DOP2018000246A - 5,6,7,8–tetrahidro[1,2,4]triazolo[4,3–a]piridin–3(2h)–onas y 2,5,6,7-tetrahydro-3h-pyrrolo[2,1-c][1,2,4]triazol-3-ones sustituidas y su uso - Google Patents

5,6,7,8–tetrahidro[1,2,4]triazolo[4,3–a]piridin–3(2h)–onas y 2,5,6,7-tetrahydro-3h-pyrrolo[2,1-c][1,2,4]triazol-3-ones sustituidas y su uso

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Publication number
DOP2018000246A
DOP2018000246A DO2018000246A DO2018000246A DOP2018000246A DO P2018000246 A DOP2018000246 A DO P2018000246A DO 2018000246 A DO2018000246 A DO 2018000246A DO 2018000246 A DO2018000246 A DO 2018000246A DO P2018000246 A DOP2018000246 A DO P2018000246A
Authority
DO
Dominican Republic
Prior art keywords
tetrahydro
ones
triazolo
pyrrolo
pyridin
Prior art date
Application number
DO2018000246A
Other languages
English (en)
Inventor
Lustig Klemens
Meier Heinrich
Brockschnieder Damian
Matthias Gericke Kersten
Moosmayer Dieter
Schäfer Martina
Terjung Carsten
Lindner Niels
Kölling Florian
Neubauer Thomas
Biber Nicole
Meding Jörg
Timmermainn Andreas
Zubov Dmitry
Badock Volker
Miyatake Ondozabal Hideki
Moore Steven
Schulz Alexander
Original Assignee
Bayer Ag
Bayer Pharma AG
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 Bayer Ag, Bayer Pharma AG filed Critical Bayer Ag
Publication of DOP2018000246A publication Critical patent/DOP2018000246A/es

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • 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
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pulmonology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

La presente solicitud se refiere a nuevas 5,6,7,8–tetrahidro[1,2,4]triazolo[4,3–a]piridin–3(2H)–onas y 2,5,6,7–tetrahidro–3H–pirrolo[2,1–c][1,2,4]triazol–3–onas sustituidas, a procesos para su preparación, a su uso, solas o en combinaciones, para el tratamiento y/o la prevención de enfermedades y a su uso para la producción de medicamentos para el tratamiento y/o la prevención de enfermedades, en especial para el tratamiento y/o la prevención de trastornos de inflamación pulmonar.
DO2018000246A 2016-05-09 2018-11-09 5,6,7,8–tetrahidro[1,2,4]triazolo[4,3–a]piridin–3(2h)–onas y 2,5,6,7-tetrahydro-3h-pyrrolo[2,1-c][1,2,4]triazol-3-ones sustituidas y su uso DOP2018000246A (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP16168809 2016-05-09

Publications (1)

Publication Number Publication Date
DOP2018000246A true DOP2018000246A (es) 2018-11-30

Family

ID=55919764

Family Applications (1)

Application Number Title Priority Date Filing Date
DO2018000246A DOP2018000246A (es) 2016-05-09 2018-11-09 5,6,7,8–tetrahidro[1,2,4]triazolo[4,3–a]piridin–3(2h)–onas y 2,5,6,7-tetrahydro-3h-pyrrolo[2,1-c][1,2,4]triazol-3-ones sustituidas y su uso

Country Status (29)

Country Link
US (1) US10722501B2 (es)
JP (1) JP6987784B2 (es)
KR (1) KR102438965B1 (es)
CN (1) CN109476658B (es)
AR (1) AR110600A1 (es)
AU (1) AU2017262960B2 (es)
CA (1) CA3023383A1 (es)
CL (1) CL2018003194A1 (es)
CO (1) CO2018012136A2 (es)
CR (1) CR20180540A (es)
CU (1) CU24536B1 (es)
DO (1) DOP2018000246A (es)
EA (1) EA037531B1 (es)
EC (1) ECSP18083950A (es)
GE (1) GEP20227365B (es)
IL (1) IL262548B (es)
JO (1) JOP20170113B1 (es)
MX (1) MX2018013797A (es)
NI (1) NI201800118A (es)
PE (1) PE20190325A1 (es)
PH (1) PH12018502359A1 (es)
SA (1) SA518400397B1 (es)
SG (1) SG11201809724PA (es)
SV (1) SV2018005783A (es)
TN (1) TN2018000376A1 (es)
TW (1) TWI758291B (es)
UA (1) UA125644C2 (es)
UY (1) UY37234A (es)
WO (1) WO2017194459A1 (es)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX2007009796A (es) 2007-08-14 2009-02-25 Cell Therapy And Technology S Gel conteniendo pirfenidona.
MX2011007675A (es) 2011-07-19 2012-07-11 Cell Therapy And Technology S A De C V Procedimiento para la fabricacion de una composicion farmaceutica en forma de tabletas de liberacion prolongada conteniendo pirfenidona y su aplicacion en la regresion de la insuficiencia renal cronica, contractura capsular mamaria y fibrosis hepatica humanas.
MX346763B (es) 2012-03-28 2017-03-31 Cell Therapy And Tech S A De C V Composición tópica semisólida conteniendo pirfenidona y dialil óxido de disulfuro modificado (odd-m) para eliminar o prevenir el acné.
MX356551B (es) 2012-08-23 2018-06-04 Grupo Medifarma S A De C V Star Composición antiséptica, antiseborreica y exfoliante para eliminar o prevenir el acné.
WO2019091847A1 (de) 2017-11-07 2019-05-16 Bayer Aktiengesellschaft Substituierte 2,4-dihydro-3h-1,2,4-triazol-3-one und ihre verwendung
CN110950797A (zh) * 2019-12-06 2020-04-03 丽水绿氟科技有限公司 一种2-三氟甲基-3-氟-4-吡啶甲酸及其衍生物的制备方法
CN115466212B (zh) * 2022-10-26 2023-09-22 河南农业大学 一种2-三氟甲基喹啉类化合物及其合成方法和应用

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3966781A (en) 1970-12-17 1976-06-29 Merck Sharp & Dohme (I.A.) Corporation Deuteration of functional group-containing hydrocarbons
HUT76640A (en) * 1995-08-17 1997-10-28 Chinoin Gyogyszer Es Vegyeszet Compounds of pharmaceutical activity cyclic amide derivatives, pharmaceutical compositions containing them, process for producing them and their use
DE19834047A1 (de) 1998-07-29 2000-02-03 Bayer Ag Substituierte Pyrazolderivate
DE19834044A1 (de) 1998-07-29 2000-02-03 Bayer Ag Neue substituierte Pyrazolderivate
DE19943636A1 (de) 1999-09-13 2001-03-15 Bayer Ag Neuartige Dicarbonsäurederivate mit pharmazeutischen Eigenschaften
DE19943634A1 (de) 1999-09-13 2001-04-12 Bayer Ag Neuartige Dicarbonsäurederivate mit pharmazeutischen Eigenschaften
DE19943639A1 (de) 1999-09-13 2001-03-15 Bayer Ag Dicarbonsäurederivate mit neuartigen pharmazeutischen Eigenschaften
DE19943635A1 (de) 1999-09-13 2001-03-15 Bayer Ag Neuartige Aminodicarbonsäurederivate mit pharmazeutischen Eigenschaften
AR031176A1 (es) 2000-11-22 2003-09-10 Bayer Ag Nuevos derivados de pirazolpiridina sustituidos con piridina
DE10110749A1 (de) 2001-03-07 2002-09-12 Bayer Ag Substituierte Aminodicarbonsäurederivate
DE10110750A1 (de) 2001-03-07 2002-09-12 Bayer Ag Neuartige Aminodicarbonsäurederivate mit pharmazeutischen Eigenschaften
DE10220570A1 (de) 2002-05-08 2003-11-20 Bayer Ag Carbamat-substituierte Pyrazolopyridine
US7618983B2 (en) 2004-11-10 2009-11-17 Janssen Pharmaceutica, N.V. Bicyclic triazole α4 integrin inhibitors
US8524654B2 (en) 2007-05-21 2013-09-03 The Uab Research Foundation Prolyl endopeptidase inhibitors for reducing or preventing neutrophilic inflammation
WO2011062864A2 (en) 2009-11-17 2011-05-26 Emory University Inhibitors of nox enzymes and methods of use thereof
DE102010021637A1 (de) 2010-05-26 2011-12-01 Bayer Schering Pharma Aktiengesellschaft Substituierte 5-Fluor-1H-Pyrazolopyridine und ihre Verwendung
PE20130779A1 (es) 2010-07-09 2013-06-21 Bayer Ip Gmbh Pirimidinas y triazinas condensadas y su uso
DE102010040233A1 (de) 2010-09-03 2012-03-08 Bayer Schering Pharma Aktiengesellschaft Bicyclische Aza-Heterocyclen 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
EP2675440B1 (en) 2011-02-14 2020-03-25 Merck Sharp & Dohme Corp. Cathepsin cysteine protease inhibitors
KR20130091464A (ko) * 2012-02-08 2013-08-19 한미약품 주식회사 타이로신 카이네이즈 억제 활성을 갖는 트리아졸로피리딘 유도체
US9624214B2 (en) * 2012-11-05 2017-04-18 Bayer Pharma Aktiengesellschaft Amino-substituted imidazo[1,2-a]pyridinecarboxamides and their use

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Publication number Publication date
CL2018003194A1 (es) 2019-04-12
CN109476658B (zh) 2021-08-10
TW201806949A (zh) 2018-03-01
CU20180139A7 (es) 2019-06-04
GEP20227365B (en) 2022-03-25
IL262548A (en) 2018-12-31
JP6987784B2 (ja) 2022-01-05
JP2019522628A (ja) 2019-08-15
SV2018005783A (es) 2019-05-06
EA201892518A1 (ru) 2019-04-30
CU24536B1 (es) 2021-07-02
CR20180540A (es) 2019-03-05
NI201800118A (es) 2019-10-30
KR102438965B1 (ko) 2022-09-02
US10722501B2 (en) 2020-07-28
TN2018000376A1 (en) 2020-06-15
ECSP18083950A (es) 2018-11-30
AR110600A1 (es) 2019-04-17
PE20190325A1 (es) 2019-03-05
UY37234A (es) 2017-11-30
EA037531B1 (ru) 2021-04-08
MX2018013797A (es) 2019-03-21
CO2018012136A2 (es) 2018-12-14
TWI758291B (zh) 2022-03-21
KR20190003954A (ko) 2019-01-10
CN109476658A (zh) 2019-03-15
IL262548B (en) 2021-12-01
JOP20170113B1 (ar) 2023-03-28
PH12018502359A1 (en) 2019-10-07
BR112018073061A2 (pt) 2019-04-09
SA518400397B1 (ar) 2021-11-24
WO2017194459A1 (de) 2017-11-16
US20190160048A1 (en) 2019-05-30
AU2017262960B2 (en) 2021-11-11
SG11201809724PA (en) 2018-12-28
CA3023383A1 (en) 2017-11-16
UA125644C2 (uk) 2022-05-11

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