Synthesis of UB-165: A novel nicotinic ligand and anatoxin-a/epibatidine hybrid

Wright, Emma; Gallagher, Timothy; Sharples, Christopher G. V.; Wonnacott, Susan

doi:10.1016/s0960-894x(97)10090-7

Cited by 64 publications

(40 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a follow-up to their initial studies, Badio and coworkers [166] synthesized the racemate isoxazole epibatidine derivative [c261] which has a ten-fold lower affinity than the parent. Wright and coworkers [167] [171]. This analog is of significant interest because it has high affinity despite the presence of an aromatic nitrogen isosteric to the 2-pyridyl carbon-a substitution that is known to be deleterious in a number of other nAChR ligand families [see for example the series c223-247].…”

Section: Ii4b Class B: Cyclic Hba/π Acyclic Cationmentioning

confidence: 99%

Exploring the Nature of Molecular Recognition in Nicotinic Acetylcholine Receptors

Schmitt

2000

CMC

View full text Add to dashboard Cite

Nicotinic acetylcholine receptors (nAChRs) are the subject of ever increasing interest because of their presumed involvement in the etiology of numerous clinical disorders. Unfortunately, the absence of atomic-level structural data, as well as the pharmacological complexity of these receptors leaves many fundamental questions unanswered. An understanding of how ligands interact with the receptor and, in-turn, how these interactions lead to pharmacological effect is vital in the advancement of nAChR-based therapeutics. We will first explore physico-chemical themes that are evidenced to be of particular importance in nAChR molecular recognition; these are- pi-cation interaction, conformational entropy and stereochemistry. The second objective of this review is an interpretive encapsulation of the extensive and disparate body of structure-activity data that now exists for nAChRs. Finally, this review will advocate a re-investigation of distance geometry based methods as well as the need for additional approaches in nicotinic receptor pharmacophore generation.

show abstract

Section: Ii4b Class B: Cyclic Hba/π Acyclic Cationmentioning

confidence: 99%

Exploring the Nature of Molecular Recognition in Nicotinic Acetylcholine Receptors

Schmitt

2000

CMC

View full text Add to dashboard Cite

show abstract

“…We found especially interesting high analgesic activity of homoepibatidine [3] (2) and unsaturated anatoxin-epibatidine hybrid [4] (3) as well as diazabicyclo[3.2.1]octane derivative [5] DBO-83 (4). The corresponding N-methyl derivatives, when described and tested, are generally equally active while bulkier N-substituents caused substantial loss of activity.…”

Section: Introductionmentioning

confidence: 88%

Synthesis, Analgesic Activity, and Binding Properties of Some Epibatidine Analogs with a Tropine Skeleton

Rádl

Hafner

Budeaínsky

et al. 2000

Arch. Pharm. Pharm. Med. Chem.

View full text Add to dashboard Cite

“…Affinity values (K i , nanomolar) are based on inhibition of ligand binding to nicotinic (α 4 β 2 /α 3 β 4 * /α 7 ) receptors. Binding and/or functional data has been reported for epiboxidine (Badio et al, 1997b); homoepiboxidine (Fitch et al, 2004); homoepibatidine (Cox et al, 2001;Malpass et al, 2001;Spang et al, 2000;Xu et al, 1996); mesohomoepibatidine (Olivo et al, 1999); dehydro-analog (Rádl et al, 2000); oxadiazole analog (Fitch et al, 2004); bishomoepibatidine ; isohomoepibatidine (Zhang et al, 1997); CMI 934 (Ellis et al, 1999); UB-165 (Sharples et al, 2002;Wright et al, 1997) and pyrimidine analogs (Seerden et al, 1998). receptors primarily with influx of sodium-22 or with efflux of rubidium-86 in cultured cells. (4) Neurotransmitter release elicited by nicotinic agonists has been primarily studied for release of acetylcholine or catecholamines with brain synaptosomes or slices (see Grady et al, 2001 and references therein).…”

Section: Figmentioning

confidence: 99%

“…13, as exemplified by U-165 (Wright et al, 1997;Sharples et al, 2002;Karig et al, 2003;Sutherland et al, 2003). The laevorotatory enantiomer (−)-U-165 had a 14-fold higher affinity for α 4 β 2 receptors than the dextro-rotatory enantiomer (+)-U-165.…”

Section: Epibatidine-based Nicotinic Agonistsmentioning

confidence: 99%

Nicotinic Agonists, Antagonists, and Modulators From Natural Sources

2005

View full text Add to dashboard Cite

1. Acetylcholine receptors were initially defined as nicotinic or muscarinic, based on selective activation by two natural products, nicotine and muscarine. Several further nicotinic agonists have been discovered from natural sources, including cytisine, anatoxin, ferruginine, anabaseine, epibatidine, and epiquinamide. These have provided lead structures for the design of a wide range of synthetic agents. 2. Natural sources have also provided competitive nicotinic antagonists, such as the Erythrina alkaloids, the tubocurarines, and methyllycaconitine. Noncompetitive antagonists, such as the histrionicotoxins, various izidines, decahydroquinolines, spiropyrrolizidine oximes, pseudophrynamines, ibogaine, strychnine, cocaine, and sparteine have come from natural sources. Finally, galanthamine, codeine, and ivermectin represent positive modulators of nicotinic function, derived from natural sources. 3. Clearly, research on acetylcholine receptors and functions has been dependent on key natural products and the synthetic agents that they inspired.

show abstract

Synthesis of UB-165: A novel nicotinic ligand and anatoxin-a/epibatidine hybrid

Cited by 64 publications

References 18 publications

Exploring the Nature of Molecular Recognition in Nicotinic Acetylcholine Receptors

Exploring the Nature of Molecular Recognition in Nicotinic Acetylcholine Receptors

Synthesis, Analgesic Activity, and Binding Properties of Some Epibatidine Analogs with a Tropine Skeleton

Nicotinic Agonists, Antagonists, and Modulators From Natural Sources

Contact Info

Product

Resources

About