US2004132993A1PendingUtilityA1

Antiviral and antimicrobial guanidine or biguanidine derivatives

Priority: Aug 28, 2000Filed: Nov 25, 2003Published: Jul 8, 2004
Est. expiryAug 28, 2020(expired)· nominal 20-yr term from priority
C07D 401/14C07D 215/56C07D 471/04A61P 31/04A61P 31/00A61P 31/12
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Claims

Abstract

Disclosed are guanidine and biguanidine derivatives which have anti-viral and anti-bacterial activity. Also disclosed are pharmaceutical compositions containing such compounds as an active ingredient, and anti-viral and anti-bacterial methods utilizing such compounds.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . A compound having one of the following structures:  
       
         
           
           
               
               
           
         
       
       wherein: 
 a) each A is the same or different, and is selected from the group consisting of i) hydrogen, ii) a nitrile, iii) an amino, iv) an antibacterial agent, v) an antibiotic, vi) a quinolone, vii) an azaquinolone, and viii) one of the following groups:  
                     
 where R 12  is hydrogen or C 1 -C 6  straight or branched alkyl, and R 11  is hydrogen, lower alkyl, an aromatic group or a heterocyclic group, with the proviso that with respect to structures I-III, both A's cannot be the adamantane structure above at the same time;  
 b) B is a straight chain or branched C 1 -C 30  alkyl group, which may be interrupted by oxygen, sulfur, optionally substituted aromatic nuclei, sulphoxide, optionally substituted cyclohexane, nitrogen optionally substituted with —NH—C (NH)—NH—C(NH)-A where A is defined above, tris (2-aminoethyl)amine, a heterocycle of the following structure:  
                     
 where D is 1-3 carbon atoms and Q is hydrogen, halogen or lower alkyl; or  
                     
 where Q is hydrogen, halogen or lower alkyl; or  
                     
 a hydrophilic moiety; and  
 c) R is hydrogen or C 1 -C 6  straight or branched alkyl.  
 
     
     
         2 . The compound of  claim 1 , wherein A is an antibacterial agent selected from the group consisting of  
       
         
           
           
               
               
           
         
       
       where Z is one or more heterocyclic rings containing at least one N atom  
       or  
       
         
           
           
               
               
           
         
       
       which may be attached to the structure above through any available point of attachment; 
 where n is 0 to 3; R 4 , R 5  and R 6  are each independently hydrogen or lower alkyl or alkylene; G and M are independently O, S or NR 10 ; where R 10  is hydrogen, —C(N)—NH—CN, halogen, a single bond, or lower alkyl or alkylene;  
 E is nitrogen or CR 10 , where R 10  is hydrogen or halogen;  
 K is nitrogen or CR 7 , where R 7  is hydrogen, nitro, halogen, nitrile, carboxamide, carboxyl or an ester;  
 R is hydrogen or lower alkyl;  
 R 1  is hydrogen, a lower arylalkyl group having 1-6 carbon atoms, an alkyl group having 1-4 carbon atoms in the aliphatic part and 6 to 10 carbon atoms in the aromatic part, or an aryl group having 6 to 10 carbon atoms;  
 R 2  is an alkyl group having one to six carbon atoms; a cycloalkyl group having 3 to 7 carbon atoms optionally substituted with halogen; 2,4-difluorophenyl or 2- or 4-fluorophenyl; amino; lower alkylamino; propylamino; N-formyl-lower alkylamino or di-lower-alkylamino; a vinyl group; a 2-fluoroethyl group; a haloalkyl group or a 2-hydroxylkyl group; phenyl or substituted phenyl wherein the phenyl ring is substituted with one or two or three substituents independently selected from C1 to C6 alkyl, halogen, methylenedioxy and hydroxy; alkoxy or trifluoromethyl; 2-, 3-, or 4- pyridine; 2- or 3-thiophene; 2-imidazole; 2-oxazole or 2-thiazole; a pyridyl or adamantyl group; or a benzoxazine group;  
 R 3  is a hydrogen, amino, substituted amino, halogen or a lower alkyl group;  
 R 8  is hydrogen or lower alkyl; and X is methylene, O, S or NR 9 , where R 9  is hydrogen or lower alkyl.  
 
     
     
         3 . A compound according to  claim 2 , wherein Z is selected from the group consisting of  
       
         
           
           
               
               
           
         
       
       where R 4  and R 5  are independently hydrogen or lower alkyl.  
     
     
         4 . A compound according to  claim 1 , selected from the group consisting of:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         5 . A compound according to  claim 1 , wherein the compound has the following structure:  
       
         
           
           
               
               
           
         
       
       where each V is independently hydrogen or halogen.  
     
     
         6 . A compound having the following structure:  
       
         
           
           
               
               
           
         
       
       where each n is independently from 1-5; 
 Y 1  and Y 2  are the same or different, and are optionally substituted alkyl; optionally substituted aryl; an optionally substituted heterocycle; or a single bond;  
 X is optionally substituted alkyl; optionally substituted aryl; or an optionally substituted heterocycle; and  
 each Z is independently —C(NH)—NH—C(NH)-A  
 where A is the same or different, and is selected from the group consisting of i) hydrogen, ii) a nitrile, iii) an amino, iv) an antibacterial agent, v) an antibiotic, vi) a quinolone, vii) an azaquinolone, and viii) one of the following groups:  
                     
 where R 12  is hydrogen or C 1 -C 6  straight or branched alkyl, and R 11  is hydrogen, lower alkyl, an aromatic group or a heterocyclic group  
 and pharmaceutically acceptable salts thereof.  
 
     
     
         7 . The compound of  claim 6 , wherein both Y 1  and Y 2  are single bonds.  
     
     
         8 . The compound of  claim 7 , wherein X is C 1 -C 10  alkyl.  
     
     
         9 . The compound of  claim 6 , wherein Y 1  and Y 2  are lower alkyl and X is phenyl optionally substituted with halogen and/or lower alkyl.  
     
     
         10 . The compound of  claim 9  wherein Y 1  and Y 2  are —CH 2 — 
     
     
         11 . The compound of  claim 6 , wherein Y 1  and Y 2  are lower alkyl and X is pyridyl optionally substituted with halogen and/or lower alkyl.  
     
     
         12 . The compound of  claim 11 , wherein Y 1  and Y 2  are —CH 2 —.  
     
     
         13 . A compound having the following structure:  
       
         
           
           
               
               
           
         
       
       where each n is independently from 1-5; 
 each m is independently from 0-12;  
 each Z is independently —C(NH)NH—C(NH)-A,  
 where each A is the same or different, and is selected from the group consisting of i) hydrogen, ii) a nitrile, iii) an amino, iv) an antibacterial agent, v) an antibiotic, vi) a quinolone, vii) an azaquinolone, and viii) one of the following groups:  
                     
 where R 12  is hydrogen or C 1 -C 6  straight or branched alkyl, and R 11  is hydrogen, lower alkyl, an aromatic group or a heterocyclic group; and  
 T is hydrogen, lower alkyl optionally substituted aryl or an optionally substituted heterocycle; and X is from 0-8.  
 
     
     
         14 . The compound of  claim 13 , wherein the compound has one of the following structures:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         15 . A compound having the following structure:  
       
         
           
           
               
               
           
         
       
       where each A is the same or different, and is selected from the group consisting of i) hydrogen, ii) nitrile, iii) an amino, iv) an antibacterial agent, v) an antibiotic, vi) a quinolone, vii) an azaquinolone, and viii) one of the following groups:  
       
         
           
           
               
               
           
         
       
       where R 12  is hydrogen or C 1 -C 6  straight or branched alkyl, and R 11  is hydrogen, lower alkyl, an aromatic group or a heterocyclic group; with the priviso that at least one A is not hydrogen.  
     
     
         16 . A compound having the following structure:  
       
         
           
           
               
               
           
         
       
       wherein each n is independently from 1-5; 
 m is from 0-3;  
 each L is independently hydrogen, lower alkyl, optionally substituted aryl, or nitro;  
 X is CH or N;  
 each Z is independently —C(NH)NH—C(NH)-A where  
 each A is the same or different, and is selected from the group consisting of i) hydrogen, ii) a nitrile, iii) an amino, iv) an antibacterial agent, v) an antibiotic, vi) a quinolone, vii) an azaquinolone, and viii) one of the following groups:  
                     
 where R 12  is hydrogen or C 1 -C 6  straight or branched alkyl, and R 11  is hydrogen, lower alkyl, an aromatic group or a heterocyclic group.  
 
     
     
         17 . A compound having the following structure:  
       
         
           
           
               
               
           
         
       
       where m is from 0-4; 
 each L is independently hydrogen, halogen, alkyl, aryl or nitro;  
 each W is independently hydrogen, halogen, alkyl, alkoxy, or aryl;  
 X and Y are each independently CH or N;  
 Y 1  and Y 2  are each independently optionally substituted alkyl or a single bond; and  
 each Z is independently —C(NH)—NH—C(NH)-A,  
 where each A is the same or different, and is selected from the group consisting of i) hydrogen, ii a nitrile, iii) an amino, iv) an antibacterial agent, v) an antibiotic, vi) a quinolone, vii) an azaquinolone, and viii) one of the following groups:  
                     
 where R 12  is hydrogen or C 1 -C 6  straight or branched alkyl, and R 11  is hydrogen, lowere alkyl, an aromatic group or a heterocyclic group;  
 and pharmaceutically acceptable salts thereof.  
 
     
     
         18 . An antiviral and/or antibacterial composition which comprises: 
 a) an effective amount of a compound according to  claim 1;     b) a pharmaceutically acceptable carrier.    
     
     
         19 . A method for preventing or treating a viral and/or bacterial infection in a mammalian host, said method comprising administering to a mammal in need thereof an effective amount of a compound in accordance with  claim 1 .  
     
     
         20 . A compound having the following structure:  
       
         
           
           
               
               
           
         
       
       where each n is independently from 1-5; 
 Y 1  and Y 2  are the same or different, and are optionally substituted alkyl; optionally substituted aryl; an optionally substituted heterocycle; or a single bond;  
 X is optionally substituted alkyl; optionally substituted aryl; or an optionally substituted heterocycle; and  
 each Z is independently —C(NH)—NH—CN or —(CH 2 ) m —NH—C(NH)—NHCN where m is from 1 to 6.  
 
     
     
         21 . A compound having the following structure:  
       
         
           
           
               
               
           
         
       
       where each n is independently from 1-5; 
 each m is independently from 0-12;  
 each Z is independently —C(NH)—NH—CN or —(CH 2 ) q —NH—C(NH)—NH—CN where q is from 1-6, and  
 T is hydrogen, lower alkyl optionally substituted aryl or an optionally substituted heterocycle; and x is from 0-8.

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