BR112018004065B1 - Compostos heterocíclicos, composições farmacêuticas compreendendo os ditos compostos e usos terapêuticos dos mesmos - Google Patents

Compostos heterocíclicos, composições farmacêuticas compreendendo os ditos compostos e usos terapêuticos dos mesmos Download PDF

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Publication number
BR112018004065B1
BR112018004065B1 BR112018004065-7A BR112018004065A BR112018004065B1 BR 112018004065 B1 BR112018004065 B1 BR 112018004065B1 BR 112018004065 A BR112018004065 A BR 112018004065A BR 112018004065 B1 BR112018004065 B1 BR 112018004065B1
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BR
Brazil
Prior art keywords
amino
methyl
nicotinamide
cyclopentyl
pyrazol
Prior art date
Application number
BR112018004065-7A
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English (en)
Portuguese (pt)
Other versions
BR112018004065A2 (pt
Inventor
Myeong-Seop Kim
Sumin KIM
Jin Kwan Kim
Hadong Kim
Ki Moon Ryu
Seong Jin Park
Taesun Park
Joon-Ho SHEEN
Taeyoung Yoon
Mi Yeon Jang
Original Assignee
Dong-A Socio Holdings Co., Ltd
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Filing date
Publication date
Application filed by Dong-A Socio Holdings Co., Ltd filed Critical Dong-A Socio Holdings Co., Ltd
Publication of BR112018004065A2 publication Critical patent/BR112018004065A2/pt
Publication of BR112018004065B1 publication Critical patent/BR112018004065B1/pt

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    • 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
    • C07D401/14—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 three or more hetero 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
    • A61K31/435—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
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K31/535—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
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • 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
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C07D213/82—Amides; Imides in position 3
    • 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
    • C07D401/10—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 carbon chain containing aromatic rings
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D405/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur 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
    • C07D417/04—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 directly linked by a ring-member-to-ring-member bond
    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Oncology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Communicable Diseases (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
BR112018004065-7A 2015-08-31 2016-08-31 Compostos heterocíclicos, composições farmacêuticas compreendendo os ditos compostos e usos terapêuticos dos mesmos BR112018004065B1 (pt)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201562212520P 2015-08-31 2015-08-31
US62/212,520 2015-08-31
PCT/KR2016/009743 WO2017039331A1 (en) 2015-08-31 2016-08-31 Heteroaryl compounds and their use as therapeutic drugs

Publications (2)

Publication Number Publication Date
BR112018004065A2 BR112018004065A2 (pt) 2018-10-02
BR112018004065B1 true BR112018004065B1 (pt) 2023-12-12

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BR112018004065-7A BR112018004065B1 (pt) 2015-08-31 2016-08-31 Compostos heterocíclicos, composições farmacêuticas compreendendo os ditos compostos e usos terapêuticos dos mesmos

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US (3) US10125118B2 (enExample)
EP (1) EP3344613B1 (enExample)
JP (2) JP2018528189A (enExample)
KR (1) KR102663118B1 (enExample)
CN (1) CN108368083B (enExample)
AU (1) AU2016317806B2 (enExample)
BR (1) BR112018004065B1 (enExample)
CA (1) CA2995675C (enExample)
CL (1) CL2018000529A1 (enExample)
CO (1) CO2018002045A2 (enExample)
CR (1) CR20180184A (enExample)
ES (1) ES2799300T3 (enExample)
IL (1) IL257391B (enExample)
MX (1) MX387785B (enExample)
MY (1) MY199607A (enExample)
PE (1) PE20181017A1 (enExample)
PH (1) PH12018500432A1 (enExample)
RU (1) RU2723480C2 (enExample)
UA (1) UA126372C2 (enExample)
WO (1) WO2017039331A1 (enExample)
ZA (1) ZA201802033B (enExample)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017039331A1 (en) 2015-08-31 2017-03-09 Dong-A Socio Holdings Co., Ltd. Heteroaryl compounds and their use as therapeutic drugs
SI3971177T1 (sl) 2016-07-20 2024-10-30 Novartis Ag Derivati aminopiridina in njihova uporaba kot selektivni zaviralci ALK-2
ES2903528T3 (es) 2016-10-10 2022-04-04 Dong A Socio Holdings Co Ltd Compuestos de heteroarilo y su uso como inhibidores de MER
GB201820458D0 (en) * 2018-12-14 2019-01-30 Heptares Therapeutics Ltd Ox1 antagonists
GB201901142D0 (en) 2019-01-28 2019-03-20 Heptares Therapeutics Ltd OX1 Antagonists
GB201905328D0 (en) * 2019-04-15 2019-05-29 Azeria Therapeutics Ltd Inhibitor compounds
CN115968289B (zh) 2020-06-16 2025-09-30 因赛特公司 用于治疗贫血的alk2抑制剂
WO2022065962A1 (ko) * 2020-09-28 2022-03-31 한국화학연구원 Mlkl 결합 또는 분해용 화합물 및 이들의 의약 용도
TWI893486B (zh) * 2022-10-20 2025-08-11 南韓商東亞Ｓｔ股份有限公司 稠合雙環化合物及其等作為mer及axl抑制劑的用途

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US20020151712A1 (en) 1999-09-14 2002-10-17 Nan-Horng Lin 3-pyrrolidinyloxy-3'-pyridyl ether compounds useful for controlling chemical synaptic transmission
GB0001930D0 (en) 2000-01-27 2000-03-22 Novartis Ag Organic compounds
AR042586A1 (es) 2001-02-15 2005-06-29 Sugen Inc 3-(4-amidopirrol-2-ilmetiliden)-2-indolinona como inhibidores de la protein quinasa; sus composiciones farmaceuticas; un metodo para la modulacion de la actividad catalitica de la proteinquinasa; un metodo para tratar o prevenir una afeccion relacionada con la proteinquinasa
WO2003093297A2 (en) * 2002-05-03 2003-11-13 Exelixis, Inc. Protein kinase modulators and methods of use
US8030336B2 (en) 2002-12-13 2011-10-04 Ym Biosciences Australia Pty Ltd Nicotinamide-based kinase inhibitors
WO2004054977A1 (en) 2002-12-13 2004-07-01 Cytopia Pty Ltd Nicotinamide-based kinase inhibitors
MXPA05009245A (es) 2003-03-11 2005-10-19 Pfizer Prod Inc Nuevos compuestos de pirazina como inhibidores del factor de crecimiento transformante (tgf).
US7361764B2 (en) 2004-07-27 2008-04-22 Sgx Pharmaceuticals, Inc. Pyrrolo-pyridine kinase modulators
WO2007011760A2 (en) 2005-07-15 2007-01-25 Kalypsys, Inc. Inhibitors of mitotic kinesin
EP2687533B1 (en) 2006-07-20 2017-07-19 Debiopharm International SA Acrylamide derivatives as FAB I inhibitors
US20140249135A1 (en) 2007-03-01 2014-09-04 Novartis Ag Pim kinase inhibitors and methods of their use
US9408873B2 (en) * 2010-08-23 2016-08-09 Kang Stem Biotech Co., Ltd. Pharmaceutical composition comprising stem cells treated with NOD2 agonist or culture thereof for prevention and treatment of immune disorders and inflammatory diseases
JP6012735B2 (ja) 2011-09-15 2016-10-25 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ 新規ジヒドロキノリン−２−オン誘導体
WO2017039331A1 (en) 2015-08-31 2017-03-09 Dong-A Socio Holdings Co., Ltd. Heteroaryl compounds and their use as therapeutic drugs

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Publication number Publication date
WO2017039331A1 (en) 2017-03-09
UA126372C2 (uk) 2022-09-28
ES2799300T3 (es) 2020-12-16
JP2018528189A (ja) 2018-09-27
NZ739648A (en) 2024-05-31
BR112018004065A2 (pt) 2018-10-02
AU2016317806A1 (en) 2018-02-22
RU2018111072A (ru) 2019-10-04
PH12018500432A1 (en) 2018-08-29
CN108368083B (zh) 2022-02-01
RU2723480C2 (ru) 2020-06-11
CN108368083A (zh) 2018-08-03
US12195446B2 (en) 2025-01-14
RU2018111072A3 (enExample) 2020-01-20
CL2018000529A1 (es) 2018-08-24
CR20180184A (es) 2018-08-23
EP3344613B1 (en) 2020-03-04
US10947215B2 (en) 2021-03-16
US20230002353A1 (en) 2023-01-05
ZA201802033B (en) 2022-07-27
IL257391B (en) 2021-05-31
JP2022058371A (ja) 2022-04-12
US20170355690A9 (en) 2017-12-14
US10125118B2 (en) 2018-11-13
CA2995675C (en) 2023-12-12
EP3344613A1 (en) 2018-07-11
MX2018002574A (es) 2019-02-25
US20190119252A1 (en) 2019-04-25
PE20181017A1 (es) 2018-06-26
MY199607A (en) 2023-11-09
EP3344613A4 (en) 2019-01-23
JP7208348B2 (ja) 2023-01-18
CA2995675A1 (en) 2017-03-09
KR20180044995A (ko) 2018-05-03
AU2016317806B2 (en) 2020-11-19
US20170066742A1 (en) 2017-03-09
CO2018002045A2 (es) 2018-05-21
MX387785B (es) 2025-03-18
KR102663118B1 (ko) 2024-05-03
IL257391A (en) 2018-04-30

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