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,

day = "15",

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

language = "English (US)",

volume = "16",

pages = "4946--4950",

journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - Synthesis and evaluation of 3-aminopropionyl substituted fentanyl analogues for opioid activity

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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DO - 10.1016/j.bmcl.2006.06.040

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IS - 18

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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