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WO2001057039A1 - Derives de la pyrrolo-isoquinoline et de la tetrahydropyrrolo-isoquinoline et leur utilisation comme mediateurs du recepteur 5-ht7 - Google Patents

Derives de la pyrrolo-isoquinoline et de la tetrahydropyrrolo-isoquinoline et leur utilisation comme mediateurs du recepteur 5-ht7 Download PDF

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Publication number
WO2001057039A1
WO2001057039A1 PCT/US2001/003430 US0103430W WO0157039A1 WO 2001057039 A1 WO2001057039 A1 WO 2001057039A1 US 0103430 W US0103430 W US 0103430W WO 0157039 A1 WO0157039 A1 WO 0157039A1
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carbon atoms
alkyl
hydrogen
compound
members
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PCT/US2001/003430
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English (en)
Inventor
Michael Gerard Kelly
Young Hee Kang
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Wyeth LLC
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Wyeth LLC
American Home Products Corp
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Filing date
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Priority to EP01903486A priority Critical patent/EP1252161A1/fr
Priority to AU2001231287A priority patent/AU2001231287A1/en
Priority to MXPA02007521A priority patent/MXPA02007521A/es
Priority to CA002399545A priority patent/CA2399545A1/fr
Priority to JP2001557871A priority patent/JP2003522178A/ja
Priority to BR0108007-5A priority patent/BR0108007A/pt
Publication of WO2001057039A1 publication Critical patent/WO2001057039A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • 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
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/32—Alcohol-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/36—Opioid-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • 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

Definitions

  • 5-hydroxytryptamine-7 The recently identified human 5-hydroxytryptamine-7 (5-HT7) receptor subtype has been cloned, and the extensive distribution of its mRNA has been reported. Highest levels of 5-HT7 receptor mRNA have been observed in the hypothalamus, thalamus. brainstem and hippocampus, while lower levels have been found in the cerebral cortex, striatum, olfactory bulb and olfactory tubercle. The presence of 5-HT7 mRNA is not limited to the brain, it has also been found in peripheral tissues, namely spleen, stomach, ileum, intestine, coronary artery, descending colon, smooth muscle cells and heart.
  • 5-HT7 receptor may be involved in the vasodilation of blood vessels, and therefore may play a role in cardiovascular indications.
  • 5-HT7 receptors also play a role in the control of circadian rhythms of spontaneous electrical activity in the suprachiasmatic nucleus.
  • the high affinity of a number of antipsychotic agents for the 5-HT7 receptor suggests that this receptor may help mediate the therapeutic actions of these compounds.
  • Octahydro-pyrrolo-isoquinoline derivatives as antipsychotic neuroleptic agents are disclosed in EP 10661 having the formula:
  • R2 is hydrogen, alkyl, cycloalkyl, alkenyl, acyl, aryl or aralkyl.
  • Ancilated indole derivatives as antiphlogistics are disclosed in DE 77- 2740836 having the formula:
  • R is phenyl or heterocycle
  • R 1 , R 2 are alkyl, carboxyalkyl, phenyl, and
  • R 3 , R 4 is a 5 or 6 membered ring optionally containing 1-3, 5, O or N atoms.
  • a series of novel 3-(2-aminoethyl)-pyrrolo[2,3-g]isoquinolin-5-one derivatives are claimed that are effective pharmaceuticals for the treatment of anxiety, depression and related CNS disorders and other conditions such as schizophrenia, sleep disorders, including instances of circadian rhythm, the treatment of alcohol and drug withdrawal and sexual dysfunction.
  • This invention relates to novel 3-(2-aminoethyl)-pyrrolo[2,3-g]isoquinolin-5- one derivatives, to processes for their preparation, to pharmaceutical compositions containing them and to their use in therapy.
  • the compounds are believed to be useful for the treatment of CNS disorders such as anxiety, depression and related CNS conditions and other conditions such as schizophrenia, sleep disorders, including instances of circadian rhythm, migraine headaches, the treatment of alcohol and drug withdrawal and sexual dysfunction by virtue of their ability to bind to the 5-HT7 receptor subtype.
  • the compounds of the present invention may also find utility in the treatment of cardiovascular and septic shock, hypotension, renal disorders, diarrhea and spastic colon.
  • Compounds of the present invention are represented by the general formula
  • Rl is hydrogen, alkyl of 1 to 8 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, heterocycloalkyl of 3 to 8 members, alkylcycloalkyl of 4 to 9 carbon atoms, alkylheterocycloalkyl of 4 to 9 members or (CH2)mAr or (CH2)mHet;
  • R2 is hydrogen, alkyl of 1 to 8 carbon atoms, (CH2)nAr or (CH2)nHet;
  • R3 is hydrogen, alkyl of 1 to 8 carbon atoms, alkylcycloalkyl of 4 to 9 carbon atoms, alkylheterocycloalkyl of 4 to 9 members, (CH2)nAr or (CH2)nHet;
  • R4 is hydrogen or alkyl of 1 to 8 carbon atoms;
  • R is hydrogen or alkyl of 1 to 4 carbon atoms;
  • Rl is hydrogen, alkyl of 1 to 8 carbon atoms, alkylcycloalkyl of 4 to 9 carbon atoms, alkylheterocycloalkyl of 4 to 9 members, (CH2)nAr or (CH2)nHet.
  • R2 is hydrogen or alkyl of 1 to 8 carbon atoms.
  • X is preferably (CH2)n, and the optional double bond is preferably absent.
  • R3 and R4 are preferably hydrogen or alkyl.
  • Alkyl refers to straight or branched chain alkyl.
  • Cycloalkyl refers to a saturated ring of 3 to 8 carbon atoms and preferably 5 to 6 carbon atoms such as cyclopentyl and cyclohexyl.
  • Heterocycloalkyl refers to a saturated ring of 3 to 8 carbon atoms having 1 or 2 heteroatoms selected from N, O and S.
  • heterocycloalkyl refers to 5 or 6 membered rings having at least one nitrogen heteroatom such as piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, morpholinyl, thiomorpholinyl, and pyrazolidinyl.
  • Ar is aryl and preferably is phenyl or naphthyl which may optionally be substituted by one or more groups selected from flourine, chlorine, bromine, iodine, hydroxy, alkyl of 1 to 6 carbon atoms, trifluoromethyl, cyano and amino.
  • Het refers to heteroaryl and refers to a monocyclic 5 or 6 membered heteroaryl group or a 9 or 10 membered bicyclic heteroaryl group.
  • Preferred heteroaryls have 1 or 2 heteroatoms selected from N, O and S, and, when 2 heteroatoms are present, it is preferred that at least one heteroatom is nitrogen.
  • Exemplary monocyclic heteroaryl groups include pyridinyl, pyriminidinyl, pyrazinyl, furyl, thienyl, pyrrolyl, indolyl.
  • Exemplary bicyclic heteraryl groups include benzodioxanyl or quinolyl.
  • Heteroaryl groups may optionally be substituted with one or more groups selected from flourine, chlorine, bromine, iodine, hydroxy, alkyl of 1 to 6 carbon atoms, trifluoromethyl, cyano and amino.
  • the pharmaceutically acceptable salts are the acid addition salts which can be formed from a compound of the above general formula and a pharmaceutically acceptable acid such as phosphoric, sulfuric, hydrochloric, hydrobromic. citric, maleic, fumaric, acetic, lactic or methanesulfonic acid.
  • the compounds of this invention contain a chiral center, providing for various steroisomeric forms such as racemic mixtures as well as optical isomers.
  • the individual optical isomers can be prepared directly or by asymmetric or sterospecific synthesis or by conventional separation of optical isomers from the racemic mixture.
  • 2-(3-chloropropyl)- 1 ,3- dioxolan is an example of suitably substituted and protected aldehyde derivative, and dilute sulfuric acid or dilute hydrochloric acid are suitable catalysts or co-solvents for the reaction.
  • the basic amine may be alkylated directly for example by the reaction of an alkyl halide or alkylaryl halide under the influence of a base such as sodium hydride, or alternatively the basic amine may be directly acylated by the action of carboxylic acid halides, and the subsequent amide can be reduced by the action of lithium aluminum hydride. These step may be repeated to provide bis-alkylated derivatives.
  • the pyrrol nitrogen may be alkylated with alkyl halides or alkylaryl halides or alkylheteroaryl halides under the influence of a base such as sodium hydride.
  • the optional double bond can be introduced by known and conventional methods.
  • Compounds of the present invention bind with very high affinity to the 5-HT7 receptor and consequently, they are useful for mediating the 5-HT7 receptor in mammals.
  • Compounds of the present invention are useful in the treatment of central nervous system disorders associated with dysfunction of the 5-HT7 receptor such as anxiety, depression and related conditions (e.g. GAD) and other conditions such as schizophrenia, sleep disorders, including instances of circadian rhythm, migraine headaches, the treatment of alcohol and drug withdrawal and sexual dysfunction by virtue of their ability to bind to the 5-HT7 receptor subtype.
  • the compounds of the present invention may also find utility in the treatment of cardiovascular and septic shock, hypotension, renal disorders, diarrhea and spastic colon.
  • High affinity for the serotonin 5HT7 receptor was established by testing the claimed compound's ability to displace [ 3 H] LSD binding in CHO cells stably transfected with the human 5HT7 receptor.
  • Human cloned receptor membranes of the serotonin-7 subtype, expressed in a Chinese Hamster Ovary (CHO) cell line are purchased from BioSignal Drug Discovery Technology, Montreal, Canada.
  • the frozen ampoules of receptor membranes are reconstituted in 50.0 mM Tris.HCl buffer, at pH 7.4 to give 15-20 ⁇ g of tissue protein per 100.0 ⁇ l of suspension.
  • the diluted membranes are kept cold on ice and immediately used in subsequent binding experiments.
  • Binding experiments are performed in a 96 well microtiter plate format, in a total volume of 200 ⁇ l. To each well is added: 80.0 ⁇ l of incubation buffer made in 50 mM Tris.HCl buffer, pH 7.4 and containing 10.0 mM MgC12 and 0.5 mM EDTA; 20 ⁇ l of [ ⁇ ] LSD (S.A., 86.0 CiJ mmol, Amersham Life Science), 5.0 - 6.0 nM.
  • the dissociation constant, K D of [ 3 H]LSD at the human serotonin 5-HT7 receptor is 2.9 nM, as determined in saturation studies with increasing concentrations of [ 3 H]LSD.
  • the reaction is initiated by the final addition of 100.0 ⁇ l of tissue suspension.
  • Nonspecific binding is measured in the presence of 10.0 ⁇ M methiothepin, added in 20.0 ⁇ l volume. Test compounds when needed are added in 20.0 ⁇ l volume.
  • the reaction proceeds in the dark for 120 minutes at room temperature, at which time, the bound ligand receptor complex is filtered off on a 96 well unifilter with a Packard ® Filter- mate 196 Harvester. The filtermate is air dried and the radioactivity is measured in a Packard TopCount ® equipped with six photomultiplier detectors, after drying and addition of 40.0 ⁇ l Microscint ® -20 scintillant to each shallow well. The unifilter plate is heat sealed and counted in a Packard TopCount ® with a tritium efficiency of 31.0%.
  • Specific binding is defined as the total radioactivity bound less the amount bound in the presence of 10.0 ⁇ M unlabeled methiothepin. Binding in the presence of varying concentrations of test drugs is expressed as percent of specific binding in the absence of drug. These results are then plotted as log % bound vs log concentration of test drug.
  • Nonlinear regression analysis of data points with a computer assisted program Prism ® yields both the IC 50 and the K ; values of test compounds with 95% confidence limits. Alternatively, linear regression line of decline of data points is plotted, from which the IC 50 value can be read off and the K .
  • the compounds of the present invention showed activity in the above test, for example:
  • composition Applicable solid carriers can include one or more substances which may also act as flavoring agents, lubricants, solubilizers, suspending agents, fillers, glidants, compression aids, binders or tablet-disintegrating agents or an encapsulating material.
  • the carrier is a finely divided solid which is in admixture with the finely divided active ingredient.
  • the active ingredient is mixed with a carrier having the necessary compression properties in suitable proportions and compacted in the shape and size desired.
  • the powders and tablets preferably contain up to 99% of the active ingredient.
  • Suitable solid carriers include, for example, calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidine, low melting waxes and ion exchange resins.
  • Liquid carriers may be used in preparing solutions, suspensions, emulsions, syrups and elixirs.
  • the active ingredient of this invention can be dissolved or suspended in a pharmaceutically acceptable liquid carrier such as water, an organic solvent, a mixture of both or pharmaceutically acceptable oils or fat.
  • a pharmaceutically acceptable liquid carrier such as water, an organic solvent, a mixture of both or pharmaceutically acceptable oils or fat.
  • the liquid carrier can contain other suitable pharmaceutical additives such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavoring agents, suspending agents, thickening agents, colors, viscosity regulators, stabilizers or osmo-regulators.
  • liquid carriers for oral and parenteral administration include water (particularly containing additives as above e g cellulose de atives, preferably sodium carboxymethyl cellulose solution), alcohols (including monohydnc alcohols and polyhydnc alcohols e g glycols) and their derivatives, and oils (e g fractionated coconut oil and arachis oil)
  • the earner can also be an oily ester such as ethyl oleate and isopropyl myristate Sterile liquid carriers are used in sterile liquid form compositions for parenteral administration
  • Liquid pharmaceutical compositions which are sterile solutions or suspensions can be utilized by, for example, intramuscular, lntrape ⁇ toneal or subcutaneous injection Sterile solutions can also be administered mtra ⁇ enously Oral administration may be either liquid or solid composition form
  • the pharmaceutical composition is in unit dosage form, e g as tablets or capsules
  • the composition is sub-divided in unit dose containing appropriate quantities of the active ingredient
  • the unit dosage forms can be packaged compositions, for example packeted powders, vials, ampoules, prefilled syringes or sachets contaming liquids
  • the unit dosage form can be. for example, a capsule or tablet itself, or it can be the appropriate number of any such compositions in package form
  • the therapeutically effective dosage to be used in the treatment of a specific disease must be subjectively determined by the attending physician
  • the novel method of the invention for treating conditions related to or are affected by the 5- HT7 receptor comprise administering to warm-blooded animals, including humans, an effective amount of at least one compound of Formula (1) and its non-toxic, pharmaceutically acceptable addition salts
  • the compounds may be administered orally, rectally, parenterally or topically to the skin and mucosa
  • the usual daily dose is depending on the specific compound, method of treatment and condition treated
  • the usual daily dose is 0 01 - 1000 mg/Kg for oral application, preferably 0 5 - 500 mg/Kg, and 0.1 - 100 mg/Kg for parenteral application, preferably 0 5 - 50 mg/Kg

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  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Psychiatry (AREA)
  • Addiction (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Cardiology (AREA)
  • Anesthesiology (AREA)
  • Nutrition Science (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

L'invention porte sur des composés de formule (1) utilisables pour le traitement de l'angoisse, de la dépression et de troubles associés du SNC, et d'autres états tels que la schizophrénie, les troubles du sommeil dont ceux du rythme circadien, le sevrage de l'alcool et de drogues, et certaines dysfonctions sexuelles.
PCT/US2001/003430 2000-02-04 2001-02-02 Derives de la pyrrolo-isoquinoline et de la tetrahydropyrrolo-isoquinoline et leur utilisation comme mediateurs du recepteur 5-ht7 Ceased WO2001057039A1 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
EP01903486A EP1252161A1 (fr) 2000-02-04 2001-02-02 Derives de la pyrrolo-isoquinoline et de la tetrahydropyrrolo-isoquinoline et leur utilisation comme mediateurs du recepteur 5-ht7
AU2001231287A AU2001231287A1 (en) 2000-02-04 2001-02-02 Pyrrolo-isoquinoline and tetrahydropyrrolo-isoquinoline derivatives and their use as mediators of the 5-ht7 receptor
MXPA02007521A MXPA02007521A (es) 2000-02-04 2001-02-02 Derivados de pirrolo-isoquinolina y tetrahidropirrolo isoquinolina y su uso como mediadores del receptor de 5-hidroxitriptamina-7(5-ht7).
CA002399545A CA2399545A1 (fr) 2000-02-04 2001-02-02 Derives de la pyrrolo-isoquinoline et de la tetrahydropyrrolo-isoquinoline et leur utilisation comme mediateurs du recepteur 5-ht7
JP2001557871A JP2003522178A (ja) 2000-02-04 2001-02-02 ピロロイソキノリンおよびテトラヒドロピロロイソキノリン誘導体ならびに５−ｈｔ７受容体の媒介物質としてのそれらの使用
BR0108007-5A BR0108007A (pt) 2000-02-04 2001-02-02 Derivados da pirrolo-isoquinolina e tetraidropirrolo-isoquinolina e seus usos como mediadores do receptor da 5-ht7

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US49737900A 2000-02-04 2000-02-04
US09/497,379 2000-02-04

Publications (1)

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WO2001057039A1 true WO2001057039A1 (fr) 2001-08-09

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PCT/US2001/003430 Ceased WO2001057039A1 (fr) 2000-02-04 2001-02-02 Derives de la pyrrolo-isoquinoline et de la tetrahydropyrrolo-isoquinoline et leur utilisation comme mediateurs du recepteur 5-ht7

Country Status (8)

Country Link
EP (1) EP1252161A1 (fr)
JP (1) JP2003522178A (fr)
CN (1) CN1168728C (fr)
AU (1) AU2001231287A1 (fr)
BR (1) BR0108007A (fr)
CA (1) CA2399545A1 (fr)
MX (1) MXPA02007521A (fr)
WO (1) WO2001057039A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007053353A3 (fr) * 2005-10-28 2007-06-28 Wyeth Corp Derives pyrrolo[2,3-f] et [3,2-f]isoquinolinone utilises en tant que ligands de la 5-hydroxytryptamine-6
WO2008013556A1 (fr) 2006-07-27 2008-01-31 Janssen Pharmaceutical N.V. Multithérapie avec antagoniste du récepteur 5-ht7 et inhibiteur du recaptage de la sérotonine
WO2013189588A1 (fr) * 2012-06-19 2013-12-27 Laboratorios Del Dr. Esteve S.A. Dérivés phényles à substitution hétérocyclyle pour le traitement du dysfonctionnement érectile
US8618288B2 (en) 2003-09-17 2013-12-31 Janssen Pharmaceutica Nv Pyrimidine compounds as serotonin receptor modulators

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8618288B2 (en) 2003-09-17 2013-12-31 Janssen Pharmaceutica Nv Pyrimidine compounds as serotonin receptor modulators
US7598255B2 (en) 2005-08-04 2009-10-06 Janssen Pharmaceutica Nv Pyrimidine compounds as serotonin receptor modulators
US8883808B2 (en) 2005-08-04 2014-11-11 Janssen Pharmaceutica N.V. Combination of 5-HT7 receptor antagonist and serotonin reuptake inhibitor therapy
WO2007053353A3 (fr) * 2005-10-28 2007-06-28 Wyeth Corp Derives pyrrolo[2,3-f] et [3,2-f]isoquinolinone utilises en tant que ligands de la 5-hydroxytryptamine-6
WO2008013556A1 (fr) 2006-07-27 2008-01-31 Janssen Pharmaceutical N.V. Multithérapie avec antagoniste du récepteur 5-ht7 et inhibiteur du recaptage de la sérotonine
WO2013189588A1 (fr) * 2012-06-19 2013-12-27 Laboratorios Del Dr. Esteve S.A. Dérivés phényles à substitution hétérocyclyle pour le traitement du dysfonctionnement érectile

Also Published As

Publication number Publication date
MXPA02007521A (es) 2002-12-13
CN1396921A (zh) 2003-02-12
EP1252161A1 (fr) 2002-10-30
BR0108007A (pt) 2002-10-29
CN1168728C (zh) 2004-09-29
CA2399545A1 (fr) 2001-08-09
JP2003522178A (ja) 2003-07-22
AU2001231287A1 (en) 2001-08-14

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