AR100049A1 - Derivados de dihidrotiazina y dihidrooxazina con actividad inhibidora de bace1 - Google Patents
Derivados de dihidrotiazina y dihidrooxazina con actividad inhibidora de bace1Info
- Publication number
- AR100049A1 AR100049A1 ARP150101090A ARP150101090A AR100049A1 AR 100049 A1 AR100049 A1 AR 100049A1 AR P150101090 A ARP150101090 A AR P150101090A AR P150101090 A ARP150101090 A AR P150101090A AR 100049 A1 AR100049 A1 AR 100049A1
- Authority
- AR
- Argentina
- Prior art keywords
- substituted
- unsubstituted
- alkyl
- compound
- halogen
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5355—Non-condensed oxazines and containing further heterocyclic rings
-
- 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
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
-
- 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
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/541—Non-condensed thiazines containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Un compuesto que tiene un efecto inhibidor de la producción de amiloide b, en especial un efecto de inhibición de BACE1 y que es útil como un agente terapéutico o preventivo para enfermedades inducidas por producción, secreción y/o deposición de proteínas amiloide b. Reivindicación 1: Un compuesto de la fórmula (1) caracterizado porque X es -S- u -O-, (i) cuando X es -S-, entonces R³ᵃ es alquilo, haloalquilo, hidroxialquilo o alquiloxialquilo, R²ᵃ es halógeno, alquiloxi o haloalquiloxi y R²ᵃ puede ser alquilo cuando R³ᵃ es haloalquilo, R²ᵇ es H, R²ᵃ y R²ᵇ junto con el átomo de carbono al que se unen pueden formar cicloalcano sustituido, R³ᵃ puede ser H cuando R²ᵃ y R²ᵇ junto con el átomo de carbono al que se unen pueden formar cicloalcano sustituido, (ii) cuando X es -O-, luego R³ᵃ es haloalquilo opcionalmente sustituido con uno o varios seleccionados de alquiloxi y cicloalquilo o cicloalquilo sustituido con uno o varios seleccionados de halógeno, R²ᵃ es H, halógeno, alquilo, alquiloxi o haloalquiloxi, R²ᵇ es H, R²ᵃ y R²ᵇ junto con el átomo de carbono al que se unen pueden formar cicloalcano sustituido, R³ᵃ puede ser H o alquilo cuando R²ᵃ y R²ᵇ junto con el átomo de carbono al que se unen pueden formar cicloalcano sustituido, R³ᵇ es H o alquilo, el resto de fórmula (2) puede ser un compuesto de fórmula (3); el anillo A es un carbociclo aromático sustituido o no sustituido, un carbociclo no aromático sustituido o no sustituido, un heterociclo aromático sustituido o no sustituido o un heterociclo no aromático sustituido o no sustituido; el anillo B es un carbociclo aromático sustituido o no sustituido, un carbociclo no aromático sustituido o no sustituido, un heterociclo aromático sustituido o no sustituido o un heterociclo no aromático sustituido o no sustituido; R¹ es alquilo sustituido o no sustituido, alquenilo sustituido o no sustituido, alquinilo sustituido o no sustituido o cicloalquilo sustituido o no sustituido; R⁵ es halógeno o alquilo sustituido o no sustituido; n es un número entero de 0 a 2; siempre que se excluyan los siguientes compuestos: (i) un compuesto, en donde X es -O-, R³ᵃ es CH₂F o CF₃, R³ᵇ es H, R²ᵃ es H o F y R²ᵇ es H, (ii) un compuesto, en donde X es -O-, R³ᵃ es CHF₂, R³ᵇ es H, R²ᵃ es OMe y R²ᵇ es H, (iii) el compuesto representado por las fórmulas (4), (5) y (6); o una de sus sales farmacéuticamente aceptables.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2014081524 | 2014-04-11 |
Publications (1)
Publication Number | Publication Date |
---|---|
AR100049A1 true AR100049A1 (es) | 2016-09-07 |
Family
ID=53284477
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ARP150101090A AR100049A1 (es) | 2014-04-11 | 2015-04-10 | Derivados de dihidrotiazina y dihidrooxazina con actividad inhibidora de bace1 |
Country Status (15)
Country | Link |
---|---|
US (1) | US20170073337A1 (es) |
EP (1) | EP3129370A1 (es) |
JP (1) | JP2017510587A (es) |
KR (1) | KR20160141849A (es) |
CN (1) | CN106414431A (es) |
AR (1) | AR100049A1 (es) |
AU (1) | AU2015244702A1 (es) |
CA (1) | CA2945272A1 (es) |
EA (1) | EA201692048A1 (es) |
IL (1) | IL248228A0 (es) |
MX (1) | MX2016013035A (es) |
PH (1) | PH12016501891A1 (es) |
SG (1) | SG11201607999VA (es) |
TW (1) | TW201623295A (es) |
WO (1) | WO2015156421A1 (es) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8999980B2 (en) † | 2009-12-11 | 2015-04-07 | Shionogi & Co., Ltd. | Oxazine derivatives |
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 |
UA117695C2 (uk) | 2014-02-19 | 2018-09-10 | Х. Луннбек А/С | 2-аміно-3,5,5-трифтор-3,4,5,6-тетрагідропіридини як інгібітори bace1 для лікування хвороби альцгеймера |
WO2016022724A1 (en) | 2014-08-08 | 2016-02-11 | Amgen Inc. | Cyclopropyl fused thiazin-2-amine compounds as beta-secretase inhibitors and methods of use |
JO3458B1 (ar) | 2014-11-10 | 2020-07-05 | H Lundbeck As | 2- أمينو-6- (دايفلوروميثيل) – 5، 5- ديفلورو-6-فينيل-3،4، 5، 6-تيتراهيدروبيريدين كمثبطات bace1 |
CR20170187A (es) | 2014-11-10 | 2018-02-01 | H Lundbeck As | 2-Amino-3,5-difluoro-6-metil-6-fenil-3,4,5,6-tetrahidropiridinas en calidad de inhibidores de BACE1 para el tratamiento de la enfermedad de Alzheimer |
MA40941A (fr) | 2014-11-10 | 2017-09-19 | H Lundbeck As | 2-amino-5,5-difluoro-6-(fluorométhyl)-6-phényl-3,4,5,6-tétrahydropyridines comme inhibiteurs de bace1 |
WO2016149057A1 (en) * | 2015-03-19 | 2016-09-22 | Eli Lilly And Company | Selective bace1 inhibitors |
TW201717948A (zh) | 2015-08-10 | 2017-06-01 | H 朗德貝克公司 | 包括給予2-胺基-3,5,5-三氟-3,4,5,6-四氫吡啶的聯合治療 |
KR20180033524A (ko) | 2015-08-12 | 2018-04-03 | 하. 룬드벡 아크티에셀스카브 | Bace1 저해제로서의 2-아미노-3-플루오로-3-(플루오로메틸)-6-메틸-6-페닐-3,4,5,6-테트라하이드로피리딘 |
WO2017061534A1 (en) | 2015-10-08 | 2017-04-13 | Shionogi & Co., Ltd. | Dihydrothiazine derivatives |
CN108699051B (zh) * | 2016-03-01 | 2021-12-24 | 豪夫迈·罗氏有限公司 | Bace1抑制剂 |
BR112020021728A2 (pt) * | 2018-04-27 | 2021-01-26 | Shionogi & Co., Ltd. | derivados de tetra-hidropiranooxazina tendo atividade inibitória de bace1 seletiva |
JP7127808B2 (ja) * | 2018-05-29 | 2022-08-30 | 国立大学法人山口大学 | フルオロアルキル基を含有するイミン類の製造方法 |
EP3875021A4 (en) * | 2018-11-01 | 2021-10-20 | FUJIFILM Corporation | MEDICAL IMAGE PROCESSING APPARATUS, MEDICAL IMAGE PROCESSING PROCESS AND DIAGNOSIS ASSISTANCE APPARATUS |
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US7763609B2 (en) | 2003-12-15 | 2010-07-27 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
WO2006138217A1 (en) | 2005-06-14 | 2006-12-28 | Schering Corporation | 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 |
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 |
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 |
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 |
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 |
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 |
US8999980B2 (en) | 2009-12-11 | 2015-04-07 | Shionogi & Co., Ltd. | Oxazine derivatives |
UA103272C2 (uk) | 2009-12-11 | 2013-09-25 | Ф. Хоффманн-Ля Рош Аг | 2-аміно-5,5-дифтор-5,6-дигідро-4h-оксазини як інгібітори bace1 і/або bace2 |
EP2518059A4 (en) | 2009-12-24 | 2013-05-29 | Shionogi & Co | 4-AMINO-1,3-THIAZINE OR OXAZINE DERIVATIVE |
EP2634186A4 (en) | 2010-10-29 | 2014-03-26 | Shionogi & Co | naphthyridine |
EP2634188A4 (en) | 2010-10-29 | 2014-05-07 | Shionogi & Co | FUSIONED AMINODIHYDROPYRIMIDINE DERIVATIVE |
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 |
US8754075B2 (en) | 2011-04-11 | 2014-06-17 | Hoffmann-La Roche Inc. | 1,3-oxazines as BACE1 and/or BACE2 inhibitors |
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 |
US8785436B2 (en) | 2011-05-16 | 2014-07-22 | Hoffmann-La Roche Inc. | 1,3-oxazines as BACE 1 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 |
CA2837252A1 (en) | 2011-06-07 | 2012-12-13 | F. Hoffmann-La Roche Ag | Halogen-alkyl-1,3 oxazines as bace1 and/or bace2 inhibitors |
EP2718287A1 (en) | 2011-06-07 | 2014-04-16 | F.Hoffmann-La Roche Ag | [1,3]oxazines |
UY34278A (es) | 2011-08-25 | 2013-04-05 | Novartis Ag | Derivados novedosos de oxazina y su uso en el tratamiento de enfermedades |
US20130073953A1 (en) | 2011-09-21 | 2013-03-21 | Timothy Onyenobi | News headline screenshot viewing system |
UA113538C2 (xx) * | 2012-01-26 | 2017-02-10 | Фторметил-5,6-дигідро-4h-$1,3]оксазини | |
KR20150023450A (ko) | 2012-06-26 | 2015-03-05 | 에프. 호프만-라 로슈 아게 | Bace1 억제제로서의 다이플루오로-헥사하이드로-사이클로펜타옥사진일 및 다이플루오로-헥사하이드로-벤조옥사진일 |
WO2014010748A1 (en) | 2012-07-10 | 2014-01-16 | Shionogi & Co., Ltd. | Cyclopropane derivative having bace1 inhibiting activity |
JP2014101354A (ja) | 2012-10-24 | 2014-06-05 | Shionogi & Co Ltd | Bace1阻害作用を有するオキサジン誘導体 |
WO2014065434A1 (en) * | 2012-10-24 | 2014-05-01 | Shionogi & Co., Ltd. | Dihydrooxazine or oxazepine derivatives having bace1 inhibitory activity |
JP2014101353A (ja) | 2012-10-26 | 2014-06-05 | 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 |
WO2014098831A1 (en) | 2012-12-19 | 2014-06-26 | Bristol-Myers Squibb Company | 4,6-diarylaminothiazines as bace1 inhibitors and their use for the reduction of beta-amyloid production |
JP2016505055A (ja) | 2013-01-22 | 2016-02-18 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | Bace1阻害剤としてのフルオロ−[1,3]オキサジン |
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 |
BR112015019412A8 (pt) | 2013-04-11 | 2019-11-12 | Hoffmann La Roche | inibidores de bace1, seus usos, e composição farmacêutica |
-
2015
- 2015-04-09 TW TW104111465A patent/TW201623295A/zh unknown
- 2015-04-10 WO PCT/JP2015/062314 patent/WO2015156421A1/en active Application Filing
- 2015-04-10 CA CA2945272A patent/CA2945272A1/en not_active Abandoned
- 2015-04-10 MX MX2016013035A patent/MX2016013035A/es unknown
- 2015-04-10 AU AU2015244702A patent/AU2015244702A1/en not_active Abandoned
- 2015-04-10 US US15/302,892 patent/US20170073337A1/en not_active Abandoned
- 2015-04-10 AR ARP150101090A patent/AR100049A1/es unknown
- 2015-04-10 EA EA201692048A patent/EA201692048A1/ru unknown
- 2015-04-10 SG SG11201607999VA patent/SG11201607999VA/en unknown
- 2015-04-10 JP JP2016558817A patent/JP2017510587A/ja active Pending
- 2015-04-10 KR KR1020167031354A patent/KR20160141849A/ko unknown
- 2015-04-10 CN CN201580031354.5A patent/CN106414431A/zh active Pending
- 2015-04-10 EP EP15727077.8A patent/EP3129370A1/en not_active Withdrawn
-
2016
- 2016-09-26 PH PH12016501891A patent/PH12016501891A1/en unknown
- 2016-10-06 IL IL248228A patent/IL248228A0/en unknown
Also Published As
Publication number | Publication date |
---|---|
MX2016013035A (es) | 2017-01-09 |
CN106414431A (zh) | 2017-02-15 |
PH12016501891A1 (en) | 2016-12-19 |
EA201692048A1 (ru) | 2017-04-28 |
EP3129370A1 (en) | 2017-02-15 |
KR20160141849A (ko) | 2016-12-09 |
TW201623295A (zh) | 2016-07-01 |
IL248228A0 (en) | 2016-11-30 |
JP2017510587A (ja) | 2017-04-13 |
AU2015244702A1 (en) | 2016-10-06 |
WO2015156421A1 (en) | 2015-10-15 |
US20170073337A1 (en) | 2017-03-16 |
SG11201607999VA (en) | 2016-10-28 |
CA2945272A1 (en) | 2015-10-15 |
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