Heteroannelated anthraquinone derivatives and the synthesis method thereof

Abstract

A heteroannelated anthraquinone derivative compound is provided. The heteroannelated anthraquinone derivative compound is represented by a formula (I): wherein R 1 is a substituent being one selected from a group consisting of i) a first substituent being one selected from a group consisting of a hydryl group, an amino group, a nitro group, a hydroxyl group and a cyan group, ii) a second substituent being one selected from a group consisting of (CH 2 ) n X, a straight (CH 2 ) n alkyl group, a (CH 2 ) n alkoxyl group, a branched (CH 2 ) n alkyl group, a C 3 ˜C 12 nephthenic group, and a C 3 ˜C 12 cyclic alkoxyl group, wherein 1=n=12, and X is a halogen, iii) a third substituent being one selected from a group consisting of a straight C 1 ˜C 8 alkyl group with a double-bond, a C 1 ˜C 8 alkoxyl group with a double-bond, a branched C 1 ˜C 8 alkyl group with a double-bond and a C 3 ˜C 8 nephthenic group with a double-bond, and iv) a fourth substituent of a C 5 ˜C 12 heterocyclic group.

1 . A heteroannelated anthraquinone derivative compound represented by a formula (I): 
     
       
         
         
             
             
         
       
       wherein R 1  is a substituent being one selected from a group consisting of: 
       i) a first substituent being one selected from a group consisting of a hydryl group, an amino group, a nitro group, a hydroxyl group and a cyan group; 
       ii) a second substituent being one selected from a group consisting of (CH 2 ) n X, a straight (CH 2 ) n  alkyl group, a (CH 2 ) n  alkoxyl group, a branched (CH 2 ) n  alkyl group, a C 3 ˜C 12 nephthenic group, and a C 3 ˜C 12  cyclic alkoxyl group, wherein 1=n=12, and X is a halogen; 
       iii) a third substituent being one selected from a group consisting of a straight C 1 ˜C 8  alkyl group with a double-bond, a C 1 ˜C 8  alkoxyl group with a double-bond, a branched C 1 ˜C 8  alkyl group with a double-bond and a C 3 ˜C 8  nephthenic group with a double-bond; and 
       iv) a fourth substituent of a C 5 ˜C 12  heterocyclic group. 
     
   
   
       2 . A compound as claimed in  claim 1 , wherein R 1  is an ethyl group. 
   
   
       3 . A compound as claimed in  claim 1 , wherein one of the nephthenic group and the heterocyclic group further has at least one of an ortho-substitution, a meta-substitution and a para-substitution, and comprises at least a fifth substituent for any of the substitutions being one selected from a group consisting of an alkyl group with a C 1 ˜C 3  substituent branch, an amino group, a nitro group, a hydroxyl group and a cyan group, a C 1 ˜C 5  alkyl group, a halogen substituted C 1 ˜C 5  alkyl group, a C 1 ˜C 5  alkoxyl group, a halogen substituted C 1 ˜C 5  alkoxyl group, a C 1 ˜C 5  cyclic alkoxyl group, and a halogen substituted C 1 ˜C 5  cyclic alkoxyl group. 
   
   
       4 . A compound as claimed in  claim 1 , wherein the halogen is one selected from a group consisting of a fluorine, a chlorine, a bromine and an iodine. 
   
   
       5 . A compound as claimed in  claim 1 , wherein the second substituent is one selected from a group consisting of a methyl group, an ethyl group, a propyl group, a butyl group, an isobutyl group, a pentyl group, an isopentyl group, a cyclopentyl group, a heptyl group, an isoheptyl group, a cycloheptyl group, an octyl group, an isooctyl group, a cyclooctyl group, a straight alkyl group with a branch substituted by a straight C 1 ˜C 5  alkyl group, a nephthenic group with a branch substituted by a straight C 1 ˜C 5  alkyl group, alkoxyl derivatives of the mentioned alkyl groups, and halogenated derivatives of the mentioned alkyl groups. 
   
   
       6 . A compound as claimed in  claim 1 , wherein the third substituent is one selected from a group consisting of a vinyl group, a propenyl group, a butenyl group, an isobutenyl group, a pentenyl group, an isopentenyl group, a cyclopentenyl group, a hexenyl group, a cyclohexenyl group, a heptenyl group, an cycloheptenyl group, a straight alkyl group with a branch substituted by a straight C 1 ˜C 3  alkyl group, a nephthenic group with a branch substituted by a straight C 1 ˜C 3  alkyl group, alkoxyl derivatives of the mentioned groups, and halogenated derivatives of the mentioned groups. 
   
   
       7 . A compound as claimed in  claim 1 , being used as an effective component together with an excipient to provide a pharmaceutic composition for inhibiting one selected from a group consisting of a growth of a cancer cell, a disease of cell proliferation, and a growth of cell telomere. 
   
   
       8 . A heteroannelated anthraquinone derivative compound represented by a formula (II): 
     
       
         
         
             
             
         
       
     
   
   
       9 . A compound as claimed in  claim 8 , being used as an effective component together with an excipient to provide a pharmaceutic composition for inhibiting one selected from a group consisting of a growth of a cancer cell, a disease of cell proliferation, and a growth of cell telomere. 
   
   
       10 . A heteroannelated anthraquinone derivative compound represented by a formula (III): 
     
       
         
         
             
             
         
       
       wherein either one of R 2  and R 3  is one of: 
       i) a first substituent being one of a hydryl group and a sulfuryl-group; and 
       ii) a second substituent being one selected from a group consisting of a C 1 ˜C 8  alkyl group, a C 1 ˜C 8  alkoxyl group, a C 3 ˜C 8  nephthenic group, and a C 3 ˜C 8  cyclic alkoxyl group, a straight alkyl group with a branch substitutent, a nephthenic group with a branch substitutent by a straight C 1 ˜C 5  alkyl group and halogenated derivatives of the mentioned substitent groups. 
     
   
   
       11 . A compound as claimed in  claim 10 , wherein the second substituent is one selected from a group consisting of a methyl group, an ethyl group, a propyl group, a butyl group, an isobutyl group, a pentyl group, an isopentyl group, a cyclopentyl group, a heptyl group, an isoheptyl group, a cycloheptyl group, an octyl group, an isooctyl group, a cyclooctyl group, a phenyl group, a benzyl group, a phenethyl group, a straight alkyl group with a branch substituted by a straight C 1 ˜C 3  alkyl group, a nephthenic group with a branch substituted by a straight C 1 ˜C 3  alkyl group, alkoxyl derivatives of the mentioned substituent groups, and halogenated derivatives of the mentioned substituent groups. 
   
   
       12 . A compound as claimed in  claim 10 , being used as an effective component together with an excipient to provide a pharmaceutic composition for inhibiting one selected from a group consisting of a growth of a cancer cell, a disease of cell proliferation, and a growth of cell telomere. 
   
   
       13 . A heteroannelated anthraquinone derivative compound represented by a formula (IV): 
     
       
         
         
             
             
         
       
       wherein R4 is one selected from a group consisting of a hydryl group, a C 1 ˜C 4  alkyl group, a C 1 ˜C 4  alkoxyl group, a C 1 ˜C 4  ketone group, a straight alkyl group with a branch substituted by a straight C 1 ˜C 3  alkyl group, a halogen substituted C 1 ˜C 4  alkyl group, and a C 1 ˜C 4  alkoxyl group. 
     
   
   
       14 . A compound as claimed in  claim 13 , wherein R 4  is a hydrogen. 
   
   
       15 . A compound as claimed in  claim 13 , being used as an effective component together with an excipient to provide a pharmaceutic composition for inhibiting one selected from a group consisting of a growth of a cancer cell, a disease of cell proliferation, and a growth of cell telomere. 
   
   
       16 . A method for manufacturing a compound having a formula (I) as claimed in  claim 1 , comprising steps of:
 a) dissolving a diaminoanthraquinone in a dimethylformamide solution for forming a solution A;   b) adding and dissolving a chloroacetyl chloride in the solution A for forming a solution B;   c) mixing and reacting the solution B by a reverse flow method, and then transferring the solution B into an icy water for forming a solution C;   d) filtering the solution C for obtaining a precipitate; and   e) washing the precipitate by using an ethanol for obtaining the compound of the formula (I).   
   
   
       17 . A method for manufacturing a compound having a formula (I) as claimed in  claim 1 , comprising steps of:
 a) dissolving a diaminoanthraquinone in a dimethylformamide solution for forming a solution A;   b) adding and dissolving a reagent in the solution A for forming a solution B, wherein the reagent is one of a benzaldehyde and a carbon disulfide;   c) catalyzing a reaction of the solution B by adding a concentrated sulfuric acid thereinto, and then transferring the solution B into an ice water for forming a solution C;   d) filtering the solution C for obtaining a precipitate; and   e) washing the precipitate by using an ethanol for obtaining the compound of the formula (I),   wherein when the reagent is the carbon disulfide, a triethylamine is further added into the solution B before the step c).   
   
   
       18 . A method for manufacturing a compound having a formula (III) as claimed in  claim 10 , comprising steps of:
 a) dissolving a diaminoanthraquinone in an acetone for forming a solution A;   b) adding a concentrated sulfuric acid into the solution A for forming a solution B;   c) transferring the solution B into a potassium carbonate column for obtaining a solution C; and   d) using a methanol to crystallize the compound of the formula (III) in the solution C.   
   
   
       19 . A method as claimed in  claim 18 , wherein the step b) is performed in a room temperature. 
   
   
       20 . A method for manufacturing a compound having a formula (IV) as claimed in  claim 13 , comprising steps of:
 a) dissolving a diaminoanthraquinone in a dimethylformamide solution for forming a solution A;   b) adding a glyoxal ethanol solution into the solution A for forming a solution B;   c) reacting the solution B by a reverse flow reaction;   d) filtering the solution B for obtaining a precipitate; and   e) washing the precipitate by using a hot alcohol and a dichloromethane for separating out the compound of the formula (IV).