WO2005021505A1 - The claimed invention relates to novel 4-piperidinecarboxamide and the use thereof for the preparation of medicaments against 5-ht2a receptor-related disorders - Google Patents
The claimed invention relates to novel 4-piperidinecarboxamide and the use thereof for the preparation of medicaments against 5-ht2a receptor-related disorders Download PDFInfo
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- WO2005021505A1 WO2005021505A1 PCT/SE2004/001236 SE2004001236W WO2005021505A1 WO 2005021505 A1 WO2005021505 A1 WO 2005021505A1 SE 2004001236 W SE2004001236 W SE 2004001236W WO 2005021505 A1 WO2005021505 A1 WO 2005021505A1
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
- C07D211/66—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4 having a hetero atom as the second substituent in position 4
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- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
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- A61P25/36—Opioid-abuse
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- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Definitions
- the claimed invention relates to novel 4-piperidinecarboxamide and the use thereof ⁇ for the preparation of medicaments against 5-HT2A receptor-related disorders.
- RELATED APPPLICATIONS This application claims priority to Swedish application number 0302369-4, filed on September 3, 2003, and U.S. provisional application 60/505,295, filed on September 23, 2003, the contents of which are incorporated herein by reference.
- the present invention relates to novel compounds, to pharmaceutical compositions comprising the compounds, to processes for their preparation, as well as to the use of the compounds for the preparation of a medicament against 5-HT2A receptor-related disorders.
- serotonin has been implicated in a number of disorders and conditions which originate in the central nervous system.
- the HT2A receptor has been implicated as a therapeutic target for the treatment or prevention of abnormalities of the serotonergic system, including psychotic disorders such as schizophrenia (A. Carlsson, N. Waters and M. L. Carlsson, Biol. Psychiatry, 46, 1388 (1999); G.J. Marek and G. K. Aghajanian, Biol. Psychiatry, 44, 1118 (1998); E. Sibelle, Z.
- 5-HT2A antagonists may also be useful in the treatment of sleep disorders such as insomnia and obstructive sleep apnea, anorexia nervosa (Zlegler A, Gorg T, Lancet (1999) 353, 929), cardiovascular conditions such as hypertension, vasospasm, angina, Raynaud's phenomenon and thrombotic illness including stroke, glaucoma (T. Mano et al. and H. Takaneka et al., Investigative Ophthalmology and Visual Science, 1995, vol. 36, pages 719 and 734, respectively) and in the inhibition of platelet aggregation.
- sleep disorders such as insomnia and obstructive sleep apnea, anorexia nervosa (Zlegler A, Gorg T, Lancet (1999) 353, 929)
- cardiovascular conditions such as hypertension, vasospasm, angina, Raynaud's phenomenon and thrombotic illness including stroke, glaucoma (T. Man
- One object of the present invention is a compound of the Formula (I)
- R is either - aryl optionally independently substituted with one or more of C 1-6 -alkyl, C ⁇ -6 - alkoxy, halogen, and halo-C ⁇ -6 -alkyl; or - aryl-C 1-6 -alkyl optionally independently substituted with one or more of C ⁇ -6 - alkoxy; or - C 3-8 -cycloalkyl;
- R' is either - aryl optionally independently substituted with one or more of halogen, C ⁇ -6 -alkoxy, halo-C ⁇ - 6 -alkyl, and cyano; or - aryloxy optionally independently substituted with one or more of halogen and C ⁇ -6 - alkoxy; or - heteroaryl optionally independently substituted with one aryl and/or one or more of halogen, C 1-6 -alkyl, and C ⁇ -6 -alkoxy, which aryl is optionally independently substituted with one or more
- R is selected from - phenyl independently substituted with one or more of methyl, methoxy, ethoxy, fluoro, and trifluoromethyl; - benzyl independently substituted with one or more of methoxy; and cyclohexyl.
- R is selected from 2-ethoxyphenyl, 2,4-difluorophenyl, 3- (trifluoromethyl)phenyl, 3,4,5-trimethoxybenzyl, and cyclohexyl.
- R' is selected from - phenyl independently substituted with one or more of fluoro; - phenoxy independently substituted with one or more of methoxy; and - indolyl independently substituted with one phenyl and/or one or more of fluoro, chloro, methyl, and methoxy, which phenyl is optionally independently substituted with one or more of fluoro, chloro, methyl, and methoxy.
- R' is selected from 4- fluorophenyl, 2,6-dimethoxyphenoxy, and 2-phenyl-3-indolyl.
- Another object of the present invention is a process for the preparation of a compound as mentioned above, which process comprises the step of a) reacting an amine RNH 2 wherein R is either - aryl optionally independently substituted with one or more of C ⁇ -6 -alkyl, C ⁇ -6 - al oxy, halogen, and halo-C ⁇ -6 -alkyl; or - aryl-C ⁇ -6 -alkyl optionally independently substituted with one or more of C ⁇ -6 - alkoxy; or - C 3 . 8 -cycloalkyl; with a cyanate, to give a compound of formula R-NH-CO-NH 2 , wherein R is as defined above,
- Another object of the present invention is a compound as mentioned above for use in therapy, especially for use in the prophylaxis or treatment of a 5-HT2A receptor-related disorder.
- Another object of the present invention is a pharmaceutical formulation comprising a compound as mentioned above as active ingredient, in combination with a pharmaceutically acceptable diluent or carrier, especially for use in the prophylaxis or treatment of a 5-HT2A receptor-related disorder.
- Another object of the present invention is a method for treating a human or animal subject suffering from a 5-HT2A receptor-related disorder.
- the method can include administering to a subject (e.g., a human or an animal, dog, cat, horse, cow) in need thereof an effective amount of one or more compounds of any of the formulae herein, their salts, or compositions containing the compounds or salts.
- a subject e.g., a human or an animal, dog, cat, horse, cow
- the methods delineated herein can also include the step of identifying that the subject is in need of treatment of the 5-HT2A receptor-related disorder. Identifying a subject in need of such treatment can be in the judgment of a subject or a health care professional and can be subjective (e.g., opinion) or objective (e.g., measurable by a test or diagnostic method).
- Another object of the present invention is a method for the prophylaxis of a 5- HT2A receptor-related disorder, which comprises administering to a subject in need of such treatment an effective amount of a compound as mentioned above.
- Another object of the present invention is a method for modulating (i e promoting or inhibiting) 5-HT2A receptor activity, which comprises administering to a subject in need of such treatment an effective amount of a compound as mentioned above.
- Another object of the present invention is the use of a compound as mentioned above for the manufacture of a medicament for use in the prophylaxis or treatment of a 5- HT2A receptor-related disorder.
- the compounds as mentioned above may be agonists, partial agonists or antagonists for the 5-HT2A receptor.
- 5-HT2A receptor-related disorders are schizophrenia, mental depression, migraine, epilepsy, obsessive-compulsive disorder, sleep disorders such as insomnia and obstructive sleep apnea, anorexia nervosa, cardiovascular conditions such as hypertension, vasospasm, angina, Raynaud's phenomenon and thrombotic illness including stroke, glaucoma, alcohol and cocaine dependence.
- the compounds and compositions are useful for treating diseases, including schizophrenia, mental depression, migraine, epilepsy, obsessive-compulsive disorder, sleep disorders such as insomnia and obstructive sleep apnea, anorexia nervosa, cardiovascular conditions such as hypertension, vasospasm, angina, Raynaud's phenomenon and thrombotic illness including stroke, glaucoma, alcohol and cocaine dependence.
- diseases including schizophrenia, mental depression, migraine, epilepsy, obsessive-compulsive disorder, sleep disorders such as insomnia and obstructive sleep apnea, anorexia nervosa, cardiovascular conditions such as hypertension, vasospasm, angina, Raynaud's phenomenon and thrombotic illness including stroke, glaucoma, alcohol and cocaine dependence.
- the invention relates to a method for treating or preventing an aforementioned disease comprising administrating to a subject in need of such treatment an effective amount of a compound or composition delineated here
- C ⁇ -6 -alkyl denotes a straight or branched alkyl group having from 1 to 6 carbon atoms.
- examples of said lower alkyl include methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl and straight- and branched-chain pentyl and hexyl.
- C 1-6 -alkyl For parts of the range "C 1-6 -alkyl" all subgroups thereof are contemplated such as C ⁇ -5 -alkyl, C ⁇ - -alkyl, C ⁇ -3 -alkyl, C 1-2 -alkyl, C 2- 6 -alkyl, C 2-5 -alkyl, C 2-4 -alkyl, C 2-3 -alkyl, C 3-6 -alkyl, C 4-5 -alkyl, etc.
- "Halo-C 1-6 -alkyl” means a C ⁇ -6 -alkyl group substituted with one or more halogen atoms.
- aryl-C 1-6 - alkyl means a Ci-e-alkyl group substituted with one or more aryl groups.
- C 3-8 -cycloalkyl denotes a cyclic alkyl group having a ring size from 3 to 8 carbon atoms. Examples of said cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclohexyl, cycloheptyl, and cyclooctyl.
- C 3-8 -cycloalkyl For parts of the range "C 3-8 -cycloalkyl" all subgroups thereof are contemplated such as C 3-7 -cycloalkyl, C 3-6 -cycloalkyl, C 3-5 -cycloalkyl, C 3-4 -cycloalkyl, C - 8 -cycloalkyl, C -7 -cycloalkyl, C 4-6 -cyclo alkyl, C -5 -cycloalkyl, C 5-7 -cyclo alkyl, C 6-7 - cycloalkyl, etc.
- C ⁇ -6 alkoxy denotes a straight or branched alkoxy group having from 1 to 6 carbon atoms.
- Examples of said lower alkoxy include methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy, t- butoxy and straight- and branched-chain pentoxy and hexoxy.
- C ⁇ -6 - alkoxy all subgroups thereof are contemplated such as C 1-5 -alkoxy, C ⁇ - -alkoxy, C 1- - alkoxy, C ⁇ -2 -alkoxy, C 2-6 -alkoxy, C 2 - 5 -alkoxy, C 2- -alkoxy, C 2-3 -alkoxy, C 3-6 -alkoxy, C -5 - alkoxy, etc.
- halogen shall mean fluorine, chlorine, bromine or iodine.
- aryl refers to a hydrocarbon ring system having at least one aromatic ring. Examples of aryls are phenyl, pentalenyl, indenyl, indanyl, isoindolinyl, cl romanyl, naphthyl, fluorenyl, anthryl, phenanthryl and pyrenyl. The aryl rings may optionally be substituted with C 1-6 -alkyl. Examples of substituted ' aryl groups are 2-methylphenyl and 3-methylphenyl.
- aryloxy refers to an aryl group bonded to an oxygen atom.
- heteroaryl refers to a hydrocarbon ring system having at least one aromatic ring having one or more ring atoms are a heteroatom such as O, N, or S, and the remaining ring atoms are carbon.
- heteroaryl groups include furyl, pyrrolyl, thienyl, oxazolyl, isoxazolyl, imidazolyl, thiazolyl, isothiazolyl, pyridinyl, pyrimidinyl, quinazolinyl, indolyl, pyrazolyl, pyridazinyl, quinolinyl, benzofuranyl, • dihydrobenzofuranyl, benzodioxolyl, benzodioxinyl, benzothiazolyl, benzothiadiazoiyl, and benzotriazolyl groups.
- leaving group refers to a group to be displaced from a molecule during a nucleophilic displacement reaction.
- leaving groups are iodide, bromide, chloride, methanesulfonate, hydroxy, methoxy, thiomethoxy, tosyl, or suitable protonated forms thereof (e.g., H 2 O, MeOH), especially bromide and methanesulfonate.
- alkylating agent refers to a compound containing one or more alkyl groups which can be added to another compound.
- alkylating agents include, but are not limited to, iodomethane, iodoethane, 1-iodopropane, 2-iodopropane, straight- and branched-iodobutane, iodopentane, iodohexane, bromomethane, bomoethane, 1- bromopropane, 2-bromopropane, straight- and branched- bromobutane, bromopentane, bromohexane, allyl bromide, ethyl methanesulfonate, methyl methanesulfonate, and propyl methanesulfonate .
- “Pharmaceutically acceptable” means being useful in preparing a pharmaceutical composition that is generally safe, non-toxic and neither biologically nor otherwise undesirable and includes being useful for veterinary use as well as human pharmaceutical use.
- “Treatment” as used herein includes prophylaxis of the named disorder or condition, or amelioration or elimination of the disorder once it has been established.
- “An effective amount” refers to an amount of a compound that confers a therapeutic effect on the treated subject. The therapeutic effect may be objective (i.e., measurable by some test or marker) or subjective (i.e., subject gives an indication of or feels an effect).
- prodrug forms means a pharmacologically acceptable derivative, such as an ester or an amide, which derivative is biotransformed in the body to form the active drug.
- pharmacologically acceptable derivative such as an ester or an amide
- ACN means acetonitrile
- CHO means Chinese hamster ovary
- DEA diethylamine
- DEPT means distortion enhancement polarisation transfer
- DMSO dimethyl sulf oxide
- ELS electron light scattering
- HPLC high performance liquid chromatography
- Rt means retention time
- TFA trifluoro acetic acid
- THF means tetrahydrofuran
- TLC thin layer chromatography.
- Compounds that have basic properties can be converted to their pharmaceutically acceptable acid addition salts by treating the base form with an appropriate acid.
- exemplary acids include inorganic acids, such as hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, phosphoric acid; and organic acids such as formic acid, acetic acid, propanoic acid, hydroxyacetic acid, lactic acid, pyruvic acid, glycolic acid, maleic acid, malonic acid, oxalic acid, benzenesulfonic acid, toluenesulfonic acid, methanesulfonic acid, trifluoroacetic acid, fumaric acid, succinic acid, malic acid, tartaric acid, citric acid, salicylic acid, p-aminosalicylic acid, pa oic acid, benzoic acid, ascorbic acid and the like.
- Exemplary base addition salt forms are the sodium, potassium, calcium salts, and salts with pharmaceutically acceptable amines such as, for example, ammonia, alkylamines, benzathine, and amino acids, such as, e.g. arginine and lysine.
- the term addition salt as used herein also comprises solvates which the compounds and salts thereof are able to form, such as, for example, hydrates, alcoholates and the like.
- the compounds of the invention are formulated into pharmaceutical formulations for oral, rectal, parenteral or other mode of administration. Pharmaceutical formulations are usually prepared by mixing the active substance, or a pharmaceutically acceptable salt thereof, with conventional pharmaceutical excipients.
- excipients examples include water, gelatin, gum arabicum, lactose, microcrystalline cellulose, starch, sodium starch glycolate, calcium hydrogen phosphate, magnesium stearate, talcum, colloidal silicon dioxide, and the like.
- Such formulations may also contain other pharmacologically active agents, and conventional additives, such as stabilizers, wetting agents, emulsifiers, flavouring agents, buffers, and the like.
- the formulations can be further prepared by known methods such as granulation, compression, microencapsulation, spray coating, etc.
- the formulations may be prepared by conventional methods in the dosage form of tablets, capsules, granules, powders, syrups, suspensions, suppositories or injections.
- Liquid formulations may be prepared by dissolving or suspending the active substance in water or other suitable vehicles. Tablets and granules may be coated in a conventional manner.
- the invention relates to methods of making compounds of any of the formulae herein comprising reacting any one or more of the compounds of the formulae delineated herein, including any processes delineated herein.
- the compounds of the formula (I) above may be prepared by, or in analogy with, conventional methods. The processes described above maybe carried out to give a compound of the invention in the form of a free base or as an acid addition salt.
- a pharmaceutically acceptable acid addition salt may be obtained by dissolving the free base in a suitable organic solvent and treating the solution with an acid, in accordance with conventional procedures for preparing acid addition salts from base compounds.
- addition salt forming acids are mentioned above.
- the compounds of formula (I) may possess one or more chiral carbon atoms, and they may therefore be obtained in the form of optical isomers, e.g. as a pure enantiomer, or as a mixture of enantiomers (racemate) or as a mixture containing diastereomers.
- the separation of mixtures of optical isomers to obtain pure enantiomers is well known in the art and may, for example, be achieved by fractional crystallization of salts with optically active (chiral) acids or by chromato graphic separation on chiral columns.
- the chemicals used in the synthetic routes delineated herein may include, for example, solvents, reagents, catalysts, and protecting group and deprotecting group reagents.
- the methods described above may also additionally include steps, either before or after the steps described specifically herein, to add or remove suitable protecting groups in order to ultimately allow synthesis of the compounds.
- various synthetic steps may be performed in an alternate sequence or order to give the desired compounds. Synthetic chemistry transformations and protecting group methodologies (protection and deprotection) useful in synthesizing applicable compounds are known in the art and include, for example, those described in R. Larock, Comprehensive Organic
- the dose level and frequency of dosage of the specific compound will vary depending on a variety of factors including the potency of the specific compound employed, the metabolic stability and length of action of that compound, the patient's age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the condition to be treated, and the patient undergoing therapy.
- the daily dosage may, for example, range from about 0.001 mg to about 100 mg per kilo of body weight, administered singly or multiply in doses, e.g. from about 0.01 mg to about 2j' mg each. Normally, such a dosage is given orally but parenteral administration may also be chosen.
- HPLC analyses were performed using a Waters Xterra MS C18 column (100 x 4.6 mm, 5 ⁇ ) eluting with a gradient of 5% ACN in 95% water to 95% ACN in 5% water (0.2% TFA buffer) over 3.5 mins, then 95% ACN in 5% water (0.2% TFA buffer) for a further 2.5 mins at a flow rate of 3 ml/min on a Waters 600E or Gilson system with monitoring at 254 nm.
- Reverse phase preparative HPLC was carried out using a Xterra MS C18 column (100 x 19 mm, 5 ⁇ m) eluting with a gradient of 5% ACN in 95% water to 95% ACN in 5% water (0.05% DEA) over 12.0 mins, then 95% ACN in 5% water (0.05% DEA) for a further 5.0 mins at a flow rate of 25 ml/min with monitoring at 254 nm.
- the fractions that contained the desired product were concentrated under reduced pressure and the resultant residue was lyophilised from a mixture of dioxane and water.
- Electrospray MS spectra were obtained on a Micromass platform LCMS spectrometer. Compounds were named using AutoNom 2000.
- Methane sulfonyl chloride (0.247mL, 3.18mmol) was added dropwise at 0°C to a solution of 2-(2-phenyl-lH-indol-3-yl)-ethanol (606mg, 2.55mmol) and triethylamine (0.56mL, 4mmol) in dry dichloromethane (5mL). After 40min the solution was poured into IN HC1, the organic layer was separated, washed with water, brine, dried over magnesium sulfate and concentrated under vacuum to afford a red oil (0.8g, 100%).
- Step 4 l-[2-(2-phenyl-lH-indol-3-yI)ethyI]-N- ⁇ [(3,4,5-trimethoxybenzyl)amino]- carbonyI ⁇ piperidine-4-carboxamide
- the organic layer was dried (MgSO 4 ) and the solvent concentrated to about 0.5mL. White crystals formed. The crystals were filtered and washed with a small amount of ethyl acetate. The product was obtained as white crystals (0.1157g, 29%).
- the active ingredient 1 is mixed with ingredients 2, 3, 4 and 5 for about 10 minutes.
- the magnesium stearate is then added, and the resultant mixture is mixed for about 5 minutes and compressed into tablet form with or without film-coating.
- the calculation of the K; values for the inhibitors was performed by use of Activity Base.
- the compounds of Formula (I) exhibit IC50 values for the 5-HT2A receptor in the range from l nM to 10 ⁇ M.
- 5-HT2A antagonist lead compounds were identified in FLJPR-based functional screening of the 5-HT2A receptor. One of these compounds were tested in equilibrium displacement binding measurements.
- Example 2 is a high affinity ligand for the 5-HT2A receptor subtype, with a Ki value in the nanomolar range.
- the compound is highly selective over five other serotonin receptors assayed (5-HT2C, 5- HT2B, 5-HTj A' 5-HT ⁇ and 5-HTi ⁇ ).
- Example 2 is shown also to be selective at 5-HT2A versus the 5-HT2C receptor in terms of efficacy.
- the table shows the selectivity of Example 2 for the 5-HT2A ove r other serotonin- binding receptors.
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Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2004268919A AU2004268919A1 (en) | 2003-09-03 | 2004-08-27 | Novel 4-piperidinecarboxamide and the use thereof for the preparation of medicaments against 5-HT2A receptor-related disorders |
CA002537349A CA2537349A1 (en) | 2003-09-03 | 2004-08-27 | The claimed invention relates to novel 4-piperidinecarboxamide and the use thereof for the preparation of medicaments against 5-ht2a receptor-related disorders |
JP2006525301A JP2007504221A (en) | 2003-09-03 | 2004-08-27 | Novel 4-piperidinecarboxamide and its use for the manufacture of a medicament against 5HT2A receptor related disorders |
EP04775342A EP1663972A1 (en) | 2003-09-03 | 2004-08-27 | The claimed invention relates to novel 4-piperidinecarboxamide and the use thereof for the preparation of medicaments against 5-ht2a receptor-related disorders |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE0302369-4 | 2003-09-03 | ||
SE0302369A SE0302369D0 (en) | 2003-09-03 | 2003-09-03 | New compounds |
US50529503P | 2003-09-23 | 2003-09-23 | |
US60/505,295 | 2003-09-23 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2005021505A1 true WO2005021505A1 (en) | 2005-03-10 |
Family
ID=34277853
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/SE2004/001236 WO2005021505A1 (en) | 2003-09-03 | 2004-08-27 | The claimed invention relates to novel 4-piperidinecarboxamide and the use thereof for the preparation of medicaments against 5-ht2a receptor-related disorders |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP1663972A1 (en) |
JP (1) | JP2007504221A (en) |
AU (1) | AU2004268919A1 (en) |
CA (1) | CA2537349A1 (en) |
WO (1) | WO2005021505A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7973069B2 (en) | 2004-07-14 | 2011-07-05 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
US8013006B2 (en) | 2004-07-14 | 2011-09-06 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB932487A (en) * | 1960-07-25 | 1963-07-31 | D G Searle & Co | Piperidine derivatives |
US5269096A (en) * | 1993-01-15 | 1993-12-14 | Rene Hade | Removable lightweight window guard |
US5763458A (en) * | 1993-05-26 | 1998-06-09 | Syntex (U.S.A.) Inc. | 1-phenylalkanone 5-HT4 receptor ligands |
WO2001029008A1 (en) * | 1999-10-15 | 2001-04-26 | Arena Pharmaceuticals, Inc. | Pyrazole derivatives which modulate human serotonin receptors |
-
2004
- 2004-08-27 WO PCT/SE2004/001236 patent/WO2005021505A1/en active Application Filing
- 2004-08-27 CA CA002537349A patent/CA2537349A1/en not_active Abandoned
- 2004-08-27 JP JP2006525301A patent/JP2007504221A/en active Pending
- 2004-08-27 EP EP04775342A patent/EP1663972A1/en not_active Withdrawn
- 2004-08-27 AU AU2004268919A patent/AU2004268919A1/en not_active Abandoned
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB932487A (en) * | 1960-07-25 | 1963-07-31 | D G Searle & Co | Piperidine derivatives |
US5269096A (en) * | 1993-01-15 | 1993-12-14 | Rene Hade | Removable lightweight window guard |
US5763458A (en) * | 1993-05-26 | 1998-06-09 | Syntex (U.S.A.) Inc. | 1-phenylalkanone 5-HT4 receptor ligands |
WO2001029008A1 (en) * | 1999-10-15 | 2001-04-26 | Arena Pharmaceuticals, Inc. | Pyrazole derivatives which modulate human serotonin receptors |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7973069B2 (en) | 2004-07-14 | 2011-07-05 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
US8013006B2 (en) | 2004-07-14 | 2011-09-06 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
Also Published As
Publication number | Publication date |
---|---|
JP2007504221A (en) | 2007-03-01 |
AU2004268919A1 (en) | 2005-03-10 |
EP1663972A1 (en) | 2006-06-07 |
CA2537349A1 (en) | 2005-03-10 |
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