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Generation of novel radiolabeled opiates through site-selective iodination.

Abstract：

:Tritiated opioid radioligands have proven valuable in exploring opioid binding sites. However, tritium has many limitations. Its low specific activity and limited counting efficiency makes it difficult to examine low abundant, high affinity sites and its disposal is problematic due to the need to use organic scintillants and its relatively long half-life. To overcome these issues, we have synthesized both unlabeled and carrier-free radioiodinated iodobenzoyl derivatives of 6β-naltrexamine ((125)I-BNtxA, 18), 6β-naloxamine ((125)I-BNalA, 19) and 6β-oxymorphamine ((125)I-BOxyA, 20) with specific activities of 2100Ci/mmol. To optimize the utility of the radioligand, we designed a synthesis in which the radiolabel is incorporated in the last synthetic step, which required the selective iodination of the benzoyl moiety without incorporation into the phenolic A ring. Competition studies demonstrated high affinity of the unlabelled compounds for opioid receptors in transfected cell lines, as did the direct binding of the (125)I-ligands to the opioid receptors. The radioligand displayed very high sensitivity, enabling a marked reduction in tissue, as well as excellent signal/noise characteristics. These new (125)I-radioligands should prove valuable in future studies of opioid binding sites.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Majumdar S,Burgman M,Haselton N,Grinnell S,Ocampo J,Pasternak AR,Pasternak GW

doi

10.1016/j.bmcl.2011.05.008

subject

Has Abstract

pub_date

2011-07-01 00:00:00

pages

4001-4

issue

13

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)00624-X

journal_volume

21

pub_type

杂志文章

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