WO2004055033A1 - Adenosine derivative in polymorph iv form - Google Patents
Adenosine derivative in polymorph iv form Download PDFInfo
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- WO2004055033A1 WO2004055033A1 PCT/EP2003/014516 EP0314516W WO2004055033A1 WO 2004055033 A1 WO2004055033 A1 WO 2004055033A1 EP 0314516 W EP0314516 W EP 0314516W WO 2004055033 A1 WO2004055033 A1 WO 2004055033A1
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- polymorphic form
- chloro
- purin
- oxadiazol
- tert
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
-
- 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
Definitions
- the present invention relates to heterocyclyl substituted adenosine derivatives. More particularly the invention is concerned with particular physical forms of (2S,3S,4R,5R)-2-(5- tert-butyl-[1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)-purin-9-yl]- tetrahydrofuran-3,4-diol, pharmaceutical formulations thereof and their use in therapy.
- (2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)- purin-9-yl]-tetrahydrofuran-3,4-diol has activity at the adenosine A1 receptor.
- WO99/67262 (Glaxo Group Limited) discloses certain heterocyclyl adenosine derivatives including (2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2- fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4-diol, Example 14 of WO99/67262, the structure of which is indicated below as the compound of formula (A):
- the preparation of the compound of formula (A) is described in WO99/67262.
- the compound of formula (A) may be prepared by the reaction of 4-chloro-2-fluoroaniline with an appropriate purinyl derivative having a suitable leaving group in the 6-position of the purine ring, optionally in the presence of a solvent at elevated temperatures.
- the compound of formula (A) may be prepared by treating 9- ⁇ (3aR,4R,6S,6aR)-6-[5-tert- butyl-1 ,3,4-oxadiazol-2-yl]-2,2-dimethyltetrahydrofuro[3,4-d][1 ,3]dioxol-4-yl ⁇ -N-(4-chloro-2- fluorophenyl)-9H-purin-6-amine with trifluoroacetic acid followed by treatment with sodium bicarbonate. Extraction of the product into ethyl acetate followed by evaporation in vacuo provides the compound of formula (A) as a buff solid.
- the compound of formula (A) may be obtained by crystallisation under certain conditions in the form of polymorphic form IV (hereinafter Polymorph IV).
- Polymorph IV polymorphic form IV
- 2S,3S,4R,5R -2-(5-tert-butyl- [1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4- diol in polymorphic form IV.
- Polymorph IV is particularly suitable for bulk preparation and handling and thus may be useful in the preparation of pharmaceutical formulations.
- the invention provides (2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]- oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4-diol in the form of Polymorph IV as herein defined substantially free of any other polymorph.
- the invention provides (2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]-oxadiazol-2- yl)-5-[6-(4-chloro-2-fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4-diol in the form of Polymorph IV as herein defined substantially free of impurities.
- substantially free is meant containing less than 10%, preferably less than 5%, more preferably less than 2%, of alternative polymorph or impurity.
- (2S,3S,4R,5R)-2-(5-tert-Butyl-[1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)- purin-9-yl]-tetrahydrofuran-3,4-diol may be prepared in polymorphic form IV by crystallisation of the compound under suitable conditions.
- Polymorph IV may be prepared substantially free from alternative polymorphs by controlling crystallisation conditions.
- (2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2- fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4-diol in the form of Polymorph IV may be obtained by crystallisation of the compound by slurrying in saturated acetone solution at ambient temperature, for example 18-25°C, preferably 20-22°C, for 15 to 25 days, preferably 18-22 days.
- Figure I shows the X-ray powder diffraction data for Polymorph IV.
- Polymorph IV has been characterised by X-ray powder diffraction (XRPD) studies.
- Polymorph IV is characterised by having an XRPD pattern with signals substantially at 4.85, 6.00, 8.94, 9.68, 9.94, 15.66, 18.00, 21.62, and 30.38 (degrees 2-theta).
- XRPD peak positions are affected by differences in sample height. The peak positions quoted herein are thus subject to a variation of +/- 0.15 degrees 2-theta. It will also be recognised that XRPD data will vary slightly according to various factors such as the temperature, concentration and instrumentation used. In order to account for this variability, signals and peak positions are quoted herein as being “substantially" at specific values.
- the present invention also provides (2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]oxadiazol-2-yl)-5- [6-(4-chloro-2-fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4-diol characterised in that it provides an XRPD spectrum substantially as illustrated in Figure 1.
- the invention additionally provides (2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]oxadiazol-2-yl)-5- [6-(4-chloro-2-fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4-diol characterised in that it provides an XRPD pattern with signals substantially at 4.85, 6.00, 8.94, 9.68, 9.94, 15.66, 18.00, 21.62, 24.29, 27.50 and 30.38 (degrees 2-theta).
- This invention further provides for a pharmaceutical composition
- a pharmaceutical composition comprising (2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)- purin-9-yl]-tetrahydrofuran-3,4-diol in polymorphic form IV, and a pharmaceutically acceptable carrier and/or excipient.
- Suitable pharmaceutically acceptable carriers and excipients are described in WO 99/67262.
- (2S,3S,4R,5R)-2-(5-tert-Butyl-[1,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)- purin-9-yl]-tetrahydrofuran-3,4-diol in polymorphic form IV may be used for decreasing plasma free fatty acid concentration; reducing heart rate; or treating ischemic heart disease, peripheral vascular disease, stroke, pain (for example inflammatory pain and neuropathic pain), migraine, CNS disorder, or sleep apnoea, as described in WO 99/67262.
- the present invention therefore provides (2S,3S,4R,5R)-2-(5-tert-butyl- [1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4- diol in polymorphic form IV for use in decreasing plasma free fatty acid concentration; reducing heart rate; or treating ischemic heart disease, peripheral vascular disease, stroke, pain, migraine, CNS disorder, or sleep apnoea.
- (2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)- purin-9-yl]-tetrahydrofuran-3,4-diol in polymorphic form IV may be used in the manufacture of a medicament for use in decreasing plasma free fatty acid concentration; reducing heart rate; or treating ischemic heart disease, peripheral vascular disease, stroke, pain (for example inflammatory pain and neuropathic pain), migraine, CNS disorder, or sleep apnoea, as described in WO 99/67262.
- the present invention provides the use of (2S,3S,4R,5R)-2-(5-tert- butyl-[1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)-purin-9-yl]- tetrahydrofuran-3,4-diol in polymorphic form IVI in the manufacture of a medicament for use in decreasing plasma free fatty acid concentration; reducing heart rate; or treating ischemic heart disease, peripheral vascular disease, stroke, pain (for example inflammatory pain and neuropathic pain), migraine, CNS disorder, or sleep apnoea.
- the present invention also provides a method of treating a patient suffering from a condition where there is an advantage in decreasing plasma free fatty acid concentration; or reducing heart rate; or treating a patient suffering from ischemic heart disease, peripheral vascular disease, stroke, pain (for example inflammatory pain and neuropathic pain), migraine, CNS disorder, or sleep apnoea comprising administering a therapeutically effective amount of of (2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]-oxadiazol-2- yl)-5-[6-(4-chloro-2-fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4-diol in polymorphic form IV.
- WO 99/67262 (Glaxo Group Limited) is incorporated by reference herein as though fully set forth.
- Form IV was prepared by slurrying (2S,3S,4R,5R)-2-(5-tert-Butyl-[1 ,3,4]oxadiazol-2-yl)-5- [6-(4-chloro-2-fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4-diol in a saturated acetone solution at room temperature for 19 days.
- the sample preparation and acquisition conditions were as follows:
- Samples were lightly ground and packed into silicon cup with a 12 mm (diameter) x 0.5 mm cavity. Data were acquired using a Bruker D8 Advance X-Ray diffractometer configured with a Cu anode, primary and secondary Soller slits, secondary monochromator and scintillation counter. The generator was operated at 40 kV 40 mA. Variable divergence and antiscatter slits were set at 12 mm irradiated area, and the detector slit was set at 0.1 mm. A locked coupled step scan with 0.02 degrees 2 -theta step was used. The sample was rotated.
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Abstract
(2S,3S,4R,5R)-2-(5-tert-butyl-[1,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4-diol in polymorphic form IV.
Description
ADENOSINE DERIVATIVE IN POLYMORPH IV FORM
The present invention relates to heterocyclyl substituted adenosine derivatives. More particularly the invention is concerned with particular physical forms of (2S,3S,4R,5R)-2-(5- tert-butyl-[1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)-purin-9-yl]- tetrahydrofuran-3,4-diol, pharmaceutical formulations thereof and their use in therapy.
(2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)- purin-9-yl]-tetrahydrofuran-3,4-diol has activity at the adenosine A1 receptor.
WO99/67262 (Glaxo Group Limited) discloses certain heterocyclyl adenosine derivatives including (2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2- fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4-diol, Example 14 of WO99/67262, the structure of which is indicated below as the compound of formula (A):
(A) The preparation of the compound of formula (A) is described in WO99/67262. The compound of formula (A) may be prepared by the reaction of 4-chloro-2-fluoroaniline with an appropriate purinyl derivative having a suitable leaving group in the 6-position of the purine ring, optionally in the presence of a solvent at elevated temperatures. Alternatively the compound of formula (A) may be prepared by treating 9-{(3aR,4R,6S,6aR)-6-[5-tert- butyl-1 ,3,4-oxadiazol-2-yl]-2,2-dimethyltetrahydrofuro[3,4-d][1 ,3]dioxol-4-yl}-N-(4-chloro-2- fluorophenyl)-9H-purin-6-amine with trifluoroacetic acid followed by treatment with sodium bicarbonate. Extraction of the product into ethyl acetate followed by evaporation in vacuo provides the compound of formula (A) as a buff solid.
We have now surprisingly found that the compound of formula (A) can be obtained in polymorphic forms.
We have further found that the compound of formula (A) may be obtained by crystallisation under certain conditions in the form of polymorphic form IV (hereinafter Polymorph IV).
There is thus provided as a first aspect of the invention (2S,3S,4R,5R)-2-(5-tert-butyl- [1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4- diol in polymorphic form IV.
Polymorph IV is particularly suitable for bulk preparation and handling and thus may be useful in the preparation of pharmaceutical formulations.
In a preferred aspect the invention provides (2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]- oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4-diol in the form of Polymorph IV as herein defined substantially free of any other polymorph.
In a further aspect the invention provides (2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]-oxadiazol-2- yl)-5-[6-(4-chloro-2-fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4-diol in the form of Polymorph IV as herein defined substantially free of impurities.
By "substantially free" is meant containing less than 10%, preferably less than 5%, more preferably less than 2%, of alternative polymorph or impurity.
(2S,3S,4R,5R)-2-(5-tert-Butyl-[1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)- purin-9-yl]-tetrahydrofuran-3,4-diol may be prepared in polymorphic form IV by crystallisation of the compound under suitable conditions.
Polymorph IV may be prepared substantially free from alternative polymorphs by controlling crystallisation conditions.
In general, (2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2- fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4-diol in the form of Polymorph IV may be obtained by crystallisation of the compound by slurrying in saturated acetone solution at ambient temperature, for example 18-25°C, preferably 20-22°C, for 15 to 25 days, preferably 18-22 days.
Conversion of polymorph IV to an alternative polymorph can occur under certain circumstances.
The methods for the preparation of Polymorph IV, described herein, constitute further aspects of the present invention.
Figure I shows the X-ray powder diffraction data for Polymorph IV.
Polymorph IV has been characterised by X-ray powder diffraction (XRPD) studies.
Polymorph IV is characterised by having an XRPD pattern with signals substantially at 4.85, 6.00, 8.94, 9.68, 9.94, 15.66, 18.00, 21.62, and 30.38 (degrees 2-theta).
The skilled person will recognise that XRPD peak positions are affected by differences in sample height. The peak positions quoted herein are thus subject to a variation of +/- 0.15 degrees 2-theta. It will also be recognised that XRPD data will vary slightly according to various factors such as the temperature, concentration and instrumentation used. In order to account for this variability, signals and peak positions are quoted herein as being "substantially" at specific values.
The present invention also provides (2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]oxadiazol-2-yl)-5- [6-(4-chloro-2-fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4-diol characterised in that it provides an XRPD spectrum substantially as illustrated in Figure 1.
The invention additionally provides (2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]oxadiazol-2-yl)-5- [6-(4-chloro-2-fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4-diol characterised in that it provides an XRPD pattern with signals substantially at 4.85, 6.00, 8.94, 9.68, 9.94, 15.66, 18.00, 21.62, 24.29, 27.50 and 30.38 (degrees 2-theta).
This invention further provides for a pharmaceutical composition comprising (2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)- purin-9-yl]-tetrahydrofuran-3,4-diol in polymorphic form IV, and a pharmaceutically acceptable carrier and/or excipient.
Suitable pharmaceutically acceptable carriers and excipients are described in WO 99/67262.
(2S,3S,4R,5R)-2-(5-tert-Butyl-[1,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)- purin-9-yl]-tetrahydrofuran-3,4-diol in polymorphic form IV may be used for decreasing plasma free fatty acid concentration; reducing heart rate; or treating ischemic heart disease, peripheral vascular disease, stroke, pain (for example inflammatory pain and neuropathic pain), migraine, CNS disorder, or sleep apnoea, as described in WO 99/67262.
In a further aspect the present invention therefore provides (2S,3S,4R,5R)-2-(5-tert-butyl- [1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4- diol in polymorphic form IV for use in decreasing plasma free fatty acid concentration; reducing heart rate; or treating ischemic heart disease, peripheral vascular disease, stroke, pain, migraine, CNS disorder, or sleep apnoea.
(2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)- purin-9-yl]-tetrahydrofuran-3,4-diol in polymorphic form IV may be used in the manufacture of a medicament for use in decreasing plasma free fatty acid concentration; reducing heart rate; or treating ischemic heart disease, peripheral vascular disease, stroke, pain (for
example inflammatory pain and neuropathic pain), migraine, CNS disorder, or sleep apnoea, as described in WO 99/67262.
In a yet further aspect the present invention provides the use of (2S,3S,4R,5R)-2-(5-tert- butyl-[1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)-purin-9-yl]- tetrahydrofuran-3,4-diol in polymorphic form IVI in the manufacture of a medicament for use in decreasing plasma free fatty acid concentration; reducing heart rate; or treating ischemic heart disease, peripheral vascular disease, stroke, pain (for example inflammatory pain and neuropathic pain), migraine, CNS disorder, or sleep apnoea.
In another aspect the present invention also provides a method of treating a patient suffering from a condition where there is an advantage in decreasing plasma free fatty acid concentration; or reducing heart rate; or treating a patient suffering from ischemic heart disease, peripheral vascular disease, stroke, pain (for example inflammatory pain and neuropathic pain), migraine, CNS disorder, or sleep apnoea comprising administering a therapeutically effective amount of of (2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]-oxadiazol-2- yl)-5-[6-(4-chloro-2-fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4-diol in polymorphic form IV.
WO 99/67262 (Glaxo Group Limited) is incorporated by reference herein as though fully set forth.
The following examples illustrate the invention but are not intended as a limitation thereof.
EXAMPLES
(2S,3S,4R,5R)-2-(5-tert-Butyl-[1 ,3,4]oxadiazol-2-yl)-5-[6-(4-chloro-2-fluorophenylamino)- purin-9-yl]-tetrahydrofuran-3,4-diol was prepared according to the methods described in WO99/67262.
Example 1 - Preparation of Polymorph IV
Form IV was prepared by slurrying (2S,3S,4R,5R)-2-(5-tert-Butyl-[1 ,3,4]oxadiazol-2-yl)-5- [6-(4-chloro-2-fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4-diol in a saturated acetone solution at room temperature for 19 days.
X-Ray Powder Diffraction
The sample preparation and acquisition conditions were as follows:
Samples were lightly ground and packed into silicon cup with a 12 mm (diameter) x 0.5 mm cavity. Data were acquired using a Bruker D8 Advance X-Ray diffractometer configured with a Cu anode, primary and secondary Soller slits, secondary monochromator and scintillation counter. The generator was operated at 40 kV 40 mA. Variable divergence and antiscatter slits were set at 12 mm irradiated area, and the detector slit was set at 0.1 mm. A locked coupled step scan with 0.02 degrees 2 -theta step was used. The sample was rotated.
Data obtained for Polymorph IV are shown in Figure I.
Claims
1. (2S,3S,4R,5R)-2-(5-tert-Butyl-[1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2- fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4-diol in polymorphic form IV.
2. A pharmaceutical formulation comprising a polymorphic form according to claim 1 and a pharmaceutically acceptable carrier and/or excipient.
3. A polymorphic form according to claim 1 for use in decreasing plasma free fatty acid concentration; reducing heart rate; or treating ischemic heart disease, peripheral vascular disease, stroke, pain, migraine, CNS disorder, or sleep apnoea.
4. Use of a polymorphic form according to claim 1 in the manufacture of a medicament for use in decreasing plasma free fatty acid concentration; reducing heart rate; or treating ischemic heart disease, peripheral vascular disease, stroke, pain, migraine.CNS disorder, or sleep apnoea.
5. A method of treating a patient suffering from a condition where there is an advantage in decreasing plasma free fatty acid concentration; or reducing heart rate; or treating a patient suffering from ischemic heart disease, peripheral vascular disease, stroke, pain, migraine, CNS disorder, or sleep apnoea comprising administering a therapeutically effective amount of a polymorphic form according to claim 1.
6. (2S,3S,4R,5R)-2-(5-tert-butyl-[1 ,3,4]-oxadiazol-2-yl)-5-[6-(4-chloro-2- fluorophenylamino)-purin-9-yl]-tetrahydrofuran-3,4-diol in polymorphic form IV substantially as described herein in the specification and/or examples.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2003290088A AU2003290088A1 (en) | 2002-12-18 | 2003-12-16 | Adenosine derivative in polymorph iv form |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US43451502P | 2002-12-18 | 2002-12-18 | |
| US60/434,515 | 2002-12-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2004055033A1 true WO2004055033A1 (en) | 2004-07-01 |
Family
ID=32595282
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2003/014516 Ceased WO2004055033A1 (en) | 2002-12-18 | 2003-12-16 | Adenosine derivative in polymorph iv form |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU2003290088A1 (en) |
| WO (1) | WO2004055033A1 (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999067262A1 (en) * | 1998-06-23 | 1999-12-29 | Glaxo Group Limited | Adenosine derivatives |
| WO2002074781A1 (en) * | 2001-03-20 | 2002-09-26 | Glaxo Group Limited | Process for preparing n6-substituted aminopurine ribofuranose nucleosides |
-
2003
- 2003-12-16 AU AU2003290088A patent/AU2003290088A1/en not_active Abandoned
- 2003-12-16 WO PCT/EP2003/014516 patent/WO2004055033A1/en not_active Ceased
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999067262A1 (en) * | 1998-06-23 | 1999-12-29 | Glaxo Group Limited | Adenosine derivatives |
| WO2002074781A1 (en) * | 2001-03-20 | 2002-09-26 | Glaxo Group Limited | Process for preparing n6-substituted aminopurine ribofuranose nucleosides |
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| Publication number | Publication date |
|---|---|
| AU2003290088A1 (en) | 2004-07-09 |
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