WO2005021543A1 - Sel d'acide phosphorique de 5-[[4-[2-(5-ethyl-2-pyridinyl) ethoxy] phenyl] methyl]-2, 4-thiazolidinedione - Google Patents

Sel d'acide phosphorique de 5-[[4-[2-(5-ethyl-2-pyridinyl) ethoxy] phenyl] methyl]-2, 4-thiazolidinedione Download PDF

Info

Publication number
WO2005021543A1
WO2005021543A1 PCT/IN2003/000295 IN0300295W WO2005021543A1 WO 2005021543 A1 WO2005021543 A1 WO 2005021543A1 IN 0300295 W IN0300295 W IN 0300295W WO 2005021543 A1 WO2005021543 A1 WO 2005021543A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
pyridinyl
thiazolidinedione
ethoxy
phenyl
Prior art date
Application number
PCT/IN2003/000295
Other languages
English (en)
Inventor
Joy Mathew
Tom Thomas Puthiaparampil
Sambasivam Ganesh
Original Assignee
Biocon 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 Biocon Limited filed Critical Biocon Limited
Priority to PCT/IN2003/000295 priority Critical patent/WO2005021543A1/fr
Priority to AU2003269479A priority patent/AU2003269479A1/en
Publication of WO2005021543A1 publication Critical patent/WO2005021543A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Definitions

  • the present invention relates to a novel compound and to a novel process for preparing the compound, to a pharmaceutical composition containing the compound and to the prophylactic and/or therapeutic use of the compound and composition.
  • BACKGROUND OF THE INVENTION US 4,687,777 discloses 5-[[4-[2-(5-ethyl-2-pyridinyl) ethoxy] phenyl] methyl]- 2,4- thiazolidinedione.
  • the compound exhibits blood-glucose and blood-lipid lowering action with lower toxicity, and may be safely administered, orally or parenterally, as it is or advantageously as a pharmaceutical composition
  • a pharmaceutical composition comprising an effective amount of the compound or its pharmacologically acceptable salt and a pharmacologically acceptable carrier, excipient or diluent therefor, in the form of powder, granule, tablet, hard capsule, soft capsule, dry syrup, suppository, injection or the like.
  • Hydrochloric acid salt of 5-[[4-[2-(5-ethyl-2-pyridinyl) ethoxy] phenyl] methyl]- 2,4- thiazolidinedione is currently marketed for treatment of Type II diabetes.
  • the present invention discloses a novel salt of 5-[[4-[2-(5- ethyl-2-pyridinyl) ethoxy] phenyl] methyl]- 2,4- thiazolidinedione namely phosphoric acid salt of 5-[[4-[2-(5-ethyl-2-pyridinyl) ethoxy] phenyl] methyl]- 2,4- thiazolidinedione which is useful in the treatment of Type II diabetes.
  • This compound shows good water solubility and good stability in solid form.
  • the present invention relates to a novel compound, phosphoric acid salt of 5-[[4-[2-(5-ethyl-2-pyridinyl) ethoxy] phenyl] methyl]- 2,4- thiazolidinedione (FORMULA I), to a novel process for preparing the compound, to a pharmaceutical composition containing the compound and to the prophylactic and/or therapeutic use of the compound and composition.
  • the present invention provides a compound of formula I or a tautomeric form thereof, for use in the treatment of and/or prophylaxis of hyperglycemia.
  • the surprising and advantageous stability and water solubility of this compound provides for significant formulation and bulk handling advantages.
  • the compound of formula I is a phosphoric acid salt of 5-[[4-
  • the compound of the invention is significantly more soluble in water than the corresponding free base or currently marketed HCI salt.
  • a convenient method for determining the stability of the compounds of the invention in aqueous solution involves determining the degree of precipitation of the parent free base from an aqueous solution of the test compound at known conditions of temperature and over known periods of time. We have found that the compound of formula I show good stability in aqueous conditions.
  • the currently marketed HCI salt of 5-[[4-[2-(5-ethyl-2- pyridinyl) ethoxy] phenyl] methyl]- 2,4- thiazolidinedione is practically insoluble in water (The Merck Index Online, 2003).
  • the compound of present invention is freely soluble in water. This has significant pharmacokinetic advantage.
  • the quantitative analysis of the test may be carried out using conventional methods e.g. HPLC.
  • the compound of the invention is indicated as having useful therapeutic properties.
  • the present invention accordingly provides a compound of formula I, and/or a tautomeric form, for use as an active therapeutic substance.
  • the present invention provides a compound of formula I, or a tautomeric form thereof, for use in the treatment of and/or prophylaxis of hyperglycemia.
  • the present invention also provides a pharmaceutical composition comprising a compound of formula I, or a tautomeric form thereof, and a pharmaceutically acceptable carrier therefor.
  • a pharmaceutical composition comprising a compound of formula I, or a tautomeric form thereof, and a pharmaceutically acceptable carrier therefor.
  • Particularly suitable compositions for oral administration are unit dosage forms such as tablets and capsules. Other fixed unit dosage forms, such as powders presented in sachets, may also be used.
  • the present invention further provides a method for the treatment and/or prophylaxis of hyperglycemia in a human or non- human mammal, which comprises administering an effective, non- toxic, amount of a compound of formula I, or a tautomeric form thereof, to a hyperglycemic human or non-human mammal in need thereof.
  • the reaction between the compound of formula I and the source of phosphoric acid counter-ion is generally carried out under conventional salt forming conditions, for example by admixing the compound of formula I and the source of counter-ion, phosphoric acid, suitably in approximately equimolar amounts but preferably using an excess of the source of counter-ion, phosphoric acid, in a solvent, generally a Cl-4 alkanolic solvent such as methanol, ethanol, or other aprotic solvents like acetonitrile, at any temperature which provides a suitable rate of formation of the required product, generally at an elevated temperature and thereafter isolating the product.
  • a solvent generally a Cl-4 alkanolic solvent such as methanol, ethanol, or other aprotic solvents like acetonitrile

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Diabetes (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Emergency Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Endocrinology (AREA)
  • Pharmacology & Pharmacy (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)

Abstract

L'invention porte sur un sel d'acide phosphorique de 5-[[4-[2-(5-ethyl-2-pyridinyl) ethoxy] phenyl] methyl]- 2,4- thiazolidinedione qui est nouveau et présente une activité de diminution de la glycémie chez les mammifères et sert d'agent prophylactique et/ou thérapeutique dans la prévention et/ou le traitement des diabètes.
PCT/IN2003/000295 2003-09-03 2003-09-03 Sel d'acide phosphorique de 5-[[4-[2-(5-ethyl-2-pyridinyl) ethoxy] phenyl] methyl]-2, 4-thiazolidinedione WO2005021543A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/IN2003/000295 WO2005021543A1 (fr) 2003-09-03 2003-09-03 Sel d'acide phosphorique de 5-[[4-[2-(5-ethyl-2-pyridinyl) ethoxy] phenyl] methyl]-2, 4-thiazolidinedione
AU2003269479A AU2003269479A1 (en) 2003-09-03 2003-09-03 Phosphoric acid salt of 5-((4-(2-(5-ethyl-2-pyridinyl) ethoxy) phenyl) methyl)-2, 4-thiazolidinedione

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IN2003/000295 WO2005021543A1 (fr) 2003-09-03 2003-09-03 Sel d'acide phosphorique de 5-[[4-[2-(5-ethyl-2-pyridinyl) ethoxy] phenyl] methyl]-2, 4-thiazolidinedione

Publications (1)

Publication Number Publication Date
WO2005021543A1 true WO2005021543A1 (fr) 2005-03-10

Family

ID=34259917

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2003/000295 WO2005021543A1 (fr) 2003-09-03 2003-09-03 Sel d'acide phosphorique de 5-[[4-[2-(5-ethyl-2-pyridinyl) ethoxy] phenyl] methyl]-2, 4-thiazolidinedione

Country Status (2)

Country Link
AU (1) AU2003269479A1 (fr)
WO (1) WO2005021543A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4687777A (en) * 1985-01-19 1987-08-18 Takeda Chemical Industries, Ltd. Thiazolidinedione derivatives, useful as antidiabetic agents
WO2003026586A2 (fr) * 2001-09-28 2003-04-03 Teva Pharmaceutical Industries Ltd. Chlorhydrate de pioglitazone

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4687777A (en) * 1985-01-19 1987-08-18 Takeda Chemical Industries, Ltd. Thiazolidinedione derivatives, useful as antidiabetic agents
WO2003026586A2 (fr) * 2001-09-28 2003-04-03 Teva Pharmaceutical Industries Ltd. Chlorhydrate de pioglitazone

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
REMINGTON ET AL.: "The science and practice of pharmacy", 2000, PHILADEPHIA COLLEGE OF PHARMACY AND SCIENCE, USA, pages: 703 - 704 *

Also Published As

Publication number Publication date
AU2003269479A1 (en) 2005-03-16

Similar Documents

Publication Publication Date Title
CA2382886C (fr) Formulation de benzamide a activite inhibitrice d'histone deacetylase
KR100716389B1 (ko) Ｎ-히드록시－４－｛５－［４－（5－이소프로필－２－메틸－１,３－티아졸－4－일）페녹시］펜톡시｝벤즈아미딘 ２메탄술폰산염
US20070203199A1 (en) Pioglitazone salts, such as pioglitazone sulfate, and pharmaceutical compositions and processes using the same
EP2404909A1 (fr) Dérivé de thiazole de type amide, sa méthode de synthèse et ses applications
EA014101B1 (ru) Антагонист cd80
WO2008085674A1 (fr) Compositions pharmaceutiques comprenant des co-cristaux de célécoxib
WO2005023803A1 (fr) Sel d'acide phosphorique de 5-[[4-[2-(methyl-2-pyridinylamino) ethoxy]phenyl]methyl]-2,4-thiazolidinedione
CZ20013759A3 (cs) Nový léčivý přípravek
WO2005021543A1 (fr) Sel d'acide phosphorique de 5-[[4-[2-(5-ethyl-2-pyridinyl) ethoxy] phenyl] methyl]-2, 4-thiazolidinedione
US10945947B2 (en) Formulations for intravenous administration
KR102170422B1 (ko) 토파시티닙의 신규 염, 이의 제조방법 및 이를 포함하는 약학 조성물
RU2646475C2 (ru) Лечение диабета I и II типа
KR101006254B1 (ko) Ｎ-히드록시-4-｛5-〔4-（5-이소프로필-2-메틸-1,3-티아졸-4-일）페녹시〕펜톡시｝벤즈아미딘 2 에탄술폰산염, 이의제조방법 및 이를 포함하는 약학 조성물
WO2005023790A1 (fr) Sel sodique d'acide (s)-(+)-2-ethoxy-4-{[3-methyl-1-(2-piperidin-1-yl-phenyl)-butylcarbamoyl]-methyl}-benzoique
EP1864664A1 (fr) Preparation pharmaceutique
WO2005023789A1 (fr) Sel phosphorique de l'acide (s)-(+)-2-ethoxy-4-{[3-methyl-1-(2-piperidin-1-yl-phenyl)-butylcarbamoyl]-methyl}-benzoique
CH641775A5 (fr) N-(1-methyl 2-pyrrolidinyl methyl) 2,3-dimethoxy 5-methylsulfamoyl benzamide et ses derives, son procede de preparation et composition le renferment.
KR20110135972A (ko) Ｎｐｙ ｙ5 수용체 길항제를 함유하는 고형 제제
JP3990728B2 (ja) Ｎ−［４−オキソ−２−（１ｈ−テトラゾール−５−イル）−４ｈ−１−ベンゾピラン−８−イル］−４−（４−フェニルブトキシ）ベンズアミドの塩
US5106859A (en) Certain 1,3,4-thiadiazole derivatives and anti-ulcer agent comprising said derivatives as active ingredient
KR100632470B1 (ko) 결정성 시부트라민 캄실레이트염과 이의 제조방법
EP1640374A1 (fr) Sels de pioglitazone tels que le sulfate de pioglitazone, et leurs compositions pharmaceutiques et leurs procédés d'utilisation
CZ12566U1 (cs) Amlodipinhemimaleát a farmaceutický prostředek

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PG PH PL PT RO RU SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP