EP0422055A1 - Novel ursodeoxycholic acid derivative - Google Patents

Novel ursodeoxycholic acid derivative

Info

Publication number
EP0422055A1
EP0422055A1 EP89907146A EP89907146A EP0422055A1 EP 0422055 A1 EP0422055 A1 EP 0422055A1 EP 89907146 A EP89907146 A EP 89907146A EP 89907146 A EP89907146 A EP 89907146A EP 0422055 A1 EP0422055 A1 EP 0422055A1
Authority
EP
European Patent Office
Prior art keywords
ursodeoxycholic acid
compound
biliary
acid derivative
novel
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Withdrawn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
EP89907146A
Other languages
German (de)
English (en)
French (fr)
Inventor
Carlo Scolastico
Camillo Maria Francesco Giulio Palazzi
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.)
Archimica SpA
Original Assignee
Istituto Chemioterapico Italiano di Lodi SpA
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 Istituto Chemioterapico Italiano di Lodi SpA filed Critical Istituto Chemioterapico Italiano di Lodi SpA
Publication of EP0422055A1 publication Critical patent/EP0422055A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
    • 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
    • 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
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics

Definitions

  • the present invention relates to a novel ursodeoxycholic acid derivative, namely ursodeoxycholic acid L-e ⁇ i-glycerophosphorylethanolamide of formula I:
  • cholesterol solubility i ⁇ known to derive from a proper cholesterol/biliary acids/phospholipides ratio.
  • compound I has been found to have surprising pharmacological activities, together with an extremely poor or no toxicity.
  • a further advantage of the compound of the invention is provided by the watersolubility of said molecule, which makes it easier to be administered and therefore suited to various pharmaceutical formulations.
  • compositions for the treatment of biliary calculosis, biliary dyscinesias, of some hepatopathies and of reflux gastritis containing as the active ingredient the ursodeoxycholic acid L-° -gl cerophosphorylethanolamide.
  • a further object of the present invention is provided by the use of amide I for the treatment of biliary calculosis, biliary dyscinesias, reflux gastritis and some hepatopathies.
  • use in the present invention means all the procedures related to the preparation of the compound of the invention, including the purification as well as the formulation into pharmaceutical compositions suited for the administration and/or the confections suited for the administration itself.
  • the invention relates to a process for the preparation of amide I, which process consists in the condensation of ursodeoxycholic acid and L-c**/ -glycero- phosphorylethanola ine by means of the condensing agent EEDQ (i.e., N-ethoxycarbonyl-2-ethoxy-l,2-dihydroquinoli- ne), which is a known reactant for the preparation of polypeptides under mild not racemizing conditions (Bellau, et al. , JACS, 90_, 1652, 1968).
  • EEDQ condensing agent
  • EXAMPLE 1 Triethylamine (21,33 ml; 153,06 mmoles) are added to a solution obtained dissolving L- o.-glycerophosphoryl- ethanolamine (21,39 g; 99,49 mmoles) in water (2,0 M; 49,3 mmoles) at room temperature. Thereafter, a solution obtained dissolving ursodeoxycholic acid (30 g; 76,53 mmoles) and EEDQ (28,39 g; 114,79 mmoles) in dimethylformamide (0,57 M; 134 ml) is added thereto at room temperature.
  • the mixture is left to react for about 72 hours at r.t., under strong stirring, then DMF and water are evaporated under 0,1 mm Hg, till obtaining an oil which is taken up into about 800 ml of water and 100 ml of methanol, adjusting pH of the resulting solution to about 3 with diluted hydrochloric acid 1:1.
  • Example 2 The procedure of Example 1 is repeated till evaporation under 0,1 mm Hg of the DMF/water mixture.
  • compound I or a pharmaceutically acceptable salt thereof is administered to the patient either in the pure form or as a pharmaceutical composition, preferably by the oral or parenteral routes.
  • the pharmaceutical compositions used are the conventional ones, prepared according to the techniques described, for example, in "Remington's Pharmaceutical Sciences Handbook”hack Pub. Co., N.Y. USA.
  • the dosage will depend on various factors, such as the severity of the pathology to be treated, the patient conditions (weight, sex, age): generally, it will be 200 to 700 mg/die for compound I or the equivalent of a salt thereof, possibly divided in more administration ⁇ .

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Steroid Compounds (AREA)
EP89907146A 1988-06-28 1989-06-21 Novel ursodeoxycholic acid derivative Withdrawn EP0422055A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT21135/88A IT1219733B (it) 1988-06-28 1988-06-28 Derivato dell' acido ursodesossicolico
IT2113588 1988-06-28

Publications (1)

Publication Number Publication Date
EP0422055A1 true EP0422055A1 (en) 1991-04-17

Family

ID=11177269

Family Applications (1)

Application Number Title Priority Date Filing Date
EP89907146A Withdrawn EP0422055A1 (en) 1988-06-28 1989-06-21 Novel ursodeoxycholic acid derivative

Country Status (5)

Country Link
EP (1) EP0422055A1 (ja)
JP (1) JPH03505455A (ja)
AU (1) AU3839489A (ja)
IT (1) IT1219733B (ja)
WO (1) WO1990000175A1 (ja)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6556129B2 (ja) 2013-08-01 2019-08-07 アメリカ合衆国 ファルネソイドｘ受容体の阻害剤及び医薬としての使用

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1167038B (it) * 1983-11-30 1987-05-06 Prodotti Chimici & Alimentari Procedimento per la sintesi di acido ursodesossicolico coniugato con la taurina

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9000175A1 *

Also Published As

Publication number Publication date
IT8821135A0 (it) 1988-06-28
IT1219733B (it) 1990-05-24
JPH03505455A (ja) 1991-11-28
AU3839489A (en) 1990-01-23
WO1990000175A1 (en) 1990-01-11

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Legal Events

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