β-amyloid and neurofibrillary tangle imaging agents
View Patent ↗Compounds, compositions and methods are contemplated in which senile plaques and/or neurofibrillary tangles are labeled using compounds with improved permeability across the blood brain barrier and improved selective binding to senile plaques and/or neurofibrillary tangles. Contemplated compounds are derivatives of FDDNP or curcumin, which most preferably have improved solubility in aqueous solvents. Labeling is typically performed using a PET detectable label, and especially 11 C and 18 F.
1. A compound having a structure according to Formula I
wherein Z is C(CN) 2 or O;
wherein W is N—Y or CH 2 , with the proviso that where W is N—Y then n is 1, and with the further proviso that where W is CH 2 then n is an integer between 0 and 2;
Y is optionally substituted lower alkyl, optionally comprising a 11 C atom;
R 1 is hydrogen, lower alkyl, lower dialkylketone, or substituted aryl;
wherein F is 18 F or 19 F; and
wherein X is H, OH, OCH 3 , OR, SH, SR, NH 2 , NHR, NR 2 R 3 , C(O)R, C(O)OR, or optionally substituted R, wherein R is lower alkyl, and wherein R 2 and R 3 are independently optionally substituted lower alkyl, or fluoroalkyl.
2. The compound of claim 1 wherein Z is C(CN) 2 , and wherein R 1 is hydrogen, lower alkyl, or lower dialkylketone.
3. The compound of claim 2 wherein F is 18 F or 19 F and Y is CH 3 .
4. The compound of claim 2 wherein Y is 11 CH 3 and F is 19 F.
5. The compound of claim 2 wherein X is OH, OCH 3 , SH, NH 2 , NHR 2 , or NR 2 R 3 ,
wherein R 2 and R 3 are independently optionally substituted lower alkyl.
6. The compound of claim 2 wherein R 1 is hydrogen or CH 2 C(O)CH 3 .
7. The compound of claim 1 having a structure according to Formula II
8. The compound of claim 1 wherein Z is O, and wherein R 1 is substituted aryl.
9. The compound of claim 8 wherein R 1 is selected from the group consisting of
10. A compound having a structure according to Formula IIa
wherein n is an integer between 0 and 4, and wherein X is OH, OR, SH, SR, NH2, NHR, C(O)R, C(O)OR, or optionally substituted R, wherein R is lower alkyl.
11. A pharmaceutical or diagnostic composition comprising the compound of claim 1 , or claim 10 and a pharmaceutically acceptable carrier.
12. The pharmaceutical or diagnostic composition comprising the compound of claim 7 .