US20010004668A1 - Process for the preparation of purine derivatives - Google Patents
Process for the preparation of purine derivatives Download PDFInfo
- Publication number
- US20010004668A1 US20010004668A1 US09/734,051 US73405100A US2001004668A1 US 20010004668 A1 US20010004668 A1 US 20010004668A1 US 73405100 A US73405100 A US 73405100A US 2001004668 A1 US2001004668 A1 US 2001004668A1
- Authority
- US
- United States
- Prior art keywords
- preparation
- chloropurine
- amino
- acetate
- acetoxymethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C31/00—Saturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C31/18—Polyhydroxylic acyclic alcohols
- C07C31/22—Trihydroxylic alcohols, e.g. glycerol
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/03—Ethers having all ether-oxygen atoms bound to acyclic carbon atoms
- C07C43/14—Unsaturated ethers
- C07C43/178—Unsaturated ethers containing hydroxy or O-metal groups
- C07C43/1782—Unsaturated ethers containing hydroxy or O-metal groups containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/007—Esters of unsaturated alcohols having the esterified hydroxy group bound to an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/62—Halogen-containing esters
- C07C69/63—Halogen-containing esters of saturated acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
- C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
Abstract
The present invention provides a process for the synthesis of penciclovir and famciclovir by 9-substituting 2-amino-6-chloropurine (ACP) with an appropriate side chain precursor, followed by conversion of the 6-chloro moiety to a hydroxy moiety (i.e. to form a guanine) or hydrogen (to form a 2-aminopurine), respectively.
Description
- This is a continuation-in-part application of U.S. Ser. No. 08/132,082, filed Oct. 5, 1993 and U.S. Ser. No. 07/918,111 filed Jul. 20, 1992.
- The present invention relates to a process for the preparation of novel compounds which are of potential use as antiviral agents, to a process for their preparation and to their use as pharmaceuticals.
- U.S. Pat. Nos. 5075445 and 5246937, the subject matter of which is incorporated herein by reference, disclose antiviral compounds penciclovir (Example 4 of '445) and famciclovir (Example 2 of '937) and methods for their preparation. 2-Amino-6-chloropurine (ACP) is 9-substituted with an appropriate side chain precursor, followed by conversion of the 6-chloro moiety to a hydroxy moiety (i.e. to form a guanine) or hydrogen (a 2-aminopurine).
- In particular, beginning column 4 of '445, and column 3 of '937, a process is described for the preparation of such purine derivatives wherein the hydroxy groups in the 9-(4-hydroxy-3-hydroxymethylbut-1-yl) substituent are in acylated form, i.e. the ACP is reacted with 2-acyloxymethyl-4-(leaving group)-but-1-yl acylate. The leaving group may be halo, such as chloro, bromo or iodo although alternative leaving groups, such as tosylate or methanesulphonate may be employed. The acyl groups have advantages over the alternative protecting groups already described in acyclonucleoside chemistry in providing a good yield of 9-substitution and avoiding by-products which are difficult to isolate.
- The following examples illustrate the process of the invention to form 9-(4-acetoxy-3-acetoxymethylbut-1-yl)-2-amino-6-chloropurine, (DACP). The following descriptions illustrate the preparation of side chain intermediates. Penciclovir is prepared from DACP according to the method described in '445 column 14, lines 4-16 and famciclovir is prepared from DACP according to the method described in Example 2 of '937.
- 2-Acetoxymethyl-4-bromobutyl acetate was reacted with ACP as described in Examples 11 and 10 of '445.
- A mixture of ACP (10.0 mmol), 2-acetoxymethyl-4-iodobutyl acetate (3.30 g, 10.5 mmol), and anhydrous potassium carbonate (2.07 g, 15.0 mmol) was stirred for 18 hours at ambient temperature in dry DMF (40 ml) under an atmosphere of dry nitrogen. The mixture was then filtered to remove insoluble material, which was washed well with DMF. The combined filtrates were evaporated under reduced pressure and the residue purified directly by column chromatography on silica gel (150 g), eluting with various dichloromethane-methanol mixtures. Fractions containing the first-eluting N-9 isomer, and the second-eluting N-7 isomer were separately combined, rigorously evaporated and weighed. The N-9:N-7 alkylated product ratio obtained from the isolated weights was checked by integration of the respective H-81HNMR signals in the spectrum of the crude residue.
- 9-(4-Acetoxy-3-acetoxymethylbutyl)-2-amino-6-chloropurine and 7-(4-acetoxy-3-acetoxymethylbutyl)-2-amino-6-chloropurine
- Column eluant dichloromethane-methanol 25:1.
- 9-isomer, 75%, m.p.134-136° (ethyl acetate-diethyl ether).
-
- 7-isomer, 15%, m.p.159-161° (dec). (butanol).
-
- 2-Acetoxymethyl-4-bromobutyl acetate was prepared as described in Examples 5-8 of '445.
- 2-Acetoxymethyl-4-iodobutyl acetate was prepared as follows:
- a) To a stirred solution of 2-(2-benzyloxyethyl)propane-1,3-diol (J. Org. Chem., 1981, 46, 3204) (10.0 g, 47.6 mmol), 4-dimethylaminopyridine (0.55 g, 4.5 mmol), and pyridine (12.3 ml, 0.15 mol) in dichloromethane (54 ml) at −10° C. was added dropwise acetic anhydride (13.2 ml, 0.14 mol) over 20 minutes. After completion of the addition, the reaction mixture was stirred for a further 1 hour at 0° C., then diluted with dichloromethane (100 ml) and washed with 2M hydrochloric acid (2×50 ml), saturated sodium bicarbonate solution (50 ml), and brine (50 ml), dried (MgSO4), and evaporated to give 2-acetoxymethyl-4-benzyloxybutyl acetate as a light yellow oil (13.2 g, 94%). b.p. 160-165°/0.5 mm.
-
- b) A solution of 2-acetoxymethyl-4-benzyloxybutyl acetate (15.5 g, 52.7 mmol) in ethanol (200 ml) was hydrogenated for 18 hours at ambient temperature over 10% palladium-carbon (2 g). Filtration and evaporation afforded the corresponding alcohol (10.2 g) as a colourless oil.
- c) To a stirred solution of the above oil and triethylamine (10.4 ml, 74.8 mmol) in dichloromethane (100 ml) cooled to −5° C. was added a solution of methanesulphonyl chloride (4.6 ml, 59.5 mmol) in dichloromethane (30 ml) dropwise over 30 minutes. After completion of the addition, the reaction mixture was stirred for a further 1 hour at −5° C., then washed with 2M hydrochloric acid (2×100 ml), saturated sodium bicarbonate solution (100 ml), and brine (10 ml), dried (MgSO4) and evaporated to afford the corresponding methanesulphonate (14.1 g) as a pale yellow oil.
- d) A mixture of the above oil and sodium iodide (15.0 g, 0.1 mol) was stirred under reflux for 2 hours in acetone (150 ml), then cooled, poured into water (300 ml), and extracted with diethyl ether (3×150 ml). The combined ether extracts were washed with10% sodium metabisulphite solution (250 ml), and brine (250 ml), dried (MgSO4) and evaporated to give a pale oil. This was purified by flash column chromatography on silica, eluant hexane-diethyl ether 3:2 affording the title compound as a colourless oil (13.1 g, 79% from 2-acetoxymethyl-4-benzyloxybutyl acetate).
-
Claims (6)
1. A process for the preparation of i) penciclovir or ii) famciclovir which process comprises the reaction of 2-amino-6-chloropurine with 2-acetoxymethyl-4-(leaving group)-but-1-yl acetate;
to give 9-(4-acetoxy-3-acetoxymethylbut-1-yl)-2-amino-6-chloropurine;
and thereafter:
i) hydrolysing to give penciclovir:
or
ii) reducing to give famciclovir.
2. A process according to wherein the leaving group is halo.
claim 1
3. A compound known as 9-(4-acetoxy-3-acetoxymethylbutyl)-2-amino-6-chloropurine.
4. A compound known as 2-acetoxymethyl-4-halo-but-1-yl acetate.
5. A compound according to wherein halo is bromo.
claim 4
6. A compound according to wherein halo is iodo.
claim 4
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/734,051 US6388074B2 (en) | 1983-08-18 | 2000-12-11 | Process for the preparation of purine derivatives |
Applications Claiming Priority (24)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB8322199 | 1983-08-18 | ||
GB838322199A GB8322199D0 (en) | 1983-08-18 | 1983-08-18 | Pharmaceutical composition |
GB8325271 | 1983-09-21 | ||
GB838325271A GB8325271D0 (en) | 1983-09-21 | 1983-09-21 | Compounds |
GB848408322A GB8408322D0 (en) | 1984-03-30 | 1984-03-30 | Compounds |
GB8408322 | 1984-03-30 | ||
US64130084A | 1984-08-16 | 1984-08-16 | |
GB8423833 | 1984-09-20 | ||
GB848423833A GB8423833D0 (en) | 1984-09-20 | 1984-09-20 | Compounds |
GB8510331 | 1985-04-23 | ||
GB858510331A GB8510331D0 (en) | 1985-04-23 | 1985-04-23 | Compounds |
GB858520618A GB8520618D0 (en) | 1985-08-16 | 1985-08-16 | Compounds |
GB8520618 | 1985-08-19 | ||
US77718885A | 1985-09-18 | 1985-09-18 | |
US07/085,216 US5075445A (en) | 1983-08-18 | 1987-08-12 | Guanine derivatives |
US28539988A | 1988-12-15 | 1988-12-15 | |
US60740390A | 1990-10-31 | 1990-10-31 | |
US07/825,440 US5250688A (en) | 1984-09-20 | 1992-01-22 | Purine derivatives |
US91811192A | 1992-07-20 | 1992-07-20 | |
US13208293A | 1993-10-05 | 1993-10-05 | |
US08/258,167 US5684153A (en) | 1984-08-16 | 1994-06-10 | Process for the preparation of purine derivatives |
US08/884,731 US5886215A (en) | 1983-08-18 | 1997-06-30 | 2-acetoxymethyl-4-halo-butyl-1-yl acetates |
US09/238,777 US6187922B1 (en) | 1983-08-18 | 1999-01-27 | Process for the preparation of purine derivatives |
US09/734,051 US6388074B2 (en) | 1983-08-18 | 2000-12-11 | Process for the preparation of purine derivatives |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/238,777 Division US6187922B1 (en) | 1983-08-18 | 1999-01-27 | Process for the preparation of purine derivatives |
Publications (2)
Publication Number | Publication Date |
---|---|
US20010004668A1 true US20010004668A1 (en) | 2001-06-21 |
US6388074B2 US6388074B2 (en) | 2002-05-14 |
Family
ID=27574624
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US08/258,167 Expired - Lifetime US5684153A (en) | 1983-08-18 | 1994-06-10 | Process for the preparation of purine derivatives |
US08/884,731 Expired - Fee Related US5886215A (en) | 1983-08-18 | 1997-06-30 | 2-acetoxymethyl-4-halo-butyl-1-yl acetates |
US09/238,777 Expired - Fee Related US6187922B1 (en) | 1983-08-18 | 1999-01-27 | Process for the preparation of purine derivatives |
US09/734,051 Expired - Fee Related US6388074B2 (en) | 1983-08-18 | 2000-12-11 | Process for the preparation of purine derivatives |
Family Applications Before (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US08/258,167 Expired - Lifetime US5684153A (en) | 1983-08-18 | 1994-06-10 | Process for the preparation of purine derivatives |
US08/884,731 Expired - Fee Related US5886215A (en) | 1983-08-18 | 1997-06-30 | 2-acetoxymethyl-4-halo-butyl-1-yl acetates |
US09/238,777 Expired - Fee Related US6187922B1 (en) | 1983-08-18 | 1999-01-27 | Process for the preparation of purine derivatives |
Country Status (1)
Country | Link |
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US (4) | US5684153A (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004110343A2 (en) * | 2003-06-13 | 2004-12-23 | Kyungdong Pharm. Co., Ltd. | 2-amino-9-(2-substituted ethyl)purines and preparing methods for 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]- 2- aminopurine using the same |
WO2010126600A1 (en) * | 2009-05-01 | 2010-11-04 | Anaspec, Inc. | Optimal fret pairs and related methods |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5684153A (en) * | 1984-08-16 | 1997-11-04 | Beecham Group Plc | Process for the preparation of purine derivatives |
GB9807116D0 (en) | 1998-04-02 | 1998-06-03 | Smithkline Beecham Plc | Novel process |
PT1380303E (en) | 1998-11-02 | 2008-11-03 | Gilead Sciences Inc | Combination therapy to treat hepatitis b virus |
US6407077B1 (en) | 1998-11-05 | 2002-06-18 | Emory University | β-L nucleosides for the treatment of HIV infection |
AUPQ806700A0 (en) * | 2000-06-08 | 2000-07-06 | Commonwealth Scientific And Industrial Research Organisation | Antiviral agents |
CN102942563A (en) * | 2001-03-01 | 2013-02-27 | 基利得科学公司 | Polymorphic and other crystalline forms of cis-ftc |
KR100573859B1 (en) * | 2002-07-15 | 2006-04-25 | 경동제약 주식회사 | A process for preparing 9-[4-acetoxy-3-acetoxymethylbut-1-yl]-2-aminopurine |
AU2003268213A1 (en) * | 2002-08-26 | 2004-03-11 | Teva Pharmaceutical Industries Ltd. | Crystalline solid famciclovir forms i, ii, iii and preparation thereof |
US9021529B2 (en) | 2004-07-15 | 2015-04-28 | Microsoft Technology Licensing, Llc | Content recordation techniques |
US8383637B2 (en) * | 2004-08-06 | 2013-02-26 | Jansssen Pharmaceutica N.V. | 2-amino-quinazoline derivatives useful as inhibitors of β-secretase (BACE) |
US8436006B2 (en) * | 2004-08-06 | 2013-05-07 | Jansssen Pharmaceutica N.V. | 2-amino-quinazoline derivatives useful as inhibitors of β-secretase (BACE) |
US8426429B2 (en) * | 2004-08-06 | 2013-04-23 | Jansssen Pharmaceutica N.V. | 2-amino-quinazoline derivatives useful as inhibitors of β-secretase (BACE) |
GB2426247A (en) * | 2005-05-20 | 2006-11-22 | Arrow Int Ltd | Methods of preparing purine derivatives such as famciclovir |
WO2007092854A2 (en) * | 2006-02-06 | 2007-08-16 | Janssen Pharmaceutica N.V. | 2-AMINO-QUINOLINE DERIVATIVES USEFUL AS INHIBITORS OF β-SECRETASE (BACE) |
WO2007092839A2 (en) * | 2006-02-06 | 2007-08-16 | Janssen Pharmaceutica N.V. | Macrocycle derivatives useful as inhibitors of beta-secretase (bace) |
WO2007092846A2 (en) * | 2006-02-06 | 2007-08-16 | Janssen Pharmaceutica N.V. | 2-AMINO-3,4-DIHYDRO-QUINOLINE DERIVATIVES USEFUL AS INHIBITORS OF β-SECRETASE (BACE) |
EP1852435A1 (en) * | 2006-04-12 | 2007-11-07 | SOLMAG S.p.A. | A process for the manufacture of famciclovir using phase-transfer catalysts |
WO2008155613A1 (en) * | 2007-06-21 | 2008-12-24 | Aurobindo Pharma Ltd | An improved process for preparing purine derivative |
JP2011510989A (en) * | 2008-01-28 | 2011-04-07 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 6-Substituted thio-2-amino-quinoline derivatives useful as inhibitors of β-secretase (BACE) |
WO2009097401A1 (en) * | 2008-01-29 | 2009-08-06 | Janssen Pharmaceutica N.V. | 2-AMINO-QUINOLINE DERIVATIVES USEFUL AS INHIBITORS OF β-SECRETASE (BACE) |
CN108484605B (en) * | 2018-03-16 | 2020-08-21 | 上药康丽(常州)药业有限公司 | Preparation method of 2-amino-6-chloro-9- (4-acetoxyl-3-acetoxymethyl butyl) purine |
Family Cites Families (24)
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GB1523865A (en) * | 1974-09-02 | 1978-09-06 | Wellcome Found | Purine compunds and salts thereof |
US4146715A (en) * | 1975-08-27 | 1979-03-27 | Burroughs Wellcome Co. | 2-amido-9-(2-acyloxyethoxymethyl)hypoxanthines |
US4197406A (en) * | 1978-05-12 | 1980-04-08 | Hoffmann-La Roche Inc. | D-Homosteroids |
IL64501A (en) * | 1980-12-22 | 1985-07-31 | Astra Laekemedel Ab | 9-substituted 4-hydroxybutyl guanine derivatives,their preparation and antiviral use |
CA1305138C (en) * | 1981-08-11 | 1992-07-14 | Howard J. Schaeffer | Antiviral acyclic nucleoside derivatives and their preparation |
US4451478A (en) * | 1982-03-12 | 1984-05-29 | Newport Pharmaceuticals International, Inc. | Imidazole compounds |
SE8203855D0 (en) * | 1982-06-21 | 1982-06-21 | Astra Laekemedel Ab | NOVEL DERIVATIVES OF GUANINE I |
SE8203856D0 (en) * | 1982-06-21 | 1982-06-21 | Astra Laekemedel Ab | NOVEL DERIVATIVES OF GUANINE II |
ATE33653T1 (en) * | 1982-10-14 | 1988-05-15 | Wellcome Found | ANTIVIRAL PURINE DERIVATIVES. |
US4609662A (en) * | 1982-10-14 | 1986-09-02 | Burroughs Wellcome Co. | Method for using purine derivatives |
US4461757A (en) * | 1983-02-23 | 1984-07-24 | Ens Bio Logicals Inc. | Dimethylaminomethylenated anti-herpes compounds |
DE3485225D1 (en) * | 1983-08-18 | 1991-12-05 | Beecham Group Plc | ANTIVIRAL GUANINE DERIVATIVES. |
US5684153A (en) * | 1984-08-16 | 1997-11-04 | Beecham Group Plc | Process for the preparation of purine derivatives |
IL73682A (en) * | 1983-12-20 | 1991-08-16 | Medivir Ab | Antiviral pharmaceutical compositions containing 9-hydroxy aliphatic derivatives of guanine,some new such derivatives and process for their preparation |
DE3571810D1 (en) * | 1984-01-26 | 1989-08-31 | Merck & Co Inc | Substituted butyl guanines and their utilization in antiviral compositions |
US4845084A (en) * | 1984-01-26 | 1989-07-04 | Merck & Co., Inc. | Phosphate derivatives of substituted butyl guanines, antiviral compositions containing them, and methods of treating viral infections with them |
US4579849A (en) * | 1984-04-06 | 1986-04-01 | Merck & Co., Inc. | N-alkylguanine acyclonucleosides as antiviral agents |
SE8406538D0 (en) * | 1984-12-21 | 1984-12-21 | Astra Laekemedel Ab | NOVEL DERIVATIVES OF PURINE |
US5246937A (en) * | 1985-09-18 | 1993-09-21 | Beecham Group P.L.C. | Purine derivatives |
GB8817270D0 (en) * | 1988-07-20 | 1988-08-24 | Beecham Group Plc | Novel process |
GB8817607D0 (en) * | 1988-07-23 | 1988-09-01 | Beecham Group Plc | Novel process |
GB8822236D0 (en) * | 1988-09-21 | 1988-10-26 | Beecham Group Plc | Chemical process |
GB8907173D0 (en) * | 1989-03-30 | 1989-05-10 | Beecham Group Plc | Novel compounds |
GB9210839D0 (en) * | 1992-05-21 | 1992-07-08 | Smithkline Beecham Plc | Novel compounds |
-
1994
- 1994-06-10 US US08/258,167 patent/US5684153A/en not_active Expired - Lifetime
-
1997
- 1997-06-30 US US08/884,731 patent/US5886215A/en not_active Expired - Fee Related
-
1999
- 1999-01-27 US US09/238,777 patent/US6187922B1/en not_active Expired - Fee Related
-
2000
- 2000-12-11 US US09/734,051 patent/US6388074B2/en not_active Expired - Fee Related
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004110343A2 (en) * | 2003-06-13 | 2004-12-23 | Kyungdong Pharm. Co., Ltd. | 2-amino-9-(2-substituted ethyl)purines and preparing methods for 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]- 2- aminopurine using the same |
WO2004110343A3 (en) * | 2003-06-13 | 2005-09-01 | Kyungdong Pharm Co Ltd | 2-amino-9-(2-substituted ethyl)purines and preparing methods for 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]- 2- aminopurine using the same |
AU2004246958B2 (en) * | 2003-06-13 | 2010-09-16 | Kyungdong Pharm. Co., Ltd. | 2-amino-9-(2-substituted ethyl)purines and preparing methods for 9-(4-acetoxy-3-(acetoxymethyl)but-1-yl)- 2- aminopurine using the same |
WO2010126600A1 (en) * | 2009-05-01 | 2010-11-04 | Anaspec, Inc. | Optimal fret pairs and related methods |
Also Published As
Publication number | Publication date |
---|---|
US5684153A (en) | 1997-11-04 |
US5886215A (en) | 1999-03-23 |
US6187922B1 (en) | 2001-02-13 |
US6388074B2 (en) | 2002-05-14 |
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