WO2005042483A1 - [r-(r*,r*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-((1-methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]- 1h-pyrrole-1-heptanoic acid iron salt - Google Patents

[r-(r*,r*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-((1-methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]- 1h-pyrrole-1-heptanoic acid iron salt Download PDF

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WO2005042483A1
WO2005042483A1 PCT/IN2003/000351 IN0300351W WO2005042483A1 WO 2005042483 A1 WO2005042483 A1 WO 2005042483A1 IN 0300351 W IN0300351 W IN 0300351W WO 2005042483 A1 WO2005042483 A1 WO 2005042483A1
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Prior art keywords
methylethyl
phenylamino
pyrrole
dihydroxy
beta
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PCT/IN2003/000351
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French (fr)
Inventor
Sambasivam Ganesh
Goutam Das
Shankara Rao Arvind Atignal
Kiran Mazumdar-Shaw
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Biocon Limited
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Priority to AU2003278597A priority Critical patent/AU2003278597A1/en
Priority to PCT/IN2003/000351 priority patent/WO2005042483A1/en
Publication of WO2005042483A1 publication Critical patent/WO2005042483A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • 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

Definitions

  • the instant invention relates to a novel compound, namely, [R-(R*, *)]-2-(4-f luorophenyl)-beta, delta-dihydroxy-5-((l- methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]-lH-pyrrole-l- heptanoic acid iron salt.
  • HMG-CoA reductase inhibitor compounds of a class called statins inhibit the enzyme from catalyzing this conversion. As such, statins are collectively potent lipid lowering agents.
  • Trans-(+-)- 5-(4-fluorophenyl)- 2-(l-methylethyl)- N,4- diphenyl- l-[2-tetra hydro- 4-hydroxy- 6-oxo- 2H-pyran-2-yl) ethyl] -lH-pyrrole -3-carboxamides are among compounds of U.S. Pat. No. 4,681,893 which have usefulness as inhibitors of HMG CoA reductase responsible for cholesterol biosynthesis.
  • the compounds therein generally include 4-hydroxypyran-2-ones and the corresponding ring-opened acids derived therefrom.
  • the amine is selected from the ⁇ o group consisting of (+-)-l,2-dimethylpropylamine, 3-(2- aminoethylamino)-propylamine, n-butylamine, secondary butylamine, tertiary butylamine, dibutylamine, tertiary amylamine, cyclopentylamine, cyclohexylamine, cycloheptylamine, dicyclohexylamine, N-methylcyclohexylamine, N,N'- i5 diisopropylethylenediamine, l ⁇ I,N'-diethylenediamine, N-methyl- 1,3- propanediamine, N-methylethylenediamine, N,N,N',N'-tetramethyl- 1,2-diaminoethane, N,N,N',N'-tetramethyl-l,4-diaminobutane, N N ⁇ N'-tetramethyl-l,
  • HMG-CoA reductase inhibitor is selected from the group consisting of mevastatin, pravastatin, lovastatin, simvastatin, fluvastatin and atorvastatin. It is known that 3-hydroxy-3-methylglutaryl coenzyme A
  • HMG-CoA HMG-CoA
  • 3R form of atorvastatin is the most active form.
  • Atorvastatin calcium disclosed in U.S. 5,273,995, which is incorporated herein by reference, is a selective, competitive inhibitor of HMG-Co A reductase.
  • the instant invention related to a novel salt of [R-(R*,R*)]-2-
  • the present invention provides for a compound [R-(R*,R*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-((l- methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]-lH-pyrrole-l- heptanoic acid iron salt.
  • the present invention also relates to a pharmaceutical composition, useful as a hypocholesterolemic agent, comprising an effective amount of [R-(R*,R*)]-2-(4-fluorophenyl)-beta, delta- dihydroxy-5-((l-methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid iron salt and a pharmaceutically acceptable carrier.
  • the present invention is also a method of treating mammals, including humans, suffering from hypercholesterolemia by administering to such mammal, a dosage form of the pharmaceutical composition described above. DESCRIPTION OF FIGURES FIGURE I. 13 C NMR of the compound of formula I. FIGURE II.
  • the other embodiment of the invention is the process for preparation of [R-(R*,R*)]- 2-(4-fluorophenyl)-beta, delta- dihydroxy -5-((l-methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid iron salt.
  • the pharmaceutically acceptable salt of the invention is generally derived from a salt of [R-(R*,R*)]-2-(4-fluorophenyl)- beta, delta-dihydroxy-5-((l-methylethyl) -3-phenyl-4- [(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid, the free acid, the lactone or a derivative thereof.
  • the pharmaceutically acceptable salt of the invention can be derived by dissolving a salt of [R-(R*,R*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-((l-methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid, in water or aqueous alcohol or other suitable solvents, extracting the free acid or lactone into water immiscible solvent, isolating the acid or lactone or mixture thereof by vaporizing the solvent; treating the residue with an alcohol or a water rniscible solvent, optionally containing base; optionally adjusting the pH; treating the solution with an iron compound or a source of iron ion and isolating the compound of present invention.
  • the pharmaceutically acceptable salt of the invention can be derived by dissolving an ester of [R-(R*,R*)]-2-(4-fluorophenyl)- beta, delta-dihydroxy-5-((l-methylethyl) -3-phenyl-4- [(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid, in aqueous or aqueous alcohol solvent or other suitable solvents, adjusting pH of the mixture; vaporizing the solvents; optionally treating with a water immiscible solvent; optionally adjusting the pH; treating the solution with a iron compound and isolating the compound of present invention.
  • the pharmaceutically acceptable salt of the invention can be derived by dissolving a salt of [R-(R*,R*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-((l-methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid; in aqueous or aqueous alcoholic solvent or other suitable solvents; optionally adjusting pH of the mixture; treating the solution with a iron compound and isolating the compound of present invention.
  • the third embodiment of the present invention is the pharmaceutical composition prepared from [R-(R*,R*)]- 2-(4- fluorophenyl)-beta, delta-dihydroxy -5-((l-methylethyl) -3-phenyl- 4-[(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid iron salt.
  • the present invention relates to a method treatment of hypolipidemia using compound of formula I.
  • the compound of the present invention utilized in the pharmaceutical method of this invention are administered to the patient at dosage levels of from 2 to 500 mg per day which for a normal human adult of approximately 75 kg is a dosage of from 0.1 to 8 mg/kg of body weight per day.
  • the dosages may be preferably from 0.4 to 1.5 mg/kg per day.
  • the dosage is preferably administered as a unit dosage form.
  • the unit dosage form for oral or parenteral use may be varied or adjusted from 10 to 500 mg, preferably from 20 to 100 mg according to the particular application and the potency of the active ingredient.
  • the compositions can, if desired, also contain other active therapeutic agents. Determinations of optimum dosages for a particular situation is within the skill of the art.
  • the compound present invention is in general equivalent for the activity of the utility as described herein. The following examples illustrate the invention but does not limit it in any way.
  • Example 2 A solution of sodium salt of [R-(R*,R*)]-2-(4-fluorophenyl beta, de!ta-dihydroxy-5-((l-methylethyl) -3-phenyl-4-
  • Example 3 A solution of sodium salt of [R-(R*,R*)]-2-(4-fluorophenyl)- beta, delta-dihydroxy-5-((l-methylethyl) -3-phenyl-4- [(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid (100 g, 0.172 mol) in water (2 L) was washed with methyl tert-butyl ether (500 ml) and warmed to 40-45°C. A solution of ferrous chloride (10.8 g, 0.086 mol) in water (200 ml) was added to the reaction mixture under stirring.

Abstract

A compound, [R-(R*, R*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)-carbonyl]-7H-pyrrole-1-heptanoic acid iron salt, a process of its preparation, a pharmaceutical composition containing the novel compound and a method of treatment comprising the novel compound is disclosed.

Description

TITLE OF THE INVENTION [R-(R*,R*)]-2-(4-FLUOROPHENYL)-BETA, DELTA-
DIHYDROXY-5-((l-METHYLETHYL) -3-PHENYL-4- [(PHENYLAMINO) CARBONYL]-lH-PYRROLE-l-HEPTANOIC ACID IRON SALT FIELD OF THE INVENTION The instant invention relates to a novel compound, namely, [R-(R*, *)]-2-(4-f luorophenyl)-beta, delta-dihydroxy-5-((l- methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]-lH-pyrrole-l- heptanoic acid iron salt. BACKGROUND OF THE INVENTION The conversion of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) to mevalonate is a rate-limiting step in the cholesterol biosynthetic pathway. This step is catalyzed by the enzyme HMG- CoA reductase. HMG CoA reductase inhibitor compounds of a class called statins inhibit the enzyme from catalyzing this conversion. As such, statins are collectively potent lipid lowering agents. Trans-(+-)- 5-(4-fluorophenyl)- 2-(l-methylethyl)- N,4- diphenyl- l-[2-tetra hydro- 4-hydroxy- 6-oxo- 2H-pyran-2-yl) ethyl] -lH-pyrrole -3-carboxamides are among compounds of U.S. Pat. No. 4,681,893 which have usefulness as inhibitors of HMG CoA reductase responsible for cholesterol biosynthesis. The compounds therein generally include 4-hydroxypyran-2-ones and the corresponding ring-opened acids derived therefrom. US 5,273,995 claims (R-(R*R*))-2-(4-fiuorophenyl)-beta, delta-dihydroxy-5-(l-methylethyl-3-phenyl- 4((phenylamino)carbonyl)-lH-pyrrolyl-l-heptanoic acid, its lactone 5 form and salts thereof. The salts specifically claimed here are monosodium, monopotassium, hemicalcium, N-methyl glucamine, hemimagnesium and hemizinc. WO 2000017150 claims a salt of an HMG-CoA reductase inhibitor with an amine. Specifically the amine is selected from the ιo group consisting of (+-)-l,2-dimethylpropylamine, 3-(2- aminoethylamino)-propylamine, n-butylamine, secondary butylamine, tertiary butylamine, dibutylamine, tertiary amylamine, cyclopentylamine, cyclohexylamine, cycloheptylamine, dicyclohexylamine, N-methylcyclohexylamine, N,N'- i5 diisopropylethylenediamine, l\I,N'-diethylenediamine, N-methyl- 1,3- propanediamine, N-methylethylenediamine, N,N,N',N'-tetramethyl- 1,2-diaminoethane, N,N,N',N'-tetramethyl-l,4-diaminobutane, N N^N'-tetramethyl-l/β-diaminohexane, 1,2-dipiperidinethane, dipiperidinemethane, 2-amino-3,3-dimethylbutane, N,N-
2o dimethylcyclohexylamine, neopentylamine, adamantylamine, N,N- diethylcyclohexylamine, N-isopropylcyclohexylamine, N- methylcyclohexylamine, cyclobutylamine, norborylamine, n- butylamine, secondary butylamine, tertiary butylamine, dibutylamine, tertiary amylamine, cyclohexylamine,
25 dicyclohexylamine, N-methylcyclohexylamine and N,N'- diisopropylethylenediamine. Specifically the HMG-CoA reductase inhibitor is selected from the group consisting of mevastatin, pravastatin, lovastatin, simvastatin, fluvastatin and atorvastatin. It is known that 3-hydroxy-3-methylglutaryl coenzyme A
30 (HMG-CoA) exists as the 3R-stereoisomer. The 3R form of atorvastatin is the most active form. Atorvastatin calcium, disclosed in U.S. 5,273,995, which is incorporated herein by reference, is a selective, competitive inhibitor of HMG-Co A reductase. The instant invention related to a novel salt of [R-(R*,R*)]-2-
(4-fluorophenyl)-beta, delta-dihydroxy-5-((l-methylethyl) -3- phenyl-4-[(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid, namely, [R-(R*,R*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-
((1-methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]-lH-pyrrole-
1-heptanoic acid iron salt.
SUMMARY OF THE INVENTION Accordingly the present invention provides for a compound [R-(R*,R*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-((l- methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]-lH-pyrrole-l- heptanoic acid iron salt. The present invention also relates to a pharmaceutical composition, useful as a hypocholesterolemic agent, comprising an effective amount of [R-(R*,R*)]-2-(4-fluorophenyl)-beta, delta- dihydroxy-5-((l-methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid iron salt and a pharmaceutically acceptable carrier. Further, the present invention is also a method of treating mammals, including humans, suffering from hypercholesterolemia by administering to such mammal, a dosage form of the pharmaceutical composition described above. DESCRIPTION OF FIGURES FIGURE I. 13C NMR of the compound of formula I. FIGURE II. XH NMR of the compound of formula I. DETAILED DESCRIPTION OF THE INVENTION The most preferred embodiment of the present invention is [R-(R*,R*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-((l- methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]-lH-pyrrole-l- heptanoic acid iron salt. The compound according to present invention inhibits biosynthesis of cholesterol. The other embodiment of the invention is the process for preparation of [R-(R*,R*)]- 2-(4-fluorophenyl)-beta, delta- dihydroxy -5-((l-methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid iron salt. The pharmaceutically acceptable salt of the invention is generally derived from a salt of [R-(R*,R*)]-2-(4-fluorophenyl)- beta, delta-dihydroxy-5-((l-methylethyl) -3-phenyl-4- [(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid, the free acid, the lactone or a derivative thereof. The pharmaceutically acceptable salt of the invention can be derived by dissolving a salt of [R-(R*,R*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-((l-methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid, in water or aqueous alcohol or other suitable solvents, extracting the free acid or lactone into water immiscible solvent, isolating the acid or lactone or mixture thereof by vaporizing the solvent; treating the residue with an alcohol or a water rniscible solvent, optionally containing base; optionally adjusting the pH; treating the solution with an iron compound or a source of iron ion and isolating the compound of present invention. The pharmaceutically acceptable salt of the invention can be derived by dissolving an ester of [R-(R*,R*)]-2-(4-fluorophenyl)- beta, delta-dihydroxy-5-((l-methylethyl) -3-phenyl-4- [(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid, in aqueous or aqueous alcohol solvent or other suitable solvents, adjusting pH of the mixture; vaporizing the solvents; optionally treating with a water immiscible solvent; optionally adjusting the pH; treating the solution with a iron compound and isolating the compound of present invention. The pharmaceutically acceptable salt of the invention can be derived by dissolving a salt of [R-(R*,R*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-((l-methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid; in aqueous or aqueous alcoholic solvent or other suitable solvents; optionally adjusting pH of the mixture; treating the solution with a iron compound and isolating the compound of present invention. The third embodiment of the present invention is the pharmaceutical composition prepared from [R-(R*,R*)]- 2-(4- fluorophenyl)-beta, delta-dihydroxy -5-((l-methylethyl) -3-phenyl- 4-[(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid iron salt. Likewise, the present invention relates to a method treatment of hypolipidemia using compound of formula I. The compound of the present invention utilized in the pharmaceutical method of this invention are administered to the patient at dosage levels of from 2 to 500 mg per day which for a normal human adult of approximately 75 kg is a dosage of from 0.1 to 8 mg/kg of body weight per day. The dosages may be preferably from 0.4 to 1.5 mg/kg per day. The dosage is preferably administered as a unit dosage form.
The unit dosage form for oral or parenteral use may be varied or adjusted from 10 to 500 mg, preferably from 20 to 100 mg according to the particular application and the potency of the active ingredient. The compositions can, if desired, also contain other active therapeutic agents. Determinations of optimum dosages for a particular situation is within the skill of the art. The compound present invention is in general equivalent for the activity of the utility as described herein. The following examples illustrate the invention but does not limit it in any way.
EXAMPLES
Example 1 To a suspension of calcium salt of [R-(R*,R*)]-2-(4- fluorophenyl)-beta, delta-dihydroxy-5-((l-methylethyl) -3-phenyl-4-
[(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid (5 g, 0.0043 mol) in water (100 ml), HCI (1.5 N) was added till pH was 3.0-4.0 and extracted with ethyl acetate (3 x 50 ml). The combined organic layer was concentrated. The residue obtained was dissolved in acetone (5 ml) and a solution of sodium hydroxide (0.4 g, 0.01 mol) in water (100 ml) was added and stirred for 30 minutes. The reaction mixture was washed with methyl tert-butyl ether (25 ml) and warmed to 40-45°C. A solution of ferric nitrate.9H20 (1.73 g, 0.0043 mol) in water (10 ml) was added to the reaction mixture under stirring. The resulting mixture was further stirred at 40-45°C for 1 hour and filtered to give iron salt of [R-(R*,R*)]-2-(4- fluorophenyl)-beta, delta-dihydroxy-5-((l-methylethyl) -3-phenyl-4-
[(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid.
Example 2 A solution of sodium salt of [R-(R*,R*)]-2-(4-fluorophenyl beta, de!ta-dihydroxy-5-((l-methylethyl) -3-phenyl-4-
[(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid (5 g, 0.0086 mol) in water (100 ml) was washed with methyl tert-butyl ether (25 ml) and warmed to 40-45°C. A solution of ferrous sulfate.7H20 (2.4 g, 0.0086 mol) in water (10 ml) was added to the reaction mixture under stirring. The resulting mixture was further stirred at 40-45°C for 1 hour and filtered to give iron salt of [R-(R*,R*)]-2-(4- fluorophenyl)-beta, delta-dihydroxy-5-((l-methylethyl) -3-phenyl-4- [(phenylamino) carbonylj-lH-pyrrole-l-heptanoic acid. Example 3 A solution of sodium salt of [R-(R*,R*)]-2-(4-fluorophenyl)- beta, delta-dihydroxy-5-((l-methylethyl) -3-phenyl-4- [(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid (100 g, 0.172 mol) in water (2 L) was washed with methyl tert-butyl ether (500 ml) and warmed to 40-45°C. A solution of ferrous chloride (10.8 g, 0.086 mol) in water (200 ml) was added to the reaction mixture under stirring. The resulting mixture was further stirred at 40-45°C for 2 hours and filtered to give iron salt of [R-(R*,R*)]-2- (4-fluorophenyl)-beta, delta-dihydroxy-5-((l-methylethyl) -3- phenyl-4-[(phenylamino) carbonyI]-lH-pyrrole-l-heptanoic acid.

Claims

We claim:
1. [R-(R*,R*)]-2-(4-fluorophenyl)-beta,delta-dihydroxy-5-(l- methylethyl)-3-phenyl-4-[(phenylamino)-carbonyl]-lH- pyrrole-1-heptanoic acid iron salt.
2. A process for the preparation of a compound of claim 1 comprising of reacting an iron compound with a salt of [R- (R*,R*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-((l- methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]-lH- pyrrole-1-heptanoic acid.
3. A process for the preparation of a compound of claim 1 comprising of reacting an iron compound with [R-(R*,R*)]-2- (4-fluorophenyl)-beta, delta-dihydroxy-5-((l-methylethyl) -3- phenyl-4-[(phenylamino) carbonyl]-lH-pyrrole-l-heptanoic acid free acid, the lactone, a salt or a derivative thereof.
4. The process of claim 2-3, wherein the iron compound is selected from a group comprising ferric nitrate, ferrous nitrate, ferric sulfate, ferrous sulfate, ferric ammonium sulfate or ferrous ammonium sulfate, ferrous chloride or any suitable iron source, or hydrates thereof.
5. A pharmaceutical composition for treating hypercholesterolemia comprising a hypocholesterolemic effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
6. A method of inhibiting cholesterol synthesis in humans suffering from hypercholesterolemia comprising administering a compound of claim 1 in unit dosage form.
10
PCT/IN2003/000351 2003-11-03 2003-11-03 [r-(r*,r*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-((1-methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]- 1h-pyrrole-1-heptanoic acid iron salt WO2005042483A1 (en)

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AU2003278597A AU2003278597A1 (en) 2003-11-03 2003-11-03 (r-(r*,r*))-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-((1-methylethyl) -3-phenyl-4-((phenylamino) carbonyl)- 1h-pyrrole-1-heptanoic acid iron salt
PCT/IN2003/000351 WO2005042483A1 (en) 2003-11-03 2003-11-03 [r-(r*,r*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-((1-methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]- 1h-pyrrole-1-heptanoic acid iron salt

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5273995A (en) * 1989-07-21 1993-12-28 Warner-Lambert Company [R-(R*R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl-3-phenyl-4-[(phenylamino) carbonyl]- 1H-pyrrole-1-heptanoic acid, its lactone form and salts thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5273995A (en) * 1989-07-21 1993-12-28 Warner-Lambert Company [R-(R*R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl-3-phenyl-4-[(phenylamino) carbonyl]- 1H-pyrrole-1-heptanoic acid, its lactone form and salts thereof

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