Heterocyclic compounds

• US 6,329,381 B1
• Filed: 05/26/2000
• Issued: 12/11/2001
• Est. Priority Date: 11/28/1997
• Status: Expired due to Fees

• Current Assignee: Dainippon Sumitomo Pharma Company Limited (Sumitomo Chemical Company Limited)
• Original Assignee: Japan Energy Corporation (ENEOS Holdings, Inc.), Sumitomo Pharmaceuticals Company Limited (Sumitomo Chemical Company Limited)
• Inventors: Kurimoto, Ayumu, Ogino, Tetsuhiro, Kawakami, Hajime
• Primary Examiner(s): Shah, Mukund J.
• Assistant Examiner(s): McKenzie, Thomas C
• Application Number:
  US09/555,292
• Time in Patent Office: 564 Days
• Field of Search: 514/262, 544/276
• US Class Current: 514/263.23
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• 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

Abstract

The present invention relates to a heterocyclic compound of the following general formula (I):

wherein X is sulfur atom, oxygen atom or —NR³— (R³ may form a heterocyclic ring or a substituted heterocyclic ring with R¹ via the nitrogen atom),

R¹ is alkyl group, substituted alkyl group, aryl group, substituted aryl group, heterocyclic group or substituted heterocyclic group, and

R² is hydrogen atom, halogen atom etc.;

or its pharmaceutically acceptable salt and interferon inducers, antiviral agents, anticancer agents and therapeutic agents for immunologic diseases comprising the compound (I) or its pharmaceutically acceptable salt as active ingredients.

Claims

1. A heterocyclic compound of the following formula (I):

wherein X is sulfur atom, oxygen atom or —

NR^3a—

(in which R^3a is hydrogen atom, C_1-10 alkyl group, C_3-7 cycloalkyl group, or C_1-10 alkyl substituted by C_3-6 cyclo-alkyl group, hydroxy group, C_3-6 alkoxy group, amino group, cyano group, aryl group, aryl group substituted by C_1-6 alkoxy, hydroxy or halogen, halogen atom, or nitro group, or

may form a heterocyclic ring or a substituted heterocyclic ring together with R¹ via the nitrogen atom, wherein said substituent means C_1-6 alkyl group, hydroxy C_1-6 alkyl group, C_1-6 alkoxy C_1-6 alkyl group, hydroxy group, C_1-6 alkoxy group, or cyano group),

R¹ is C_1-10 alkyl group;

C_3-7 cycloalkyl group;

C_3-7 cycloalkyl substituted by C_1-6 alkyl;

a group selected from C_1-10 alkyl group, C_3-7 cycloalkyl group or C_1-6 alkyl-substituted C_3-7 cycloalkyl group, which is substituted by

C_3-6 cycloalkyl group, hydroxy group, C_1-6 alkoxy group,

C_1-6 alkoxy group substituted by C_1-6 alkoxy, hydroxy or halogen,

amino group, C_1-6 alkylamino group, cyano group, nitro group, acyl group, carboxyl group, C_2-7 alkoxycarbonyl group, halogen atom, mercapto group, C_1-6 alkylthio group,

C_1-6 alkylthio group substituted by C_1-6 alkoxy, C_1-6 alkylthio, hydroxy or halogen, aryl group, aryl group substituted by C_1-6 alkoxy, hydroxy or halogen, or heterocyclic group;

aryl group;

aryl group substituted by

C_1-6 alkyl group, hydroxy C_1-6 alkyl group,

C_1-6 alkoxy C_1-6 alkyl group, hydroxy group, C_1-6 alkoxy group, cyano group, amino group, C_1-6 alkylamino group, C_2-7 alkoxycarbonyl group, acyl group, nitro group, halogen atom, aryl group, aryl group substituted by C_1-6 alkoxy, hydroxy or halogen, or heterocyclic group;

heterocyclic group;

or heterocyclic group substituted by

C_1-6 alkyl group, hydroxy C_1-6 alkyl group, C_1-6 alkoxy C_1-6 alkyl group, hydroxy group, C_1-6 alkoxy group, cyano group, nitro group, halogen atom, amino group, C_1-6 alkylamino group, C_2-7 alkoxycarbonyl group, acyl group, aryl group, aryl group substituted by C_1-6 alkoxy, hydroxy or halogen or

heterocyclic group, and

R² is hydrogen atom, or one or more substituents on the benzene ring, and said substituent is the same or different and is hydroxy group, C_1-6 alkyl group, C_1-6 alkyl group substituted by hydroxy group, C_1-6 alkoxy group, carboxyl, C_2-7 alkoxycarbonyl group or halogen atom, C_1-6 alkoxy group,

C_1-6 alkoxy group substituted by hydroxy group, C_1-6 alkoxy group, carboxyl, C_2-7 alkoxycarbonyl group or halogen atom, C_1-6 alkanoyl group,

C_1-6 alkanoyl group substituted by hydroxy group, C_1-6 alkoxy group, carboxyl, C_2-7 alkoxycarbonyl group or halogen atom, aroyl group, aroyl group substituted by hydroxy group, C_1-6 alkoxy group, carboxyl, C_2-7 alkoxycarbonyl group or halogen atom, carboxyl group, C_2-7 alkoxycarbonyl group, C_2-7 alkoxycarbonyl group substituted by hydroxy group, C_1-6 alkoxy group, carboxyl,

C_2-7 alkoxycarbonyl group or halogen atom,

amino group, C_1-6 alkylamino group, di(C_1-6 alkyl)amino group, carbamoyl group, C_1-6 alkylcarbamoyl group, di(C_1-6 alkyl)carbamoyl group, halogen atom, nitro group, or cyano group,

or a pharmaceutically acceptable salt thereof.

2. The heterocyclic compound of claim 1, wherein X is sulfur atom, or its pharmaceutically acceptable salt.

3. The heterocyclic compound of claim 1, wherein X is oxygen atom, or its pharmaceutically acceptable salt.

4. The heterocyclic compound of claim 1, wherein X is —

NH—

, or its pharmaceutically acceptable salt.

5. The heterocyclic compound of claim 1, wherein X is —

NR^3a—

in which R^3a means C_1-6 alkyl group or substituted C_1-6 alkyl substituted by

C_3-6 cycloalkyl group, hydroxy group, C_1-6 alkoxy group,

amino group, cyano group, aryl group,

aryl group substituted by C_1-6 alkoxy, hydroxy or halogen,

halogen atom, or nitro group,

or its pharmaceutically acceptable salt.

6. The heterocyclic compound of claim 1, wherein R^3a forms a heterocyclic ring or a substituted heterocyclic ring together with R¹ via the nitrogen atom, or its pharmaceutically acceptable salt.

7. The heterocyclic compound of claim 1, wherein R¹ means C_1-6 alkyl group or substituted C_1-6 alkoxy, C_1-6 alkylthio, C_2-7 alkoxycarbonyl, hydroxy, halogen atom, cyano, amino, cyclohexyl, trifluoromethyl, pyridyl, phenyl, methoxyphenyl, hydroxyphenyl, halophenyl or thienyl, or its pharmaceutically acceptable salt.

8. The heterocyclic compound of claim 1, wherein R¹ means C_1-6 substituted alkyl group and said substituent is hydroxyl, or its pharmaceutically acceptable salt.

12. A pharmaceutical composition comprising a heterocyclic compound or its pharmaceutically acceptable salt of claim 1, as an active ingredient.

13. A method for inducing interferons in a patient having virus infected disease, cancer or allergic disease by administering the heterocyclic compound of claim 1, or its pharmaceutically acceptable salt to the patient in an amount effective to induce interferons.

9. 6-Amino-9-benzyl-8-hydroxy-2-[(2-hydroxyethyl)thio]purine or its pharmaceutically acceptable salt.

10. 6-Amino-9-(4-fluorobenzyl)-8-hydroxy-2-(2-methoxyethoxy)purine or its pharmaceutically acceptable salt.

11. 6-Amino-9-benzyl-8-hydroxy-2-(2-methoxyethoxy)purine or its pharmaceutically acceptable salt.