TW330202B - Substituted heterocyclic carboxamide esters, their preparation and their use as pharmaceuticals - Google Patents

Substituted heterocyclic carboxamide esters, their preparation and their use as pharmaceuticals

Info

Publication number
TW330202B
TW330202B TW083111258A TW83111258A TW330202B TW 330202 B TW330202 B TW 330202B TW 083111258 A TW083111258 A TW 083111258A TW 83111258 A TW83111258 A TW 83111258A TW 330202 B TW330202 B TW 330202B
Authority
TW
Taiwan
Prior art keywords
alkyl
alkoxy
pharmaceuticals
preparation
substituted heterocyclic
Prior art date
Application number
TW083111258A
Other languages
English (en)
Inventor
Weidmann Klaus
Baringhaus Karl-Heinz
Tschank Geogr
Bickel Martin
Original Assignee
Hoechst 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
Priority claimed from DE4337270A external-priority patent/DE4337270A1/de
Priority claimed from DE19944434288 external-priority patent/DE4434288A1/de
Application filed by Hoechst Ag filed Critical Hoechst Ag
Application granted granted Critical
Publication of TW330202B publication Critical patent/TW330202B/zh

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • 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
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
    • C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
    • C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D237/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • 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
    • C07D409/12—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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biophysics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Quinoline Compounds (AREA)
  • Pyridine 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)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Hydrogenated Pyridines (AREA)
  • Steroid Compounds (AREA)
TW083111258A 1993-11-02 1994-12-05 Substituted heterocyclic carboxamide esters, their preparation and their use as pharmaceuticals TW330202B (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE4337270A DE4337270A1 (de) 1993-11-02 1993-11-02 Substituierte heterocyclische Carbonsäureamidester, ihre Herstellung und ihre Verwendung als Arzneimittel
DE19944434288 DE4434288A1 (de) 1994-09-26 1994-09-26 Substituierte heterocyclische Carbonsäureamidester, ihre Herstellung und ihre Verwendung als Arzneimittel

Publications (1)

Publication Number Publication Date
TW330202B true TW330202B (en) 1998-04-21

Family

ID=25930886

Family Applications (1)

Application Number Title Priority Date Filing Date
TW083111258A TW330202B (en) 1993-11-02 1994-12-05 Substituted heterocyclic carboxamide esters, their preparation and their use as pharmaceuticals

Country Status (21)

Country Link
US (1) US5658933A (zh)
EP (1) EP0650960B1 (zh)
JP (1) JPH07224039A (zh)
KR (1) KR950014069A (zh)
CN (1) CN1084736C (zh)
AT (1) ATE149485T1 (zh)
AU (1) AU689135B2 (zh)
CA (1) CA2134865A1 (zh)
CZ (1) CZ287767B6 (zh)
DE (1) DE59401923D1 (zh)
DK (1) DK0650960T3 (zh)
ES (1) ES2101420T3 (zh)
GR (1) GR3023177T3 (zh)
HK (1) HK1006712A1 (zh)
IL (1) IL111455A0 (zh)
NO (1) NO302028B1 (zh)
NZ (1) NZ264822A (zh)
PH (1) PH31264A (zh)
PL (1) PL179687B1 (zh)
RU (1) RU2145959C1 (zh)
TW (1) TW330202B (zh)

Families Citing this family (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6046219A (en) * 1995-01-20 2000-04-04 Cornell Research Foundation, Inc. Method for the treatment of conditions mediated by collagen formation together with cell proliferation by application of inhibitors of protein hydroxylation
IL135495A (en) * 1995-09-28 2002-12-01 Hoechst Ag Intermediate compounds for the preparation of quinoline-converted amines - 2 - carboxylic acid
EP0900202A1 (de) * 1996-04-30 1999-03-10 Hoechst Aktiengesellschaft 3-alkoxypyridin-2-carbonsäureamidester, ihre herstellung und ihre verwendung als arzneimittel
JPH1067674A (ja) * 1996-06-19 1998-03-10 Advanced Sukin Res Kenkyusho:Kk 細胞外マトリツクスの異常蓄積抑制剤
DE19746287A1 (de) * 1997-10-20 1999-04-22 Hoechst Marion Roussel De Gmbh Substituierte Isochinolin-2-Carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel
JP4689042B2 (ja) * 1998-11-04 2011-05-25 明治製菓株式会社 ピコリン酸アミド誘導体、それを有効成分として含有する有害生物防除剤
FR2803592A1 (fr) * 2000-01-06 2001-07-13 Aventis Cropscience Sa Nouveaux derives de l'acide 3-hydroxypicolinique, leur procede de preparation et compositions fongicides les contenant.
WO2001092258A1 (en) * 2000-05-30 2001-12-06 Neurogen Corporation Imidazoloisoquinolines
EP2295060B1 (en) 2001-12-06 2018-10-31 Fibrogen, Inc. Treatment or prevention of ischemic or hypoxic conditions
CN101664552B (zh) * 2001-12-06 2013-04-10 法布罗根股份有限公司 低氧诱导因子(HIF)α的稳定化
EP1463823B1 (en) 2001-12-06 2013-03-06 Fibrogen, Inc. Methods of increasing endogenous erythropoietin (epo)
US8124582B2 (en) 2002-12-06 2012-02-28 Fibrogen, Inc. Treatment of diabetes
US7618940B2 (en) * 2002-12-06 2009-11-17 Fibrogen, Inc. Fat regulation
US8614204B2 (en) 2003-06-06 2013-12-24 Fibrogen, Inc. Enhanced erythropoiesis and iron metabolism
CN102977015B (zh) 2003-06-06 2015-05-06 菲布罗根有限公司 含氮杂芳基化合物及其在增加内源性***中的用途
EP1866318B1 (en) 2005-03-02 2011-06-22 Fibrogen, Inc. Thienopyridine compounds, and methods of use thereof
CN101394843A (zh) * 2005-06-06 2009-03-25 菲布罗根公司 使用HIFα稳定剂的改进的贫血治疗
CN101242817B (zh) 2005-06-15 2016-08-31 菲布罗根公司 HIF1α调节剂在治疗癌症中的用途
US7928120B2 (en) 2006-01-27 2011-04-19 Fibrogen, Inc. Cyanoisoquinoline compounds and methods of use thereof
US20070265270A1 (en) * 2006-02-21 2007-11-15 Hitchcock Stephen A Cinnoline derivatives as phosphodiesterase 10 inhibitors
AU2007223801A1 (en) * 2006-03-08 2007-09-13 Amgen Inc. Quinoline and isoquinoline derivatives as phosphodiesterase 10 inhibitors
CN101460497A (zh) 2006-04-04 2009-06-17 菲布罗根有限公司 作为hif调节剂的吡咯并吡啶和噻唑并吡啶化合物
JO2934B1 (en) 2006-06-23 2015-09-15 سميث كلاين بيتشام كوربوريشن Prolyl hydroxylase inhibitors
AU2013231191B2 (en) * 2006-06-23 2015-09-03 Glaxosmithkline Llc Prolyl hydroxylase inhibitors
PL2044005T3 (pl) * 2006-06-26 2011-04-29 Akebia Therapeutics Inc Inhibitory hydroksylazy prolilowej oraz metody ich wykorzystania
WO2008000408A1 (en) * 2006-06-28 2008-01-03 Sanofi-Aventis Cxcr2 antagonists
JP5352455B2 (ja) * 2006-06-30 2013-11-27 サノフイ Ｃｘｃｒ２阻害剤
TW200845991A (en) * 2007-01-12 2008-12-01 Smithkline Beecham Corp N-substituted glycine derivatives: hydroxylase inhibitors
WO2009002533A1 (en) 2007-06-27 2008-12-31 The Brigham And Women's Hospital, Inc. Inflammatory bowel disease therapies
CN102272117B (zh) 2008-11-14 2015-06-17 菲布罗根有限公司 作为hif羟化酶抑制剂的苯并噻喃衍生物
WO2010093727A1 (en) * 2009-02-10 2010-08-19 Janssen Pharmaceutica Nv Quinazolinones as prolyl hydroxylase inhibitors
DK2649998T3 (en) * 2009-11-06 2015-05-04 Aerpio Therapeutics Inc Prolyl hydroxylase inhibitors
US8247436B2 (en) 2010-03-19 2012-08-21 Novartis Ag Pyridine and pyrazine derivative for the treatment of CF
CN103608346B (zh) 2011-02-02 2016-06-15 菲布罗根有限公司 作为缺氧诱导因子(hif)羟化酶抑制剂的萘啶衍生物
US20120329836A1 (en) 2011-06-06 2012-12-27 The Ohio State University Methods for stabilizing hypoxia inducible factor-2 alpha as a method for treating cancer
NO2686520T3 (zh) 2011-06-06 2018-03-17
JP6122862B2 (ja) 2011-10-25 2017-04-26 ヤンセン ファーマシューティカ エヌ．ベー． １−（５，６−ジクロロ−１ｈ−ベンゾ［ｄ］イミダゾール−２−イル）−１ｈ−ピラゾール−４−カルボン酸のメグルミン塩製剤
CN104470899B (zh) * 2012-03-09 2017-12-26 菲布罗根有限公司 作为hif羟化酶抑制剂的4‑羟基‑异喹啉化合物
RS57795B1 (sr) 2012-07-16 2018-12-31 Fibrogen Inc Kristalni oblici inhibitora prolil hidroksilaze
US8883823B2 (en) 2012-07-16 2014-11-11 Fibrogen, Inc. Crystalline forms of a prolyl hydroxylase inhibitor
MY171483A (en) 2012-07-16 2019-10-15 Fibrogen Inc Process for making isoquinoline compounds
WO2014116849A1 (en) 2013-01-24 2014-07-31 Fibrogen, Inc. Crystalline forms of {[1-cyano-5-(4-chlorophenoxy)-4-hydroxy-isoquinoline-3-carbonyl]-amino}-acetic acid
RU2019134558A (ru) 2013-06-13 2020-02-20 Экебиа Терапьютикс, Инк. Композиции и способы лечения анемии
EP3578546A1 (en) 2013-11-15 2019-12-11 Akebia Therapeutics Inc. Solid forms of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, compositions, and uses thereof
MX2017008418A (es) * 2014-12-30 2017-09-28 Dow Agrosciences Llc Picolinamidas con actividad fungicida.
BR112017015852A2 (pt) 2015-01-23 2018-03-27 Akebia Therapeutics Inc forma de cristal, sal hemicálcico, sal hemicálcico di-hidratado, sal monossódico hidratado, sal bissódico monoidratado, sal monossódico anidro e método para preparar o composto 1
CN106146395B (zh) * 2015-03-27 2019-01-01 沈阳三生制药有限责任公司 3-羟基吡啶化合物、其制备方法及其制药用途
UA123308C2 (uk) 2015-04-01 2021-03-17 Екебіа Терапьютікс, Інк. Композиції і способи для лікування анемії
CA3097219A1 (en) 2018-05-09 2019-11-14 Akebia Therapeutics, Inc. Process for preparing 2-[[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino]acetic acid
JP7470106B2 (ja) * 2019-04-26 2024-04-17 株式会社カネカ Ｖａｄａｄｕｓｔａｔ中間体の製造方法
CN110305143B (zh) * 2019-07-19 2021-03-09 济南新科医药科技有限公司 一种呋喃[2，3-c]并吡啶衍生物及其制备方法和用途
US11524939B2 (en) 2019-11-13 2022-12-13 Akebia Therapeutics, Inc. Solid forms of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino} acetic acid

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4015255A1 (de) * 1990-05-12 1991-11-14 Hoechst Ag Oxalyl-aminosaeurederivate, verfahren zu ihrer herstellung und ihrer verwendung als arzneimittel zur inhibierung der prolyl-hydroxylase
US5192773A (en) * 1990-07-02 1993-03-09 Vertex Pharmaceuticals, Inc. Immunosuppressive compounds
EP0541042A1 (de) * 1991-11-05 1993-05-12 Hoechst Aktiengesellschaft Pyridin-2,4- und 2,5-dicarbonsäureamide und deren Derivate, Verfahren zu ihrer Herstellung sowie deren Verwendung als Arzneimittel
TW352384B (en) * 1992-03-24 1999-02-11 Hoechst Ag Sulfonamido- or sulfonamidocarbonylpyridine-2-carboxamides, process for their preparation and their use as pharmaceuticals

Also Published As

Publication number Publication date
AU7756694A (en) 1995-05-18
NZ264822A (en) 1997-02-24
DE59401923D1 (de) 1997-04-10
NO302028B1 (no) 1998-01-12
CA2134865A1 (en) 1995-05-03
PH31264A (en) 1998-06-18
ATE149485T1 (de) 1997-03-15
CN1084736C (zh) 2002-05-15
CZ268294A3 (en) 1995-05-17
KR950014069A (ko) 1995-06-15
RU2145959C1 (ru) 2000-02-27
HK1006712A1 (en) 1999-03-12
RU94040163A (ru) 1997-02-20
DK0650960T3 (da) 1997-09-01
EP0650960B1 (de) 1997-03-05
NO944161D0 (no) 1994-11-01
AU689135B2 (en) 1998-03-26
JPH07224039A (ja) 1995-08-22
EP0650960A1 (de) 1995-05-03
PL179687B1 (pl) 2000-10-31
NO944161L (no) 1995-05-03
CN1107144A (zh) 1995-08-23
PL305647A1 (en) 1995-05-15
CZ287767B6 (en) 2001-01-17
IL111455A0 (en) 1994-12-29
US5658933A (en) 1997-08-19
GR3023177T3 (en) 1997-07-30
ES2101420T3 (es) 1997-07-01

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