Isatin derivatives for use as in vivo imaging agents
Isatin 5-sulfonamide derivatives, pharmaceutical compositions comprising the derivatives, their use as molecular imaging agents, their use for the diagnosis or treatment of diseases or disorders associated with dysregulation of apoptosis, methods for synthesizing the derivatives, methods for the molecular imaging of caspase activity and apoptosis, and methods of assessing the therapeutic effect of a test substance on caspase activity are disclosed.
1. A compound of formula A:
or a salt or hydrate thereof, wherein
R is 3-fluorophenyl, 2,4-difluorophenyl, 3,5-difluorophenyl, an optionally substituted tetrahydropyran, an optionally substituted diazine or an optionally substituted triazole;
R′ is an optionally substituted phenyl or an optionally substituted triazole; and
wherein R and R′ are chosen such that when R′ is an optionally substituted phenyl, R is an optionally substituted triazole.
2. The compound of claim 1 , wherein the optionally substituted triazole is substituted with a substituted alkyl group.
3. The compound of claim 1 , wherein R and R′ are defined as follows:
Com-
pound
No.
R
R′
6
7
8
9
11
29
30
31
12
32
33
34
4. The compound of claim 1 , additionally comprising an imaging moiety.
5. The compound of claim 4 , wherein the imaging moiety is 18 F.
6. A pharmaceutical composition comprising the compound of claim 1 , and optionally one or more additional active ingredients, pharmaceutically acceptable excipients, carriers or diluents.
7. A compound of formula A:
or a salt, hydrate or prodrug thereof,
wherein R is selected from the group consisting of 3-fluorophenyl, 2,4-difluorophenyl and 3,5-difluorophenyl; and wherein R′ is a 2-fluoroethyl-substituted triazole.
8. A compound of formula [ 18 F]11: