PC33813A
-1-
CLAIMS
1.
A compound of formula (I)
R2
R6
R3
O
O
NH
R4
R5
N
N
R1
N
N
NH2
N
(I)
5
or a pharmaceutically acceptable salt thereof,
wherein:
R1 is selected from the group consisting of C1-C6 alkyl, C1-C6 alkyl substituted
with 1 to 6 fluorine, C1-C6 alkyl substituted with 1 to 2 chlorine and up to six fluorine, C3C8 cycloalkyl, and C3-C8 cycloalkyl substituted with 1 to 6 groups selected from fluorine,
10
chlorine and C1-C3 alkyl;
R2 and R3 are independently selected from the group consisting of chlorine,
fluorine, -CN, C1-C3 alkoxyl, C1-C3 alkyl and C1-C3 alkyl substituted with 1 to 6 fluorine;
R4 is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, CN, C1-C3 alkyl and C1-C3 alkyl substituted with 1 to 6 fluorine;
R5 and R6 are independently selected from the group consisting of hydrogen,
15
fluorine, chlorine, bromine, -CN, C1-C3 alkyl and C1-C3 alkyl substituted with 1 to 6
fluorine;
provided that
(1) when R4, R5 and R6 are all hydrogen, then R2 and R3 are not both chlorine;
20
and
(2) the compound of formula I is not any of the following compounds,
-2-
O
O
NH
N
H2N
N
N
CH3
N
O
N
N
H2N
Cl
CH3
NH
N
Cl
,
N
N
O
CH3
N
Cl
Cl
and
O
CH3
NH
N
N
H2N
N
N
O
N
Cl
Cl
.
2. The compound or salt of claim 1, wherein R4 is hydrogen, R5 is hydrogen, R6 is
hydrogen, and R3 is selected from the group consisting of fluorine, C1-C3 alkyl and C1-C3
5
alkyl substituted with 1 to 6 fluorine.
3. The compound or salt of claim 1, wherein R4 is hydrogen, R5 is hydrogen, R6 is
hydrogen, and R2 is selected from the group consisting of fluorine, C1-C3 alkyl and C1-C3
alkyl substituted with 1 to 6 fluorine.
4. The compound or salt of claim 1, wherein R4 is selected from fluorine, chlorine, C2-C3
10
alkyl and C1-C3 alkyl substituted with 1 to 6 fluorine.
5. The compound or salt of claim 1, wherein R4 is fluorine or chlorine, R5 is hydrogen,
and R6 is hydrogen.
6. The compound or salt of claim 1, wherein R4 is fluorine or chlorine, R5 is hydrogen,
R6 is hydrogen, R2 is methyl or chlorine, and R3 is methyl or chlorine.
15
7. The compound or salt of claim 1, wherein R5 is C1-C3 alkyl substituted with 1 to 6
fluorine.
8. The compound or salt of claim 1, wherein R6 is C1-C3 alkyl substituted with 1 to 6
fluorine.
-39. The compound or salt of any of claims 1-8, wherein R1 is selected from the group
consisting of cyclopropyl, cyclobutyl, bicyclo[1.1.1]pent-1-yl, and C1-C6 alkyl substituted
with 1 to 6 fluorine.
10. The compound or salt of any of claims 1-8, wherein R1 is C3-C8 cycloalkyl or C3-C8
5
cycloalkyl substituted with 1 to 6 groups selected from fluorine, chlorine and C1-C3 alkyl.
11. The compound or salt of any of claims 1-8, wherein R1 is C1-C6 alkyl, C1-C6 alkyl
substituted with 1 to 6 fluorine, or C1-C6 alkyl substituted with 1 to 2 chlorine and up to
six fluorine.
12. The compound or salt of any of claims 1 and 4-11, wherein R2 is chlorine and R3 is
10
chlorine.
13. The compound or salt of any of claims 1, 2 and 4-11, wherein R2 is chlorine and R3
is C1-C3 alkyl.
14. A compound selected from the group consisting of
Cl
N
N
O
Cl
O
Cl
N
N
NH
NH2
N
,
Cl
O
Cl
O
NH
Cl
N
N
15
N
N
N
NH2
,
-4Cl
N
N
O
H3C
O
N
N
NH
NH2
N
,
Cl
N
N
O
Cl
O
F
N
N
NH
N
NH2
,
Cl
O
Cl
O
F
N
N
F
F
N
N
NH
N
NH2
F
,
Cl
N
O
Cl
O
NH
H3C
F
F
N
N
F
N
N
NH2
,
-5-
Cl
N
H3C
O
F
N
O
N
N
NH
N
NH2
,
Cl
N
O
H3C
O
N
N
NH
F
F
F
N
N
NH2
F
,
Cl
N
O
N
N
NH
F
H3C
F
N
O
H3C
NH2
N
F
,
Cl
N
O
H3C
O
NH
F
N
N
5
N
N
NH2
,
-6Cl
N
O
Cl
H3C F
F
O
CN
N
N
N
NH
N
NH2
,
Cl
N
N
O
Cl
O
N
N
NH
N
NH2
,
O
F
NH
F
N
N
F
N
N
H2N
O
N
Cl
Cl
,
O
NH
N
N
H2N
Br
N
N
O
F
N
F
F
Cl
Cl
,
-7-
O
CH3
NH
N
N
N
H2N
N
O
F
N
F
F
Cl
Cl
and
O
F
F
F
NH
N
N
N
H2N
N
O
CH3
N
Cl
Cl
or a pharmaceutically acceptable salt thereof.
15. A compound of the formula
Cl
N
O
H3C
O
NH
5
H3C
F
N
N
F
N
N
NH2
F
,
or a pharmaceutically acceptable salt thereof.
16. A pharmaceutical composition comprising the compound of any of claims 1-15, or a
pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
17. The use of the compound of any of claims 1-15, or a pharmaceutically acceptable
10
salt thereof, in the preparation of a medicament for the treatment of cancer.
18. A method of modulating the activity of HSP-90, comprising contacting a cell with a
compound of any of claims 1-15, or a pharmaceutically acceptable salt thereof.
19. A combination of a compound or salt of claim 1 and a further therapeutic agent.