Synthesis and evaluation of 3-aminopropionyl substituted fentanyl analogues for opioid activity

Ravil R. Petrov; Ruben S Vardanyan; Yeon S. Lee; Shou wu Ma; Peg Davis; Lucinda J. Begay; Josephine Y. Lai; Frank Porreca; Victor J Hruby

doi:10.1016/j.bmcl.2006.06.040

Synthesis and evaluation of 3-aminopropionyl substituted fentanyl analogues for opioid activity

Ravil R. Petrov, Ruben S Vardanyan, Yeon S. Lee, Shou wu Ma, Peg Davis, Lucinda J. Begay, Josephine Y. Lai, Frank Porreca, Victor J Hruby

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

26 Scopus citations

Abstract

An enkephalin analogue coupled to 'aminofentanyl' has been synthesized and tested for biological activities at the μ and δ opioid receptors. Aminofentanyl which represents a structural derivative of fentanyl has been synthesized by acylation of 1-(2-phenethyl)-4-(N-anilino)piperidine with phthaloyl protected β-alaninyl chloride in the presence of DIPEA, followed by deprotection with hydrazine hydrate. Aminofentanyl has also been successfully acylated with ethyl isocyanate, various acid anhydrides, to further investigate structure-activity relationships of these new fentanyl derivatives. Among the new derivatives compound 7 which carries a Tyr-d-Ala-Gly-Phe opioid message sequence showed good opioid affinity (1 nM at both δ and μ opioid receptors) and bioactivity (34.9 nM in MVD and 42 nM in GPI/LMMP bioassays).

Original language	English (US)
Pages (from-to)	4946-4950
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	18
DOIs	https://doi.org/10.1016/j.bmcl.2006.06.040
State	Published - Sep 15 2006

Keywords

Enkephalin analogue
Fentanyl derivatives
Opioid agonists

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2006.06.040

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title = "Synthesis and evaluation of 3-aminopropionyl substituted fentanyl analogues for opioid activity",

abstract = "An enkephalin analogue coupled to 'aminofentanyl' has been synthesized and tested for biological activities at the μ and δ opioid receptors. Aminofentanyl which represents a structural derivative of fentanyl has been synthesized by acylation of 1-(2-phenethyl)-4-(N-anilino)piperidine with phthaloyl protected β-alaninyl chloride in the presence of DIPEA, followed by deprotection with hydrazine hydrate. Aminofentanyl has also been successfully acylated with ethyl isocyanate, various acid anhydrides, to further investigate structure-activity relationships of these new fentanyl derivatives. Among the new derivatives compound 7 which carries a Tyr-d-Ala-Gly-Phe opioid message sequence showed good opioid affinity (1 nM at both δ and μ opioid receptors) and bioactivity (34.9 nM in MVD and 42 nM in GPI/LMMP bioassays).",

keywords = "Enkephalin analogue, Fentanyl derivatives, Opioid agonists",

author = "Petrov, {Ravil R.} and Vardanyan, {Ruben S} and Lee, {Yeon S.} and Ma, {Shou wu} and Peg Davis and Begay, {Lucinda J.} and Lai, {Josephine Y.} and Frank Porreca and Hruby, {Victor J}",

note = "Funding Information: This work was supported by grants from USPHS and NIDA.",

year = "2006",

month = sep,

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doi = "10.1016/j.bmcl.2006.06.040",

language = "English (US)",

volume = "16",

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AU - Petrov, Ravil R.

AU - Vardanyan, Ruben S

AU - Lee, Yeon S.

AU - Ma, Shou wu

AU - Davis, Peg

AU - Begay, Lucinda J.

AU - Lai, Josephine Y.

AU - Porreca, Frank

AU - Hruby, Victor J

N1 - Funding Information: This work was supported by grants from USPHS and NIDA.

PY - 2006/9/15

Y1 - 2006/9/15

N2 - An enkephalin analogue coupled to 'aminofentanyl' has been synthesized and tested for biological activities at the μ and δ opioid receptors. Aminofentanyl which represents a structural derivative of fentanyl has been synthesized by acylation of 1-(2-phenethyl)-4-(N-anilino)piperidine with phthaloyl protected β-alaninyl chloride in the presence of DIPEA, followed by deprotection with hydrazine hydrate. Aminofentanyl has also been successfully acylated with ethyl isocyanate, various acid anhydrides, to further investigate structure-activity relationships of these new fentanyl derivatives. Among the new derivatives compound 7 which carries a Tyr-d-Ala-Gly-Phe opioid message sequence showed good opioid affinity (1 nM at both δ and μ opioid receptors) and bioactivity (34.9 nM in MVD and 42 nM in GPI/LMMP bioassays).

AB - An enkephalin analogue coupled to 'aminofentanyl' has been synthesized and tested for biological activities at the μ and δ opioid receptors. Aminofentanyl which represents a structural derivative of fentanyl has been synthesized by acylation of 1-(2-phenethyl)-4-(N-anilino)piperidine with phthaloyl protected β-alaninyl chloride in the presence of DIPEA, followed by deprotection with hydrazine hydrate. Aminofentanyl has also been successfully acylated with ethyl isocyanate, various acid anhydrides, to further investigate structure-activity relationships of these new fentanyl derivatives. Among the new derivatives compound 7 which carries a Tyr-d-Ala-Gly-Phe opioid message sequence showed good opioid affinity (1 nM at both δ and μ opioid receptors) and bioactivity (34.9 nM in MVD and 42 nM in GPI/LMMP bioassays).

KW - Enkephalin analogue

KW - Fentanyl derivatives

KW - Opioid agonists

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Synthesis and evaluation of 3-aminopropionyl substituted fentanyl analogues for opioid activity

Abstract

Keywords

ASJC Scopus subject areas

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