WO2003022251A1 - Novel stable crystal form of n-trans-4-isopropylcyclohexyl carbonyl)-d-phenylalanine and process of preparation - Google Patents
Novel stable crystal form of n-trans-4-isopropylcyclohexyl carbonyl)-d-phenylalanine and process of preparation Download PDFInfo
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- WO2003022251A1 WO2003022251A1 PCT/IB2001/002080 IB0102080W WO03022251A1 WO 2003022251 A1 WO2003022251 A1 WO 2003022251A1 IB 0102080 W IB0102080 W IB 0102080W WO 03022251 A1 WO03022251 A1 WO 03022251A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/57—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C233/63—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
Definitions
- the present invention relates to novel stable crystal form of N-(trans-4- isopropylcyclohexylcarbonyl)-D-phenylalanine.
- the Crystals of N-(trans-4- isopropylcyclohexylcarbonyl)-D-phenylalanine have different melting point, infra red spectrum and X-ray diffraction patterns from previously known forms, " B- Type” and " H-Type" of the compound .
- N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine is disclosed in Japanese Patent Application Laid Open No. 63-54321 (equivalent to EP-A- 196222 and US 4,816,484) and in J. Med. Chem. 32, 1436-41 ( 1989 ).
- "The Japanese application describes how the compound may be crystallized from aqueous methanol to yield crystals having a melting point of 129° to 130° C. These crystals are in a crystalline form referred to herein as "B-type”.
- An infra red absorption spectrum and powder X-ray diffraction pattern are disclosed in the US patent no. 5463116 Oct. 31 1995".
- N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine of formula (1) is a known substance having therapeutic utility in depressing blood glucose levels.
- the present inventors have made a novel stable crystalline form of N-(trans-4- isopropylcyclohexylcarbonyl)-D-phenylalanine.
- the crystals as formed by the present invention hereinafter designated as the "AL-type" crystals of N-(trans-4- isopropylcyclohexyl carbonyl)-D-phenylalanine are substantially stable to the physical grinding. Such crystals are therefore more suitable for use in medicines than the existing crystals of N-(trans-4- isopropylcyclohexyl carbonyl)-D-phenylalanine
- the new form is different than previously known disclosed forms : so called “B- type” and "H-type".
- the inventors have designated the new stable crystalline form of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine as "AL-type”.
- N-(cyclohexylcarbonyl)-D-phenylalanines and related compounds A new class of oral hypoglycemic agents. 2.
- the " AL-type" Crystals of N-(trans-4-isopropylcyclohexyl carbonyl)-D- phenylalanine may be formed by crystallization from solution, the crystallization from solution taking place at a temperature between 30°C and the boiling point of the solvent.
- the crystals thus formed generally comprise enhanced amounts of " AL-type" crystals relative to the starting N-(trans-4-isopropylcyclohexylcarbonyl)-D- phenylalanine.
- crystallization at about 30 °C may be performed in several ways as will be apparent to those of skill in the art.
- -(trans-4-isopropylcyclohexylcarbonyl)-D- phenylalanine " B-type" crystals may be dissolved in a solvent in which it is readily soluble at higher temperature but in which it is only sparingly soluble at lower temperatures.
- Solvents which are suitable for use in this invention may be selected from the group comprising dimethyl formamide, dimethylacetamide and acetonitrile.
- the solvent is acetonitrile.
- the dissolution volume of the solvent is preferably from 8 to 60 vol % of the solvent.
- the temperature of the solution is preferably 55° C to 75°C.
- the new crystals were obtained from the solution by filtration or centrifuging and then dried at a temperature in the range 50° C to 90°C
- FIGURE 1 Shows differential scanning calorimeter (DSC) of "AL-type" crystal form of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylaIanine.
- FIGURE. 2 Shows a powder X-ray diffraction pattern of "AL-type" crystal form of N-(trans-4-isopropyIcyclohexylcarbonyl)-D-phenylalanine in accordance with the present invention.
- FIGURE. 3 Shows an infra red absorption spectrum of "AL-type" crystal form of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine in accordance with the present invention.
- FIGURE 4 Shows a crystals photograph of "AL-type" form of N-(trans-4- isopropylcyclohexylcarbonyl)-D-phenylalanine in accordance with the present invention.
- FIGURE. 5 Shows a crystals photograph of "H-type” form of N-(trans-4- isopropy!cyclohexylcarbonyI)-D-phenylalanine.
- FIGURE 6 Shows a crystals photograph of "B-type” form of N-(trans-4- isopropylcyclohexylcarbonyl)-D-phenylalanine.
- the present invention provides a stable "AL- type” crystalline form of N-(trans- 4-isopropylcyclohexyl carbonyl)-D-phenylalanine.
- the various examples of the physical properties of the "AL-type" crystal form of N-(trans-4- isopropylcyclohexyl carbonyl)-D-phenylalanine are as follows.
- the inventors have measured the melting point of new "AL-type" crystals of N- (trans-4-isopropylcyclohexyl carbonyl)-D-phenylalanine and found it to be in the range of 174° to 178° C.
- the powder X-ray diffraction patterns of new " AL-type” crystals of N-(trans-4- isopropylcyclohexyl carbonyl)-D-phenylalanine as shown in Anex-2 is obtained by using a Philips PW1700 powder diffractometer and a scan speed of 0.05.degree./sec.
- the observed powder X-ray diffraction patterns of new " AL- type” crystals is different than the disclosed X-ray diffraction patterns in patent US 5463116 for " B-type” & " H-type” crystals of N-(trans-4-isopropyIcyclohexyl carbonyl)-D-phenylalanine.
- the new "AL-type" crystals of N-(trans-4- isopropylcyclohexyl carbonyl)-D- phenylalanine are preferably substantially stable to the physical grinding. Stability to grinding may be assessed by measurement of physical property before and after grinding. Where the physical property remains substantially unchanged. Suitable physical properties for measurement includes melting point, differential scanning calorimeter and infra red absorption spectrum.
- the " AL-type" Crystals of N-(trans-4-isopropylcyclohexyl carbonyl)-D- phenylalanine may be formed by crystallization from solution, the crystallization from solution taking place at a temperature between 30°C and the boiling point of the solvent.
- the crystals thus formed generally comprise enhanced amounts of " AL-type” crystals relative to the starting N-(trans-4- isopropylcyclohexylcarbonyl)-D-phenylalanine.
- the crystallization at about 30 °C may be performed in several ways as will be apparent to those of skill in the art.
- -(trans-4-isopropylcyclohexylcarbonyl)-D- phenylalanine " B-type" crystals may be dissolved in a solvent in which it is readily soluble at higher temperature but in which it is only sparingly soluble at lower temperatures.
- Solvents which are suitable for use in this invention include dimethyl formamide, dimethylacetamide and acetonitrile. .
- a preferred solvent is acetonitrile.
- the dissolution volume of the solvent is preferably from 8 to 60 vol % of the solvent.
- the temperature of the solution is preferably 55° C to 75°C.
- the new crystals were obtained from the solution by filtration or centrifuging and then dried at a temperature in the range 50° C to 90°C.
- N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine " B-type" (5 g) was dissolved in acetonitrile 60 ml. at 55 - 60° C. The solution was cooled with stirring.
- "AL-type" crystal form of N-(trans-4-isopropylcyclohexylcarbonyl)-D- phenylalanine (0.1 g) prepared in Example 1 were added at a temperature of 30 - 38° C and the solution was cooled further to 25° C. The crystals were filtered and dried at 70-80° C. overnight and at reduced pressure. 1.5 g of dry crystals were obtained. The crystals had a melting-point of 174° to 178° C.
- the powder X-ray diffraction pattern and the infra-red absorption spectrum enabled the crystals to be identified as "AL-type".
Abstract
This invention relates to novel stable crystal form of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine may be produced by crystallisation of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine with a solvent at 25 - 38 °C and forming crystals in the solvent. The crystal form may be formed by recrystallisation out of solution. The Crystal form obtained in this way have different melting point, infra red spectrum and X-ray diffraction patterns from previously known forms 'B-type' and 'H-Type' of the compound.
Description
FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
COMPLETE SPECIFICATION
1. NOVEL STABLE CRYSTAL FORM OF N- (TRANS-4- ISOPROPYLCYCLOHEXYL CARBONYL)-D-PHENYLALANINE AND PROCESS OF PREPARATION.
2. M/S. ALEMBIC LIMITED, ALEMBIC ROAD, VADODARA - 390 003, GUJARAT, India, an Indian Company incorporated under the Companies Act, 1956.
3. The following specification describes and ascertains the nature of the invention and the manner in which it is to be performed.
FIELD OF THE INVENTION -
The present invention relates to novel stable crystal form of N-(trans-4- isopropylcyclohexylcarbonyl)-D-phenylalanine. The Crystals of N-(trans-4- isopropylcyclohexylcarbonyl)-D-phenylalanine have different melting point, infra red spectrum and X-ray diffraction patterns from previously known forms, " B- Type" and " H-Type" of the compound .
BACKGROUND OF THE INVENTION
N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine is disclosed in Japanese Patent Application Laid Open No. 63-54321 (equivalent to EP-A- 196222 and US 4,816,484) and in J. Med. Chem. 32, 1436-41 ( 1989 ). "The Japanese application describes how the compound may be crystallized from aqueous methanol to yield crystals having a melting point of 129° to 130° C. These crystals are in a crystalline form referred to herein as "B-type". An infra red absorption spectrum and powder X-ray diffraction pattern are disclosed in the US patent no. 5463116 Oct. 31 1995".
The U.S. Pat no. 5463116 also describes how the compound may be crystallized from aqueous acetone, ethanol and isopropanoi to yield different type of crystals having a melting point of 136° to 142° C. These crystals are in a crystalline form referred to herein as "H-type"."
N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine of formula (1) is a known substance having therapeutic utility in depressing blood glucose levels.
( 1 )
The present inventors have made a novel stable crystalline form of N-(trans-4- isopropylcyclohexylcarbonyl)-D-phenylalanine.
The crystals as formed by the present invention hereinafter designated as the "AL-type" crystals of N-(trans-4- isopropylcyclohexyl carbonyl)-D-phenylalanine are substantially stable to the physical grinding. Such crystals are therefore more suitable for use in medicines than the existing crystals of N-(trans-4- isopropylcyclohexyl carbonyl)-D-phenylalanine
It is an objective of the present invention to provide a novel stable crystalline form of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine.
It is a further objective of the present invention to provide a novel method for manufacturing the a stable crystalline new form of N-(trans-4- isopropylcyclohexyl carbonyl)-D-phenylalanine.
The new form is different than previously known disclosed forms : so called "B- type" and "H-type". The inventors have designated the new stable crystalline form of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine as "AL-type".
REFERENCES-
1. US Patent 5463116.
Crystals of N-(trans-4-isopropylcyclohexylcarbonyl)-D- phenylalanine and methods for preparing them.
Sumikawa M, Koguchi K, Ohgane T, Irie Y and Takahashi S.
Ajinomoto Co., Inc., Tokyo, Japan.
2. US Patent 4,816,484. Hypoglycemic agent.
Toyoshima S, Seto Y, Shinkai H, Toi K and Kumashiro I. Ajinomoto Co., Inc., Tokyo, Japan.
3. Shinkai H, Nishikawa M, Sato Y, Toi K, Kumashiro I, Seto Y, Fukuma M, Dan K, Toyoshima S.
N-(cyclohexylcarbonyl)-D-phenylalanines and related compounds. A new class of oral hypoglycemic agents. 2.
J Med Chem. 1989 Jul;32 (7): 1436-41.
DETAILED DESCRIPTION OF THE INVENTION-
The " AL-type" Crystals of N-(trans-4-isopropylcyclohexyl carbonyl)-D- phenylalanine may be formed by crystallization from solution, the crystallization from solution taking place at a temperature between 30°C and the boiling point of the solvent.
The crystals thus formed generally comprise enhanced amounts of " AL-type" crystals relative to the starting N-(trans-4-isopropylcyclohexylcarbonyl)-D- phenylalanine.
The crystallization at about 30 °C may be performed in several ways as will be apparent to those of skill in the art.-(trans-4-isopropylcyclohexylcarbonyl)-D- phenylalanine " B-type" crystals may be dissolved in a solvent in which it is readily soluble at higher temperature but in which it is only sparingly soluble at lower temperatures.
Solvents which are suitable for use in this invention may be selected from the group comprising dimethyl formamide, dimethylacetamide and acetonitrile.
More preferably the solvent is acetonitrile.
The dissolution volume of the solvent is preferably from 8 to 60 vol % of the solvent.
The temperature of the solution is preferably 55° C to 75°C.
The new crystals were obtained from the solution by filtration or centrifuging and then dried at a temperature in the range 50° C to 90°C
BRIEF DESCRIPTION OF THE ANNEXURES INCLUDING DRAWINGS
FIGURE 1. Shows differential scanning calorimeter (DSC) of "AL-type" crystal form of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylaIanine.
FIGURE. 2 :: Shows a powder X-ray diffraction pattern of "AL-type" crystal form of N-(trans-4-isopropyIcyclohexylcarbonyl)-D-phenylalanine in accordance with the present invention.
FIGURE. 3 :: Shows an infra red absorption spectrum of "AL-type" crystal form of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine in accordance with the present invention.
FIGURE 4 :: Shows a crystals photograph of "AL-type" form of N-(trans-4- isopropylcyclohexylcarbonyl)-D-phenylalanine in accordance with the present invention.
FIGURE. 5 :: Shows a crystals photograph of "H-type" form of N-(trans-4- isopropy!cyclohexylcarbonyI)-D-phenylalanine.
FIGURE 6 :: Shows a crystals photograph of "B-type" form of N-(trans-4- isopropylcyclohexylcarbonyl)-D-phenylalanine.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention provides a stable "AL- type" crystalline form of N-(trans- 4-isopropylcyclohexyl carbonyl)-D-phenylalanine. The various examples of the physical properties of the "AL-type" crystal form of N-(trans-4- isopropylcyclohexyl carbonyl)-D-phenylalanine are as follows.
The inventors have measured the melting point of new "AL-type" crystals of N- (trans-4-isopropylcyclohexyl carbonyl)-D-phenylalanine and found it to be in the range of 174° to 178° C.
Similarly , when the melting points of both the previously known " B-type" & " H- type" crystals were taken by same technique, melting points were found 127° to 130° C and 136° to 140° C. respectively.
The powder X-ray diffraction patterns of new " AL-type" crystals of N-(trans-4- isopropylcyclohexyl carbonyl)-D-phenylalanine as shown in Anex-2 is obtained by using a Philips PW1700 powder diffractometer and a scan speed of 0.05.degree./sec. The observed powder X-ray diffraction patterns of new " AL- type" crystals is different than the disclosed X-ray diffraction patterns in patent
US 5463116 for " B-type" & " H-type" crystals of N-(trans-4-isopropyIcyclohexyl carbonyl)-D-phenylalanine.
The inventors carried out the CHN analysis of all three "B-type" , "H-type" and "AL-type" crystals of N-(trans-4-isopropylcyclohexyl carbonyl)-D-phenylalanine and the results are shown as below.
These results confirm that the ail three "B-type", "H-type"and new "AL- type"crystals of N-(trans-4-isopropylcyclohexyl carbonyl)-D-phenylalanine have the similar composition.
The new "AL-type" crystals of N-(trans-4- isopropylcyclohexyl carbonyl)-D- phenylalanine are preferably substantially stable to the physical grinding. Stability to grinding may be assessed by measurement of physical property before and after grinding. Where the physical property remains substantially unchanged. Suitable physical properties for measurement includes melting point, differential scanning calorimeter and infra red absorption spectrum.
The photographs as shown in Anex - 4 - 6 of all three " AL-type", "H-type" and "B-type", crystals of N-(trans-4-isopropylcyclohexyl carbonyl)-D-phenylalanine were taken by using a Phillips XL-30 electron microscope. The crystal shape of new " AL-type" crystals is substantially different than the other known both " B- type" & " H-type" crystals of N-(trans-4-isopropylcyclohexyl carbonyl)-D- phenylalanine.
The " AL-type" Crystals of N-(trans-4-isopropylcyclohexyl carbonyl)-D- phenylalanine may be formed by crystallization from solution, the crystallization from solution taking place at a temperature between 30°C and the boiling point of the solvent. The crystals thus formed generally comprise enhanced amounts of " AL-type" crystals relative to the starting N-(trans-4- isopropylcyclohexylcarbonyl)-D-phenylalanine.
The crystallization at about 30 °C may be performed in several ways as will be apparent to those of skill in the art.-(trans-4-isopropylcyclohexylcarbonyl)-D- phenylalanine " B-type" crystals may be dissolved in a solvent in which it is readily soluble at higher temperature but in which it is only sparingly soluble at lower temperatures. Solvents which are suitable for use in this invention include dimethyl formamide, dimethylacetamide and acetonitrile. . A preferred solvent is acetonitrile. The dissolution volume of the solvent is preferably from 8 to 60 vol % of the solvent. The temperature of the solution is preferably 55° C to 75°C. The new crystals were obtained from the solution by filtration or centrifuging and then dried at a temperature in the range 50° C to 90°C.
The invention will now be more concretely illustrated by the following examples but the invention may note be construed to be limited thereto.
EXAMPLES
N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine for use in the following examples was obtained by the method described in Example 3 of Japanese patent application laid open no. 63-54321. The product consists crystals of "B-type".
Example-1
A solution of 10 g of N-(trans-4-isopropylcyclohexyIcarbonyl)-D-phenylalanine " B-type " in 120 ml of an acetonitrile is stirred at 55 - 60° C. After cooling to 30 - 35° C, the precipitated crystals were filtered and dried at 70-80° C. at reduced pressure overnight. 3.5 g of dry crystals were obtained. The crystals had a melting point of 174° to 178° C. The powder X-ray diffraction pattern and the infra-red absorption spectrum were measured and the crystals were identified as "AL-type", and the required analytical tests are carried { NMR, I.R., XRD, DSC, as depicted in the annexures }, by which it can be concluded that the novel crystal formed are stable The formed crystale are "AL-type". "AL-type
Example- 2
N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine " B-type " (5 g) was dissolved in acetonitrile 60 ml. at 55 - 60° C. The solution was cooled with stirring. "AL-type" crystal form of N-(trans-4-isopropylcyclohexylcarbonyl)-D- phenylalanine (0.1 g) prepared in Example 1 were added at a temperature of 30 - 38° C and the solution was cooled further to 25° C. The crystals were filtered and dried at 70-80° C. overnight and at reduced pressure. 1.5 g of dry crystals were obtained. The crystals had a melting-point of 174° to 178° C. The powder X-ray diffraction pattern and the infra-red absorption spectrum enabled the crystals to be identified as "AL-type".
Claims
1. An isolated novel stable crystal form of N-(trans-4-isopropylcyclo hexyl carbonyl)-D-phenylalanine having the following physical properties:
(a) A melting point in the range of 174°-178°C. Anex.-1.
(b) A powder X-ray diffraction pattern with reflection maxima at, 2.theta. of about 7.5.O., 15.5.0., 19.8.0. and 20.2.0.; Anex.-2.
(c) An infra red absorption spectrum with critical absorption bands in the region of 1711.5, 1646.5, 1538.7,1238.8 ,1215.1 and 700.5 cm. Anex.-3.
2. An isolated novel stable crystal form of N-(trans-4- isopropyIcyclohexylcarbonyl)-D-phenylalanine having an X-ray powder diffraction pattern as shown in Anex.-2.and an infra red spectrum as shown in Anex.-3.
3. Novel stable crystal form of N-(trans-4-isopropylcyclohexyl carbonyl)-D- phenylalanine according to any one of claims 1 and 2 being substantially free of solvent.
4. A process for preparing the novel stable crystal form of N-(trans-4- isopropylcyclo hexylcarbonyl)-D-phenylalanine which comprises dissolving N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine in a solvent in which it is soluble at a temperature greater than 60°C to form a solution, crystallizing the said solution by cooling to a temperature of 28°C or higher, and obtaining the desired crystals at a temperature in excess of 28°C.
5. A process as claimed in claim 4 wherein N-(trans-4- isopropylcyclohexylcarbonyl)-D-phenylalanine is dissolved in the solvent at a temperature between 60°C to 75°C.
6. A process as claimed in claim 4 wherein the precipitation of the solution is carried out at a temperature between 28°C to 35 °C.
7. The process as claimed in claim 4 wherein the said crystals are separated from the solvent at a temperature of 38°C.
8. The process as claimed in claims 4 and 5 wherein the solvent is a water miscible polar solvents, selected from the group comprising acetonitrile, dimethyl formamide and dimethyl acetamide.
9. The process as claimed in claim 4 and 8 wherein the water miscible polar solvent is acetonitrile.
10. The process as claimed in claim 4 wherein the concentration of the said solvent is from 8 to 20 vol % of the product.
11. An isolated novel stable crystal form of N-(trans-4-isopropylcyclo hexyl carbonyl)-D-phenylalanine substantially as herein described with reference to the foregoing description and the accompanying examples.
2. A process for preparing the novel stable crystal form of N-(trans-4- isopropylcyclo hexylcarbonyl)-D-phenylalanine substantially as herein described with reference to the foregoing description and the accompanying examples.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01978760A EP1435912A4 (en) | 2001-09-12 | 2001-11-05 | Novel stable crystal form of n-trans-4-isopropylcyclohexyl carbonyl)-d-phenylalanine and process of preparation |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN871MU2001 | 2001-09-12 | ||
| IN872MU2001 IN191354B (en) | 2001-09-12 | 2001-09-12 | |
| IN871/MUM/2001 | 2001-09-12 | ||
| IN872/MUM/2001 | 2001-09-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2003022251A1 true WO2003022251A1 (en) | 2003-03-20 |
Family
ID=26324909
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IB2001/002080 WO2003022251A1 (en) | 2001-09-12 | 2001-11-05 | Novel stable crystal form of n-trans-4-isopropylcyclohexyl carbonyl)-d-phenylalanine and process of preparation |
Country Status (2)
| Country | Link |
|---|---|
| EP (1) | EP1435912A4 (en) |
| WO (1) | WO2003022251A1 (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003087038A1 (en) * | 2002-04-15 | 2003-10-23 | Novartis Ag | Crystal forms of n-(trans-4-isopropylcyclohexylcarbonyl)-d-phenylalanine |
| WO2004009532A1 (en) * | 2002-07-18 | 2004-01-29 | Teva Pharmaceutical Industries Ltd. | Polymorphic forms of nateglinide |
| WO2004020396A1 (en) * | 2002-08-28 | 2004-03-11 | Dr. Reddy's Laboratories Limited | Crystalline form of nateglinide and process for preparation thereof |
| US6861553B2 (en) | 2002-07-03 | 2005-03-01 | Teva Pharmaceuticals Industries Ltd. | Process for preparing nateglinide and intermediates thereof |
| WO2005110972A1 (en) * | 2004-05-07 | 2005-11-24 | Teva Pharmaceutical Industries Ltd. | Polymorphic forms of nateglinide |
| US7148376B2 (en) | 2002-07-18 | 2006-12-12 | Teva Pharmaceutical Industries Ltd. | Polymorphic forms of nateglinide |
| US7358390B2 (en) | 2002-07-18 | 2008-04-15 | Teva Pharmaceutical Industries Ltd. | Polymorphic forms of nateglinide |
| US7420084B2 (en) | 2002-07-18 | 2008-09-02 | Teva Pharmaceutical Industries Ltd. | Polymorphic forms of nateglinide |
| US7534913B2 (en) | 2002-07-18 | 2009-05-19 | Teva Pharmaceutica Industries Ltd. | Crystalline form of nateglinide |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5463116A (en) * | 1991-07-30 | 1995-10-31 | Ajinomoto Co., Inc. | Crystals of N- (trans-4-isopropylcyclohexlycarbonyl)-D-phenylalanine and methods for preparing them |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2508949B2 (en) * | 1991-07-30 | 1996-06-19 | 味の素株式会社 | Crystal of N- (trans-4-isopropylcyclohexylcarbonyl) -D-phenylalanine and process for producing the same |
-
2001
- 2001-11-05 WO PCT/IB2001/002080 patent/WO2003022251A1/en not_active Application Discontinuation
- 2001-11-05 EP EP01978760A patent/EP1435912A4/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5463116A (en) * | 1991-07-30 | 1995-10-31 | Ajinomoto Co., Inc. | Crystals of N- (trans-4-isopropylcyclohexlycarbonyl)-D-phenylalanine and methods for preparing them |
Non-Patent Citations (1)
| Title |
|---|
| See also references of EP1435912A4 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003087038A1 (en) * | 2002-04-15 | 2003-10-23 | Novartis Ag | Crystal forms of n-(trans-4-isopropylcyclohexylcarbonyl)-d-phenylalanine |
| US7247746B2 (en) | 2002-04-15 | 2007-07-24 | Novartis, Ag | Crystal forms of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine |
| US6861553B2 (en) | 2002-07-03 | 2005-03-01 | Teva Pharmaceuticals Industries Ltd. | Process for preparing nateglinide and intermediates thereof |
| WO2004009532A1 (en) * | 2002-07-18 | 2004-01-29 | Teva Pharmaceutical Industries Ltd. | Polymorphic forms of nateglinide |
| US7148376B2 (en) | 2002-07-18 | 2006-12-12 | Teva Pharmaceutical Industries Ltd. | Polymorphic forms of nateglinide |
| US7358390B2 (en) | 2002-07-18 | 2008-04-15 | Teva Pharmaceutical Industries Ltd. | Polymorphic forms of nateglinide |
| US7420084B2 (en) | 2002-07-18 | 2008-09-02 | Teva Pharmaceutical Industries Ltd. | Polymorphic forms of nateglinide |
| US7534913B2 (en) | 2002-07-18 | 2009-05-19 | Teva Pharmaceutica Industries Ltd. | Crystalline form of nateglinide |
| WO2004020396A1 (en) * | 2002-08-28 | 2004-03-11 | Dr. Reddy's Laboratories Limited | Crystalline form of nateglinide and process for preparation thereof |
| WO2005110972A1 (en) * | 2004-05-07 | 2005-11-24 | Teva Pharmaceutical Industries Ltd. | Polymorphic forms of nateglinide |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1435912A4 (en) | 2005-03-30 |
| EP1435912A1 (en) | 2004-07-14 |
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