Granted Patent B2

US 9,006,277 · App. 14/473,366 · Granted Apr 14, 2015

Inventors: Lijun Sun (Harvard, MA); Weiwen Ying (Lexington, MA); Junghyun Chae (Youngdengpo-Yu, KR); Teresa Kowalczyk-Przewloka (Tewksbury, MA); Shijie Zhang (Nashua, NH); Dinesh U. Chimmanamada (Arlington, MA); Kevin Paul Foley (Waltham, MA); Zhenjian Du (Northborough, MA); Hao Li (Brookline, MA); David James (Boston, MA); Howard P. Ng (Harrison, NJ); Zachary Demko (Los Altos Hills, CA); Dan Zhou (Lexington, MA); Shuzhen Qin (West Roxbury, MA)

Assignee: Synta Pharmaceuticals Corp.

C07D413/14C07D401/14A61K31/4439C07D403/04A61K31/4196A61K31/422C07D405/14A61K31/475C07D249/12C07D403/12A61K31/496A61K31/5377

Abstract

Claims (16)

1. A compound represented by the following structural formula:

or a tautomer, pharmaceutically acceptable salt, solvate, clathrate or a prodrug thereof, wherein:

X′ is —O—O— or —S—S—;

R′ 2 and R′ 3 are, independently, —OH, —SH, or —NHR 7 ;

R′ 5 is an optionally substituted heteroaryl or an optionally substituted aryl;

R′ 6 is —H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, cyano, halo, nitro, an optionally substituted cycloalkyl, haloalkyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, an optionally substituted heteroaralkyl, —OR 7 , —SR 7 , —NR 10 R 11 , —OC(O)NR 10 R 11 , —SC(O)NR 10 R 11 , —NR 7 C(O)NR 10 R 11 , —OC(O)R 7 , —SC(O)R 7 , —NR 7 C(O)R 7 , —OC(O)OR 7 , —SC(O)OR 7 , —NR 7 C(O)OR 7 , —OCH 2 C(O) R 7 , —SCH 2 C(O) R 7 , —NR 7 CH 2 C(O) R 7 , —OCH 2 C(O)OR 7 , —SCH 2 C(O)OR 7 , —NR 7 CH 2 C(O)OR 7 , —OcH 2 C(O)NR 10 R 11 , —SCH 2 C(O)NR 10 R 11 , —NR 7 CH 2 C(O)NR 10 R 11 , —OS(O) p R 7 , —SS(O) p R 7 , —NR 7 S(O) p R 7 , —OS(O) p NR 10 R 11 , —SS(O) p NR 10 R 11 , —NR 7 S(O) p NR 10 R 11 , —OS(O) p OR 7 , —SS(O) p OR 7 , —NR 7 S(O) p OR 7 , —OC(S)R 7 , —SC(S)R 7 , —NR 7 C(S)R 7 , —OC(S)OR 7 , —SC(S)OR 7 , —NR 7 C(S)OR 7 , —OC(S)NR 10 R 11 , —SC(S)NR 10 R 11 , —NR 7 C(S)NR 10 R 11 , —OC(NR 8 )R 7 , —SC(NR 8 )R 7 , —NR 7 C(NR 8 )R 7 , —OC(NR 8 )OR 7 , —SC(NR 8 )OR 7 , —NR 7 C(NR 8 )OR 7 , —OC(NR 8 )NR 10 R 11 , —SC(NR 8 )NR 10 R 11 , —NR 7 C(NR 8 )NR 10 R 11 , —C(O)R 7 , —C(O)OR 7 , —C(O)NR 10 R 11 , —C(O)SR 7 , —C(S)R 7 , —C(S)OR 7 , —C(S)NR 10 R 11 , —C(S)SR 7 , —C(NR 8 )OR 7 , —C(NR 8 )R 7 , —C(NR 8 )NR 10 R 11 , —C(NR 8 )SR 7 , —S(O) p OR 7 , —S(O) p NR 10 R 11 , or —S(O) p R 7 ;

R 7 and R 8 , for each occurrence, is independently, —H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;

R 10 and R 11 , for each occurrence, is independently —H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; or R 10 and R 11 , taken together with the nitrogen to which they are attached, form an optionally substituted heterocyclyl or an optionally substituted heteroaryl;

p, for each occurrence, is independently 1 or 2.

2. The compound of claim 1 , wherein R′ 5 is an optionally substituted phenyl.

3. The compound of claim 1 , wherein R′ 2 and R′ 3 are each —OH.

4. The compound of claim 1 , wherein X′ is —S—S—.

5. The compound of claim 1 , wherein R′ 6 is a C1-C6 alkyl, a C1-C6 haloalkyl, a C1-C6 alkoxy, a C1-C6 haloalkoxy, a C1-C6 alkyl sulfanyl or a C3-C6 cycloalkyl.

6. The compound of claim 1 , wherein the compound is 6,6′-(5,5′-disulfanediylbis(4-(4-(dimethylamino)phenyl)-4H-1,2,4-triazole-5,3-diyl))bis(4-isopropylbenzene-1,3-diol) or a tautomer, pharmaceutically acceptable salt, solvate, clathrate, or a prodrug thereof.

7. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a compound of claim 1 .

8. The pharmaceutical composition of claim 7 , further comprising one or more additional therapeutic agents.

Assignments (1)

Continuity (9)