Certain chemical entities, compositions, and methods

Abstract

Chemical entities that are novel compounds, pharmaceutical compositions and methods of treatment of cancer are described.

What is claimed is: 
     
         1 . At least one chemical entity chosen from compounds of Formula I 
       
         
           
           
               
               
           
         
       
       and pharmaceutically acceptable salts thereof, wherein
 R 1 , R 2 , R 3 , R 5 , R 6 , R 9 , R 10 , R 11  and R 12 , are independently chosen from hydrogen, hydroxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocycloalkyloxy, optionally substituted aminocarbonyloxy, optionally substituted acyloxy, optionally substituted alkoxycarbonyloxy, and optionally substituted amino; or 
 R 1  and R 2 , or R 5  and R 6 , or R 7  and R 8 , or R 9  and R 10 , or R 11  and R 12  mutually independently, together in each case denote an oxo group (═O); 
 R 4  is hydroxy, or R 4  and R 5  may optionally be joined together with any intervening atoms to form an optionally substituted heterocycloalkyl ring; 
 R 7  is chosen from hydrogen, hydroxy, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocycloalkyloxy, optionally substituted aminocarbonyloxy, optionally substituted acyloxy, optionally substituted alkoxycarbonyloxy, and optionally substituted amino; 
 R 8  is chosen from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, and optionally substituted alkynyl; 
 R 13  is chosen from hydrogen, optionally substituted alkyl, and formyl; 
 Z is chosen from OR 14  and NR 15 R 16 ; wherein 
 R 14  is chosen from optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl; 
 R 15  is chosen from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl; 
 R 16  is chosen from optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl; 
 or R 15  and R 16  may optionally be joined together with any intervening atoms to form an optionally substituted heterocycloalkyl ring; 
 W 1  is chosen from the following moieties: 
 
       
         
           
           
               
               
           
         
         wherein Y is chosen from O and NR 18 ; 
         R 17  is chosen from cyano, halo, hydroxy, azido, nitro, carboxy, sulfinyl, sulfanyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocycloalkyloxy, optionally substituted alkoxycarbonyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted aryloxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amino, optionally substituted acyl, optionally substituted alkoxycarbonyl, optionally substituted al—Enocarbonyl, optionally substituted aminosulfonyl, optionally substituted carbaminodoyl, and optionally substituted alkynyl; 
         R 18  is chosen from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl; 
         W 2  is chosen from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, and optionally substituted alkynyl; 
         m is selected from 0, 1, 2, and 3; 
         n is selected from 0 and 1, and 
         the dotted line represents a single bond or a double bond; 
       
       provided that when R 4  is OH, R 13  is methyl, W 1  is 
       
         
           
           
               
               
           
         
       
       (2-oxo-2H-pyran-5-yl), and R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and W 2  are hydrogen then R 12  is not hydrogen. 
     
     
         2 . At least one chemical entity of  claim 1  wherein R 1 , R 2 , R 3 , R 5 , R 6 , R 9 , R 10 , R 11  and R 12  are independently chosen from hydrogen, hydroxy, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aminocarbonyloxy, optionally substituted acyloxy, optionally substituted alkoxycarbonyloxy, and optionally substituted amino. 
     
     
         3 . At least one chemical entity of  claim 2  wherein R 1 , R 2 , R 3 , R 5 , R 6 , R 9 , R 10 , R 11  and R 12  are independently chosen from hydrogen, hydroxy, and optionally substituted alkyl. 
     
     
         4 . At least one chemical entity of  claim 3  wherein R 1 , R 2 , R 3 , R 5 , R 6 , R 9 , R 10 , R 11  and R 12  are independently chosen from hydrogen, hydroxy, and methyl. 
     
     
         5 . At least one chemical entity of any one of  claims 1  to  4  wherein R 4  is hydroxy. 
     
     
         6 . At least one chemical entity of any one of  claims 1  to  4  wherein R 4  and R 5  are joined together with any intervening atoms to form an optionally substituted 3- to 8-membered heterocycloalkyl ring. 
     
     
         7 . At least one chemical entity of  claim 6  wherein R 4  and R 5  are joined together with any intervening atoms to form an oxirane ring. 
     
     
         8 . At least one chemical entity of any one of  claims 1  to  7  wherein R 7  is chosen from hydrogen, hydroxy, optionally substituted alkoxy, optionally substituted aminocarbonyloxy, optionally substituted acyloxy, optionally substituted alkoxycarbonyloxy, and optionally substituted amino. 
     
     
         9 . At least one chemical entity of  claim 8  wherein R 7  is chosen from hydrogen and optionally substituted acyloxy. 
     
     
         10 . At least one chemical entity of  claim 9  wherein R 7  is chosen from hydrogen and —OCOCH 3 . 
     
     
         11 . At least one chemical entity of any one of  claims 1  to  10  wherein R 8  and W 2  are independently chosen from hydrogen and optionally substituted alkyl. 
     
     
         12 . At least one chemical entity of any one of  claims 1  to  11  wherein R 13  is chosen from hydrogen and optionally substituted alkyl. 
     
     
         13 . At least one chemical entity of  claim 12  wherein R 13  is chosen from hydrogen, methyl, and hydroxymethyl. 
     
     
         14 . At least one chemical entity of any one of  claims 1  to  13  wherein Y is chosen from O, NH and NCH 3 . 
     
     
         15 . At least one chemical entity of  claim 14  wherein Y is O. 
     
     
         16 . At least one chemical entity of any one of  claims 1  to  15  wherein R 17  is chosen from cyano, halo, hydroxy, carboxy, sufonyl, optionally substituted alkoxy, optionally substituted alkoxycarbonyl, optionally substituted alkyl, optionally substituted amino, optionally substituted acyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, and optionally substituted aminosulfonyl. 
     
     
         17 . At least one chemical entity of any one of  claims 1  to  16  wherein m is 0. 
     
     
         18 . At least one chemical entity of any one of  claims 1  to  17  wherein the dotted line represents a single bond. 
     
     
         19 . At least one chemical entity of any one of  claims 1  to  17  wherein the dotted line represents a double bond. 
     
     
         20 . At least one chemical entity of  claim 1  wherein the compound of Formula I is chosen from compounds of Formula Ia. 
       
         
           
           
               
               
           
         
       
     
     
         21 . At least one chemical entity of  claim 1  wherein the compound of Formula I is chosen from compounds of Formula Ib. 
       
         
           
           
               
               
           
         
       
     
     
         22 . At least one chemical entity of  claim 1  wherein the compound of Formula I is chosen from compounds of Formula Ic. 
       
         
           
           
               
               
           
         
       
     
     
         23 . At least one chemical entity of  claim 1  wherein the compound of Formula I is chosen from compounds of Formula Id. 
       
         
           
           
               
               
           
         
       
     
     
         24 . At least one chemical entity of  claim 1  wherein the compound of Formula I is chosen from compounds of Formula Ie 
       
         
           
           
               
               
           
         
       
     
     
         25 . At least one chemical entity of  claim 1  wherein the compound of Formula I is chosen from compounds of Formula If. 
       
         
           
           
               
               
           
         
       
     
     
         26 . At least one chemical entity of  claim 1  wherein the compound of Formula I is chosen from compounds of Formula 1g. 
       
         
           
           
               
               
           
         
       
     
     
         27 . At least one chemical entity of  claim 1  wherein the compound of Formula I is chosen from compounds of Formula Ih. 
       
         
           
           
               
               
           
         
       
     
     
         28 . At least one chemical entity of  claim 1  wherein the compound of Formula I is chosen from compounds of Formula Ii. 
       
         
           
           
               
               
           
         
       
     
     
         29 . At least one chemical entity of any one of  claims 1  to  28 , wherein Z is OR 14 . 
     
     
         30 . At least one chemical entity of  claim 29  wherein R 14  is chosen from optionally substituted alkyl, optionally substituted cycloalkyl, and optionally substituted heterocycloalkyl. 
     
     
         31 . At least one chemical entity of  claim 30  wherein R 14  is optionally substituted lower alkyl. 
     
     
         32 . At least one chemical entity of  claim 31  wherein R 14  is chosen from 2-morpholinoethyl, 2-(pyrrolidin-1-yl)ethyl, and 2-(3-oxopiperazin-1-yl)ethyl. 
     
     
         33 . At least one chemical entity of any one of  claims 1  to  28 , wherein Z is NR 15 R 16 . 
     
     
         34 . At least one chemical entity of  claim 33  wherein R 15  is chosen from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, and optionally substituted heterocycloalkyl, and R 16  is chosen from optionally substituted alkyl, optionally substituted cycloalkyl, and optionally substituted heterocycloalkyl. 
     
     
         35 . At least one chemical entity of  claim 34  wherein R 15  is hydrogen and R 16  is chosen from optionally substituted alkyl. 
     
     
         36 . At least one chemical entity of  claim 35  wherein R 15  is hydrogen and R 16  is chosen from lower alkyl optionally substituted with carboxyl or heterocycloalkyl optionally substituted with one or two groups independently chosen from lower alkyl, hydroxyl, and oxo. 
     
     
         37 . At least one chemical entity of  claim 36  wherein R 15  is hydrogen and R 16  is chosen from 3-carboxypropyl, 2-(pyrrolidin-1-yl)ethyl, 2-morpholinoethyl, (4-methylpiperazin-1-yl)ethyl, 2-(4-methyl-2-oxopiperazin-1-yl)ethyl, 2-(3-oxopiperazin-1-yl)ethyl, 2-((S)-3-hydroxypyrrolidin-1-yl)ethyl, (2-((R)-3-hydroxypyrrolidin-1-yl)ethyl, and 2-(2-oxopiperazin-1-yl)ethyl. 
     
     
         38 . At least one chemical entity of  claim 33  wherein R 15  and R 16  are joined together to form an optionally substituted 4- to 8-membered heterocycloalkyl ring. 
     
     
         39 . At least one chemical entity of  claim 38  wherein R 15  and R 16  are joined together to form a 4-to 8-membered heterocycloalkyl ring optionally substituted with one or two groups independently chosen from amino, hydroxyl, oxo, and lower alkyl. 
     
     
         40 . At least one chemical entity of  claim 39  wherein R 15  and R 16  are joined together to form a 5-to 7-membered heterocycloalkyl ring chosen from 3-hydroxypyrrolidine-1-yl, 3-aminopyrrolidine-1-yl, 3-oxopiperazine-1-yl, 4-methyl-1,4-diazepane-1-yl, 1,4-diazepane-1-yl, piperazine-1-yl, 4-methylpiperazine-1-yl, and morpholine-4-yl. 
     
     
         41 . At least one chemical entity is chosen from
 (1R,2aR,3aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl) hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-7-yl (2-(pyrrolidin-1-yl)ethyl) carbonate,   (1R,2aR,3aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl) hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-7-yl (2-morpholinoethyl) carbonate,   (1R,2aR,3aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl) hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-7-yl (2-(pyrrolidin-1-yl) ethyl)carbamate,   (1R,2aR,3aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl) hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-7-yl (2-morpholinoethyl)carbamate,   (1R,2aR,3aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl) hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-7-yl4-methylpiperazine-1-carboxylate,   (1R,2aR,3aS,3bR,5aR,7S,9aS,9b S,11aR)-9a,11 a -dimethyl-1-(2-oxo-2H-pyran-5-yl) hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-7-yl (2-(4-methylpiperazin-1-yl) ethyl)carbamate,   (1R,2aR,3aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl) hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-7-ylmorpholine-4-carboxylate,   4-(((((1R,2aR,3aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl) hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-7-yl)oxy)carbonyl)amino)butanoic acid,   (1R,2R,2aR,3 aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl)-7-(((2-(pyrrolidin-1-yl)ethoxy)carbonyl)oxy)hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b] oxiren-2-yl acetate,   (1R,2R,2aR,3 aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-7-(((2-morpholinoethoxy)carbonyl)oxy)-1-(2-oxo-2H-pyran-5-yl) hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-2-yl acetate,   (1R,2R,2aR,3 aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl)-7-(((2-(pyrrolidin-1-yl)ethyl)carbamoyl)oxy)hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b] oxiren-2-yl acetate,   (1R,2R,2aR,3 aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-7-(((2-morpholinoethyl)carbamoyl)oxy)-1-(2-oxo-2H-pyran-5-yl) hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-2-yl acetate,   (1R,2R,2aR,3 aS,3bR,5aR,7S,9aS,9bS,11aR)-2-acetoxy-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl) hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-7-yl 4-methylpiperazine-1-carboxylate,   (1R,2R,2aR,3 aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-7-(((2-(4-methylpiperazin-1-yl) ethyl)carbamoyl)oxy)-1-(2-oxo-2H-pyran-5-yl)hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b] oxiren-2-yl acetate,   (1R,2R,2aR,3 aS,3bR,5aR,7S,9aS,9bS,11aR)-2-acetoxy-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl) hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-7-yl morpholine-4-carboxylate,   4-(((((1R,2R,2aR,3aS,3bR,5aR,7S,9aS,9bS,11aR)-2-acetoxy-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl)hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-7-yl) oxy)carbonyl)amino)butanoic acid,   (1R,2R,2aR,3 aS,3bR,5aS,7S,9aR,9bS,11aR)-5a-hydroxy-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl)-7-(((2-(pyrrolidin-1-yl) ethoxy)carbonyl)oxy)hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-2-yl acetate,   (1R,2R,2aR,3 aS,3bR,5aS,7S,9aR,9bS,11aR)-5a-hydroxy-9a,11a-dimethyl-7-(((2-morpholinoethoxy)carbonyl)oxy)-1-(2-oxo-2H-pyran-5-yl) hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-2-yl acetate,   (1R,2R,2aR,3aS,3bR,5aS,7S,9aR,9b S,11aR)-5a-hydroxy-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl)-7-(((2-(pyrrolidin-1-yl) ethyl)carbamoyl)oxy)hexadecahydronaphtho[1′,2′: 6,7]indeno[1,7a-b]oxiren-2-yl acetate,   (1R,2R,2aR,3aS,3bR,5aS,7S,9aR,9b S,11aR)-5a-hydroxy-9a,11a-dimethyl-7-(((2-morpholinoethyl)carbamoyl)oxy)-1-(2-oxo-2H-pyran-5-yl) hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-2-yl acetate,   (1R,2R,2aR,3aS,3bR,5aS,7S,9aR,9b S,11aR)-2-acetoxy-5a-hydroxy-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl)hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-7-yl 4-methylpiperazine-1-carboxylate,   (1R,2R,2aR,3aS,3bR,5aS,7S,9aR,9b S,11aR)-5a-hydroxy-9a,11a-dimethyl-7-(((2-(4-methylpiperazin-1-yl)ethyl)carbamoyl)oxy)-1-(2-oxo-2H-pyran-5-yl) hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-2-yl acetate,   (1R,2R,2aR,3aS,3bR,5aS,7S,9aR,9b S,11aR)-2-acetoxy-5a-hydroxy-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl)hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-7-yl morpholine-4-carboxylate,   4-(((((1R,2R,2aR,3aS,3bR,5aS,7S,9aR,9b S,11aR)-2-acetoxy-5a-hydroxy-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl)hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-7-yl) oxy)carbonyl)amino)butanoic acid,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-3-(((2-(pyrrolidin-1-yl)ethoxy)carbonyl)oxy)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-14-hydroxy-10,13-dimethyl-3-(((2-morpholinoethoxy)carbonyl)oxy)-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-3-(((2-(pyrrolidin-1-yl)ethyl)carbamoyl)oxy)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-14-hydroxy-10,13-dimethyl-3-(((2-morpholinoethyl)carbamoyl)oxy)-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-16-acetoxy-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 4-methylpiperazine-1-carboxylate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-14-hydroxy-10,13-dimethyl-3-(((2-(4-methylpiperazin-1-yl) ethyl)carbamoyl)oxy)-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-16-acetoxy-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl morpholine-4-carboxylate,   4-(((((3S,5R,8R,9S,10S,13R,14S,16 S,17R)-16-acetoxy-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl) oxy)carbonyl)amino)butanoic acid,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-16-acetoxy-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl piperazine-1-carboxylate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-16-acetoxy-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 1,4-diazepane-1-carboxylate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-16-acetoxy-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 4-methyl-1,4-diazepane-1-carboxylate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-16-acetoxy-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-oxopiperazine-1-carboxylate,   (S)-(3S,5R,8R,9S,10S,13R,14S,16 S,17R)-16-acetoxy-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-hydroxypyrrolidine-1-carboxylate,   (R)-(3S,5R,8R,9S,10S,13R,14S,16S,17R)-16-acetoxy-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-hydroxypyrrolidine-1-carboxylate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-3-(((2-(2-oxopiperazin-1-yl)ethyl)carbamoyl)oxy)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-14-hydroxy-10,13-dimethyl-3-(((2-(4-methyl-2-oxopiperazin-1-yl)ethyl)carbamoyl)oxy)-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-3-(((2-(3-oxopiperazin-1-yl)ethyl)carbamoyl)oxy)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-14-hydroxy-3-(((2-((S)-3-hydroxypyrrolidin-1-yl) ethyl)carbamoyl)oxy)-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-14-hydroxy-3-(((2-((R)-3-hydroxypyrrolidin-1-yl) ethyl)carbamoyl)oxy)-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-3-(((2-(3-oxopiperazin-1-yl)ethoxy)carbonyl)oxy)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(pyrrolidin-1-yl)ethyl) carbonate,   (3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-morpholinoethyl) carbonate,   (3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(pyrrolidin-1-yl)ethyl)carbamate,   (3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-morpholinoethyl)carbamate,   (3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl piperazine-1-carboxylate,   (3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(piperazin-1-yl)ethyl)carbamate,   (3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl morpholine-4-carboxylate,   4-(((((3S,5 S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl)oxy)carbonyl)amino)butanoic acid,   (3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl4-methylpiperazine-1-carboxylate,   (3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 1,4-diazepane-1-carboxylate,   (3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 4-methyl-1,4-diazepane-1-carboxylate,   (3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-oxopiperazine-1-carboxylate,   (S)-(3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-hydroxypyrrolidine-1-carboxylate,   (R)-(3S,5 S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-hydroxypyrrolidine-1-carboxylate,   (S)-(3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-aminopyrrolidine-1-carboxylate,   (R)-(3S,5 S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-aminopyrrolidine-1-carboxylate,   (3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(2-oxopiperazin-1-yl)ethyl)carbamate,   (3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(4-methyl-2-oxopiperazin-1-yl) ethyl)carbamate,   (3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(3-oxopiperazin-1-yl)ethyl)carbamate,   (3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-((S)-3-hydroxypyrrolidin-1-yl) ethyl)carbamate,   (3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-((R)-3-hydroxypyrrolidin-1-yl) ethyl)carbamate,   (3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(3-oxopiperazin-1-yl)ethyl) carbonate,   (3 S, 8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(pyrrolidin-1-yl)ethyl) carbonate,   (3 S, 8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-morpholinoethyl) carbonate,   (3 S, 8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(pyrrolidin-1-yl)ethyl)carbamate,   (3 S, 8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-morpholinoethyl)carbamate,   (3 S, 8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl piperazine-1-carboxylate,   (3 S, 8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(piperazin-1-yl)ethyl)carbamate,   (3 S, 8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl morpholine-4-carboxylate,   4-(((((3 S,8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl) oxy)carbonyl)amino)butanoic acid,   (3 S, 8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl 4-methylpiperazine-1-carboxylate,   (3 S, 8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl 1,4-diazepane-1-carboxylate,   (3 S, 8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl 4-methyl-1,4-diazepane-1-carboxylate,   (3 S, 8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-oxopiperazine-1-carboxylate,   (S)-(3 S, 8R,9S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-hydroxypyrrolidine-1-carboxylate,   (R)-(3 S, 8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-hydroxypyrrolidine-1-carboxylate,   (S)-(3 S, 8R,9S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-aminopyrrolidine-1-carboxylate,   (R)-(3 S, 8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-aminopyrrolidine-1-carboxylate,   (3 S, 8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(2-oxopiperazin-1-yl)ethyl)carbamate,   (3 S, 8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(4-methyl-2-oxopiperazin-1-yl)ethyl)carbamate,   (3 S, 8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(3-oxopiperazin-1-yl)ethyl)carbamate,   (3 S, 8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-((S)-3-hydroxypyrrolidin-1-yl)ethyl)carbamate,   (3 S, 8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-((R)-3-hydroxypyrrolidin-1-yl)ethyl)carbamate,   (3 S, 8R,9 S,10R,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(3-oxopiperazin-1-yl)ethyl) carbonate,   (3S,5R,8R,9 S,10 S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(pyrrolidin-1-yl)ethyl) carbonate,   (3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-morpholinoethyl) carbonate,   (3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(pyrrolidin-1-yl)ethyl)carbamate,   (3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-morpholinoethyl)carbamate,   (3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl piperazine-1-carboxylate,   (3S,5R,8R,9 S,10 S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(piperazin-1-yl)ethyl)carbamate,   (3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl morpholine-4-carboxylate,   4-(((((3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl) oxy)carbonyl)amino)butanoic acid,   (3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 4-methylpiperazine-1-carboxylate,   (3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 1,4-diazepane-1-carboxylate,   (3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 4-methyl-1,4-diazepane-1-carboxylate,   (3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-oxopiperazine-1-carboxylate,   (S)-(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-hydroxypyrrolidine-1-carboxylate,   (R)-(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-hydroxypyrrolidine-1-carboxylate,   (3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(2-oxopiperazin-1-yl)ethyl)carbamate,   (3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(4-methyl-2-oxopiperazin-1-yl) ethyl)carbamate,   (3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(3-oxopiperazin-1-yl)ethyl)carbamate,   (3S,5R,8R,9 S,10 S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-((S)-3-hydroxypyrrolidin-1-yl) ethyl)carbamate,   (3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-((R)-3-hydroxypyrrolidin-1-yl) ethyl)carbamate,   (3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(3-oxopiperazin-1-yl)ethyl) carbonate,   (3S,5R,8R,9S,10S,12R,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(pyrroli din-1-yl)ethyl) carbonate,   (3S,5R,8R,9S,10S,12R,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-morpholinoethyl) carbonate,   (3S,5R,8R,9S,10S,12R,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(pyrrolidin-1-yl) ethyl)carbamate,   (3S,5R,8R,9S,10S,12R,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-morpholinoethyl)carbamate,   (3S,5R,8R,9S,10S,12R,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl piperazine-1-carboxylate,   (3S,5R,8R,9S,10S,12R,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(piperazin-1-yl) ethyl)carbamate,   (3S,5R,8R,9S,10S,12R,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl morpholine-4-carboxylate,   4-(((((3S,5R,8R,9S,10S,12R,13 5,14 S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl) oxy)carbonyl)amino)butanoic acid,   (3S,5R,8R,9S,10S,12R,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 4-methylpiperazine-1-carboxylate,   (3S,5R,8R,9S,10S,12R,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 1,4-diazepane-1-carboxylate,   (3S,5R,8R,9S,10S,12R,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 4-methyl-1,4-diazepane-1-carboxylate,   (3S,5R,8R,9S,10S,12R,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-oxopiperazine-1-carboxylate,   (S)-(3S,5R,8R,9S,10S,12R,13 5,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-hydroxypyrrolidine-1-carboxylate,   (R)-(3S,5R,8R,9S,10S,12R,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-hydroxypyrrolidine-1-carboxylate,   (3S,5R,8R,9S,10S,12R,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(2-oxopiperazin-1-yl) ethyl)carbamate,   (3S,5R,8R,9S,10S,12R,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(4-methyl-2-oxopiperazin-1-yl)ethyl)carbamate,   (3S,5R,8R,9S,10S,12R,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(3-oxopiperazin-1-yl) ethyl)carbamate,   (3S,5R,8R,9S,10S,12R,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-((S)-3-hydroxypyrrolidin-1-yl)ethyl)carbamate,   (3S,5R,8R,9S,10S,12R,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-((R)-3-hydroxypyrrolidin-1-yl)ethyl)carbamate,   (3S,5R,8R,9S,10S,12R,13S,14S,17R)-12,14-dihydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(3-oxopiperazin-1-yl) ethyl) carbonate,   (3S,5R,8R,9S,10S,13R,14S,16 S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)-3-(((2-(pyrrolidin-1-yl)ethoxy)carbonyl)oxy)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-14-hydroxy-10,13-dimethyl-3-(((2-morpholinoethoxy)carbonyl)oxy)-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5R,8R,9S,10S,13R,14S,16 S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)-3-(((2-(pyrrolidin-1-yl)ethyl)carbamoyl)oxy)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-14-hydroxy-10,13-dimethyl-3-(((2-morpholinoethyl)carbamoyl)oxy)-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-16-acetoxy-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl piperazine-1-carboxylate,   (3S,5R,8R,9S,10S,13R,14S,16 S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)-3-(((2-(piperazin-1-yl)ethyl)carbamoyl)oxy)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-16-acetoxy-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl morpholine-4-carboxylate,   4-(((((3S,5R,8R,9 S,10 S,13R,14S,16 S,17R)-16-acetoxy-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl) oxy)carbonyl)amino)butanoic acid,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-16-acetoxy-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 4-methylpiperazine-1-carboxylate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-16-acetoxy-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 1,4-diazepane-1-carboxylate   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-16-,acetoxy-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 4-methyl-1,4-diazepane-1-carboxylate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-16-acetoxy-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-oxopiperazine-1-carboxylate,   (S)-(3S,5R,8R,9S,10S,13R,14S,16S,17R)-16-acetoxy-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-hydroxypyrrolidine-1-carboxylate,   (R)-(3S,5R,8R,9S,10S,13R,14S,16S,17R)-16-acetoxy-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-hydroxypyrrolidine-1-carboxylate,   (3S,5R,8R,9S,10S,13R,14S,16S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)-3-(((2-(2-oxopiperazin-1-yl)ethyl)carbamoyl)oxy)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5R,8R,9S,10S,13R,14S,16 S,17R)-14-hydroxy-10,13-dimethyl-3-(((2-(4-methyl-2-oxopiperazin-1-yl)ethyl)carbamoyl)oxy)-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5R,8R,9S,10S,13R,14S,16 S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)-3-(((2-(3-oxopiperazin-1-yl)ethyl)carbamoyl)oxy)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5R,8R,9 S,10 S,13R,14S,16S,17R)-14-hydroxy-3-(((2-((S)-3-hydroxypyrrolidin-1-yl) ethyl)carbamoyl)oxy)-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   (3S,5R,8R,95,10 S,13R,14S,16S,17R)-14-hydroxy-3-(((2-((R)-3-hydroxypyrrolidin-1-yl) ethyl)carbamoyl)oxy)-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate, and   (3S,5R,8R,9S,10 S,13R,14S,16S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydrofuran-3-yl)-3-(((2-(3-oxopiperazin-1-yl)ethoxy)carbonyl)oxy)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate,   and pharmaceutically acceptable salts thereof.   
     
     
         42 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one chemical entity of any one of  claims 1  to  41 . 
     
     
         43 . A pharmaceutical composition of  claim 42  wherein the composition is formulated in a form chosen from tablets, capsules, powders, liquids, suspensions, suppositories, and aerosols. 
     
     
         44 . A packaged pharmaceutical composition comprising a pharmaceutical composition of  claim 42  or  43  and instructions for using the composition to treat a subject suffering from cancer. 
     
     
         45 . A method of treating cancer in a subject which comprises administering to a subject in need thereof a therapeutically effective amount of at least one chemical entity of any one of  claims 1  to  41 .