Solid-phase synthesis and pharmacological evaluation of analogues of PhTX-12-A potent and selective nicotinic acetylcholine receptor antagonist

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Solid-phase synthesis and pharmacological evaluation of analogues of PhTX-12-A potent and selective nicotinic acetylcholine receptor antagonist. / Strømgaard, Kristian; Mellor, Ian R; Andersen, Kim; Neagoe, Ioana; Pluteanu, Florentina; Usherwood, Peter N R; Krogsgaard-Larsen, Povl; Jaroszewski, Jerzy W.

In: Bioorganic & Medicinal Chemistry Letters, Vol. 12, No. 8, 22.04.2002, p. 1159-1162.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Strømgaard, K, Mellor, IR, Andersen, K, Neagoe, I, Pluteanu, F, Usherwood, PNR, Krogsgaard-Larsen, P & Jaroszewski, JW 2002, 'Solid-phase synthesis and pharmacological evaluation of analogues of PhTX-12-A potent and selective nicotinic acetylcholine receptor antagonist', Bioorganic & Medicinal Chemistry Letters, vol. 12, no. 8, pp. 1159-1162.

APA

Strømgaard, K., Mellor, I. R., Andersen, K., Neagoe, I., Pluteanu, F., Usherwood, P. N. R., ... Jaroszewski, J. W. (2002). Solid-phase synthesis and pharmacological evaluation of analogues of PhTX-12-A potent and selective nicotinic acetylcholine receptor antagonist. Bioorganic & Medicinal Chemistry Letters, 12(8), 1159-1162.

Vancouver

Strømgaard K, Mellor IR, Andersen K, Neagoe I, Pluteanu F, Usherwood PNR et al. Solid-phase synthesis and pharmacological evaluation of analogues of PhTX-12-A potent and selective nicotinic acetylcholine receptor antagonist. Bioorganic & Medicinal Chemistry Letters. 2002 Apr 22;12(8):1159-1162.

Author

Strømgaard, Kristian ; Mellor, Ian R ; Andersen, Kim ; Neagoe, Ioana ; Pluteanu, Florentina ; Usherwood, Peter N R ; Krogsgaard-Larsen, Povl ; Jaroszewski, Jerzy W. / Solid-phase synthesis and pharmacological evaluation of analogues of PhTX-12-A potent and selective nicotinic acetylcholine receptor antagonist. In: Bioorganic & Medicinal Chemistry Letters. 2002 ; Vol. 12, No. 8. pp. 1159-1162.

Bibtex

@article{bde62c7d4aab4bd6839d84bb4e595d2c,
title = "Solid-phase synthesis and pharmacological evaluation of analogues of PhTX-12-A potent and selective nicotinic acetylcholine receptor antagonist",
abstract = "Philanthotoxin-12 (PhTX-12) is a novel potent and selective, noncompetitive antagonist of nicotinic acetylcholine receptors (nAChRs). Homologues of PhTX-12 with 7-11 methylene groups between the primary amino group and the aromatic head-group were synthesized using solid-phase methodology. In vitro electrophysiological studies of nAChR demonstrated that decreasing the number of methylene groups from 12 to 11 significantly increased potency. Antagonism by PhTX-11, like that of PhTX-12, was only weakly voltage-dependent. When the methylene spacer was reduced further, antagonism was decreased below that of PhTX-12, and in some cases potentiation of ACh responses by up to 60{\%} was observed.",
keywords = "Chromatography, High Pressure Liquid, Drug Evaluation, Preclinical, Mass Spectrometry, Nicotinic Antagonists, Patch-Clamp Techniques, Polyamines, Tyrosine",
author = "Kristian Str{\o}mgaard and Mellor, {Ian R} and Kim Andersen and Ioana Neagoe and Florentina Pluteanu and Usherwood, {Peter N R} and Povl Krogsgaard-Larsen and Jaroszewski, {Jerzy W}",
year = "2002",
month = "4",
day = "22",
language = "English",
volume = "12",
pages = "1159--1162",
journal = "Bioorganic & Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Pergamon Press",
number = "8",

}

RIS

TY - JOUR

T1 - Solid-phase synthesis and pharmacological evaluation of analogues of PhTX-12-A potent and selective nicotinic acetylcholine receptor antagonist

AU - Strømgaard, Kristian

AU - Mellor, Ian R

AU - Andersen, Kim

AU - Neagoe, Ioana

AU - Pluteanu, Florentina

AU - Usherwood, Peter N R

AU - Krogsgaard-Larsen, Povl

AU - Jaroszewski, Jerzy W

PY - 2002/4/22

Y1 - 2002/4/22

N2 - Philanthotoxin-12 (PhTX-12) is a novel potent and selective, noncompetitive antagonist of nicotinic acetylcholine receptors (nAChRs). Homologues of PhTX-12 with 7-11 methylene groups between the primary amino group and the aromatic head-group were synthesized using solid-phase methodology. In vitro electrophysiological studies of nAChR demonstrated that decreasing the number of methylene groups from 12 to 11 significantly increased potency. Antagonism by PhTX-11, like that of PhTX-12, was only weakly voltage-dependent. When the methylene spacer was reduced further, antagonism was decreased below that of PhTX-12, and in some cases potentiation of ACh responses by up to 60% was observed.

AB - Philanthotoxin-12 (PhTX-12) is a novel potent and selective, noncompetitive antagonist of nicotinic acetylcholine receptors (nAChRs). Homologues of PhTX-12 with 7-11 methylene groups between the primary amino group and the aromatic head-group were synthesized using solid-phase methodology. In vitro electrophysiological studies of nAChR demonstrated that decreasing the number of methylene groups from 12 to 11 significantly increased potency. Antagonism by PhTX-11, like that of PhTX-12, was only weakly voltage-dependent. When the methylene spacer was reduced further, antagonism was decreased below that of PhTX-12, and in some cases potentiation of ACh responses by up to 60% was observed.

KW - Chromatography, High Pressure Liquid

KW - Drug Evaluation, Preclinical

KW - Mass Spectrometry

KW - Nicotinic Antagonists

KW - Patch-Clamp Techniques

KW - Polyamines

KW - Tyrosine

M3 - Journal article

VL - 12

SP - 1159

EP - 1162

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

SN - 0960-894X

IS - 8

ER -

ID: 45823749