UA75891C2 - Pharmaceutically active sulfonamides derivatives having either lipophilic fragments and those capable to ionize as inhibitors of protein- jun-kinases, a pharmaceutical composition, a method for obtaining these compounds (variants) and intermediary compounds - Google Patents

Pharmaceutically active sulfonamides derivatives having either lipophilic fragments and those capable to ionize as inhibitors of protein- jun-kinases, a pharmaceutical composition, a method for obtaining these compounds (variants) and intermediary compounds Download PDF

Info

Publication number: UA75891C2
Authority: UA; Ukraine
Prior art keywords: amino; thien; sulfonyl; methyl; benzamide
Prior art date: 2000-09-27

Application number

UA2003032606A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Applied Research Systems

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.)

2000-09-27

Filing date

2001-09-27

Publication date

2006-06-15

2001-09-27 Application filed by Applied Research Systems filed Critical Applied Research Systems

2006-06-15 Publication of UA75891C2 publication Critical patent/UA75891C2/uk

Links

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125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 216
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BSXLLFUSNQCWJP-UHFFFAOYSA-M thiophene-2-sulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CS1 BSXLLFUSNQCWJP-UHFFFAOYSA-M 0.000 description 1
YNVOMSDITJMNET-UHFFFAOYSA-M thiophene-3-carboxylate Chemical compound [O-]C(=O)C=1C=CSC=1 YNVOMSDITJMNET-UHFFFAOYSA-M 0.000 description 1
125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
230000000451 tissue damage Effects 0.000 description 1
231100000827 tissue damage Toxicity 0.000 description 1
239000003053 toxin Substances 0.000 description 1
231100000765 toxin Toxicity 0.000 description 1
108700012359 toxins Proteins 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
108091006106 transcriptional activators Proteins 0.000 description 1
230000009466 transformation Effects 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
230000009529 traumatic brain injury Effects 0.000 description 1
230000000472 traumatic effect Effects 0.000 description 1
229910052905 tridymite Inorganic materials 0.000 description 1
JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
230000004614 tumor growth Effects 0.000 description 1
208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
230000004222 uncontrolled growth Effects 0.000 description 1
210000005167 vascular cell Anatomy 0.000 description 1
238000012795 verification Methods 0.000 description 1
230000035899 viability Effects 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
PXQPEWDEAKTCGB-UHFFFAOYSA-N vitamin B13 Natural products OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 description 1
239000011534 wash buffer Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
239000000230 xanthan gum Substances 0.000 description 1
229920001285 xanthan gum Polymers 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
229940082509 xanthan gum Drugs 0.000 description 1
125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1

Classifications

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- 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
- C07D409/12—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 linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- 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
- A61P27/00—Drugs for disorders of the senses
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- 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
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- 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
- A—HUMAN NECESSITIES
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- 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
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
- 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
- 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

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Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicinal Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Pulmonology (AREA)
Urology & Nephrology (AREA)
Rheumatology (AREA)
Immunology (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Pain & Pain Management (AREA)
Psychology (AREA)
Psychiatry (AREA)
Hospice & Palliative Care (AREA)
Ophthalmology & Optometry (AREA)
Vascular Medicine (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Hydrogenated Pyridines (AREA)

UA2003032606A 2000-09-27 2001-09-27 Pharmaceutically active sulfonamides derivatives having either lipophilic fragments and those capable to ionize as inhibitors of protein- jun-kinases, a pharmaceutical composition, a method for obtaining these compounds (variants) and intermediary compounds UA75891C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP00810887A EP1193268A1 (en)	2000-09-27	2000-09-27	Pharmaceutically active sulfonamide derivatives bearing both lipophilic and ionisable moieties as inhibitors of protein Junkinases
PCT/IB2001/001772 WO2002026733A2 (en)	2000-09-27	2001-09-27	sHARMACEUTICALLY ACTIVE SULFONAMIDE DERIVATIVES BEARING BOTH LIPOPHILIC AND IONISABLE MOIETIES AS INHIBITORS OF PROTEIN JUNKINASES

Publications (1)

Publication Number	Publication Date
UA75891C2 true UA75891C2 (en)	2006-06-15

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ID=8174937

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA2003032606A UA75891C2 (en)	2000-09-27	2001-09-27	Pharmaceutically active sulfonamides derivatives having either lipophilic fragments and those capable to ionize as inhibitors of protein- jun-kinases, a pharmaceutical composition, a method for obtaining these compounds (variants) and intermediary compounds

Country Status (26)

Country	Link
US (1)	US7544700B2 (et)
EP (2)	EP1193268A1 (et)
JP (1)	JP4927304B2 (et)
KR (1)	KR20030057532A (et)
CN (1)	CN1288150C (et)
AR (1)	AR033999A1 (et)
AU (2)	AU8799101A (et)
BG (1)	BG107633A (et)
BR (1)	BR0114223A (et)
CA (1)	CA2421209A1 (et)
CZ (1)	CZ2003884A3 (et)
EA (1)	EA005819B1 (et)
EE (1)	EE200300119A (et)
ES (1)	ES2438185T3 (et)
HR (1)	HRP20030214A2 (et)
HU (1)	HUP0302980A3 (et)
IL (1)	IL154965A0 (et)
MX (1)	MXPA03002568A (et)
NO (1)	NO20031375D0 (et)
NZ (1)	NZ524542A (et)
PL (1)	PL361687A1 (et)
SK (1)	SK3662003A3 (et)
UA (1)	UA75891C2 (et)
WO (1)	WO2002026733A2 (et)
YU (1)	YU21803A (et)
ZA (1)	ZA200301746B (et)

Families Citing this family (48)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP1193256A1 (en)	2000-09-27	2002-04-03	Applied Research Systems ARS Holding N.V.	Pharmaceutically active benzsulfonamide derivatives as inhibitors of JNK proteins
EP1193267A1 (en) *	2000-09-27	2002-04-03	Applied Research Systems ARS Holding N.V.	Pharmaceutically active hydrophilic sulfonamide derivatives as inhibitors of protein JunKinases
EP1193268A1 (en)	2000-09-27	2002-04-03	Applied Research Systems ARS Holding N.V.	Pharmaceutically active sulfonamide derivatives bearing both lipophilic and ionisable moieties as inhibitors of protein Junkinases
DE60230625D1 (de) *	2001-07-23	2009-02-12	Serono Lab	Arylsulfonamidderivate als hemmer c-jun-terminaler kinasen (jnk)
CA2534312A1 (en) *	2003-09-12	2005-03-24	Applied Research Systems Ars Holding N.V.	Sulfonamide derivatives for the treatment of diabetes
DK1701940T3 (da) *	2003-12-23	2008-09-08	Lundbeck & Co As H	2-(1H-indolylsulfanyl)-bensylaminderivater som SSRI
AR052308A1 (es) *	2004-07-16	2007-03-14	Lundbeck & Co As H	Derivados de 2-(1h-indolilsulfanil)-arilamina y una composicion farmaceutica que contiene al compuesto
AR054393A1 (es) *	2005-06-17	2007-06-20	Lundbeck & Co As H	Derivados de benzo(b)furano y benzo(b)tiofeno, composiciones farmaceuticas que los contienen y su uso en la fabricacion de un medicamento para el tratamiento de enfermedades mediadas por la inhibicion de la reabsorcion de neurotransmisores de amina biogenicos.
US7629473B2 (en) *	2005-06-17	2009-12-08	H. Lundbeck A/S	2-(1H-indolylsulfanyl)-aryl amine derivatives
KR20080044836A (ko)	2005-07-15	2008-05-21	라보라뚜와르 세로노 에스. 에이.	자궁내막증 치료용 ｊｎｋ 억제제
AU2011265521B8 (en) *	2005-07-15	2014-05-22	Merck Serono Sa	JNK inhibitors for the treatment of endometreosis
BRPI0613042A2 (pt)	2005-07-15	2010-12-14	Serono Lab	inibidores de jnk para o tratamento de endometriose
WO2007141224A2 (en) *	2006-06-02	2007-12-13	Laboratoires Serono Sa	Jnk inhibitors for treatment of skin diseases
EP2361242B1 (en)	2008-10-17	2018-08-01	Oryzon Genomics, S.A.	Oxidase inhibitors and their use
EP2389362B1 (en)	2009-01-21	2019-12-11	Oryzon Genomics, S.A.	Phenylcyclopropylamine derivatives and their medical use
JP5699152B2 (ja)	2009-09-25	2015-04-08	オリゾン・ジェノミックス・ソシエダッド・アノニマＯｒｙｚｏｎＧｅｎｏｍｉｃｓＳ．Ａ．	リジン特異的デメチラーゼ−１阻害剤およびその使用
US8946296B2 (en)	2009-10-09	2015-02-03	Oryzon Genomics S.A.	Substituted heteroaryl- and aryl-cyclopropylamine acetamides and their use
WO2011106105A2 (en)	2010-02-24	2011-09-01	Oryzon Genomics, S.A.	Inhibitors for antiviral use
US9186337B2 (en)	2010-02-24	2015-11-17	Oryzon Genomics S.A.	Lysine demethylase inhibitors for diseases and disorders associated with Hepadnaviridae
WO2011131697A1 (en)	2010-04-19	2011-10-27	Oryzon Genomics S.A.	Lysine specific demethylase-1 inhibitors and their use
EP2598480B1 (en)	2010-07-29	2019-04-24	Oryzon Genomics, S.A.	Cyclopropylamine derivatives useful as lsd1 inhibitors
EP3375775A1 (en)	2010-07-29	2018-09-19	Oryzon Genomics, S.A.	Arylcyclopropylamine based demethylase inhibitors of lsd1 and their medical use
WO2012045883A1 (en)	2010-10-08	2012-04-12	Oryzon Genomics S.A.	Cyclopropylamine inhibitors of oxidases
WO2012072713A2 (en)	2010-11-30	2012-06-07	Oryzon Genomics, S.A.	Lysine demethylase inhibitors for diseases and disorders associated with flaviviridae
EP2712315B1 (en)	2011-02-08	2021-11-24	Oryzon Genomics, S.A.	Lysine demethylase inhibitors for myeloproliferative disorders
WO2012156531A2 (en) *	2011-05-19	2012-11-22	Oryzon Genomics, S.A.	Lysine demethylase inhibitors for inflammatory diseases or conditions
WO2012156537A2 (en) *	2011-05-19	2012-11-22	Oryzon Genomics, S.A.	Lysine demethylase inhibitors for thrombosis and cardiovascular diseases
EP3736265A1 (en)	2011-10-20	2020-11-11	Oryzon Genomics, S.A.	(hetero)aryl cyclopropylamine compounds as lsd1 inhibitors
EP2776394B1 (en)	2011-10-20	2018-12-26	Oryzon Genomics, S.A.	(hetero)aryl cyclopropylamine compounds as lsd1 inhibitors
SG10201608528YA (en)	2011-12-21	2016-12-29	Novira Therapeutics Inc	Hepatitis b antiviral agents
JP2015533782A (ja)	2012-08-28	2015-11-26	ヤンセン・サイエンシズ・アイルランド・ユーシー	スルファモイル−アリールアミド及びｂ型肝炎の治療のための薬剤としてのその使用
EP2961732B1 (en)	2013-02-28	2017-04-12	Janssen Sciences Ireland UC	Sulfamoyl-arylamides and the use thereof as medicaments for the treatment of hepatitis b
AU2014247138B2 (en)	2013-04-03	2018-06-28	Janssen Sciences Ireland Uc	N-phenyl-carboxamide derivatives and the use thereof as medicaments for the treatment of hepatitis B
CA2909742C (en)	2013-05-17	2020-08-04	Janssen Sciences Ireland Uc	Sulphamoylthiophenamide derivatives and the use thereof as medicaments for the treatment of hepatitis b
JO3603B1 (ar)	2013-05-17	2020-07-05	Janssen Sciences Ireland Uc	مشتقات سلفامويل بيرولاميد واستخدامها كادوية لمعالجة التهاب الكبد نوع بي
ES2774749T3 (es)	2013-07-25	2020-07-22	Janssen Sciences Ireland Unlimited Co	Derivados de pirrolamida sustituidos con glioxamida y su uso como medicamentos para el tratamiento de la hepatitis B
JP6452119B2 (ja)	2013-10-23	2019-01-16	ヤンセン・サイエンシズ・アイルランド・アンリミテッド・カンパニー	カルボキサミド誘導体およびｂ型肝炎の処置のための医薬品としてのその使用
US10392349B2 (en)	2014-01-16	2019-08-27	Novira Therapeutics, Inc.	Azepane derivatives and methods of treating hepatitis B infections
US9169212B2 (en)	2014-01-16	2015-10-27	Novira Therapeutics, Inc.	Azepane derivatives and methods of treating hepatitis B infections
KR20160128305A (ko)	2014-02-05	2016-11-07	노비라 테라퓨틱스, 인코포레이티드	Hbv 감염의 치료를 위한 병용 요법
CA2932551A1 (en)	2014-02-06	2015-08-13	Janssen Sciences Ireland Uc	Sulphamoylpyrrolamide derivatives and the use thereof as medicaments for the treatment of hepatitis b
CN107847762A (zh)	2015-03-19	2018-03-27	诺维拉治疗公司	氮杂环辛烷和氮杂环壬烷衍生物以及治疗乙型肝炎感染的方法
US10875876B2 (en)	2015-07-02	2020-12-29	Janssen Sciences Ireland Uc	Cyclized sulfamoylarylamide derivatives and the use thereof as medicaments for the treatment of hepatitis B
HK1259410A1 (zh)	2015-09-29	2019-11-29	诺维拉治疗公司	乙型肝炎抗病毒剂的晶体形式
EP3848026A1 (en)	2016-04-15	2021-07-14	Novira Therapeutics Inc.	Combinations and methods comprising a capsid assembly inhibitor
WO2019175657A1 (en)	2018-03-14	2019-09-19	Janssen Sciences Ireland Unlimited Company	Capsid assembly modulator dosing regimen
KR20210130753A (ko)	2019-02-22	2021-11-01	얀센 사이언시즈 아일랜드 언리미티드 컴퍼니	Hbv 감염 또는 hbv-유발성 질환의 치료에 유용한 아미드 유도체
AR119732A1 (es)	2019-05-06	2022-01-05	Janssen Sciences Ireland Unlimited Co	Derivados de amida útiles en el tratamiento de la infección por vhb o de enfermedades inducidas por vhb

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2553414B1 (fr) *	1983-10-18	1986-08-14	Choay Sa	Nouveaux benzenesulfonamides n-cyclises, leur procede de preparation et leur utilisation comme substance active de compositions pharmaceutiques
US5238950A (en) *	1991-12-17	1993-08-24	Schering Corporation	Inhibitors of platelet-derived growth factor
US5744320A (en) *	1995-06-07	1998-04-28	Promega Corporation	Quenching reagents and assays for enzyme-mediated luminescence
CA2255612A1 (en) *	1996-05-31	1997-12-04	Pharmacia & Upjohn Company	Aryl substituted cyclic amines as selective dopamine d3 ligands
US6043083A (en)	1997-04-28	2000-03-28	Davis; Roger J.	Inhibitors of the JNK signal transduction pathway and methods of use
EP1001764A4 (en) *	1997-05-29	2005-08-24	Merck & Co Inc	HETEROCYCLIC AMIDE COMPOUNDS AS INHIBITORS OF CELL ADHESION
DE19743435A1 (de) *	1997-10-01	1999-04-08	Merck Patent Gmbh	Benzamidinderivate
AR019322A1 (es) *	1998-06-18	2002-02-13	Smithkline Beecham Corp	Derivados de sulfonilo sustituido por heterociclo-etanodionanilina sustituida por heterociclo, composicion farmaceutica que los contiene y su uso para lamanufactura de un medicamento
DE69928260T2 (de) *	1998-07-08	2006-07-20	Sanofi-Aventis Deutschland Gmbh	Schwefel-substituierte sulfonylaminocarbonsäure n-arylamide, ihre herstellung, ihre anwendung und diese enthaltende pharmazeutische zusammensetzungen
EP1088821A1 (en)	1999-09-28	2001-04-04	Applied Research Systems ARS Holding N.V.	Pharmaceutically active sulfonamide derivatives
EP1193256A1 (en) *	2000-09-27	2002-04-03	Applied Research Systems ARS Holding N.V.	Pharmaceutically active benzsulfonamide derivatives as inhibitors of JNK proteins
EP1193267A1 (en) *	2000-09-27	2002-04-03	Applied Research Systems ARS Holding N.V.	Pharmaceutically active hydrophilic sulfonamide derivatives as inhibitors of protein JunKinases
EP1193268A1 (en)	2000-09-27	2002-04-03	Applied Research Systems ARS Holding N.V.	Pharmaceutically active sulfonamide derivatives bearing both lipophilic and ionisable moieties as inhibitors of protein Junkinases

2000
- 2000-09-27 EP EP00810887A patent/EP1193268A1/en not_active Withdrawn
2001
- 2001-09-27 ZA ZA200301746A patent/ZA200301746B/en unknown
- 2001-09-27 AU AU8799101A patent/AU8799101A/xx active Pending
- 2001-09-27 KR KR10-2003-7004265A patent/KR20030057532A/ko not_active Ceased
- 2001-09-27 CZ CZ2003884A patent/CZ2003884A3/cs unknown
- 2001-09-27 CN CNB01819141XA patent/CN1288150C/zh not_active Expired - Fee Related
- 2001-09-27 HR HR20030214A patent/HRP20030214A2/hr not_active Application Discontinuation
- 2001-09-27 EP EP01967622.0A patent/EP1322642B1/en not_active Expired - Lifetime
- 2001-09-27 BR BR0114223-2A patent/BR0114223A/pt not_active IP Right Cessation
- 2001-09-27 EE EEP200300119A patent/EE200300119A/et unknown
- 2001-09-27 IL IL15496501A patent/IL154965A0/xx unknown
- 2001-09-27 CA CA002421209A patent/CA2421209A1/en not_active Abandoned
- 2001-09-27 SK SK366-2003A patent/SK3662003A3/sk not_active Application Discontinuation
- 2001-09-27 PL PL36168701A patent/PL361687A1/xx not_active Application Discontinuation
- 2001-09-27 YU YU21803A patent/YU21803A/sh unknown
- 2001-09-27 WO PCT/IB2001/001772 patent/WO2002026733A2/en not_active Ceased
- 2001-09-27 EA EA200300412A patent/EA005819B1/ru not_active IP Right Cessation
- 2001-09-27 JP JP2002531117A patent/JP4927304B2/ja not_active Expired - Fee Related
- 2001-09-27 US US10/381,665 patent/US7544700B2/en not_active Expired - Fee Related
- 2001-09-27 AR ARP010104565A patent/AR033999A1/es unknown
- 2001-09-27 UA UA2003032606A patent/UA75891C2/uk unknown
- 2001-09-27 ES ES01967622.0T patent/ES2438185T3/es not_active Expired - Lifetime
- 2001-09-27 NZ NZ524542A patent/NZ524542A/en unknown
- 2001-09-27 HU HU0302980A patent/HUP0302980A3/hu unknown
- 2001-09-27 AU AU2001287991A patent/AU2001287991B2/en not_active Ceased
- 2001-09-27 MX MXPA03002568A patent/MXPA03002568A/es not_active Application Discontinuation
2003
- 2003-03-13 BG BG107633A patent/BG107633A/bg unknown
- 2003-03-26 NO NO20031375A patent/NO20031375D0/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
CA2421209A1 (en)	2002-04-04
BR0114223A (pt)	2003-07-01
MXPA03002568A (es)	2003-10-06
AR033999A1 (es)	2004-01-21
HUP0302980A3 (en)	2007-09-28
WO2002026733A3 (en)	2002-08-01
US7544700B2 (en)	2009-06-09
EE200300119A (et)	2005-04-15
NO20031375L (no)	2003-03-26
SK3662003A3 (en)	2003-10-07
EA200300412A1 (ru)	2003-08-28
WO2002026733A2 (en)	2002-04-04
EA005819B1 (ru)	2005-06-30
EP1322642A2 (en)	2003-07-02
NO20031375D0 (no)	2003-03-26
HK1072768A1 (en)	2005-09-09
US20040077854A1 (en)	2004-04-22
KR20030057532A (ko)	2003-07-04
CN1288150C (zh)	2006-12-06
ES2438185T3 (es)	2014-01-16
HUP0302980A2 (hu)	2003-12-29
IL154965A0 (en)	2003-10-31
AU2001287991B2 (en)	2006-12-07
PL361687A1 (en)	2004-10-04
HRP20030214A2 (en)	2005-02-28
YU21803A (sh)	2006-05-25
EP1193268A1 (en)	2002-04-03
CN1568322A (zh)	2005-01-19
AU8799101A (en)	2002-04-08
JP4927304B2 (ja)	2012-05-09
ZA200301746B (en)	2004-03-03
BG107633A (bg)	2003-11-28
JP2004509957A (ja)	2004-04-02
EP1322642B1 (en)	2013-09-04
NZ524542A (en)	2004-09-24
CZ2003884A3 (cs)	2003-08-13

Publication	Publication Date	Title
UA75891C2 (en)	2006-06-15	Pharmaceutically active sulfonamides derivatives having either lipophilic fragments and those capable to ionize as inhibitors of protein- jun-kinases, a pharmaceutical composition, a method for obtaining these compounds (variants) and intermediary compounds
US8008341B2 (en)	2011-08-30	Pharmaceutically active benzsulfonamide derivatives as inhibitors of protein junkinases
NO324792B1 (no)	2007-12-10	Farmasoytisk aktive sulfonamidderivater
AU2001287991A1 (en)	2002-06-20	Pharmaceutically active sulfonamide derivatives bearing both lipophilic and ionisable moieties as inhibitors of protein junkinases
JP2012111777A (ja)	2012-06-14	薬剤活性のあるスルホニルアミノ酸誘導体
AU2001287992A1 (en)	2002-06-20	Pharmaceutically active benzsulfonamide derivatives as inhibitors of protein junkinases
JP4927306B2 (ja)	2012-05-09	タンパク質Ｊｕｎ−キナーゼのインヒビターとしての医薬的活性親水性スルホンアミド誘導体
AU2001287990A1 (en)	2002-06-27	Pharmaceutically active hydrophilic sulfonamide derivatives as inhibitors of protein junkinases
JP4414219B2 (ja)	2010-02-10	Ｃ−ｊｕｎ−ｎ−末端キナーゼ（ｊｎｋ）インヒビターとしてのアリールスルホンアミド誘導体