A1 (de) | 2012-01-11 | 2013-07-11 | Bayer Intellectual Property Gmbh | Substituierte annellierte Pyrimidine und Triazine und ihre Verwendung |
| US9498480B2 (en) | 2012-03-06 | 2016-11-22 | Bayer Intellectual Property Gmbh | Substituted azabicycles and use thereof |
| WO2013144191A1 (de) | 2012-03-29 | 2013-10-03 | Bayer Intellectual Property Gmbh | Substituierte 2 -amino - 3 - cyanopyridine als inhibitoren des natrium calcium austausches und ihre verwendung bei kardiovaskulären erkrankungen |
| AU2013292046C1 (en) | 2012-07-20 | 2018-03-15 | Bayer Pharma Aktiengesellschaft | Novel 5-aminotetrahydroquinoline-2-carboxylic acids and use thereof |
| JP6324956B2 (ja) | 2012-07-20 | 2018-05-16 | バイエル・ファルマ・アクティエンゲゼルシャフト | 置換アミノインダン−およびアミノテトラリンカルボン酸ならびにその使用 |
| US9278968B2 (en) | 2012-11-30 | 2016-03-08 | Astellas Pharma Inc. | Imidazopyridine compounds |
| EP2958914B1 (en) | 2013-02-21 | 2020-07-15 | Adverio Pharma GmbH | Forms of methyl {4,6-diamino-2-[1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridino-3-yl]pyrimidino-5-yl}methyl carbamate |
| WO2014131760A1 (de) | 2013-03-01 | 2014-09-04 | Bayer Pharma Aktiengesellschaft | Trifluormethyl-substituierte annellierte pyrimidine und ihre verwendung |
| HK1222852A1 (zh) | 2013-06-21 | 2017-07-14 | Bayer Pharma Aktiengesellschaft | 二氨基杂芳基取代的吡唑 |
| CA2917682A1 (en) | 2013-07-10 | 2015-01-15 | Bayer Pharma Aktiengesellschaft | Benzyl-1h-pyrazolo[3,4-b]pyridines and use thereof |
| US10265314B2 (en) | 2013-07-25 | 2019-04-23 | Bayer Pharma Aktiengesellschaft | SGC stimulators in combination with additional treatment for the therapy of cystic fibrosis |
| UY35735A (es) | 2013-09-16 | 2015-04-30 | Bayer Pharma AG | Trifluorometilpirimidinonas disustituidas y su uso |
| MX2016004250A (es) | 2013-10-07 | 2016-07-12 | Bayer Pharma AG | Tienouracilcarboxamidas ciclicas y usos de las mismas. |
| EP3079700B1 (en) | 2013-12-11 | 2020-11-25 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
| WO2015088885A1 (en) | 2013-12-11 | 2015-06-18 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
| WO2015106268A1 (en) | 2014-01-13 | 2015-07-16 | Ironwood Pharmaceuticals, Inc. | USE OF sGC STIMULATORS FOR THE TREATMENT OF NEUROMUSCULAR DISORDERS |
| JP2017511319A (ja) | 2014-04-03 | 2017-04-20 | バイエル ファーマ アクチエンゲゼルシャフト | キラル２，５−ジ置換されたシクロペンタンカルボン酸誘導体およびそれの使用 |
| EP3126339A1 (de) | 2014-04-03 | 2017-02-08 | Bayer Pharma Aktiengesellschaft | 2,5-disubstituierte cyclopentancarbonsäuren und ihre verwendung |
| US20170114049A1 (en) | 2014-04-03 | 2017-04-27 | Bayer Pharma Aktiengesellschaft | 2,5-disubstituted cyclopentane carboxylic acids for the treatment of respiratory tract diseases |
| WO2015187470A1 (en) | 2014-06-04 | 2015-12-10 | Merck Sharp & Dohme Corp. | Imidazo-pyrazine derivatives useful as soluble guanylate cyclase activators |
| US10189788B2 (en) | 2014-09-09 | 2019-01-29 | Bayer Pharma Aktiengesellschaft | Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents |
| WO2016046157A1 (de) | 2014-09-24 | 2016-03-31 | Bayer Pharma Aktiengesellschaft | Faktor xia hemmende pyridobenzazepin- und pyridobenzazocin-derivate |
| SG11201703199UA (en) | 2014-11-03 | 2017-05-30 | Bayer Pharma AG | Hydroxyalkyl-substituted phenyltriazole derivatives and uses thereof |
| TW201625635A (zh) | 2014-11-21 | 2016-07-16 | 默沙東藥廠 | 作為可溶性鳥苷酸環化酶活化劑之三唑并吡基衍生物 |
| WO2016113205A1 (de) | 2015-01-13 | 2016-07-21 | Bayer Pharma Aktiengesellschaft | Substituierte pentafluorethylpyrimidinone und ihre verwendung |
| UY36586A (es) | 2015-03-26 | 2016-10-31 | Bayer Pharma AG | Heterociclilmetiltienouracilos y uso de los mismos |
| WO2016177660A1 (en) | 2015-05-06 | 2016-11-10 | Bayer Pharma Aktiengesellschaft | The use of sgc stimulators, sgc activators, alone and combinations with pde5 inhibitors for the treatment of digital ulcers (du) concomitant to systemic sclerosis (ssc) |
| WO2016191334A1 (en) | 2015-05-27 | 2016-12-01 | Merck Sharp & Dohme Corp. | Imidazo-pyrazinyl derivatives useful as soluble guanylate cyclase activators |
| US10213429B2 (en) | 2015-05-28 | 2019-02-26 | Merck Sharp & Dohme Corp. | Imidazo-pyrazinyl derivatives useful as soluble guanylate cyclase activators |
| LT3325013T (lt) | 2015-07-23 | 2020-11-10 | Bayer Pharma Aktiengesellschaft | Tirpios guanilatciklazės (sgc) stimuliatoriai/aktyvatoriai derinyje su nep inhibitoriumi ir (arba) angiotenzino aii antagonistu ir jų naudojimas |
| US10759794B2 (en) | 2015-12-10 | 2020-09-01 | Bayer Pharma Aktiengesellschaft | 2-phenyl-3-(piperazinomethyl)imidazo[1,2-A]pyridine derivatives as blockers of task-1 and task-2 channels, for the treatment of sleep-related breathing disorders |
| EP3386993A1 (de) | 2015-12-10 | 2018-10-17 | Bayer Pharma Aktiengesellschaft | Substituierte perhydropyrrolo[3,4-c]pyrrol-derivate und ihre verwendung |
| JP2019502686A (ja) | 2015-12-14 | 2019-01-31 | アイアンウッド ファーマシューティカルズ インコーポレイテッド | 消化管括約筋機能障害の治療へのｓＧＣ刺激薬の使用 |
| CN105461715B (zh) * | 2015-12-15 | 2017-03-29 | 郑州大明药物科技有限公司 | 一种利奥西呱中间体的合成方法 |
| WO2017107052A1 (en) | 2015-12-22 | 2017-06-29 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase stimulators |
| WO2017121692A1 (de) | 2016-01-15 | 2017-07-20 | Bayer Pharma Aktiengesellschaft | Substituierte sulfamide und ihre verwendung |
| US11357777B2 (en) * | 2016-02-01 | 2022-06-14 | Cyclerion Therapeutics, Inc. | Use of sGC stimulators for the treatment of nonalcoholic steatohepatitis (NASH) |
| WO2017153231A1 (de) | 2016-03-09 | 2017-09-14 | Bayer Pharma Aktiengesellschaft | Substituierte n-cyclo-2-arylisochinolinon-4-carboxamide und ihre verwendung |
| WO2017153234A1 (de) | 2016-03-09 | 2017-09-14 | Bayer Pharma Aktiengesellschaft | Substituierte n-cyclo-2-arylchinolin-4-carboxamide und ihre verwendung |
| WO2017153235A1 (de) | 2016-03-09 | 2017-09-14 | Bayer Pharma Aktiengesellschaft | Substituierte n-cyclo-3-aryl-1-naphthamide und ihre verwendung |
| WO2017191114A1 (en) | 2016-05-03 | 2017-11-09 | Bayer Aktiengesellschaft | Hydroxyalkyl-substituted heteroaryltriazole derivatives and uses thereof |
| US10525041B2 (en) | 2016-05-03 | 2020-01-07 | Bayer Pharma Aktiengesellschaft | Fluoroalkyl-substituted aryltriazole derivatives and uses thereof |
| CA3022755A1 (en) | 2016-05-03 | 2017-11-09 | Carsten Schmeck | Oxoalkyl-substituted phenyltriazole derivatives and uses thereof |
| WO2017191117A1 (en) | 2016-05-03 | 2017-11-09 | Bayer Pharma Aktiengesellschaft | V1a receptor antagonists for use in the treatment of renal diseases |
| AR108263A1 (es) | 2016-05-03 | 2018-08-01 | Bayer Pharma AG | Procedimiento para la preparación de derivados de 1-fenilo-1,2,4-triazol sustituidos por 5-hidroxialquilo |
| US9988367B2 (en) | 2016-05-03 | 2018-06-05 | Bayer Pharma Aktiengesellschaft | Amide-substituted pyridinyltriazole derivatives and uses thereof |
| US20190119251A1 (en) | 2016-05-03 | 2019-04-25 | Bayer Pharma Aktiengesellschaft | Amide-substituted aryltriazole derivatives and uses thereof |
| JOP20170113B1 (ar) | 2016-05-09 | 2023-03-28 | Bayer Pharma AG | مركبات 5، 6، 7، 8-رباعي هيدرو [1، 2، 4] تريازولو [4، 3-أ] بيريدين 3(2h)-ون مستبدلة ومركبات 2، 5، 6، 7-رباعي هيدرو-3h-بيرولو [2، 1-ج] [1، 2، 4] تريازول-3-ون واستخداماتها |
| WO2017197555A1 (en) | 2016-05-16 | 2017-11-23 | Merck Sharp & Dohme Corp. | Fused pyrazine derivatives useful as soluble guanylate cyclase stimulators |
| US10925876B2 (en) | 2016-05-18 | 2021-02-23 | Merck Sharp & Dohme Corp. | Methods for using triazolo-pyrazinyl soluble guanylate cyclase activators in fibrotic disorders |
| CA3030204A1 (en) | 2016-07-11 | 2018-01-18 | Bayer Pharma Aktiengesellschaft | 7-substituted 1-pyridyl-naphthyridine-3-carboxylic acid amides and use thereof |
| JOP20190005A1 (ar) | 2016-07-20 | 2019-01-20 | Bayer Ag | مركبات ديازاهيترو ثنائية الحلقة مستبدلة واستخداماتها |
| WO2018041771A1 (de) | 2016-09-02 | 2018-03-08 | Bayer Pharma Aktiengesellschaft | (1-methylcyclopropyl)methyl-substituierte thienouracile und ihre verwendung |
| JOP20190045A1 (ar) | 2016-09-14 | 2019-03-14 | Bayer Ag | مركبات أميد حمض 1- أريل-نفثيريدين-3-كربوكسيليك مستبدلة في الموضع 7 واستخدامها. |
| EP3296298A1 (de) | 2016-09-14 | 2018-03-21 | Bayer Pharma Aktiengesellschaft | 7-substituierte 1-aryl-naphthyridin-3-carbonsäureamide und ihre verwendung |
| RU2019111357A (ru) | 2016-09-23 | 2020-10-23 | Байер Акциенгезельшафт | N3-циклически замещенные тиеноурацилы и их применение |
| CA3039734A1 (en) * | 2016-10-11 | 2018-04-19 | Bayer Pharma Aktiengesellschaft | Combination containing sgc stimulators and mineralocorticoid receptor antagonists |
| CN109890379A (zh) | 2016-10-11 | 2019-06-14 | 拜耳制药股份公司 | 包含sGC活化剂和盐皮质激素受体拮抗剂的组合产品 |
| JOP20190080A1 (ar) | 2016-10-14 | 2019-04-11 | Bayer Pharma AG | مركبات مشتقة من 6-(1h-بيرازول-1-يل) بيريميدين-4- أمين مستبدل واستخداماتها |
| US10927098B2 (en) | 2016-10-20 | 2021-02-23 | Bayer Pharma Aktiengesellschaft | Hydroxyalkyl-substituted triazole derivatives and uses thereof |
| US20190381039A1 (en) | 2016-12-13 | 2019-12-19 | Cyclerion Therapeutics, Inc. | USE OF sGC STIMULATORS FOR THE TREATMENT OF ESOPHAGEAL MOTILITY DISORDERS |
| EP3338764A1 (de) | 2016-12-21 | 2018-06-27 | Bayer Pharma Aktiengesellschaft | Pharmazeutische darreichungsformen enthaltend inhibitoren von task-1 und task-3 kanälen und deren verwendung für die therapie von atemstörungen |
| EP3338803A1 (de) | 2016-12-21 | 2018-06-27 | Bayer Pharma Aktiengesellschaft | Pharmazeutische darreichungsformen enthaltend inhibitoren von task-1 und task-3 kanälen und deren verwendung für die therapie von atemstörungen |
| JOP20190141A1 (ar) | 2016-12-21 | 2019-06-12 | Bayer Pharma AG | أشكال جرعات صيدلية تحتوي على مثبطات لقناة task-1 و task-3 واستخدامها في معالجة اضطراب تنفسي |
| JOP20190148A1 (ar) | 2016-12-21 | 2019-06-18 | Bayer Pharma AG | أشكال جرعات صيدلية تحتوي على مثبطات قنوات task-1 و task-3 واستخدامها لمعالجة الاضطرابات التنفسية |
| WO2018153899A1 (de) * | 2017-02-22 | 2018-08-30 | Bayer Pharma Aktiengesellschaft | Selektive partielle adenosin a1 rezeptor-agonisten in kombination mit stimulatoren und/oder aktivatoren der löslichen guanylatcyclase (sgc) |
| BR112019021136A2 (pt) | 2017-04-10 | 2020-07-21 | Bayer Aktiengesellschaft | n-ariletil-2-arilquinolina-4-carboxamidas substituídas e uso das mesmas |
| TWI770157B (zh) | 2017-04-10 | 2022-07-11 | 德商拜耳廠股份有限公司 | 經取代之n-芳基乙基-2-胺基喹啉-4-甲醯胺及其用途 |
| CN108690016B (zh) * | 2017-04-11 | 2022-08-12 | 广东东阳光药业有限公司 | 吡唑并吡啶类化合物及其用途 |
| JP7090639B2 (ja) | 2017-04-11 | 2022-06-24 | サンシャイン・レイク・ファーマ・カンパニー・リミテッド | フッ素置換されたインダゾール化合物及びその使用 |
| JOP20190284A1 (ar) | 2017-06-14 | 2019-12-11 | Bayer Pharma AG | مركبات إيميدازوبيريميدين مستبدلة بديازا ثنائي الحلقة واستخدامها للمعالجة من اضطرابات التنفس |
| WO2018227427A1 (en) | 2017-06-14 | 2018-12-20 | Bayer Aktiengesellschaft | Substituted bridged diazepane derivatives and use thereof |
| RS62984B1 (sr) | 2017-10-24 | 2022-03-31 | Bayer Ag | Prolekovi supstituisanih derivata triazola i njihova upotreba |
| BR112020007967A2 (pt) * | 2017-10-24 | 2020-10-20 | Bayer Aktiengesellschaft | imidazopiridina amidas substituídas e uso das mesmas |
| EP3700897A1 (en) | 2017-10-24 | 2020-09-02 | Bayer Pharma Aktiengesellschaft | Substituted triazole derivatives and uses thereof |
| CA3079771A1 (en) | 2017-10-24 | 2019-05-02 | Bayer Pharma Aktiengesellschaft | Substituted triazole derivatives and uses thereof |
| EP3700898A1 (en) | 2017-10-24 | 2020-09-02 | Bayer Pharma Aktiengesellschaft | Substituted triazole derivatives and uses thereof |
| WO2019081299A1 (en) | 2017-10-24 | 2019-05-02 | Bayer Pharma Aktiengesellschaft | AMINE SUBSTITUTED TRIAZOLE DERIVATIVES AND USES THEREOF |
| US11173151B2 (en) | 2017-10-24 | 2021-11-16 | Bayer Aktiengesellschaft | Substituted triazole derivatives and uses thereof |
| WO2019081291A1 (en) | 2017-10-24 | 2019-05-02 | Bayer Aktiengesellschaft | PRODRUGS OF SUBSTITUTED TRIAZOLE DERIVATIVES AND USES THEREOF |
| US11337973B2 (en) | 2017-11-07 | 2022-05-24 | Bayer Aktiengesellschaft | Substituted [1,2,4]triazolo[4,3-A]pyrazines as prolyl endopeptidase inhibitors |
| US11332435B2 (en) | 2017-12-01 | 2022-05-17 | Bayer Pharma Aktiengesellschaft | Method for producing (3S)-3-(4-chloro-3-{[(2S,3R)-2-(4- chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)-3-cyclo-propylpropanoic acid and the crystalline form thereof for use as a pharmaceutical ingredient |
| MX2020006433A (es) * | 2017-12-19 | 2020-09-17 | Cyclerion Therapeutics Inc | Estimuladores de guanilato ciclasa soluble (sgc). |
| EP3553079A1 (en) | 2018-04-12 | 2019-10-16 | Bayer Aktiengesellschaft | C-type natriuretic peptide engrafted antibodies |
| EP3553082A1 (en) | 2018-04-12 | 2019-10-16 | Bayer Aktiengesellschaft | Brain natriuretic peptide engrafted antibodies |
| EP3553081A1 (en) | 2018-04-12 | 2019-10-16 | Bayer Aktiengesellschaft | Atrial natriuretic peptide engrafted antibodies |
| CN112055584A (zh) * | 2018-04-30 | 2020-12-08 | 拜耳公司 | sGC活化剂和sGC刺激剂用于治疗认知障碍的用途 |
| EP3566704A1 (en) | 2018-05-11 | 2019-11-13 | Bayer Aktiengesellschaft | The use of non-steroidal mineralocorticoid receptor antagonists alone or in combination for the treatment of muscular or neuromuscular diseases |
| CN112384213A (zh) | 2018-05-15 | 2021-02-19 | 拜耳公司 | 用于治疗与神经纤维敏化有关的疾病的1,3-噻唑-2-基取代的苯甲酰胺 |
| MX2020012201A (es) | 2018-05-17 | 2021-01-29 | Bayer Ag | Derivados sustituidos de la carboxamida dihidropirazolo pirazina. |
| US11508483B2 (en) | 2018-05-30 | 2022-11-22 | Adverio Pharma Gmbh | Method of identifying a subgroup of patients suffering from dcSSc which benefits from a treatment with sGC stimulators and sGC activators in a higher degree than a control group |
| AU2019301683B9 (en) | 2018-07-11 | 2025-04-24 | Tisento Therapeutics Inc. | Use of sGC stimulators for the treatment of mitochondrial disorders |
| MX2021000904A (es) | 2018-07-24 | 2021-03-31 | Bayer Ag | Forma de dosificacion farmaceutica administrable por via oral con liberacion modificada. |
| CN112469398A (zh) | 2018-07-24 | 2021-03-09 | 拜耳公司 | 可口服给药并具有缓释作用的药物剂型 |
| US10905667B2 (en) | 2018-07-24 | 2021-02-02 | Bayer Pharma Aktiengesellschaft | Orally administrable modified-release pharmaceutical dosage form |
| SG11202105551YA (en) | 2018-11-27 | 2021-06-29 | Bayer Ag | Process for producing pharmaceutical dosage forms containing task-1 and task-3 channel inhibitors, and the use of same in breathing disorder therapy |
| TWI830835B (zh) | 2018-12-17 | 2024-02-01 | 德商亞德維瑞醫藥有限公司 | 具改善性質之{4,6-二胺基-2-[5-氟-1-(2-氟芐基)-1H-吡唑並[3,4-b]吡啶-3-基]嘧啶-5-基}胺基甲酸甲酯活性化合物產物、其製造及調配物 |
| WO2020164008A1 (en) | 2019-02-13 | 2020-08-20 | Bayer Aktiengesellschaft | Process for the preparation of porous microparticles |
| WO2020216669A1 (de) | 2019-04-23 | 2020-10-29 | Bayer Aktiengesellschaft | Phenylsubstituierte imidazopyridinamide und ihre verwendung |
| PE20220431A1 (es) | 2019-05-07 | 2022-03-29 | Bayer Ag | Compuestos inhibidores de la masp y usos de estos |
| TW202112359A (zh) | 2019-06-07 | 2021-04-01 | 德商拜耳廠股份有限公司 | sGC活化劑於治療眼科疾病之用途 |
| PE20221025A1 (es) | 2019-11-06 | 2022-06-16 | Bayer Ag | Inhibidores de los receptores a2c adrenergicos |
| WO2021094209A1 (en) | 2019-11-12 | 2021-05-20 | Bayer Aktiengesellschaft | Substituted pyrrolo triazine carboxamide derivatives as prostaglandin ep3 receptor antagonists |
| WO2021094208A1 (en) | 2019-11-12 | 2021-05-20 | Bayer Aktiengesellschaft | Substituted imidazo pyrimidine ep3 antagonists |
| WO2021094210A1 (en) | 2019-11-12 | 2021-05-20 | Bayer Aktiengesellschaft | Substituted pyrazine carboxamide derivatives as prostaglandin ep3 receptor antagonists |
| EP3822268A1 (en) | 2019-11-15 | 2021-05-19 | Bayer Aktiengesellschaft | Substituted hydantoinamides as adamts7 antagonists |
| EP3822265A1 (en) | 2019-11-15 | 2021-05-19 | Bayer AG | Substituted hydantoinamides as adamts7 antagonists |
| JP7780442B2 (ja) | 2020-02-03 | 2025-12-04 | アドヴェリオ・ファーマ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | メチル｛４，６－ジアミノ－２－［５－フルオロ－１－（２－フルオロベンジル）－１Ｈ－ピラゾロ［３，４－ｂ］ピリジン－３－イル］ピリミジン－５－イル｝カルバメートのナノ製剤 |
| EP4106741A1 (en) | 2020-02-21 | 2022-12-28 | Universiteit Maastricht | Use of a soluble guanylate cyclase (sgc) stimulator or of a combination of a sgc stimulator and an sgc activator for conditions wherein the heme group of sgc is oxidized or wherein sgc is deficient in heme |
| CA3170508A1 (en) | 2020-02-26 | 2021-09-02 | Universiteit Maastricht | Therapeutic combination for the treatment of brain ischemia and said therapeutic combination for use in the treatment of brain ischemia |
| US20230130739A1 (en) | 2020-03-26 | 2023-04-27 | Cyclerion Therapeutics, Inc. | DEUTERATED sGC STIMULATORS |
| EP3925953A1 (en) * | 2020-06-16 | 2021-12-22 | Adverio Pharma GmbH | Process for preparing methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate |
| EP4240750A1 (en) | 2020-11-04 | 2023-09-13 | Bayer Aktiengesellschaft | Masp inhibitory compounds and uses thereof |
| EP4011904A1 (en) | 2020-12-14 | 2022-06-15 | Bayer Aktiengesellschaft | Masp inhibitory compounds and uses thereof |
| WO2022112213A1 (en) | 2020-11-30 | 2022-06-02 | Bayer Aktiengesellschaft | Crystalline forms of 3-[[3-(4-chlorophenyl)-5-oxo-4-((2s)-3,3,3-trifluoro- 2-hydroxypropyl)-4,5-dihydro-1h-1,2,4-triazol-1-yl]methyl]-1-[3- (trifluoromethyl)pyridin-2-yl]-1h-1,2,4-triazole-5-carboxamide |
| WO2022122916A1 (en) | 2020-12-10 | 2022-06-16 | Bayer Aktiengesellschaft | Substituted pyrazolyl piperidine carboxylic acids |
| WO2022122917A1 (en) | 2020-12-10 | 2022-06-16 | Bayer Aktiengesellschaft | The use of sgc activators for the treatment of ophthalmologic diseases |
| EP4011873A1 (en) | 2020-12-10 | 2022-06-15 | Bayer Aktiengesellschaft | Substituted pyrazolo piperidine carboxylic acids |
| EP4011874A1 (en) | 2020-12-10 | 2022-06-15 | Bayer Aktiengesellschaft | Substituted pyrazolo piperidine carboxylic acids |
| RS66294B1 (sr) | 2020-12-10 | 2025-01-31 | Bayer Ag | Supstituisane pirazolo piperidinske karboksilne kiseline |
| JP2024516623A (ja) | 2021-04-20 | 2024-04-16 | ティセント セラピューティクス インコーポレーテッド | ｓＧＣ刺激剤でのＣＮＳ疾患の処置 |
| JP2024515119A (ja) | 2021-04-20 | 2024-04-04 | ティセント セラピューティクス インコーポレーテッド | ｓＧＣ刺激剤 |
| WO2023034364A1 (en) | 2021-08-31 | 2023-03-09 | Teva Pharmaceuticals International Gmbh | Solid state forms of vericiguat and process for preparation thereof |
| AR128147A1 (es) | 2021-12-29 | 2024-03-27 | Bayer Ag | Procedimiento para la preparación del ácido (5s)-[2-(4-carboxifenil)etil][2-(2-[3-cloro-4-(trifluorometil)bifenil-4-il]metoxifenil)etil]amino-5,6,7,8-tetrahidroquinolina-2-carboxílico y sus formas cristalinas para su uso como compuesto farmacéuticamente activo |
| JP2025501309A (ja) | 2021-12-29 | 2025-01-17 | バイエル アクツィエンゲゼルシャフト | 心肺障害の治療 |
| CN118804741A (zh) | 2021-12-29 | 2024-10-18 | 拜耳股份公司 | 药物干粉吸入制剂 |
| ES2956054B2 (es) * | 2022-05-03 | 2024-07-01 | Moehs Iberica Sl | 2-(5-FLUORO-1-(2-FLUOROBENCIL)-1H-PIRAZOLO[3,4-b]PIRIDIN-3-IL)-5-NITROSOPIRIMIDIN-4,6-DIAMINA O UNA SAL DE LA MISMA, PROCEDIMIENTO PARA SU PREPARACION Y SU USO EN LA SINTESIS DE VERICIGUAT |
| TW202412753A (zh) | 2022-06-09 | 2024-04-01 | 德商拜耳廠股份有限公司 | 用於治療女性心臟衰竭合併保留射出分率的可溶性鳥苷酸環化酶活化劑 |
| CN120112293A (zh) | 2022-10-18 | 2025-06-06 | 帝善多制药公司 | 使用sGC刺激剂治疗线粒体疾病 |
| CN120225524A (zh) | 2022-10-18 | 2025-06-27 | 帝善多制药公司 | 嘧啶sGC刺激剂 |
| CN116239609A (zh) * | 2022-12-06 | 2023-06-09 | 山东百诺医药股份有限公司 | 一种维立西呱的关键杂质及其制备方法 |
| TW202529751A (zh) | 2023-09-28 | 2025-08-01 | 德商拜耳廠股份有限公司 | 經取代之雜環醯胺及其用途 |
| WO2025114276A1 (en) | 2023-12-01 | 2025-06-05 | Krka, D.D., Novo Mesto | Solid oral composition comprising vericiguat |
| WO2025132065A1 (en) | 2023-12-20 | 2025-06-26 | Adverio Pharma Gmbh | Dose regimen for vericiguat |
| CN117924280B (zh) * | 2024-03-20 | 2024-07-12 | 中国人民解放军军事科学院军事医学研究院 | 取代噻吩基-5-氟-1h-吡唑并吡啶类化合物及其用途 |
Family Cites Families (71)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01198481A (ja) * | 1988-02-01 | 1989-08-10 | Canon Inc | マイクロ波プラズマｃｖｄ法による堆積膜形成法 |
| GB9013750D0 (en) | 1990-06-20 | 1990-08-08 | Pfizer Ltd | Therapeutic agents |
| EP0463754A1 (en) | 1990-06-25 | 1992-01-02 | Rohm And Haas Company | Stabilization of glutarimide polymers |
| DK181190D0 (da) | 1990-07-30 | 1990-07-30 | Lundbeck & Co As H | 3-aryl-indol- eller 3-aryl-indazolderivater |
| GB9311920D0 (en) | 1993-06-09 | 1993-07-28 | Pfizer Ltd | Therapeutic agents |
| GB9314412D0 (en) | 1993-07-13 | 1993-08-25 | Rhone Poulenc Agriculture | New compositions of matter |
| GB9401090D0 (en) | 1994-01-21 | 1994-03-16 | Glaxo Lab Sa | Chemical compounds |
| EP0934311B1 (de) | 1996-10-14 | 2009-05-13 | Bayer HealthCare AG | Neue heterocyclylmethyl-substituierte pyrazolderivate und ihre verwendung in der behandlung von herz-kreislauf-erkrankungen |
| DE19642255A1 (de) | 1996-10-14 | 1998-04-16 | Bayer Ag | Verwendung von 1-Benzyl-3-(substituierten-hetaryl) -kondensierten Pyrazol-Derivaten |
| US6008243A (en) | 1996-10-24 | 1999-12-28 | Agouron Pharmaceuticals, Inc. | Metalloproteinase inhibitors, pharmaceutical compositions containing them, and their use |
| FR2757157B1 (fr) | 1996-12-13 | 1999-12-31 | Sanofi Sa | Derives d'indolin-2-one, procede pour leur preparation et compositions pharmaceutiques les contenant |
| PT1049695E (pt) | 1997-11-12 | 2002-07-31 | Bayer Ag | Imidazotriazinonas 2-fenil substituidas enquanto inibidores de fosfodiesterase |
| US6451805B1 (en) | 1997-11-14 | 2002-09-17 | Bayer Aktiengesellschaft | Substituted pyrazole derivatives for the treatment of cardiocirculatory diseases |
| DE19834047A1 (de) | 1998-07-29 | 2000-02-03 | Bayer Ag | Substituierte Pyrazolderivate |
| DE19834045A1 (de) | 1998-07-29 | 2000-02-03 | Bayer Ag | (4-Amino-5-ethylpyrimidin-2-yl)-1-(2-fluorbenzyl)-1H-pyrazolo[3,4-b]pyridin |
| DE19834044A1 (de) | 1998-07-29 | 2000-02-03 | Bayer Ag | Neue substituierte Pyrazolderivate |
| DE19846514A1 (de) | 1998-10-09 | 2000-04-20 | Bayer Ag | Neue Heterocyclyl-methyl-substituierte Pyrazole |
| GB0002666D0 (en) | 2000-02-04 | 2000-03-29 | Univ London | Blockade of voltage dependent sodium channels |
| DE10057754A1 (de) | 2000-11-22 | 2002-05-23 | Bayer Ag | Neue Sulfonamid-substituierte Pyrazolopyridinderivate |
| AR031176A1 (es) | 2000-11-22 | 2003-09-10 | Bayer Ag | Nuevos derivados de pirazolpiridina sustituidos con piridina |
| CA2429308C (en) | 2000-11-22 | 2010-09-21 | Bayer Aktiengesellschaft | Novel lactam-substituted pyrazolopyridine derivatives |
| DE10057751A1 (de) | 2000-11-22 | 2002-05-23 | Bayer Ag | Neue Carbamat-substituierte Pyrazolopyridinderivate |
| NZ526871A (en) | 2001-01-25 | 2006-01-27 | Bristol Myers Squibb Co | Pharmaceutical dosage forms of epothilones for oral administration |
| DE10122894A1 (de) | 2001-05-11 | 2002-11-14 | Bayer Ag | Neue Sulfonat-substituierte Pyrazolopyridinderivate |
| DE10132416A1 (de) | 2001-07-04 | 2003-01-16 | Bayer Ag | Neue Morpholin-überbrückte Pyrazolopyridinderivate |
| CA2464333C (en) | 2001-10-26 | 2011-07-26 | University Of Connecticut | Heteroindanes: a new class of potent cannabimimetic ligands |
| US7790905B2 (en) | 2002-02-15 | 2010-09-07 | Mcneil-Ppc, Inc. | Pharmaceutical propylene glycol solvate compositions |
| WO2003076408A2 (en) | 2002-03-08 | 2003-09-18 | Abbott Laboratories | Indazole derivatives that are activators of soluble guanylate cyclase |
| GR1004350B (el) * | 2002-03-29 | 2003-09-26 | Συσκευη εισπνοων ξηρης σκονης | |
| DE10220570A1 (de) * | 2002-05-08 | 2003-11-20 | Bayer Ag | Carbamat-substituierte Pyrazolopyridine |
| DE10222550A1 (de) | 2002-05-17 | 2003-11-27 | Bayer Ag | Substituierte Benzyl-pyrazolopyridine |
| DE10232572A1 (de) | 2002-07-18 | 2004-02-05 | Bayer Ag | Neue 2,5-disubstituierte Pyrimidinderivate |
| DE10232571A1 (de) | 2002-07-18 | 2004-02-05 | Bayer Ag | 4-Aminosubstituierte Pyrimidinderivate |
| DE10242941A1 (de) | 2002-09-16 | 2004-03-18 | Bayer Ag | Substituiertes Pyrazolderivat |
| DE10244810A1 (de) | 2002-09-26 | 2004-04-08 | Bayer Ag | Neue Morpholin-überbrückte Indazolderivate |
| DE60329318D1 (de) | 2002-11-20 | 2009-10-29 | Japan Tobacco Inc | 4-oxochinolinverbindungen und deren verwendung als hiv-integrase-inhibitoren |
| AU2004236085B2 (en) | 2003-05-09 | 2010-03-25 | Asahi Glass Company, Limited | Processes for producing 3-substituted 2-chloro-5-fluoropyridine or salt thereof |
| EP1646382A4 (en) | 2003-06-30 | 2010-07-21 | Hif Bio Inc | COMPOUNDS, COMPOSITIONS AND METHODS |
| PE20050483A1 (es) | 2003-10-31 | 2005-08-25 | Arena Pharm Inc | Derivados de tetrazol de formula (i), sus composiciones farmaceuticas y procesos para producir composiciones farmaceuticas |
| CN100355732C (zh) | 2003-11-03 | 2007-12-19 | 上海药明康德新药开发有限公司 | 2－氯－5－氟－烟酸酯及酸的制备方法 |
| DE10351903A1 (de) | 2003-11-06 | 2005-06-09 | Bayer Healthcare Ag | Neue Kombination |
| GB0403819D0 (en) | 2004-02-20 | 2004-03-24 | Merck Sharp & Dohme | New compounds |
| US7514463B2 (en) | 2004-08-20 | 2009-04-07 | University Of Kansas | Lonidamine analogues and their use in male contraception and cancer treatment |
| WO2006037491A1 (en) | 2004-10-05 | 2006-04-13 | Bayer Healthcare Ag | A guanylane cyclase stimulator and nitric oxide for treating bronchoconstriction and pulmonary vasoconstriction |
| DE102005047945A1 (de) | 2005-07-16 | 2007-01-18 | Bayer Healthcare Ag | Verwendung von Aktivatoren der löslichen Guanylatzyklase zur Behandlung von Raynaud Phänomenen |
| KR20080030669A (ko) | 2005-07-18 | 2008-04-04 | 바이엘 헬스케어 아게 | 신장병의 예방 또는 치료를 위한 가용성 구아닐레이트시클라제 활성화제 및 자극제의 신규 용도 |
| DE102006021733A1 (de) | 2006-05-09 | 2007-11-22 | Bayer Healthcare Ag | 3-Tetrazolylindazole und 3-Tetrazolylpyrazolopyridine sowie ihre Verwendung |
| DE102006043443A1 (de) | 2006-09-15 | 2008-03-27 | Bayer Healthcare Ag | Neue aza-bicyclische Verbindungen und ihre Verwendung |
| JP5588339B2 (ja) | 2007-06-25 | 2014-09-10 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規化学化合物 |
| AU2008282156B2 (en) | 2007-07-31 | 2014-07-17 | Vertex Pharmaceuticals Incorporated | Process for preparing 5-fluoro-1H-pyrazolo [3, 4-b] pyridin-3-amine and derivatives thereof |
| WO2009145814A2 (en) | 2008-03-10 | 2009-12-03 | Vertex Pharmaceuticals Incorporated | Pyrimidines and pyridines useful as inhibitors of protein kinases |
| DE102008063992A1 (de) * | 2008-12-19 | 2010-09-02 | Lerner, Zinoviy, Dipl.-Ing. | Neue aliphatisch substituierte Pyrazolopyridine und ihre Verwendung |
| DE102009004245A1 (de) | 2009-01-09 | 2010-07-15 | Bayer Schering Pharma Aktiengesellschaft | Neue anellierte, Heteroatom-verbrückte Pyrazol- und Imidazol-Derivate und ihre Verwendung |
| AR077898A1 (es) | 2009-08-26 | 2011-09-28 | Nycomed Gmbh | Metilpirrolopirimidincarboxamidas |
| UY33040A (es) | 2009-11-27 | 2011-06-30 | Bayer Schering Pahrma Akitengesellschaft | Nuevas formas polimorfas de {4,6diamino-2-[1-(2-fluorobencil-1h-pirazol[3,4-b]piridin-3-il]pirimidin-5-il}carbamato de metilo |
| EP3699180A1 (de) | 2009-11-27 | 2020-08-26 | Adverio Pharma GmbH | Verfahren zur herstellung von methyl-{4,6-diamino-2-[1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}methylcarbamat und dessen aufreinigung für die verwendung als pharmazeutischer wirkstoff |
| UY33041A (es) | 2009-11-27 | 2011-06-30 | Bayer Schering Pharma Aktienegesellschaft | Procedimiento para la preparaciòn de {4,6-diamino-2-[1-(2-fluorobencil)-1h-pirazolo[3,4-b]piridin-3-il]pirimidin-5-il}carbamato de metilo y su purificaciòn para el uso como principio activo farmacèutico |
| WO2011075655A1 (en) | 2009-12-18 | 2011-06-23 | Exodos Life Sciences Limited Partnership | Methods and compositions for treating peripheral vascular disease |
| US20130178475A1 (en) | 2010-03-17 | 2013-07-11 | Ironwood Pharmaceuticals, Inc. | sGC STIMULATORS |
| MY170094A (en) * | 2010-05-26 | 2019-07-05 | Adverio Pharma Gmbh | The use of sgc stimulators, sgc activators, alone and combinations with pde5 inhibitors for the treatment of systemic sclerosis (ssc). |
| DE102010021637A1 (de) | 2010-05-26 | 2011-12-01 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 5-Fluor-1H-Pyrazolopyridine und ihre Verwendung |
| PE20130222A1 (es) | 2010-05-27 | 2013-03-14 | Merck Sharp & Dohme | Activadores de guanilato ciclasa soluble |
| MX2013000198A (es) | 2010-07-09 | 2013-01-28 | Bayer Ip Gmbh | Pirimidinadas y triazinas condensadas y su uso. |
| DE102010040234A1 (de) | 2010-09-03 | 2012-03-08 | Bayer Schering Pharma Aktiengesellschaft | Verfahren zur Herstellung von 5-Flour-1H-pyrazolo[3,4-b]pyridin-3-carbonitril |
| DE102010040233A1 (de) | 2010-09-03 | 2012-03-08 | Bayer Schering Pharma Aktiengesellschaft | Bicyclische Aza-Heterocyclen und ihre Verwendung |
| DE102010043380A1 (de) | 2010-11-04 | 2012-05-10 | Bayer Schering Pharma Aktiengesellschaft | Benzyl-substituierte Carbamate und ihre Verwendung |
| DE102010043379A1 (de) | 2010-11-04 | 2012-05-10 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 6-Fluor-1H-Pyrazolo[4,3-b]pyridine und ihre Verwendung |
| US9499487B2 (en) | 2011-05-31 | 2016-11-22 | Theravance Biopharma R&D Ip, Llc | Neprilysin inhibitors |
| US8859569B2 (en) | 2011-09-02 | 2014-10-14 | Bayer Pharma Aktiengesellschaft | Substituted annellated pyrimidines and use thereof |
| BR112014012414B1 (pt) | 2011-11-25 | 2022-01-11 | Adverio Pharma Gmbh | Processos para preparar 5-flúor-1h-pirazolopiridinas substituídas |
| DE102012200352A1 (de) | 2012-01-11 | 2013-07-11 | Bayer Intellectual Property Gmbh | Substituierte, annellierte Imidazole und Pyrazole und ihre Verwendung |
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