Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• . Keywords: acetylcholine receptors; bidirectional; photoswitchable drug; tetrafluoroazobenzene; visible light; Introduction Starting in 1937, azobenzenes (ABs) have attracted much attention because they undergo a photoreversible chemical transformation of the thermodynamically favored trans configuration

• regular AB-based photoswitch called "MAHoCh" [16]. The MAHoCh probe was originally designed [16] to activate nicotinic acetylcholine receptors in vivo. However, it was found that the trimethylammonium (TA) head group blocked acetylcholine binding when the photoprobe was cross-linked to the channel near

• the neurotransmitter binding site, via a (still) mysterious mechanism [15][16]. Normally, TA-based drugs can activate nicotinic acetylcholine receptors, as shown, for example, by Trauner and co-workers [17] (azo-choline, Scheme 1). Here we explore the effects of addition of the tetrafluoro motif onto

Azologization of serotonin 5-HT₃ receptor antagonists

• Karin Rustler,
• Galyna Maleeva,
• Piotr Bregestovski and
• Burkhard König

Beilstein J. Org. Chem. 2019, 15, 780–788, doi:10.3762/bjoc.15.74

• nicotinic acetylcholine receptors (nAChRs), γ-aminobutyric acid type A receptors (GABAARs), and glycine receptors (GlyRs). To date, five subunits of the 5-HT3 receptor are identified (5-HT3A–5-HT3E) [21]. Functional receptors are either constructed as 5-HT3A homopentamers or as heteropentamers containing 5

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• heterocylic amidines (1,4,5,6-tetrahydropyrimidines) display biological activity as anthelmintics used in medical practice (pyrantel, morantel and oxantel) [5][6], nicotinic agonists [7], antidepressants [8] and selective inhibitors of M1 acetylcholine receptors [9][10], among others. Their benzannulated

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• recently envisaged that its substituted C-threofuranose ring could serve as an excellent scaffold to build muscarine analogues [11]. Cholinergic agents targeting muscarinic acetylcholine receptors (mAChRs) have historically served for diverse applications in medicine [12][13] and recently regained interest

A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE

• Tue Heesgaard Jepsen,
• Emil Glibstrup,
• François Crestey,
• Anders A. Jensen and
• Jesper Langgaard Kristensen

Beilstein J. Org. Chem. 2017, 13, 988–994, doi:10.3762/bjoc.13.98

• pharmacological evaluations support the notion that the key pharmacophores of DHβE are located in the A and B rings. Keywords: DhβE; Mizoroki–Heck cross-coupling reaction; 6π-electrocyclization; [6,6]-bicyclic lactone; vinyl halide; Introduction The neuronal nicotinic acetylcholine receptors (nAChRs) have been

Facile synthesis of two diastereomeric indolizidines corresponding to the postulated structure of alkaloid 5,9E- 259B from a Bufonid toad (Melanophryniscus)

• Angela Nelson,
• H. Martin Garraffo,
• Thomas F. Spande,
• John W. Daly and
• Paul J. Stevenson

Beilstein J. Org. Chem. 2008, 4, No. 6, doi:10.1186/1860-5397-4-6

• alkaloids from the natural sources, for the most part the biological properties of these materials have not been fully evaluated. However, synthetic 5,8-disubstituted indolizidine 5,9Z-235B' (Figure 1), has recently been shown to be a potent and selective non-competitive inhibitor of nicotinic acetylcholine

• receptors [3]. Earlier work had reported that indolizidines 5,9Z-203A and 5,9Z-235B' (Figure 1), and other 5,8-disubstituted indolizidines were non-competitive blockers of the ganglionic subtype of nicotinic receptors [4]. For most of the 5,8-disubstituted indolizidines the structures have been assigned by

Flexible synthesis of poison- frog alkaloids of the 5,8-disubstituted indolizidine- class. II: Synthesis of (-)-209B, (-)-231C, (-)-233D, (-)-235B", (-)-221I, and an epimer of 193E and pharmacological effects at neuronal nicotinic acetylcholine receptors

• Soushi Kobayashi,
• Naoki Toyooka,
• Dejun Zhou,
• Hiroshi Tsuneki,
• Tsutomu Wada,
• Toshiyasu Sasaoka,
• Hideki Sakai,
• Hideo Nemoto,
• H. Martin Garraffo,
• Thomas F. Spande and
• John W. Daly

Beilstein J. Org. Chem. 2007, 3, No. 30, doi:10.1186/1860-5397-3-30

• shown to act as noncompetitive blockers at nicotinic acetylcholine receptors but the proposed structures and the biological activities of most of the 5,8-disubstituted indolizidines have not been determined because of limited supplies of the natural products. We have therefore conducted experiments to

• (-)-203A, (-)-205A from 1, and of (-)-219F from 2. Although the biological activity of most of the 5,8-disubstituted indolizidines has not been investigated, certain 5,8-disubstituted indolizidines have been shown to act as noncompetitive blockers of nicotinic acetylcholine receptors. [2][3] Nicotinic

• epimer of 193E). Supporting Information Supporting Information File 62: Experimental details for the synthesis of (-)-209B, (-)-231C, (-)-233D, (-)-235B", (-)-221I, and an epimer of 193E and pharmacological effects at neuronal nicotinic acetylcholine receptors. Experimental data which includes

Flexible synthetic routes to poison- frog alkaloids of the 5,8-disubstituted indolizidine- class I: synthesis of common lactam chiral building blocks and application to the synthesis of (-)-203A, (-)-205A, and (-)-219F

• Naoki Toyooka,
• Dejun Zhou,
• Hideo Nemoto,
• H. Martin Garraffo,
• Thomas F. Spande and
• John W. Daly

Beilstein J. Org. Chem. 2007, 3, No. 29, doi:10.1186/1860-5397-3-29

• nicotinic acetylcholine receptors. Many synthetic strategies for the construction of this nucleus have been reported: however, a flexible route has not been reported to date. Results Synthesis of lactam chiral building blocks for the flexible synthesis of the title alkaloids has been achieved using a

• indolizidines. Furthermore, many of such poison-frog alkaloids show significant activities, for example with nicotinic acetylcholine receptors (nAChRs) of the central nervous system. [3] Our syntheses and then biological evaluations of poison-frog alkaloids, [4][5][6][7][8][9][10] revealed that the 5,8