PE20161225A1 - 2-amino-3,5,5-trifluoro-3,4,5,6-tetrahidropiridinas como inhibidores de bace1 para el tratamiento de la enfermedad de alzheimer - Google Patents

2-amino-3,5,5-trifluoro-3,4,5,6-tetrahidropiridinas como inhibidores de bace1 para el tratamiento de la enfermedad de alzheimer

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Publication number
PE20161225A1
PE20161225A1 PE2016001299A PE2016001299A PE20161225A1 PE 20161225 A1 PE20161225 A1 PE 20161225A1 PE 2016001299 A PE2016001299 A PE 2016001299A PE 2016001299 A PE2016001299 A PE 2016001299A PE 20161225 A1 PE20161225 A1 PE 20161225A1
Authority
PE
Peru
Prior art keywords
trifluoro
amino
alzheimer
treatment
tetrahydropyridines
Prior art date
Application number
PE2016001299A
Other languages
English (en)
Inventor
Thomas Jensen
Lena Tagmose
Mauro Marigo
Karsten Juhl
Original Assignee
H Lundbeck As
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by H Lundbeck As filed Critical H Lundbeck As
Publication of PE20161225A1 publication Critical patent/PE20161225A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D227/00—Heterocyclic compounds containing rings having one nitrogen atom as the only ring hetero atom, according to more than one of groups C07D203/00 - C07D225/00
    • C07D227/02—Heterocyclic compounds containing rings having one nitrogen atom as the only ring hetero atom, according to more than one of groups C07D203/00 - C07D225/00 with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D227/06—Heterocyclic compounds containing rings having one nitrogen atom as the only ring hetero atom, according to more than one of groups C07D203/00 - C07D225/00 with only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D227/10—Nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • 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

Abstract

La presente invencion se refiere a un compuesto de formula (I) o una sal de la misma farmaceuticamente aceptable donde: Ar es fenilo, piridilo, entre otros; R1 es alquilo C1-C3 o fluoroalquilo C1-C3; R2 es H, halogeno, entre otros; R3 es alquilo C1-C3 o una sal de este. Son compuestos preferidos N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-fluoropicolinamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-cloropicolinamida, entre otros. Dichos compuestos inhiben la enzima BACE1 y son utiles en el tratamiento del Alzheimer
PE2016001299A 2014-02-19 2015-02-17 2-amino-3,5,5-trifluoro-3,4,5,6-tetrahidropiridinas como inhibidores de bace1 para el tratamiento de la enfermedad de alzheimer PE20161225A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DKPA201400086 2014-02-19
DKPA201400349 2014-07-01

Publications (1)

Publication Number Publication Date
PE20161225A1 true PE20161225A1 (es) 2016-12-04

Family

ID=59009438

Family Applications (1)

Application Number Title Priority Date Filing Date
PE2016001299A PE20161225A1 (es) 2014-02-19 2015-02-17 2-amino-3,5,5-trifluoro-3,4,5,6-tetrahidropiridinas como inhibidores de bace1 para el tratamiento de la enfermedad de alzheimer

Country Status (25)

Country Link
US (2) US20170066741A1 (es)
EP (1) EP3107897A1 (es)
JP (1) JP6483146B2 (es)
KR (1) KR20160115936A (es)
CN (1) CN106029639B (es)
AP (1) AP2016009370A0 (es)
AR (1) AR099489A1 (es)
AU (1) AU2015220873A1 (es)
CA (1) CA2940028A1 (es)
CL (1) CL2016002072A1 (es)
CR (1) CR20160352A (es)
DO (1) DOP2016000194A (es)
EA (1) EA031132B1 (es)
EC (1) ECSP16072941A (es)
GE (1) GEP20186892B (es)
IL (1) IL246875A0 (es)
MA (1) MA39225A1 (es)
MX (1) MX2016010777A (es)
PE (1) PE20161225A1 (es)
PH (1) PH12016501600A1 (es)
RU (1) RU2016133626A (es)
SG (1) SG11201606812WA (es)
TW (1) TW201609700A (es)
UA (1) UA117695C2 (es)
WO (1) WO2015124576A1 (es)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GEP20186892B (en) 2014-02-19 2018-09-10 Lundbeck A/S H 2-amino-3, 5, 5-trifluoro-3, 4, 5, 6-tetrahydropyridines as bace1 inhibitors for treatment of alzheimer's disease
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
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
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
JO3627B1 (ar) 2015-04-30 2020-08-27 H Lundbeck As إيميدازو بيرازينونات على هيئة مثبطات pde1
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
WO2017025559A1 (en) 2015-08-12 2017-02-16 H. Lundbeck A/S 2-amino-3-fluoro-3-(fluoromethyl)-6-methyl-6-phenyl-3,4,5,6-tetrahydropyridins as bace1 inhibitors
AU2016321298A1 (en) 2015-09-09 2018-03-29 The Trustees Of Columbia University In The City Of New York Reduction of ER-MAM localized APP-C99 and methods of treating Alzheimer's Disease
TW201726651A (zh) * 2015-09-23 2017-08-01 健生藥品公司 ２，３，４，５－四氫吡啶－６－胺衍生物
US10034861B2 (en) 2016-07-04 2018-07-31 H. Lundbeck A/S 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
CN109803653A (zh) 2016-10-28 2019-05-24 H.隆德贝克有限公司 包括给予咪唑并吡嗪酮的组合治疗
SI3532064T1 (sl) 2016-10-28 2020-10-30 H. Lundbeck A/S Kombinirana zdravljenja, ki obsegajo imidazopirazinone za zdravljenje psihiatričnih in/ali kognitivnih motenj
BR112018017058A2 (pt) 2016-12-21 2019-07-02 H Lundbeck As 6-amino-5-fluoro-5-(fluorometil)-2,3,4,5-tetra-hidropiridin-2-il-fenil-5-(metóxi-d3)-pirazina-2-carboxamidas e derivados fluorados do mesmo como inibidores de bace1
EP4159212A1 (en) 2017-10-05 2023-04-05 Fulcrum Therapeutics, Inc. P38 kinase inhibitors reduce dux4 and downstream gene expression for the treatment of fshd
US10342786B2 (en) 2017-10-05 2019-07-09 Fulcrum Therapeutics, Inc. P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD
HRP20211784T1 (hr) 2017-12-14 2022-02-18 H. Lundbeck A/S Kombinacijski tretmani koji se sastoje od primjene 1h-pirazolo[4,3-b]piridina
AR113926A1 (es) 2017-12-14 2020-07-01 H Lundbeck As Derivados de 1h-pirazolo[4,3-b]piridinas
JP7194738B2 (ja) 2017-12-20 2022-12-22 ハー・ルンドベック・アクチエゼルスカベット ＰＤＥ１阻害剤としてのピラゾロ［３，４－ｂ］ピリジン及びイミダゾ［１，５－ｂ］ピリダジン
KR102507861B1 (ko) 2018-04-19 2023-03-09 삼성에스디에스 주식회사 부채널 공격에 안전한 연산 장치 및 방법
KR102510077B1 (ko) 2018-04-24 2023-03-14 삼성에스디에스 주식회사 부채널 공격에 안전한 연산 장치 및 방법

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005505506A (ja) * 2001-06-12 2005-02-24 イーラン ファーマスーティカルズ、インコーポレイテッド アルツハイマー病の治療に有用な大環状分子
GB0124928D0 (en) * 2001-10-17 2001-12-05 Glaxo Group Ltd Chemical compounds
DE60334651D1 (de) * 2002-02-12 2010-12-02 Glaxosmithkline Llc Nicotinamide und deren Verwendung als P38 Inhibitoren
TWI431004B (zh) * 2008-05-02 2014-03-21 Lilly Co Eli Ｂａｃｅ抑制劑
KR101730937B1 (ko) 2010-06-09 2017-04-27 얀센 파마슈티카 엔.브이. 베타-세크레타아제(ｂａｃｅ) 저해제로 유용한 5,6-디하이드로-2ｈ-[1,4]옥사진-3-일-아민 유도체
WO2012057248A1 (ja) * 2010-10-29 2012-05-03 塩野義製薬株式会社 ナフチリジン誘導体
WO2012095463A1 (en) 2011-01-12 2012-07-19 Novartis Ag Oxazine derivatives and their use in the treatment of neurological disorders
PT2663561E (pt) * 2011-01-13 2016-06-07 Novartis Ag Derivados heterocíclicos novos e sua utilização no tratamento de distúrbios neurológicos
US8754075B2 (en) 2011-04-11 2014-06-17 Hoffmann-La Roche Inc. 1,3-oxazines as BACE1 and/or BACE2 inhibitors
US8883779B2 (en) * 2011-04-26 2014-11-11 Shinogi & Co., Ltd. Oxazine derivatives and a pharmaceutical composition for inhibiting BACE1 containing them
BR112013031098A2 (pt) * 2011-06-07 2016-12-06 Hoffmann La Roche halogeno-alquil-1,3 oxazinas como inibidores de bace1 e/ou bace2
UY34278A (es) * 2011-08-25 2013-04-05 Novartis Ag Derivados novedosos de oxazina y su uso en el tratamiento de enfermedades
US8338413B1 (en) * 2012-03-07 2012-12-25 Novartis Ag Oxazine derivatives and their use in the treatment of neurological disorders
WO2013142613A1 (en) 2012-03-20 2013-09-26 Elan Pharmaceuticals, Inc. Spirocyclic dihydro-thiazine and dihydro-oxazine bace inhibitors, and compositions and uses thereof
WO2014056816A1 (en) 2012-10-10 2014-04-17 F. Hoffmann-La Roche Ag COMBINATION OF AN Aβ ANTIBODY AND A BACE INHIBITOR
US9540359B2 (en) 2012-10-24 2017-01-10 Shionogi & Co., Ltd. Dihydrooxazine or oxazepine derivatives having BACE1 inhibitory activity
CA2902212C (en) 2013-03-01 2020-10-13 Amgen Inc. Perfluorinated 5,6-dihydro-4h-1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use
GEP20186892B (en) 2014-02-19 2018-09-10 Lundbeck A/S H 2-amino-3, 5, 5-trifluoro-3, 4, 5, 6-tetrahydropyridines as bace1 inhibitors for treatment of alzheimer's disease
TW201623295A (zh) 2014-04-11 2016-07-01 塩野義製藥股份有限公司 具有ｂａｃｅ１抑制活性之二氫噻及二氫衍生物

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RU2016133626A3 (es) 2018-09-25
CL2016002072A1 (es) 2017-01-20
JP2017506237A (ja) 2017-03-02
CN106029639A (zh) 2016-10-12
AU2015220873A1 (en) 2016-08-11
CA2940028A1 (en) 2015-08-27
PH12016501600A1 (en) 2017-02-06
CR20160352A (es) 2016-10-20
UA117695C2 (uk) 2018-09-10
DOP2016000194A (es) 2016-09-30
US20150232449A1 (en) 2015-08-20
ECSP16072941A (es) 2017-02-24
US9353084B2 (en) 2016-05-31
KR20160115936A (ko) 2016-10-06
JP6483146B2 (ja) 2019-03-13
GEP20186892B (en) 2018-09-10
SG11201606812WA (en) 2016-09-29
WO2015124576A1 (en) 2015-08-27
AR099489A1 (es) 2016-07-27
CN106029639B (zh) 2019-01-08
EA031132B1 (ru) 2018-11-30
AP2016009370A0 (en) 2016-08-31
MA39225A1 (fr) 2017-04-28
IL246875A0 (en) 2016-08-31
MX2016010777A (es) 2016-10-26
TW201609700A (zh) 2016-03-16
EP3107897A1 (en) 2016-12-28
US20170066741A1 (en) 2017-03-09
EA201691447A1 (ru) 2016-12-30
RU2016133626A (ru) 2018-03-20

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