Radiosynthesis of Tau Radiopharmaceuticals

Patent metadata

Field	Value
Publication number	US-2016115162-A1
Application number	US-201414892949-A
Country	US
Kind code	A1
Filing date	May 30, 2014
Priority date	May 31, 2013
Publication date	Apr 28, 2016
Grant date	—

Abstract

This disclosure relates to a one-step method for preparing the tau radiopharmaceutical, [18F]T807, using an unprotected or protected precursor (e.g., tertbutyl 7-(6-nitropyridin-3-yl)-SH-pyrido[4,3-b]indole-5-carboxylate). An improved one-step synthesis method to prepare [18F]T807 was achieved with a protected (e.g., t-BOC) precursor, offering increased solubility, a faster synthesis as well as simpler purification and automation. [18F]T807 was validated for human use with a GE TRACERlab™ FXFN radiosynthesis module. The methodology demonstrated herein should facilitate multi-center trials and widespread use for tauopathy imaging with this radiopharmaceutical.

First claim

1 . A process for preparing a compound of formula (II):

the method comprising:
reacting a compound of formula (I):

wherein:
X is H or a protecting group; and
Z is a leaving group,
with a radiofluorinating agent to prepare the compound of formula (II).

2 . The process of claim 1 , wherein X is a carbamate protecting group.

3 . (canceled)

4 . The process of claim 1 , wherein Z is selected from the group consisting of: triflate, mesylate, nonaflate, hexaflate, tosylate, nosylate, brosylate, perfluoroalkyl sulfonate, tetraphenylborate, hexafluorophosphate, trifluoroacetate, tetrafluoroborate, perchlorate, perfluoroalkylcarboxylate, nitro, azide, chloride, bromide, or iodide.

5 . (canceled)

6 . The process of claim 1 , wherein the radio fluorinating agent is potassium cryptand [ 18 F]fluoride (K[ 18 F]/K 222 ).

7 . The process of claim 1 , wherein the process is performed at a temperature ranging from about 60 to about 200° C.

8 . (canceled)

9 . The process of claim 7 , wherein the heating occurs for a time period ranging from about 1 minutes to about 30 minutes.

10 .- 13 . (canceled)

14 . The process of claim 1 , wherein the compound of formula (II) is formulated with a carrier.

15 . The process of claim 1 , wherein the carrier is sodium chloride for injection.

16 . (canceled)

17 . The process of claim 1 , wherein the process is performed in an automated radiosynthesis module.

18 . A process for preparing a compound of formula (II):

the method comprising:
reacting a compound:

with a potassium cryptand [ 18 F]fluoride (K[ 18 F]/K 222 ) in DMSO at 130° C. to prepare the compound of formula (II).

19 . The process of claim 18 , wherein the reacting occurs for a time period ranging from about 1 minutes to about 30 minutes.

20 .- 22 . (canceled)

23 . The process of claim 18 , wherein the compound of formula (II) is formulated with a pharmaceutically acceptable carrier.

24 . The process of claim 18 , wherein the carrier is sodium chloride for injection.

25 . The process of claim 24 , wherein the sodium chloride is 0.9% sodium chloride.

26 . A compound of formula (II):

prepared by a process comprising:
reacting a compound of formula (I):

wherein X is H or a protecting group,
with a radiofluorinating agent to prepare the compound of formula (II).

27 . A compound of formula (I):

wherein X is a protecting group; and
Z is a leaving group.

28 . The compound of claim 27 , wherein X is a carbamate protecting group.

29 . (canceled)

30 . The compound of claim 27 , wherein Z is selected from the group consisting of triflate, mesylate, nonaflate, hexaflate, tosylate, nosylate, brosylate, perfluoroalkyl sulfonate, tetraphenylborate, hexafluorophosphate, trifluoroacetate, tetrafluoroborate, perchlorate, perfluoroalkylcarboxylate, nitro, azide, chloride, bromide, or iodide.

31 . (canceled)

32 . The compound of claim 27 , wherein the compound of formula (I) is:

Assignees

• Gen Hospital Corp

Inventors

• Vasdev Neil
• Shoup Timothy M

Classifications

• C07B59/002

  Heterocyclic compounds · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title