ES2103221A1 - New 2,3-di:hydro-benzimidazole-2-thione derivs - used as serotonin 5HT-3 receptor antagonists for treat CNS and gastrointestinal disorders eg nausea - Google Patents

New 2,3-di:hydro-benzimidazole-2-thione derivs - used as serotonin 5HT-3 receptor antagonists for treat CNS and gastrointestinal disorders eg nausea

Info

Publication number
ES2103221A1
ES2103221A1 ES09301754A ES9301754A ES2103221A1 ES 2103221 A1 ES2103221 A1 ES 2103221A1 ES 09301754 A ES09301754 A ES 09301754A ES 9301754 A ES9301754 A ES 9301754A ES 2103221 A1 ES2103221 A1 ES 2103221A1
Authority
ES
Spain
Prior art keywords
thione
benzimidazole
oct
nausea
derivs
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.)
Granted
Application number
ES09301754A
Other languages
Spanish (es)
Other versions
ES2103221B1 (en
Inventor
Vidal Ramon Merce
Constansa Jordi Frigola
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.)
Esteve Pharmaceuticals SA
Original Assignee
Laboratorios del Dr Esteve SA
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 Laboratorios del Dr Esteve SA filed Critical Laboratorios del Dr Esteve SA
Publication of ES2103221A1 publication Critical patent/ES2103221A1/en
Application granted granted Critical
Publication of ES2103221B1 publication Critical patent/ES2103221B1/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • 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
    • C07D451/02—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
    • 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

Landscapes

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

Abstract

1-(Azabicycloalkoxycarbonyl or N-azabicycloalkyl-carbamoyl) -2,3-dihydro-benzimidazole-2(1H)-thione derivs. of formula (I) and their tautomers and acid addn. salts are new. In the formula, R = H or 1-4C alkyl, pref. Et or isopropyl Z = N (sic) or O and Y = endo-8-methyl-8-azabicyclo(3.2.1)oct-3-yl or 1-azabicyclo(2.1.2)oct-3-yl. USE - (I) are serotonin (esp. 5HT3 receptor) antagonists. They are used for treatment of CNS disorders (e.g. migraine, anxiety and psychosis) and gastrointestinal disorders (e.g. intestinal motility disorders, nausea and dyspepsia). (I) are typically used for treating emesis and nausea induced by chemotherapy or radiation. (I) are also pharmaceutical intermediates. 5 Cpds. are claimed e.g. endo-8-methyl-8-azabicyclo-(3.2.1) oct-3-yl 2,3-dihydro-2-thione-1H-benzimidazole-1- carboxylate hydrochloride (Ia). In an example, a soln. of 1.5g 2,3-dihydro-1H-benzimidazole-2-thione in 40 ml pyridine was treated slowly with endo-8-methyl-8-aza-bicyclo (3.2.1)oct-3-yl chloroformate hydrochloride, refluxed for 3 hrs. and evaporated. The residue was triturated with ether to give 2.4g of (Ia), m.pt. 215-219 deg.C. (Ia) had rat cortex 5HT3 receptor binding affinity Ki 5.3 nM, compared with 186 nM for metoclopramide.
ES9301754A 1992-07-29 1993-07-28 NEW DERIVATIVES OF BENCIMIDAZOLE-2-TIONA, ITS PREPARATION AND ITS APPLICATION AS MEDICINES. Expired - Fee Related ES2103221B1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR9209382A FR2694292B1 (en) 1992-07-29 1992-07-29 Benzimidazole-2-thione- derivatives, their preparation and their use as medicaments.

Publications (2)

Publication Number Publication Date
ES2103221A1 true ES2103221A1 (en) 1997-09-01
ES2103221B1 ES2103221B1 (en) 1998-07-01

Family

ID=9432404

Family Applications (1)

Application Number Title Priority Date Filing Date
ES9301754A Expired - Fee Related ES2103221B1 (en) 1992-07-29 1993-07-28 NEW DERIVATIVES OF BENCIMIDAZOLE-2-TIONA, ITS PREPARATION AND ITS APPLICATION AS MEDICINES.

Country Status (2)

Country Link
ES (1) ES2103221B1 (en)
FR (1) FR2694292B1 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7737163B2 (en) 2004-06-15 2010-06-15 Pfizer Inc. Benzimidazolone carboxylic acid derivatives
CA2569654C (en) 2004-06-15 2010-12-21 Pfizer Inc. Benzimidazolone carboxylic acid derivatives
KR100908547B1 (en) 2005-02-22 2009-07-20 화이자 인코포레이티드 Oxyindole Derivatives as 5TH4 Receptor Agonists

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0309423A2 (en) * 1987-09-23 1989-03-29 BOEHRINGER INGELHEIM ITALIA S.p.A. New benzimidazoline-2-oxo-1-carboxylic acid derivatives useful as 5-ht receptor antagonists

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3687980T2 (en) * 1986-01-07 1993-06-17 Beecham Group Plc INDOLDER DERIVATIVES WITH AN AZABICYCLIC SIDE CHAIN, METHOD FOR THEIR PRODUCTION, INTERMEDIATE PRODUCTS AND PHARMACEUTICAL COMPOSITIONS.

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0309423A2 (en) * 1987-09-23 1989-03-29 BOEHRINGER INGELHEIM ITALIA S.p.A. New benzimidazoline-2-oxo-1-carboxylic acid derivatives useful as 5-ht receptor antagonists

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
TURCONI, M. et al.: "Pharmacological properties of a novel class of 5-HT3 receptor antagonists." European Journal of Pharmacology, Vol. 203, 1991, pßginas 203-211 * Figura 1 * *
TURCONI, M. et al.: "Synthesis of a new class of 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylic Acid derivatives as highly potent 5HT3 receptor antagonists." J. Med. Chem. Vol. 33, 1990, pßginas 2101-2108 * Figura 12a; tabla I * *

Also Published As

Publication number Publication date
ES2103221B1 (en) 1998-07-01
FR2694292A1 (en) 1994-02-04
FR2694292B1 (en) 1994-10-21

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