Hydroxysteroid compounds, their intermediates, process of preparation, composition and uses thereof

1. A hydroxysteroid compound having formula (I):

or a salt thereof, wherein

is independently either a single bond, a double bond or a cyclopropyl ring, provided that adjacent double bonds are not allowed;

A 1 , A 2 , and A 3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, and C 1 -C 6 alkyl;

B and C are each independently selected from the group consisting of hydrogen, hydroxyl, halogen, —OR 6 , —COR 6 , —COOR 6 , —OCOR 6 , —CH 2 OH, —CH 2 OR 6 , —CONHR 6 , —CONR 6 R 7 , —C(OH)R 6 R 7 , —NHR 6 , —NR 6 R 7 , C 1 -C 12 straight or branched chain alkyl, and 5-6 membered heterocycloalkyl;

wherein the C 1 -C 12 straight or branched chain alkyl or 5-6 membered heterocycloalkyl is further optionally substituted with one or more substituents selected from the group consisting of halogen, C 1 -C 6 alkyl, —OR 6 , —COOR 6 , —CONHR 6 , —OCOR 6 , ═NOH, —NR 6 R 7 , —NR 6 COR 7 , 5-6 membered heterocycloalkyl, and C 1 -C 12 alkyl substituted 5-6 membered heterocycloalkyl;

or B and C combine together to form ═O or ═NOR 6 ;

or B and C combine together with the carbon atom to which they are attached to form a 5-6 membered heterocycloalkyl, wherein said 5-6 membered heterocycloalkyl comprises one or more heteroatoms selected from the group consisting of O and N;

R 1 is selected from the group consisting of hydroxyl, ═O, —OR 6 , and -Otert-butyldimethylsilyl;

R 2 and R 4 are independently selected from the group consisting of hydrogen, deuterium, and C 1 -C 3 straight or branched chain alkyl;

R 3 is hydroxyl;

wherein R 3 is in a beta configuration;

R 5 is hydrogen;

R 6 and R 7 are each independently selected from the group consisting of hydrogen, C 1 -C 12 alkyl, —NH 2 , —(CH 2 ) n NH 2 , 3-6 membered cycloalkyl, and 4-6 membered heterocycloalkyl;

X is selected from the group consisting of NH and NR 6 ; and

n is 0 to 3;

wherein when R 1 is ═O, then B and C are not —CONHR 6 or —CONR 6 R 7 .

2. The hydroxysteroid compound of claim 1 , wherein the hydroxysteroid compound has formula (II):

or a salt thereof, wherein:

is independently either a single bond, a double bond or a cyclopropyl ring, provided that adjacent double bonds are not allowed;

A 1 and A 2 are independently selected from the group consisting of hydrogen, halogen, and C 1 -C 6 alkyl;

B and C are each independently selected from the group comprising consisting of hydrogen, hydroxyl, halogen, —COR 6 , —COOR 6 , —CH 2 OH, —CH 2 OR 6 , —CONHR 6 , —CONR 6 R 7 , —C(OH)R 6 R 7 , —NHR 6 , —NR 6 R 7 , C 1 -C 12 straight or branched chain alkyl, and 5-6 membered heterocycloalkyl;

wherein the C 1 -C 12 straight or branched chain alkyl or 5-6 membered heterocycloalkyl is further optionally substituted with one or more substituents selected from the group consisting of halogen, C 1 -C 6 alkyl, —OR 6 , —COOR 6 , —CONHR 6 , —OCOR 6 , ═NOH, —NR 6 R 7 , —NR 6 COR 7 , 5-6 membered heterocycloalkyl, and C 1 -C 12 alkyl substituted 5-6 membered heterocycloalkyl;

or B and C combine together to form ═O or ═NOR 6 ;

or B and C combine together with the carbon atom to which they are attached to form a 5-6 membered heterocycloalkyl, wherein the said 5-6 membered heterocycloalkyl, comprises one or more heteroatoms selected from the group consisting of O or N;

R 1 is selected from the group consisting of hydroxyl, ═O, —OR 6 , and —Otert—butyldimethylsilyl;

R 2 and R 4 are independently selected from the group consisting of hydrogen, deuterium, and C 1 -C 3 alkyl;

R 6 and R 7 are each independently selected from the group consisting of hydrogen, C 1 -C 12 straight or branched chain alkyl, —(CH 2 ) n NH 2 , 3-6 membered cycloalkyl, and 4-6 membered heterocycloalkyl; and

n is 0 to 3;

wherein when R 1 is ═O, then B and C are not —CONHR 6 or —CONR 6 R 7 .

3. The hydroxysteroid compound of claim 1 , or a salt thereof,

wherein:

A 1 and A 2 are each C 1 -C 6 alkyl; and

A 3 is hydrogen.

4. The hydroxysteroid compound of claim 1 , or a salt thereof, wherein:

B and C are each independently selected from the group consisting of hydrogen, halogen, —OCOR 6 , —CH 2 OH, —CH 2 OR 6 , —C(OH)R 6 R 7 , —NHR 6 , —NR 6 R 7 , C 1 -C 12 straight or branched chain alkyl, and 5-6 membered heterocycloalkyl.

5. The hydroxysteroid compound of claim 1 , or a salt thereof, wherein:

B and C are each independently selected from the group consisting of —OR 6 , —COR 6 , and —COOR 6 .

6. The hydroxysteroid compound of claim 1 , wherein:

B and C are each independently selected from the group consisting of hydrogen and 5-6 membered heterocycloalkyl;

wherein the 5-6 membered heterocycloalkyl is further optionally substituted with a C 1 -C 6 alkyl.

7. The hydroxysteroid compound of claim 1 , or a salt thereof, wherein:

B and C combine together to form ═O or ═NOR 6 .

8. The hydroxysteroid compound of claim 1 , or a salt thereof, wherein:

B and C combine together with the carbon atom to which they are attached to form a 5-6 membered heterocycloalkyl, wherein said 5-6 membered heterocycloalkyl comprises one or more heteroatom selected from the group consisting of O and N.

9. The hydroxysteroid compound of claim 1 , wherein:

R 1 is ═O.

10. The hydroxysteroid compound of claim 1 , or a salt thereof, wherein:

R 2 and R 4 are hydrogen.

11. The hydroxysteroid compound of claim 1 , or a salt thereof, wherein:

R 2 is hydrogen; and

R 4 is C 1 -C 3 alkyl.

12. The hydroxysteroid compound of claim 1 , or a salt thereof,

wherein:

A 1 and A 2 are each C 1 -C 6 alkyl;

A 3 is hydrogen;

R 1 is ═O; and

R 2 is hydrogen.

13. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof.

14. A hydroxysteroid compound selected from the group consisting of:

i. (4aR,5S,6aS)-5-hydroxy-4a,6a-dimethyl-4,4a,4b,5,6,6a,9,9a,9b,10-decahydro-1H-indeno[5,4-f]quinoline-2,7(3H,8H)-dione;

ii. (4a′R,5'S,6a'S)-5′-hydroxy-4a′,5′,6a′-trimethyl-3′,4′,4a′,4b′,5′,6′,6a′,8′,9′,9a′,9b′,10′-dodecahydrospiro[[1,3]dioxolane-2,7′-indeno[5,4-f]quinolin]-2′(1′H)-one;

iii. (4aR,5S,6aS)-4,4a,4b,5,6,6a,9,9a,9b,10-decahydro-5-hydroxy-4a,6a-dimethyl-1H-indeno[5,4-f]quinoline-2,7(3H,8H)-dione;

iv. (4aR,5S,6aS)-7-acetyl-4,4a,4b,5,6,6a,7,8,9,9a,9b,10-dodecahydro-5-hydroxy-4a,5,6a-trimethyl-1H-indeno[5,4-f]quinolin-2(3H)-one;

v. (4aR,6aS)-2,3,4,4a,4b,5,6,6a,7,8,9,9a,9b,10-tetradecahydro-4a,6a-dimethyl-2,5-dioxo-1H-indeno[5,4-f]quinoline-7-carboxylic acid;

vi. (4a′R,5'S,6a'S)-5′-hydroxy-4a′,6a′-dimethyl-3′,4′,4a′,4b′,5′,6′,6a′,8′,9′,9a′,9b′,10′-dodecahydrospiro[[1,3]dioxolane-2,7′-indeno[5,4-f]quinolin]-2′(1′H)-one;

vii. (4aR,5R,6aS)-5-hydroxy-4a,5,6a-trimethyl-4,4a,4b,5,6,6a,9,9a,9b,10-decahydro-1H-indeno[5,4-f] quinoline-2,7(3H,8H)-dione;

viii. (4aR,5S,6aS)-5,7-dihydroxy-4a,6a-dimethyl-4,4a,4b,5,6,6a,7,8,9,9a,9b,10-dodecahydro-1H-indeno[5,4-f]quinolin-2(3H)-one;

ix. (4aR,5S,6aS)-7-fluoro-5-hydroxy-4a,6a-dimethyl-4,4a,4b,5,6,6a,7,8,9,9a,9b,10-dodecahydro-1H-indeno[5,4-f]quinolin-2(3H)-one;

x. (4aR,5S,6aS,Z)-5-hydroxy-7-(hydroxyimino)-4a,6a-dimethyl-4,4a,4b,5,6,6a,7,8,9,9a,9b,10-dodecahydro-1H-indeno[5,4-f]quinolin-2(3H)-one;

xi. (4aR,5S,6aS)-5,7-dihydroxy-1,4a,6a-trimethyl-4,4a,4b,5,6,6a,7,8,9,9a,9b,10-dodecahydro-1H-indeno[5,4-f]quinolin-2(3H)-one;

xii. (4aR,5S,6aS)-5,7-dihydroxy-4a,6a-dimethyltetradecahydro-1H-indeno[5,4-f]quinolin-2(3H)-one;

xiii. (4aR,5S,6aS)-7-amino-5-hydroxy-4a,6a-dimethyltetradecahydro-1H-indeno[5,4-f]quinolin-2(3H)-one;

xiv. (4aR,5S,6aS,7S)-5-hydroxy-4a,6a-dimethyl-7-(2-methyl-1,3-dioxolan-2-yl)-4,4a,4b,5,6,6a,7,8,9,9a,9b,10-dodecahydro-1H-indeno[5,4-f]quinolin-2(3H)-one;

xv. (4aR,5S,6aS,7S)-5-hydroxy-4a,5,6a-trimethyl-7-(2-methyl-1,3-dioxolan-2-yl)-4,4a,4b,5,6,6a,7,8,9,9a,9b,10-dodecahydro-1H-indeno[5,4-f]quinolin-2(3H)-one;

xvi. (4aR,5S,6aS,7S)-5-hydroxy-4a,6a-dimethyl-2-oxo-2,3,4,4a,4b,5,6,6a,7,8,9,9a,9b,10-tetradecahydro-1H-indeno[5,4-f]quinoline-7-carboxylic acid;

xvii. (4aR,5S,6aS,7S)-7-acetyl-5-hydroxy-4a,6a-dimethyl-4,4a,4b,5,6,6a,7,8,9,9a,9b,10-dodecahydro-1H-indeno[5,4-f]quinolin-2(3H)-one;

xviii. (4aR,5S,6aS,7S)-5-hydroxy-7-(2-hydroxypropan-2-yl)-4a,6a-dimethyl-4,4a,4b,5,6,6a,7,8,9a,9b,10-dodecahydro-1H-indeno[5,4-f]quinolin-2(3H)-one;

xix. (4aR,5S,6aS,7S)-5-hydroxy-4a,6a-dimethyl-7-(2-methyl-1,3-dioxolan-2-yl)-4,4a,4b,5,6,6a,7,8,9,9a,9b,10-dodecahydro-1H-indeno[5,4-f]quinolin-2(3H)-one; and

xx. (4aR,5S,6aS,7S)-5-hydroxy-4a,6a-dimethyl-2-oxo-2,3,4,4a,4b, 5,6,6a,7,8,9,9a,9b, 10-tetradecahydro-1H-indeno[5,4-f]quinoline-7-carboxylic acid,

or a pharmaceutically acceptable salt or stereoisomer each thereof.