Isoxazolidine derivatives

Abstract

Anti-inflammatory and antiallergic compounds of the glucocorticosteroid series, according to formula (I) according to formula (I) defined herein are useful for treating diseases of the respiratory tract characterized by airway obstruction.

1 . A compound of formula (I): 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is —(CH 2 ) n —Z—(CH 2 ) n′ —R 2 , —R 3  wherein n and n′ are each independently 0, 1 or 2; 
 Z is a single bond or is selected from —S—, —O— and —OC(R 4 R 5 )—; 
 R 3  is selected from the group consisting of:
 H, halogen, —CN, —OH, —CONH 2 , (C 1 -C 6 )alkyl, (C 2 -C 4 )alkenyl, (C 1 -C 6 )haloalkyl, (C 2 -C 4 )alkynyl, (C 1 -C 6 )alkylsulfonyl, and (C 1 -C 6 )alkylcarbonyl; 
 —NR 4 R 5 , wherein R 4  and R 5  are independently selected from the group consisting of (C 1 -C 6 )alkyl and (C 1 -C 6 )alkoxy; 
 (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )heterocycloalkyl, ary,1 and heteroaryl, each of which is optionally substituted by one or more halogen atoms or oxo groups or —CN groups; and 
 
 R 2  is selected from the group consisting of:
 linear or branched (C 1 -C 8 )alkyl, (C 1 -C 6 )alkoxy, and (C 1 -C 6 )haloalkyl, optionally substituted by one or more CN groups or halogen atoms; 
 —(CH 2 ) m R 6 , wherein R 6  is selected from the group consisting of (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )heterocycloalkyl, aryl, (C 1 -C 6 )arylalkyl, aryloxy, arylthio, and heteroaryl, each of which optionally substituted by one or more substituents selected from the group consisting of oxo, —OH, halogen, —CN, —NH 2 , —CONH 2 , —NO 2 , —NHC(O)H, linear or branched (C 1 -C 6 )alkyl, linear or branched (C 1 -C 6 )haloalkyl, linear or branched (C 1 -C 6 )alkoxy, linear or branched (C 1 -C 6 )haloalkoxy, (C 1 -C 6 )hydroxyalkoxy, (C 1 -C 6 )haloalkoxy, (C 1 -C 6 )alkoxycarbonyl, (C 1 -C 6 )alkylcarboxyl, (C 1 -C 6 )alkylsulfonyl and (C 1 -C 6 )alkylsulfanyl, (C 1 -C 6 )alkyloxysulfonyl, (C 1 -C 6 )haloalkylsulfonyloxy, aminosulfonyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 6 )heterocycloalkyl, and heteroaryl, wherein m is 0 or an integer from 1 to 3; and 
 
 X and Y are independently H or halogen, 
 or a pharmaceutically acceptable salt thereof, 
 with the proviso that when R 1  is a group —CH 2 OH and R 2  is (C 1 -C 6 )alkyl or (C 3 -C 8 )cycloalkyl, then X and Y are fluorine atoms; 
 or pharmaceutically acceptable salts thereof. 
 
     
     
         2 . A compound or salt thereof according to  claim 1 , wherein stereogenic carbons have a stereochemistry as depicted in formula (I′): 
       
         
           
           
               
               
           
         
       
     
     
         3 . A compound or salt thereof according to  claim 1 , wherein X and Y are fluorine atoms. 
     
     
         4 . A compound or salt thereof according to  claim 1 , which is a compound of formula (IF): 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is —(CH 2 ) n —Z—(CH 2 ) n′ —R 3  wherein n is 1 and n′ is zero; 
 Z is a single bond; 
 R 3  is a fluorine atom; 
 R 2  is selected from the group consisting of:
 linear or branched (C 1 -C 8 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )haloalkyl, optionally substituted by one or more CN groups; 
 —(CH 2 ) m R 6 , wherein R 6  is selected from the group consisting of (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )heterocycloalkyl, aryl, aryloxy, arylthion and heteroaryl, each of which optionally substituted by one or more substituents selected from the group consisting of oxo, —OH, halogen, —CN, —NH 2 , —NO 2 , linear or branched (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, aryl, (C 1 -C 6 )hydroxyalkoxy, (C 1 -C 6 )haloalkoxy, straight or branched (C 1 -C 6 )alkoxycarbonyl, (C 1 -C 6 )alkylcarboxyl, arylthio, and (C 1 -C 6 )alkylsulfanyl, wherein m is 0 or an integer from 1 to 3; 
 
 with the proviso that R 2  is not 4-chloro-benzyl; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         5 . A compound or salt thereof according to  claim 1 , which is a compound of formula (IH): 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is —(CH 2 ) n —Z—(CH 2 ) n′ —R 3  wherein n is zero and n′ is 1; 
 Z is —S—; 
 R 3  is a fluorine atom; 
 R 2  is selected from the group consisting of:
 linear or branched (C 1 -C 8 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )haloalkyl, optionally substituted by one or more —CN groups or halogen atoms; 
 —(CH 2 ) m R 6 , wherein R 6  is selected from the group consisting of (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )heterocycloalkyl, aryl, aryloxy, arylthio, and heteroaryl, each of which optionally substituted by one or more substituents selected from the group consisting of oxo, —OH, halogen, —CN, —NH 2 , —NO 2 , linear or branched (C 1 -C 6 )alkyl, linear or branched (C 1 -C 6 )haloalkyl, linear or branched (C 1 -C 6 )alkoxy, aryl, (C 1 -C 6 )hydroxyalkoxy, (C 1 -C 6 )haloalkoxy, (C 1 -C 6 )alkoxycarbonyl, (C 1 -C 6 )alkylcarboxyl, arylthio, and (C 1 -C 6 )alkylsulfanyl, wherein m is 0 or an integer from 1 to 3; 
 
 with the proviso that R 2  is neither 4-chloro-benzyl nor propyl-benzene; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         6 . A compound or salt thereof according to of  claim 1 , of formula (IM): 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is —(CH 2 ) n —Z—(CH 2 ) n′ —R 3  wherein n is zero and n′ is 1; 
 Z is a single bond; 
 R 3  is —OH; 
 R 2  is selected from the group consisting of:
 linear or branched (C 1 -C 8 )alkyl; 
 —(CH 2 ) m R 6 , wherein R 6  is (C 3 -C 8 )cycloalkyl, wherein m is 0 or an integer from 1 to 3 and 
 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         7 . A compound or salt thereof according to  claim 1 , of formula (IN): 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is —(CH 2 ) n —Z—(CH 2 ) n′ —R 3  wherein n is zero and n′ is 1; 
 Z is a single bond; 
 R 3  is —OH; 
 R 2  is —(CH 2 ) m R 6 , wherein R 6  is aryl optionally substituted by one or more substituents selected from the group consisting of halogen, —CN, —CONH 2 , —NHC(O)H, linear or branched (C 1 -C 6 )alkyl, (C 1 -C 6 )alkylsulfonyl, linear or branched (C 1 -C 6 )haloalkyl, linear or branched (C 1 -C 6 )haloalkoxy, (C 1 -C 6 )alkoxycarbonyl, (C 1 -C 6 )alkoxysulfonyl, (C 1 -C 6 )haloalkylsulfonyloxy, (C 3 -C 8 )cycloalkyl, (C 3 -C 6 )heterocycloalkyl, aminosulfonyl, and heteroaryl, and m is 0, 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         8 . A compound or salt thereof according to  claim 1 , which is:
 (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(3,3-dimethyl-butyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-(4-fluoro-benzyl)-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-thiophen-2-ylmethyl-4a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-furan-2-ylmethyl-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(2-ethyl-butyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   3-[(4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,6b,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-8-ylmethyl]-benzoic acid methyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-cyclohexylmethyl-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-(4-methylsulfanyl-benzyl)-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-((R,S)-sec-butyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-cyclopentylmethyl-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   4-[(4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,6b,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-8-ylmethyl]-benzoic acid tert-butyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-benzyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-(1-propyl-butyl)-4a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-tert-butyl-benzyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-(4-propyl-benzyl)-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-cyclohexyl-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-(3-methyl-butyl)-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-(5-methylsulfanyl-thiophen-2-ylmethyl)-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6bR,9aS,10aS,10bS,12S)-8-(1-ethyl-2-methyl-propyl)-4b,12-difluoro-5-hydroxy-6b-((S)-2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-butoxy-benzyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(2-cyclohexyl-ethyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-((S)-2-hydroxy-acetyl)-4-a,6a-dimethyl-8-(1-methyl-1H-indol-3-ylmethyl)-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-bicyclo[2.2.1]hept-2-yl-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-(3-pyridin-3-yl-propyl)-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-(3,3,3-trifluoro-propyl)-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-8-(2-imidazol-1-yl-ethyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b-(R)-fluoro-12-fluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-quinolin-5-ylmethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-thiazol-2-ylmethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   Methanesulfonic acid 2-[(4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-benzyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-6b-yl]-2-oxo-ethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-6b-acetyl-8-(4-chloro-benzyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-benzyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(3,3-dimethyl-butyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-(4-fluoro-benzyl)-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-thiophen-2-ylmethyl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-furan-2-ylmethyl-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-8-(5-methyl-thiophen-2-ylmethyl)-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-8-(4-methoxy-benzyl)-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-8-(3-methyl-butyl)-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-cyclopentylmethyl-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-(4-propyl-benzyl)-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-8-(3-methyl-benzyl)-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(5-chloro-thiophen-2-ylmethyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-8-(4-methyl-benzyl)-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-tert-butyl-benzyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-(2-phenylsulfanyl-ethyl)-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-(1-propyl-butyl)-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-(2-phenoxy-ethyl)-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(5-chloro-furan-2-ylmethyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-cyclohexyl-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(2-ethyl-butyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-tert-butoxy-benzyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-butoxy-benzyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-8-(5-methyl-furan-2-ylmethyl)-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-8-(5-methylsulfanyl-thiophen-2-ylmethyl)-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(1-ethyl-2-methyl-propyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-(3,3,3-trifluoro-propyl)-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-cyclopropylmethyl-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(2-cyclohexyl-ethyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-bicyclo[2.2.1]hept-2-yl-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-8-(1-methyl-1H-indol-3-ylmethyl)-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-benzyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-(2-oxo-[1,3]dioxolan-4-yl) ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-benzyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid methoxy-methyl-amide;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-thiophen-2-ylmethyl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-(4-fluoro-benzyl)-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-(4-fluoro-benzyl)-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid cyanomethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-thiophen-2-ylmethyl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid cyanomethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-furan-2-ylmethyl-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-(4-fluoro-benzyl)-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-thiophen-2-ylmethyl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(3,3-dimethyl-butyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-(5-methyl-thiophen-2-yl-methyl)-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-8-(4-methoxy-benzyl)-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-8-(3-methyl-butyl)-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-cyclopentylmethyl-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-(4-propyl-benzyl)-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-8-(3-methyl-benzyl)-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]henanthrene-6b-carbothioic acid S—((S)-fluoromethyl)ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-(5-chloro-thiophen-2-yl-methyl-)-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-8-(4-methyl-benzyl)-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-tert-butyl-benzyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-(2-phenylsulfanyl-ethyl)-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-(1-propyl-butyl)-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-(2-phenoxy-ethyl)-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-(5-chloro-furan-2-yl-methyl-)-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-cyclohexyl-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(2-ethyl-butyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-tert-butoxy-benzyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-butoxy-benzyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-8-(5-methyl-furan-2-ylmethyl)-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-(5-methylsulfanyl-thiophen-2-ylmethyl)-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6bR,9aS,10aS,10bS,12S)-8-((S)-1-ethyl-2-methyl-propyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-(3,3,3-trifluoro-propyl)-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-cyclopropylmethyl-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(2-cyclohexyl-ethyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-bicyclo[2.2.1]hept-2-yl-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-8-((S)-1-methyl-1H-indol-3-yl-methyl)-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid 5-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-6b-(2-fluoro-acetyl)-5-hydroxy-4-a,6a-dimethyl-8-(4-methyl-benzyl)-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-6b-(2-fluoro-acetyl)-5-hydroxy-4-a,6a-dimethyl-8-thiophen-2-ylmethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-6b-(2-fluoro-acetyl)-8-(4-fluoro-benzyl)-5-hydroxy-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-6b-(2-fluoro-acetyl)-8-furan-2-ylmethyl-5-hydroxy-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-6b-(2-fluoro-acetyl)-5-hydroxy-8-(4-methoxy-benzyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-cyclopentylmethyl-4-b,12-difluoro-6b-(2-fluoro-acetyl)-5-hydroxy-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(3,3-dimethyl-butyl)-4-b,12-difluoro-6b-(2-fluoro-acetyl)-5-hydroxy-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(5-chloro-thiophen-2-ylmethyl)-4-b,12-difluoro-6b-(2-fluoro-acetyl)-5-hydroxy-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-8-[4-(2-hydroxy-ethoxy)-benzyl]-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-phenyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-p-tolyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-S-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-quinolin-6-yl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-pyridin-3-yl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-m-tolyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-(4-fluoro-phenyl)-5-hydroxy-6b-((S)-2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(3-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-(4-trifluoromethyl-phenyl)-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-(3-fluoro-phenyl)-5-hydroxy-6b-((S)-2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-o-tolyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-3-methyl-phenyl)-4b,12-difluoro-5-hydroxy-6b-((S)-2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-3-trifluoromethyl-phenyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(3,4-dichloro-phenyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-bromo-phenyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   4-[(4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS)-4-b-fluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,6b,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-8-yl]-benzonitrile;   4-[(4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,6b,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-8-yl]-benzamide;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-(4-trifluoromethoxy-phenyl)-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   Methanesulfonic acid 4-[(4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,6b,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-8-yl]-phenyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-cyclohexyl-phenyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-(4-thiophen-2-yl-phenyl)4a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   4-[(4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,6b,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-8-yl]-benzoic acid methyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-8-(4-methanesulfonyl-phenyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   3-[(4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,6b,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-8-yl]-benzonitrile;   4-[(4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,6b,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-8-yl]-benzene sulfonamide;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-cyclopropyl-phenyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-tert-butyl-phenyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,1011,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   N-{4-[(4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,6b,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-8-yl]-phenyl}-formamide;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-(3-trifluoromethyl-phenyl)-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-(3-trifluoromethoxy-phenyl)-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(3-bromo-phenyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-benzothiazol-6-yl-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-8-(4-hydroxy-phenyltrifluoromethansulfonate)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(3-cyclopropyl-phenyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-(4-piperidin-4-ylmethyl-phenyl)-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-phenyl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-m-tolyl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-o-tolyl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-p-tolyl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(3-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-(4-fluoro-phenyl)-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-pyridin-3-yl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-(3-fluoro-phenyl)-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-(4-trifluoromethyl-phenyl)-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-phenyl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-m-tolyl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-o-tolyl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-p-tolyl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(3-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-(4-fluoro-phenyl)-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioicacid S—((S)-fluoromethyl)ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-pyridin-3-yl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-(3-fluoro-phenyl)-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioicacid S—((S)-fluoromethyl)ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-(4-trifluoromethyl-phenyl)-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-6b-(2-fluoro-acetyl)-5-hydroxy-4-a,6a-dimethyl-8-phenyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-6b-(2-fluoro-acetyl)-5-hydroxy-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   Methanesulfonic acid 2-[(4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-6b-yl]-2-oxo-ethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-6b-(2-chloro-acetyl)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-6b-(2-methylsulfanyl-acetyl)-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid chloromethyl thioester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid cyclopropylmethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid cyanomethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid carbamoylmethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid 2,2,2-trifluoro-ethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid 2-fluoro-ethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-cyanomethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-(2-fluoro-ethyl)ester;   4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-(2,2,2-trifluoro-ethyl)ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-carbamoylmethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-prop-2-ynyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-cyclobutyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothoic acid S-(2-oxo-propyl)ester;   4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid methyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid cyanomethyl-methyl-amide;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-methyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-6b-acetyl-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid 1,1-dimethyl-prop-2-ynyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid 1,1-dimethyl-allyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(3,3-dimethyl-butyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-(4-fluoro-benzyl)-5-hydroxy-6b-(2-hydroxy-acetyl)-4a,6a-dimethyl-4a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-thiophen-2-ylmethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-furan-2-ylmethyl-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(2-ethyl-butyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   3-[(4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,6b,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-8-ylmethyl]-benzoic acid methyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-cyclohexylmethyl-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-(4-methylsulfanyl-benzyl)-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-((R,S)-sec-butyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-cyclopentylmethyl-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   4-[(4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,6b,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-8-ylmethyl]-benzoic acid tert-butyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-benzyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   Methanesulfonic acid 2-[(4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-benzyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-6b-yl]-2-oxo-ethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-6b-acetyl-8-(4-chloro-benzyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-4a,4b,5,6,6a,6b,8,9,9a,10,10a,10b, 11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-benzyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(3,3-dimethyl-butyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-(4-fluoro-benzyl)-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-thiophen-2-ylmethyl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-furan-2-ylmethyl-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-benzyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-(2-oxo-[1,3]dioxolan-4-yl) ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-benzyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid methoxy-methyl-amide;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-thiophen-2-ylmethyl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-(4-fluoro-benzyl)-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-(4-fluoro-benzyl)-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid cyanomethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-thiophen-2-ylmethyl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid cyanomethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-furan-2-ylmethyl-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-8-(4-fluoro-benzyl)-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-thiophen-2-ylmethyl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(3,3-dimethyl-butyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-6b-(2-fluoro-acetyl)-5-hydroxy-4-a,6a-dimethyl-8-(4-methyl-benzyl)-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-6b-(2-fluoro-acetyl)-5-hydroxy-4-a,6a-dimethyl-8-thiophen-2-ylmethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-6b-(2-fluoro-acetyl)-8-(4-fluoro-benzyl)-5-hydroxy-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-6b-(2-fluoro-acetyl)-8-furan-2-ylmethyl-5-hydroxy-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-6b-(2-fluoro-acetyl)-5-hydroxy-8-(4-methoxy-benzyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-cyclopentylmethyl-4-b,2-difluoro-6b-(2-fluoro-acetyl)-5-hydroxy-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(3,3-dimethyl-butyl)-4-b,12-difluoro-6b-(2-fluoro-acetyl)-5-hydroxy-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(5-chloro-thiophen-2-ylmethyl)-4-b,12-difluoro-6b-(2-fluoro-acetyl)-5-hydroxy-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-8-[4-(2-hydroxy-ethoxy)-benzyl]-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-8-phenyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4-a,6a-dimethyl-4-a,4b,5,6,6a,6b,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-phenyl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-8-(4-chloro-phenyl)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carboxylic acid;   (4aS,4bR,5S,6aS,6bR,9aS,10aS,10bS,12S)-4-b,12-difluoro-5-hydroxy-4-a,6a-dimethyl-2-oxo-8-phenyl-2,4-a,4b,5,6,6a,8,9,9a,10,10a,10b,11,12-tetradecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthrene-6b-carbothioic acid S-fluoromethyl ester;   or a pharmaceutically acceptable salt thereof.   
     
     
         9 . A pharmaceutical composition, comprising a compound or salt thereof according to  claim 1  and one or more pharmaceutically acceptable carriers and/or excipients. 
     
     
         10 . A combination, comprising a compound or salt thereof according to  claim 1  and one or more active ingredients selected from the group consisting of a beta2-agonist, an antimuscarinic agent, a corticosteroid, a mitogen-activated protein kinase (P38 MAP kinase) inhibitor, a nuclear factor kappa-B kinase subunit beta (IKK2) inhibitor, a human neutrophil elastase (FINE) inhibitor, a phosphodiesterase 4 (PDE4) inhibitor, a leukotriene modulator, a non-steroidal anti-inflammatory agents (NSAID), and a mucus regulator. 
     
     
         11 . A method for the prevention and/or treatment of any disease wherein the decrease in the number, activity, and movement of inflammatory cells is involved, said method comprising administering an effective amount of a compound or salt thereof according to  claim 1  to a subject in need thereof. 
     
     
         12 . A method for the prevention and/or treatment a respiratory disease, said method comprising administering an effective amount of a compound or salt thereof according to  claim 1  to a subject in need thereof. 
     
     
         13 . A method for the prevention and/or treatment of asthma or COPE), said method comprising administering an effective amount of a compound or salt thereof according to  claim 1  to a subject in need thereof. 
     
     
         14 . A device, comprising a pharmaceutical composition according to  claim 9 . 
     
     
         15 . A device according to  claim 14 , which is a single-dose dry powder inhaler. 
     
     
         16 . A device according to  claim 14 , which is a multi-dose dry powder inhaler. 
     
     
         17 . A device according to  claim 14 , which is a a metered dose inhaler. 
     
     
         18 . A device according to  claim 14 , which is a soft mist nebulizer.