Certain steroids and methods for using the same in the treatment of cancer

Patent metadata

Field	Value
Publication number	US-10487108-B2
Application number	US-201715586710-A
Country	US
Kind code	B2
Filing date	May 4, 2017
Priority date	Apr 29, 2012
Publication date	Nov 26, 2019
Grant date	Nov 26, 2019

Abstract

Chemical entities that are novel compounds, pharmaceutical compositions and methods of treatment of cancer are described.

First claim

What is claimed is:

1. A compound of Formula I:

or pharmaceutically acceptable salt thereof, wherein:
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 9 , R 10 , R 11 and R 12 are independently selected from the group consisting of hydrogen, hydroxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocycloalkyloxy, optionally substituted aminocarbonyloxy, optionally substituted acyloxy, optionally substituted alkoxycarbonyloxy, and optionally substituted amino; or
R 1 and R 2 , or R 5 and R 6 , or R 7 and R 8 , or R 9 and R 10 , or R 11 and R 12 mutually independently, together in each case denote an oxo group (═O); or
R 4 and R 5 may optionally be joined together with any intervening atoms to form an optionally substituted heterocycloalkyl ring;
R 7 is selected from the group consisting of hydrogen, hydroxy, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocycloalkyloxy, optionally substituted aminocarbonyloxy, optionally substituted acyloxy, optionally substituted alkoxycarbonyloxy, and optionally substituted amino;
R 8 is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, and optionally substituted alkynyl;
R 13 is selected from the group consisting of hydrogen, optionally substituted alkyl, and formyl;
R 14 is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
R 15 is selected from the group consisting of —CONR 17 R 18 , —C(NR 19 )NR 17 R 18 , —C(NCN)NR 17 R 18 , —SO 2 R 16 , and —SO 2 NR 17 R 18 ;
R 16 is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
R 17 is selected from the group consisting of optionally alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl and optionally substituated heteroaryl;
R 18 and R 19 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
W 1 is:

Y is selected from the group consisting of O and NR 21 ;
R 20 is selected from the group consisting of cyano, halo, hydroxy, azido, nitro, carboxy, sulfinyl, sulfanyl, sulfonyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocycloalkyloxy, optionally substituted alkoxycarbonyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amino, optionally substituted acyl, optionally substituted aminocarbonyl, optionally substituted aminosulfonyl, optionally substituted carbaminodoyl, and optionally substituted alkynyl;
R 21 is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
W 2 is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, and optionally substituted alkynyl;
m is selected from 0, 1, 2, and 3;
n, p, and q are independently selected from 0 and 1; and
each independently represents a single bond or a double bond.

2. The compound of claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 9 , R 10 , R 11 and R 12 are independently selected from the group consisting of hydrogen, hydroxy, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aminocarbonyloxy, optionally substituted acyloxy, optionally substituted alkoxycarbonyloxy, and optionally substituted amino.

3. The compound of claim 2 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 9 , R 10 , R 11 and R 12 are independently selected from the group consisting of hydrogen, hydroxy, and optionally substituted alkyl.

4. The compound of claim 1 , wherein R 4 is hydroxy.

5. The compound of claim 1 , wherein R 4 and R 5 are joined together with any intervening atoms to form an optionally substituted 3- to 8-membered heterocycloalkyl ring.

6. The compound of claim 1 , wherein R 7 is selected from the group consisting of hydrogen, hydroxy, optionally substituted alkoxy, optionally substituted aminocarbonyloxy, optionally substituted acyloxy, optionally substituted alkoxycarbonyloxy, and optionally substituted amino.

7. The compound of claim 6 , wherein R 7 is selected from the group consisting of hydrogen and —OCOCH 3 .

8. The compound of claim 1 , wherein R 8 and W 2 are independently selected from the group consisting of hydrogen and optionally substituted alkyl.

9. The compound of claim 1 , wherein R 13 is selected from the group consisting of hydrogen, methyl, and hydroxymethyl.

10. The compound of claim 1 , wherein Y is selected from the group consisting of O, NH and NCH 3 .

11. The compound of claim 1 , wherein R 20 is selected from the group consisting of cyano, halo, hydroxy, carboxy, sufonyl, optionally substituted alkoxy, optionally substituted alkoxycarbonyl, optionally substituted alkyl, optionally substituted amino, optionally substituted acyl, optionally substituted aminocarbonyl, and optionally substituted aminosulfonyl.

12. The compound of claim 1 , wherein each represents a single bond.

13. The compound of claim 1 , wherein each represents a double bond.

14. The compound of claim 1 , wherein the compound of Formula I is selected from the group consisting of compounds of Formula Ia:

15. The compound of claim 1 , wherein R 14 is selected from the group consisting of optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl.

16. The compound of claim 15 , wherein R 14 is selected from the group consisting of optionally substituted lower alkyl.

17. The compound of claim 1 , wherein R 15 is selected from the group consisting of —CONR 17 R 18 and —SO 2 NR 17 R 18 .

18. The compound of claim 1 , wherein R 14 is optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted heterocycloalkyl.

19. The compound of claim 1 , wherein R 16 is selec

Assignees

• Neupharma Inc

Inventors

• Qian Xiangping

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07J19/00

  Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 by a lactone ring · CPC title

• C07J43/003

  not condensed · CPC title

• C07J41/0011 Primary

  Unsubstituted amino radicals · CPC title

• C07J41/0005

  the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton · CPC title