Compositions and methods of use of electron transport system inhibitors
View Patent ↗The invention provides compounds of the formula: or a pharmaceutically acceptable salt thereof, where m, n, R 1 , R 2 , R 3 R 4 , R 5 , R 6 , R 7 are those defined herein. The invention also provides pharmaceutical compositions comprising a compound of the invention, methods for using compounds and/or pharmaceutical compositions of the invention, and methods for synthesizing compounds of the invention.
1. A compound of the Formula:
or a pharmaceutically acceptable salt thereof,
wherein:
m is an integer from 0 to 4;
n is an integer from 0 to 5;
each of R 1 and R 2 is independently bromine, chlorine, haloalkyl, or —OR 8 ;
each of R 3 and R 4 is independently hydrogen or —OR 8 ;
or R 3 and R 4 together form ═X, wherein X is O, S, or NR 9 ;
R 5 is a linker having from 8 to 12 atoms, each of which is independently selected from the group consisting of C, N, O, S, provided no two heteroatoms are adjacent to one another, forming a substituted or unsubstituted alkylene, alkenylene, or alkynylene;
R 6 is hydrogen, alkyl, or —NR 10 R 11 ;
each of R 7 and R 10 is independently hydrogen, alkyl, aralkyl, alkenyl, or alkynyl;
each of R 8 and R 9 is independently hydrogen or alkyl; and
R 11 is hydrogen or alkyl,
wherein one of R 3 and R 4 is hydrogen and the other is —OR 8 .
2. A compound of the Formula:
or a pharmaceutically acceptable salt thereof,
wherein:
m is an integer from 0 to 4;
n is an integer from 0 to 5;
each of R 1 and R 2 is independently bromine, chlorine, haloalkyl, or —OR 8 ;
each of R 3 and R 4 is independently hydrogen or —OR 8 ;
or R 3 and R 4 together form ═X, wherein X is O, S, or NR 9 ;
R 5 is a linker having from 8 to 12 atoms, each of which is independently selected from the group consisting of C, N, O, S, provided no two heteroatoms are adjacent to one another, forming a substituted or unsubstituted alkylene, alkenylene, or alkynylene;
R 6 is hydrogen, alkyl, or —NR 10 R 11 ;
each of R 7 and R 10 is independently hydrogen, alkyl, aralkyl, alkenyl, or alkynyl;
each of R 8 and R 9 is independently hydrogen or alkyl; and
R11 is hydrogen or alkyl,
wherein R 5 is a substituted alkylene, alkenylene or alkynylene, substituted with one or more halogens.
3. A compound selected from the group consisting of compounds 14 through 18 and 20 through 22 shown in Table 1:
TABLE 1
Representative compounds of Formula A and the corresponding activities
Cpd
n
R 1
R 2
R 3 , R 4
R 5
R 6
R 7
1
1
4-Br
H
O
—(CH 2 ) 7 —
Me
Allyl
2
1
4-Br
H
O
—(CH 2 ) 8 —
Me
Allyl
3
1
4-Br
H
H, OH
—(CH 2 ) 7 —
Me
Allyl
4
1
4-Br
H
H, OH
—(CH 2 ) 8 —
Me
Allyl
5
1
4-Cl
H
O
—(CH 2 ) 8 —
Me
Allyl
6
1
4-Cl
H
H, OH
—(CH 2 ) 8 —
Me
Allyl
7
2
2,4-Cl
H
O
—(CH 2 ) 8 —
Me
Allyl
8
2
2,4-Cl
H
H, OH
—(CH 2 ) 8 —
Me
Allyl
9
1
4-Cl
Cl
O
—(CH 2 ) 8 —
Me
Allyl
10
1
4-Cl
Cl
H, OH
—(CH 2 ) 8 —
Me
Allyl
11
1
4-Cl
Cl
O
—(CH 2 ) 8 —
Me
—CH 2 C≡CH
12
1
4-Cl
Cl
O
—(CH 2 ) 8 —
Me
—CH 2 Ph
13
1
4-Cl
OH
O
—(CH 2 ) 8 —
Me
Allyl
14
—(CH 2 ) 4 —O—(CH 2 ) 3 —
15
—CH 2 —CH═CH—CH 2 —O—(CH 2 ) 3 —
16
—(CH 2 ) 5 —C≡C—CH 2 —
17
—(CH 2 ) 4 —O—(CH 2 ) 3 —
—NR 10 R 11
H
18
—CH 2 —CH═CH—CH 2 —O—(CH 2 ) 3 —
—NR 10 R 11
H
19
—(CH 2 ) 5 —C≡C—CH 2 —
—NR 10 R 11
H
20
1
4-Cl
2-Cl
O
—(CH 2 ) 8 —
Me
Allyl
21
1
4-Cl
2-Cl
H, OH
—(CH 2 ) 8 —
Me
Allyl
22
1
4-Cl
2-OH
O
—(CH 2 ) 8 —
Me
Allyl.