BH4 antagonists and methods related thereto

Patent metadata

Field	Value
Publication number	US-9980936-B2
Application number	US-201515309382-A
Country	US
Kind code	B2
Filing date	May 5, 2015
Priority date	May 5, 2014
Publication date	May 29, 2018
Grant date	May 29, 2018

Abstract

The disclosure relates to BH4 inhibitors and therapeutic uses relates thereto. In certain embodiments, the disclosure relates to methods of treating or preventing cancer, such as lung cancer, comprising administering therapeutically effective amount of a pharmaceutical composition comprising a compound disclosed herein or pharmaceutically acceptable salt to a subject in need thereof.

First claim

The invention claimed is:

1. A method of treating lung cancer comprising administering an effective amount of an mTOR inhibitor in combination with 1-((3-(diethylamino)-2-hydroxypropyl)amino)-4-((oxiran-2-ylmethyl)amino)anthracene-9,10-dione or salt thereof to a subject diagnosed with lung cancer.

2. The method of claim 1 , wherein the mTOR inhibitor is sirolimus, everolimus, ridaforolimus, or temsirolimus.

3. The method of claim 1 , wherein the mTOR inhibitor has the following formula,

or salts thereof wherein,
the dotted lines each individually represent a single or double bond;
Y is the bridging group ═CH—CH═CH—CH═CH—;
X is —(CHR 8 ) n —;
n is 1 or 2
R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , and R 14 are each the same or different, individually and independently at each occurrence, hydrogen, alkyl, alkenyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, alkanoyl, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl) 2 amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, phosphinyl, carbocyclyl, aryl, or heterocyclyl, wherein each R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , and R 14 are optionally substituted with one or more, the same or different, R 20 ;
R 20 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, alkanoyl, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl) 2 amino, alkylsulfinyl, alkyl sulfonyl, arylsulfonyl, phosphinyl, carbocyclyl, aryl, or heterocyclyl, wherein R 20 is optionally substituted with one or more, the same or different, R 21 ; and
R 21 is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethyl sulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

Assignees

• Univ Emory
• Univ Texas

Inventors

• Deng Xingming
• Zhou Jia
• Ding Chunyong

Classifications

• C07D303/04

  containing only hydrogen and carbon atoms in addition to the ring oxygen atoms · CPC title

• C07C15/28

  Anthracenes · CPC title

• C07C2603/24

  Anthracenes; Hydrogenated anthracenes · CPC title

• A61K31/122

  having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin · CPC title

• C07C233/78

  with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom · CPC title