WO2005018643A1 - Metabolites de 1-{3-4`4-(2-methoxyphenyl)piperazin-1-yl!-propyl}-piperidine-2, 6-dione utilisables dans le traitement de l'hypertrophie benigne de la prostate - Google Patents

Metabolites de 1-{3-4`4-(2-methoxyphenyl)piperazin-1-yl!-propyl}-piperidine-2, 6-dione utilisables dans le traitement de l'hypertrophie benigne de la prostate Download PDF

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Publication number
WO2005018643A1
WO2005018643A1 PCT/IB2003/003509 IB0303509W WO2005018643A1 WO 2005018643 A1 WO2005018643 A1 WO 2005018643A1 IB 0303509 W IB0303509 W IB 0303509W WO 2005018643 A1 WO2005018643 A1 WO 2005018643A1
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WO
WIPO (PCT)
Prior art keywords
formula
compound
phenyl
metabolite
pharmaceutically acceptable
Prior art date
Application number
PCT/IB2003/003509
Other languages
English (en)
Inventor
Mohammad Salman
Gyan Chand Yadav
Somesh Sharma
Gobind Singh Kapkoti
Anita Mehta
Sanjay Jain
Neelima Sinha
Anita Chugh
Jyoti Kumar Paliwal
Nitya Anand
Original Assignee
Ranbaxy Laboratories Limited
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 Ranbaxy Laboratories Limited filed Critical Ranbaxy Laboratories Limited
Priority to AU2003259391A priority Critical patent/AU2003259391A1/en
Priority to PCT/IB2003/003509 priority patent/WO2005018643A1/fr
Publication of WO2005018643A1 publication Critical patent/WO2005018643A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • 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
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • 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
    • C07D211/80—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 two double bonds between ring members or between ring members and non-ring members
    • C07D211/84—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 two 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 directly attached to ring carbon atoms
    • C07D211/86—Oxygen atoms
    • C07D211/88—Oxygen atoms attached in positions 2 and 6, e.g. glutarimide

Definitions

  • R represents hydrogen, methyl, n represents an integer 0 or 1
  • Solid form preparations for oral administration may include capsules, tablets, pills, powder, granules and suppositories.
  • the metabolite is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate, dicalcium phosphate and/or a filter and extender such as starch, lactose, sucrose, glucose, mannitol or silicic acid; binders such as carboxymethyl cellulose, alginates, gelatins, polyvinylpyrrolidinone, sucrose, or acacia; disintegrating agents such as agar- agar, calcium carbonate, potato starch, or aliginic acid, certain silicates and sodium carbonate; abso ⁇ tion accelerators such as quaternary ammonium compounds; wetting agents such as cetyl alcohol, glycerol, or monostearate; adsorbents such as kaolin; or lubricants such as talc, calcium stearate, magnesium stearate
  • bioabsorbable it is meant that the polymeric formulation is broken down and absorbed within the human body, for example, by a cell or tissue.
  • Biocompatible means that the polymeric formulation does not cause substantial tissue irritation or necrosis.
  • the metabolites described herein can also be administered in the form of liposome delivery systems, for example, small unilamellar vesicles, large unilamellar vesicles and multilamellar vesicles.
  • Liposomes can be formed from a variety of phospholipids, for example, cholesterol, stearylamine or phosphatidylcholines.
  • Aqueous parenteral compositions, containing therapeutically effective amounts of metabolite are disclosed herein.
  • R represents alkyl of from one to four carbon atoms, aryl, for example, phenyl or naphthyl,
  • reaction of metabolite of Formula XV or XVII with a compound of Formula Cl — W — R can be carried out in the presence of an inorganic base, for example, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate or sodium hydride.
  • an inorganic base for example, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate or sodium hydride.
  • Example 18 Estimation of Compound No. 9 and Compound No. 11 in urine by LC/MS/MS Method (By Solid phase extraction): To 950 ⁇ L of urine, 500 ⁇ L of potassium dihydrogen phosphate buffer (0.1 M, pH 3.510.1) and 50 ⁇ L of solution of 2- ⁇ 3-[4-(2- Methoxyphenyl)-piperazin-l-yl]-propyl ⁇ -3a,4,7,7a-tetrahydro-isoindole-l,3-dione (Internal Standard) was added and vortexed to ensure proper mixing. Drug test cartridges (130mg) were used for processing the samples.
  • reaction mixture To the reaction mixture is added ethanoyl chloride (1.5 equi) at 0 °C to 5 °C for half to one hour.
  • the reaction mixture is poured in 5% sodium bicarbonate solution.
  • Organic layer is separated and washed with water, dried over anhydrous sodium sulphate and solvent is removed under reduced pressure to yield the desired product.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Urology & Nephrology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)

Abstract

La présente invention se rapporte aux métabolites de 1-{3-[4-(2-Méthoxyphényl) pipérazin-1-yl]-propyl}-pipéridine-2, 6-dione répondant à la formule (I). Ces composés peuvent servir d'antagonistes des adrénocepteurs α1a et sont donc utilisables dans le traitement de l'hypertrophie bénigne de la prostate et des symptômes associés. On a également prévu des procédés de préparation de ces métabolites, des compositions pharmaceutiques renfermant ces métabolites et un procédé de traitement de l'hypertrophie bénigne de la prostate et des symptômes associés.
PCT/IB2003/003509 2003-08-25 2003-08-25 Metabolites de 1-{3-4`4-(2-methoxyphenyl)piperazin-1-yl!-propyl}-piperidine-2, 6-dione utilisables dans le traitement de l'hypertrophie benigne de la prostate WO2005018643A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2003259391A AU2003259391A1 (en) 2003-08-25 2003-08-25 Metabolites of 1-{3-4`4-(2-methoxyphenyl) piperazin-1-yl!-propyl}-piperidine-2, 6-dione for use in the treatment of benign prostatic hyperplasia
PCT/IB2003/003509 WO2005018643A1 (fr) 2003-08-25 2003-08-25 Metabolites de 1-{3-4`4-(2-methoxyphenyl)piperazin-1-yl!-propyl}-piperidine-2, 6-dione utilisables dans le traitement de l'hypertrophie benigne de la prostate

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IB2003/003509 WO2005018643A1 (fr) 2003-08-25 2003-08-25 Metabolites de 1-{3-4`4-(2-methoxyphenyl)piperazin-1-yl!-propyl}-piperidine-2, 6-dione utilisables dans le traitement de l'hypertrophie benigne de la prostate

Publications (1)

Publication Number Publication Date
WO2005018643A1 true WO2005018643A1 (fr) 2005-03-03

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2003/003509 WO2005018643A1 (fr) 2003-08-25 2003-08-25 Metabolites de 1-{3-4`4-(2-methoxyphenyl)piperazin-1-yl!-propyl}-piperidine-2, 6-dione utilisables dans le traitement de l'hypertrophie benigne de la prostate

Country Status (2)

Country Link
AU (1) AU2003259391A1 (fr)
WO (1) WO2005018643A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005118537A2 (fr) * 2004-05-31 2005-12-15 Ranbaxy Laboratories Limited Antagonistes des recepteurs adrenergiques
WO2007029078A2 (fr) * 2005-09-05 2007-03-15 Ranbaxy Laboratories Limited Derives de succinimide et de glutarimide comme antagonistes de recepteurs adrenergiques
WO2007039809A1 (fr) * 2005-10-05 2007-04-12 Ranbaxy Laboratories Limited Métabolites de 2- {3-[4-(5-fluoro-2-isopropoxy-phényl)-pipérazin-1-yl]-propyl} -5,6-dihydroxy-hexahydro-isoindol-1,3-dione
CN104030933A (zh) * 2014-05-16 2014-09-10 烟台恒迪克能源科技有限公司 一种β-异烷醇基氨基戊酸环己胺的合成方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6083950A (en) * 1997-11-13 2000-07-04 Ranbaxy Laboratories Limited 1-(4-arylpiperazin-1-yl)-ω-[n-(α,ω-dicarboximido)]-alka nes useful as uro-selective α1-adrenoceptor blockers
WO2003084541A1 (fr) * 2002-04-08 2003-10-16 Ranbaxy Laboratories Limited Derives de carboximide utiles comme bloqueurs uroselectifs du recepteur adrenergique $g(a)1a
WO2003084928A1 (fr) * 2002-04-08 2003-10-16 Ranbaxy Laboratories Limited Derives d'alpha, omega-dicarboximide utiles en tant qu'inhibiteurs uroselectifs de l'adreno-recepteur ?1?

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6083950A (en) * 1997-11-13 2000-07-04 Ranbaxy Laboratories Limited 1-(4-arylpiperazin-1-yl)-ω-[n-(α,ω-dicarboximido)]-alka nes useful as uro-selective α1-adrenoceptor blockers
WO2003084541A1 (fr) * 2002-04-08 2003-10-16 Ranbaxy Laboratories Limited Derives de carboximide utiles comme bloqueurs uroselectifs du recepteur adrenergique $g(a)1a
WO2003084928A1 (fr) * 2002-04-08 2003-10-16 Ranbaxy Laboratories Limited Derives d'alpha, omega-dicarboximide utiles en tant qu'inhibiteurs uroselectifs de l'adreno-recepteur ?1?

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005118537A2 (fr) * 2004-05-31 2005-12-15 Ranbaxy Laboratories Limited Antagonistes des recepteurs adrenergiques
WO2005118537A3 (fr) * 2004-05-31 2006-06-01 Ranbaxy Lab Ltd Antagonistes des recepteurs adrenergiques
WO2007029078A2 (fr) * 2005-09-05 2007-03-15 Ranbaxy Laboratories Limited Derives de succinimide et de glutarimide comme antagonistes de recepteurs adrenergiques
WO2007029078A3 (fr) * 2005-09-05 2007-07-12 Ranbaxy Lab Ltd Derives de succinimide et de glutarimide comme antagonistes de recepteurs adrenergiques
WO2007039809A1 (fr) * 2005-10-05 2007-04-12 Ranbaxy Laboratories Limited Métabolites de 2- {3-[4-(5-fluoro-2-isopropoxy-phényl)-pipérazin-1-yl]-propyl} -5,6-dihydroxy-hexahydro-isoindol-1,3-dione
CN104030933A (zh) * 2014-05-16 2014-09-10 烟台恒迪克能源科技有限公司 一种β-异烷醇基氨基戊酸环己胺的合成方法

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Publication number Publication date
AU2003259391A1 (en) 2005-03-10

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