FLORBETABEN F18


Synonyms	BAY-949172 Florbetaben (18f) Florbetaben f-18 Florbetaben f18 Neuraceq UNII-TLA7312TOI
Status
Molecule Category	UNKNOWN
UNII	TLA7312TOI
EPA CompTox	DTXSID20238065


Active Pharmaceutical Ingredients Bioactive chemicals	Exact Similarity SubStructure	Threshold (%) >= 70

Structure


InChI Key	NCWZOASIUQVOFA-FWZJPQCDSA-N
Smiles	CNc1ccc(/C=C/c2ccc(OCCOCCOCC[18F])cc2)cc1
InChI	InChI=1S/C21H26FNO3/c1-23-20-8-4-18(5-9-20)2-3-19-6-10-21(11-7-19)26-17-16-25-15-14-24-13-12-22/h2-11,23H,12-17H2,1H3/b3-2+/i22-1

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C21H26FNO3
Molecular Weight	358.44
AlogP	4.28
Hydrogen Bond Acceptor	4.0
Hydrogen Bond Donor	1.0
Number of Rotational Bond	12.0
Polar Surface Area	39.72
Molecular species	NEUTRAL
Aromatic Rings	2.0
Heavy Atoms	26.0

Bioactivity

Mechanism of Action	Action	Reference
Diagnostic agent	None	DailyMed

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Membrane receptor	-	-	-	2-2	-

Reference

Journal : J. Med. Chem.

Title : Fluoro-pegylated chalcones as positron emission tomography probes for in vivo imaging of beta-amyloid plaques in Alzheimer's disease.

PubMed ID : 19757822

DOI : 10.1021/jm901057p

Year : 2009

Volume : 52

Issue : 20

First Page : 6394

Last Page : 6401

Authors : Ono M, Watanabe R, Kawashima H, Cheng Y, Kimura H, Watanabe H, Haratake M, Saji H, Nakayama M.

Abstract : This paper describes the synthesis and biological evaluation of fluoro-pegylated (FPEG) chalcones for the imaging of beta-amyloid (Abeta) plaques in patients with Alzheimer's disease (AD). FPEG chalcone derivatives were prepared by the aldol condensation reaction. In binding experiments conducted in vitro using Abeta(1-42) aggregates, the FPEG chalcone derivatives having a dimethylamino group showed higher Ki values (20-50 nM) than those having a monomethylamino or a primary amine group. When the biodistribution of 11C-labeled FPEG chalcone derivatives having a dimethyamino group was examined in normal mice, all four derivatives were found to display sufficient uptake for imaging Abeta plaques in the brain. 18F-labeled 7c also showed good uptake by and clearance from the brain, although a slight difference between the 11C and 18F tracers was observed. When the labeling of Abeta plaques was carried out using brain sections of AD model mice and an AD patient, the FPEG chalcone derivative 7c intensely labeled Abeta plaques. Taken together, the results suggest 7c to be a useful candidate PET tracer for detecting Abeta plaques in the brain of patients with AD.

Reference

Journal : J. Med. Chem.

Title : Multidentate (18)F-polypegylated styrylpyridines as imaging agents for Aβ plaques in cerebral amyloid angiopathy (CAA).

PubMed ID : 22011144

DOI : 10.1021/jm2009106

Year : 2011

Volume : 54

Issue : 23

First Page : 8085

Last Page : 8098

Authors : Zha Z, Choi SR, Ploessl K, Lieberman BP, Qu W, Hefti F, Mintun M, Skovronsky D, Kung HF.

Abstract : β-Amyloid plaques (Aβ plaques) in the brain are associated with cerebral amyloid angiopathy (CAA). Imaging agents that could target the Aβ plaques in the living human brain would be potentially valuable as biomarkers in patients with CAA. A new series of (18)F styrylpyridine derivatives with high molecular weights for selectively targeting Aβ plaques in the blood vessels of the brain but excluded from the brain parenchyma is reported. The styrylpyridine derivatives, 8a-c, display high binding affinities and specificity to Aβ plaques (K(i) = 2.87, 3.24, and 7.71 nM, respectively). In vitro autoradiography of [(18)F]8a shows labeling of β-amyloid plaques associated with blood vessel walls in human brain sections of subjects with CAA and also in the tissue of AD brain sections. The results suggest that [(18)F]8a may be a useful PET imaging agent for selectively detecting Aβ plaques associated with cerebral vessels in the living human brain.

Reference

Journal : ACS Med. Chem. Lett.

Title : The β-Amyloid Hypothesis in Alzheimer's Disease: Seeing Is Believing.

PubMed ID : 24936237

DOI : 10.1021/ml300058m

Year : 2012

Volume : 3

Issue : 4

First Page : 265

Last Page : 267

Authors : Kung HF.

Reference

Journal : Eur. J. Med. Chem.

Title : ¹⁸F-labeled 2-phenylquinoxaline derivatives as potential positron emission tomography probes for in vivo imaging of β-amyloid plaques.

PubMed ID : 23047223

DOI : 10.1016/j.ejmech.2012.08.031

Year : 2012

Volume : 57

First Page : 51

Last Page : 58

Authors : Yu P, Cui M, Wang X, Zhang X, Li Z, Yang Y, Jia J, Zhang J, Ono M, Saji H, Jia H, Liu B.

Abstract : In continuation of our study on the 2-phenylquinoxaline scaffold as potential β-amyloid imaging probes, two [(18)F]fluoro-pegylated 2-phenylquinoxaline derivatives, 2-(4-(2-[(18)F]fluoroethoxy)phenyl)-N-methylquinoxalin-6-amine ([(18)F]4a) and 2-(4-(2-(2-(2-[(18)F]fluoroethoxy)ethoxy)ethoxy)phenyl)-N-methylquinoxalin-6-amine ([(18)F]4b) were prepared. Both of them displayed high binding affinity to Aβ(1-42) aggregates (K(i) = 10.0 ± 1.4 nM for 4a, K(i) = 5.3 ± 3.2 nM for 4b). The specific and high binding of [(18)F]4a and [(18)F]4b to Aβ plaques was confirmed by in vitro autoradiography on brain sections of AD human and transgenic mice. In biodistribution in normal mice, [(18)F]4a displayed high initial brain uptake (8.17% ID/g at 2 min) and rapid washout from the brain. These preliminary results suggest [(18)F]4a may be a potential PET imaging agent for Aβ plaques in the living human brain.

Reference

Journal : J. Med. Chem.

Title : Synthesis and evaluation of ¹⁸F-labeled styryltriazole and resveratrol derivatives for β-amyloid plaque imaging.

PubMed ID : 22236086

DOI : 10.1021/jm201400q

Year : 2012

Volume : 55

Issue : 2

First Page : 883

Last Page : 892

Authors : Lee I, Choe YS, Choi JY, Lee KH, Kim BT.

Abstract : In the present study, a styryltriazole and four resveratrol derivatives were synthesized as candidates for β-amyloid (Aβ) plaque imaging. On the basis of their binding affinities to Aβ(1-42) aggregates, the styryltriazole (1, K(i) = 12.8 nM) and one resveratrol derivative (5, K(i) = 0.49 nM) were labeled with (18)F. In normal mice, tissue distribution of [(18)F]5 showed good initial brain uptake (3.26% ID/g at 2 min) but slow wash-out from brains (2-to-60 min uptake ratio: 2.9). Furthermore, it underwent in vivo metabolic defluorination (1.88% ID/g at 2 min and 9.73% ID/g at 60 min). In contrast, [(18)F]1 displayed high initial brain uptake (5.38% ID/g at 2 min) with rapid wash-out from brains (0.52% ID/g at 60 min; 2-to-60 min uptake ratio: 10.3). These results indicate that [(18)F]1 has in vivo kinetics comparable to PET radiopharmaceuticals currently under commercial development, demonstrating that [(18)F]1 is a desirable PET radioligand for Aβ plaque imaging.

Reference

Journal : J. Med. Chem.

Title : Synthesis and evaluation of ¹⁸F-labeled styryltriazole and resveratrol derivatives for β-amyloid plaque imaging.

PubMed ID : 22236086

DOI : 10.1021/jm201400q

Year : 2012

Volume : 55

Issue : 2

First Page : 883

Last Page : 892

Authors : Lee I, Choe YS, Choi JY, Lee KH, Kim BT.

Reference

Journal : J. Med. Chem.

Title : Synthesis and evaluation of novel ¹⁸F labeled 2-pyridinylbenzoxazole and 2-pyridinylbenzothiazole derivatives as ligands for positron emission tomography (PET) imaging of β-amyloid plaques.

PubMed ID : 22974116

DOI : 10.1021/jm300973k

Year : 2012

Volume : 55

Issue : 21

First Page : 9283

Last Page : 9296

Authors : Cui M, Wang X, Yu P, Zhang J, Li Z, Zhang X, Yang Y, Ono M, Jia H, Saji H, Liu B.

Abstract : A series of fluoro-pegylated (FPEG) 2-pyridinylbenzoxazole and 2-pyridinylbenzothiazole derivatives were synthesized and evaluated as novel β-amyloid (Aβ) imaging probes for PET. They displayed binding affinities for Aβ(1-42) aggregates that varied from 2.7 to 101.6 nM. Seven ligands with high affinity were selected for (18)F labeling. In vitro autoradiography results confirmed the high affinity of these radiotracers. In vivo biodistribution experiments in normal mice indicated that the radiotracers with a short FPEG chain (n = 1) displayed high initial uptake into and rapid washout from the brain. One of the 2-pyridinylbenzoxazole derivatives, [(18)F]-5-(5-(2-fluoroethoxy)benzo[d]oxazol-2-yl)-N-methylpyridin-2-amine ([(18)F]32) (K(i) = 8.0 ± 3.2 nM) displayed a brain(2min)/brain(60min) ratio of 4.66, which is highly desirable for Aβ imaging agents. Target specific binding of [(18)F]32 to Aβ plaques was validated by ex vivo autoradiographic experiment with transgenic model mouse. Overall, [(18)F]32 is a promising Aβ imaging agent for PET and merits further evaluation in human subjects.

Reference

Journal : Bioorg. Med. Chem.

Title : Synthesis and biological evaluation of 18F-labled 2-phenylindole derivatives as PET imaging probes for β-amyloid plaques.

PubMed ID : 23673220

DOI : 10.1016/j.bmc.2013.04.028

Year : 2013

Volume : 21

Issue : 13

First Page : 3708

Last Page : 3714

Authors : Fu H, Yu L, Cui M, Zhang J, Zhang X, Li Z, Wang X, Jia J, Yang Y, Yu P, Jia H, Liu B.

Abstract : A novel series of fluorinated 2-phenylindole derivatives were synthesized and evaluated as β-amyloid imaging probes for PET. The in vitro inhibition assay demonstrated that their binding affinities for Aβ(1-42) aggregates ranged from 28.4 to 1097.8 nM. One ligand was labeled with (18)F ([(18)F]1a) for its high affinity (K(i)=28.4 nM), which was also confirmed by in vitro autoradiography experiments on brain sections of transgenic mouse (C57BL6, APPswe/PSEN1, 11 months old, male). In vivo biodistribution experiments in normal mice showed that this radiotracer displayed high initial uptake (5.82±0.51% ID/g at 2 min) into and moderate washout (2.77±0.31% ID/g at 60 min) from the brain. [(18)F]1a could be developed as a promising new PET imaging probe for Aβ plaques although necessary modifications are still needed.

Assay Description	Organism	Bioactivity
Binding affinity to amyloid beta (1 to 42) peptide	None	6.7 nM
Displacement of [18F]-amyvid from amyloid-beta aggregates in alzheimer's disease patient brain homogenates after 1 hr	Homo sapiens	2.22 nM
Binding affinity to human amyloid beta plaque	Homo sapiens	2.2 nM
Binding affinity to beta-amyloid	None	2.22 nM
Binding affinity to amyloid beta (1-42) aggregates	None	2.22 nM
Binding affinity to amyloid beta (1-42) aggregates in human Alzheimer's disease brain sections	Homo sapiens	2.22 nM
Displacement of [125I]-IMPY from amyloid beta (1 to 42) fibrils after 2 hrs by gamma-counting analysis	None	6.7 nM
Displacement of [125I]IMPY from amyloid beta in brain homogenate of Alzheimer's disease patient after 2 hrs by gamma counting analysis	Homo sapiens	2.22 nM

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Cross References

Resources	Reference
ChEBI	79033
ChEMBL	CHEMBL566752
DrugBank	DB09148
DrugCentral	4818
FDA SRS	TLA7312TOI
Guide to Pharmacology	7769
SureChEMBL	SCHEMBL11301755
ZINC	ZINC000100529288

CONTENTS

Structure
Chemical and Physical Properties
Pharmacology
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