Novel betulinic proline imidazole derivatives as hiv inhibitors

Abstract

The invention relates to novel betulinic proline substituted derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.

1 . A compound of the formula (1): 
       
         
           
           
               
               
           
         
         wherein,
 R 1  is substituted or unsubstituted alkyl, substituted or unsubstituted aryl, 
 
       
       
         
           
           
               
               
           
         
         (wherein R b  is H, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl);
 R 2  is H, substituted or unsubstituted alkyl, substituted or unsubstituted aminoacids, substituted or unsubstituted alkoxy or substituted or unsubstituted cycloalkyl; 
 X is absent, O, S, CH 2  or NR a  (wherein R a  is H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, or R a  can be with their adjacent N and Carbon together form N-contained heterocycle (Preferably, pyrrolidine, piperdine, piperzine, or morpholine); 
 R 3  and R 4  are independently selected from H, OH, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkoxylalkoxy, or substituted or unsubstituted aminoacids and preferably amino acids are substituted by substituted or unsubstituted alkyl, phosphoric acid, or phosphorus prodrugs or R 3  and R 4  are together with their adjacent carbons to form a bond or R 3  and R 4  are together with their adjacent carbons to form cyclopropyl or R 3  and R 4  are together with their adjacent carbons to form epoxide; 
 W is C(O), C(S), or CR 7 R 8 ; 
 R x  is H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted heteroaryl and specifically heterocycles are imidazoles, oxazoles, oxadiazoles, triazoles, thiazoles, thiadizoles, isothiazoles, isothiadiazoles, pyridines, pyrazines, pyrimidines, or pyridazines; 
 R c  is hydrogen or substituted or unsubstituted alkyl; 
 R 6  is H, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy; 
 R c  and R 6  on different carbon atoms to form a bond; 
 R 5 , R 7  and R 8  are independently selected from H, CO 2 R d  (wherein R d  is H, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl), or substituted or unsubstituted alkyl; 
 ‘n’ is an integer from 1 to 3; including pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, tautomers, stereoisomers, ester prodrugs, or combination thereof. 
 
       
     
     
         2 . The compound of  claim 1 , wherein W is —C(O)—. 
     
     
         3 . A compound of the formula (1A): 
       
         
           
           
               
               
           
         
         wherein,
 R 1  is H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, 
 
       
       
         
           
           
               
               
           
         
         
            (wherein R b  is H, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl); 
           R 2  is H, substituted or unsubstituted alkyl, substituted or unsubstituted aminoacids, substituted or unsubstituted alkoxy or substituted or unsubstituted cycloalkyl; 
           X is absent, O, S, CH 2 , or NR a  (wherein R a  is H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, or R a  is with their adjacent N and Carbon together form N-contained heterocycle (Preferably, pyrrolidine, piperdine, piperzine, or morpholine); 
           R 3  and R 4  are independently selected from H, OH, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkoxylalkoxy, or substituted or unsubstituted aminoacids and preferably amino acids are substituted by substituted or unsubstituted alkyl, phosphoric acid, or phosphorus prodrugs or R 3  and R 4  can be together with their adjacent carbons to form a bond or R 3  and R 4  are together with their adjacent carbons to form cyclopropyl or R 3  and R 4  are together with their adjacent carbons to form epoxide; 
           W is C(O), C(S), or CR 8 R 9 ; 
           R 6  is H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted heteroaryl and most preferably alkyl is methyl, ethyl, isopropyl, and t-butyl, most preferably aryl is substituted or unsubstituted phenyl, most preferably heteroaryl is pyridine and R 6  is preferably substituted or unsubstituted isopropyl, t-butyl, phenyl, pyridine, pyrazine, pyrimidine or chromene; 
           R 5 , R 8  and R 9  are independently selected from H, CO 2 R d  (wherein R d  is H, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl), or substituted or unsubstituted alkyl; 
           R 7  is H, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy; 
           ‘n’ is an integer from 1 to 3; including pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, tautomers, stereoisomers, ester prodrugs, or combination thereof. 
         
       
     
     
         4 . The compound of  claim 3 , wherein W is —C(O)—. 
     
     
         5 . A compound selected from the group consisting of:
 (1R,3S)-2,2-dimethyl-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-((S)-2-(5-(pyridin-2-yl)-1H-imidazol-2-yl) pyrrolidine-1-carbonyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)cyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(5-(3-fluoro-4-methylphenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclo butane-1-carboxylic acid,   (1R,3S)-2,2-dimethyl-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-((S)-2-(5-(pyri din-3-yl)-1H-imidazol-2-yl) pyrrolidine-1-carbonyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)cyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(5-(3-fluoro phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(5-(4-ethoxyphenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-2,2-dimethyl-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-((S)-2-(5-(4-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)cyclo butane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((2S,4R)-4-(2-methoxyethoxy)-2-(4-phenyl-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-penta methyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((2S,4R)-2-(4-(3-fluorophenyl)-1H-imidazol-2-yl)-4-(2-methoxyethoxy)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((2S,4R)-2-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-4-(2-methoxyethoxy)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((2S,4R)-4-(2-methoxyethoxy)-2-(4-(pyridin-3-yl)-H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-2,2-dimethyl-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((S)-2-(5-phenyl-1,3,4-oxadiazol-2-yl)pyrrolidine-1-carbonyl)-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)cyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(4-(tert-butyl)oxazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl) icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-2,2-dimethyl-3-((((1R,3 aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((S)-2-(5-methyl-4-phenyl-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)cyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(4-isopropyl-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-2,2-dimethyl-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((S)-2-(5-phenyloxazol-2-yl)pyrrolidine-1-carbonyl)-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)cyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(5-(tert-butyl)oxazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)Icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-2,2-dimethyl-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((S)-2-(4-phenyloxazol-2-yl)pyrrolidine-1-carbonyl)-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)cyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(4-(tert-butyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(5-(4-chloro phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-2,2-dimethyl-3-((((1R,3aS,5aR,5bR,7aR,9S,1 aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((S)-3-(5-phenyl-1H-imidazol-2-yl)piperidine-1-carbonyl)-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)cyclobutane-1-carboxylic acid,   (1R,3R)-2,2-dimethyl-3-(2-oxo-2-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((S)-2-(5-phenyl-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)ethyl)cyclo butane-1-carboxylic acid,   2,2-dimethyl-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((S)-2-(5-phenyl-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-1-(prop-1-en-2-yl)-icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)cyclopropane-1-carboxylic acid,   2-methyl-2-(4-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((S)-2-(5-phenyl-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)phenoxy)propanoic acid,   (1R,3S)-2,2-dimethyl-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((S)-2-(5-phenyl-4H-1,2,4-triazol-3-yl)pyrrolidine-1-carbonyl)-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)cyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13 aR,13bR)-3a-((S)-2-(4-(3-fluoro-4-methoxyphenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclo butane-1-carboxylic acid,   (1R,3S)-3-((((R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(5-(2,4-difluorophenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclo butane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(5-(2-fluoro phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(4-(3-chloro phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((2S,4R)-4-hydroxy-2-(4-phenyl-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethyl cyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((2S,4R)-4-iso propoxy-2-(4-phenyl-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclo butane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((2S,4R)-2-(4-(tert-butyl)-1H-imidazol-2-yl)-4-(2-methoxyethoxy)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-penta methyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((2S,4R)-4-methoxy-2-(4-phenyl-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclo butane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((2S,4R)-2-(4-(3-fluorophenyl)-1H-imidazol-2-yl)-4-methoxypyrrolidine-1-carbonyl)-5a,5b,8,8,11a-penta methyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-2,2-dimethyl-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-((S)-2-(5-(trifluoromethyl)-1H-imidazol-2-yl) pyrrolidine-1-carbonyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)cyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(4,5-dimethyl-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl) icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((1R,3R,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane-8-carbonyl)-5a,5b,8,8, 11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   2,2-dimethyl-4-oxo-4-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-((S)-2-(5-(pyridin-2-yl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)butanoic acid,   4-(((1R,3 aS,5 aR,5bR,7aR,9S,11aR,11bR,13 aR,13bR)-3a-((S)-2-(5-(3-fluoro-4-methylphenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxobutanoic acid,   5-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13 aR,13bR)-3a-((S)-2-(5-(4-fluorophenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-3,3-dimethyl-5-oxopentanoic acid,   4-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bS)-1-(1,2-dihydroxypropan-2-yl)-5a,5b,8,8,11a-pentamethyl-3a-((R)-2-(3-phenyl-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carbonyl) icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxobutanoic acid,   4-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13 aR,13bR)-3a-((2S,4R)-4-(2-methoxy ethoxy)-2-(4-phenyl-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8, 8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxobutanoic acid,   4-(((1R,3 aS,5 aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((2S,4R)-2-(4-(3-fluoro phenyl)-1H-imidazol-2-yl)-4-(2-methoxyethoxy)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-penta methyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxo butanoic acid,   4-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((2S,4R)-2-(4-(4-fluoro phenyl)-1H-imidazol-2-yl)-4-(2-methoxyethoxy)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-penta methyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxo butanoic acid,   4-(((1R,3aS,5aR,5bR,7aR,9 S,11aR,11bR,13aR,13bR)-3a-((S)-2-(5-(4-methoxy phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxobutanoic acid,   2,2-dimethyl-4-oxo-4-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8, 11a-pentamethyl-3a-((S)-3-(5-phenyl-1H-imidazol-2-yl)piperidine-1-carbonyl)-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)butanoic acid,   2,2-dimethyl-4-oxo-4-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8, 11a-pentamethyl-3a-((S)-2-(5-phenyl-4H-1,2,4-triazol-3-yl)pyrrolidine-1-carbonyl)-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)butanoic acid,   4-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((1R,3R,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane-8-carbonyl)-5a,5b,8,8,11a-penta methyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxo butanoic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(5-(3-fluoro phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(1-methyl cyclopropyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclo butane-1-carboxylic acid,   (1R,3S)-2,2-dimethyl-3-((((1R,3aS,5aR,5bR,7aR,9S,1 aR,11bR,13aR,13bR)-5a,5b,   8,8,11a-pentamethyl-1-(1-methylcyclopropyl)-3a-((S)-2-(5-(pyridin-2-yl)-1H-imidazol-2-yl) pyrrolidine-1-carbonyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)cyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(5-(4-(2-methoxyethoxy)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-penta methyl-1-(1-methylcyclopropyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   3-(2-((S)-1-((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-(((1 S,3R)-3-carboxy-2,2-dimethylcyclobutane-1-carbonyl)oxy)-5a,5b,8,8,11a-pentamethyl-1-(1-methylcyclopropyl)icosahydro-1H-cyclopenta[a]chrysene-3a-carbonyl)pyrrolidin-2-yl)-1H-imidazol-5-yl) pyridine 1-oxide,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((2S,4R)-2-(4-(3-fluorophenyl)-1H-imidazol-2-yl)-4-(2-methoxyethoxy)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(1-methylcyclopropyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,1 aR,11bR,13aR,13bR)-3a-((2S,4R)-2-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-4-(2-methoxyethoxy)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(1-methylcyclopropyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(4-(tert-butyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8, 1a-pentamethyl-1-(1-methyl cyclopropyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclo butane-1-carboxylic acid,   (1R,3S)-2,2-dimethyl-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(1-methylcyclopropyl)-3a-(4-(5-phenyl-1H-imidazol-2-yl)piperidine-1-carbonyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)cyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-(4-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)piperidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(1-methyl cyclopropyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclo butane-1-carboxylic acid,   (1R,3S)-2,2-dimethyl-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(1-methylcyclopropyl)-3a-((S)-2-(5-(trifluoromethyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)cyclo butane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((1R,3R,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane-8-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(1-methylcyclopropyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   (1R,3S)-3-((((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(1-methylcyclopropyl) icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)carbonyl)-2,2-dimethylcyclobutane-1-carboxylic acid,   2,2-dimethyl-4-oxo-4-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(1-methylcyclopropyl)-3a-((S)-2-(5-(pyridin-2-yl)-1H-imidazol-2-yl) pyrrolidine-1-carbonyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)butanoic acid,   3,3-dimethyl-5-oxo-5-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(1-methylcyclopropyl)-3a-((S)-2-(5-(pyridin-2-yl)-1H-imidazol-2-yl) pyrrolidine-1-carbonyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)pentanoic acid,   5-(((1R,3 aS,5 aR,5bR,7aR,9S,11aR,11bR,13 aR,13bR)-3a-((S)-2-(5-(3-fluorophenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(1-methylcyclopropyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-3,3-dimethyl-5-oxopentanoic acid,   4-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(5-(3-fluorophenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(1-methylcyclopropyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxobutanoic acid,   4-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((S)-2-(5-(4-(2-methoxy ethoxy)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(1-methylcyclopropyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxo butanoic acid,   4-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((2S,4R)-2-(4-(4-fluoro phenyl)-1H-imidazol-2-yl)-4-(2-methoxyethoxy)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-penta methyl-1-(1-methylcyclopropyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxobutanoic acid,   2,2-dimethyl-4-oxo-4-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8, 11a-pentamethyl-1-(1-methylcyclopropyl)-3a-(4-(5-phenyl-1H-imidazol-2-yl)piperidine-1-carbonyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)butanoic acid,   4-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-(4-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)piperidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(1-methylcyclopropyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxobutanoic acid,   5-(((1R,3 aS,5 aR,5bR,7aR,9S,11aR,11bR,13 aR,13bR)-3a-((S)-2-(5-(4-fluorophenyl)-1H-imidazol-2-yl)pyrrolidine-1-carbonyl)-5a,5b,8,8,11a-pentamethyl-1-(1-methylcyclopropyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-3,3-dimethyl-5-oxopentanoic acid,   4-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((1R,3R,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane-8-carbonyl)-5a,5b,8,8,11a-penta methyl-1-(1-methylcyclopropyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxobutanoic acid and   5-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((1R,3R,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane-8-carbonyl)-5a,5b,8,8,11a-penta methyl-1-(1-methylcyclopropyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-3,3-dimethyl-5-oxopentanoic acid and pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, tautomers, stereoisomers, ester prodrugs, or combination thereof.   
     
     
         6 . A pharmaceutical composition comprising a compound according to  claim 1  and at least one pharmaceutically acceptable excipient. 
     
     
         7 . The pharmaceutical composition according to  claim 6 , wherein the pharmaceutically acceptable excipient is a carrier or diluent. 
     
     
         8 . A method for preventing, ameliorating or treating a viral mediated disease, disorder or syndrome in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         9 . The method according to  claim 8 , wherein the viral mediated disease, disorder or syndrome is HIV infection, HBV infection, HCV infection. 
     
     
         10 . A method of treating HIV in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         11 . A method for preventing, ameliorating or treating an HIV mediated disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition according to  claim 6 . 
     
     
         12 . The method according to  claim 11 , wherein the HIV mediated disease is HIV infection, HBV infection, or HCV infection. 
     
     
         13 . A pharmaceutical composition comprising a compound according to  claim 5  and at least one pharmaceutically acceptable excipient. 
     
     
         14 . A method for preventing, ameliorating or treating a viral mediated disease, disorder or syndrome in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound according to  claim 5 . 
     
     
         15 . A method of treating HIV in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound according to  claim 5 .