Investigation of the 4-O-alkylamine substituent of non-peptide quinolone GnRH receptor antagonists

Robert J. DeVita; Mark T. Goulet; Matthew J. Wyvratt; Michael H. Fisher; Jane L. Lo; Yi Tien Yang; Kang Cheng; Roy G. Smith

doi:10.1016/S0960-894X(99)00447-3

Investigation of the 4-O-alkylamine substituent of non-peptide quinolone GnRH receptor antagonists

Robert J. DeVita, Mark T. Goulet, Matthew J. Wyvratt, Michael H. Fisher, Jane L. Lo, Yi Tien Yang, Kang Cheng, Roy G. Smith

Research output: Contribution to journal › Article › peer-review

60 Scopus citations

Abstract

Synthesis and in vitro activity of the enantiomers of quinolone GnRH antagonist (±)-1 are reported. Chiral amino alcohols were prepared from the appropriate cyclic D- or L-amino acids by the Arndt-Eistert homologation followed by reduction of the resulting esters. Incorporation of these pharmacophores was achieved via a novel Mitsunobu alkylation of 4-hydroxyquinolones. The key amine pharmacophore for binding to the rat GnRH receptor was most active in the S-configuration. Ring size was not important for potency with 4, 5, 6, and 7-membered ring amines exhibiting similar potency.

Original language	English
Pages (from-to)	2621-2624
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	9
Issue number	17
DOIs	https://doi.org/10.1016/S0960-894X(99)00447-3
State	Published - 6 Sep 1999
Externally published	Yes

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title = "Investigation of the 4-O-alkylamine substituent of non-peptide quinolone GnRH receptor antagonists",

abstract = "Synthesis and in vitro activity of the enantiomers of quinolone GnRH antagonist (±)-1 are reported. Chiral amino alcohols were prepared from the appropriate cyclic D- or L-amino acids by the Arndt-Eistert homologation followed by reduction of the resulting esters. Incorporation of these pharmacophores was achieved via a novel Mitsunobu alkylation of 4-hydroxyquinolones. The key amine pharmacophore for binding to the rat GnRH receptor was most active in the S-configuration. Ring size was not important for potency with 4, 5, 6, and 7-membered ring amines exhibiting similar potency.",

author = "DeVita, {Robert J.} and Goulet, {Mark T.} and Wyvratt, {Matthew J.} and Fisher, {Michael H.} and Lo, {Jane L.} and Yang, {Yi Tien} and Kang Cheng and Smith, {Roy G.}",

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T1 - Investigation of the 4-O-alkylamine substituent of non-peptide quinolone GnRH receptor antagonists

AU - DeVita, Robert J.

AU - Goulet, Mark T.

AU - Wyvratt, Matthew J.

AU - Fisher, Michael H.

AU - Lo, Jane L.

AU - Yang, Yi Tien

AU - Cheng, Kang

AU - Smith, Roy G.

PY - 1999/9/6

Y1 - 1999/9/6

N2 - Synthesis and in vitro activity of the enantiomers of quinolone GnRH antagonist (±)-1 are reported. Chiral amino alcohols were prepared from the appropriate cyclic D- or L-amino acids by the Arndt-Eistert homologation followed by reduction of the resulting esters. Incorporation of these pharmacophores was achieved via a novel Mitsunobu alkylation of 4-hydroxyquinolones. The key amine pharmacophore for binding to the rat GnRH receptor was most active in the S-configuration. Ring size was not important for potency with 4, 5, 6, and 7-membered ring amines exhibiting similar potency.

AB - Synthesis and in vitro activity of the enantiomers of quinolone GnRH antagonist (±)-1 are reported. Chiral amino alcohols were prepared from the appropriate cyclic D- or L-amino acids by the Arndt-Eistert homologation followed by reduction of the resulting esters. Incorporation of these pharmacophores was achieved via a novel Mitsunobu alkylation of 4-hydroxyquinolones. The key amine pharmacophore for binding to the rat GnRH receptor was most active in the S-configuration. Ring size was not important for potency with 4, 5, 6, and 7-membered ring amines exhibiting similar potency.

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JO - Bioorganic and Medicinal Chemistry Letters

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ER -

Investigation of the 4-O-alkylamine substituent of non-peptide quinolone GnRH receptor antagonists

Abstract

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