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WO1997035860A1 - Nouveaux derives du benzimidazol ayant une affinite pour les recepteurs serotoninergiques 5-ht3 et 5-ht¿4? - Google Patents

Nouveaux derives du benzimidazol ayant une affinite pour les recepteurs serotoninergiques 5-ht3 et 5-ht¿4? Download PDF

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Publication number
WO1997035860A1
WO1997035860A1 PCT/ES1997/000068 ES9700068W WO9735860A1 WO 1997035860 A1 WO1997035860 A1 WO 1997035860A1 ES 9700068 W ES9700068 W ES 9700068W WO 9735860 A1 WO9735860 A1 WO 9735860A1
Authority
WO
WIPO (PCT)
Prior art keywords
azabicyclo
methyl
oct
exo
chloro
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.)
Ceased
Application number
PCT/ES1997/000068
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English (en)
Spanish (es)
Inventor
Maria Luz Lopez Rodriguez
Maria Jose Morcillo Ortega
Bellinda Benhamu Salama
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.)
Universidad Complutense de Madrid
Original Assignee
Universidad Complutense de Madrid
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 Universidad Complutense de Madrid filed Critical Universidad Complutense de Madrid
Priority to AU21607/97A priority Critical patent/AU2160797A/en
Publication of WO1997035860A1 publication Critical patent/WO1997035860A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
    • C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
    • C07D451/06—Oxygen atoms
    • C07D451/12—Oxygen atoms acylated by aromatic or heteroaromatic carboxylic acids, e.g. cocaine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • C07D451/14—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantane; Cyclic acetals thereof

Definitions

  • the present invention concerns new compounds of general formula I. where X is oxygen or nitrogen, R is hydrogen or chlorine, R 'is hydrogen, nitro or amino, and Y is azab ⁇ c ⁇ clo [x and zjalkyl, N-alkylpyridyl or dialkylaminoalkyl
  • the methods of preparing said compounds are described, which have shown a high affinity for serotonergic receptors 5-HT 3 and / or 5-HT 4 , indicating their therapeutic interest in the treatment of emesis caused by chemotherapy, and in the treatment of gastrointestinal and neuronal disorders, such as anxiety, psychosis, drug dependence and cognitive disorders
  • 5-HT 3 receptor antagonists - ondansetron, grarusetron, tropisetron, zacopride, renzapride - show enormous therapeutic interest in the treatment of emesis caused by chemotherapy (MS Aapro. Drugs. 1991. 42 (4). 551) and in the treatment of gastrointestinal disorders (S Bingham and cois. J Pharm Pharmaco!. 1994. 4 ⁇ . 219) or neuronal, such as anxiety (R Young. DN Johnson. Eur J Pharmacol. 1991
  • the present invention relates to new benzimidazole derivatives, which have shown a high affinity for 5-HT 3 and / or 5-HT 4 serotonergic receptors.
  • the compounds of general formula I have been synthesized by treatment of the benzimidazolcarboxylic acids II with 1,1'-carbonyldiimidazole (CDI) and subsequent reaction of the intermediate imidazolide with the corresponding aminoalcohol 1TJ or the corresponding diamine IV, in the presence of l, 8 -diazabicyclo [5 4 0] undec-7-ene (DBU) and anhydrous N, N-dimethylformamide (DMF) as the reaction solvent (Scheme I)
  • affinities of the compounds of general structure I for the serotonergic 5-HT 3 receptor in rat cerebral cortex membranes, in vitro were determined by radioligand displacement techniques, using [ 3 H] LY 278584 ([ 3 H] - 1- methyl-N- (enc / o-8-methyl-8-azabicyclo [3.2. L] oct-3-yl) -lH-3-indazolcarboxamide) as a selective ligand.
  • mice male albino rats, Rat ⁇ us norvegicus albinus
  • Sprague-Dawley breed weighing approximately 200 g
  • Brains are quickly removed and frozen in liquid nitrogen. The tissue is stored at -80 ° C until it is used.
  • the cerebral cortex is homogenized in 9 volumes of 0.32 M sucrose and centrifuged at 1000 xg for 10 min, at 4 ° C.
  • the sediment is neglected and the supernatant is centrifuged at 17000 xg for 20 min, at 4 ° C.
  • the sediment is washed twice by resuspension in 60 volumes of 50 mM Tris-HCl buffer (pH 7.4 at 25 C C), and centrifugation at 48000 xg for 10 min, at 4 ° C. After the second wash the resuspended sediment is incubated at 37 ° C for 10 min.
  • the membranes are centrifuged again under the same conditions and the sediment is resuspended in 2.75 volumes of the incubation buffer, consisting of 50 mM Tris-HCl, 10 ⁇ M pargiline, 0.6 mM ascorbic acid and 5 mM CaCl 2 (pH 7 , 4 to 25 ° C). 100 ⁇ L fractions (approximately 2 mg / mL protein) of the final membrane suspension are incubated for 30 min at 25 ° C with
  • LY 278584 (Amersham, 83 Ci / mmol) 0.7 nM, in the presence or absence of the compound under study at 1 ⁇ M concentration, in a final volume of 2 mL of incubation buffer.
  • Nonspecific binding is determined with 10 ⁇ M 5-HT.
  • the bound radioactive ligands are separated from the free ones by vacuum filtration on Whatman GF / B filters, washed twice with 4 mL of 50 mM Tris-HCl buffer. After drying the filters for 1 hour at At 60 ° C, 4 mL of scintillation liquid (Aquasol) is added and the membrane-bound radioactivity is measured by liquid scintillation spectrometry
  • affinities of the compounds of general structure I for the serotonergic 5-HT 4 receptor in rat brain striatum, m vitro were determined by radioligand displacement techniques, using [ 3 H] GR 1 13808 ([ 3 H] L- [2 - [(Methylsulfonyl) amino] ethyl] -4-piperidylmethyl) -1-methyl-lH-3-indolcarboxylate) as selective ligand
  • the striatum is rapidly dissected on ice, homogenized in 15 volumes of 50 mM HEPES buffer (pH 7.4 at 4 ° C) and centrifuged at 48000 xg for 10 min, at 4 ° C. The supernatant is neglected and the sediment resuspended in 4.5 mL

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne de nouveaux composés de formule générale (I), où X représente oxygène ou azote; R représente hydrogène ou chlore; R' représente hydrogène, nitro ou amino; et Y représente azabicyclo [x.y.z] alkyle, N-alkylpipéridyle ou dialalkylaminoalkyle. L'invention décrit également les procédés de préparation desdits composés, lesquels ont montré une grande affinité pour les récepteurs sérotoninergiques 5-HT3 et/ou 5-HT4. Ils sont donc particulièrement intéressants du point de vue thérapeutique pour le traitement de l'émèse provoquée par la chimiothérapie, et dans le traitement de troubles gastro-intestinaux et neuronaux tels que l'anxiété, la psychose, la toxicomanie et les troubles cognitifs.
PCT/ES1997/000068 1996-03-22 1997-03-18 Nouveaux derives du benzimidazol ayant une affinite pour les recepteurs serotoninergiques 5-ht3 et 5-ht¿4? Ceased WO1997035860A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU21607/97A AU2160797A (en) 1996-03-22 1997-03-18 Novel benzimidazol derivatives having an affinity for the serotoninergic 5-ht3/5 ht4 receptors

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ESP9600700 1996-03-22
ES9600700A ES2109190B1 (es) 1996-03-22 1996-03-22 Nuevos derivados de bencimidazol con afinidad por los receptores serotoninergicos 5-ht /5-ht

Publications (1)

Publication Number Publication Date
WO1997035860A1 true WO1997035860A1 (fr) 1997-10-02

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PCT/ES1997/000068 Ceased WO1997035860A1 (fr) 1996-03-22 1997-03-18 Nouveaux derives du benzimidazol ayant une affinite pour les recepteurs serotoninergiques 5-ht3 et 5-ht¿4?

Country Status (3)

Country Link
AU (1) AU2160797A (fr)
ES (1) ES2109190B1 (fr)
WO (1) WO1997035860A1 (fr)

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2154605A1 (es) * 1999-09-14 2001-04-01 Univ Madrid Complutense Nuevos derivados mixtos de bencimidazol-arilpiperazina con afinidad por los receptores serotoninergicos 5-ht1a y 5-ht3
WO2002100857A1 (fr) * 2001-06-12 2002-12-19 Pharmacia & Upjohn Company Multi-heteroaryles cycliques substitues par quinuclidines pour le traitement de maladies
US6828330B2 (en) 2001-06-12 2004-12-07 Pharmacia & Upjohn Company Quinuclidine-substituted hetero-bicyclic aromatic compounds for the treatment of disease
US6849620B2 (en) 2001-10-26 2005-02-01 Pfizer Inc N-(azabicyclo moieties)-substituted hetero-bicyclic aromatic compounds for the treatment of disease
US6858613B2 (en) 2002-02-19 2005-02-22 Pfizer Inc. Fused bicyclic-N-bridged-heteroaromatic carboxamides for the treatment of disease
US6894042B2 (en) 2002-02-19 2005-05-17 Pharmacia & Upjohn Company Azabicyclic compounds for the treatment of disease
US6911543B2 (en) 2001-10-02 2005-06-28 Pfizer Inc. Azabicyclic-substituted fused-heteroaryl compounds for the treatment of disease
US6951868B2 (en) 2001-11-09 2005-10-04 Pfizer Inc. Azabicyclic-phenyl-fused-heterocyclic compounds for treatment of disease
WO2006014134A1 (fr) * 2004-08-02 2006-02-09 Astrazeneca Ab Nouveau dérivatif de la pipéridine pour le traitement de la dépression
US7256294B2 (en) 2005-05-25 2007-08-14 Theravance, Inc. Crystalline form of a benzimidazole-carboxamide medicinal compound
WO2005021040A3 (fr) * 2003-08-29 2008-01-03 Dynogen Pharmaceuticals Inc Compositions utiles pour le traitement de troubles de motilite gastro-intestinale
US7351704B2 (en) 2004-02-18 2008-04-01 Theravance, Inc. Indazole-carboxamide compounds as 5-HT4 receptor agonists
US7351732B2 (en) 2002-07-31 2008-04-01 Schwarz Pharma S.L. Cycloalkanedione derivatives, method for the production thereof and their pharmacological applications
US7375114B2 (en) 2004-04-07 2008-05-20 Theravance, Inc. Quinolinone-carboxamide compounds as 5-HT4 receptor agonists
US7396933B2 (en) 2004-11-05 2008-07-08 Theravance, Inc. Quinolinone-carboxamide compounds
US7399862B2 (en) 2004-11-05 2008-07-15 Theravance, Inc. 5-HT4 receptor agonist compounds
US7419989B2 (en) 2004-12-22 2008-09-02 Theravance, Inc. Indazole-carboxamide compounds
US7446114B2 (en) 2005-03-02 2008-11-04 Theravance, Inc. Quinolinone compounds as 5-HT4 receptor agonists
US7728006B2 (en) 2004-04-07 2010-06-01 Theravance, Inc. Quinolinone-carboxamide compounds as 5-HT4 receptor agonists
US7759363B2 (en) 2005-05-25 2010-07-20 Theravance, Inc. Benzimidazole-carboxamide compounds as 5-HT4, receptor agonists
US7781430B2 (en) 2005-02-17 2010-08-24 Albany Molecular Research, Inc. Benzoxazole carboxamides for treating CINV and IBS-D
US8309575B2 (en) 2004-04-07 2012-11-13 Theravance, Inc. Quinolinone-carboxamide compounds as 5-HT4 receptor agonists

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WO1994000449A1 (fr) * 1992-06-24 1994-01-06 G.D. Searle & Co. Composes de benzimidazole
WO1994000454A1 (fr) * 1992-06-24 1994-01-06 G.D. Searle & Co. Composes de benzimidazoles
WO1995003298A1 (fr) * 1993-07-19 1995-02-02 Fujisawa Pharmaceutical Co., Ltd. DERIVES BENZIMIDAZOLIQUES UTILISABLES COMME AGONISTE DU RECEPTEUR DOPAMINERGIQUE, ANTAGONISTE DU RECEPTEUR SEROTONINERGIQUE, OU ANTAGONISTE DU RECEPTEUR α¿1?

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WO1994000449A1 (fr) * 1992-06-24 1994-01-06 G.D. Searle & Co. Composes de benzimidazole
WO1994000454A1 (fr) * 1992-06-24 1994-01-06 G.D. Searle & Co. Composes de benzimidazoles
WO1995003298A1 (fr) * 1993-07-19 1995-02-02 Fujisawa Pharmaceutical Co., Ltd. DERIVES BENZIMIDAZOLIQUES UTILISABLES COMME AGONISTE DU RECEPTEUR DOPAMINERGIQUE, ANTAGONISTE DU RECEPTEUR SEROTONINERGIQUE, OU ANTAGONISTE DU RECEPTEUR α¿1?

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DENNY, WILLIAM A. ET AL: "Potential antitumor agents. 59. Structure-activity relationships for 2-phenylbenzimidazole-4-carboxamides, a new class of minimal DNA-intercalating agents which may not act via topoisomerase II", J. MED. CHEM. (1990), 33(2), 814-19 CODEN: JMCMAR;ISSN: 0022-2623, 1990, XP002007402 *
FLIPPIN, L. A. ET AL: "(R)-3-(6-chloro-1-isopropylbenzimidazole-4-carboxamido)quinuclidine: a high affinity ligand for the (R)-zacopride binding site", BIOORG. MED. CHEM. LETT. (1996), 6(4), 477-80 CODEN: BMCLE8;ISSN: 0960-894X, 1996, XP000674844 *
LOPEZ-RODRIGUEZ, MARIA L. ET AL: "Novel benzimidazole-4-carboxylic acid derivatives as potent and selective 5-HT3 receptor ligands", BIOORG. MED. CHEM. LETT. (1996), 6(11), 1195-1198 CODEN: BMCLE8;ISSN: 0960-894X, 1996, XP000674824 *

Cited By (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2154605A1 (es) * 1999-09-14 2001-04-01 Univ Madrid Complutense Nuevos derivados mixtos de bencimidazol-arilpiperazina con afinidad por los receptores serotoninergicos 5-ht1a y 5-ht3
US7067515B2 (en) 2001-06-12 2006-06-27 Pfizer Inc. Quinuclidines-substituted-multi-cyclic-heteroaryls for the treatment of disease
WO2002100857A1 (fr) * 2001-06-12 2002-12-19 Pharmacia & Upjohn Company Multi-heteroaryles cycliques substitues par quinuclidines pour le traitement de maladies
US6828330B2 (en) 2001-06-12 2004-12-07 Pharmacia & Upjohn Company Quinuclidine-substituted hetero-bicyclic aromatic compounds for the treatment of disease
US6911543B2 (en) 2001-10-02 2005-06-28 Pfizer Inc. Azabicyclic-substituted fused-heteroaryl compounds for the treatment of disease
US6849620B2 (en) 2001-10-26 2005-02-01 Pfizer Inc N-(azabicyclo moieties)-substituted hetero-bicyclic aromatic compounds for the treatment of disease
US6951868B2 (en) 2001-11-09 2005-10-04 Pfizer Inc. Azabicyclic-phenyl-fused-heterocyclic compounds for treatment of disease
US6894042B2 (en) 2002-02-19 2005-05-17 Pharmacia & Upjohn Company Azabicyclic compounds for the treatment of disease
US6858613B2 (en) 2002-02-19 2005-02-22 Pfizer Inc. Fused bicyclic-N-bridged-heteroaromatic carboxamides for the treatment of disease
US7351732B2 (en) 2002-07-31 2008-04-01 Schwarz Pharma S.L. Cycloalkanedione derivatives, method for the production thereof and their pharmacological applications
WO2005021040A3 (fr) * 2003-08-29 2008-01-03 Dynogen Pharmaceuticals Inc Compositions utiles pour le traitement de troubles de motilite gastro-intestinale
US8044045B2 (en) 2004-02-18 2011-10-25 Theravance, Inc. Indazole-carboxamide compounds as 5-HT4 receptor agonists
US7351704B2 (en) 2004-02-18 2008-04-01 Theravance, Inc. Indazole-carboxamide compounds as 5-HT4 receptor agonists
US7728006B2 (en) 2004-04-07 2010-06-01 Theravance, Inc. Quinolinone-carboxamide compounds as 5-HT4 receptor agonists
US8309575B2 (en) 2004-04-07 2012-11-13 Theravance, Inc. Quinolinone-carboxamide compounds as 5-HT4 receptor agonists
US8962653B2 (en) 2004-04-07 2015-02-24 Theravance Biopharma R&D Ip, Llc Quinolinone-carboxamide compounds as 5-HT4 receptor agonists
US7375114B2 (en) 2004-04-07 2008-05-20 Theravance, Inc. Quinolinone-carboxamide compounds as 5-HT4 receptor agonists
US9873692B2 (en) 2004-04-07 2018-01-23 Theravance Biopharma R&D Ip, Llc Quinolinone-carboxamide compounds as 5-HT4 receptor agonists
US9630960B2 (en) 2004-04-07 2017-04-25 Theravance Biopharma R&D Ip, Llc Quinolinone-carboxamide compounds as 5-HT4 receptor agonists
US7763637B2 (en) 2004-04-07 2010-07-27 Theravance, Inc. Quinolinone-carboxamide compounds as 5-HT4, receptor agonists
US9353106B2 (en) 2004-04-07 2016-05-31 Theravance Biopharma R&D Ip, Llc Quinolinone-carboxamide compounds as 5-HT4 receptor agonists
WO2006014134A1 (fr) * 2004-08-02 2006-02-09 Astrazeneca Ab Nouveau dérivatif de la pipéridine pour le traitement de la dépression
US7396933B2 (en) 2004-11-05 2008-07-08 Theravance, Inc. Quinolinone-carboxamide compounds
US7399862B2 (en) 2004-11-05 2008-07-15 Theravance, Inc. 5-HT4 receptor agonist compounds
US7498442B2 (en) 2004-11-05 2009-03-03 Theravance, Inc. Quinolinone-carboxamide compounds
US7534889B2 (en) 2004-11-05 2009-05-19 Theravance, Inc. 5-HT4 receptor agonist compounds
US7786136B2 (en) 2004-12-22 2010-08-31 Theravance, Inc. Indazole-carboxamide compounds
US8003664B2 (en) 2004-12-22 2011-08-23 Theravance, Inc. Indazole-carboxamide compounds
US7419989B2 (en) 2004-12-22 2008-09-02 Theravance, Inc. Indazole-carboxamide compounds
US7781430B2 (en) 2005-02-17 2010-08-24 Albany Molecular Research, Inc. Benzoxazole carboxamides for treating CINV and IBS-D
US7875629B2 (en) 2005-03-02 2011-01-25 Theravance, Inc. Quinolinone compounds as 5-HT4 receptor agonists
US7446114B2 (en) 2005-03-02 2008-11-04 Theravance, Inc. Quinolinone compounds as 5-HT4 receptor agonists
US7622587B2 (en) 2005-05-25 2009-11-24 Theravance, Inc. Crystalline form of a benzimidazole-carboxamide medicinal compound
US8288550B2 (en) 2005-05-25 2012-10-16 Theravance, Inc. Crystalline form of a benzimidazole-carboxamide medicinal compound
US8377964B2 (en) 2005-05-25 2013-02-19 Theravance, Inc. Benzimidazole-carboxamide compounds as 5-HT4 receptor agonists
US8143279B2 (en) 2005-05-25 2012-03-27 Theravance, Inc. Benzimidazole-carboxamide compounds as 5-HT4 receptor agonists
US7897775B2 (en) 2005-05-25 2011-03-01 Theravance, Inc. Crystalline form of a benzimidazole-carboxamide medicinal compound
US9428489B2 (en) 2005-05-25 2016-08-30 Theravance Biopharma R&D Ip, Llc Benzimidazole-carboxamide compounds as 5-HT4 receptor agonists
US7759363B2 (en) 2005-05-25 2010-07-20 Theravance, Inc. Benzimidazole-carboxamide compounds as 5-HT4, receptor agonists
US7256294B2 (en) 2005-05-25 2007-08-14 Theravance, Inc. Crystalline form of a benzimidazole-carboxamide medicinal compound
US9975877B2 (en) 2005-05-25 2018-05-22 Theravance Biopharma R&D Ip, Llc Benzimidazole-carboxamide compounds as 5-HT4 receptor agonists
US10233172B2 (en) 2005-05-25 2019-03-19 Theravance Biopharma R&D Ip, Llc Benzimidazole-carboxamide compounds as 5-HT4 receptor agonists
US10696656B2 (en) 2005-05-25 2020-06-30 Theravance Biopharma R&D Ip, Llc Benzimidazole-carboxamide compounds as 5-HT4 receptor agonists
US11254655B2 (en) 2005-05-25 2022-02-22 Theravance Biopharma R&D Ip, Llc Benzimidazole-carboxamide compounds as 5-HT4 receptor agonists

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Publication number Publication date
ES2109190A1 (es) 1998-01-01
ES2109190B1 (es) 1998-07-01
AU2160797A (en) 1997-10-17

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