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WO1994013650A1 - Derives heterocycliques et leur utilisation comme produits pharmaceutiques - Google Patents

Derives heterocycliques et leur utilisation comme produits pharmaceutiques Download PDF

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Publication number
WO1994013650A1
WO1994013650A1 PCT/EP1993/003269 EP9303269W WO9413650A1 WO 1994013650 A1 WO1994013650 A1 WO 1994013650A1 EP 9303269 W EP9303269 W EP 9303269W WO 9413650 A1 WO9413650 A1 WO 9413650A1
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Prior art keywords
formula
pharmaceutically acceptable
compound
group
alkyl
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PCT/EP1993/003269
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English (en)
Inventor
David Haigh
Harshad Kantilal Rami
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Smithkline Beecham Plc
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Priority to JP6513713A priority Critical patent/JPH08504199A/ja
Publication of WO1994013650A1 publication Critical patent/WO1994013650A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • 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
    • A61P3/06—Antihyperlipidemics
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/06—Antiarrhythmics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2

Definitions

  • This invention relates to certain novel compounds, to a process for preparing such compounds, to pharmaceutical compositions containing such compounds and to the use of such compounds and compositions in medicine.
  • R is (C ⁇ -Cg)alkyl, (C3-C 7 )cycloalkyl, (C3-Cg)alkenyl, (C 3 -Cg)alkynyl, phenyl, (C7_Cg)phenylall yl, (C2-Cg)alkanoyl, or one of said groups mono- or disubstituted with (Cj-C3)alkyl, trifluoromomethyl, hydroxy, (C ⁇ -C3)alkoxy, fluoro or chloro;
  • R.2 is hydrogen, (C ⁇ -C3)alkyl, phenyl or benzyl; Y is CH or N; Z is H, amino, (C ⁇ -C7)alkyl, (C3- ⁇ 7)cycloalkyl, phenyl, or phenyl mono- or disubstituted with (C ⁇ -C3)alkyl, trifluoromethyl, (C ⁇ -C3)alkoxy, phenyl, phenoxy, benzyl, benzyloxy, fluoro or chloro;
  • Z 1 is hydrogen or (C ⁇ -C3)al yl; x s O, S, SO or SO ⁇ and ⁇ l is hydroxy, (C ⁇ -C3)alko y, phenoxy, benzyloxy, amino, (C ⁇ _C4)alkanoylamino, (C ⁇ -C4)alkanesulfonyl-a ino, benzenesulfonylamino, naphthalenesulfonylamino, di[(C ⁇ -C3)alkyl]aminosulfonylamino, or one of said groups mono- or disubstituted with (C ⁇ -C3)alkyl, trifluoromethyl, hydroxy, (C ⁇ _C3)alkoxy, fluoro or chloro; the pharmaceutically-acceptable cationic salts thereof when Y* is hydroxy; and the pharmaceutically-acceptable acid addition salts thereof when the compounds contain a basic nitrogen atom.
  • the compounds of formula (A) are stated to be useful as hypoglycaemic and hypocholesterolaemic agents. It has surprisingly been discovered that certain novel compounds show good blood-glucose lowering activity and are therefore of potential use in the treatment and/or prophylaxis of hyperglycaemia and are of particular use in the treatment of Type II diabetes.
  • These compounds are also indicated to be of potential use for the treatment and/or prophylaxis of other diseases including hyperlipidaemia and hypertension. They are also indicated to be of use in the treatment and/or prophylaxis of cardiovascular disease, especially atherosclerosis.
  • these compounds are considered to be useful for treating certain eating disorders, in particular the regulation of appetite and food intake in subjects suffering from disorders associated with under-eating, such as anorexia nervosa, and disorders associated with over ⁇ eating, such as obesity and anorexia bulimia.
  • Al represents a substituted or unsubstituted aromatic heterocyclyl group
  • a 2 represents a benzene ring having three optional substituents
  • R! and R 2 each independently represents hydrogen or R* together with R 2 represents a bond;
  • R3 and R ⁇ each independently represents a nitrile group or a group of formula -COR 5 wherein R ⁇ represents hydroxy, alkoxy, alkyl, aryl or a group of formula -NR6R7 wherein R6 and R ⁇ each independently represents hydrogen or alkyl or R > and R?
  • X represents NR wherein R represents a hydrogen atom, an alkyl group, an acyl group, an aralkyl group wherein the aryl moiety may be substituted or unsubstituted, or a substituted or unsubstituted aryl group;and n represents an integer in the range of from 2 to 6.
  • Suitable aromatic heterocyclyl groups include substituted or unsubstituted, single or fused ring aromatic heterocyclyl groups comprising up to 4 hetero atoms in each ring selected from oxygen, sulphur or nitrogen.
  • Favoured aromatic heterocyclyl groups include substituted or unsubstituted single ring aromatic heterocyclyl groups having 4 to 7 ring atoms, preferably 5 or 6 ring atoms.
  • the aromatic heterocyclyl group comprises 1 , 2 or 3 heteroatoms, especially 1 or 2, selected from oxygen, sulphur or nitrogen.
  • Suitable values for A ⁇ when it represents a 5- membered aromatic heterocyclyl group include thiazolyl and oxazolyl, especially oxazolyl.
  • Suitable values for A* when it represents a 6- membered aromatic heterocyclyl group include pyridyl or pyrimidinyl, especially pyridyl.
  • A represents a moiety of formula (a), (b) or (c):
  • R° and R ⁇ each independently represents a hydrogen or halogen atom, an alkyl or alkoxy group or a substituted or unsubstituted aryl group or when R ⁇ and R ⁇ are each attached to adjacent carbon atoms, then R ⁇ and R ⁇ together with the carbon atoms to which they are attached may form a benzene ring wherein each carbon atom represented by R ⁇ and R ⁇ together is substituted or unsubstituted; and in the moiety of formula (a) ⁇ l represents oxygen or sulphur.
  • Al represents a moiety of the abovedefined formula (a).
  • a * represents a moiety of the abovedefined formula (b).
  • Al represents a moiety of the abovedefined formula (c).
  • a particular form of moiety (c) is a moiety (c')_
  • R ⁇ and R ⁇ are as defined in relation to formula (c).
  • R ⁇ and R ⁇ together represent a moiety of formula (d):
  • R 0 and R ⁇ each independently represent hydrogen, halogen, substituted or unsubstituted alkyl or substituted or unsubstituted alkoxy.
  • R 0 and R ⁇ each independently represent hydrogen, halogen, alkyl or alkoxy.
  • R ⁇ represents hydrogen.
  • RH represents hydrogen.
  • R 0 and R ⁇ both represent hydrogen.
  • R° and R" each independently represent hydrogen, alkyl or a substituted or unsubstituted phenyl group and more favourably, R8 and R each independently represent hydrogen, alkyl or phenyl.
  • R ⁇ and R ⁇ together represent the moiety of formula (d).
  • R ⁇ and R ⁇ both represent hydrogen.
  • Optional substituents for A 2 are selected from the group consisting of: halogen, substituted or unsubstituted alkyl and alkoxy.
  • a 2 represents a moiety of formula (e):
  • R*2 and R 3 each independently represent hydrogen, halogen, substituted or unsubstituted alkyl or alkoxy.
  • R represents hydrogen or alkyl, especially alkyl.
  • suitable acyl groups include alkylcarbonyl groups, for example acetyl.
  • R ⁇ and R ⁇ each independently represent hydrogen, halogen, alkyl or alkoxy.
  • R 2 and R 3 each represent hydrogen.
  • R- ⁇ and R 4 each independently represents a group of formula -C0R5 wherein R ⁇ is as defined above.
  • R ⁇ represents hydroxy or alkoxy.
  • R ⁇ is alkyl
  • examples of R ⁇ include methyl.
  • R5 is aryl
  • examples of R ⁇ include phenyl
  • R ⁇ is CO2CH3.
  • R 4 is CO2CH3.
  • heterocyclic rings When -NR ⁇ R ⁇ represents a heterocyclic ring, favoured heterocyclic rings are saturated or unsamrated, fused or monocyclic heterocyclic rings comprising 5, 6 or 7 ring atoms and optionally comprising 1 or 2 additional hetero-atoms, selected from O,S or N, in each ring.
  • Favoured rings are saturated rings.
  • Favoured rings are monocyclic rings.
  • Favoured, additional hetero-atoms are N or O. Examples of such heterocyclic rings include N- pyrrolidinyl, N-piperidinyl and N-morpholinyl.
  • n is 2.
  • a compound of formula (I), and the pharmaceutically acceptable salts thereof may exist in one of several tautomeric forms, all of which are encompassed by the present invention as individual tautomeric forms or as mixtures thereof.
  • the compounds of formula (I) may contain at least one chiral carbon, and hence they may exist in one or more stereoisomeric forms. For example, when
  • R* together with R 2 represents a bond and R3 ⁇ R4, the compounds of formula (I) exist as geometric isomers.
  • the present invention encompasses all of the stereoisomeric forms of the compounds of formula (I) and the pharmaceutically acceptable salts thereof, whether as individual stereoisomers or as mixtures of isomers, including racemates.
  • Suitable substituents for any heterocyclyl group include up to 4 substituents selected from the group consisting of: alkyl, alkoxy, aryl and halogen or any two substituents on adjacent carbon atoms, together with the carbon atoms to which they are attached, may form an aryl group, preferably a phenylene group, and wherein the carbon atoms of the aryl group represented by the said two substituents may themselves be substituted or unsubstituted.
  • the term 'aryl' includes phenyl and naphthyl; any aryl group mentioned herein may be optionally substituted with up to five, preferably up to three, groups selected from halogen, alkyl, phenyl, alkoxy, haloalkyl, hydroxy, amino, nitro, carboxy, alkoxycarbonyl, alkoxycarbonylalkyl, alkylcarbonyloxy, or alkylcarbonyl groups.
  • 'halogen' refers to fluorine, chlorine, bromine and iodine; preferably chlorine.
  • alkyl groups are alkyl groups having straight or branched carbon chains, containing up to 12 carbon atoms.
  • suitable alkyl groups are -12 alkyl groups, especially C . alkyl groups e.g. methyl, ethyl, n-propyl, iso-propyl, n-butyl, isobutyl or tert-butyl groups.
  • Suitable substituents for any alkyl group include those indicated above in relation to the term "aryl”.
  • Suitable acyl groups include alkylcarbonyl groups
  • Suitable pharmaceutically acceptable salts include salts of carboxy groups and acid addition salts.
  • Suitable pharmaceutically acceptable salts of carboxy groups include metal salts, such as for example aluminium, alkali metal salts such as lithium, sodium or potassium, alkaline earth metal salts such as calcium or magnesium and ammonium or substituted ammonium salts, for example those with lower alkylamines such as triethylamine, hydroxy alkylamines such as 2-hydroxyethylamine, bis-(2-hydroxyethyl)-amine or tri-(2-hydroxyethyl)-amine, cycloalkylamines such as bicyclohexylamine, or with procaine, dibenzylpiperidine,
  • metal salts such as for example aluminium
  • alkali metal salts such as lithium, sodium or potassium
  • alkaline earth metal salts such as calcium or magnesium
  • ammonium or substituted ammonium salts for example those with lower alkylamines such as triethylamine, hydroxy alkylamines such as 2-hydroxyethylamine, bis-(2-hydroxyethy
  • Suitable acid addition salts include pharmaceutically acceptable inorganic salts such as the sulphate, nitrate, phosphate, borate, hydrochloride and hydrobromide and pharmaceutically acceptable organic acid addition salts such as acetate, tartrate, maleate, citrate, succinate, benzoate, ascorbate, methane-sulphonate, ⁇ -keto glutarate and ⁇ -glycerophosphate.
  • pharmaceutically acceptable inorganic salts such as the sulphate, nitrate, phosphate, borate, hydrochloride and hydrobromide
  • pharmaceutically acceptable organic acid addition salts such as acetate, tartrate, maleate, citrate, succinate, benzoate, ascorbate, methane-sulphonate, ⁇ -keto glutarate and ⁇ -glycerophosphate.
  • Suitable pharmaceutically acceptable solvates include hydrates.
  • the present invention also provides a process for the preparation of a compound of formula (I), or a tautomeric form thereof, and/or a pharmaceutically acceptable salt thereof, and/or a pharmaceutically acceptable solvate thereof, which process comprises reacting a compound of formula (II):
  • R (ii) wherein A 2 , R! and R 2 are as defined in relation to formula (I), R ⁇ represents R ⁇ as defined in relation to formula (I) or a protected form thereof, R ⁇ represents R 4 as defined in relation to formula (I) or a protected form thereof and R a is a moiety convertible to a moiety of formula (f):
  • A*, X and n are as defined in relation to formula (I), with an appropriate reagent capable of converting R a to the said moiety (f) and thereafter, if required, carrying out one or more of the following optional steps:
  • an appropriate reagent capable of converting R a to the said moiety (f) is a compound of formula (III):
  • a , X and n are as defined in relation to formula (I) and L ⁇ represents a leaving group, such as a tosylate or mesylate group.
  • R a is OH the compound of formula (II) is in an activated form.
  • a suitable activated form of a compound of formula (II) is an anionic form such as a salted form and especially an alkali metal salted form, for example a sodium salted form.
  • the activated form of the compound of formula (II) may be prepared using any appropriate method, thus when the activated form is a salted form the compound of formula (II) may be treated with an appropriate salting agent, for example an appropriate metal hydride base such as sodium hydride.
  • reaction between the compound of formula (II) and the salting agent may be carried out in any appropriate solvent such as an aprotic solvent for example dimethylformamide at any temperature providing a convenient rate of formation of the required product, such as a low to ambient temperature, for example a temperature in the range of from -10°C to 30°C, conveniently at 0°C.
  • an aprotic solvent for example dimethylformamide
  • a low to ambient temperature for example a temperature in the range of from -10°C to 30°C, conveniently at 0°C.
  • reaction between the compound of formula (II) and the appropriate reagent capable of convening R a to the said moiety (f) may be carried out under conditions suitable to the particular compound of formula (II) and the reagent chosen:
  • the abovementioned reaction between the activated form of the compound of formula (II) wherein R a represents OH, and the reagent of the abovedefined formula (III) may be carried out under conventional alkylation conditions, for example in an aprotic solvent, such as dimethylformamide, at any temperature providing a convenient rate of formation of the required product, such as an elevated temperature, for example in the range from 40°C to 120°C, for example at 80°C.
  • the formation of the activated form of (II)- for example the formation of a salted form of (II) - may be carried out in-situ prior to the reaction of the activated form of (II) with the above defined compound of formula (III).
  • the compounds of formula (II) are known compounds or they may be prepared using methods analogous to those used to prepare known compounds, for example those disclosed in Chemical Abstracts 101 (4) 31523f or Chem. Pharm. Bull., 1983, 31, 560.
  • the compounds of formula (HI) are known compounds or they may be prepared using methods analogous to those used to prepare known compounds, for example those disclosed in EP0306228.
  • a compound of formula (I), or a tautomeric form thereof, and/or a pharmaceutically acceptable salt thereof and/or a pharmaceutically acceptable solvate thereof, may also be prepared by reacting a compound of formula (IV):
  • R 3 represents R 3 as defined in relation to formula (I) or a protected form thereof and R 4 ' represents R 4 as defined in relation to formula (I) or a protected form thereof; and thereafter if required carrying out one or more of the following optional steps:
  • R 3 or (R 4 ) in the required compound of formula (I) is COOH
  • the corresponding group R 3 (or R 4 ') in the compound of formula (V) is usually in the form of a protected COOH group, suitably an ester, for example a C ⁇ . alkyl ester.
  • R 3 ' is R 3 and R 4 ' is R 4 .
  • the reduction of the compound of formula (I) wherein R and R 2 together represent a bond may be carried out as described below.
  • the compounds of formula (IV) are known compounds or they may be prepared using methods analogous to those used to prepare known compounds, for example those disclosed in EP0306228.
  • the compounds of formula (V) are known compounds or they may be prepared using methods analogous to those used to prepare known compounds, for example those disclosed in Advanced Organic Chemistry, J. March, New York, Wiley.
  • the abovementioned conversion of a compound of formula (I) into a further compound of formula (I) includes: a) converting one group R into another group R; b) converting compounds wherein R and R 2 together represent a bond into compounds wherein R and R 2 each represent hydrogen; and c) conversion of one group R 3 into another group R 3 and/or conversion of one group R 4 into another group R 4 .
  • the conversion of a compound of formula (I) to a further compound of formula (I) may be carried out by using any appropriate conventional procedure.
  • Suitable conversions of one group R into another group R include converting a group R which represents hydrogen into a group R which represents an acyl group; such conversion may be carried out using an appropriate conventional acylation procedure, for example treating an appropriately protected compound of formula (I) with an acylating agent.
  • acetic anhydride may be used to prepare the compound of formula (I) wherein R is acetyl.
  • conversion (b) may be carried out using conventional hydrogenation methods, such as catalytic hydrogenation, or by dissolving metal reduction, for example using magnesium in methanol reduction as disclosed in Tetrahedron Lett. 1986, 27, 2409.
  • conversion (c) may be carried out using the appropriate conventional procedure, for example when R 3 and R 4 each independently represent a group CO2CH3, they may each be converted to a group CO2H by using lithium hydroxide in aqueous tetrahydrofuran or aqueous methanol. It will be appreciated that in any of the abovementioned reactions including the abovementioned conversions (a), (b) and (c) any reactive group in the substrate molecule may be protected, according to conventional chemical practice.
  • Suitable protecting groups in any of the abovementioned reactions are those used conventionally in the art.
  • suitable hydroxyl protecting groups include benzyl or trialkylsilyl groups.
  • benzyloxy group may be prepared by treatment of the appropriate compound with a benzyl halide, such as benzyl bromide, and thereafter, if required, the benzyl group may be conveniently removed using catalytic hydrogenation or a mild ether cleavage reagent such as trimethylsilyl iodide or boron tribromide.
  • a benzyl halide such as benzyl bromide
  • the isomeric forms of the compounds of formula (I) and the pharmaceutically acceptable salts thereof may be prepared as individual isomers using conventional chemical procedures.
  • the compounds of the invention are indicated as having useful therapeutic properties:
  • the present invention accordingly provides a compound of formula (I), or a tautomeric form thereof and/or a pharmaceutically acceptable salt thereof and/or a pharmaceutically acceptable solvate thereof, for use as an active therapeutic substance.
  • the present invention provides a compound of formula (I), or a tautomeric form thereof and/or a pharmaceutically acceptable salt thereof and/or a pharmaceutically acceptable solvate thereof, for use in the treatment of and/or prophylaxis of hyperglycaemia.
  • the present invention also provides a compound of formula (I), or a tautomeric form thereof and/or a pharmaceutically acceptable salt thereof and/or a pharmaceutically acceptable solvate thereof, for use in the treatment and/or prophylaxis of hyperlipidaemia.
  • the present invention also provides a compound of formula (I) or a tautomeric form thereof and/or a pharmaceutically acceptable salt thereof and/or a pharmaceutically acceptable solvate thereof for use in the treatment of hypertension, cardiovascular disease and certain eating disorders.
  • Cardiovascular disease includes in particular atherosclerosis.
  • Certain eating disorders include in particular the regulation of appetite and food intake in subjects suffering from disorders associated with under-eating , such as anorexia nervosa, and disorders associated with over-eating, such as obesity and anorexia bulimia.
  • a compound of formula (I), or a tautomeric form thereof and/or a pharmaceutically acceptable salt thereof and/or a pharmaceutically acceptable solvate thereof may be administered p ⁇ r $£ or, preferably, as a pharmaceutical composition also comprising a pharmaceutically acceptable carrier.
  • the present invention also provides a pharmaceutical composition
  • a pharmaceutical composition comprising a compound of the general formula (I), or a tautomeric form thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, and a pharmaceutically acceptable carrier therefor.
  • the term 'pharmaceutically acceptable embraces compounds, compositions and ingredients for both human and veterinary use: for example the term 'pharmaceutically acceptable salt' embraces a veterinarily acceptable salt.
  • composition may, if desired, be in the form of a pack accompanied by written or printed instructions for use.
  • compositions of the present invention will be adapted for oral administration, although compositions for administration by other routes, such as by injection and percutaneous absorption are also envisaged.
  • 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 carrier may comprise a diluent, filler, disintegrant, wetting agent, lubricant, colourant, flavourant or other conventional adjuvant.
  • Typical carriers include, for example, microcrystalline cellulose, starch, sodium starch glycollate, polyvinylpyrrolidone, polyvinylpolypyrrolidone, magnesium stearate or sodium lauryl sulphate.
  • composition will be formulated in unit dose form.
  • unit dose will normally contain an amount of the active ingredient in the range of from 0.1 to 1000 g, more usually 0.1 to 500 mg, and more especially 0.1 to 250 mg.
  • the present invention further provides a method for the treatment and/or prophylaxis of hyperglycaemia in a human or non-human mammal which comprises administering an effective, non-toxic, amount of a compound of the general formula (I), or a tautomeric form thereof and/or a pharmaceutically acceptable salt thereof and/or a pharmaceutically acceptable solvate thereof to a hyperglycaemic human or non-human mammal in need thereof.
  • the present invention further provides a method for the treatment of hyperlipidaemia 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 and/or a pharmaceutically acceptable salt thereof and/or a pharmaceutically acceptable solvate thereof, to a hyperlipidaemic human or non-human mammal in need thereof.
  • the active ingredient may be administered as a pharmaceutical composition hereinbefore defined, and this forms a particular aspect of the present invention.
  • the compound of the general formula (I), or a tautomeric form thereof and/or a pharmaceutically acceptable salt thereof and/or a pharmaceutically acceptable solvate thereof may be taken in doses, such as those described above, one to six times a day in a manner such that the total daily dose for a 70 kg adult will generally be in the range of from 0.1 to 6000 mg, and more usually about 1 to 1500 mg.
  • the active ingredient may be adminstered by mouth, usually once or twice a day and in an amount in the range of from about 0.025 mg kg to 25 mg kg, for example 0.1 mg/kg to 20 mg/kg. Similar dosage regimens are suitable for the treatment and/or prophylaxis of hyperlipidaemia in non-human mammals.
  • the dosages regimens for the treatment of hypertension, cardiovascular disease and eating disorders will generally be those mentioned above in relation to hyperglycaemia.
  • the present invention provides the use of a compound of formula (I), or a tautomeric form thereof and/or a pharmaceutically acceptable salt thereof and/or a pharmaceutically acceptable solvate thereof, for the manufacture of a medicament for the treatment and/or prophylaxis of hyperglycaemia.
  • the present invention also provides the use of a compound of formula (I), or a tautomeric form thereof and/or a pharmaceutically acceptable salt thereof, and/or a pharmaceutically acceptable solvate thereof, for the manufacture of a medicament for the treatment and/or prophylaxis of hyperlipidaemia, hypertension, cardiovascular disease or certain eating disorders.
  • the title compound was prepared from methyl 2-acetyl-3-(4- hydroxyphenyl)propanoate and 2-[N-(2-benzoxazolyl)-N-methylamino]ethanol metiianesulphonyl ester (Eur. Patent. AppL, Publication No. 0306228) by a procedure similar to that described in Example 1.
  • the crude product was chromatographed on silica gel using 10 to 50% (gradient elution) ethyl acetate in hexane. Further chromatography on silica gel with 50 to 75% diethyl ether in hexane as eluent gave the title compound as an oil.
  • mice C57bll/6 obese (ob/ob) mice were fed on powdered oxoid diet. After at least one week, the mice continued on a powdered oxoid diet or were fed powered oxoid diet containing the test compound. After 8 days on the supplemented diet all of the mice were fasted for 5 hours prior to receiving an oral load of glucose (3g/kg). Blood samples for glucose analysis were taken 0,45,90 and 135 minutes after glucose administration and the results appear below as the percentage reduction in area under the blood glucose curve where test compound treated groups are compared with the control group. 8 mice were used for each treatment.

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  • Pyridine Compounds (AREA)

Abstract

L'invention concerne un composé de la formule (I) ou une forme tautomère et/ou ses sels acceptables sur le plan pharmaceutique, et/ou un solvate pharmaceutiquement acceptable dudit composé. Dans cette formule, A1 représente un groupe aromatique hétérocyclique substitué ou non substitué; A2 représente un noyau benzène ayant trois substituants facultatifs; R1 et R2 représentent d'une manière indépendante hydrogène, ou R1 et R2 forment ensemble une liaison; R3 et R4 représentent chacun d'une manière indépendante un groupe nitrile ou un groupe de la formule -COR5, dans laquelle R5 représente un hydroxy, un alcoxy, un alkyle, un aryle ou un groupe de la formule -NR6R7 dans laquelle R6 et R7 représentent d'une manière indépendante l'hydrogène ou un alkyle, ou R6 et R7 forment ensemble un noyau hétérocyclique avec l'atome d'azote auquel ils sont liés; X représente NR, R représentant un atome d'hydrogène, un groupe alkyle, un groupe acyle, un groupe aralkyle avec une fraction aryle substituée ou non, ou encore un groupe aryle substitué ou non; et n est un nombre entier de 2 à 6. L'invention concerne également un procédé de préparation d'un tel composé, une composition pharmaceutique contenant un tel composé et l'utilisation d'un tel composé et d'une telle composition en médecine.
PCT/EP1993/003269 1992-12-04 1993-11-22 Derives heterocycliques et leur utilisation comme produits pharmaceutiques WO1994013650A1 (fr)

Priority Applications (1)

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JP6513713A JPH08504199A (ja) 1992-12-04 1993-11-22 複素環誘導体および医薬におけるそれらの使用

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GB9225386.3 1992-12-04
GB929225386A GB9225386D0 (en) 1992-12-04 1992-12-04 Novel compounds

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Cited By (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999016758A1 (fr) * 1997-10-27 1999-04-08 Dr. Reddy's Research Foundation Nouvelles compositions heterocycliques et leur utilisation en medecine; procedes de leur fabrication et compositions pharmaceutiques les contenant
WO1999019313A1 (fr) * 1997-10-27 1999-04-22 Dr. Reddy's Research Foundation Nouveaux composes tricycliques et leur utilisation en medecine, procede de preparation de ces derniers et compositions pharmaceutiques les contenant
EP0930299A4 (fr) * 1996-08-19 1999-07-21
US6054453A (en) * 1997-10-27 2000-04-25 Redd's Research Foundation Tricyclic compounds and their use in medicine process for their preparation and pharmaceutical compositions containing them
WO2000066572A1 (fr) * 1999-04-28 2000-11-09 Dr. Reddy's Research Foundation Heterocycles bicycliques substitues, procede pour leur preparation et leur utilisation comme agents contre l'obesite et comme agents hypocholesterolemiques
US6194446B1 (en) 1996-07-01 2001-02-27 Eli Lilly And Company Hypoglycemic and hypolipidemic compounds
US6265401B1 (en) 1997-10-27 2001-07-24 Reddy-Cheminor, Inc. Bicyclic compounds and their use in medicine, process for their preparation and pharmaceutical compositions containing them
US6294580B1 (en) 1996-02-28 2001-09-25 Glaxo Wellcome Inc. Substituted 4-hydroxy-phenylalcanoic acid derivatives with agonist activity to PPAR-gamma
US6369067B1 (en) 1997-10-27 2002-04-09 Dr. Reddy's Research Foundation Monocyclic compounds and their use in medicine: process for their preparation and pharmaceutical compositions containing them
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WO2002100812A1 (fr) * 2001-04-20 2002-12-19 Eisai Co., Ltd. Dérivé de l'acide carboxylique et son sel
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US6555577B1 (en) 2000-01-28 2003-04-29 Novo Nordisk A/S Compounds, their preparation and use
WO2003053974A1 (fr) * 2001-12-21 2003-07-03 Dr. Reddy's Laboratories Ltd. Nouveaux composes et leur utilisation en medecine, procede de preparation de ceux-ci et compositions pharmaceutiques les contenant
US6642389B2 (en) 2001-05-15 2003-11-04 Hoffmann-La Roche Inc. Oxazole derivatives
US6747049B2 (en) 2002-07-03 2004-06-08 Hoffmann-La Roche Inc. Oxazole derivatives
US6809095B2 (en) 1997-10-27 2004-10-26 Dr. Reddy's Laboratories Ltd. Bicyclic compounds and their use in medicine; process for their preparation and pharmaceutical compositions containing them
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US7098228B2 (en) 2002-11-25 2006-08-29 Hoffmann-La Roche Inc. Indolyl derivatives
US7192970B2 (en) * 2002-11-26 2007-03-20 Chipscreen Biosciences, Ltd. Noncyclic 1,3-dicarbonyl compounds as dual PPAR agonists with potent antihyperglycemic and antihyperlipidemic activity
US7220877B2 (en) 2001-10-17 2007-05-22 Novo Nordisk A/S Compounds, their preparation and use
BG65370B1 (bg) * 2000-01-19 2008-04-30 Cadila Healthcare Ltd. Съединения с хиполипидемично и хипохолестеремичнодействие, метод за производството им и фармацевтични композиции, които ги съдържат
US7371777B2 (en) 2001-08-17 2008-05-13 Eisai Co., Ltd. Cyclic compound and PPAR agonist
US7816385B2 (en) 2002-12-20 2010-10-19 High Point Pharmaceuticals, Llc Dimeric dicarboxylic acid derivatives, their preparation and use
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US9814697B2 (en) 2013-04-22 2017-11-14 Cadila Healthcare Limited Composition for nonalcoholic fatty liver disease (NAFLD)
US10098868B2 (en) 2013-07-25 2018-10-16 Cadila Healthcare Limited Formula comprising a hypolipidemic agent
US10112898B2 (en) 2013-09-06 2018-10-30 Cadila Healthcare Limited Process for the preparation of saroglitazar pharmaceutical salts
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991019702A1 (fr) * 1990-06-14 1991-12-26 Pfizer Inc. Derives d'acide 3-aryl-2-hydroxypropionique et leurs analogues utilises comme agents hypoglycemiques
WO1992002520A1 (fr) * 1990-08-06 1992-02-20 Beecham Group P.L.C. Derives d'oxazolidine dione

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991019702A1 (fr) * 1990-06-14 1991-12-26 Pfizer Inc. Derives d'acide 3-aryl-2-hydroxypropionique et leurs analogues utilises comme agents hypoglycemiques
WO1992002520A1 (fr) * 1990-08-06 1992-02-20 Beecham Group P.L.C. Derives d'oxazolidine dione

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
TAKASHI SOHDA ET AL: "Studies on antidiabetic agents.II. Synthesis of 5-[4-(1-methylcyclohexylmethoxy)-benzyl]thiazolidine-2,4-dione(ADD-3878) and its derivatives", CHEMICAL AND PHARMACEUTICAL BULLETIN., vol. 30, no. 10, October 1982 (1982-10-01), TOKYO JP, pages 3580 - 3600 *

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