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Carboline and carbazole based imaging agents for detecting neurological dysfunction

An alkyl, aryl-based technology in the field of carboline- and carbazole-based imaging agents for the detection of neurological dysfunction, which can solve problems such as accurate distinctions not expected

Inactive Publication Date: 2017-08-04
ELI LILLY & CO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

To date, FDDNP and PIB are not known to bind neurotoxic soluble oligomers and aggregate, and thus are not expected to accurately differentiate between early AD and late AD in patients

Method used

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  • Carboline and carbazole based imaging agents for detecting neurological dysfunction
  • Carboline and carbazole based imaging agents for detecting neurological dysfunction
  • Carboline and carbazole based imaging agents for detecting neurological dysfunction

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Embodiment Construction

[0094] detail

[0095] "Halogen" or "halo" means F, Cl, Br and I.

[0096] "Alkyl" means a saturated monovalent hydrocarbon radical having straight or branched chain portions. Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, and tert-butyl.

[0097] "Alkenyl" means an alkyl moiety having at least one carbon-carbon double bond, wherein alkyl is as defined above. Examples of alkenyl groups include, but are not limited to, ethenyl and propenyl.

[0098] "Alkynyl" means an alkyl moiety having at least one carbon-carbon triple bond, wherein alkyl is as defined above. Examples of alkynyl include, but are not limited to, ethynyl and 2-propynyl.

[0099] "Alkylene" or "alkenylene" means a saturated divalent hydrocarbon radical having a straight or branched chain portion, ie, typically present as a bridging or linking group between two other groups. Examples of alkylene include -CH 2 -(methylene); -CH 2 CH 2 -(ethylene);-CH 2 CH 2 ...

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Abstract

Disclosed herein are compounds and methods of diagnosing Alzheimer's Disease or a predisposition thereto in a mammal, the method comprising administering to the mammal a diagnostically effective amount of a radiolabeled compound, allowing the compound to distribute into the brain tissue, and imaging the brain tissue, wherein an increase in binding of the compound to the brain tissue compared to a normal control level of binding indicates that the mammal mal is suffering from or is at risk of developing Alzheimer's Disease. The claimed compounds have the structure of formula (I) wherein: L is N or CR5, M is N or CR6; P is N or CR7; and Q is N or CR8; X is a bond or is Cl-14alkyl, wherein at least one carbon is optionally replaced by C(O), 0, S, S02, or NH, NH-Cl-8alkyl, and wherein at least one H of Cl-8alkyl is optionally replaced by halo, OH, Cl-6alkyl; wherein at least one halo is optionally replaced with a radionuclide or a fluorescent tag. The other variables are as defined in the claims.

Description

[0001] This application is a divisional application of an invention patent application with the application number 201280073373.0, the date of entering the Chinese national phase on November 21, 2014, the international application number PCT / US2012 / 061912, and the international application date on October 25, 2012. [0002] Cross References to Related Applications [0003] This application claims priority to US Application Serial No. 13 / 477,095, filed May 22, 2012 (the "'095 application"), which is incorporated herein by reference in its entirety. The '095 application claims priority to US Provisional Patent Application No. 61 / 489,284, filed May 24, 2011; the entire contents of which application are incorporated herein by reference. The '095 application is a continuation-in-part of US Application No. 12 / 372,717, filed February 17, 2009; the entire contents of said application are hereby incorporated by reference. USSN 12 / 372,717 claims priority to US Provisional Patent Applicat...

Claims

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Application Information

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IPC IPC(8): C07D471/04C07D209/88C07D311/18C07D403/12C07D209/82C07D471/14A61K51/04A61K101/02
CPCA61K51/0446A61K51/0455C07B59/002C07B2200/05C07D209/80C07D209/82C07D209/88C07D311/18C07D403/12C07D471/04C07D471/14
Inventor A.K.萨德宁斯H.C.科尔布J.C.沃尔什G.陈U.B.甘加哈马思D.卡西C.刘A.辛哈E.王C.余W.张K.陈V.P.莫查拉P.J.H.斯科特
Owner ELI LILLY & CO
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