Certain chemical entities, compositions, and methods

Patent metadata

Field	Value
Publication number	US-2020354398-A1
Application number	US-202016939893-A
Country	US
Kind code	A1
Filing date	Jul 27, 2020
Priority date	Feb 2, 2011
Publication date	Nov 12, 2020
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 . At least one chemical entity chosen from compounds of Formula I

and pharmaceutically acceptable salts thereof, wherein
R 1 , R 2 , R 3 , 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);
R 4 is hydroxy, 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;
Z is chosen from OR 14 and NR 15 R 16 ; wherein
R 14 is chosen from optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
R 15 is chosen from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
R 16 is chosen from optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
or R 15 and R 16 may optionally be joined together with any intervening atoms to form an optionally substituted heterocycloalkyl ring;
W 1 is chosen from the following moieties:

wherein Y is chosen from O and NR 18 ;
R 17 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 al—Enocarbonyl, optionally substituted aminosulfonyl, optionally substituted carbaminodoyl, and optionally substituted alkynyl;
R 18 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 is selected from 0 and 1, and
the dotted line represents a single bond or a double bond;

provided that when R 4 is OH, R 13 is methyl, W 1 is

(2-oxo-2H-pyran-5-yl), and R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and W 2 are hydrogen then R 12 is not hydrogen.

2 . At least one chemical entity of claim 1 wherein R 1 , R 2 , R 3 , 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 . At least one chemical entity of claim 2 wherein R 1 , R 2 , R 3 , R 5 , R 6 , R 9 , R 10 , R 11 and R 12 are independently chosen from hydrogen, hydroxy, and optionally substituted alkyl.

4 . At least one chemical entity of claim 3 wherein R 1 , R 2 , R 3 , R 5 , R 6 , R 9 , R 10 , R 11 and R 12 are independently chosen from hydrogen, hydroxy, and methyl.

5 . At least one chemical entity of any one of claims 1 to 4 wherein R 4 is hydroxy.

6 . At least one chemical entity of any one of claims 1 to 4 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 . At least one chemical entity of claim 6 wherein R 4 and R 5 are joined together with any intervening atoms to form an oxirane ring.

8 . At least one chemical entity of any one of claims 1 to 7 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 . At least one chemical entity of claim 8 wherein R 7 is chosen from hydrogen and optionally substituted acyloxy.

10 . At least one chemical entity of claim 9 wherein R 7 is chosen from hydrogen and —OCOCH 3 .

11 . At least one chemical entity of any one of claims 1 to 10 wherein R 8 and W 2 are independently chosen from hydrogen and optionally substituted alkyl.

12 . At least one chemical entity of any one of claims 1 to 11 wherein R 13 is chosen from hydrogen and optionally substituted alkyl.

13 . At least one chemical entity of claim 12 wherein R 13 is chosen from hydrogen, methyl, and hydroxymethyl.

14 . At least one chemical entity of any one of claims 1 to 13 wherein Y is chosen from O, NH and NCH 3 .

15 . At least one chemical entity of claim 14 wherein Y is O.

16 . At least one chemical entity of any one of claims 1 to 15 wherein R 17 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 . At least one chemical entity of any one of claims 1 to 16 wherein m is 0.

18 . At least one chemical entity of any one of claims 1 to 17 wherein the dotted line represents a single bond.

19 . At least one chemical entity of any one of claims 1 to 17 wherein the dotted line represents a double bond.

20 . At least one chemical entity of claim 1 wherein the compound of Formula I is chosen from compounds of Formula Ia.

21 . At least one chemical entity of claim 1

Assignees

• Neupharma Inc

Inventors

• Qian Xiangping

Classifications

• C07J19/00

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

• C07J41/0055

  the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives · CPC title

• C07J71/0021

  at position 14(15) · CPC title

• C07J43/003 Primary

  not condensed · CPC title

• A61P35/00

  Antineoplastic agents · CPC title