WO1994007496A1 - Antagonistes recepteurs d'oxytocine tocolytique - Google Patents

Antagonistes recepteurs d'oxytocine tocolytique Download PDF

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Publication number
WO1994007496A1
WO1994007496A1 PCT/US1993/009152 US9309152W WO9407496A1 WO 1994007496 A1 WO1994007496 A1 WO 1994007496A1 US 9309152 W US9309152 W US 9309152W WO 9407496 A1 WO9407496 A1 WO 9407496A1
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
hydrogen
mammal
chr
compound
Prior art date
Application number
PCT/US1993/009152
Other languages
English (en)
Inventor
Ben E. Evans
Douglas W. Hobbs
Joseph M. Pawluczyk
Douglas J. Pettibone
Kenneth E. Rittle
Peter D. Williams
Original Assignee
Merck & Co., Inc.
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 Merck & Co., Inc. filed Critical Merck & Co., Inc.
Priority to US08/411,619 priority Critical patent/US5670509A/en
Priority to EP93923134A priority patent/EP0663827A4/fr
Priority to AU52923/93A priority patent/AU5292393A/en
Priority to JP6509222A priority patent/JPH08502474A/ja
Publication of WO1994007496A1 publication Critical patent/WO1994007496A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/20—Spiro-condensed ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Definitions

  • Tocolytic (uterine-relaxing) agents that are currently in use include B2-adrenergic agonists, magnesium sulfate and ethanol.
  • Ritodrine the leading B2-adrenergic agonist, causes a number of cardiovascular and metabolic side effects in the mother, including tachycardia, increased renin secretion, hyperglycemia (and reactive hypoglycemia in the infant).
  • Other B2-adrenergic agonists, including terbutaline and albuterol have side effects similar to those of ritodrine.
  • R 9 is hydrogen or C 1-5 alkyl
  • pharmaceutically effective amount shall mean that amount of a drug or pharmaceutical agent that will elicit the biological or medical response of a tissue, system, animal or human that is being sought by a researcher or clinician.
  • IC 50 the concentration of tested compound that inhibits 50% of OT was reported, unless otherwise noted.

Abstract

Composés ayant la formule X-Y-Z-R1, dans laquelle X représente (I) ou (II); W représente hydrogène ou acétate; Y représente -CO-, -SO¿2?- -CO(CH2)m- ou -(CH2)m-; Z représente N, O, S, -CHR-, -CR=CH-, -CH=, -(CH2)m- ou -CHCHOH-; R représente hydrogène, C1-5 alkyle, C1-5 alcoxycarbonylamino ou quinuclidinylaminocarbonylamino; R?1¿ représente -CH¿3?, -CH(CH3)2, C1-5 alcoxycarbonyle, aryle, cycloalkyle inférieur et hétérocyclique substituté par R?2¿ et/ou R?3, -NR4R5¿ ou -NCOR6; R2 représente hydrogène, hydroxy, carboxyle, acétyle, nitro, halogène, mono-, di- ou tri-C¿1-3? alkyle indényle spirocyclique, N-spiroindanepipéridinyle, O-R où R est tel que défini ci-dessus, O-Het où Het représente imidazole ou benzimidazole ou azimidobenzène, ou lorsque R?2¿ est défini par -COR6, -(CH¿2?)m-NHCOR?7¿, -(CH¿2?)mNHCOOR?7¿, -(CH¿2?)m-NR?8R9¿, -(CH¿2?)m-NHCO-(CH2)mR?7¿, -(CH¿2?)m-NHCO-CHR?7R7¿, -(CH¿2?)m-NHCO-CH=CHR?7¿, -(CH¿2?)m-CO-O-R?7¿, -(CH¿2?)m-CO-O-(CH2)mR?7¿, -(CH¿2?)m-CO-O-CHR?7R7¿, -(CH)¿m?-CO-O-CH=CHR?7¿, -NHSO¿2?R- où R est tel que défini ci-dessus, NHSO2R?7¿, -(CH¿2?)m-O-R?10, -SO¿2R?10, -COR11¿, aryle alkyle inférieur, alkyle sulfonylalkyle, alkylsulfonylalkylamido, R3 représente un ou deux des éléments suivants: hydrogène, hydroxyle ou C¿1-5? alkyle; R?4¿ représente hydrogène, C¿1-5? alkyle ou C6-10 cycloalkyle; R?5¿ représente hydrogène ou acétyle; R6 représente (A) ou (B); R7 représente alkyle carbamate alkyle, aryle alkyle ou hétérocyclylalkyle substitué par R12, hydrogène, C¿1-4? alkyle, NSO2R?12¿ ou NHO-C¿1-4? alkyle; R?8¿ représente hydrogène ou C¿1-5? alkyle; R?9¿ représente hydrogène ou C¿1-5? alkyle; R?10¿ représente -CH¿3?, alkaryle, alkarylalkyle ou azimidobenzene; R?11¿ représente -CH¿3?, aralkyle ou hétérocyclylalkyle; R?12¿ représente hydrogène, C¿1-5? alkyle ou C1-5 alcoxy; et m est un nombre entier compris entre 0 et 5. De tels composés sont utiles en tant qu'antagonistes de l'oxytocine et de la vasopressine.
PCT/US1993/009152 1992-10-07 1993-09-27 Antagonistes recepteurs d'oxytocine tocolytique WO1994007496A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US08/411,619 US5670509A (en) 1993-09-27 1993-09-27 Tocolytic oxytocin receptor antagonists
EP93923134A EP0663827A4 (fr) 1992-10-07 1993-09-27 Antagonistes recepteurs d'oxytocine tocolytique.
AU52923/93A AU5292393A (en) 1992-10-07 1993-09-27 Tocolytic oxytocin receptor antagonists
JP6509222A JPH08502474A (ja) 1992-10-07 1993-09-27 トコリティックオキシトシンレセプターアンタゴニスト

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US95793892A 1992-10-07 1992-10-07
US957,938 1992-10-07

Publications (1)

Publication Number Publication Date
WO1994007496A1 true WO1994007496A1 (fr) 1994-04-14

Family

ID=25500372

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1993/009152 WO1994007496A1 (fr) 1992-10-07 1993-09-27 Antagonistes recepteurs d'oxytocine tocolytique

Country Status (5)

Country Link
EP (1) EP0663827A4 (fr)
JP (1) JPH08502474A (fr)
AU (1) AU5292393A (fr)
CA (1) CA2143117A1 (fr)
WO (1) WO1994007496A1 (fr)

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0751773A1 (fr) * 1994-03-24 1997-01-08 Merck & Co. Inc. Antagonistes tocolytique des recepteurs de l'ocytocine
US5665719A (en) * 1993-07-16 1997-09-09 Merck & Co., Inc. Benzoxazinone and benzopyrimidinone piperidinyl tocolytic oxytocin receptor antagonists
US5686454A (en) * 1993-07-16 1997-11-11 Merck & Co., Inc. Camphorcarbonyl
US5707985A (en) * 1995-06-07 1998-01-13 Tanabe Seiyaku Co. Ltd. Naphthyl-, quinolyl- and isoquinolyl- sulfonamide derivatives as cell adhesion modulators
WO1998046569A1 (fr) * 1997-04-11 1998-10-22 Sumitomo Pharmaceuticals Co., Ltd. Derives de benzene
WO2002002531A1 (fr) * 2000-07-05 2002-01-10 Ortho-Mcneil Pharmaceutical, Inc. Spirobenzoazepines non peptidiques substituees, antagonistes de la vasopressine
US6770627B1 (en) 1998-09-12 2004-08-03 Astrazeneca Ab Piperizine-4-phenyl derivatives as inhibitors of the interaction between mdm2 and p 53
WO2006072393A2 (fr) * 2005-01-04 2006-07-13 Sanofi-Aventis Sulfonylpyrrolidines, procede pour les produire et leur utilisation comme medicaments
JP2007521272A (ja) * 2003-06-17 2007-08-02 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ 置換スピロベンズアゼピン
US7329673B2 (en) 2003-04-04 2008-02-12 Merck & Co., Inc. Acylated spiropiperidine derivatives as melanocortin-4 receptor agonists
US20080153863A1 (en) * 2006-12-22 2008-06-26 Caterina Bissantz Spiropiperidine derivatives
WO2008077811A1 (fr) * 2006-12-22 2008-07-03 F. Hoffmann-La Roche Ag Dérivés de spiropipéridine
WO2010007794A1 (fr) 2008-07-18 2010-01-21 興和株式会社 Nouveau composé spiro et préparation pharmaceutique le comprenant
US7825110B2 (en) 2006-09-22 2010-11-02 Janssen Pharmaceutica Nv Substituted spiroheterocycles
US7825111B2 (en) 2006-09-22 2010-11-02 Janssen Pharmaceutica Nv Substituted spiroheterocycles
US8202993B2 (en) 2006-12-07 2012-06-19 Hoffmann-La Roche Inc. Spiro-piperidine derivatives
US8541585B2 (en) 2010-03-11 2013-09-24 Dainippon Sumitomo Pharma Co., Ltd. N-acyl cyclic amine derivative or pharmaceutically acceptable salt thereof
US20140005272A1 (en) * 2011-06-28 2014-01-02 Sandra Eve Reznik Administration of n,n-dimethylacetamide and its monomethylated metabolites for the treatment of inflammatory disorders

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5715605B2 (ja) * 2011-09-14 2015-05-07 大日本住友製薬株式会社 Ｎ−アシル環状アミン誘導体またはその医薬上許容される塩からなる医薬
WO2014024993A1 (fr) * 2012-08-09 2014-02-13 国立大学法人京都大学 Dérivé de pipérazine et utilisation de celui-ci

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0414289A1 (fr) * 1989-07-26 1991-02-27 Merck Sharp & Dohme Ltd. Agents antipsychotiques spirocycliques
EP0445974A2 (fr) * 1990-03-05 1991-09-11 MERCK SHARP & DOHME LTD. Agents antipsychotiques spirocycliques
US5091387A (en) * 1990-03-02 1992-02-25 Merck & Co., Inc. Spirocyclic oxytocin antagonists

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0444945A3 (en) * 1990-03-02 1992-05-13 Merck & Co. Inc. Use of spirocyclic compounds as oxytocin antagonists
IL99957A0 (en) * 1990-11-13 1992-08-18 Merck & Co Inc Piperidinylcamphorsulfonyl oxytocin antagonists and pharmaceutical compositions containing them

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0414289A1 (fr) * 1989-07-26 1991-02-27 Merck Sharp & Dohme Ltd. Agents antipsychotiques spirocycliques
US5091387A (en) * 1990-03-02 1992-02-25 Merck & Co., Inc. Spirocyclic oxytocin antagonists
EP0445974A2 (fr) * 1990-03-05 1991-09-11 MERCK SHARP & DOHME LTD. Agents antipsychotiques spirocycliques

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP0663827A4 *

Cited By (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5665719A (en) * 1993-07-16 1997-09-09 Merck & Co., Inc. Benzoxazinone and benzopyrimidinone piperidinyl tocolytic oxytocin receptor antagonists
US5686454A (en) * 1993-07-16 1997-11-11 Merck & Co., Inc. Camphorcarbonyl
EP0751773A4 (fr) * 1994-03-24 1997-07-16 Merck & Co Inc Antagonistes tocolytique des recepteurs de l'ocytocine
EP0751773A1 (fr) * 1994-03-24 1997-01-08 Merck & Co. Inc. Antagonistes tocolytique des recepteurs de l'ocytocine
US5707985A (en) * 1995-06-07 1998-01-13 Tanabe Seiyaku Co. Ltd. Naphthyl-, quinolyl- and isoquinolyl- sulfonamide derivatives as cell adhesion modulators
WO1998046569A1 (fr) * 1997-04-11 1998-10-22 Sumitomo Pharmaceuticals Co., Ltd. Derives de benzene
US6770627B1 (en) 1998-09-12 2004-08-03 Astrazeneca Ab Piperizine-4-phenyl derivatives as inhibitors of the interaction between mdm2 and p 53
WO2002002531A1 (fr) * 2000-07-05 2002-01-10 Ortho-Mcneil Pharmaceutical, Inc. Spirobenzoazepines non peptidiques substituees, antagonistes de la vasopressine
US7001898B2 (en) 2000-07-05 2006-02-21 Ortho-Mcneil Pharmaceutical, Inc. Nonpeptide substituted spirobenzoazepines as vasopressin antagonists
CN1449386B (zh) * 2000-07-05 2012-07-04 奥索-麦克尼尔药品公司 作为血管升压素拮抗剂的非肽取代的螺苯并氮杂*
US7691844B2 (en) 2000-07-05 2010-04-06 Ortho-Mcneil Pharmaceutical, Inc. Nonpeptide substituted spirobenzoazepines as vasopressin antagonists
US7238687B2 (en) 2000-07-05 2007-07-03 Ortho-Mcneil Pharmaceutical, Inc. Nonpeptide substituted spirobenzoazepines as vasopressin antagonists
US7329673B2 (en) 2003-04-04 2008-02-12 Merck & Co., Inc. Acylated spiropiperidine derivatives as melanocortin-4 receptor agonists
JP2007521272A (ja) * 2003-06-17 2007-08-02 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ 置換スピロベンズアゼピン
US7687494B2 (en) 2003-06-17 2010-03-30 Janssen Pharmaceutica Nv Substituted spirobenzazepines
US7468369B2 (en) 2005-01-04 2008-12-23 Sanofi-Aventis Sulfonyl pyrrolidines, method for producing the same and their use as drugs
WO2006072393A3 (fr) * 2005-01-04 2006-08-31 Sanofi Aventis Deutschland Sulfonylpyrrolidines, procede pour les produire et leur utilisation comme medicaments
WO2006072393A2 (fr) * 2005-01-04 2006-07-13 Sanofi-Aventis Sulfonylpyrrolidines, procede pour les produire et leur utilisation comme medicaments
US7825111B2 (en) 2006-09-22 2010-11-02 Janssen Pharmaceutica Nv Substituted spiroheterocycles
US7825110B2 (en) 2006-09-22 2010-11-02 Janssen Pharmaceutica Nv Substituted spiroheterocycles
US8202993B2 (en) 2006-12-07 2012-06-19 Hoffmann-La Roche Inc. Spiro-piperidine derivatives
US8084609B2 (en) 2006-12-22 2011-12-27 Hoffman-La Roche Inc. Spiropiperidine derivatives
WO2008077810A3 (fr) * 2006-12-22 2008-09-25 Hoffmann La Roche Dérivés de spiropipéridine
US20080153863A1 (en) * 2006-12-22 2008-06-26 Caterina Bissantz Spiropiperidine derivatives
WO2008077811A1 (fr) * 2006-12-22 2008-07-03 F. Hoffmann-La Roche Ag Dérivés de spiropipéridine
EP2535329A3 (fr) * 2006-12-22 2013-03-27 F. Hoffmann-La Roche AG Dérivés de spiro-pipéridine
WO2008077810A2 (fr) * 2006-12-22 2008-07-03 F. Hoffmann-La Roche Ag Dérivés de spiropipéridine
US7495008B2 (en) 2006-12-22 2009-02-24 Hoffmann-La Roche Inc. Spiro-piperidine derivatives
KR101122969B1 (ko) * 2006-12-22 2012-03-22 에프. 호프만-라 로슈 아게 스피로-피페리딘 유도체
AU2007338116B2 (en) * 2006-12-22 2012-04-26 F. Hoffmann-La Roche Ag Spiro-piperidine derivatives
US7501432B2 (en) 2006-12-22 2009-03-10 Hoffman-La Roche Inc. Spiro-piperidine derivatives
US7678806B2 (en) 2006-12-22 2010-03-16 Hoffmann-La Roche Inc. Spiro-piperidine derivatives
CN101563323B (zh) * 2006-12-22 2012-07-04 弗·哈夫曼-拉罗切有限公司 螺-哌啶衍生物
WO2010007794A1 (fr) 2008-07-18 2010-01-21 興和株式会社 Nouveau composé spiro et préparation pharmaceutique le comprenant
US8541585B2 (en) 2010-03-11 2013-09-24 Dainippon Sumitomo Pharma Co., Ltd. N-acyl cyclic amine derivative or pharmaceutically acceptable salt thereof
US20140005272A1 (en) * 2011-06-28 2014-01-02 Sandra Eve Reznik Administration of n,n-dimethylacetamide and its monomethylated metabolites for the treatment of inflammatory disorders
US11717499B2 (en) * 2011-06-28 2023-08-08 Sandra Eve Reznik Administration of N,N-dimethylacetamide for the treatment of preterm birth

Also Published As

Publication number Publication date
AU5292393A (en) 1994-04-26
CA2143117A1 (fr) 1994-04-14
EP0663827A1 (fr) 1995-07-26
EP0663827A4 (fr) 1995-11-15
JPH08502474A (ja) 1996-03-19

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