8-Oxoadenine Compound

• US 20070225303A1
• Filed: 03/25/2005
• Published: 09/27/2007
• Est. Priority Date: 03/26/2004
• Status: Abandoned Application

• Current Assignee: Astrazeneca AB (Astrazeneca PLC), Dainippon Sumitomo Pharma Company Limited (Sumitomo Chemical Company Limited)
• Original Assignee: Astrazeneca AB (Astrazeneca PLC), Dainippon Sumitomo Pharma Company Limited (Sumitomo Chemical Company Limited)
• Inventors: Hashimoto, Kazuki, Kurimoto, Ayumu, Isobe, Yoshiaki, Nakamura, Tomoaki, Ogita, Haruhisa
• Application Number:
  US10/594,074
• Publication Number:
  US 20070225303A1
• Time in Patent Office: Days
• US Class Current: 514/263.220
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 11/14 Antitussive agents
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 27/14 : Decongestants or antiallergics
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/06 : for tuberculosis
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/16 : for influenza or rhinoviruses
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07D 473/16 : two nitrogen atoms
• CPC Class Codes: C07D 473/18 : one oxygen and one nitrogen atom, e.g. guanine
• CPC Class Codes: C07D 473/24 : one nitrogen and one sulfur atom
• CPC Class Codes: C07D 473/34 : attached in position 6, e.g. adenine

Abstract

An 8-oxoadenine compound useful as an immuno-modulator having specific activity against Th1/Th2, specifically a prophylactic and therapeutic agent for a topical application for allergic diseases, viral diseases and cancers, which is represented by the following formula (1):
wherein A is a group of a formula represented by the formula (2):

• • wherein R² is a substituted or unsubstituted alkyl group and so on, R³ is hydrogen atom or an alkyl group, R is a halogen atom and so on, n is 0˜2,
• X¹ is oxygen atom, Z is straight or branched chain alkylene, and R¹ is an alkyl group which is optionally substituted by hydroxy group, an alkoxy group, alkoxycarbonyl group and so on, or its pharmaceutically acceptable salt.

Claims

1. An 8-oxoadenine compound represented by the following formula (1):

, wherein A is a group selected from the group consisting of the following formulas (2) to (8);

, wherein R² is hydrogen atom, or a substituted or unsubstituted alkyl group;

R³ is hydrogen atom or an alkyl group;

R is a halogen atom, a haloalkyl group, a haloalkoxy group, an alkyl group, an alkoxy group, amino group, an alkylamino group or dialkylamino group;

n is an integer of 0 to 2, and when n is 2, R_S may be the same or different;

X¹ is oxygen atom, sulfur atom, SO₂, NR⁴ (wherein R⁴ is hydrogen atom or an alkyl group.), or a single bond;

Z is a straight or branched chain alkylene;

R¹ is hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group or a substituted or unsubstituted cycloalkyl group,

or a pharmaceutically acceptable salt thereof.

2. The 8-oxoadenine compound according to claim 1, wherein

R² is a substituted or unsubstituted C_1-8 alkyl group, wherein said alkyl group may be substituted by one or plural substituents which may be the same or different,

and the substituents on said alkyl group are selected from the group consisting of a halogen atom, hydroxy group, carboxy group, C_3-8 cycloalkyl group, an C_1-6 alkoxy group, an C_1-6 alkylthio group, a C_3-8 cycloalkoxy group, an C_2-10 acyloxy group, an C_1-6 alkylsulfonyl group, an C_1-6 alkylsulfinyl group, a substituted or unsubstituted carbamoyl group, a substituted or unsubstituted sulfamoyl group, a substituted or unsubstituted amino group, a substituted or unsubstituted 6 to 10 membered aryl group, a substituted or unsubstituted 5 to 10 membered heteroaryl group which contains 1 to 4 hetero atoms consisting of 0 to 2 nitrogen atoms, 0 to 1 oxygen atom and 0 to 1 sulfur atom, and a substituted or unsubstituted 4 to 7 membered saturated heterocyclic group which contains 1 to 4 hetero atoms consisting of 0 to 2 nitrogen atoms, 0 to 2 oxygen atoms and 0 to 2 sulfur atoms;

R³ is hydrogen atom or an alkyl group.

R is a halogen atom, a C_1-6 haloalkyl group, a C_1-6 haloalkoxy group, an C_1-6 alkyl group, an C_1-6 alkoxy group, amino group, an C_1-6 alkylamino group, or a di C_1-6 alkyl amino group;

n is an integer of 0 to 2, and when n is 2, Rs may be the same or different;

X¹ is oxygen atom, sulfur atom, SO₂, NR⁴ (wherein R⁴ is hydrogen atom or an C_1-6 alkyl group.), or a single bond;

Z is a straight or branched chain C_1-8 alkylene;

R¹ is hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heteroaryl group;

and the substituents of the said alkyl group, alkenyl group and alkynyl group are selected from the group consisting of a halogen atom, hydroxy group, carboxy group, an C_1-6 alkoxy group, a C_1-6 haloalkoxy group, an C_1-6 alkylthio group, an C_1-6 alkylsulfonyl group, an C_1-6 alkylsulfinyl group, an C_2-5 alkoxycarbonyl group, an C_2-10 acyloxy group, a substituted or unsubstituted amino group, a substituted or unsubstituted carbamoyl group, a substituted or unsubstituted sulfamoyl group, an ureido group which may be substituted by the same or different one or two alkyl groups, a substituted or unsubstituted 6 to 10 membered aryl group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted arylthio group, a substituted or unsubstituted 5 to 10 membered heteroaryl group which contains 1 to 4 hetero atom selected from 0 to 2 nitrogen atoms, 0 to 1 oxygen atom and 0 to 1 sulfur atom, a substituted or unsubstituted heteroaryloxy group, a substituted or unsubstituted heteroarylthio group, a substituted or unsubstituted C_3-8 cycloalkyl group, a substituted or unsubstituted C_3-8 cycloalkoxy group, a substituted or unsubstituted cycloalkylthio group, a substituted or unsubstituted 4 to 7 membered saturated heterocyclic group which contains 1 to 4 hetero atoms selected from 0 to 2 nitrogen atoms, 0 to 2 oxygen atoms and 0 to 2 sulfur atoms, a substituted or unsubstituted saturated heterocycle-oxy group, and a substituted or unsubstituted saturated heterocycle-thio group;

and the substituents of said amino group, carbamoyl group and sulfamoyl group are selected from the group consisting an C_1-6 alkyl group, an C_2-6 alkenyl group, an C_2-6 alkynyl group, an C_3-6 acycloalkyl group, an C_2-5 alkylcarbonyl group, an C_2-5 alkoxycarbonyl group and an C_1-6 alkylsulfonyl group (the above seven groups may be substituted by a halogen atom, hydroxy group or an alkoxy group, respectively.), or the two substituents may be combined together to form a substituted or unsubstituted 4 to 7 membered saturated heterocyclic group containing 1 to 4 hetero atoms selecting from 1 to 2 nitrogen atoms, 0 to 1 oxygen atom and 0 to 1 sulfur atom;

the substituents of said aryl group, aryloxy group, arylthio group, heteroaryl group, heteroaryloxy group, heteroarylthio group, cycloalkyl group, cycloalkoxy group, cycloalkylthio group, saturated heterocyclic group, saturated heterocycle-oxy group, saturated heterocycle-thio group and saturated nitrogen containing heterocyclic group are selected from the group consisting of a halogen atom, hydroxy group, carboxy group, an C_1-6 alkyl group, an C_1-6 alkoxy group, an C_2-5 alkylcarbonyl group, an C_2-5 alkoxycarbonyl group (the above four groups may be substituted by a halogen atom, hydroxy group or an alkoxy group, respectively), a C_1-6 haloalkyl group, a C_1-6 haloalkoxy group, amino group, an C_1-6 alkylamino group, and a di C_1-6 alkyl amino group, in the formula (1),

or its pharmaceutically acceptable salt.

3. The 8-oxoadenine compound or a pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein R² in the formula (1) is methyl group.

4. The 8-oxoadenine compound or a pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein R² in the formula (1) is a substituted C_2-6 alkyl group.

5. The 8-oxoadenine compound or a pharmaceutically acceptable salt thereof according to claim 4, wherein R² in the formula (1) is an C_2-10 alkyl group substituted by a substituted or unsubstituted amino group.

6. The 8-oxoadenine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R³ in the formula (1) is hydrogen atom.

7. The 8-oxoadenine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein Z in the formula (1) is a straight chain C_1-6 alkylene group.

8. The 8-oxoadenine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein X¹ in the formula (1) is a single bond, oxygen atom or sulfur atom.

9. The 8-oxoadenine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R¹ in the formula (1) is an C_1-6 alkyl group which is optionally substituted by an alkoxycarbonyl group, hydroxy group or an alkoxy group.

10. The 8-oxoadenine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein X¹ in the formula (1) is a single bond, R¹ is an C_1-6 alkyl group which is substituted by methoxycarbonyl group.

11. A pharmaceutical composition containing the 8-oxoadenine compound or a pharmaceutically acceptable salt thereof as claimed in claim 1 as an active ingredient.

12. A medicament for topical administration containing the 8-oxoadenine compound or a pharmaceutically acceptable salt thereof as clamed in claim 1 as an active ingredient.

13. An immuno-modulator containing the 8-oxoadenine compound or a pharmaceutically acceptable salt thereof as claimed in claim 1 as an active ingredient.

14. A therapeutic or prophylactic agent for viral diseases, cancers or allergic diseases containing the 8-oxoadenine compound or a pharmaceutically acceptable salt thereof as claimed in claim 1 as an active ingredient.

15. Use of the 8-oxoadenine compound, or a pharmaceutically acceptable salt thereof as claimed in claim 1 as a medicament.

16. Use of the 8-oxoadenine compound, or a pharmaceutically acceptable salt thereof as claimed in claim 1 for manufacturing an immuno-modulator.

17. Use of the 8-oxoadenine compound, or a pharmaceutically acceptable salt thereof as claimed in claim 1 for manufacturing a therapeutic or prophylactic agent for viral diseases, cancers or allergic diseases.

18. A method for modulating immune response which comprises administering, to a patient an effective amount of the 8-oxoadenine compound, or a pharmaceutically acceptable salt thereof as claimed in claim 1.

19. A method for treating or preventing viral diseases, cancers or allergic diseases which comprises administering, to a patient an effective amount of the 8-oxoadenine compound, or a pharmaceutically acceptable salt thereof as claimed in claim 1.

20. A process for preparing the 8-oxoadenine compound as claimed in claim 1, which comprises brominating a compound represented by the formula (9):

, wherein A, Z, R¹ and X¹ are the same as defined above, and hydrolyzing the resultant or reacting the resultant with a metal alkoxide and then hydrolyzing.

21. A compound represented by the formula (9):

, wherein A, Z, R¹ and X¹ are the same as defined in claim 1.

22. An 8-oxoadenine compound or its pharmaceutically acceptable salt selected from the group consisting of the following compounds:

8-hydroxy-2-(3-hydroxypropyl thio)-9-(3-methoxycarbonylmethylbenzyl)adenine,

8-hydroxy-2-(4-hydroxybutylthio)-9-(3-methoxycarbonylmethylbenzyl)adenine,

8-hydroxy-2-(2-methoxyethylthio)-9-(3-methoxycarbonylmethylbenzyl)adenine,

8-hydroxy-2-(3-hydroxypropoxy)-9-(3-methoxycarbonylmethylbenzyl)adenine,

8-hydroxy-2-(2-hydroxyethoxy)-9-(3-methoxycarbonylmethylbenzyl)adenine,

8-hydroxy-2-(4-hydroxybutoxy)-9-(3-methoxycarbonylmethylbenzyl)adenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-(4,4,4-trifluorobutoxy)adenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-[N-(2-methoxyethyl)amino]adenine,

2-butoxy-8-hydroxy-9-[2-(3-methoxycarbonylmethylphenyl)ethyl]adenine,

2-butoxy-8-hydroxy-9-[3-(3-methoxycarbonylmethylphenyl)propyl]adenine,

2-(2,3-dihydroxy-1-propoxy)-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine,

2-(2-ethoxyethoxy)-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine,

2-cyclohexylmethoxy-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine,

2-benzyloxy-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine,

8-hydroxy-2-(2-methoxycarbonylethyl)-9-(3-methoxycarbonylmethylbenzyl)adenine,

2-butoxy-8-hydroxy-9-{(5-methoxycarbonylmethyl-2-thienyl)methyl} adenine,

2-butoxy-8-hydroxy-9-{(2-methoxycarbonylmethyl-4-pyridyl)methyl} adenine,

2-butoxy-8-hydroxy-9-{(6-methoxycarbonylmethyl-2-pyridyl)methyl} adenine,

2-butoxy-8-hydroxy-9-{(4-methoxycarbonylmethyl-2-pyridyl)methyl} adenine,

2-butoxy-8-hydroxy-9-[(2-methoxy-5-methoxycarbonylmethyl)benzyl]adenine,

2-butoxy-9-[(4-fluoro-3-methoxycarbonylmethyl)benzyl]-8-hydroxyadenine,

2-butoxy-8-hydroxy-9-[(4-methoxy-3-methoxycarbonylmethyl)benzyl]adenine,

2-butylthio-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine,

2-[3-(ethylsulfonyl)propoxy]-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-[3-(methylsulfonyl)propoxy]adenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-(4-pyridylmethylamino)adenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-[2-methoxyethyl(N-methyl)amino]adenine,

2-benzylamino-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-[(4-pyridylmethyl)oxy]adenine,

2-ethoxy-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-propoxyadenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-pentoxyadenine,

2-butoxy-8-hydroxy-9-{3-[(4-dimethylaminobutoxy)carbonylmethyl]benzyl} adenine,

2-ethoxy-8-hydroxy-9-(3-[(4-dimethylaminobutoxy)carbonylmethyl]adenine,

2-butoxy-8-hydroxy-9-{3-[(2-dimethylaminoethoxy)carbonylmethyl]benzyl}adenine,

2-butoxy-8-hydroxy-9-{3-[(3-dimethylaminopropoxy)carbonylmethyl]benzyl}adenine,

2-butoxy-8-hydroxy-9-{3-[(6-dimethylaminohexanoxy)carbonylmethyl]benzyl}adenine,

2-butoxy-8-hydroxy-9-{3-[(3-diethylaminopropoxy)carbonylmethyl]benzyl}adenine,

2-butoxy-8-hydroxy-9-{3-[(2-morpholinoethoxy)carbonylmethyl]benzyl}adenine,

2-butoxy-8-hydroxy-9-{3-[(2-piperidinoethoxy)carbonylmethyl]benzyl}adenine,

2-butoxy-8-hydroxy-9-{3-[(2,2,2-trifluoroethoxy)carbonylmethyl]benzyl}adenine,

2-butoxy-8-hydroxy-9-{3-[(2-hydroxyethoxy)carbonylmethyl]benzyl}adenine,

2-butoxy-8-hydroxy-9-{3-[(2,3-dihydroxypropoxy)carbonylmethyl]benzyl}adenine,

2-butoxy-8-hydroxy-9-{5-[(4-dimethylaminobutoxy)carbonylmethyl]-2-methoxybenzyl}adenine,

8-hydroxy-2-(4-hydroxybutylthio)-9-{3-[(2-hydroxyethoxy)carbonylmethyl]benzyl}adenine,

8-hydroxy-9-{3-[(4-dimethylaminobutoxy)carbonylmethyl]benzyl}-2-[(4-pyridylmethyl)oxy] adenine,

2-[2-(4-bromophenyloxy)ethoxy]-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-(2-phenyloxyethoxy)adenine,

2-(3-aminopropoxy)-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine,

2-[3-(N-acetylamino)propoxy]-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine,

8-hydroxy-2-[3-(N-methanesulfonylamino)propoxy]-9-(3-methoxycarbonylmethylbenzyl)adenine,

8-hydroxy-2-[3-(N-methoxycarbonylamino)propoxy]-9-(3-methoxycarbonylmethylbenzyl)adenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-(3-ureidopropoxy)adenine,

2-(2-diethylaminoethoxy)-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-trifluoromethyladenine,

2-butyl-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-pentyladenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-(3-methoxypropyl)adenine,

2-ethoxymethyl-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine,

2-ethoxymethyl-8-hydroxy-9-{3-[(4-dimethylaminobutoxy)carbonylmethyl]benzyl}adenine,

2-cyclopentyl-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine,

8-hydroxy-2-(3-hydroxypropyl)-9-(3-methoxycarbonylbenzyl)adenine,

2-(4-fluorobenzyl)-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-(2-pyridylmethoxy)adenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-(3-pyridylmethoxy)adenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-(3-morpholinopropoxy)adenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-{2-(phenylsulfanyl)ethoxy}adenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-(2-methylsulfanylethoxy)adenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-phenylsulfanyladenine,

8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)-2-(tetrahydrofuran-2-ylmethoxy)adenine,

9-(3-carboxymethylbenzyl)-8-hydroxy-2-(3-hydroxypropylthio)adenine,

9-(3-carboxymethylbenzyl)-8-hydroxy-2-(4-hydroxybutylthio)adenine,

9-(3-carboxymethylbenzyl)-8-hydroxy-2-(2-methoxyethylthio)adenine,

9-(3-carboxymethylbenzyl)-8-hydroxy-2-(3-hydroxypropoxy)adenine,

9-(3-carboxymethylbenzyl)-8-hydroxy-2-(2-hydroxyethoxy)adenine,

9-(3-carboxymethylbenzyl)-8-hydroxy-2-(4-hydroxybutoxy)adenine,

9-(3-carboxymethylbenzyl)-8-hydroxy-2-(4,4,4-trifluorobutoxy)adenine,

9-(3-carboxymethylbenzyl)-8-hydroxy-2-[N-(2-methoxyethyl)amino]adenine,

2-butoxy-9-[2-(3-carboxymethylphenyl)ethyl]-8-hydroxyadenine,

2-butoxy-9-[3-(3-carboxymethylphenyl)propyl]-8-hydroxyadenine,

9-(3-carboxymethylbenzyl)-2-(2,3-dihydroxy-1-propoxy)-8-hydroxyadenine,

9-(3-carboxymethylbenzyl)-2-(2-ethoxyethoxy)-8-hydroxyadenine,

9-(3-carboxymethylbenzyl)-2-cyclohexylmethoxy-8-hydroxyadenine,

2-benzyloxy-9-(3-carboxymethylbenzyl)-8-hydroxyadenine,

2-(2-carboxyethyl)-9-(3-carboxymethylbenzyl)-8-hydroxyadenine,

2-butoxy-9-{(5-carboxymethyl-2-thienyl)methyl}-8-hydroxyadenine,

2-butoxy-9-{(6-carboxymethyl-2-pyridyl)methyl}-8-hydroxyadenine,

2-butoxy-9-{(4-carboxymethyl-2-pyridyl)methyl}-8-hydroxyadenine,

2-butoxy-9-(5-carboxymethyl-2-methoxy)benzyl-8-hydroxyadenine,

2-butoxy-9-(3-carboxymethyl-4-fluoro)benzyl-8-hydroxyadenine,

2-butoxy-9-(3-carboxymethyl-4-methoxy)benzyl-8-hydroxyadenine,

9-(3-carboxymethylbenzyl)-2-ethoxy-8-hydroxyadenine,

9-(3-carboxymethylbenzyl)-8-hydroxy-2-propoxyadenine,

9-(3-carboxymethylbenzyl)-8-hydroxy-2-pentoxyadenine,

9-(3-carboxymethylbenzyl)-8-hydroxy-2-(2-phenyloxyethoxy)adenine,

2-[3-(N-acetylamino)propoxy]-9-(3-carboxymethylbenzyl)-8-hydroxyadenine,

9-(3-carboxymethylbenzyl)-8-hydroxy-2-[3-(N-methanesulfonylamino)propoxy]adenine,

9-(3-carboxymethylbenzyl)-2-cyclopentyl-8-hydroxyadenine

9-(3-carboxymethylbenzyl)-8-hydroxy-2-(3-hydroxypropane-1-yl)adenine,

9-(3-carboxymethylbenzyl)-8-hydroxy-2-(2-pyridylmethoxy)adenine,

9-(3-carboxymethylbenzyl)-8-hydroxy-2-(3-pyridylmethoxy)adenine,

9-(3-carboxymethylbenzyl)-8-hydroxy-2-(2-phenylsulfanylethoxy)adenine, and

9-(3-carboxymethylbenzyl)-8-hydroxy-2-(tetrahydrofuran-2-ylmethoxy)adenine.