Certain chemical entities, compositions, and methods

Patent metadata

Field	Value
Publication number	US-2016039865-A1
Application number	US-201314397845-A
Country	US
Kind code	A1
Filing date	Apr 29, 2013
Priority date	Apr 29, 2012
Publication date	Feb 11, 2016
Grant date	—

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 a pharmaceutically acceptable salts 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 chosen from 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 chosen from 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 chosen from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, and optionally substituted alkynyl;
R 13 is chosen from hydrogen, optionally substituted alkyl, and formyl;
R 14 and R 15 are joined together with any intervening atoms to form an optionally substituted 4- to 8-membered heterocycloalkyl or optionally substituted 5- to 8-membered heteroaryl ring;
W 1 is chosen from the following moieties:

wherein Y is chosen from O and NR 21 ;
R 20 is chosen from cyano, halo, hydroxy, azido, nitro, carboxy, sulfinyl, sulfanyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocycloalkyloxy, optionally substituted alkoxycarbonyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted aryloxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amino, optionally substituted acyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted aminosulfonyl, optionally substituted carbaminodoyl, and optionally substituted alkynyl;
R 21 is chosen from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
W 2 is chosen from 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 is independently selected from 0 and 1; and
the dotted line 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 chosen from 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 chosen from hydrogen, hydroxy, and optionally substituted alkyl.

4 . (canceled)

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

6 . 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.

7 . (canceled)

8 . The compound of claim 1 , wherein R 7 is chosen from hydrogen, hydroxy, optionally substituted alkoxy, optionally substituted aminocarbonyloxy, optionally substituted acyloxy, optionally substituted alkoxycarbonyloxy, and optionally substituted amino.

9 . (canceled)

10 . The compound of claim 1 , wherein R 7 is chosen from hydrogen and —OCOCH 3 .

11 . The compound of claim 1 , wherein R 8 and W 2 are independently chosen from hydrogen and optionally substituted alkyl.

12 . (canceled)

13 . The compound of claim 1 , wherein R 13 is chosen from hydrogen, methyl, and hydroxymethyl.

14 . The compound of claim 1 , wherein Y is chosen from O, NH and NCH 3 .

15 . (canceled)

16 . The compound of claim 1 , wherein R 20 is chosen from cyano, halo, hydroxy, carboxy, sufonyl, optionally substituted alkoxy, optionally substituted alkoxycarbonyl, optionally substituted alkyl, optionally substituted amino, optionally substituted acyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, and optionally substituted aminosulfonyl.

17 . (canceled)

18 . The compound of claim 1 , wherein each dotted line represents a single bond.

19 . The compound of claim 1 , wherein each dotted line represents a double bond.

20 . The compound of claim 1 , wherein the compound of Formula I is chosen from compounds of

21 .- 40 . (canceled)

41 . The compound of claim 1 , wherein R 14 and R 15 form an optionally substituted 5- or 6-membered heterocycloalkyl or heteroaryl ring.

42 . The compound of claim 41 , wherein the ring is an optionally substituted morpholino, piperazino, piperidino, pyrrolidino, imidazolyl, or pyrazolyl group.

43 .- 51 . (canceled)

52 . The compound of claim 1 , wherein R 14 and R 15 are joined together with any intervening atoms to form an optionally substituted 4- to 8-membered heterocycloalkyl ring.

53 . A compound chosen from:
2-aminoethyl((3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl)carbamate, 2-hydroxyethyl((3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl)carbamate, 2-(pyrrolidin-1-yl)ethyl((3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl)carbamate, 2-((R)-3-hydroxypyrrolidin-1-yl)ethyl((3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl)carbamate, 2-morpholinoethyl((3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl)carbamate, 2-(3-oxopiperazin-1-yl)ethyl((3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl)carbamate, 1-(2-aminoethyl)-3-43S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-

Assignees

• Neupharma Inc

Inventors

• Qian Xiangping

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07J41/0011 Primary

  Unsubstituted amino radicals · CPC title

• C07J43/003

  not condensed · CPC title

• C07J19/00 Primary

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

• C07J41/0005

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