Dithio ETP derivatives

Patent metadata

Field	Value
Publication number	US-10822353-B2
Application number	US-201716333577-A
Country	US
Kind code	B2
Filing date	Sep 15, 2017
Priority date	Sep 15, 2016
Publication date	Nov 3, 2020
Grant date	Nov 3, 2020

Abstract

Disclosed herein, inter alia, are compositions and methods of using the same for the treatment of cancer.

First claim

What is claimed is:

1. A compound having the formula:

or a pharmaceutically acceptable salt thereof,
wherein:
R 1 is hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 1A , —NR 1B R 1C , —C(O)OR 1A , —C(O)NR 1B R 1C , —NO 2 , —SR 1D , —S(O) n1 R 1B , —SO v1 NR 1B R 1C , —NHNR 1B R 1C , —ONR 1B R 1C , —NHC(O)NHNR 1B R 1C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 2 is hydrogen, —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —COOR 2A , —CONR 2B R 2C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 3 is hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 3A , —NR 3B R 3C , —COOR 3A , —CONR 3B R 3C , —NO 2 , —SR 3D , —SO n3 R 3B , —SO v3 NR 3B R 3C , —NHNR 3B R 3C , —ONR 3B R 3C , —NHC(O)NHNR 3B R 3C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 4 is —C(O)-L 1 -R 18 or —C(S)-L 1 -R 18 ;
R 5 is —C(O)-L 2 -R 19 or —C(S)-L 2 -R 19 ; or
R 4 and R 5 may optionally be joined to form

L 1 is a bond, —O—, —NH—, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene;
L 2 is a bond, —O—, —NH—, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene;
R 18 and R 19 are independently halogen, substituted or unsubstituted C 1 -C 3 alkyl, substituted or unsubstituted aryl;
R 25 is hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 25A , —NR 25B R 25C , —C(O)OR 25A , —C(O)NR 25B R 25C , —NO 2 , —SR 25D , —S(O) n25 R 25B , —SO v25 NR 25B R 25C , —NHNR 25B R 25C , ONR 25B R 25C , —NHC(O)NHNR 25B R 25C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 1A , R 1B , R 1C , R 1D , R 2A , R 2B , R 2C , R 3A , R 3B , R 3C , R 3D , R 25A , R 25B , R 25C , and R 25D are independently hydrogen, halogen, —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)—OH, —NHOH, —OCF 3 , —OCCl 3 , —OCBr 3 , —OCI 3 , —OCHF 2 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and R 1B and R 1C , R 2B and R 2C , R 3B and R 3C , and R 25B and R 25C substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
z3 is an integer from 0 to 5;
n1, n3, and n25 are independently an integer from 0 to 4; and
v1, v3, and v25 are independently 1 or 2.

2. The compound of claim 1 , wherein the compound has the formula:

or a pharmaceutically acceptable salt thereof,
wherein:
X 1 is N or CR 10 ;
X 2 is N or CR 11 ;
X 3 is N or CR 12 ;
R 6 is hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 6A , —NR 6B R 6C , —COOR 6A , —CONR 6B R 6C , —NO 2 , —SR 6D , —SO n6 R 6B , —SO v6 NR 6B R 6C , —NHNR 6B R 6C , —ONR 6B R 6C , —NHC(O)NHNR 6B R 6C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 7 is hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 7A , —NR 7B R 7C , —COOR 7A , —CONR 7B R 7C , —NO 2 , —SR 7D , —SO n7 R 7B , —SO v7 NR 7B R 7C , —NHNR 7B R 7C , —ONR 7B R 7C , —NHC(O)NHNR 7B R 7C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 10 is hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 10A , —NR 10B R 10C , —COOR 10A , —CONR 10B R 10C , —NO 2 , —SR 10D , —SO n10 R 10B , —SO v10 NR 10B R 10C , —NHNR 10B R 10C , —ONR 10B R 10C , —NHC(O)NHNR 10B R 10C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 11 is hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 11A , —NR 11B R 11C , —COOR 11A , —CONR 11B R 11C , —NO 2 , —SR 11D , —SO n11 R 11B , —SO v11 NR 11B R 11C , —NHNR 11B R 11C , —ONR 11B R 11C , —NHC(O)NHNR 11B R 11C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 10 and R 11 may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl;
R 12 is hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 12A , —NR 12B R 12C , —COOR 12A , —CONR 12B R 12C , —NO 2 , —SR 12D , —SO n12 R 12B , —SO v12 NR 12B R 12C , —NHNR 12B R 12C , —ONR 12B R 12C , —NHC(O)NHNR 12B R 12C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 11 and R 12 may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl;
R 6A , R 6B , R 6C , R 6D , R 7A , R 7B , R 7C , R 7D , R 10A , R 10B , R 10C , R 10D , R 11A , R 11B , R 11C , R 11D , R 12A , R 12B , R 12C , and R 12D are independently hydrogen, halogen, —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)—OH, —NHOH, —OCF 3 , —OCCl 3 , —OCBr 3 , —OCI 3 , —OCHF 2 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and R 6B and R 6C , R 7B and R 7C , R 10B and R 10C , R 11B and R 11C , and R 12B and R 12C , substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
n6, n7, n10, n11 and n12 are independ

Assignees

• Hope City
• Univ California

Inventors

• Nam Sangkil
• Horne David
• Overman Larry Eugene
• Loertscher Brad

Classifications

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title

• C07D513/18 Primary

  Bridged systems · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title