- SELECTIVE LIGANDS FOR TAU AGGREGATES
-
The present invention provides a compound of formula (I) and compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt, ester, amide or carbamate thereof, or a salt of such an ester, amide or carbamate. The present invention also provides a compound of formula (X) and compositions comprising a compound of formula (X) or a pharmaceutically acceptable salt, ester, amide or carbamate thereof, or a salt of such an ester, amide or carbamate. The present invention further provides uses of the compounds of formula (I) and (X) and compositions comprising compounds of formula (I) and (X), including the use of such compounds and compositions for the diagnosis and treatment of neurodegenerative diseases, and especially tauopathies such as Alzheimer′s disease.
- -
-
Page/Page column 124
(2021/04/23)
-
- N-(3-[18F]fluoropropyl)-N-nordiprenorphine: synthesis and characterization of a new agent for imaging opioid receptors with positron emission tomography.
-
A series of N-fluoroalkyl (1-5) and N-alkyl (6-8) analogues of the high-affinity opioid receptor antagonist diprenorphine (9) has been synthesized and evaluated with in vitro binding assays. Three of the N-fluoroalkyl compounds were prepared with the positron-emitting radionuclide 18F (1a, 2a, 5a), and their biodistribution was determined in rats. Compounds 2a and 5a were made by using a two-step labeling procedure, [18F]fluoride displacement of an iodoalkyl triflate followed by N-alkylation, that required 2 h and proceeded in 4-6% overall radiochemical yield at the end of synthesis. The effective specific activity of compounds 2a and 5a, determined by competitive receptor binding assay, was 840-1820 Ci/mmol. Compound 1a was made by the same two-step procedure, with the bromoalkyl triflate, in 0.3-0.6% radiochemical yield at an effective specific activity of 106-264 Ci/mmol. Specificity of binding in vivo was measured as the percent injected dose/gram of striatal tissue divided by the percent injected dose/gram of cerebellar tissue. The best striatum to cerebellum ratio (3.32 +/- 0.74 at 30 min) was achieved with N-(3-[18F]-fluoropropyl)-N-nordiprenorphine (2a, [18F]FPND). The high specific binding demonstrated by this compound indicates that it may be useful for in vivo imaging of opioid receptors with positron emission tomography.
- Chesis,Hwang,Welch
-
p. 1482 - 1490
(2007/10/02)
-