HK1001973A1 - Sulfonamides - Google Patents

Sulfonamides

Info

Publication number
HK1001973A1
HK1001973A1 HK98100968A HK98100968A HK1001973A1 HK 1001973 A1 HK1001973 A1 HK 1001973A1 HK 98100968 A HK98100968 A HK 98100968A HK 98100968 A HK98100968 A HK 98100968A HK 1001973 A1 HK1001973 A1 HK 1001973A1
Authority
HK
Hong Kong
Prior art keywords
pct
sec
compounds
date
endothelin
Prior art date
Application number
HK98100968A
Other languages
English (en)
Inventor
Volker Breu
Kaspar Burri
Jean-Marie Cassal
Martine Clozel
Georges Hirth
Bernd-Michael Loffler
Marcel Muller
Werner Neidhart
Henri Ramuz
Original Assignee
Hoffmann La Roche
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 Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of HK1001973A1 publication Critical patent/HK1001973A1/xx

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/04Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/08Vasodilators for multiple indications
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members 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
    • C07D239/69Benzenesulfonamido-pyrimidines
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/14Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic 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
    • C07D403/10Heterocyclic 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 linked by a carbon chain containing aromatic rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Cardiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Bipolar Transistors (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Steroid Compounds (AREA)
  • Surgical Instruments (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Lubricants (AREA)
HK98100968A 1994-12-20 1998-02-09 Sulfonamides HK1001973A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CH383794 1994-12-20
CH241995 1995-08-24
PCT/EP1995/004843 WO1996019459A1 (en) 1994-12-20 1995-12-08 Novel sulfonamides

Publications (1)

Publication Number Publication Date
HK1001973A1 true HK1001973A1 (en) 1998-07-24

Family

ID=25690401

Family Applications (1)

Application Number Title Priority Date Filing Date
HK98100968A HK1001973A1 (en) 1994-12-20 1998-02-09 Sulfonamides

Country Status (26)

Country Link
US (1) US6004965A (ko)
EP (1) EP0799209B1 (ko)
JP (1) JP2989014B2 (ko)
KR (1) KR100445085B1 (ko)
CN (1) CN1098254C (ko)
AT (1) ATE246681T1 (ko)
AU (1) AU701767B2 (ko)
BR (1) BR9510104A (ko)
CA (1) CA2208018C (ko)
CY (1) CY2495B1 (ko)
CZ (1) CZ287916B6 (ko)
DE (1) DE69531457T2 (ko)
DK (1) DK0799209T3 (ko)
ES (1) ES2203649T3 (ko)
FI (1) FI120397B (ko)
HK (1) HK1001973A1 (ko)
HU (1) HU228619B1 (ko)
IL (1) IL116385A (ko)
MA (1) MA23744A1 (ko)
MY (1) MY131126A (ko)
NO (1) NO316645B1 (ko)
NZ (1) NZ297797A (ko)
PT (1) PT799209E (ko)
SA (1) SA95160421B1 (ko)
TW (1) TW313568B (ko)
WO (1) WO1996019459A1 (ko)

Families Citing this family (70)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6063911A (en) * 1993-12-01 2000-05-16 Marine Polymer Technologies, Inc. Methods and compositions for treatment of cell proliferative disorders
TW555765B (en) 1996-07-09 2003-10-01 Amgen Inc Low molecular weight soluble tumor necrosis factor type-I and type-II proteins
CA2273852C (en) 1996-12-06 2009-09-29 Amgen Inc. Combination therapy using an il-1 inhibitor for treating il-1 mediated diseases
ES2221696T3 (es) * 1997-08-19 2005-01-01 F. Hoffmann-La Roche Ag Procedimiento para la preparacion de piridinas 2,5.disustituidas.
US7329670B1 (en) 1997-12-22 2008-02-12 Bayer Pharmaceuticals Corporation Inhibition of RAF kinase using aryl and heteroaryl substituted heterocyclic ureas
US7517880B2 (en) 1997-12-22 2009-04-14 Bayer Pharmaceuticals Corporation Inhibition of p38 kinase using symmetrical and unsymmetrical diphenyl ureas
DK0979822T3 (da) * 1998-08-10 2006-03-27 Hoffmann La Roche Fremgangsmåde til fremstilling af 2-carbamoyl-pyridiner
CA2359244C (en) 1999-01-13 2013-10-08 Bayer Corporation .omega.-carboxy aryl substituted diphenyl ureas as p38 kinase inhibitors
ME00275B (me) 1999-01-13 2011-02-10 Bayer Corp ω-KARBOKSIARIL SUPSTITUISANI DIFENIL KARBAMIDI KAO INHIBITORI RAF KINAZE
EP1140840B1 (en) 1999-01-13 2006-03-22 Bayer Pharmaceuticals Corp. -g(v)-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
US8124630B2 (en) 1999-01-13 2012-02-28 Bayer Healthcare Llc ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
US7928239B2 (en) 1999-01-13 2011-04-19 Bayer Healthcare Llc Inhibition of RAF kinase using quinolyl, isoquinolyl or pyridyl ureas
TWI284642B (en) * 1999-01-18 2007-08-01 Hoffmann La Roche Novel heterocyclic sulfonamides
US6417360B1 (en) * 1999-03-03 2002-07-09 Hoffmann-La Roche Inc. Heterocyclic sulfonamides
AU747596B2 (en) * 1999-05-22 2002-05-16 Actelion Pharmaceuticals Ltd Aqueous pharmaceutical composition
ZA200002318B (en) * 1999-05-22 2000-11-16 Actelion Pharmaceuticals Ltd Aqueous pharmaceutical composition.
CA2315614C (en) 1999-07-29 2004-11-02 Pfizer Inc. Pyrazoles
ATE380180T1 (de) * 1999-09-03 2007-12-15 Actelion Pharmaceuticals Ltd Bis-sulfonamiden
JP2003518102A (ja) * 1999-12-22 2003-06-03 アクテリオン ファマシューティカルズ リミテッド ブチンジオール誘導体
AU2001265871A1 (en) * 2000-04-25 2001-11-07 Actelion Pharmaceuticals Ltd Substituted sulfonylaminopyrimidines
US6387915B2 (en) 2000-05-31 2002-05-14 Pfizer Inc. Isoxazole-sulfonamide endothelin antagonists
US6670362B2 (en) 2000-09-20 2003-12-30 Pfizer Inc. Pyridazine endothelin antagonists
US8168616B1 (en) 2000-11-17 2012-05-01 Novartis Ag Combination comprising a renin inhibitor and an angiotensin receptor inhibitor for hypertension
NZ525614A (en) * 2000-12-18 2005-03-24 Actelion Pharmaceuticals Ltd Novel sulfamides and their use as endothelin receptor antagonists
US7235576B1 (en) 2001-01-12 2007-06-26 Bayer Pharmaceuticals Corporation Omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
WO2002083650A1 (en) * 2001-04-11 2002-10-24 Actelion Pharmaceuticals Ltd Novel sulfonylamino-pyrimidines
US7371763B2 (en) 2001-04-20 2008-05-13 Bayer Pharmaceuticals Corporation Inhibition of raf kinase using quinolyl, isoquinolyl or pyridyl ureas
WO2003068746A1 (en) 2002-02-11 2003-08-21 Bayer Pharmaceuticals Corporation Aryl ureas as kinase inhibitors
WO2003068229A1 (en) 2002-02-11 2003-08-21 Bayer Pharmaceuticals Corporation Pyridine, quinoline, and isoquinoline n-oxides as kinase inhibitors
DK1478358T3 (da) 2002-02-11 2013-10-07 Bayer Healthcare Llc Sorafenibtosylat til behandling af sygdomme kendetegnet ved unormal angiogenese
US20040002451A1 (en) 2002-06-20 2004-01-01 Bruce Kerwin Compositions of pegylated soluble tumor necrosis factor receptors and methods of preparing
EP1569914B1 (en) * 2002-12-02 2009-02-18 Actelion Pharmaceuticals Ltd. Pyrimidine-sulfamides and their use as endothelian receptor antagonist
UY28213A1 (es) 2003-02-28 2004-09-30 Bayer Pharmaceuticals Corp Nuevos derivados de cianopiridina útiles en el tratamiento de cáncer y otros trastornos.
PT1626714E (pt) 2003-05-20 2007-08-24 Bayer Pharmaceuticals Corp Diarilureias para doenças mediadas por pdgfr
ES2297490T3 (es) 2003-07-23 2008-05-01 Bayer Pharmaceuticals Corporation Omega-carboxiarildifenilurea fluoro sustituida para el tratamiento y prevencion de enfermadades y afecciones.
GB0327839D0 (en) 2003-12-01 2003-12-31 Novartis Ag Organic compounds
BRPI0508880A (pt) 2004-03-17 2007-09-04 Novartis Ag uso de compostos orgánicos
TW200628467A (en) 2004-11-11 2006-08-16 Actelion Pharmaceuticals Ltd Novel sulfamides
US7402730B1 (en) 2005-02-03 2008-07-22 Lexicon Pharmaceuticals, Inc. Knockout animals manifesting hyperlipidemia
GT200600381A (es) 2005-08-25 2007-03-28 Compuestos organicos
CA2657258A1 (en) 2006-07-20 2008-01-24 Novartis Ag Amino-piperidine derivatives as cetp inhibitors
AR062501A1 (es) 2006-08-29 2008-11-12 Actelion Pharmaceuticals Ltd Composiciones terapeuticas
PL2121751T3 (pl) 2006-12-08 2017-07-31 Lexicon Pharmaceuticals, Inc. Przeciwciała monoklonalne przeciwko ANGPTL3
ES2621018T3 (es) 2007-02-19 2017-06-30 Marine Polymer Technologies, Inc. Composiciones hemostáticas y regímenes terapéuticos
MX2010001837A (es) 2007-08-17 2010-03-10 Actelion Pharmaceuticals Ltd Derivados de 4-pirimidinasulfamida.
FR2921062A1 (fr) * 2007-09-17 2009-03-20 Commissariat Energie Atomique Composes utiles comme ligands et notamment comme chromophores organiques de complexation des lanthanides et leurs applications
PE20090982A1 (es) 2007-11-05 2009-08-13 Novartis Ag Derivados de piperidina como inhibidores de la proteina de transferencia de colesteril-ester (cetp)
US8759365B2 (en) 2007-12-03 2014-06-24 Novartis Ag Organic compounds
CA2761853A1 (en) 2009-05-15 2010-11-18 Novartis Ag Benzoxazolone derivatives as aldosterone synthase inhibitors
PE20120403A1 (es) 2009-05-15 2012-05-03 Novartis Ag Aril-piridinas como inhibidoras de sintasa de aldosterona
AU2010251967B9 (en) 2009-05-28 2014-04-03 Novartis Ag Substituted aminopropionic derivatives as neprilysin inhibitors
EA201101672A1 (ru) 2009-05-28 2012-06-29 Новартис Аг Замещенные производные аминомасляной кислоты в качестве ингибиторов неприлизина
CN102712589B (zh) 2009-11-17 2015-05-13 诺华股份有限公司 作为醛固酮合酶抑制剂的芳基-吡啶衍生物
JO2967B1 (en) 2009-11-20 2016-03-15 نوفارتس ايه جي Acetic acid derivatives of carbamoyl methyl amino are substituted as new NEP inhibitors
JP5575913B2 (ja) 2009-11-30 2014-08-20 ノバルティス アーゲー アルドステロン合成酵素阻害剤としてのイミダゾール誘導体
WO2011130646A1 (en) 2010-04-15 2011-10-20 Marine Polymer Technologies, Inc. Anti-bacterial applications of poly -n-acetylglucosamine nanofibers
US8673974B2 (en) 2010-11-16 2014-03-18 Novartis Ag Substituted amino bisphenyl pentanoic acid derivatives as NEP inhibitors
US8877815B2 (en) 2010-11-16 2014-11-04 Novartis Ag Substituted carbamoylcycloalkyl acetic acid derivatives as NEP
US20130302346A1 (en) 2010-11-24 2013-11-14 Lexicon Pharmaceuticals, Inc. Antibodies that bind notum pectinacetylesterase
CN107362171A (zh) 2011-04-15 2017-11-21 海洋聚合物技术公司 用聚‑n‑乙酰基葡糖胺纳米纤维治疗疾病
UY35144A (es) 2012-11-20 2014-06-30 Novartis Ag Miméticos lineales sintéticos de apelina para el tratamiento de insuficiencia cardiaca
US9383357B2 (en) 2012-12-07 2016-07-05 Northwestern University Biomarker for replicative senescence
PE20151666A1 (es) 2013-02-14 2015-11-19 Novartis Ag Derivados sustituidos del acido bisfenil butanoico fosfonico como inhibidores de la nep
CN105612172A (zh) 2013-07-25 2016-05-25 诺华股份有限公司 用于治疗心力衰竭的环状多肽
PE20160991A1 (es) 2013-07-25 2016-10-15 Novartis Ag Bioconjugados de polipeptidos de apelina sintetica
BR112017014194A2 (pt) 2015-01-23 2018-01-09 Novartis Ag conjugados de ácido graxo de apelina sintéticos com meia-vida melhorada
UY38072A (es) 2018-02-07 2019-10-01 Novartis Ag Compuestos derivados de éster butanoico sustituido con bisfenilo como inhibidores de nep, composiciones y combinaciones de los mismos
TWI835843B (zh) 2018-10-03 2024-03-21 瑞士商亨斯邁紡織染化(瑞士)有限公司 新的經吡啶及經嘧啶取代之三uv吸收劑
EP4240732A1 (en) 2020-11-05 2023-09-13 Idorsia Pharmaceuticals Ltd A stable crystalline hydrate of clazosentan disodium salt
EP4448511A1 (en) 2021-12-17 2024-10-23 Idorsia Pharmaceuticals Ltd Clazosentan disodium salt, its preparation and pharmaceutical compositions comprising the same

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW270116B (ko) * 1991-04-25 1996-02-11 Hoffmann La Roche
RU2086544C1 (ru) * 1991-06-13 1997-08-10 Хоффманн-Ля Рош АГ Бензолсульфонамидные производные пиримидина или их соли, фармацевтическая композиция для лечения заболеваний, связанных с активностью эндотелина
TW287160B (ko) * 1992-12-10 1996-10-01 Hoffmann La Roche
TW394761B (en) * 1993-06-28 2000-06-21 Hoffmann La Roche Novel Sulfonylamino Pyrimidines
IL111959A (en) * 1993-12-17 2000-07-16 Tanabe Seiyaku Co N-(polysubstituted pyrimidin-4-yl) benzenesulfonamide derivatives their preparation and pharmaceutical compositions containing them

Also Published As

Publication number Publication date
DE69531457D1 (en) 2003-09-11
FI972628A0 (fi) 1997-06-18
MA23744A1 (fr) 1996-07-01
ES2203649T3 (es) 2004-04-16
CN1170407A (zh) 1998-01-14
US6004965A (en) 1999-12-21
MX9704587A (es) 1998-07-31
IL116385A (en) 2000-07-16
EP0799209A1 (en) 1997-10-08
FI972628A (fi) 1997-06-18
NO972538L (no) 1997-06-04
MY131126A (en) 2007-07-31
CA2208018A1 (en) 1996-06-27
NO972538D0 (no) 1997-06-04
CZ187497A3 (en) 1997-10-15
ATE246681T1 (de) 2003-08-15
AU701767B2 (en) 1999-02-04
JPH10509182A (ja) 1998-09-08
CY2495B1 (en) 2005-09-02
KR100445085B1 (ko) 2004-10-14
NZ297797A (en) 1999-10-28
HU228619B1 (en) 2013-04-29
CN1098254C (zh) 2003-01-08
WO1996019459A1 (en) 1996-06-27
EP0799209B1 (en) 2003-08-06
CA2208018C (en) 2007-03-27
PT799209E (pt) 2003-12-31
SA95160421B1 (ar) 2006-05-01
JP2989014B2 (ja) 1999-12-13
BR9510104A (pt) 1997-11-25
HUT77884A (hu) 1998-09-28
FI120397B (fi) 2009-10-15
IL116385A0 (en) 1996-03-31
DE69531457T2 (de) 2004-06-24
DK0799209T3 (da) 2003-11-24
AU4304196A (en) 1996-07-10
CZ287916B6 (cs) 2001-03-14
TW313568B (ko) 1997-08-21
NO316645B1 (no) 2004-03-22

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Effective date: 20151207