GLUCOCORTICOID RECEPTOR AGONISTS

Abstract

The present invention provides a compound of Formula I:

##STR00001##

wherein R is H or

##STR00002##

R.sup.1 is H, halogen, C1-C3 alkyl, C3-C6 cycloalkyl, C1-C3 alkoxy, C2-C3 alkenyl, OCF.sub.3,

##STR00003##

R.sup.2 is H, halogen, C1-C3 alkyl, C1-C3 alkoxy, or C2-C4 alkenyl;
R.sup.3 is NH.sub.2, or CH.sub.2NH.sub.2; and
X is O, OCH.sub.2, OCH.sub.2CH.sub.2, OCH(CH.sub.3), CH.sub.2O, SCH.sub.2, CH.sub.2S, CH.sub.2, NHCH.sub.2, CH.sub.2NH, N(CH.sub.3)CH.sub.2, CH.sub.2CH.sub.2, C≡C, or a bond, wherein X is connected to phenyl ring A at the ortho or the meta position, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I, or pharmaceutically acceptable salt thereof is useful for treating autoimmune and inflammatory diseases, such as atopic dermatitis and rheumatoid arthritis.

Claims

1. A compound of the formula: ##STR00351## wherein R is H or ##STR00352## R.sup.1 is H, halogen, CN, C1-C3 alkyl, C3-C6 cycloalkyl, C1-C3 alkoxy, C2-C3 alkenyl, OCF.sub.3, ##STR00353## R.sup.2 is H, halogen, C1-C3 alkyl, C1-C3 alkoxy, or C2-C3 alkenyl; R.sup.3 is NH.sub.2, or CH.sub.2NH.sub.2; and X is O, OCH.sub.2, OCH.sub.2CH.sub.2, CH.sub.2O, SCH.sub.2, CH.sub.2S, CH.sub.2, NHCH.sub.2, CH.sub.2NH, N(CH.sub.3)CH.sub.2, CH.sub.2CH.sub.2, C≡C, or a bond, wherein X is connected to phenyl ring A at the ortho or the meta position, or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 wherein R.sup.3 is NH.sub.2, or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 2 wherein R is H, or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 2 wherein R is ##STR00354## or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 3 wherein R.sup.1 is C1-C3 alkyl, or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 3 wherein R.sup.1 is CH.sub.3, or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 3 wherein R.sup.1 is C1-C3 alkoxy, or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 3 wherein R.sup.1 is OCH.sub.3, or a pharmaceutically acceptable salt thereof.

9. The compound according to claim 3 wherein R.sup.1 is F, or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 3 wherein R.sup.2 is F, or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 3 wherein X is OCH.sub.2, or a pharmaceutically acceptable salt thereof.

12. The compound according to claim 3 wherein X is O, or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 3 wherein X is CH.sub.2, or a pharmaceutically acceptable salt thereof.

14. The compound according to claim 3 wherein X is SCH.sub.2, or a pharmaceutically acceptable salt thereof.

15. The compound according to claim 3 wherein X is a bond, or a pharmaceutically acceptable salt thereof.

16. The compound according to claim 1 wherein the compound is of the formula: ##STR00355## or a pharmaceutical acceptable salt thereof.

17. The compound according to claim 1 wherein the compound is of the formula: ##STR00356## or a pharmaceutical acceptable salt thereof.

18. The compound according to claim 17 wherein the compound is: ##STR00357## or a pharmaceutically acceptable salt thereof.

19. The compound according to claim 18 which is: ##STR00358##

20. The compound according to claim 1 wherein the compound is: ##STR00359## or a pharmaceutically acceptable salt thereof.

21. The compound according to claim 20, which is: ##STR00360##

22. The compound according to claim 16 wherein the compound is: ##STR00361## or a pharmaceutically acceptable salt thereof.

23. The compound according to claim 22 which is: ##STR00362##

24. The compound according to claim 1 wherein the compound is: ##STR00363## or a pharmaceutically acceptable salt thereof.

25. The compound according to claim 24 which is: ##STR00364##

26. The compound according to claim 1 wherein the compound is: ##STR00365## or a pharmaceutically acceptable salt thereof.

27. The compound according to claim 26 which is: ##STR00366##

28. The compound according to claim 1 wherein the compound is: ##STR00367## or a pharmaceutically acceptable salt thereof.

29. The compound according to claim 28 which is: ##STR00368##

30. The compound according to claim 1 selected from the group consisting of: ##STR00369## ##STR00370## ##STR00371## ##STR00372## ##STR00373## ##STR00374## ##STR00375## ##STR00376## ##STR00377## ##STR00378## ##STR00379## ##STR00380## ##STR00381## ##STR00382## ##STR00383## ##STR00384## ##STR00385## ##STR00386## ##STR00387## ##STR00388## ##STR00389## ##STR00390## ##STR00391## ##STR00392## ##STR00393## ##STR00394## ##STR00395## ##STR00396## ##STR00397## ##STR00398## and pharmaceutically acceptable salts thereof.

31. A method of treating atopic dermatitis in a patient, comprising administering to a patient in need of such treatment an effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof.

32. A method of treating rheumatoid arthritis in a patient, comprising administering to a patient in need of such treatment an effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof.

33. A pharmaceutical composition, comprising a compound or a pharmaceutically acceptable salt thereof, according to claim 1 with one or more pharmaceutically acceptable carriers, diluents, or excipients.

34. A process for preparing a pharmaceutical composition, comprising admixing a compound or a pharmaceutically acceptable salt thereof according to claim 1 with one or more pharmaceutically acceptable carriers, diluents, or excipients.

Description

EXAMPLE 1

(6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-Aminobenzyl)oxy)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one

[0163] ##STR00191##

[0164] Perchloric acid (70% in water, 4.8 mL) was added to a suspension of (8S,9S,10R,11S,13S,14S,16R,17S)-11,16,17-trihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-one (4.4 g, 12 mmol, also referred to as “16alpha-hydroxyprednisolone”) and tert-butyl N-[3-[(2-fluoro-3-formyl-4-methyl-phenoxy)methyl]phenyl]carbamate (4.0 g, 11 mmol, preparation 4) in acetonitrile (110 mL) at −10° C. and was warmed to rt. After 1 h, DMF (10 mL) was added to the suspension at rt. After 18 h, the reaction was quenched with saturated aqueous sodium bicarbonate and extracted with 9:1 methylene chloride:isopropanol. The organic layers were combined; dried over magnesium sulfate; filtered, and concentrated under reduced pressure to give a residue. The residue was purified by reverse phase chromatography, eluting with 1:1 10 mM ammonium bicarbonate water+5% methanol:acetonitrile to give the title compound, peak 1 (1.72 g, 25% yield). ES/MS m/z 618.6 (M+H). .sup.1H NMR (400.13 MHz, d.sub.6-DMSO) δ 0.93-0.87 (m, 6H), 1.40 (s, 3H), 1.71-1.60 (m, 1H), 1.89-1.76 (m, 4H), 2.18-2.12 (m, 2H), 2.29 (s, 4H), 4.23-4.17 (m, 1H), 4.32-4.30 (m, 1H), 4.50-4.43 (m, 1H), 4.81 (d, J=3.2 Hz, 1H), 4.98-4.95 (m, 3H), 5.16-5.10 (m, 3H), 5.61 (s, 1H), 5.95 (s, 1H), 6.18-6.15 (m, 1H), 6.53-6.48 (m, 2H), 6.58 (s, 1H), 6.90-6.86 (m, 1H), 6.99 (t, J=7.7 Hz, 1H), 7.12 (t, J=8.5 Hz, 1H), 7.33-7.30 (m, 1H).

EXAMPLE 2

(6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-Aminobenzyl)oxy)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one

[0165] ##STR00192##

[0166] From Example 1, the residue was purified by reverse phase chromatography, eluting with 1:1 10 mM ammonium bicarbonate water+5% methanol:acetonitrile to give the title compound, peak 2 (1.24 g, 18% yield). ES/MS m/z 618.6 (M+H). .sup.1H NMR (400.13 MHz, d.sub.6-DMSO) δ .sup.1H NMR (400.13 MHz, DMSO): 0.88 (s, 3H), 1.24-1.12 (m, 2H), 1.40 (s, 3H), 1.69-1.56 (m, 1H), 1.91-1.76 (m, 4H), 2.08-2.01 (m, 2H), 2.22 (s, 3H), 2.39-2.29 (m, 1H), 3.18 (d, J=5.2 Hz, 1H), 4.12-4.00 (m, 1H), 4.37-4.30 (m, 2H), 4.79 (d, J=3.1 Hz, 1H), 5.00-4.93 (m, 2H), 5.10-5.06 (m, 3H), 5.31 (d, J=6.7 Hz, 1H), 5.95 (s, 1H), 6.18 (dd, J=1.8, 10.1 Hz, 1H), 6.34 (s, 1H), 6.53-6.48 (m, 2H), 6.58 (s, 1H), 6.87 (d, J=8.5 Hz, 1H), 6.99 (t, J=7.7 Hz, 1H), 7.09 (t, J=8.5 Hz, 1H), 7.33 (d, J=10.1 Hz, 1H).

EXAMPLE 3

(6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-Aminobenzyl)oxy)-2-fluoro-6-methylphenyl)-7-hydroxy-6a,8a-dimethyl-8b-(2-(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)acetyl)-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one

[0167] ##STR00193##

[0168] (2R,3 S,4S,5R,6R)-2-(Acetoxymethyl)-6-(2-((6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)-2-fluoro-6-methylphenyl)-7-hydroxy-6a,8a-dimethyl-4-oxo-1,2,4,6a,6b,7,8,8a,11a,12,12a,12b-dodecahydro-8bH-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-8b-yl)-2-oxoethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (40 mg, 0.04 mmol, Preparation 5) was added to methanol (2 mL) and potassium carbonate (20 mg, 0.20 mmol). After 1 h, the mixture was loaded onto a diatomaceous earth and was purified by reverse phase chromatography, eluting with 1:2 10 mM ammonium bicarbonate water+5% methanol:acetonitrile to give the title compound (19 mg, 57% yield). ES/MS m/z 780.4 (M+H). .sup.1H NMR (500.11 MHz, d.sub.6-DMSO) δ 0.90 (s, 3H), 1.28-1.27 (m, 2H), 1.41 (s, 3H), 1.72-1.69 (m, 1H), 1.92-1.88 (m, 4H), 2.11-2.10 (m, 2H), 2.22 (s, 3H), 2.40-2.35 (m, 1H), 3.50-3.46 (m, 1H), 3.57-3.53 (m, 1H), 3.64-3.61 (m, 1H), 4.17-4.15 (m, 1H), 4.34-4.32 (m, 1H), 4.43-4.39 (m, 2H), 4.57-4.52 (m, 1H), 4.64-4.62 (m, 1H), 4.75-4.72 (m, 2H), 5.00-4.93 (m, 3H), 5.12-5.08 (m, 2H), 5.31-5.29 (m, 1H), 5.95 (d, J=0.4 Hz, 1H), 6.20-6.17 (m, 1H), 6.34 (s, 1H), 6.54-6.49 (m, 2H), 6.59 (s, 1H), 6.88 (d, J=8.5 Hz, 1H), 7.00 (t, J=7.7 Hz, 1H), 7.12-7.08 (m, 1H), 7.35-7.33 (m, 1H).

EXAMPLE 4

(6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-Aminobenzyl)oxy)-2-fluoro-6-methoxyphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one

[0169] ##STR00194##

[0170] To a suspension of tert-butyl (3-((2-fluoro-3-formyl-4-methoxyphenoxy)methyl)phenyl)carbamate (2.6 g, 6.9 mmol, preparation 8) and 16alpha-hydroxyprednisolone (2.5 g, 6.6 mmol) in acetonitrile (100 mL) at −20° C. was added perchloric acid (70% in water, 3.3 mL, 5 equiv) dropwise. The mixture was stirred at −20° C. for 7 h. The solution was transferred to a separatory funnel. The solution was added dropwise to an aqueous solution of sodium hydroxide (7.5 mL 5N aq NaOH in 1 L water). After the addition was completed, the pH was measured at 5 and the pH was adjusted to 8 with 5N aq NaOH. The suspension was stirred for 10 minutes. The solid was collected by vacuum filtration and the solid was washed with water. The solid was dried on the filter overnight. The solid was purified by reverse phase chromatography, eluting with 1:1 10 mM ammonium bicarbonate water+5% methanol:acetonitrile to give the title compound, peak 1 (804 mg, 18% yield). MS m/z 634.2 (M+H). .sup.1H NMR (399.8 MHz, d.sub.6-DMSO) δ 7.33 (d, J=10.1 Hz, 1H), 7.17 (t, J=9.2 Hz, 1H), 6.98 (t, J=7.8 Hz, 1H), 6.76 (dd, J=1.0, 9.2 Hz, 1H), 6.56 (d, J=1.6 Hz, 1H), 6.52-6.48 (m, 2H), 6.17 (dd, J=1.9, 10.1 Hz, 1H), 5.96 (s, 1H), 5.71 (s, 1H), 5.17 (t, J=6.0 Hz, 1H), 5.10 (s, 2H), 4.94-4.90 (m, 3H), 4.79 (d, J=3.1 Hz, 1H), 4.44-4.38 (m, 1H), 4.33-4.31 (m, 1H), 4.22-4.15 (m, 1H), 3.70 (s, 3H), 2.37-2.33 (m, 1H), 2.14-2.04 (m, 2H), 1.96-1.88 (m, 1H), 1.82-1.70 (m, 3H), 1.64-1.56 (m, 1H), 1.41 (s, 3H), 0.86 (s, 5H).

EXAMPLE 5

(6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-Aminobenzyl)oxy)-2-fluoro-6-methoxyphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one

[0171] ##STR00195##

[0172] From Example 4, the residue was purified by reverse phase chromatography, eluting with 1:1 10 mM ammonium bicarbonate water+5% methanol:acetonitrile to give the title compound peak 2 (1.19 g, 27% yield). MS m/z 634.2 (M+H). .sup.1H NMR (399.8 MHz, d.sub.6-DMSO) δ 7.32 (d, J=10.0 Hz, 1H), 7.17-7.12 (m, 1H), 6.99 (t, J=7.7 Hz, 1H), 6.72 (d, J=8.8 Hz, 1H), 6.58 (s, 1H), 6.53-6.46 (m, 3H), 6.18 (dd, J=1.7, 10.1 Hz, 1H), 5.95 (s, 1H), 5.25 (d, J=6.5 Hz, 1H), 5.10 (s, 2H), 5.00-4.90 (m, 3H), 4.78 (d, J=3.1 Hz, 1H), 4.37-4.31 (m, 2H), 4.02-3.96 (m, 1H), 3.63 (s, 3H), 2.34-2.31 (m, 1H), 2.11-2.02 (m, 2H), 1.88-1.76 (m, 4H), 1.60-1.54 (m, 1H), 1.40 (s, 3H), 1.23-1.18 (m, 2H), 0.87 (s, 3H).

Alternative Preparation of Example 5

[0173] All solid handling steps were handled in a disposable glove bag including charging the flask with 16alpha-hydroxyprednisolone, solid filtration steps and solid transfer steps.

[0174] To a suspension of tert-butyl (3-((2-fluoro-3-formyl-4-methoxyphenoxy)methyl)phenyl)carbamate (25 g, 67 mmol, preparation 8) and 16alpha-hydroxyprednisolone (25 g, 65 mmol) in ACN (1000 mL) at −25° C. in a 2-L round bottom flask was added perchloric acid in water (31 mL, 330 mmol, 10.6 mol/L) dropwise. The mixture was stirred at −20° C. while monitoring the reaction by LCMS. Internal temperature monitoring indicated a small exotherm upon addition of perchloric acid. The internal temperature was kept below −19° C. with dry ice addition. The mixture was kept below −19° C. for 2 h and then was allowed to warm to −10° C. The mixture split in two and added dropwise to two separate beakers (Beaker 1 and Beaker 2) containing 76 mL of 5 M aq NaOH in 2 L of water, each. A solid formed upon addition and complete quench of perchloric acid was tested (pH 10). The sticky solid from each addition was transferred and combined to a third beaker (Beaker 3) containing 10% MeOH in DCM. The mixture was stirred until the sticky solid completely dissolved. The remaining solutions (Beaker 1 and Beaker 2) were then filtered through paper to collect residual solids. The isolated solids were rinsed with water and transferred to Beaker 3. Beaker 3 was stirred until all solids were dissolved. The solution was dried for 2 h with Na.sub.2SO.sub.4, filtered and evaporated to give a tan foam. The filtrates from the solid collection were extracted with three portions 10% IPA in DCM. The combined organic extracts were dried over Na.sub.2SO.sub.4 with stirring overnight, then filtered and evaporated to give additional crude residue. The crude products were dissolved in 150 mL 1% MeOH in DCM and purified by normal phase chromatography using 0-5% MeOH in DCM to give a solid. It was diluted with 600 mL EtOH and spun on the rotary evaporator at 45° C. for 5 minutes. The heat bath was turned up to 60° C. When the heat bath reached 60° C. it was turned off and the flask spun until the bath reached rt. The flask was taken off the rotary evaporator, capped and allowed to stand overnight at room temperature.

[0175] The solid was collected by vacuum filtration in a glove bag. The solids were rinsed with EtOH and dried on the filter for 5 h. The solid redissolved in 20% EtOH in DCM (1.5 L). Additional DCM was added to achieve a near clear solution (some haze persisted). Solvent exchange was achieved by rotary evaporation at 450 mbar and 45° C. to remove DCM. Once distillation had stopped, the pressure was decreased to 100 mbar to bring off EtOH to approximately 600 mL. The mixture was removed from the rotary evaporator and allowed to stand for 5 h at rt. The solid was collected by vacuum filtration and the solids washed twice with additional EtOH. The filter cake was dried in a vacuum oven at rt for 48 h to give the title compound (42 g, 38% yield). MS m/z 634.6 (M+H).

Structural Assignment by NMR

[0176] ##STR00196##

[0177] Two dimensional through-space ROE NMR analysis of acetal isomers consistently gave a cross peak for H22 (acetal) and H16 in the R configuration. Alternatively, H22 in the S configuration consistently gave about 1 ppm larger shift. All other compounds were assigned essentially by the same method.

[0178] The following compounds in Table 18a were prepared in a manner essentially analogous to the procedures described in Examples 1 to 4 utilizing the corresponding starting material of structure 1a and starting material of structure 2 as prepared in the corresponding preparations and tables 2-17 described above or prepared using standard procedures well known to one of ordinary skill in the art. Purification of final products was performed essentially by the following methods:

[0179] A. C18 column using eluent 10 mM NH.sub.4HCO.sub.3 in water+5% MeOH:ACN

[0180] B. C18 column using eluent 0.1% FA in water:ACN

[0181] C. SFC Chiralpak AY using eluent EtOH+0.05% DEA:CO.sub.2

[0182] D. Chiralpak IC using eluent MeOH+0.2% IPAm

[0183] E. SFC Lux Amylose-2 using eluent IPA+0.5% DMEA:CO.sub.2

[0184] F. SFC Chiralpak AD-H using eluent IPA+0.5% DMEA:CO.sub.2

[0185] G. Chiralpak IC using eluent EtOH+0.1% NH.sub.3H.sub.2O:heptane

[0186] H. SFC Chiralpack AD using eluent IPA+0.1% NH.sub.3H.sub.2O:CO.sub.2

[0187] I. Chiralcel IH using eluent EtOH+ACN (0.1% DEA):heptane

[0188] J. SFC Chiralpak AD using eluent EtOH+0.5% DEA:CO.sub.2

[0189] K. Chiralpak IE using eluent EtOH+0.1% NH.sub.3H.sub.2O:ACN

[0190] L. Chiralpak AD-H using eluent EtOH:ACN+0.2% IPAm

[0191] M. Chiralpak AD-H using eluent EtOH:ACN

[0192] N. SFC Chiralpak IC using eluent EtOH+0.05% DMEA:CO.sub.2

[0193] O. SFC Chiralcel OJ-H using eluent MeOH+0.5% DMEA:CO.sub.2

TABLE-US-00018 TABLE 18a Examples 6-158 (structures) ES/MS Ex (m/z) Purification No. Structure (M + H) method*  6 [00197] 570.4 A  7 [00198] 570.4 A  8 [00199] 570.4 A  9 [00200] 570.4 A  10 [00201] 571.4 B  11 [00202] 570.4 B  12 [00203] 572.2 A  13 [00204] 572.2 A  14 [00205] 572.2 A  15 [00206] 272.2 A  16 [00207] 600.2 A  17 [00208] 600.2 A  18 [00209] 600.2 A  19 [00210] 586.2 A  20 [00211] 586.2 A  21 [00212] 604.2 A  22 [00213] 604.2 A, O  23 [00214] 620.2 A  24 [00215] 620.2 A  25 [00216] 620.2 A  26 [00217] 620.2 A  27 [00218] 620.2 A  28 [00219] 620.2 A  29 [00220] 604.2 A  30 [00221] 604.2 A  31 [00222] 620.4 M  32 [00223] 620.4 M  33 [00224] 556.2 A  34 [00225] 556.2 A  35 [00226] 600.2 A  36 [00227] 600.2 A  37 [00228] 604.2 A  38 [00229] 604.2 A  39 [00230] 556.2 A  40 [00231] 556.2 A  41 [00232] 638.4 A, L  42 [00233] 586.4 A, L  43 [00234] 638.4 A, L  44 [00235] 586.4 A, L  45 [00236] 604.4 A, O  46 [00237] 604.4 A, O  47 [00238] 638.2 A  48 [00239] 638.2 A  49 [00240] 622.3 A  50 [00241] 622.3 A  51 [00242] 620.5 A, O  52 [00243] 620.5 A, O  53 [00244] 588.2 A  54 [00245] 588.2 A  55 [00246] 617.5 B, C  56 [00247] 618.4 A  57 [00248] 618.4 A  58 [00249] 622.0 A  59 [00250] 622.4 A  60 [00251] 634.3 A  61 [00252] 634.3 A  62 [00253] 632.4 A  63 [00254] 632.4 A  64 [00255] 617.6 B, J  65 [00256] 634.5 B  66 [00257] 634.5 B  67 [00258] 618.5 B, I  68 [00259] 618.5 B  69 [00260] 617.5 B  70 [00261] 617.0 B, K  71 [00262] 634.5 A, G  72 [00263] 634.1 B, H  73 [00264] 617.5 B, C  74 [00265] 670.4 A  75 [00266] 632.2 A  76 [00267] 632.2 A  77 [00268] 604.4 A  78 [00269] 604.3 A  79 [00270] 670.4 A  80 [00271] 600.6 A  81 [00272] 600.6 A  82 [00273] 622.4 A  83 [00274] 622.3 A  84 [00275] 632.4 B, H  85 [00276] 632.4 A  86 [00277] 631.5 B, G  87 [00278] 616.5 B  88 [00279] 616.4 A  89 [00280] 616.4 A  90 [00281] 616.4 A  91 [00282] 616.6 A  92 [00283] 664.4 A  93 [00284] 664.4 A  94 [00285] 638.4 D  95 [00286] 638.4 D  96 [00287] 618.6 N  97 [00288] 618.6 N  98 [00289] 600.2 B  99 [00290] 600.2 B 100 [00291] 634.4 A 101 [00292] 634.4 A 102 [00293] 634.5 B, H 103 [00294] 634.5 B, G 104 [00295] 617.1 B, K 105 [00296] 617.5 B 106 [00297] 618.5 B 107 [00298] 618.5 B, I 108 [00299] 634.5 B 109 [00300] 634.5 B 110 [00301] 617.6 B, J 111 [00302] 632.2 A 112 [00303] 631.4 B, G 113 [00304] 616.5 B 114 [00305] 632.4 B, H 115 [00306] 602.2 A 116 [00307] 602.2 A 117 [00308] 682.2 A 118 [00309] 682.2 A 119 [00310] 666.4 F 120 [00311] 616.4 A 121 [00312] 616.4 A 122 [00313] 680.6 B 123 [00314] 679.8 B 124 [00315] 711.6 A 125 [00316] 712.0 A 126 [00317] 667.8 B 127 [00318] 597.8 A 128 [00319] 597.8 A 129 [00320] 614.6 F 130 [00321] 614.6 F 131 [00322] 651.8 B 132 [00323] 651.8 B 133 [00324] 630.4 A 134 [00325] 630.4 A 135 [00326] 613.6 E 136 [00327] 613.6 E 137 [00328] 666.4 F 138 [00329] 646.4 A 139 [00330] 646.4 A 140 [00331] 638.1 A 141 [00332] 604.4 A 142 [00333] 604.4 A 143 [00334] 622.2 A 144 [00335] 651.8 B 145 [00336] 651.8 B 146 [00337] 622.0 A 147 [00338] 634.2 A 148 [00339] 634.4 A 149 [00340] 606.4 A 150 [00341] 644.4 A 151 [00342] 644.4 A 152 [00343] 662.4 A 153 [00344] 662.4 A 154 [00345] 634.5 B 155 [00346] 630.4 A 156 [00347] 630.4 A 157 [00348] 606.4 A 158 [00349] 634.5 B

TABLE-US-00019 TABLE 18b Examples 6-158 (chemical names) Ex No. Chemical Name 6 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-(4- aminobenzyl)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 7 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-(4- aminobenzyl)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 8 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-(3- aminobenzyl)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 9 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-(3- aminobenzyl)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 10 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-(2- aminobenzyl)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 11 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-(2- aminobenzyl)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 12 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-(4- aminophenoxy)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 13 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-(4- aminophenoxy)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 14 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-(3- aminophenoxy)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 15 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-(3- aminophenoxy)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 16 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 17 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 18 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 19 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3- aminobenzyl)oxy)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 20 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3- aminobenzyl)oxy)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 21 (6aR,6bS,7S,8aS,8bS,10RS,11aR,12aS,12bS)-10-(5-((3- aminobenzyl)oxy)-2-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)- 6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 22 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 23 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 4-chlorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 24 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 4-chlorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 25 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 5-chlorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 26 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 5-chlorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 27 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-chlorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 28 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-chlorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 29 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 5-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 30 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 5-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 31 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2-chlorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 32 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2-chlorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 33 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3′-amino-[1,1′- biphenyl]-3-yl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 34 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3′-amino-[1,1′-biphenyl]- 3-yl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 35 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 5-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 36 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 5-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 37 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 38 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 39 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(4′-amino-[1,1′- biphenyl]-3-yl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 40 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(4′-amino-[1,1′-biphenyl]- 3-yl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 41 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2-chloro-6-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 42 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(2-((3- aminobenzyl)oxy)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 43 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2-chloro-6-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 44 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(2-((3- aminobenzyl)oxy)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 45 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(2-((3-aminobenzyl)oxy)- 6-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 46 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(2-((3-aminobenzyl)oxy)- 6-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 47 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 6-chloro-2-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 48 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 6-chloro-2-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 49 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2,6-difluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 50 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2,6-difluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 51 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(2-((3-aminobenzyl)oxy)- 6-chlorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 52 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(2-((3-aminobenzyl)oxy)- 6-chlorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 53 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(5-(4-aminobenzyl)-2- fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 54 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(5-(4-aminobenzyl)-2- fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 55 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3- aminobenzyl)amino)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 56 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((2-aminobenzyl)oxy)- 2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 57 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((2-aminobenzyl)oxy)- 2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 58 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2,4-difluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 59 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2,4-difluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 60 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 6-fluoro-2-methoxyphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 61 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 6-fluoro-2-methoxyphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 62 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((2- (aminomethyl)benzyl)oxy)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 63 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((2- (aminomethyl)benzyl)oxy)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 64 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((2- aminobenzyl)amino)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 65 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((2-aminobenzyl)thio)- 2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 66 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)thio)- 2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 67 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((2- aminophenoxy)methyl)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 68 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3- aminophenoxy)methyl)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 69 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-(((3- aminophenyl)amino)methyl)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 70 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-(((2- aminophenyl)amino)methyl)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 71 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-(((2- aminophenyl)thio)methyl)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 72 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-(((3- aminophenyl)thio)methyl)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 73 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3- aminobenzyl)amino)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 74 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-(trifluoromethoxy)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 75 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3- (aminomethyl)benzyl)oxy)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 76 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3- (aminomethyl)benzyl)oxy)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 77 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((2-aminobenzyl)oxy)- 2-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 78 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((2-aminobenzyl)oxy)- 2-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 79 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-(trifluoromethoxy)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 80 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(5-((2-aminobenzyl)oxy)- 2-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 81 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(5-((2-aminobenzyl)oxy)- 2-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 82 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((2-aminobenzyl)oxy)- 2,6-difluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 83 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((2-aminobenzyl)oxy)- 2,6-difluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 84 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-(4-aminophenethoxy)- 2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 85 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-(3-aminophenethoxy)- 2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 86 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3- aminobenzyl)(methyl)amino)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 87 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-(4-aminophenethyl)-2- fluoro-6-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 88 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-methoxyphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 89 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-methoxyphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 90 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2-methoxyphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 91 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2-methoxyphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 92 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-bromophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 93 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-bromophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 94 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((2-aminobenzyl)oxy)- 2-chloro-6-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 95 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((2-aminobenzyl)oxy)- 2-chloro-6-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 96 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 6-fluoro-2-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 97 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 6-fluoro-2-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 98 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((2-aminobenzyl)oxy)- 2-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 99 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((2-aminobenzyl)oxy)- 2-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 100 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((2-aminobenzyl)oxy)- 2-fluoro-6-methoxyphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 101 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((2-aminobenzyl)oxy)- 2-fluoro-6-methoxyphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 102 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-(((3- aminophenyl)thio)methyl)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 103 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-(((2- aminophenyl)thio)methyl)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 104 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-(((2- aminophenyl)amino)methyl)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 105 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-(((3- aminophenyl)amino)methyl)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 106 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3- aminophenoxy)methyl)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 107 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((2- aminophenoxy)methyl)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 108 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)thio)- 2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 109 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((2-aminobenzyl)thio)- 2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 110 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((2- aminobenzyl)amino)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 111 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-(3-aminophenethoxy)- 2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 112 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3- aminobenzyl)(methyl)amino)-2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 113 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-(4-aminophenethyl)-2- fluoro-6-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 114 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-(4-aminophenethoxy)- 2-fluoro-6-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 115 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(5-(4-aminophenoxy)-2- methoxyphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 116 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(5-(3-aminophenoxy)-2- methoxyphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 117 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 6-bromo-2-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 118 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 6-bromo-2-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 119 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2-bromophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 120 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(5-((2-aminobenzyl)oxy)- 2-methoxyphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 121 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(5-((2-aminobenzyl)oxy)- 2-methoxyphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 122 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(4-((3-aminobenzyl)oxy)- 3-fluoro-[1,1′-biphenyl]-2-yl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 123 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(4-((3-aminobenzyl)oxy)- 3-fluoro-[1,1′-biphenyl]-2-yl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 124 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-iodophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 125 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-iodophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 126 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-(thiophen-2-yl)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 127 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3- aminophenyl)ethynyl)-2-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)- 6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 128 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3- aminophenyl)ethynyl)-2-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)- 6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 129 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2,6-dimethylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 130 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2,6-dimethylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 131 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-(furan-3-yl)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 132 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-(furan-3-yl)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 133 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-ethoxyphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 134 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-ethoxyphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 135 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3- aminobenzyl)amino)-2,6-dimethylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 136 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3- aminobenzyl)amino)-2,6-dimethylphenyl)-7-hydroxy-8b-(2- hydroxyacetyl)-6a,8a-dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b- dodecahydro-4H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 137 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2-bromophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 138 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2-fluoro-6-isopropylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 139 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2-fluoro-6-isopropylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 140 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((2-aminobenzyl)oxy)- 6-chloro-2-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 141 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(5-(3-aminobenzyl)-2- chlorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 142 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(5-(4-aminobenzyl)-2- chlorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 143 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-(3-aminobenzyl)-6- chloro-2-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 144 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-(furan-2-yl)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 145 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(5-((3-aminobenzyl)oxy)- 2-(furan-2-yl)phenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 146 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-(4-aminobenzyl)-6- chloro-2-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 147 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2-fluoro-4-methoxyphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 148 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2-fluoro-4-methoxyphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 149 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-(3-aminobenzyl)-2,6- difluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 150 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 6-cyclopropyl-2-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 151 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 6-cyclopropyl-2-fluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 152 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(4-((3-aminobenzyl)oxy)- [1,1′-biphenyl]-2-yl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 153 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(4-((3-aminobenzyl)oxy)- [1,1′-biphenyl]-2-yl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 154 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)thio)- 2-fluoro-4-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 155 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2-fluoro-6-vinylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 156 (6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)oxy)- 2-fluoro-6-vinylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 157 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-(3-aminobenzyl)-2,6- difluorophenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl- 1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one 158 (6aR,6bS,7S,8aS,8bS,10R,11aR,12aS,12bS)-10-(3-((3-aminobenzyl)thio)- 2-fluoro-4-methylphenyl)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a- dimethyl-1,2,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-4H- naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-4-one

EXAMPLE 159

4-((3-Aminobenzyl)oxy)-3-fluoro-2-((6aR,6bS,7S,8aS,8bS,10S,11aR,12aS,12bS)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a-dimethyl-4-oxo-2,4,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-1H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-10-yl)benzonitrile

[0194] ##STR00350##

[0195] Trifluoromethanesulfonic acid (920 μL, 10 mmol) was added dropwise to a suspension of 16alpha-hydroxyprednisolone (140 mg, 0.36 mmol) and tert-butyl (3-((4-cyano-3-(1,3-dioxolan-2-yl)-2-fluorophenoxy)methyl)phenyl)carbamate (140 mg, 0.34 mmol) in ACN (5 mL, 95 mmol) at 0° C. The reaction was quenched with satd aq NaHCO.sub.3 and extracted with 10% IPA in DCM. The combined organic layers were dried with MgSO.sub.4, filtered, and concentrated to a crude residue. The crude residue was purified by reverse phase purification, eluting with 1:1 10 mM NH.sub.4HCO.sub.3 in water+5% MeOH:ACN to give the title compound (12 mg, 6% yield). MS m/z 630.0 (M+H). .sup.1H NMR (400.13 MHz, d.sub.6-DMSO) δ 7.70-7.67 (m, 1H), 7.45-7.41 (m, 1H), 7.33 (d, J=10.1 Hz, 1H), 7.04-7.00 (m, 1H), 6.61-6.51 (m, 3H), 6.45 (s, 1H), 6.20-6.17 (m, 1H), 5.95 (s, 1H), 5.37-5.35 (m, 1H), 5.15 (s, 4H), 4.86-4.84 (m, 1H), 4.32-4.31 (m, 2H), 4.07-4.01 (m, 1H), 2.14-2.12 (m, 2H), 1.92-1.88 (m, 4H), 1.67-1.66 (m, 1H), 1.40-1.39 (m, 3H), 1.25-1.20 (m, 2H), 0.89-0.88 (m, 3H).

hGR CoActivator Recruitment Assay

[0196] The activity of glucocorticoid compounds was measured using the LanthaScreen TR-Fret GR Coactivator Assay from Life Technologies (A15899). The compounds were acoustically transferred to an assay plate in a 3-fold 10-point serial dilution with a top concentration of 200 nM. Ten microliters of a 2× solution of GR-LBD was added to the compound plate and incubated for 10 min. Then ten microliters of a 2× solution of Fluoresein-SRC1-4 and Tb labelled anti-GST antibody were added to the plate. The plate was incubated in the dark for two hours and then read on an Envision plate reader, with excitation at 340 nm and emission at 520 nm (Fluorescein) and 490 nm (Terbium). The emission ratio of 520/490 was analyzed in Genedata. To obtain percent activity, the data was compared to a negative control of DMSO and positive control of 4 uM dexamethasone. The following exemplified compounds were tested following the procedure as essentially described above and exhibited the following activity as listed in Table 19.

TABLE-US-00020 TABLE 19 In vitro potency of compounds of Examples 1, 2, 4, and 5 in the hGR CoActivator Recruitment Assay Example No. IC.sub.50 (nM) 1 2.12 2 1.44 4 2.47 5 1.40
The compounds of Examples 6-44, 46-51, 53-79, and 81-158 provided a relative IC.sub.50 of less than 200 nM. The compounds of Examples 45, 52, and 80 provided a relative IC.sub.50 of greater than 200 nM.