WO1990000175A1 - Nouveau derive d'acide ursodesoxycholique - Google Patents

Nouveau derive d'acide ursodesoxycholique Download PDF

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Publication number
WO1990000175A1
WO1990000175A1 PCT/EP1989/000699 EP8900699W WO9000175A1 WO 1990000175 A1 WO1990000175 A1 WO 1990000175A1 EP 8900699 W EP8900699 W EP 8900699W WO 9000175 A1 WO9000175 A1 WO 9000175A1
Authority
WO
WIPO (PCT)
Prior art keywords
ursodeoxycholic acid
compound
biliary
acid derivative
novel
Prior art date
Application number
PCT/EP1989/000699
Other languages
English (en)
Inventor
Carlo Scolastico
Camillo Maria Francesco Giulio Palazzi
Original Assignee
Istituto Chemioterapico Di Lodi S.P.A.
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 Di Lodi S.P.A. filed Critical Istituto Chemioterapico Di Lodi S.P.A.
Publication of WO1990000175A1 publication Critical patent/WO1990000175A1/fr

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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 ⁇ .

Abstract

Le dérivé d'acide ursodésoxycholique décrit, qui est représenté par la formule (I), présente une activité thérapeutique contre les calculs biliaires, contre les diskynésies biliaires, contre les gastrites par reflux et contre certaines hépatopathies.
PCT/EP1989/000699 1988-06-28 1989-06-21 Nouveau derive d'acide ursodesoxycholique WO1990000175A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT21135A/88 1988-06-28
IT21135/88A IT1219733B (it) 1988-06-28 1988-06-28 Derivato dell' acido ursodesossicolico

Publications (1)

Publication Number Publication Date
WO1990000175A1 true WO1990000175A1 (fr) 1990-01-11

Family

ID=11177269

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1989/000699 WO1990000175A1 (fr) 1988-06-28 1989-06-21 Nouveau derive d'acide ursodesoxycholique

Country Status (5)

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

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015017813A2 (fr) * 2013-08-01 2015-02-05 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Inhibiteurs du récepteur farnésoïde x et leurs utilisations en médecine

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE901069A (fr) * 1983-11-30 1985-03-15 Prodotti Chimici Alimentari Procede de synthese d'acide ursodesoxycholique conjugue avec la taurine et produit ainsi obtenu.

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE901069A (fr) * 1983-11-30 1985-03-15 Prodotti Chimici Alimentari Procede de synthese d'acide ursodesoxycholique conjugue avec la taurine et produit ainsi obtenu.

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Patent Abstracts of Japan, vol. 7, no. 263 (C-196)(1408), 24 November 1983; & JP-A-58146598 (YUKIO NIIDA) 1 September 1983 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015017813A2 (fr) * 2013-08-01 2015-02-05 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Inhibiteurs du récepteur farnésoïde x et leurs utilisations en médecine
WO2015017813A3 (fr) * 2013-08-01 2015-04-02 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Inhibiteurs du récepteur farnésoïde x et leurs utilisations en médecine
US9540415B2 (en) 2013-08-01 2017-01-10 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Inhibitors of the farnesoid X receptor and uses in medicine
US10233209B2 (en) 2013-08-01 2019-03-19 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Inhibitors of the farnesoid x receptor and uses in medicine

Also Published As

Publication number Publication date
IT8821135A0 (it) 1988-06-28
JPH03505455A (ja) 1991-11-28
EP0422055A1 (fr) 1991-04-17
IT1219733B (it) 1990-05-24
AU3839489A (en) 1990-01-23

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