Novel [(Diazomethyl)carbonyl]-l,2,3,4-tetrahydronaphthalene Derivatives as Potential Photoaffinity Ligands for the 5-HT1AReceptor

Document Type

Article

Publication Date

1-1-1990

Abstract

The photolabile (diazomethyl)carbonyl function was introduced into the 8-position of 2-(N,N-di-n-propyl-amino)-1,2,3,4-tetrahydronaphthalene in three ways, resulting in the ether 8-[[(diazomethyl)carbonyl]methoxy]-2-(N,N-di-n-propylamino)-1,2,3,4-tetrahydronaphthalene (2), the ester 8-(diazoacetoxy)-2-(N,N-di-n-propyl-amino)-1,2,3,4-tetrahydronaphthalene (3), and the ketone 8-[(diazomethyl)carbonyl]-2-(N,N-di-n-propylamino)-1,2,3,4-tetrahydronaphthalene (4). Specific binding of these compounds at the 5-hydroxytryptamine1Asites in rat brain membranes labeled with 1 nM [3H]-8-hydroxy-2-(N,N-di-n-propylamino)-1,2,3,4-tetrahydronaphthalene (8-OH-DPAT) showed IC50 values of ca. 75, 125, and 25 nM, respectively, for the three compounds. Photolysis of methanolic solutions of 2-4 in the absence of receptor proteins lead in each case to an abundance of Wolff-rearranged products. In the case of ether 2, subsequent β-elimination to 8-OH-DPAT removed this compound from serious consideration as a photoaffinity ligand. Ester 3 and ketone 4 were photolysed in vitro. Whereas ester 3 was ineffective in decreasing the specific binding of [3H]-8-OH-DPAT, ketone 4 decreased 40% of the specific binding of [3H]-8-OH-DPAT in the presence (but not the absence) of ultraviolet light. Thus this ketone emerges from these studies as a good candidate for a photoaffinity label for the 5-hydroxytryptamine1Areceptor. © 1990, American Chemical Society. All rights reserved.

Identifier

0025237376 (Scopus)

Publication Title

Journal of Medicinal Chemistry

External Full Text Location

https://doi.org/10.1021/jm00165a011

e-ISSN

15204804

ISSN

00222623

PubMed ID

2137880

First Page

950

Last Page

955

Issue

3

Volume

33

Grant

R01DA001875

Fund Ref

National Institute on Drug Abuse

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