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WO1999041239A1 - Inhibiteurs de lymphocytes b - Google Patents

Inhibiteurs de lymphocytes b Download PDF

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Publication number
WO1999041239A1
WO1999041239A1 PCT/EP1999/000817 EP9900817W WO9941239A1 WO 1999041239 A1 WO1999041239 A1 WO 1999041239A1 EP 9900817 W EP9900817 W EP 9900817W WO 9941239 A1 WO9941239 A1 WO 9941239A1
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
compound
halogen
formula
cell
Prior art date
Application number
PCT/EP1999/000817
Other languages
English (en)
Inventor
Rainer Albert
Elsebeth Andersen
Markus Christen
Alexander Hagenbach
Christoph Heusser
Christos Papageorgiou
Max H. Schreier
Anette Wienand
Original Assignee
Novartis Ag
Novartis-Erfindungen Verwaltungsgesellschaft M.B.H.
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 GBGB9802842.6A external-priority patent/GB9802842D0/en
Priority claimed from GBGB9810688.3A external-priority patent/GB9810688D0/en
Priority claimed from GBGB9826553.1A external-priority patent/GB9826553D0/en
Application filed by Novartis Ag, Novartis-Erfindungen Verwaltungsgesellschaft M.B.H. filed Critical Novartis Ag
Priority to AU28323/99A priority Critical patent/AU2832399A/en
Publication of WO1999041239A1 publication Critical patent/WO1999041239A1/fr

Links

Classifications

    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen

Definitions

  • heterocyclic ring group or moiety is meant e.g. a 5 or 6 membered saturated or unsaturated heterocyclic ring comprising 1 or 2 heteroatoms, preferably selected from N, O and S, e.g. pyrrolyl, imidazolyl, pyridyl, pyrrolidinyl, piperidyl, piperazinyl or morpholino. Preferred are e.g. pyrrolidinyl, piperazinyl or morpholino.
  • Rn, R 13 , R i5 and R 16 is H, R ⁇ 2 is C 2 H 5 and R i is CF 3 or OCF 3 , preferably in position para;
  • T-CO-ZH II wherein T and Z are as defined above, or a functional derivative thereof, with a compound of formula III
  • T-6769 ratio of 16 ⁇ g TNP/mg LPS; Sigma.
  • the stimulated spleen cells are cultured for 4 days at 37°C in a humidified CO2 incubator (5.5%).
  • microtiter plates are centrifuged at 300 x g for 10 min, and supernatant from each of the two replicate cultures are pooled and diluted 4 fold in PBS/BSA and then assayed in an ELISA.
  • the graft is monitored daily by palpation of the abdomen. Rejection is concluded with cessation of heart beat. In the present series of experiments, the endpoint is set to 28 days. Animals are terminated and the transplant is subjected to conventional histology.
  • the kit or package may comprise instructions for its administration.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des dérivés quinoléine et indole en tant qu'inhibiteurs de lymphocytes B, notamment des nouveaux amides; elle concerne également un procédé de production de ces inhibiteurs, leur utilisation en tant que médicament, par exemple en tant qu'inhibiteur de lymphocytes B ne bloquant pas l'activité de la dihydroorotate déshydrogénase (DHODH), ainsi que des compositions pharmaceutiques contenant ces inhibiteurs.
PCT/EP1999/000817 1998-02-10 1999-02-08 Inhibiteurs de lymphocytes b WO1999041239A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU28323/99A AU2832399A (en) 1998-02-10 1999-02-08 B cell inhibitors

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
GB9802842.6 1998-02-10
GBGB9802842.6A GB9802842D0 (en) 1998-02-10 1998-02-10 Organic compounds
GBGB9810688.3A GB9810688D0 (en) 1998-05-19 1998-05-19 Organic compounds
GB9810688.3 1998-05-19
GB9826553.1 1998-12-02
GBGB9826553.1A GB9826553D0 (en) 1998-12-02 1998-12-02 Organic compounds

Publications (1)

Publication Number Publication Date
WO1999041239A1 true WO1999041239A1 (fr) 1999-08-19

Family

ID=27269204

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1999/000817 WO1999041239A1 (fr) 1998-02-10 1999-02-08 Inhibiteurs de lymphocytes b

Country Status (5)

Country Link
AR (1) AR015514A1 (fr)
AU (1) AU2832399A (fr)
CO (1) CO4980854A1 (fr)
PE (1) PE20000281A1 (fr)
WO (1) WO1999041239A1 (fr)

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002012189A1 (fr) * 2000-08-09 2002-02-14 Mitsubishi Pharma Corporation Composes amide bicycliques condenses et utilisations medicales associees
WO2002072549A1 (fr) * 2001-03-12 2002-09-19 Millennium Pharmaceuticals, Inc. Heterocycles fonctionnalises en tant que modulateurs de la fonction du recepteur de chimiokines et procedes de mise en oeuvre
WO2002046181A3 (fr) * 2000-12-07 2002-12-27 Cv Therapeutics Inc Composes elevant abca-1
WO2003016304A1 (fr) * 2001-08-15 2003-02-27 E. I. Du Pont De Nemours And Company Amides aryle ortho-heterocycliques substitues permettant de lutter contre des ravageurs invertebres
US6908923B2 (en) * 2001-12-21 2005-06-21 Cytokinetics, Inc. Compositions and methods for treating heart failure
WO2012109329A2 (fr) 2011-02-08 2012-08-16 Children's Medical Center Corporation Méthodes de traitement d'un mélanome
US20130079306A1 (en) * 2010-07-02 2013-03-28 Hiroshi Uchida HETEROCYCLIC COMPOUND AND p27Kip1 DEGRADATION INHIBITOR
EP2583678A2 (fr) 2004-06-24 2013-04-24 Novartis Vaccines and Diagnostics, Inc. Immunopotentiateurs de petites molécules et dosages pour leur détection
US8686048B2 (en) 2010-05-06 2014-04-01 Rhizen Pharmaceuticals Sa Immunomodulator and anti-inflammatory compounds
EP2847165A2 (fr) * 2012-04-02 2015-03-18 Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. Dérivés d'indole, d'indoline, compositions les contenant et leurs utilisations
US9266883B2 (en) 2013-10-25 2016-02-23 Novartis Ag Ring-fused bicyclic pyridyl derivatives as FGFR4 inhibitors
US9802917B2 (en) 2015-03-25 2017-10-31 Novartis Ag Particles of N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide
WO2019057053A1 (fr) * 2017-09-20 2019-03-28 北京加科思益新药研发有限公司 Dérivé à cycle fusionné utilisé en tant qu'inhibiteur de fgfr4
US10463653B2 (en) 2014-10-03 2019-11-05 Novartis Ag Use of ring-fused bicyclic pyridyl derivatives as FGFR4 inhibitors
US10730839B2 (en) * 2016-11-27 2020-08-04 Russell Dahl Quinolines as cytoprotective agents

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2008692A1 (de) * 1969-02-26 1970-09-17 Agence Nationale de Valorisation de La Recherche (ANVAR), Puteaux, Hautsde-Seine (Prankreich) Verfahren zur Herstellung von Indol-3carbonsäurederivaten und nach dem Verfahren erhältliche, neue Verbindungen
DE2113733A1 (de) * 1970-03-24 1971-10-14 Sandoz Ag Verfahren zur Herstellung neuer heterocyclischer Verbindungen
FR2121394A1 (fr) * 1971-01-08 1972-08-25 Anvar Procédé d'obtention de dérivés d'acides indole carboxyliques et produits préparables par ce procédé.
WO1995011885A1 (fr) * 1993-10-27 1995-05-04 Neurogen Corporation Pyrrolecarboxanilides fusionnes constituant une nouvelle classe de ligands des recepteurs gaba du cerveau

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2008692A1 (de) * 1969-02-26 1970-09-17 Agence Nationale de Valorisation de La Recherche (ANVAR), Puteaux, Hautsde-Seine (Prankreich) Verfahren zur Herstellung von Indol-3carbonsäurederivaten und nach dem Verfahren erhältliche, neue Verbindungen
DE2113733A1 (de) * 1970-03-24 1971-10-14 Sandoz Ag Verfahren zur Herstellung neuer heterocyclischer Verbindungen
FR2121394A1 (fr) * 1971-01-08 1972-08-25 Anvar Procédé d'obtention de dérivés d'acides indole carboxyliques et produits préparables par ce procédé.
WO1995011885A1 (fr) * 1993-10-27 1995-05-04 Neurogen Corporation Pyrrolecarboxanilides fusionnes constituant une nouvelle classe de ligands des recepteurs gaba du cerveau

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
A.N. GRINEV ET AL.: "Quinons. XXXVII. Condensation of p-benzoquinone with anilidides of beta-aminocrotonic acids", ZHUR. OBSHCHEI KHIM., vol. 31, 1961, pages 2303 - 6 *
C. KUEHM-CAUBERE ET AL.: "Novel Indole-2-carboxamide and cycloalkeno[1,2-b]indole derivatives. Structure-activity relationships for high inhibition of human LDL peroxidation", JOURNAL OF MEDICINAL CHEMISTRY, vol. 40, no. 8, 1997, pages 1201 - 1210, XP002105908 *
CHEMICAL ABSTRACTS, vol. 56, no. 9, 1962, Columbus, Ohio, US; abstract no. 10075, XP002105911 *
P. CARAMELLA ET AL.: "Cycloadditions of nitrile oxides to indoles. Reactivity and regiochemistry", TETRAHEDRON, vol. 38, no. 1, - 1982, pages 173 - 82, XP002105910 *
W. SCHÄFER; P. NEUBERT: "MASSENSPEKTREN HETEROCYCLISCHERARBONSÄUREAMIDE-I PYRIDIN- UND CHINOLINCARBONSÄUREANILIDE", TETRAHEDRON, vol. 25, 1969, pages 315 - 327, XP002105909 *

Cited By (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002012189A1 (fr) * 2000-08-09 2002-02-14 Mitsubishi Pharma Corporation Composes amide bicycliques condenses et utilisations medicales associees
US7112594B2 (en) 2000-08-09 2006-09-26 Mitsubishi Pharma Corporation Fused bicyclic amide compounds and medicinal use thereof
JP2009149602A (ja) * 2000-12-07 2009-07-09 Cv Therapeutics Inc Ａｂｃａ−１を上昇させる化合物
WO2002046181A3 (fr) * 2000-12-07 2002-12-27 Cv Therapeutics Inc Composes elevant abca-1
US6548548B2 (en) 2000-12-07 2003-04-15 Cv Therapeutics, Inc. ABCA-1 elevating compounds
AU2002225978B2 (en) * 2000-12-07 2005-08-11 Gilead Palo Alto, Inc. ABCA-1 elevating compounds against coronary artery disease or atherosclerosis
WO2002072549A1 (fr) * 2001-03-12 2002-09-19 Millennium Pharmaceuticals, Inc. Heterocycles fonctionnalises en tant que modulateurs de la fonction du recepteur de chimiokines et procedes de mise en oeuvre
US6951848B2 (en) 2001-03-12 2005-10-04 Millennium Pharmaceuticals, Inc., Functionalized heterocycles as modulators of chemokine receptor function and methods of use therefor
WO2003016304A1 (fr) * 2001-08-15 2003-02-27 E. I. Du Pont De Nemours And Company Amides aryle ortho-heterocycliques substitues permettant de lutter contre des ravageurs invertebres
US7629463B2 (en) 2001-08-15 2009-12-08 E. I. Du Pont De Nemours And Company Ortho-heterocyclic substituted aryl amides for controlling invertebrate pests
US7375232B2 (en) 2001-08-15 2008-05-20 E.I. Du Pont De Nemours And Company Ortho-heterocyclic substituted aryl amides for controlling invertebrate pests
US7053094B2 (en) 2001-12-21 2006-05-30 Cytokinetics, Inc. Compositions and methods for treating heart failure
US7605164B2 (en) 2001-12-21 2009-10-20 Cytokinetics, Inc. Compositions and methods for treating heart failure
US6908923B2 (en) * 2001-12-21 2005-06-21 Cytokinetics, Inc. Compositions and methods for treating heart failure
EP2583678A2 (fr) 2004-06-24 2013-04-24 Novartis Vaccines and Diagnostics, Inc. Immunopotentiateurs de petites molécules et dosages pour leur détection
US8686048B2 (en) 2010-05-06 2014-04-01 Rhizen Pharmaceuticals Sa Immunomodulator and anti-inflammatory compounds
US9758474B2 (en) 2010-05-06 2017-09-12 Incozen Therapeutics Pvt. Ltd. Immunomodulator and anti-inflammatory compounds
US9200008B2 (en) * 2010-07-02 2015-12-01 Aska Pharmaceutical Co., Ltd. Heterocyclic compound and p27Kip1 degradation inhibitor
US20130079306A1 (en) * 2010-07-02 2013-03-28 Hiroshi Uchida HETEROCYCLIC COMPOUND AND p27Kip1 DEGRADATION INHIBITOR
WO2012109329A2 (fr) 2011-02-08 2012-08-16 Children's Medical Center Corporation Méthodes de traitement d'un mélanome
EP2847165A2 (fr) * 2012-04-02 2015-03-18 Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. Dérivés d'indole, d'indoline, compositions les contenant et leurs utilisations
US9266883B2 (en) 2013-10-25 2016-02-23 Novartis Ag Ring-fused bicyclic pyridyl derivatives as FGFR4 inhibitors
US9533988B2 (en) 2013-10-25 2017-01-03 Novartis Ag Ring-fused bicyclic pyridyl derivatives as FGFR4 inhibitors
US9896449B2 (en) 2013-10-25 2018-02-20 Novartis Ag Ring-fused bicyclic pyridyl derivatives as FGFR4 inhibitors
US10463653B2 (en) 2014-10-03 2019-11-05 Novartis Ag Use of ring-fused bicyclic pyridyl derivatives as FGFR4 inhibitors
US10507201B2 (en) 2014-10-03 2019-12-17 Novartis Ag Use of ring-fused bicyclic pyridyl derivatives as FGFR4 inhibitors
US9802917B2 (en) 2015-03-25 2017-10-31 Novartis Ag Particles of N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide
US10730839B2 (en) * 2016-11-27 2020-08-04 Russell Dahl Quinolines as cytoprotective agents
WO2019057053A1 (fr) * 2017-09-20 2019-03-28 北京加科思益新药研发有限公司 Dérivé à cycle fusionné utilisé en tant qu'inhibiteur de fgfr4
CN111164075A (zh) * 2017-09-20 2020-05-15 北京加科思新药研发有限公司 用作fgfr4抑制剂的稠环衍生物

Also Published As

Publication number Publication date
AU2832399A (en) 1999-08-30
PE20000281A1 (es) 2000-05-15
CO4980854A1 (es) 2000-11-27
AR015514A1 (es) 2001-05-02

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