US 2017/0158730 A1Published application

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

AssigneeSphaera Pharma Pvt. Ltd.

InventorsSundeep DUGAR, Dinesh MAHAJAN, George Frederick SCHREINER

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Abstract

The present invention relates to novel steroidal compounds of formula (I), process for preparation of the same and composition comprising these compounds.

Claims12

Dependent claims

Hydroxysteroid compounds and their intermediates of 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;
A1, A2, A3 are independently selected from the group comprising hydrogen, hydroxyl, hydroxymethyl, halogen, C1-C6 alkyl.
B and C are each independently selected from the group comprising hydrogen, hydroxyl, halogen, —OR6, —COR6, —COOR6, OCOR6, CH2OH, CH2OR6, —CONHR6, CONHR6R7, —C(OH)R6R7, NHR6, NHR5CONHR6, —R6NHCOOR7, —NR6R7, C(O)heteroaryl, C(O)heterocyclyl, C1-C12 straight or branched chain alkyl, 5-6 membered heterocycloalkyl, 5-6 membered heteroaryl;
wherein the C1-C12 straight or branched chain alkyl or 5-6 membered heterocycloalkyl or 5-6 membered heteroaryl;
may be further optionally substituted with one or more substituents selected from the group comprising halogen, C1-C6 alkyl, —OR6, —COOR6, —CONHR6, —OCOR6, ═NOH, NR6R7, —NR6COR7, 5-6 membered heterocycloalkyl or 5-6 membered heteroaryl;
C1-C12 alkyl substituted 5-6 membered heterocycloalkyl or C1-C12 alkyl substituted 5-6 membered heteroaryl;
or B and C may combine together to form ═O, ═NOR6, NHR6, 5-6 membered heterocycloalkyl, or 5-6 membered heteroaryl;
wherein the said 5-6 membered heterocycloalkyl, 5-6 membered heteroaryl may optionally contain one or more heteroatom;
wherein, the heteroatom may be O, N, S;
R1, R2, and R4 are independently selected from the group comprising hydrogen, deuterium, hydroxyl, halogen, ═O, —OR6, —NR6R7, —COR6, —COOR6, —OCOR6, —CONR6R7, C1-C6 alkyl, —Otert-butyldimethylsilyl;
R3 is hydroxyl, carbonyl, OCOR6,
wherein R3 is in beta configuration
R5 is selected from hydrogen, hydroxyl, halogen, OR6;
R6 and Rare each independently selected from the group comprising hydrogen, halogen, hydroxyl, C1-C12 alkyl, —NH2, —(CH2)nNH2, 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl;
X is selected from CH, NH, NR6, O or S.
n is 0 to 3.

14 more elements

The compounds as claimed in 1, selected from the group comprising:

i. (10R,11S,13S,17S)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-11-hydroxy-10,13-dimethyl-3-oxo-1H-cyclopenta[a]phenanthrene-17-carboxylic acid;
ii. (3S,8S,9S,10S,11S,13S,14S,17S)-hexadecahydro-3,11-dihydroxy-N,10,13-trimethyl-1H-cyclopenta[a]phenanthrene-17-carboxamide;
iii. (3S,8S,9S,10S,11S,13S,14S,17S)—N-(2-aminoethyl)-hexadecahydro-3,11-dihydroxy-10,13-dimethyl-1H-cyclopenta[a]phenanthrene-17-carboxamide;
iv. (3S,5R,6R,10R,11S,13S,17S)-hexadecahydro-6-methoxy-10,13-dimethyl-17-(2-methyl-1,3-dioxolan-2-yl)-1H-cyclopenta[a]phenanthrene-3,5,11-triol;
v. (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-2,7βH,8H)-dione;
vi. (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;
vii. (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-2,7βH,8H)-dione;
viii. (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;
ix. (11S)-7,8,9,11,12,13,14,15,16,17-decahydro-3,11-dihydroxy-6H-cyclopenta[a]phenanthrene-17-carboxylic acid;
x. (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;
xi. (17S)-17-acetyl-7,8,13,15,16,17-hexahydro-3-hydroxy-1-methyl-6H-cyclopenta [a]phenanthren-11(9H,12H,14H)-one;
xii. (13S,17S)-17-acetyl-7,8,13,15,16,17-hexahydro-3-hydroxy-13-methyl-6H-cyclopenta[a]phenanthren-11(9H,12H,14H)-one;
xiii. (10R,11S,13S,17S)-11-hydroxy-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylic acid;
xiv. (10R,11S,13S,17S)-11-hydroxy-N,N,10,13-tetramethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxamide;
xv. (10R,115,135,175)-17-acetyl-11-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;
xvi. (10R,11S,13S,17S)-11-hydroxy-17-((R)-1-hydroxyethyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;
xvii. (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;
xviii. (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-2,7βH,8H)-dione;
xix. (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;
xx. (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;
xxi. (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;
xxii. (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;
xxiii. (4aR,5S,6aS)-5,7-dihydroxy-4a,6a-dimethyltetradecahydro-1H-indeno[5,4-f]quinolin-2(3H)-one;
xxiv. (4aR,5S,6aS)-7-amino-5-hydroxy-4a,6a-dimethyltetradecahydro-1H-indeno[5,4-f]quinolin-2(3H)-one;
xxv. (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;
xxvi. (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;
xxvii. (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;
xxviii. (11S,13S)-17-(1-hydroxyethyl)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3,11-diol;
xxix. 1-((11S,13S)-3,11-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-yl)ethanone;
xxx. (11S,13S)-17-(1-hydroxyethyl)-3-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-11-ol;
xxxi. (11S,13S)-3-((tert-butyldimethylsilyl)oxy)-13-methyl-17-(2-methyl-1,3-dioxolan-2-yl)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-11-ol;
xxxii. (11S,13S)-13-methyl-17-(2-methyl-1,3-dioxolan-2-yl)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3,11-diol;
xxxiii. (10R,11S,13S,17S)-11,17-dihydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;
xxxiv. (10R,11S,13S)-11-hydroxy-10,13-dimethyl-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione;
xxxv. (11S,13S,17S)-4,11-dihydroxy-1,13-dimethyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-17-carboxylic acid;
xxxvi. (11S,13S,17S)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3,11,17-triol;
xxxvii. (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;
xxxviii. (4aR,5S,6aS,7S)-5-hydroxy-7-(2-hydroxypropan-2-yl)-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;
xxxix. 1-((8S,9S,10R,11S,13S,14S)-3,11-dihydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethanone;
xl. (8S,9S,10R,11S,13S,14S)-17-acetyl-11-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3(2H)-one;
xli. (10R,11S,13S,17S)-11-hydroxy-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxamide;
xlii. (10R,11S,13S,17S)-11-hydroxy-17-(hydroxymethyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;
xliii. (10R,11S,13S,17S)-17-((dimethylamino)methyl)-11-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;
xliv. (11S,13S,17S)-methyl 4,11-dihydroxy-1,13-dimethyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-17-carboxylate;
xlv. (11S,13S,17S)-4,11-dihydroxy-1,13-dimethyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-17-carboxamide;
xlvi. (11S,13S,17S)-4,11-dihydroxy-N,N,1,13-tetramethyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-17-carboxamide;
xlvii. ((11S,13S,17S)-4,11-dihydroxy-1,13-dimethyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-yl)(piperazin-1-yl)methanone;
xlviii. (11S,13S,17S)-17-(hydroxymethyl)-1,13-dimethyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-4,11-diol;
xlix. (11S,13S,17S)-11-hydroxy-4-methoxy-1,13-dimethyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-17-carboxylic acid;
l. (11S,13S,17S)-17-((dimethylamino)methyl)-1,13-dimethyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-4,11-diol;
li. 1-((11S,13S)-11-hydroxy-3-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-yl)ethanone;
lii. (E)-1-((11S,13S)-3,11-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-yl)ethanone oxime;
liii. (E)-1-((11S,13S)-3,11-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-yl)ethanone oxime;
liv. (11S,13S)-17-(2-hydroxypropan-2-yl)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3,11-diol;
lv. (11S,13R)-17-ethyl-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3,11-diol;
lvi. (8S,9S,10R,11S,13S,14S,Z)-11-hydroxy-17-(hydroxyimino)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;
lvii. (8S,9S,10R,11S,13S,14S)-17-amino-11-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;
lviii. (8S,9S,10R,11S,13S,14S)-11-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;
lix. (8S,9S,10R,11S,13S,14S,17S)-11,17-dihydroxy-10,13,17-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;
lx. (11R,13S,17S)-11,13,17-trimethyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3,11,17-triol;
lxi. (11S,13S)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3,11-diol;
lxii. (11S,13S,17S)-17-amino-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3,11-diol;
lxiii. (11S,13S,Z)-3,11-dihydroxy-13-methyl-7,8,9,11,12,13,15,16-octahydro-6H-cyclopenta[a]phenanthren-17(14H)-one oxime;
lxiv. (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;
lxv. (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.

62 more elements

Dependencies are inferred from the claim text.

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