ZA200007447B - Inhibitors of transcription factor NF-kB. - Google Patents

Inhibitors of transcription factor NF-kB. Download PDF

Info

Publication number: ZA200007447B
Authority: ZA; South Africa
Prior art keywords: group; compound; galkyl; disease; hydroxy
Prior art date: 1998-06-19

Application number

ZA200007447A

Other languages

English (en)

Inventor

Callahan James Francis

Marie C Chabot-Fletcher

Original Assignee

Smithkline Beecham Corp

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.)

1998-06-19

Filing date

2000-12-13

Publication date

2002-02-13

2000-12-13 Application filed by Smithkline Beecham Corp filed Critical Smithkline Beecham Corp

2002-02-13 Publication of ZA200007447B publication Critical patent/ZA200007447B/en

Links

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231100000161 signs of toxicity Toxicity 0.000 description 1
238000002741 site-directed mutagenesis Methods 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
239000000344 soap Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
238000000527 sonication Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
210000004876 tela submucosa Anatomy 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000012360 testing method Methods 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
230000002110 toxicologic effect Effects 0.000 description 1
231100000759 toxicological effect Toxicity 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000013519 translation Methods 0.000 description 1
230000005945 translocation Effects 0.000 description 1
230000032258 transport Effects 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
210000001692 type a synoviocyte Anatomy 0.000 description 1
230000006663 ubiquitin-proteasome pathway Effects 0.000 description 1
239000001993 wax Substances 0.000 description 1
238000001262 western blot Methods 0.000 description 1
210000002268 wool Anatomy 0.000 description 1

Classifications

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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- 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
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- 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]
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- A—HUMAN NECESSITIES
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- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A—HUMAN NECESSITIES
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- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/58—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/64—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Immunology (AREA)
Physical Education & Sports Medicine (AREA)
Rheumatology (AREA)
Epidemiology (AREA)
Orthopedic Medicine & Surgery (AREA)
Pulmonology (AREA)
Dermatology (AREA)
Virology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Tropical Medicine & Parasitology (AREA)
Hospice & Palliative Care (AREA)
Transplantation (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
AIDS & HIV (AREA)
Molecular Biology (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

ZA200007447A 1998-06-19 2000-12-13 Inhibitors of transcription factor NF-kB. ZA200007447B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US8982798P	1998-06-19	1998-06-19

Publications (1)

Publication Number	Publication Date
ZA200007447B true ZA200007447B (en)	2002-02-13

Family

ID=22219773

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200007447A ZA200007447B (en)	1998-06-19	2000-12-13	Inhibitors of transcription factor NF-kB.

Country Status (21)

Country	Link
US (3)	US6492425B1 (ja)
EP (1)	EP1085848B1 (ja)
JP (1)	JP2002518307A (ja)
KR (1)	KR20010052991A (ja)
CN (1)	CN1311629A (ja)
AR (1)	AR019692A1 (ja)
AT (1)	ATE383769T1 (ja)
AU (1)	AU4690099A (ja)
BR (1)	BR9911152A (ja)
CA (1)	CA2335294A1 (ja)
CO (1)	CO5021213A1 (ja)
CZ (1)	CZ20004761A3 (ja)
DE (1)	DE69937997T2 (ja)
ES (1)	ES2299251T3 (ja)
HU (1)	HUP0102782A3 (ja)
IL (1)	IL140328A0 (ja)
NO (1)	NO20006451L (ja)
PL (1)	PL348969A1 (ja)
TR (1)	TR200003781T2 (ja)
WO (1)	WO1999065449A2 (ja)
ZA (1)	ZA200007447B (ja)

Families Citing this family (45)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE69738841D1 (de)	1996-12-23	2008-08-28	Immunex Corp	Ligand für rezeptor aktivator of nf-kappa b, ligand ist mitglied der tnf superfamilie
US6316408B1 (en)	1997-04-16	2001-11-13	Amgen Inc.	Methods of use for osetoprotegerin binding protein receptors
EP2009025B1 (en)	1998-05-14	2011-07-27	Immunex Corporation	Method of inhibiting osteoclast activity
GB9930616D0 (en) *	1999-12-24	2000-02-16	Mathilda & Terence Kennedy Ins	Activation and inhibition of the immune system
EP1134221A1 (en) *	2000-03-15	2001-09-19	Aventis Pharma Deutschland GmbH	Substituted beta-carbolines as lkB kinase inhibitors
FR2813315B1 (fr) *	2000-08-23	2002-10-18	Genfit S A	Procede d'identification de substances utiles pour le traitement de l'inflammation mettant en oeuvre l'element de reponse du recepteur ror du gene ikbalpha
EP1352650B1 (en) *	2000-12-18	2012-03-07	Institute of Medicinal Molecular Design, Inc.	Inhibitors against the production and release of inflammatory cytokines
DE60217532T8 (de)	2001-11-07	2008-02-07	Millennium Pharmaceuticals, Inc., Cambridge	Carboline derivate als ikb-inhibitoren zur behandlung des m ultiplen myelomas
US7119120B2 (en)	2001-12-26	2006-10-10	Genzyme Corporation	Phosphate transport inhibitors
EP1510210A4 (en) *	2002-06-05	2009-01-07	Inst Med Molecular Design Inc	IMMUNITY-CONTAINING PROTEIN KINASE HEMMER
EA008769B1 (ru) *	2002-06-05	2007-08-31	Инститьют Оф Медисинал Молекьюлар Дизайн. Инк.	Лекарственное средство для лечения диабета
EP1514544A4 (en) *	2002-06-06	2009-01-07	Inst Med Molecular Design Inc	HYPO-ALLERGENIC
JP4743382B2 (ja) *	2002-06-06	2011-08-10	株式会社医薬分子設計研究所	Ｏ−置換ヒドロキシアリール誘導体
CN100506221C (zh) *	2002-06-10	2009-07-01	株式会社医药分子设计研究所	癌症治疗药
EA010470B1 (ru) *	2002-06-10	2008-08-29	Инститьют Оф Медисинал Молекьюлар Дизайн. Инк.	ИНГИБИТОРЫ АКТИВАЦИИ NF-kB
TWI280127B (en) *	2002-06-11	2007-05-01	Inst Med Molecular Design Inc	Remedies for neurodegenerative diseases
US7324455B2 (en)	2003-03-14	2008-01-29	International Business Machines Corporation	Transfer of error-analysis and statistical data in a fibre channel input/output system
US20050256132A1 (en) *	2003-04-30	2005-11-17	Wyeth	Use of ER selective NF-kB inhibitors for the treatment of sepsis
US20050004164A1 (en) *	2003-04-30	2005-01-06	Caggiano Thomas J.	2-Cyanopropanoic acid amide and ester derivatives and methods of their use
WO2004098510A2 (en) *	2003-04-30	2004-11-18	Beth Israel Deaconess Medical Center	Cystic fibrosis therapy
US7981915B2 (en) *	2003-04-30	2011-07-19	Beth Israel Deaconess Medical Center	Methods for modulating PPAR biological activity for the treatment of diseases caused by mutations in the CFTR gene
DE602004030689D1 (de) *	2003-07-23	2011-02-03	Synta Pharmaceuticals Corp	Verbindungen gegen entzündungen und immun-relevante verwendungen
US7425580B2 (en)	2004-05-19	2008-09-16	Wyeth	(Diaryl-methyl)-malononitriles and their use as estrogen receptor ligands
US20080207673A1 (en) *	2005-05-04	2008-08-28	Michel Xilinas	Method for Treating Cancer, Coronary, Inflammatory and Macular Disease, Combining the Modulation of Zinc-and/or Copper Dependent Proteins
CN100418532C (zh) *	2005-06-17	2008-09-17	吕志民	治疗多种疾病的NF-κB化合物抑制剂
US7671058B2 (en) *	2006-06-21	2010-03-02	Institute Of Medicinal Molecular Design, Inc.	N-(3,4-disubstituted phenyl) salicylamide derivatives
EP2201946A4 (en)	2007-10-23	2012-01-25	Inst Med Molecular Design Inc	HAMMER OF PAI-1 PRODUCTION
JP2011500853A (ja) *	2007-10-25	2011-01-06	ファィトシューティカ，インコーポレイテッド	炎症性腸疾患および／または過敏性腸管症候群に対する処置としてのｐｈｙ９０６の使用
EP2242367A4 (en) *	2008-01-08	2012-07-04	Univ Pennsylvania	REL INHIBITORS AND METHODS OF USE
US20090264514A1 (en) *	2008-04-18	2009-10-22	The Research Foundation Of State University Of New York	SPHINGOMYELIN SYNTHASE 2 (SMS2) DEFICIENCY ATTENUATES NFkB ACTIVATION, A POTENTIAL ANTI-ATHEROGENIC PROPERTY
US10640457B2 (en)	2009-12-10	2020-05-05	The Trustees Of Columbia University In The City Of New York	Histone acetyltransferase activators and uses thereof
JP6616057B2 (ja) *	2010-12-22	2019-12-04	ザトラスティーズオブコロンビアユニヴァーシティインザシティオブニューヨーク	ヒストンアセチル基転移酵素モジュレーターおよびその使用
TWI492920B (zh) *	2012-04-18	2015-07-21	Nat Defense Medical Ct	水楊酸苯胺衍生小分子之醫藥組合物及其製備與醫藥用途
US9562002B2 (en)	2013-01-15	2017-02-07	Board Of Regents, The University Of Texas System	STAT3 inhibitor
CN106659909B (zh)	2013-08-21	2022-01-11	德克萨斯州大学***董事会	用于靶向连接蛋白半通道的组合物和方法
JP2017511340A (ja)	2014-03-31	2017-04-20	ザトラスティースオブコロンビアユニバーシティインザシティオブニューヨーク	ヒストンアセチルトランスフェラーゼ活性剤及びその使用
ES2970434T3 (es)	2014-09-12	2024-05-28	Union Therapeutics As	Uso antibacteriano de salicilanilidas halogenadas
CN105797154B (zh) *	2014-12-31	2020-03-10	中国科学院上海生命科学研究院	软骨干细胞的分离及其应用
GB201509326D0 (en)	2015-05-29	2015-07-15	Antibio Tx Aps	Novel use
WO2017122209A2 (en) *	2016-01-12	2017-07-20	Yeda Research And Development Co. Ltd.	NF-kappaB INHIBITORS
EP3419998A4 (en)	2016-02-26	2019-09-25	The Board of Regents of The University of Texas System	CONNEXIN (CX) 43 HEMICANAL BINDING ANTIBODIES AND USES THEREOF
GB201604484D0 (en) *	2016-03-16	2016-04-27	Antibiotx Aps And Københavns Uni University Of Copenhagen	Topical antibacterial compositions
CA3057284A1 (en) *	2017-03-21	2018-09-27	Novalead Pharma Inc.	Therapeutic agent for phosphodiesterase inhibition and its related disorders
US11419834B2 (en)	2019-02-25	2022-08-23	Rhode Island Hospital	Methods for treating diseases or infections caused by or associated with H. pylori using a halogenated salicylanilide
CN114727975A (zh) *	2019-11-18	2022-07-08	加利福尼亚大学董事会	双雄激素受体/akr1c3抑制剂

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1079177A (en) *	1963-06-11	1967-08-16	Stecker Internat S P A	Improvements in pesticide composition for destroying internal worm parasites in animals
GB1079178A (en) *	1966-07-27	1967-08-16	Stecker Internat S P A	Improvements in pesticide compositions for destroying internal worm parasites in animals
US4742083A (en) *	1983-08-24	1988-05-03	Lever Brothers Company	Method of relieving pain and inflammatory conditions employing substituted salicylamides
US4803279A (en) *	1985-05-23	1989-02-07	Smithkline Beckman Corporation	1.4-dihydro-4-pyridyl-substituted imidazo (2,1-b) thiazoles and the corresponding thiazines.
ATE120753T1 (de)	1990-08-21	1995-04-15	Upjohn Co	Bisphosphonsäurederivate als antiarthritische mittel.
AU2140592A (en) *	1991-05-17	1992-12-30	Chiron Corporation	Inhibitor of nf-kappa b transcriptional activator and uses thereof
US5466715A (en) *	1991-12-31	1995-11-14	Sterling Winthrop Inc.	3,4-disubstituted phenols-immunomodulating agents
DE4200534A1 (de) *	1992-01-11	1993-07-15	Henkel Kgaa	Neue n-benzyl-4-aminophenole und deren verwendung als entwicklerkomponente in oxidationshaarfaerbemitteln
ZA944191B (en) *	1993-06-15	1995-02-08	Univ Australian	Synergistic anthelmintic compositions
CA2298824A1 (en) *	1997-08-06	1999-02-18	Smithkline Beecham Corporation	Macrophage scavenger receptor antagonists for use in the treatment of cardiovascular diseases

1998
- 1998-06-19 HU HU0102782A patent/HUP0102782A3/hu unknown
1999
- 1999-06-18 KR KR1020007014386A patent/KR20010052991A/ko not_active Application Discontinuation
- 1999-06-18 CN CN99807571A patent/CN1311629A/zh active Pending
- 1999-06-18 JP JP2000554329A patent/JP2002518307A/ja not_active Withdrawn
- 1999-06-18 AU AU46900/99A patent/AU4690099A/en not_active Abandoned
- 1999-06-18 ES ES99930345T patent/ES2299251T3/es not_active Expired - Lifetime
- 1999-06-18 AT AT99930345T patent/ATE383769T1/de not_active IP Right Cessation
- 1999-06-18 DE DE69937997T patent/DE69937997T2/de not_active Expired - Fee Related
- 1999-06-18 TR TR2000/03781T patent/TR200003781T2/xx unknown
- 1999-06-18 IL IL14032899A patent/IL140328A0/xx unknown
- 1999-06-18 WO PCT/US1999/013652 patent/WO1999065449A2/en active IP Right Grant
- 1999-06-18 CZ CZ20004761A patent/CZ20004761A3/cs unknown
- 1999-06-18 PL PL99348969A patent/PL348969A1/xx unknown
- 1999-06-18 BR BR9911152-7A patent/BR9911152A/pt not_active Application Discontinuation
- 1999-06-18 CO CO99038264A patent/CO5021213A1/es unknown
- 1999-06-18 AR ARP990102955A patent/AR019692A1/es unknown
- 1999-06-18 CA CA002335294A patent/CA2335294A1/en not_active Abandoned
- 1999-06-18 US US09/720,018 patent/US6492425B1/en not_active Expired - Fee Related
- 1999-06-18 EP EP99930345A patent/EP1085848B1/en not_active Expired - Lifetime
2000
- 2000-12-13 ZA ZA200007447A patent/ZA200007447B/en unknown
- 2000-12-18 NO NO20006451A patent/NO20006451L/no not_active Application Discontinuation
2002
- 2002-07-31 US US10/210,560 patent/US20030092771A1/en not_active Abandoned
2005
- 2005-10-03 US US11/242,572 patent/US20060035979A1/en not_active Abandoned

Also Published As

Publication number	Publication date
AU4690099A (en)	2000-01-05
TR200003781T2 (tr)	2001-07-23
JP2002518307A (ja)	2002-06-25
US20060035979A1 (en)	2006-02-16
IL140328A0 (en)	2002-02-10
PL348969A1 (en)	2002-06-17
US20030092771A1 (en)	2003-05-15
EP1085848A4 (en)	2004-09-08
EP1085848A2 (en)	2001-03-28
DE69937997T2 (de)	2009-02-19
HUP0102782A3 (en)	2002-12-28
NO20006451D0 (no)	2000-12-18
ES2299251T3 (es)	2008-05-16
CA2335294A1 (en)	1999-12-23
AR019692A1 (es)	2002-03-13
CO5021213A1 (es)	2001-03-27
HUP0102782A2 (hu)	2001-12-28
KR20010052991A (ko)	2001-06-25
DE69937997D1 (ja)	2008-03-06
US6492425B1 (en)	2002-12-10
CZ20004761A3 (cs)	2001-08-15
EP1085848B1 (en)	2008-01-16
WO1999065449A3 (en)	2000-03-30
ATE383769T1 (de)	2008-02-15
NO20006451L (no)	2000-12-18
CN1311629A (zh)	2001-09-05
BR9911152A (pt)	2001-03-06
WO1999065449A2 (en)	1999-12-23
WO1999065449A8 (en)	2001-03-08

Publication	Publication Date	Title
US6492425B1 (en)	2002-12-10	Inhibitors of transcription factor-NF-κB
EP1448545B1 (en)	2008-11-19	Nf-kb inhibitors
US20060116419A1 (en)	2006-06-01	Nf-kb inhibitors
WO2002030353A2 (en)	2002-04-18	NF-λB INHIBITORS
WO2009051909A1 (en)	2009-04-23	Compounds having activity in correcting mutant-cftr cellular processing and uses thereof
EP1328272A1 (en)	2003-07-23	Nf-kappa-b inhibitors
AU4699699A (en)	2000-01-05	Inhibitors of transcription factor NF-KappaB
KR20120041070A (ko)	2012-04-30	Ｈｉｆ-1 활성을 저해하는 아릴옥시페녹시아크릴계 화합물, 이의 제조방법 및 이를 유효성분으로 함유하는 약학적 조성물
US7300952B2 (en)	2007-11-27	NF-κb inhibitors
US7183311B2 (en)	2007-02-27	NF-κB inhibitors
US20060030596A1 (en)	2006-02-09	NF-kappaB inhibitors
MXPA00012498A (en)	2001-11-21	INHIBITORS OF TRANSCRIPTION FACTOR NF-&kgr;B
MXPA00012499A (en)	2001-11-21	INHIBITORS OF TRANSCRIPTION FACTOR NF-&kgr;B
US20040006118A1 (en)	2004-01-08	Nf-kb inhibitors