IP Library › Granted Patent US 9,670,247

Granted Patent B2

US 9,670,247 · App. 13/932,778 · Granted Jun 6, 2017

Contraceptive agents

Inventors: Gustavo Blanco (Overland Park, KS); Gunda I. Georg (St. Paul, MN); Shameem Sultana Syeda (St. Paul, MN)

Assignees: The University of Kansas; Regents of The University of Minnesota

C07J43/003 C07C49/653 C07C49/757 C07C247/14 C07C281/18 C07D249/04 C07D249/06 C07J17/005 C07J19/00 C07J19/005 C07J71/0026 C07J1/0011 C07J7/00 C07J7/002 C07J41/0005 C07J41/005 C07J41/0027 C07J51/00

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Quick Facts

Patent No.: US 9,670,247
App. No.: 13/932,778
Granted: Jun 6, 2017
Kind: B2

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Abstract

The invention provides compounds of formula I, II, III, or IV: wherein R 1 to R 11 , X, and Y have any of the values defined in the specification. The compounds inhibit Na, K-ATPase α4 and are useful as contraceptive agents.

Claims (135)

1. A compound of formula:

wherein:

R 1 is H, (C 1 -C 6 )alkyl, or R c , wherein the (C 1 -C 6 )alkyl is optionally substituted with one or more halo or (C 1 -C 6 )alkoxy;

R 2 is H or (C 1 -C 6 )alkyl, wherein the (C 1 -C 6 )alkyl is optionally substituted with one or more halo or (C 1 -C 6 )alkoxy;

R 3 is H or (C 1 -C 6 )alkyl, wherein the (C 1 -C 6 )alkyl is optionally substituted with one or more halo or (C 1 -C 6 )alkoxy;

R 4 is R a , cyano, formyl, carboxy, hydroximinomethyl, (C 1 -C 4 )alkyl, (C 2 -C 4 )alkenyl, (C 2 -C 4 )alkynyl, aryl, heteroaryl, or (C 1 -C 4 )alkanoyl, wherein the (C 1 -C 4 )alkyl, (C 2 -C 4 )alkenyl, (C 2 -C 4 )alkynyl, and (C 1 -C 4 )alkanoyl is optionally substituted with one or more groups selected from hydroxy, halo, aryl, and heteroaryl; wherein any aryl and heteroaryl of R 4 is optionally substituted with one or more R b ;

R 5 is H or (C 1 -C 6 )alkyl, wherein the (C 1 -C 6 )alkyl is optionally substituted with one or more halo or (C 1 -C 6 )alkoxy;

R 6 is H or (C 1 -C 6 )alkyl, wherein the (C 1 -C 6 )alkyl is optionally substituted with one or more halo or (C 1 -C 6 )alkoxy; and

R 7 is H or (C 1 -C 6 )alkyl, wherein the (C 1 -C 6 )alkyl is optionally substituted with one or more halo or (C 1 -C 6 )alkoxy; or R 6 and R 7 taken together form a (C 1 -C 6 )alkylene;

R a , is a 4, 5, or 6 membered saturated or partially unsaturated heterocyclic ring comprising at least one carbon atom and at least one heteroatom selected from S, or NH in the ring, which ring is optionally substituted with one or more oxo (═O);

R b , is aryl or aryl(C 1 -C 6 )alkyl, wherein the aryl or aryl(C 1 -C 6 )alkyl is optionally substituted with one or more (C 1 -C 6 )alkoxy or halo;

R c , is a C-linked amino acid, a C-linked dipeptide, —C(═O)CH 2 CH 2 COOH, —P(═O)(OH) 2 , or:

R d is H, (C 1 -C 6 )alkanoyl, or (C 1 -C 6 )alkyl, wherein the (C 1 -C 6 )alkanoyl and the (C 1 -C 6 )alkyl are each optionally substituted with one or more halo or (C 1 -C 6 )alkoxy; and R e is H, (C 1 -C 6 )alkanoyl, or (C 1 -C 6 )alkyl, wherein the (C 1 -C 6 )alkanoyl and the (C 1 -C 6 )alkyl are each optionally substituted with one or more halo or (C 1 -C 6 )alkoxy; or R d and R e taken together form a (C 1 -C 6 )alkylene; and

R f is H, (C 1 -C 6 )alkanoyl, or (C 1 -C 6 )alkyl, wherein the (C 1 -C 6 )alkanoyl and the (C 1 -C 6 )alkyl are each optionally substituted with one or more halo or (C 1 -C 6 )alkoxy;

or a salt thereof,

when R c , is

then R 4 is

with R being 4-fluorobenzyl or benzyl,

when R 4 is carboxy, then R 1 is methoxymethyl, R 2 is H, R 3 is methoxymethyl, R 5 is methoxymethyl, and R 6 and R 7 taken together form —C(CH 3 ) 2 − .

2. The compound of claim 1 , wherein R 1 is H, methoxymethyl,

3. The compound of claim 1 , wherein R 2 is H.

4. The compound of claim 1 , wherein R 3 is H or methoxymethyl.

5. The compound of claim 1 , wherein R 4 is 1,2-dihydroxyethyl, formyl, cyano, hydroxymethyl, ethynyl, carboxy, 2,2,2-trifluoro-1-hydroxyethyl, hydroximinomethyl,

6. The compound of claim 1 , wherein R 5 is H or methoxymethyl.

7. The compound of claim 1 , wherein R 6 is H.

8. The compound of claim 1 , wherein R 7 is H.

9. The compound of claim 1 , wherein R 6 and R 7 taken together form —C(CH 3 ) 2 − .

10. The compound of claim 1 , wherein the compound is not one of the compounds:

4-((3R,3aR,5R,5bR,9aR,11S,12aS,14bS)-5,12a,14b-trihydroxy-11-(((3aR,4R,6S,7S,7aR)-7-hydroxy-2,2,6-trimethyltetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-4-yl)oxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-3-yl)furan-2(5H)-one (1);

(2R,3R,4R,5S,6S)-2-(((1R,3S,5S,10R,11R,13R,14S,17R)-1,11-diacetoxy-10-(acetoxymethyl)-5,14-dihydroxy-13-methyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl)oxy)-6-methyltetrahydro-2H-pyran-3,4,5-triyl triacetate (1a); or

4-((3R,3aR,5R,5bR,9aR,11S,12aS,14bS)-5,11,12a,14b-tetrahydroxy-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-3-yl)furan-2(5H)-one (12).

11. A compound selected from the group consisting of:

4-((3R,3aR,5R,5bR,9aR,11S,12aS,14bS)-12a,14b-dihydroxy-5-(methoxymethoxy)-11-(((3aR,4R,6S,7S,7aR)-7-(methoxymethoxy)-2,2,6-trimethyltetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-4-yl)oxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-3-yl)furan-2(5H)-one (2);

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-3-(1,2-dihydroxyethyl)-5-(methoxymethoxy)-11-(((3aR,4R,6S,7S,7aR)-7-(methoxymethoxy)-2,2,6-trimethyltetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-4-yl)oxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxine-12a,14b-diol (3);

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-12a,14b-dihydroxy-5-(methoxymethoxy)-11-(((3aR,4R,6S,7S,7aR)-7-(methoxymethoxy)-2,2,6-trimethyltetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-4-yl)oxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxine-3-carbaldehyde (4);

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-3-(1-hydroxyprop-2-yn-1-yl)-5-(methoxymethoxy)-11-(((3aR,4R,6S,7S,7aR)-7-(methoxymethoxy)-2,22,6-trimethyltetrahydro-3a-[1,3]dioxolo[4,5-c]pyran-4-yl)oxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxine-12a,14b-diol (5);

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-3-((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)(hydroxy)methyl)-5-(methoxymethoxy)-11-(((3aR,4R,6S,7S,7aR)-7-(methoxymethoxy)-2,2,6-trimethyltetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-4-yl)oxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxine-12a,14b-diol (6);

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-3-((1-benzyl-1H-1,2,3-triazol-4-yl)(hydroxy)methyl)-5-(methoxymethoxy)-11-(((3aR,4R,6S,7S,7aR)-7-(methoxymethoxy)-2,2,6-trimethyltetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-4-yl)oxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxine-12a,14b-diol (7);

(1R,3S,5S,10R,11R,13R,14S,17S)-17-((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)(hydroxy)methyl)-10-(hydroxymethyl)-13-methyl-3-(((2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)hexadecahydro-1H-cyclopenta[a]phenanthrene-1,5,11,14-tetraol (8);

(1R,3S,5S,10R,11R,13R,14S,17S)-17-((1-benzyl-1H-1,2,3-triazol-4-yl)(hydroxy)methyl)-10-(hydroxymethyl)-13-methyl-3-(((2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)hexadecahydro-1H-cyclopenta[a]phenanthrene-1,5,11,14-tetraol (9);

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-3-(hydroxymethyl)-5-(methoxymethoxy)-11-(((3aR,4R,6S,7S,7aR)-7-(methoxymethoxy)-2,2,6-trimethyltetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-4-yl)oxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxine-12a,14b-diol (10);

4-((3R,3aR,5R,5bR,9aR,11S,12aS,14bS)-12a-hydroxy-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-3-yl)furan-2(5H)-one (13);

2-hydroxy-1-((3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-12a-hydroxy-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-3-yl)ethanone (14);

1-((3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-12a-hydroxy-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-3-yl)ethane-1,2-diol (15);

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-12a-hydroxy-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxine-3-carbaldehyde (16);

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-3-(1-hydroxyprop-2-yn-1-yl)-5,11,12a-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-14b-ol (17);

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-3-((1-benzyl-1H-1,2,3-triazol-4-yl)(hydroxy)methyl)-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-12a-ol (18);

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-3-((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)(hydroxy)methyl)-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-12a-ol (19);

(1R,3S,5S,10R,11R,13R,14S,17S)-17-((1-benzyl-1H-1,2,3-triazol-4-yl)(hydroxy)methyl)-10-(hydroxymethyl)-13-methylhexadecahydro-1H-cyclopenta[a]phenanthrene-1,3,5,11,14-pentaol (20);

(1R,3S,5S,10R,11R,13R,14S,17S)-17-((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)(hydroxy)methyl)-10-(hydroxymethyl)-13-methylhexadecahydro-1H-cyclopenta[a]phenanthrene-1,3,5,11,14-pentaol (21);

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-3-(hydroxymethyl)-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-12a-ol (22);

((3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-12a-hydroxy-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-3-yl)methyl4-methylbenzenesulfonate (23);

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-3-(azidomethyl)-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-12a-ol (24);

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-5,11,14b-tris(methoxymethoxy)-3-((4-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl)methyl)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-12a-ol (25);

(1R,3S,5S,10R,11R,13R,14S,17S)-10-(hydroxymethyl)-17-((4-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl)methyl)-13-methylhexadecahydro-1H-cyclopenta[a]phenanthrene-1,3,5,11,14-pentaol (26);

(3R,3aR,5R,5bR,9aR,11S,12aS,14bS)-3-ethynyl-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-12a-ol (28);

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-3-(1-benzyl-1H-1,2,3-triazol-4-yl)-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-12a-ol (29);

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-3-(1-(4-chlorobenzyl)-1H-1,2,3-triazol-4-yl)-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-12a-ol (30);

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-3-(1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-12a-ol (31);

(1R,3S,5S,10R,11R,13R,14S,17S)-17-(1-benzyl-1H-1,2,3-triazol-4-yl)-10-(hydroxymethyl)-13-methylhexadecahydro-1H-cyclopenta[a]phenanthrene-1,3,5,11,14-pentaol (32);

(1R,3S,5S,10R,11R,13R,14S,17S)-17-(1-(4-chlorobenzyl)-1H-1,2,3-triazol-4-yl)-10-(hydroxymethyl)-13-methylhexadecahydro-1H-cyclopenta[a]phenanthrene-1,3,5,11,14-pentaol (33);

(1R,3S,5S,10R,11R,13R,14S,17S)-17-(1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)-10-(hydroxymethyl)-13-methylhexadecahydro-1H-cyclopenta[a]phenanthrene-1,3,5,11,14-pentaol (34);

12a-hydroxy-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxine-3-carbaldehyde oxime (35);

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-12a-hydroxy-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxine-3-carbonitrile (36);

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethyl-3-(2,2,2-trifluoro-1-hydroxyethyl)hexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-12a-ol (37); and

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-12a-hydroxy-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxine-3-carboxylic acid (38).

12. The compound of claim 11 , wherein the chemical structure is one of:

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-3-(hydroxymethyl)-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-12a-ol (22); or

(1R,3S,5S,10R,11R,13R,14S,17S)-17-(1-benzyl-1H-1,2,3-triazol-4-yl)-10-(hydroxymethyl)-13-methylhexadecahydro-1H-cyclopenta[a]phenanthrene-1,3,5,11,14-pentaol (32).

13. The compound of claim 11 , wherein the chemical structure is one of:

2-hydroxy-1-((3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-12a-hydroxy-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-3-yl)ethanone (14);

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-12a-hydroxy-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxine-3-carbaldehyde (16);

((3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-12a-hydroxy-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-3-yl)methyl4-methylbenzenesulfonate (23); or

(3S,3aR,5R,5bR,9aR,11S,12aS,14bS)-3-(azidomethyl)-5,11,14b-tris(methoxymethoxy)-3a,8,8-trimethylhexadecahydro-1H-cyclopenta[7,8]phenanthro[4,4a-d][1,3]dioxin-12a-ol (24).

14. The compound of claim 1 , wherein

R 1 is H, methoxymethyl,

R 2 is H;

R 3 is H or methoxymethyl;

R 5 is H or methoxymethyl;

R 6 and R 7 are each H or R 6 and R 7 taken together form —C(CH 3 ) 2 − ; and

R 4 is 1,2-dihydroxyethyl, formyl, cyano, hydroxymethyl, ethynyl, carboxy, 2,2,2-trifluoro-1-hydroxyethyl, hydroximinomethyl,

15. The compound of claim 14

R 1 is methoxymethyl,

R 2 is H;

R 3 is H or methoxymethyl;

R 5 is H or methoxymethyl;

R 6 and R 7 are each H or R 6 and R 7 taken together form —C(CH 3 ) 2 − ; and

R 4 is 1,2-dihydroxyethyl, formyl, cyano, hydroxymethyl, ethynyl, 2,2,2-trifluoro-1-hydroxyethyl, hydroximinomethyl,

16. The compound of claim 14

R 1 is H, methoxymethyl,

R 2 is H;

R 3 is H or methoxymethyl;

R 5 is H or methoxymethyl;

R 6 and R 7 are each H or R 6 and R 7 taken together form —C(CH 3 ) 2 —; and

R 4 is 1,2-dihydroxyethyl, formyl, cyano, hydroxymethyl, ethynyl, 2,2,2-trifluoro-1-hydroxyethyl, hydroximinomethyl,

17. A compound of formula I:

wherein:

R 1 is H, (C 1 -C 6 )alkyl, or R c , wherein the (C 1 -C 6 )alkyl is optionally substituted with one or more halo or (C 1 -C 6 )alkoxy;

R 2 is H or (C 1 -C 6 )alkyl, wherein the (C 1 -C 6 )alkyl is optionally substituted with one or more halo or (C 1 -C 6 )alkoxy;

R 3 is H or (C 1 -C 6 )alkyl, wherein the (C 1 -C 6 )alkyl is optionally substituted with one or more halo or (C 1 -C 6 )alkoxy;

R 5 is H or (C 1 -C 6 )alkyl, wherein the (C 1 -C 6 )alkyl is optionally substituted with one or more halo or (C 1 -C 6 )alkoxy;

R 6 is H or (C 1 -C 6 )alkyl, wherein the (C 1 -C 6 )alkyl is optionally substituted with one or more halo or (C 1 -C 6 )alkoxy; and

R 7 is H or (C 1 -C 6 )alkyl, wherein the (C 1 -C 6 )alkyl is optionally substituted with one or more halo or (C 1 -C 6 )alkoxy; or R 6 and R 7 taken together form a (C 1 -C 6 )alkylene;

R a , is a 4, 5, or 6 membered saturated or partially unsaturated heterocyclic ring comprising at least one carbon atom and at least one heteroatom selected from O, S, or NH in the ring, which ring is optionally substituted with one or more oxo (═O);

R b , is aryl or aryl(C 1 -C 6 )alkyl, wherein the aryl or aryl(C 1 -C 6 )alkyl is optionally substituted with one or more (C 1 -C 6 )alkoxy or halo;

R c , is a C-linked amino acid, a C-linked dipeptide, —C(═O)CH 2 CH 2 COOH, —P(═O)(OH) 2 , or:

R f is H, (C 1 -C 6 )alkanoyl, or (C 1 -C 6 )alkyl, wherein the (C 1 -C 6 )alkanoyl and the (C 1 -C 6 )alkyl are each optionally substituted with one or more halo or (C 1 -C 6 )alkoxy;

or a salt thereof,

when R c , is

then R 4 is

with R being 4-fluorobenzyl or benzyl,

when R1 is H, then the compound is one of:

(1R,3S,5S,10R,11R,13R,14S,17S)-17-((1-benzyl-1H-1,2,3-triazol-4-yl)(hydroxy)methyl)-10-(hydroxymethyl)-13-methylhexadecahydro-1H-cyclopenta[a]phenanthrene-1,3,5,11,14-pentaol (20);

(1R,3S,5S,10R,11R,13R,14S,17S)-17-((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)(hydroxy)methyl)-10-(hydroxymethyl)-13-methylhexadecahydro-1H-cyclopenta[a]phenanthrene-1,3,5,11,14-pentaol (21);

(1R,3S,5S,10R,11R,13R,14S,17S)-10-(hydroxymethyl)-17-((4-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl)methyl)-13-methylhexadecahydro-1H-cyclopenta[a]phenanthrene-1,3,5,11,14-pentaol (26);

(1R,3S,5S,10R,11R,13R,14S,17S)-17-(1-benzyl-1H-1,2,3-triazol-4-yl)-10-(hydroxymethyl)-13-methylhexadecahydro-1H-cyclopenta[a]phenanthrene-1,3,5,11,14-pentaol (32);

(1R,3S,5S,10R,11R,13R,14S,17S)-17-(1-(4-chlorobenzyl)-1H-1,2,3-triazol-4-yl)-10-(hydroxymethyl)-13-methylhexadecahydro-1H-cyclopenta[a]phenanthrene-1,3,5,11,14-pentaol (33); or

(1R,3S,5S,10R,11R,13R,14S,17S)-17-(1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)-10-(hydroxymethyl)-13-methylhexadecahydro-1H-cyclopenta[a]phenanthrene-1,3,5,11,14-pentaol (34).

18. The compound of claim 17 , wherein

R 1 is methoxymethyl,

R 2 is H;

R 3 is H or methoxymethyl;

R 5 is H or methoxymethyl;

R 6 and R 7 are each H or R 6 and R 7 taken together form —C(CH 3 ) 2 − ; and

R 4 is 1,2-dihydroxyethyl, formyl, cyano, hydroxymethyl, ethynyl, carboxy, 2,2,2-trifluoro-1-hydroxyethyl, hydroximinomethyl,

19. A pharmaceutical composition comprising:

a compound of claim 1 , or a pharmaceutically acceptable salt thereof; and

a pharmaceutically acceptable diluent or carrier.

20. A method for decreasing sperm motility in a mammal comprising:

administering the compound of claim 1 , or a pharmaceutically acceptable salt thereof to the mammal.

Assignments (3)

CONFIRMATORY LICENSE Recorded Nov 20, 2013

From: REGENTS OF THE UNIVERSITY OF MINNESOTA

To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT

Reel/Frame 031690/0303 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 1, 2013

From: BLANCO, GUSTAVO

To: THE UNIVERSITY OF KANSAS

Reel/Frame 030723/0406 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 1, 2013

From: GEORG, GUNDA I.; SYEDA, SHAMEEM SULTANA

To: REGENTS OF THE UNIVERSITY OF MINNESOTA

Reel/Frame 030723/0437 →

Continuity (2)

Provisional Application 61667240 · Jul 2, 2012

Related Publication 20140005132A1 · Jan 2, 2014