EP1966138A2 - Derives piperidone tricycliques substitues - Google Patents

Derives piperidone tricycliques substitues

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Publication number
EP1966138A2
EP1966138A2 EP06846988A EP06846988A EP1966138A2 EP 1966138 A2 EP1966138 A2 EP 1966138A2 EP 06846988 A EP06846988 A EP 06846988A EP 06846988 A EP06846988 A EP 06846988A EP 1966138 A2 EP1966138 A2 EP 1966138A2
Authority
EP
European Patent Office
Prior art keywords
unsubstituted
substituted
general formula
ethyl
optionally
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.)
Withdrawn
Application number
EP06846988A
Other languages
German (de)
English (en)
Inventor
Stefan Schunk
Stefan OBERBÖRSCH
Hagen-Heinrich Hennies
Martin Maier
Anton Khartulyari
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.)
Gruenenthal GmbH
Original Assignee
Gruenenthal GmbH
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Filing date
Publication date
Application filed by Gruenenthal GmbH filed Critical Gruenenthal GmbH
Publication of EP1966138A2 publication Critical patent/EP1966138A2/fr
Withdrawn legal-status Critical Current

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Classifications

    • 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
    • C07D471/08—Bridged 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
    • A61P1/12—Antidiarrhoeals
    • 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
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • 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
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the present invention relates to substituted tricyclic piperidone derivatives, processes for their preparation, medicaments containing these compounds and the use of substituted tricyclic piperidone derivatives for the preparation of medicaments.
  • Classic opioids such as morphine are effective in the treatment of severe to severe pain. Their use is, however, by the known side effects z. As respiratory depression, vomiting, sedation, constipation and tolerance development limited. In addition, they are less effective in the case of neuropathic or incidental pain, in particular tumor patients.
  • WO 9951602 discloses bridged keto-substituted cyclohexane rings which affect the nicotinic acetylcholine receptor. However, these compounds carry neither a carboxylic acid ester nor a phenyl ring is fused.
  • An object underlying the invention was to provide novel analgesic substances which are suitable for the treatment of pain - especially chronic and neuropathic pain.
  • the invention therefore relates to substituted tricyclic piperidone derivatives derivatives of the general formula I 1
  • the invention relates to substituted tricyclic piperidone derivatives of the general formula I.
  • R 1 is methyl, ethyl or phenyl
  • X 1 is NR 2 and X 2 is CH 2 or X 2 is NR 2 and X 1 is CH 2 ;
  • R 3 is H 1 F, Cl, Br, OH, OCH 3 , SCH 3 , NO 2 , CN; d. 8- alkyl or Cs- ⁇ -cycloalkyl, each saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted; Phenyl, benzyl or phenethyl, each unsubstituted or mono- or polysubstituted by F, Cl 1 OH, OCH 3 , SCH 3 , NO 2 , CN, CF 3 , methyl or ethyl;
  • R 4, R 7 and R 8 is Ci -8 alkyl or C 3-8 cycloalkyl, respectively saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted, optionally having a hetero atom N, O, S as a chain member ;
  • Aryl, or heteroaryl in each case monosubstituted or polysubstituted or unsubstituted; via a saturated or unsaturated, branched or unbranched, substituted or unsubstituted C 1-8 -alkyl group, optionally with one heteroatom N, O, S as chain member, attached aryl or C 3-8 -cycloalkyl or heteroaryl, in each case unsubstituted or simple or substituted several times; stand;
  • R 5 and R 6 are independently H; Ci -8 alkyl or C 3-8 cycloalkyl, respectively saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted, optionally having a hetero atom N, O, S as a chain member; Aryl, or heteroaryl, in each case monosubstituted or polysubstituted or unsubstituted; via a saturated or unsaturated, branched or unbranched, substituted or unsubstituted Ci -8 alkyl group, optionally in each case unsubstituted with a hetero atom N, O, S as a chain member, bound aryl or C 3-8 -cycloalkyl or heteroaryl or mono- or substituted several times; where R 5 and R 6 may not be H at the same time;
  • R 5 and R 6 together form a five-, six- or seven-membered ring which may be saturated or unsaturated, but not aromatic, which optionally contains one further heteroatom from the group S, O or NR 9 and with benzyl or may be substituted Ci- 5 alkyl, wherein R 9 is Ci -5- alkyl, branched or unbranched; Phenyl or benzyl, unsubstituted or mono- or polysubstituted by F, Cl 1 OH 1 OCH 3 , SCH 3 , NO 2 , CN, CF 3 , methyl or ethyl.
  • Ci -5 alkyl "and” Ci -8 alkyl include for the purposes of this invention acyclic saturated or unsaturated hydrocarbon radicals which have branched or straight chained and unsubstituted or may be mono- or polysubstituted, having 1 to 3 carbon atoms and 1 to 5 C atoms or 1 to 8 carbon atoms, ie, C -3 -Alkanyle, C 2-3 alkenyls and C2-3 alkynyls or Ci -5 -Alkanyle, C 2 -5 alkenyls and C2-5 alkynyls or Ci -8 -Alkanyle, C2-8 alkenyls and C2-8 alkynyls.
  • alkenyls have at least one C-C double bond and alkynyls at least one C-C triple bond.
  • Octyl, octenyl and octynyl includes.
  • Especially vorteihaft are methyl, ethyl, n-propyl, n-butyl, sec-butyl, iso-butyl. Very particularly advantageous is methyl.
  • Particularly preferred are piperidine, piperazine, morpholine and thiomorpholine.
  • aryl in the context of this invention means aromatic hydrocarbons, including phenyls and naphthyls.
  • the aryl radicals can also be with be condensed further saturated, (partially) unsaturated or aromatic ring systems.
  • Each aryl radical may be unsubstituted or monosubstituted or polysubstituted, wherein the aryl substituents may be the same or different and may be in any desired and possible position of the aryl.
  • aryl is selected from the group consisting of phenyl, 1-naphthyl, 2-naphthyl, which may each be unsubstituted or mono- or polysubstituted. Particularly advantageous is the phenyl radical.
  • heteroaryl represents a 5-, 6- or 7-membered cyclic aromatic radical containing at least 1, optionally, also 2, 3, 4 or 5 heteroatoms, wherein the heteroatoms are the same or different and the heterocycle is unsubstituted or in the case of substitution on the heterocycle, the substituents may be the same or different and may be in any and possible position of the heteroaryl
  • the heterocycle may also be part of a bicyclic or polycyclic system Preferred heteroatoms are nitrogen It is preferred that the heteroaryl moiety is selected from the group consisting of pyrrolyl, indolyl, furyl (furanyl), benzofuranyl, thienyl (thiophenyl), benzothienyl, benzothiadiazolyl, benzothiazolyl, benzotriazolyl, benzodioxolanyl, benzodioxanyl, phthalazinyl , Pyrazolyl, imidazolyl, thiazolyl,
  • aryl or heteroaryl bonded via C 1-3 -alkyl means for the purposes of the present invention that C i. 3 alkyl and aryl or heteroaryl have the meanings defined above and the aryl or heteroaryl radical is bonded via a Ci_ 3 - alkyl group to the compound of general structure I.
  • Benzyl is particularly advantageous for the purposes of this invention.
  • substitution can be with the same or different substituents.
  • "mono- or polysubstituted" in connection with alkyl or a saturated or unsaturated ring which may not be aromatic means benzyl or methyl.
  • aryl and “heteroaryl” are understood as meaning “mono- or polysubstituted” the substitution of one or more, for example two, three or four times, substitution of one or more hydrogen atoms of the ring system by F, Cl , Br, I 1 CN, NH 2, NH-C 1-6 alkyl, NH- Ci -6 alkyl-OH, N (C 1-6 alkyl) 2, N (C 1-6 - alkyl-OH) 2
  • NO 2, SH, SC 1-6 alkyl, OH, OC 1-6 alkyl, O-Ci-6-alkyl-OH, C ( O) C 1-6 alkyl, CO 2 H, CO 2 -Ci -6- alkyl, CF 3 , Ci- 6 -alkyl, on one or optionally, different atoms (where a substituent may optionally be substituted in turn.) The multiple substitution takes place with the same or different substituents "and" heteroaryl "are preferred substituent
  • the term salt formed with a physiologically acceptable acid means salts of the respective active ingredient with inorganic or organic acids which are physiologically compatible, in particular when used in humans and / or mammals.
  • Particularly preferred is the hydrochloride.
  • physiologically tolerated acids are: hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid, formic acid, acetic acid, oxalic acid, succinic acid, tartaric acid, mandelic acid, fumaric acid, lactic acid, citric acid, glutamic acid, 1,1-dioxo-1,2-dihydro1 ⁇ 6 - benzo [cisothiazol-3-one (saccharic acid), monomethyl sebacic acid, 5-oxoproline, hexane-1-sulfonic acid, nicotinic acid, 2-, 3- or 4-aminobenzoic acid, 2,4,6-trimethylbenzoic acid, ⁇ -lipoic acid , Acetyl
  • tricyclic piperidone derivatives are of the general formula I, wherein R 2 is saturated Ci -5 alkyl, or unsaturated, branched or unbranched; via a saturated or unsaturated, branched or unbranched, substituted or unsubstituted C- ⁇ - 3 alkyl group, bound aryl, C 3-8 -cycloalkyl or heteroaryl, in each case unsubstituted or mono- or poly-substituted.
  • Particularly preferred tricyclic piperidone derivatives are of the general formula I, wherein R 2 represents Ci -5 alkyl, branched or unbranched, unsubstituted and saturated; a Ci -3 alkyl group bonded phenyl, naphthyl, pyridyl, furyl, thienyl and indolyl, each unsubstituted or mono- or polysubstituted with -F, -Cl, - CF 3, -0-CH 3, methyl, ethyl , n-propyl, nitro, tert-butyl, and -CN;
  • tricyclic piperidone derivatives are preferred of the general formula I, wherein R 4, R 7 and R 8 represents Ci -5 alkyl or C 3-8 cycloalkyl, branched or unbranched; Aryl, or heteroaryl, in each case monosubstituted or polysubstituted or unsubstituted; a Ci -3 alkyl group-bound aryl, C 3-8 -cycloalkyl or heteroaryl, in each case unsubstituted or mono- or polysubstituted; stand; Particular preference is given to tricyclic piperidone derivatives of the general formula I in which R 4 , R 7 and R 8 are methyl, ethyl, n-propyl.
  • Phenyl, naphthyl, thienyl, furyl or pyridyl each singly or multiply substituted with F, Cl, CF 3 , NO 2 , CH 3 , OH, SH, OCH 3 or SCH 3 or unsubstituted
  • a Ci -3 alkyl group bonded phenyl, naphthyl, thienyl, furyl or pyridyl respectively unsubstituted or singly or multiply substituted with F, Cl, CF 3, NO 2, CH 3, OH, SH, OCH 3 or SCH 3 ; stand
  • R 5 and R 6 independently of one another are H; Methyl, ethyl, ⁇ -propyl. / so-propyl, ⁇ -butyl or tert-butyl; Phenyl, naphthyl, thienyl, furyl or pyridyl, each singly or multiply substituted with F, Cl, CF 3 , NO 2 , CH 3 , OH, SH, OCH 3 or SCH 3 or unsubstituted; via a C- ⁇ -3 alkyl group bonded phenyl, naphthyl, thienyl, furyl or pyridyl, respectively unsubstituted or singly or multiply substituted with F, Cl, CF 3, NO 2, CH 3, OH, SH, OCH 3, or SCH 3 ; stand;
  • Tricyclic piperidone derivatives of general formula I in which X 1 is NR 2 and X 2 is CH 2 can be prepared according to the following synthesis scheme:
  • R 2a is Ci -8- alkyl, saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted, optionally with a heteroatom as a chain member; via a saturated or unsaturated, branched or unbranched, substituted or unsubstituted Ci- ⁇ -alkyl group, optionally, with a heteroatom as a chain member, attached aryl, C 3 - 8 -cycloalkyl or heteroaryl, each unsubstituted or mono- or polysubstituted .
  • piperidone derivatives of the general formula A are added with the addition of a base, for example diisopropylethylamine, triethylamine, pyridine, diethylamine, diisopropylamine, butyl lithium, lithium diisopropylamide, sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate in an organic solvent, for example acetone, dichloromethane, THF, diethyl ether Benzene, toluene reacted with diethyl carbonate.
  • a base for example diisopropylethylamine, triethylamine, pyridine, diethylamine, diisopropylamine, butyl lithium, lithium diisopropylamide, sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate in an organic solvent, for example acetone, dichloromethane, THF, diethyl
  • the products of general formula B are in an organic solvent, for example acetone, acetonitrile, benzene, toluene, methanol, ethanol, dichloromethane, diethyl ether, tetrahydrofuran with the addition of a base, for example K 3 PO 4 , K 2 CO 3 , Na 2 CO 3 , NaOH, KOH, KOtBu, diisopropylethylamine, triethylamine, pyridine, diethylamine, diisopropylamine with the corresponding benzyl bromide at a temperature of 0-100 ° C to give compounds of general formula C.
  • a base for example K 3 PO 4 , K 2 CO 3 , Na 2 CO 3 , NaOH, KOH, KOtBu, diisopropylethylamine, triethylamine, pyridine, diethylamine, diisopropylamine with the corresponding benzyl bromide at a temperature
  • the compounds of general formula C are in an organic solvent, for example acetone, benzene, toluene, acetonitrile, dichloromethane, diethyl ether, tetrahydrofuran with the addition of a base, for example K 3 PO 4 , K 2 CO 3 , Na 2 CO 3 , NaOH , KOH,
  • a catalyst such as Pd (dba) 2) PdCl 2 , Pd (OAc) 2 and a corresponding ligand, for example, t-Bu 3 P, Ph 3 P at a temperature of 40-130 0 C reacted under inert gas to compounds of general formula Ia.
  • the compounds of the general formula Ia are dissolved in a compound of the general formula CIC (O) OR 8 , for example benzyloxycarbonyl chloride, optionally dissolved in acetone, acetonitrile, benzene, dichloromethane, diethyl ether, toluene or tetrahydrofuran, and at a temperature from 0 to 10O 0 C converted to compounds of general formula Ib.
  • the products of general formula Ib are dissolved in an organic solvent, for example acetone, acetonitrile,
  • an organic solvent for example acetone, benzene, toluene, acetonitrile, dichloromethane, diethyl ether, tetrahydrofuran with the addition of a base, for example K 3 PO 4 , K 2 CO 3 , Na 2 CO 3 , NaOH, KOH, diisopropylethylamine, triethylamine , Pyridine, diethylamine, diisopropylamine, butyllithium, lithium diisopropylamide, sodium hydride, potassium hydride with the corresponding electrophile, for example acid chlorides, acid anhydrides, sulfonyl chlorides, isocyanates or isothiocyanates at a temperature of - 20 0 C-100 I 0 C to compounds of general formula Ic reacted.
  • a base for example K 3 PO 4 , K 2 CO 3 , Na 2 CO 3 , NaOH, KOH, diisopropylethylamine, tri
  • Tricyclic piperidone derivatives of general formula I in which X 1 is CH 2 and X 2 NR 2 may be prepared according to the following synthesis scheme:
  • Compounds of general formula H are in an organic solvent, for example acetone, acetonitrile, benzene, toluene, methanol, ethanol, dichloromethane, diethyl ether, tetrahydrofuran with the addition of a base, for example K 3 PO 4 , K 2 CO 3 , Na 2 CO 3 , NaOH, KOtBu, KOH, diisopropylethylamine, triethylamine, pyridine, diethylamine, diisopropylamine with the corresponding benzyl bromide at a temperature of 0-10O 0 C to compounds of general formula J implemented.
  • a base for example K 3 PO 4 , K 2 CO 3 , Na 2 CO 3 , NaOH, KOtBu, KOH, diisopropylethylamine, triethylamine, pyridine, diethylamine, diisopropylamine with the corresponding benzyl bromide at
  • the compounds of general formula J are in an organic solvent, for example acetone, benzene, toluene, acetonitrile, dichloromethane, diethyl ether, tetrahydrofuran with the addition of a base, for example K 3 PO 4 , K 2 CO 3 , Na 2 CO 3 , NaOH , KOH, diisopropylethylamine, triethylamine, pyridine, diethylamine, diisopropylamine with a Katralysator as the addition of Pd (dba) 2 , PdCl 2 , Pd (OAc) 2 and a corresponding ligand, for example, t-Bu 3 P, Ph 3 P at a temperature of 40-130 0 C reacted under inert gas to compounds of general formula Id.
  • a base for example K 3 PO 4 , K 2 CO 3 , Na 2 CO 3 , NaOH , KOH, diisopropylethylamine
  • the compounds of general formula Id are in benzyloxycarbonyl chloride, optionally dissolved in acetone, acetonitrile, benzene, dichloromethane, diethyl ether, toluene or tetrahydrofuran, dissolved and reacted at a temperature of 0 to 100 0 C to compounds of general formula Ie.
  • the products of general formula Ie are in an organic solvent, for example acetone, acetonitrile, benzene, toluene, methanol, ethanol, dichloromethane, diethyl ether, tetrahydrofuran with Trimethylsilyliodide reacted at a temperature of -20 to 100 0 C.
  • an organic solvent for example acetone, benzene, toluene, acetonitrile, dichloromethane, diethyl ether, tetrahydrofuran with the addition of a base, for example K 3 PO 4 , K 2 CO 3 , Na 2 CO 3 , NaOH, KOH, diisopropylethylamine, triethylamine , Pyridine, diethylamine, diisopropylamine, butyllithium, lithium diisopropylamide, sodium hydride, potassium hydride with the corresponding electrophile example, acid chlorides, acid anhydrides, sulfonyl chlorides, isocyanates, isothiocyanates at a temperature of -2O 0 C-100 ° C to compounds of general formula If implemented.
  • a base for example K 3 PO 4 , K 2 CO 3 , Na 2 CO 3 , NaOH, KOH, diisopropylethylamine, triethylamine
  • benzyl bromides are in principle the methods known to those skilled in the preparation of benzyl bromides into consideration.
  • the benzyl bromides are prepared from the corresponding alcohols, esters or aldehydes by reduction and subsequent bromination. Friedel-Crafts or metallation strategies can be used to prepare the aldehydes.
  • Noradrenaline and serotonin reuptake inhibitors have antidepressant and anxiolytic effects, but are also useful in the treatment of pain (Analgesics - from Chemistry and Pharmacology to Clinical Application, Wiley 2002, pp. 265-284).
  • the substances according to the invention are suitable as pharmaceutical active ingredients in medicaments.
  • Another object of the invention are therefore medicaments containing at least one inventive substituted tricyclic piperidone derivative, and optionally suitable additives and / or adjuvants and / or optionally other active ingredients.
  • the medicaments according to the invention contain, in addition to at least one substituted tricyclic piperidone derivative according to the invention, optionally suitable additives and / or adjuvants, as well as carrier materials, fillers, solvents, diluents, dyes and / or binders and can be used as liquid dosage forms in the form of injection solutions, drops or juices, as semi-solid dosage forms in the form of granules, tablets, pellets, patches, capsules, patches or aerosols. The choice of excipients etc.
  • the amounts to be used depend on whether the drug is oral, peroral, parenteral, intravenous, intraperitoneal, intradermal, intramuscular, intranasal, buccal, rectal or topical, for example on the skin, mucous membranes or in the eyes, to be applied.
  • preparations in the form of tablets, dragees, capsules, granules, drops, juices and syrups are suitable, for parenteral, topical and inhalative administration solutions, suspensions, readily reconstitutable dry preparations and sprays.
  • Inventive tricyclic piperidone derivatives in a depot, in dissolved form or in a plaster, optionally with the addition of skin penetration promoting agents are suitable percutaneous administration preparations.
  • Orally or percutaneously applicable preparation forms can release the tricyclic piperidone derivatives according to the invention with a delay.
  • other active compounds known to the person skilled in the art may be added to the medicaments according to the invention.
  • the amount of drug to be administered to the patient varies depending on the weight of the patient, the mode of administration, the indication and the severity of the disease. Usually, 0.005 to 20 mg / kg, preferably 0.05 to 5 mg / kg of at least one tricyclic piperidone derivative according to the invention are administered.
  • the pharmaceutical composition may contain a tricyclic piperidone derivative according to the invention as a pure diastereomer and / or enantiomer, as a racemate or as a non-equimolar or equimolar mixture of the diastereomers and / or enantiomers.
  • Another object of the invention is the use of a tricyclic piperidone derivative of the invention for the manufacture of a medicament for Treatment of pain, especially acute, neuropathic or chronic pain.
  • Another object of the invention is the use of a tricyclic piperidone derivative of the invention for the manufacture of a medicament for the treatment of depression and / or anxiolysis.
  • the substituted tricyclic piperidone derivatives of the general formula I are also suitable for the treatment of urinary incontinence, diarrhea, pruritus, alcohol and drug abuse, drug dependence and listlessness.
  • the invention therefore also relates to the use of a substituted tricyclic piperidone derivative of general formula I for the manufacture of a medicament for the treatment of urinary incontinence, diarrhea, pruritus, alcohol and drug abuse, drug dependence and listlessness.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
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  • Animal Behavior & Ethology (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Addiction (AREA)
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  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Urology & Nephrology (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

La présente invention concerne des dérivés pipéridone tricycliques substitués, représentés par la formule (I), des procédés de fabrication de ces dérivés, des médicaments contenant ces composés et l'utilisation de dérivés pipéridone tricycliques substitués dans la fabrication de médicaments à effet analgésique.
EP06846988A 2005-12-22 2006-12-19 Derives piperidone tricycliques substitues Withdrawn EP1966138A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102005061426A DE102005061426A1 (de) 2005-12-22 2005-12-22 Substituierte tricyclische Piperidon-Derivate
PCT/EP2006/012223 WO2007079929A2 (fr) 2005-12-22 2006-12-19 Derives piperidone tricycliques substitues

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EP1966138A2 true EP1966138A2 (fr) 2008-09-10

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EP06846988A Withdrawn EP1966138A2 (fr) 2005-12-22 2006-12-19 Derives piperidone tricycliques substitues

Country Status (5)

Country Link
US (1) US20080312268A1 (fr)
EP (1) EP1966138A2 (fr)
JP (1) JP2009520719A (fr)
DE (1) DE102005061426A1 (fr)
WO (1) WO2007079929A2 (fr)

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3576812A (en) * 1968-07-02 1971-04-27 American Home Prod 1,5-methano-3-benzazocine derivatives
US3687937A (en) * 1970-06-23 1972-08-29 Us Of America The 1,5-methano-3-benzazocine derivatives
JPS5211149B2 (fr) * 1972-06-01 1977-03-29
WO1999055680A1 (fr) * 1998-04-29 1999-11-04 Pfizer Products Inc. Composes azapolycycliques a fusion aryle

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2007079929A2 *

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US20080312268A1 (en) 2008-12-18
WO2007079929A3 (fr) 2007-09-27
JP2009520719A (ja) 2009-05-28
DE102005061426A1 (de) 2007-07-05

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