EP0625144A1 - Derives de pyridone, leur prepartion et leur utilisation comme medicaments - Google Patents

Derives de pyridone, leur prepartion et leur utilisation comme medicaments

Info

Publication number
EP0625144A1
EP0625144A1 EP93902251A EP93902251A EP0625144A1 EP 0625144 A1 EP0625144 A1 EP 0625144A1 EP 93902251 A EP93902251 A EP 93902251A EP 93902251 A EP93902251 A EP 93902251A EP 0625144 A1 EP0625144 A1 EP 0625144A1
Authority
EP
European Patent Office
Prior art keywords
pyridone
hydrochloride
benzylamidino
benzyl
amidino
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP93902251A
Other languages
German (de)
English (en)
Inventor
Robert John Ife
Colin Andrew Leach
Dashyant Dhanak
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SmithKline Beecham Intercredit BV
Original Assignee
SmithKline Beecham Intercredit BV
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 SmithKline Beecham Intercredit BV filed Critical SmithKline Beecham Intercredit BV
Publication of EP0625144A1 publication Critical patent/EP0625144A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • 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
    • 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
    • C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3

Definitions

  • Ar 1 is an optionally substituted phenyl ring
  • Ar 2 i.s an optionally substituted phenyl ring
  • R 1 is hydrogen or C 1-4 alkyl
  • R 2 i.s hydrogen or C 1-4 alkyl
  • R 3 i.s hydrogen or C 1-4 alkyl
  • X is CH 2 or NR 6 in which R 6 is hydrogen or C 1-4 alkyl
  • Ar is an optionally substituted phenyl ring.
  • Suitable substituents for the phenyl ring Ar include, for example, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, halogen, cyano, amino, C 1-4 alkylamino, diC 1-4 alkylanri.no, hydroxy, carbamoyl, carboxy, C 1-6 alkanoyl trifluoromethyl, and
  • Ar is unsubstituted phenyl, or phenyl substituted by a single substituent selected from C 1-6 alkyl, C 1-6 alkoxy or halogen.
  • X is CH 2 or NR 6 ; preferably X is CH 2 or NR 6 in which R 6 is C 1-4 alkyl, in particular methyl.
  • reaction between compounds of structure (II) and compounds of structure (III) can be carried out in a
  • pharmaceutically acceptable salts exert an anti-secretory effect by inhibition of the gastrointestinal H K ATPase enzyme (Fellenius, E., Berglindh, T., Sachs, G., Olke, L., Elander, B., Sjostrand, S.E., and Wallmark, B., 1981, Nature, 290, 159-61 ) .
  • the present invention provides compounds of structure (I) and pharmaceutically acceptable salts thereof for use in therapy.
  • the compounds of structure (I) and their pharmaceutically acceptable salts inhibit exogenously and endogenously stimulated gastric acid secretion and are useful in the treatment of
  • the compounds of the present invention are usually administered in a standard
  • a typical suppository formulation comprises a compound of formula (I) or a pharmaceutically acceptable salt thereof which is active when administered in this way, with a binding and/or lubricating agent such as polymeric glycols, gelatins or cocoa butter or other low melting vegetable or synthetic waxes or fats.
  • a binding and/or lubricating agent such as polymeric glycols, gelatins or cocoa butter or other low melting vegetable or synthetic waxes or fats.
  • the present invention also provides a method of
  • intramuscular dose of between 0.1 mg and 100 mg, preferably between 0.1 mg and 25 mg, of the compound of the formula (I) or a pharmaceutically acceptable salt thereof calculated as the free base, the compound being administered 1 to 4 times per day.
  • the compounds will be administered for a period of continuous therapy, for example for a week or more.
  • Helicobacter pylori organisms for example antibiotics such as amoxicillin.
  • the compounds of examples 1 to 23 had IC 50 values of less than 20 ⁇ M.

Landscapes

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

Abstract

L'invention se rapporte à des dérivés de 2-pyridone de formule générale (I) dans laquelle Ar1 représente un cycle de phényle éventuellement substitué; Ar2 représente un cycle de phényle éventuellement substitué; R1 représente hydrogène ou alkyleC1-4; R2 représente hydrogène ou alkyleC1-4; R3 représente hydrogène ou alkyleC1-4; R4 et R5 sont identiques ou différents et représentent chacun hydrogène, alkyleC1-4 ou alkyleC1-4 Arl, ou R4 et R5 forment conjointement un groupe (CH=CH)2; et X représente CH2 ou NR6 dans lequel R6 représente hydrogène au alkyleC1-4. L'invention concerne également un sel desdits dérivés ainsi que l'utilisation de ceux-ci comme inhibiteurs de sécrétion d'acide gastrique.
EP93902251A 1992-01-27 1993-01-26 Derives de pyridone, leur prepartion et leur utilisation comme medicaments Withdrawn EP0625144A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB9201694 1992-01-27
GB929201694A GB9201694D0 (en) 1992-01-27 1992-01-27 Compounds
PCT/EP1993/000175 WO1993015056A1 (fr) 1992-01-27 1993-01-26 Derives de pyridone, leur prepartion et leur utilisation comme medicaments

Publications (1)

Publication Number Publication Date
EP0625144A1 true EP0625144A1 (fr) 1994-11-23

Family

ID=10709307

Family Applications (1)

Application Number Title Priority Date Filing Date
EP93902251A Withdrawn EP0625144A1 (fr) 1992-01-27 1993-01-26 Derives de pyridone, leur prepartion et leur utilisation comme medicaments

Country Status (5)

Country Link
EP (1) EP0625144A1 (fr)
JP (1) JPH07503022A (fr)
AU (1) AU3352693A (fr)
GB (1) GB9201694D0 (fr)
WO (1) WO1993015056A1 (fr)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
UA80393C2 (uk) 2000-12-07 2007-09-25 Алтана Фарма Аг Фармацевтична композиція, яка містить інгібітор фде 4, диспергований в матриці
MY140561A (en) 2002-02-20 2009-12-31 Nycomed Gmbh Dosage form containing pde 4 inhibitor as active ingredient
AR059898A1 (es) 2006-03-15 2008-05-07 Janssen Pharmaceutica Nv Derivados de 3-ciano-piridona 1,4-disustituida y su uso como moduladores alostericos de los receptores mglur2
TW200900065A (en) 2007-03-07 2009-01-01 Janssen Pharmaceutica Nv 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives
TW200845978A (en) 2007-03-07 2008-12-01 Janssen Pharmaceutica Nv 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives
NZ584145A (en) 2007-09-14 2012-03-30 Ortho Mcneil Janssen Pharm 1',3'-disubstituted-4-phenyl-3,4,5,6-tetrahydro-2h, 1'h-[1,4'] bipyridinyl-2'-ones
ES2439291T3 (es) 2008-09-02 2014-01-22 Janssen Pharmaceuticals, Inc. Derivados de 3-azabiciclo[3.1.0]hexilo como moduladores de receptores de glutamato metabotrópicos
MX2011005242A (es) 2008-11-28 2011-09-06 Ortho Mcneil Janssen Pharm Derivados de indol y benzoxazina como moduladores de los receptores de glutamato metabotropicos.
CA2760259C (fr) 2009-05-12 2018-05-01 Janssen Pharmaceuticals, Inc. Derives de la 1,2,4-triazolo [4,3-a] pyridine et leur utilisation en tant que modulateurs allosteriques positifs des recepteurs mglur2
MY153913A (en) 2009-05-12 2015-04-15 Janssen Pharmaceuticals Inc 7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors
MY161325A (en) 2009-05-12 2017-04-14 Janssen Pharmaceuticals Inc 1, 2, 4-triazolo[4,3-a]pyridine derivatives and their use for the treatment or prevention of neurological and psychiatric disorders
ES2536433T3 (es) 2010-11-08 2015-05-25 Janssen Pharmaceuticals, Inc. Derivados de 1,2,4-triazolo[4,3-a]piridina y su uso como moduladores alostéricos positivos de receptores mGluR2
JP5852664B2 (ja) 2010-11-08 2016-02-03 ジヤンセン・フアーマシユーチカルズ・インコーポレーテツド １，２，４−トリアゾロ［４，３−ａ］ピリジン誘導体およびｍＧｌｕＲ２受容体のポジティブアロステリックモジュレーターとしてのそれらの使用
CN103298809B (zh) 2010-11-08 2016-08-31 杨森制药公司 1,2,4-三唑并[4,3-a]吡啶衍生物及其作为MGLUR2受体的正变构调节剂的用途
JO3368B1 (ar) 2013-06-04 2019-03-13 Janssen Pharmaceutica Nv مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2
JO3367B1 (ar) 2013-09-06 2019-03-13 Janssen Pharmaceutica Nv مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2
ME03518B (fr) 2014-01-21 2020-04-20 Janssen Pharmaceutica Nv Combinaisons comprenant des modulateurs allostériques positifs de sous-type 2 de récepteurs glutamatergiques métabotropes et leur utilisation
WO2015110435A1 (fr) 2014-01-21 2015-07-30 Janssen Pharmaceutica Nv Combinaisons comprenant des modulateurs allostériques positifs ou des agonistes orthostériques de sous-type 2 de récepteur glutamatergique métabotrope, et leur utilisation

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3299081A (en) * 1963-09-13 1967-01-17 Merck & Co Inc Chemical processes for preparing nu-substituted amidines
US4028084A (en) * 1974-10-11 1977-06-07 Rohm And Haas Company Derivatives of 3-carboxy pyrid-2-ones
US4284768A (en) * 1980-07-02 1981-08-18 American Home Products Corporation 1,2-Dihydro-4-amino-2-oxo-3-quinoline-carboxylic acid derivatives
GB8804445D0 (en) * 1988-02-25 1988-03-23 Smithkline Beckman Intercredit Compounds
IL100917A0 (en) * 1991-02-16 1992-11-15 Fisons Plc Pyridinone and pyrimidinone derivatives,their preparation and pharmaceutical compositions containing them

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9315056A1 *

Also Published As

Publication number Publication date
AU3352693A (en) 1993-09-01
WO1993015056A1 (fr) 1993-08-05
JPH07503022A (ja) 1995-03-30
GB9201694D0 (en) 1992-03-11

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