Benzamide compounds and related methods of use

Patent metadata

Field	Value
Publication number	US-9371277-B2
Application number	US-201314139763-A
Country	US
Kind code	B2
Filing date	Dec 23, 2013
Priority date	Dec 21, 2012
Publication date	Jun 21, 2016
Grant date	Jun 21, 2016

Abstract

Benzamide compounds and derivatives thereof, as can be used for selective inhibition of the SIRT2 enzyme and/or therapeutic use in the treatment of Huntington's disease.

First claim

We claim:

1. A compound selected from compounds of a formula

wherein each of R 1 and R 2 is independently selected from phenyl, benzyl, heteroaryl, and heteroarylalkyl moieties; each of E 1 and E 2 is independently selected from CH and N, provided at least one of E 1 and E 2 is CH; A is a divalent moiety selected from carbonyl, amino, carboxamido (—C(O)NH—), imidocarbyl (—C(NH)—) and a tautomer thereof (—N ═C(NH 2 )—) with X; X is a divalent moiety selected from methylene, carbonyl, amino, and aza-substituted ethylene (—NHCH 2 —) moieties; Y is a divalent moiety selected from oxy, amino, alkylene, and aza-substituted alkylene moieties; and Z is a divalent moiety selected from sulfonyl, sulfinyl, thio, oxy, amino, and methylene moieties, providing where A is carbonyl, Z is sulfonyl and R 1 and R 2 are selected from phenyl and substituted phenyl, X is not amino or methylamino and Y is not amino, alkylamino, allylamino or benzylamino, and wherein each of R 1 , R 2 , A, X, Y and Z is optionally substituted with 1-10 substituents independently selected from halo, cyano, nitro, hydroxy, amino, alkyl, cycloalkyl, cycloheteroalkyl, aryl, arylalkyl, alkoxy, alkenyl, haloalkyl, aminoalkyl, hydroxyalkyl, alkylene, alkylsulfonyl, haloalkylsulfonyl, haloalkylsulfinyl, alkylamido, alkylsulfonamido, alkylthio, alkylcarbonyl, alkoxycarbonyl and combinations of such substituents; R 3 is selected from said substituents and combinations thereof; and n is an integer from 0-4, and salts of said compounds.

2. The compound of claim 1 where A is carbonyl and E 2 is CH, said compound of a formula

3. The compound of claim 2 wherein X is selected from amino and alkylamino moieties, and Z is methylene, said compound of a formula

4. The compound of claim 3 wherein Y is selected from oxy, alkylene, alkyl-substituted alkylene, amino and substituted amino moieties.

5. The compound of claim 4 wherein R 2 is a substituted benzyl moiety, said substituents selected from 1-3 halo and cyano substituents and combinations thereof.

6. The compound of claim 4 wherein Y is a substituted amino moiety and R 2 is selected from phenyl, substituted phenyl, benzyl, substituted benzyl, heteroaryl, substituted heteroaryl, heteroarylalkyl and substituted heteroarylalkyl moieties.

7. The compound of claim 6 wherein said amino substituent is selected from alkyl and cycloalkyl moieties.

8. The compound of claim 7 wherein said amino substituent is selected from methyl, ethyl, isopropyl and cyclopropyl moieties.

Assignees

• Univ Northwestern
• Gen Hospital Corp

Inventors

• Silverman Richard B
• Wang Hua
• Khanfar Mohammad
• Kazantsev Aleksey G

Classifications

• C07D213/82

  in position 3 · CPC title

• C07D213/81

  Amides; Imides · CPC title

• C07C311/47

  Y being a hetero atom · CPC title

• C07C323/62

  having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton · CPC title

• C07D305/06

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring atoms · CPC title