Compounds having selective hydrolytic potentials

Abstract

Disclosed are compounds having selective hydrolytic potential. The disclosed compounds are useful as compounds having selective stability and are capable of undergoing programmed hydrolysis in biologic systems.

1 . A selectively stable compound comprising the formula I:  
     
       
         
         
             
             
         
       
     
     wherein one of R 1  or R 2  is independently an aliphatic hydrocarbon having the formula II:  
     
       
         
         
             
             
         
       
     
     R 1  or R 2 , which is other than formula II, and R 3  are independently C (1-12)  alkyl; and wherein: 
 C* is a chiral carbon atom;  
 n is an integer from about four to about eight;  
 R 4  is an amino acid or carbohydrate attached to the chiral carbon atom C* by an ester linkage, or —O—X—(R 5 ) m ; m being two or three and X being selected from the group consisting of C, P or S; wherein:  
 R 5  is a member selected from the group consisting of:  
 hydrogen atom;  
 hydroxyl group;  
 ═O;  
 substituted or unsubstituted C (1-10)  alkyl, C (1-10)  alkenyl, C (1-10)  alkynyl, C (1-10)  alkoxyl, C (1-10)  oxoalkyl, or C (1-10)  acetoxyl, C (1-10)  carboxyalkyl or C (1-10)  hydroxyalkyl group;  
 —OR 6 , R 6  being a substituted or unsubstituted C (1-10)  alkyl, C (1-10)  alkenyl or C (1-10)  alkynyl, or C (1-10)  oxoalkyl; and  
 substituted or unsubstituted cyclic or heterocylic group having from one- to three-rings, each ring containing from four to seven atoms.  
 
   
   
       2 . The compound of  claim 1 , wherein the amino acid is selected from the group consisting of: alaninyl, argininyl, asparaginyl, aspartyl, cysteinyl, glutaminyl, glutamyl, glycinyl, histidinyl, isoleucinyl, leucinyl, lysinyl, methioninyl, phenylalaninyl, prolinyl, serinyl, threoninyl, tryptophanyl, tyrosinyl and valinyl.  
   
   
       3 . The compound of  claim 1 , wherein the carbohydrate is selected from the group consisting of: glucosyl, glucosidyl, maltosyl, glucopyranosidyl, glyceraldehydyl, erythrosyl, arabinosyl, ribolucosyl, fructosyl, erythritolyl, xylosyl, lyxosyl, allosyl, altrosyl, mannosyl, mannosidyl, gulosyl, idosyl, galactosyl and talosyl.  
   
   
       4 . The compound of  claim 1 , wherein X is C.  
   
   
       5 . The compound of  claim 1 , wherein m is two and at least one R 5  is ═O.  
   
   
       6 . The compound of  claim 1 , wherein- substituents for the substituted C (1-10)  alkyl, C (1-10)  alkenyl, C (1-10)  alkynyl, C (1-10)  alkoxyl, C (1-10)  oxoalkyl, or C (1-10)  acetoxyl, cyclic or heterocylic are selected from the group consisting of amido, amino, C (1-6)  alkenyl, C (1-6)  alkyl, C (1-6)  alkoxyl, primary, secondary or tertiary C (1-6)  hydroxyalkyl, C (1-6)  oxoalkyl, azido, carbonyl, carboxylic acid, cyano, C (1-6)  haloalkyl, isocyano, isothiocyano, phosphatyl, phosphonatyl, sulfonatyl, sulfonyl, sulfoxyl, imino, thioamido, thiocarbonyl, thioalkoxyl, thioloxoalkyl and thio groups or a single atom.  
   
   
       7 . The compound of  claim 6 , wherein the C (1-6)  haloalkyl is a mono-, di- or tri-haloalkyl and the C (1-6)  alkoxyl is a methoxy or ethoxy group.  
   
   
       8 . The compound of  claim 6 , wherein the single atom is selected from the group consisting of chlorine, bromine, fluorine and oxygen.  
   
   
       9 . The compound of  claim 1 , wherein the R 1  or R 2 , other than formula II, contains one or two, nonadjacent oxygen atoms, each oxygen atom replacing a single carbon atom of the C (1-12)  alkyl.  
   
   
       10 . The compound of  claim 1 , wherein the cyclic or heterocyclic is selected from the group consisting of benzyl, phenyl, biphenyl, cyclohexyl, cyclohexenyl, cyclopentyl, nicotinyl, cyclopentenyl, cyclopentanedionyl, napthlalenyl, phenolyl, quinonyl, cyclopropyl, cyclobutyl, cycloheptyl, cycloheptenyl, indanyl, indenyl, decalinyl, resorcinolyl, tetralinyl, α-tetralonyl, 1-indanonyl, cyclohexanedionyl, cyclopentanedionyl, dimethylxanthinyl, methylxanthinyl, phthalimidyl, homophthalimidyl, methylbenzoyleneureayl, quinazolinonyl, octylcarboxamidobenzenyl, methylbenzamidyl, methyldioxotetrahydropteridinyl, glutarimidyl, piperidonyl, succinimidyl, dimethoxybenzenyl, methyldihydrouracilyl, methyluracilyl, methylthyminyl, piperidinyl, dihydroxybenzenyl, methylpurinyl, methylxanthinyl and dimethylxanthinyl.  
   
   
       11 . The compound of  claim 1 , wherein n is 4, m is 2, and R 2  and R 3  are methyl and at least one R 5  is ═O.  
   
   
       12 . The compound of  claim 11 , wherein the other R 5 , other than ═O, is selected from the group consisting of trimethoxy-substituted phenyl, phenolyl and benzamino.  
   
   
       13 . The compound of  claim 1 , wherein R 4  is glycinyl, isoleucinyl or valinyl.  
   
   
       14 . The compound of  claim 1 , wherein the compound is selected from:  
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
   
   
       15 . A pharmaceutical composition comprising a pharmaceutically acceptable excipient or carrier and a compound having the following formula I:  
     
       
         
         
             
             
         
       
     
     wherein one of R 1  or R 2  is independently an aliphatic hydrocarbon having the formula II:  
     
       
         
         
             
             
         
       
     
     R 1  or R 2 , which is other than formula II, and R 3  are independently C (1-12)  alkyl; and wherein: 
 C* is a chiral carbon atom;  
 n is an integer from about four to about eight;  
 R 4  is an amino acid or carbohydrate attached to the chiral carbon atom C* by an ester linkage, or —O—X—(R 5 ) m ; m being two or three and X being selected from the group consisting of C, P or S; wherein:  
 R 5  is a member selected from the group consisting of:  
 hydrogen atom;  
 hydroxyl group;  
 ═O;  
 substituted or unsubstituted C (1-10)  alkyl, C (1-10)  alkenyl, C (1-10)  alkynyl, C (1-10)  alkoxyl, C (1-10)  oxoalkyl, or C (1-10)  acetoxyl, C (1-10)  carboxyalkyl or C (1-10)  hydroxyalkyl group;  
 —OR 6 , R 6  being a substituted or unsubstituted C (1-10)  alkyl, C (1-10)  alkenyl or C (1-10)  alkynyl, or C (1-10)  oxoalkyl; and  
 substituted or unsubstituted cyclic or heterocylic group having from one- to three-rings, each ring containing from four to seven atoms.  
 
   
   
       16 . The pharmaceutical composition of  claim 15 , wherein the pharmaceutical composition is formulated for oral administration.  
   
   
       17 . The pharmaceutical composition of  claim 15 , wherein n is 4, R 4  is —O—X—(R 5 ) m , m is 2, R 2  and R 3  are methyl and at least one R 5  is ═O.  
   
   
       18 . The pharmaceutical composition of  claim 15 , wherein R 5  is selected from the group consisting of trimethoxy-substituted phenyl, phenolyl and benzamino.  
   
   
       19 . The pharmaceutical composition of  claim 15 , wherein R 4  is glycinyl, isoleucinyl or valinyl.