Chiral compounds substituted with phosphonate acid ester functions or phosphonic acid functions

Abstract

The present invention relates to novel compounds that contain PNA units substituted with phosphonic acid ester functions or phosphonic acid functions, and have at least one chiral center. The compounds may be used for the treatment of viral diseases, such as AIDS.

1 . Compound of the formula I, 
     
       
         
         
             
             
         
       
     
     wherein
 n represents an integer from 7 to 35, 
 each E independently of each other represents a hydrogen atom, a substituted or unsubstituted phenyl rest, a substituted or unsubstituted heterocycle, a nucleobase, optionally substituted with protecting groups, or a DNA intercalator, 
 each R 1  independently of each other represents a hydrogen atom or a side chain of a naturally occurring or non-naturally occurring amino acid, or an optionally substituted alkyl, alkenyl, alkylaryl, aryl, heterocyclic or alicyclic rest having up to 20 carbon atoms, wherein at least one of the optionally substituted alkyl, alkenyl, alkylaryl, aryl, heterocyclic or alicyclic rests having up to 20 carbon atoms is substituted with one or more phosphonic acid ester functions or phosphononic acid functions, 
 K represents a group of the formula —NR 2 R 3 , —N ⊕ R 2 R 3 R 4 , —NR 2 (CO)R 3  or —NR 2 (CS)R 3 , wherein R 2 , R 3  and R 4  independently of each other represent a hydrogen atom, an alkyl rest, amino protecting group, reporter ligand, fluorescence marker, intercalator, chelator, amino acid, peptide, protein, carbohydrate, lipid, steroid, fatty acid, oligonucleotide, quantum dot, FRET quencher (fluorescence resonance energy transfer quencher) or a polymer soluble or insoluble in water, wherein each of the above mentioned rests optionally may be substituted, 
 L represents a group of the formula —NR 5 R 6 , —NR 5 (CO)R 6 , —NR 5 (CS)R 6 , —OR 7  or —SR 7 , wherein R 5  and R 6  independently of each other represent a hydrogen atom, an alkyl rest, reporter ligand, fluorescence marker, intercalator, chelator, amino acid, amino acid amide, peptide, peptide amide, protein, carbohydrate, lipid, steroid, fatty acid, oligonucleotide, quantum dot, FRET quencher (fluorescence resonance energy transfer quencher) or a polymer soluble or insoluble in water, wherein each of the above mentioned rests optionally may be substituted, and wherein R 7  represents a hydrogen atom, an alkyl rest, reporter ligand, fluorescence marker, intercalator, chelator, amino acid, amino acid amide, peptide, peptide amide, protein, carbohydrate, lipid, steroid, fatty acid, oligonucleotide, quantum dot, FRET quencher or a polymer soluble or insoluble in water, wherein each of the above mentioned rests optionally may be substituted, 
 wherein the compound of the formula I has at least two asymmetric centers. 
 
   
   
       2 . Compound according to  claim 1 , wherein at least two rests R 1  do not represent hydrogen atoms, and the compound according to formula I has at least two asymmetric centers. 
   
   
       3 . Compound according to  claim 1 , wherein each second rest R 1  independently of each other represents an optionally substituted alkyl, alkenyl, alkylaryl, aryl or alicyclic rest having up to 20 carbon atoms, and the remaining rests R 1  represent hydrogen atoms. 
   
   
       4 . Compound according to  claim 1 , wherein each third rest R 1  independently of each other represents an optionally substituted alkyl, alkenyl, alkylaryl, aryl or alicyclic rest having up to 20 carbon atoms, and the remaining rests R 1  represent hydrogen atoms. 
   
   
       5 . Compound according to  claim 1 , wherein two, three or more adjacent rests R 1  independently of each other represent optionally substituted alkyl, alkenyl, alkylaryl, aryl or alicyclic rests having up to 20 carbon atoms, and the remaining rests R 1  represent hydrogen atoms. 
   
   
       6 . Compound according to  claim 1 , wherein each R 1  independently of each other represents an optionally substituted alkyl, alkenyl, alkylaryl, aryl or alicyclic rest having up to 20 carbon atoms. 
   
   
       7 . Compound according to  claim 1 , wherein one or more of the rests R 1  independently of each other has phosphonic acid ester functions or phosphonic acid functions. 
   
   
       8 . Compound according to  claim 1 , wherein all asymmetric centers have the same configuration. 
   
   
       9 . Compound according to  claim 1 , wherein all asymmetric centers have a (S) configuration. 
   
   
       10 . Compound according to  claim 1 , wherein all asymmetric centers have a (R)-configuration. 
   
   
       11 . Compound according to  claim 1 , wherein each rest R 1  independently of each other has one or more phosphonic acid ester functions or phosphonic acid functions, wherein the phosphonic acid ester functions possess the formula —P(═O)(OV) 2  or —P(═O)(OV)(OH), wherein each V independently of each other represents an unsubstituted alkyl, alkenyl, alkylaryl, aryl, or alicyclic rest having up to 20 carbon atoms. 
   
   
       12 . Compound according to  claim 11 , wherein each V independently of each other represents a methyl, ethyl, cyclohexyl or benzyl rest. 
   
   
       13 . Compound containing at least two compounds according to  claim 1  which are bound to each other via a linker. 
   
   
       14 . Compound according to  claim 13 , wherein the linker represents an alkyl chain, a peptide, an oligonucleotide, or an oligomer which is composed of at least three 8-amino-3,6-dioxaoctanoic acid units. 
   
   
       15 . Composition which contains at least one compound according to  claim 1 . 
   
   
       16 . Pharmaceutical composition, which contains at least one compound or composition according to  claim 1 , optionally in combination with at least one carrier, solvent or other pharmaceutical adjuvant. 
   
   
       17 . Use of a compound or a composition according to  claim 1  for the preparation of a medicament for the treatment of virus diseases, cancer, inflammation diseases, neurological diseases, diseases of the gastrointestinal tract or metabolic diseases. 
   
   
       18 . Use of a compound or a composition according to  claim 1  for the treatment of virus diseases, cancer, inflammation diseases, neurological diseases, diseases of the gastrointestinal tract or metabolic diseases. 
   
   
       19 . Use according to  claim 17  for the treatment of HIV, AIDS or hepatitis. 
   
   
       20 . Use according to  claim 17  for the treatment of skin cancer, lung cancer, liver cancer, prostate cancer, leukemia or brain tumors. 
   
   
       21 . Use according to  claim 17  for the treatment of asthma or psoriasis. 
   
   
       22 . Use according to  claim 17  for the treatment of Parkinson's disease. 
   
   
       23 . Use according to  claim 17  for the treatment of colon cancer, Morbus Crohn or adiposity. 
   
   
       24 . Use according to  claim 17  for the treatment of diseases that are correlated with an increased cholesterol concentration in the blood. 
   
   
       25 . Use of a pharmaceutical composition according to  claim 16  for the preparation of a medicament for the treatment of virus diseases, cancer, inflammation diseases, neurological diseases, diseases of the gastrointestinal tract or metabolic diseases. 
   
   
       26 . Use of a pharmaceutical composition according to  claim 16  for the treatment of virus diseases, cancer, inflammation diseases, neurological diseases, diseases of the gastrointestinal tract or metabolic diseases.