Purine derivative

• US 6,028,076 A
• Filed: 03/03/1998
• Issued: 02/22/2000
• Est. Priority Date: 07/03/1996
• Status: Expired due to Term

• Current Assignee: Dainippon Sumitomo Pharma Company Limited (Sumitomo Chemical Company Limited)
• Original Assignee: Japan Energy Corporation (ENEOS Holdings, Inc.)
• Inventors: Satoh, Harumi, Hirota, Kohsaku, Chiba, Nobuyoshi, Matsui, Hiroyuki, Isobe, Yoshiaki, Ogita, Haruhisa, Takaku, Haruo
• Primary Examiner(s): Berch, Mark L.
• Application Number:
  US09/029,076
• Time in Patent Office: 721 Days
• Field of Search: 544/277, 544/276, 544/265, 514/261, 514/262, 514/266
• US Class Current: 514/263.37
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07D 473/00 Heterocyclic compounds containing purine ring systems
• CPC Class Codes: C07D 473/30 attached in position 6, e.g. hypoxanthine
• CPC Class Codes: C07D 473/34 attached in position 6, e.g. adenine

Abstract

This invention relates to novel purine derivatives of formula (I): ##STR1## where R² and R⁹ are hydrocarbon groups, R⁶ is an amino group and R⁸ is a hydroxyl, or acyloxy group. These purine derivatives are effective at promoting secretion of interferon in patients, and can be used to treat diseases against which interferon is effective.

Claims

1. A purine derivative represented by the following formula (Ia):

##STR15## wherein R² is a hydrocarbon group containing at most 14 carbon atoms;

any --CH₂ -- group in said hydrocarbon group may be replaced with a carbonyl group, a sulfonyl group --O-- or --S-- when said --CH₂ -- group is not directly attached to the purine ring or is in --CH₃ group not directly attached to the purine ring;

any ═

CH₂ group may be replaced with ═

O or ═

S;

C--H group in said hydrocarbon group may be replaced with N, a C-halogen group or a C--CN group when said C--H group is in --CH₂ -- group not directly attached to the purine ring, in --CH₃ group not directly attached to the purine ring, in >

CH-- group not directly attached to the purine ring, in ═

CH-- group not directly attached to the purine ring or in ═

CH₂ group;

R⁶ is an amino group;

R⁸ is a hydroxyl group, a mercapto group, a group of the formula;

space="preserve" listing-type="equation">R.sup.10 --CO.sub.2 --

wherein R¹⁰ is a hydrogen atom or a hydrocarbon group containing at most 17 carbon atoms,

or an oxycarbonyloxy group substituted with a hydrocarbon group containing at most 19 carbon atoms;

R⁹ is a hydrocarbon group containing at most 14 carbon atoms;

any --CH₂ -- group in said R⁹ may be replaced with a carbonyl group, a sulfonyl group, --O-- or --S-- when said --CH₂ -- group is not directly attached to the purine ring or is in --CH₃ group not directly attached to the purine ring;

any ═

CH₂ group may be replaced with ═

O or ═

S;

C--H group in said R⁹ may be replaced with a C-halogen group or a C--CN group when said C--H group is in --CH₂ -- group not directly attached to the purine ring, in --CH₃ group not directly attached to the purine ring, in >

CH-- group not directly attached to the purine ring, in ═

CH-- group not directly attached to the purine ring, in ═

CH₂ group or in .tbd.CH group;

or its tautomer or pharmaceutically acceptable salts thereof.

3. A compound according to claim 1, wherein R⁸ is a hydroxyl group.

4. A compound according to claim 1, wherein R⁹ is a non-substituted benzyl group or a benzyl group substituted on the aromatic ring with a substituent or substituents selected from halogen groups and lower alkyl groups.

2. A method for inducing α

-interferon in a patient having Hepatitis B or C, comprising;

administering to said patient an effective amount of a purine derivative represented by formula (I);

##STR16## wherein R² is a hydrocarbon group containing at most 14 carbon atoms;

any --CH₂ -- group in said hydrocarbon group may be replaced with a carbonyl group, a sulfonyl group, --O-- or --S-- when said --CH₂ -- group is not directly attached to the purine ring or is in --CH₃ group not directly attached to the purine ring;

any ═

CH₂ group may be replaced with ═

O or ═

S;

C--H group in said hydrocarbon group may be replaced with N, a C-halogen group or a C--CN group when said C--H group is in --CH₂ -- group not directly attached to the purine ring, in --CH₃ group not directly attached to the purine ring, in >

CH-- group not directly attached to the purine ring, in ═

CH-- group not directly attached to the purine ring or in ═

CH₂ group;

R⁶ is an amino group;

R⁸ is a hydroxyl group, a mercapto group, a group of the formula;

space="preserve" listing-type="equation">R.sup.10 --CO.sub.2 --

wherein R¹⁰ is a hydrogen atom or a hydrocarbon group containing at most 17 carbon atoms,

or an oxycarbonyloxy group substituted with a hydrocarbon group containing at most 19 carbon atoms,

R⁹ is a hydrocarbon group containing at most 14 carbon atoms;

any --CH₂ -- group in said R⁹ may be replaced with a carbonyl group, a sulfonyl group, --O-- or --S-- when said --CH₂ -- group is not directly attached to the purine ring or is in --CH₃ group not directly attached to the purine ring;

any ═

CH₂ group may be replaced with ═

O or ═

S;

C--H group in said R⁹ may be replaced with a C-halogen group or a C--CN group when said C--H group is in --CH₂ -- group not directly attached to the purine ring, in --CH₃ group not directly attached to the purine ring, in >

CH-- group not directly attached to the purine ring, in ═

CH-- group not directly attached to the purine ring, in ═

CH₂ group or in .tbd.CH group;

or its tautomer or pharmaceutically acceptable salts thereof, effective to treat said patient having Hepatitis B or C.

5. A method for promoting a secretion of α

-interferon in a cell capable of secreting α

-interferon, comprising administering an amount of a purine derivative represented by formula (I) to said cell;

##STR17## wherein R² is a hydrocarbon group containing at most 14 carbon atoms;

any --CH₂ -- group in said hydrocarbon group may be replaced with a carbonyl group, a sulfonyl group, --O-- or --S-- when said --CH₂ -- group is not directly attached to the purine ring or is in --CH₃ group not directly attached to the purine ring;

any ═

CH₂ group may be replaced with ═

O or ═

S;

C--H group in said hydrocarbon group may be replaced with N, a C-halogen group or a C--CN group when said C--H group is in --CH₂ -- group not directly attached to the purine ring, in --CH₃ group not directly attached to the purine ring, in >

CH-- group not directly attached to the purine ring, in ═

CH-- group not directly attached to the purine ring or in ═

CH₂ group;

R⁶ is an amino group;

R⁸ is a hydroxyl group, a mercapto group, a group of the formula;

space="preserve" listing-type="equation">R.sup.10 --CO.sub.2 --

wherein R¹⁰ is a hydrogen atom or a hydrocarbon group containing at most 17 carbon atoms,

or an oxycarbonyloxy group substituted with a hydrocarbon group containing at most 19 carbon atoms;

R⁹ is a hydrocarbon group containing at most 14 carbon atoms;

any --CH₂ -- group in said R⁹ may be replaced with a carbonyl group a sulfonyl group, --O-- or --S-- when said --CH₂ -- group is not directly attached to the purine ring or is in --CH₃ group not directly attached to the purine ring;

any ═

CH₂ group may be replaced with ═

O or ═

S;

C--H group in said R⁹ may be replaced with a C-halogen group or a C--CN group when said C--H group is in --CH₂ -- group not directly attached to the purine ring, in --CH₃ group not directly attached to the purine ring, in >

CH-- group not directly attached to the purine ring, in ═

CH-- group not directly attached to the purine ring, in ═

CH₂ group or in .tbd.CH group;

or its tautomer or pharmaceutically acceptable salts thereof, effective to promote a secretion of interferon in said cell.