CYCLOBUTYL PURINE DERIVATIVE, ANGIOGENESIS PROMOTING AGENT, LUMEN FORMATION PROMOTING AGENT, NEUROCYTE GROWTH PROMOTING AGENT, AND DRUG

• US 20110230659A1
• Filed: 11/27/2009
• Published: 09/22/2011
• Est. Priority Date: 11/27/2008
• Status: Active Grant

• Current Assignee: National University Corporation Kagawa University
• Original Assignee: National University Corporation Kagawa University
• Inventors: Tokuda, Masaaki, Igarashi, Junsuke, Kosaka, Hiroaki, Konishi, Ryoji, Maruyama, Tokumi, Kubota, Yasuo, Tsukamoto, Ikuko
• Granted Patent: US 9,273,050 B2
• Time in Patent Office: Days
• US Class Current: 544/276
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• 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
• CPC Class Codes: C07D 473/40 with halogen atoms or perhalogeno-alkyl radicals directly attached in position 2 or 6

Abstract

Provided is a compound having at least one selected from the group consisting of cell growth promoting activity, angiogenesis promoting activity, lumen formation promoting activity, cell migration promoting activity, and neurocyte growth promoting activity, which is a chemically stable low-molecular-weight substance that has high absorbability and can be supplied stably at a low cost because of its low molecular weight. A cyclobutyl purine derivative, a tautomer or stereoisomer thereof, or a salt, solvate, or hydrate thereof according to the present invention is a cyclobutyl purine derivative represented by the following general formula (1), a tautomer or stereoisomer thereof, or a salt, solvate, or hydrate thereof.

Claims

1. A cyclobutyl purine derivative represented by the following general formula (1), a tautomer or stereoisomer thereof, or a salt, solvate, or hydrate thereof.

2. The cyclobutyl purine derivative, the tautomer or stereoisomer thereof, or the salt, solvate, or hydrate thereof according to claim 1, wherein, in the general formula (1), X₁ is a chloro group.

3. The cyclobutyl purine derivative, the tautomer or stereoisomer thereof, or the salt, solvate, or hydrate thereof according to claim 1, wherein, in the general formula (1), X₂ is an amino group.

4. The cyclobutyl purine derivative, the tautomer or stereoisomer thereof, or the salt., solvate, or hydrate thereof according to claim 1, wherein, in the general formula (1), R₁ and R₂ are hydroxymethyl groups.

5. The cyclobutyl purine derivative, the tautomer or stereoisomer thereof, or the salt, solvate, or hydrate thereof according to claim 1, wherein, in the general formula (1), X₁ is a chloro group or a thiomethoxy group, X₂ is an amino group, and R₁ and R₂ are hydroxymethyl groups.

6. The cyclobutyl purine derivative, the tautomer or stereoisomer thereof, or the salt, solvate, or hydrate thereof according to claim 1, which is 6-amino-2-chloro-9-[trans-trans-2,3-bis(hydroxymethyl)cyclobutyl]purine or 6-amino-2-thiomethoxy-9-[trans-trans-2,3-bis(hydroxymethyl)cyclobutyl]purine, a tautomer or stereoisomer thereof, or a salt, solvate, or hydrate thereof.

12. A promoting agent having at least one function selected from the group consisting of an angiogenesis-promoting function, a lumen formation-promoting function, and a neurocyte growth-promoting function, the promoting agent comprising:

the cyclobutyl purine derivative, the tautomer or stereoisomer thereof, or the salt, solvate, or hydrate thereof according to claim 6.

13. A drug for use in at least one selected from the group consisting of promoting angiogenesis, promoting lumen formation, and promoting neurocyte growth, the drug comprising:

at least one selected from the group consisting of the cyclobutyl purine derivative, the tautomers and stereoisomers thereof, the salts, solvates, and hydrates thereof according to claim 1, and the promoting agent according to claim 7.

14. The drug according to claim 13, which is at least one selected from the group consisting of wound healing agents, therapeutic agents for Alzheimer'"'"'s disease, prophylactic agents for Alzheimer'"'"'s disease, therapeutic agents for infarction diseases, prophylactic agents for infarction diseases, and hair growth agents.

7. A promoting agent having at least one function selected from the group consisting of an angiogenesis-promoting function, a lumen formation-promoting function, and a neurocyte growth-promoting function, the promoting agent comprising:

a cyclobutyl purine derivative represented by the following general formula (1′

), a tautomer or stereoisomer thereof, or a salt, solvate, or hydrate thereof;

8. The promoting agent according to claim 7, wherein, in the general formula (1′

), X_1′

is a chloro group.

9. The promoting agent according to claim 7, wherein, in the general formula (1′

), X_2′

is an amino group.

10. The promoting agent according to claim 7, wherein, in the general formula (1′

), R_1′

and R_2′

are hydroxymethyl groups.

11. The promoting agent according to claim 7, wherein, in the general formula (1′

), X_1′

is a chloro group or a thiomethoxy group, X_2′

is an amino group, X_3′

is a hydrogen atom, and R_1′

and R_2′

are hydroxymethyl groups.