WO1993008185A1 - N-aryle-n1-azabicyclo-urees utilisees comme antagonistes de 5-ht3 - Google Patents

N-aryle-n1-azabicyclo-urees utilisees comme antagonistes de 5-ht3 Download PDF

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Publication number
WO1993008185A1
WO1993008185A1 PCT/GB1992/001876 GB9201876W WO9308185A1 WO 1993008185 A1 WO1993008185 A1 WO 1993008185A1 GB 9201876 W GB9201876 W GB 9201876W WO 9308185 A1 WO9308185 A1 WO 9308185A1
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WO
WIPO (PCT)
Prior art keywords
methyl
endo
azabicyclo
urea
compound according
Prior art date
Application number
PCT/GB1992/001876
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English (en)
Inventor
Francis David King
Laramie Mary Gaster
Original Assignee
Smithkline Beecham Plc
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 Plc filed Critical Smithkline Beecham Plc
Publication of WO1993008185A1 publication Critical patent/WO1993008185A1/fr

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    • 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

Definitions

  • This invention relates to novel compounds having pharmacological activity, to a process for their preparation and their use as pharmaceuticals.
  • EP-A-235878 and 377967 (Beecham Group p.l.c.) describe phenylurea derivatives having an azabicyclic side chain and having 5-HT3 receptor antagonist activity.
  • the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof:
  • a 1 , A 2 , A 3 and the carbon atoms to which they are attached form a 5- or 6- membered non-aromatic heterocyclic ring containing at least one -0-, -CO- or -N-;
  • R 1 and R 2 are hydrogen or C 1 -6 alkyl
  • Y is hydrogen, halo, C 1 -6 alkyl or C 1 -6 alkoxy
  • L is O or NH
  • Z is an azabicyclic side chain
  • Values for A 1 -A 2 -A 3 include :-
  • any of A 1 -A 2 -A 3 containing one or more hydrogen atoms may be substituted by R 1 /R 2 when C 1 -6 alkyl.
  • a 1 -A 2 -A 3 is O-(CH 2 ) 2 -O orCO-O-CH 2 .
  • Suitable examples of alkyl moieties in R 1 and R 2 and Y include methyl, ethyl, n- and iso-propyl, n-, iso-, seo and tert-butyl.
  • halo moieties include fluoro, chloro and bromo.
  • Suitable examples of Z are described in the art relating to 5-HT 3 receptor antagonists, ie. as follows: i) GB 2125398A (Sandoz Limited)
  • EP-A-215545 (Beecham Group p.l.c.)
  • EP-A-214772 (Beecham Group p.l.c.)
  • R is hydrogen or methyl; and X is oxygen, sulphur or nitrogen optionally substituted by C 1-6 alkyl, C 3-8 cycloalkyl, C 3-8 cycloalkyl C 1-4 alkyl, phenyl, naphthyl, phenyl C 1-4 alkyl or naphthyl C 1-4 alkyl wherein a phenyl or naphthyl moiety is optionally substituted by one or more of halo, C 1-6 alkoxy or C 1-6 alkyl.
  • Side chains Z of particular interest include tropane, oxagranatane and azagranatane, where R is methyl.
  • Suitable values for N-substituents when X is N are as described in WO 92/05174 , for example, iso-propyl or ethyl.
  • L is preferably NH.
  • the pharmaceutically acceptable salts of the compounds of the formula (I) include acid addition salts with conventional acids such as hydrochloric, hydrobromic, boric, phosphoric, sulphuric acids and pharmaceutically acceptable organic acids such as acetic, tartaric, maleic, citric, succinic, benzoic, ascorbic, methanesulphonic, ⁇ -keto glutaric, ⁇ -glycerophosphoric, and glucose-1-phosphoric acids.
  • conventional acids such as hydrochloric, hydrobromic, boric, phosphoric, sulphuric acids
  • pharmaceutically acceptable organic acids such as acetic, tartaric, maleic, citric, succinic, benzoic, ascorbic, methanesulphonic, ⁇ -keto glutaric, ⁇ -glycerophosphoric, and glucose-1-phosphoric acids.
  • Examples of pharmaceutically acceptable salts include quaternary derivatives of the compounds of formula (I) such as the compounds quaternised by compounds R x -T wherein R x is C 1-6 alkyl, phenyl- C 1-6 alkyl or C 5-7 cycloalkyl, and T is a radical corresponding to an anion of an acid.
  • R x include methyl, ethyl and n- and /so-propyl; and benzyl and phenethyl.
  • Suitable examples of T include halide such as chloride, bromide and iodide.
  • Examples of pharmaceutically acceptable salts also include internal salts such as N-oxides.
  • the L - Z function intermediates are generally prepared from the
  • exocyclic keto derivative of the azabicyclic side chain prepared by condensation methods, often using a substituted piperidine. They may be prepared by processes described in the aforementioned Patent Publications relating to values of the side chain Z. It will be realised that in the compounds of the formula (I) having a tropane, granatane or oxa/thia/aza-granatane side chain, the -COL- linkage has an e ⁇ do orientation with respect to the ring of the bicyclic moiety to which it is attached. A mixture of endo and exo isomers of the compound of the formula (I) may be synthesised non-stereospecifically and the desired isomer separated conventionally therefrom e.g.
  • compositions of this invention may be formed conventionally.
  • the salts may be formed for example by reaction of the base compound of formula (I) with a pharmaceutically acceptable organic or inorganic acid.
  • the compounds of the present invention are 5-HT3 receptor antagonists and it is thus believed may generally be used in the treatment or prophylaxis of pain, emesis, CNS disorders and gastrointestinal disorders. Pain includes migraine, cluster headache, trigeminal neuralgia and visceral pain; emesis, includes, in particular, that of preventing vomiting and nausea associated with cancer therapy, post-operative emesis, and nausea associated with migraine. Examples of such cancer therapy include that using cytotoxic agents, such as platinum complexes including cisplatin, and also doxorubicin and
  • CNS disorders include anxiety, psychosis, cognitive disorders such as senile dementia and age associated memory inpairment (AAMI), and drug
  • Gastrointestinal disorders include irritable bowel syndrome and diarrohea.
  • 5-HT3 receptor antagonists may also be of potential use in the treatment of obesity and/or arrhythmia.
  • the invention also provides a pharmaceutical composition
  • a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
  • compositions are prepared by admixture and are usually adapted for oral or parenteral administration, and as such may be in the form of tablets, capsules, oral liquid preparations, powders, granules, lozenges,
  • compositions are preferred, since they are more convenient for general use.
  • Tablets and capsules for oral administration are usually presented in a unit dose, and contain conventional excipients such as binding agents, fillers, diluents, tabletting agents, lubricants, disintegrants, colourants, flavourings, and wetting agents.
  • the tablets may be coated according to well known methods in the art, for example with an enteric coating.
  • Suitable fillers for use include cellulose, mannitol, lactose and other similar agents.
  • Suitable disintegrants include starch, polyvinylpolypyrrolidone and starch derivatives such as sodium starch glycollate.
  • Suitable lubricants include, for example, magnesium stearate.
  • Suitable pharmaceutically acceptable wetting agents include sodium lauryl sulphate.
  • Oral liquid preparations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups, or elixirs, or may be presented as a dry product for reconstitution with water or other suitable vehicle before use.
  • Such liquid preparations may contain conventional additives such as suspending agents, for example sorbitol, syrup, methyl cellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminium stearate gel or hydrogenated edible fats, emulsifying agents, for example lecithin, sorbitan monooleate, or acacia; non-aqueous vehicles (which may include edible oils), for example, almond oil, fractionated coconut oil, oily esters such as esters of glycerine, propylene glycol, or ethyl alcohol;
  • suspending agents for example sorbitol, syrup, methyl cellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminium stearate gel or hydrogenated edible fats, emulsifying agents, for example lecithin, sorbitan monooleate, or acacia
  • non-aqueous vehicles which may include edible oils
  • almond oil fractionated coconut oil
  • oily esters such as esters of g
  • preservatives for example methyl or propyl p-hydroxybenzoate or sorbic acid, and if desired conventional flavouring or colouring agents.
  • Oral liquid preparations are usually in the form of aqueous or oily
  • suspensions, solutions, emulsions, syrups, or elixirs are presented as a dry product for reconstitution with water or other suitable vehicle before use.
  • Such liquid preparations may contain conventional additives such as suspending agents, emulsifying agents, non-aqueous vehicles (which may include edible oils), preservatives, and flavouring or colouring agents.
  • the oral compositions may be prepared by conventional methods of blending, filling or tabletting. Repeated blending operations may be used to distribute the active agent throughout those compositions employing large quantities of fillers. Such operations are, of course, conventional in the art.
  • fluid unit dose forms are prepared containing a compound of the present invention and a sterile vehicle. The compound, depending on the vehicle and the concentration, can be either suspended or dissolved.
  • Parenteral solutions are normally prepared by dissolving the compound in a vehicle and filter sterilising before filling into a suitable vial or ampoule and sealing.
  • adjuvants such as a local
  • the composition can be frozen after filling into the vial and the water removed under vacuum.
  • Parenteral suspensions are prepared in substantially the same manner except that the compound is suspended in the vehicle instead of being dissolved and sterilised by exposure of ethylene oxide before suspending in the sterile vehicle.
  • a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound of the invention.
  • the invention further provides a method of treatment or prophylaxis of pain, emesis, CNS disorders and/or gastrointestinal disorders in mammals, such as humans, which comprises the administration of an effective amount of a compound of the formula (I) or a pharmaceutically acceptable salt thereof.
  • An amount effective to treat the disorders hereinbefore described depends on the relative efficacies of the compounds of the invention, the nature and severity of the disorder being treated and the weight of the mammal.
  • a unit dose for a 70kg adult will normally contain 0.05 to 1000mg for example 0.5 to 500mg, of the compound of the invention.
  • Unit doses may be administered once or more than once a day, for example, 2, 3 or 4 times a day, more usually 1 to 3 times a day, that is in the range of approximately 0.0001 to 50mg/kg/day, more usually 0.0002 to 25 mg/kg/day.
  • the invention also provides a compound of formula (I) or a pharmaceutically acceptable salt thereof for use as an active therapeutic substance, in particular for use in the treatment of pain, emesis, CNS disorders and/or gastrointestinal disorders.
  • a compound of formula (I) or a pharmaceutically acceptable salt thereof for use as an active therapeutic substance, in particular for use in the treatment of pain, emesis, CNS disorders and/or gastrointestinal disorders.
  • the following Examples illustrate the preparation of compounds of formula (I), and the following descriptions illustrate the preparation of intermediates.
  • dichloromethane 150 ml was cooled in an ice bath.
  • Phosgene 9.5 ml of a 12.5% solution in toluene
  • Triethylamine 3.2 ml was then added and the reaction mixture was stirred at room temperature for another 10 minutes.
  • dichloromethane The dichloromethane extract was washed with water, dried (MgSO 4 ) and concentrated in vacuo to give a cream solid.
  • 5-HT 3 RECEPTOR ANTAGONIST ACTIVITY Compounds are evaluated for antagonism of the von Bezold-Jarisch reflex evoked by 5-HT in the anaesthetised rat according to the following method:
  • the ED 50 values were: E1 - 10, E2 - 15, E3 - 6.6

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

Abstract

Composés de la formule (I) et leurs sels pharmaceutiquement acceptables, formule dans laquelle A1, A2, A3 et les atomes de carbone auxquels ils sont fixés forment un cycle hétérocyclique non-aromatique à 5 ou 6 élements, contenant au moins -O- et/ou -CO- et/ou -N-; R1 et R2 représentent hydrogène ou alkyle C1-6; Y représente hydrogène, halo, alkyle C1-6 ou alcoxy C1-6; L représente O ou NH; et Z représente une chaîne latérale azabicyclique. Ces composés présentent une activité antagoniste par rapport au récepteur de 5-HT3.
PCT/GB1992/001876 1991-10-15 1992-10-13 N-aryle-n1-azabicyclo-urees utilisees comme antagonistes de 5-ht3 WO1993008185A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB919121835A GB9121835D0 (en) 1991-10-15 1991-10-15 Pharmaceuticals
GB9121835.4 1991-10-15

Publications (1)

Publication Number Publication Date
WO1993008185A1 true WO1993008185A1 (fr) 1993-04-29

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AU (1) AU2759892A (fr)
GB (1) GB9121835D0 (fr)
WO (1) WO1993008185A1 (fr)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997034892A1 (fr) * 1996-03-20 1997-09-25 Wake Forest University Recepteurs sigma-2 utilises en tant que biomarqueurs de la proliferation des cellules tumorales
WO2003057688A2 (fr) * 2002-01-07 2003-07-17 Pfizer Japan Inc. Composes oxo ou oxy-pyridine utilises comme modulateurs du recepteur 5-ht4
US6669925B1 (en) 2000-04-27 2003-12-30 Wake Forest University Sigma-2 receptors as biomarkers of tumor cell proliferation
US7396833B2 (en) 2003-12-22 2008-07-08 Memory Pharmaceuticals Corporation Indoles, 1H-indazoles, 1,2-benzisoxazoles, and 1,2-benzisothiazoles, and preparation and uses thereof
US7429664B2 (en) 2002-09-25 2008-09-30 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, and benzoisothiazoles, and preparation and uses thereof
US7488737B2 (en) 2004-04-22 2009-02-10 Memory Pharmaceutical Corporation Indoles, 1H-indazoles, 1,2-benzisoxazoles, 1,2-benzoisothiazoles, and preparation and uses thereof
US7595329B2 (en) 2004-06-15 2009-09-29 Pfizer Inc Benzimidazolone carboxylic acid derivatives
US7625924B2 (en) 2004-12-22 2009-12-01 Memory Pharmaceuticals Corporation Nicotinic alpha-7 receptor ligands and preparation and uses thereof
US7632831B2 (en) 2004-05-07 2009-12-15 Memory Pharmaceuticals Corporation 1H-indazoles, benzothiazoles, 1,2-benzoisoxazoles, 1,2-benzoisothiazoles, and chromones and preparation and uses thereof
US7737163B2 (en) 2004-06-15 2010-06-15 Pfizer Inc. Benzimidazolone carboxylic acid derivatives
US8106066B2 (en) 2005-09-23 2012-01-31 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof
US8263619B2 (en) 2004-03-25 2012-09-11 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and uses thereof
EP2728017A1 (fr) 2007-11-19 2014-05-07 Celera Corporation Marqueurs du cancer du poumon et utilisations de ceux-ci
US8829028B2 (en) 2002-05-16 2014-09-09 Serodus As 5-HT4 receptor antagonists for the treatment of heart failure

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PH30413A (en) * 1992-03-26 1997-05-09 Boehringer Ingelheim Italia Crystalline forms of endo-2,3-dihydro-n-(8-methyl)-8-azabicyclo-(3,2,1)oct-3-yl)-2-oxo-1h-benzimidazole-1-carboxamides

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0235878A2 (fr) * 1986-01-16 1987-09-09 Beecham Group Plc Nouveaux composés
EP0307172A2 (fr) * 1987-09-08 1989-03-15 Eli Lilly And Company 5-HT3-antagonistes spécifiques
EP0323077A1 (fr) * 1987-12-24 1989-07-05 JOHN WYETH &amp; BROTHER LIMITED Composes hétérocycliques
US4935511A (en) * 1989-09-26 1990-06-19 Rorer Pharmaceutical Corporation Benzoxazine and benzoxazepine carboxamide 5-HT3 antagonists
EP0407137A2 (fr) * 1989-07-03 1991-01-09 Yoshitomi Pharmaceutical Industries, Ltd. Dérivés de benzazine et leurs applications pharmaceutiques
EP0419397A1 (fr) * 1989-09-08 1991-03-27 Novo Nordisk A/S Dérivés de l'urée, leur préparation et leur utilisation

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0235878A2 (fr) * 1986-01-16 1987-09-09 Beecham Group Plc Nouveaux composés
EP0307172A2 (fr) * 1987-09-08 1989-03-15 Eli Lilly And Company 5-HT3-antagonistes spécifiques
EP0323077A1 (fr) * 1987-12-24 1989-07-05 JOHN WYETH &amp; BROTHER LIMITED Composes hétérocycliques
EP0407137A2 (fr) * 1989-07-03 1991-01-09 Yoshitomi Pharmaceutical Industries, Ltd. Dérivés de benzazine et leurs applications pharmaceutiques
EP0419397A1 (fr) * 1989-09-08 1991-03-27 Novo Nordisk A/S Dérivés de l'urée, leur préparation et leur utilisation
US4935511A (en) * 1989-09-26 1990-06-19 Rorer Pharmaceutical Corporation Benzoxazine and benzoxazepine carboxamide 5-HT3 antagonists

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6113877A (en) * 1996-03-20 2000-09-05 Wake Forest University σ-2 receptors as biomarkers of tumor cell proliferation
WO1997034892A1 (fr) * 1996-03-20 1997-09-25 Wake Forest University Recepteurs sigma-2 utilises en tant que biomarqueurs de la proliferation des cellules tumorales
US6669925B1 (en) 2000-04-27 2003-12-30 Wake Forest University Sigma-2 receptors as biomarkers of tumor cell proliferation
WO2003057688A2 (fr) * 2002-01-07 2003-07-17 Pfizer Japan Inc. Composes oxo ou oxy-pyridine utilises comme modulateurs du recepteur 5-ht4
EP1325921A3 (fr) * 2002-01-07 2003-10-22 Pfizer Inc. Oxo ou oxy-pyridines comme modulateurs des récepteurs 5-HT4
WO2003057688A3 (fr) * 2002-01-07 2003-11-13 Pfizer Pharma Composes oxo ou oxy-pyridine utilises comme modulateurs du recepteur 5-ht4
US6979690B2 (en) 2002-01-07 2005-12-27 Pfizer Inc. Oxo or oxy-pyridine compounds as 5-HT4 receptor modulators
US8829028B2 (en) 2002-05-16 2014-09-09 Serodus As 5-HT4 receptor antagonists for the treatment of heart failure
US7943773B2 (en) 2002-09-25 2011-05-17 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, and benzoisothiazoles, and preparation and uses thereof
US7429664B2 (en) 2002-09-25 2008-09-30 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, and benzoisothiazoles, and preparation and uses thereof
US8252811B2 (en) 2002-09-25 2012-08-28 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, and benzoisothiazoles, and preparation and uses thereof
US8134003B2 (en) 2002-09-25 2012-03-13 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, and benzoisothiazoles, and preparation and uses thereof
US8158629B2 (en) 2003-12-22 2012-04-17 Memory Pharmaceuticals Corporation Indoles, 1H-indazoles, 1,2-benzisoxazoles, and 1,2-benzisothiazoles, and preparation and uses thereof
US7396833B2 (en) 2003-12-22 2008-07-08 Memory Pharmaceuticals Corporation Indoles, 1H-indazoles, 1,2-benzisoxazoles, and 1,2-benzisothiazoles, and preparation and uses thereof
US7790722B2 (en) 2003-12-22 2010-09-07 Memory Pharmaceuticals Corporation Indoles, 1H-indazoles, 1,2-benzisoxazoles, and 1,2-benzisothiazoles, and preparation and uses thereof
US7964600B2 (en) 2003-12-22 2011-06-21 Memory Pharmaceuticals Corporation Indoles, 1H-indazoles, 1,2-benzisoxazoles, and 1,2-benzisothiazoles, and preparation and uses thereof
US8691841B2 (en) 2004-03-25 2014-04-08 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and use thereof
US8486937B2 (en) 2004-03-25 2013-07-16 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and use thereof
US8263619B2 (en) 2004-03-25 2012-09-11 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and uses thereof
US7488737B2 (en) 2004-04-22 2009-02-10 Memory Pharmaceutical Corporation Indoles, 1H-indazoles, 1,2-benzisoxazoles, 1,2-benzoisothiazoles, and preparation and uses thereof
US7902217B2 (en) 2004-04-22 2011-03-08 Memory Pharmaceuticals Corporation Indoles, 1H-indazoles, 1,2-benzisoxazoles, 1,2-benzoisothiazoles, and preparation and uses thereof
US7632831B2 (en) 2004-05-07 2009-12-15 Memory Pharmaceuticals Corporation 1H-indazoles, benzothiazoles, 1,2-benzoisoxazoles, 1,2-benzoisothiazoles, and chromones and preparation and uses thereof
US7595329B2 (en) 2004-06-15 2009-09-29 Pfizer Inc Benzimidazolone carboxylic acid derivatives
US7705020B2 (en) 2004-06-15 2010-04-27 Pfizer Inc. Benzimidazolone carboxylic acid derivatives
US7737163B2 (en) 2004-06-15 2010-06-15 Pfizer Inc. Benzimidazolone carboxylic acid derivatives
US7625924B2 (en) 2004-12-22 2009-12-01 Memory Pharmaceuticals Corporation Nicotinic alpha-7 receptor ligands and preparation and uses thereof
US8106066B2 (en) 2005-09-23 2012-01-31 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof
US8273891B2 (en) 2006-09-22 2012-09-25 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof
EP2728017A1 (fr) 2007-11-19 2014-05-07 Celera Corporation Marqueurs du cancer du poumon et utilisations de ceux-ci

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Publication number Publication date
GB9121835D0 (en) 1991-11-27
AU2759892A (en) 1993-05-21

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