2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• significantly lower potency of 32. Ulotaront (33, SEP-363856) [38] is a phase-3 clinical lead for the treatment of schizophrenia, displaying TAAR1 (trace-amine-associated receptor 1) [39] and 5-HT1A agonism as mode of action, lacking dopamine D2 and 5-HT2A antagonism. SAR exploration of the ulotaront family was

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• associated biological activities and relevance to the naturally occurring alkaloids [1], 1,4-dihydro-3(2H)-isoquinolones (1,4-DHIQs) undoubtedly represent a privileged scaffold [2] for drug design considering such diversely bioactive compounds documented in the literature as ligand for serotonin 5-HT1A

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• -known biologically active analogs (Scheme 5) [3]. Pd-catalyzed reactions were effected on bromotriazolochromene 5e. The piperazin-1-ylchromenes have been identified to be potent inhibitors at the 5-HT1A receptor and at the 5-HT transporter [45][46]. Thus, Buchwald–Hartwig amination of 1-phenylpiperazine

Microfluidic radiosynthesis of [¹⁸F]FEMPT, a high affinity PET radiotracer for imaging serotonin receptors

• Thomas Lee Collier,
• Steven H. Liang,
• J. John Mann,
• Neil Vasdev and
• J. S. Dileep Kumar

Beilstein J. Org. Chem. 2017, 13, 2922–2927, doi:10.3762/bjoc.13.285

• -18; 5-HT1A; microfluidics; PET; Introduction The development of serotonin 1A receptor (5-HT1AR) agonist radiotracers for applications in molecular imaging with positron emission tomography (PET) has been avidly sought over the past two decades, albeit with limited success. The current status of

• supersensitivity. Significant research has been directed at the differences between agonist and antagonist binding to 5-HT1A receptors in Alzheimer's disease [10] and this interest has led to the development of a high-resolution in vivo atlas for four of the human brain's serotonin receptors and transporters [11

Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• unit and its analogues are found in several pharmacologically active derivatives such as the selective 5-HT1A agonist SUN 8399 (1) [1], the neuroprotective piclozotan (2) [2][3], the antihistaminic rocastine (3) [4][5], and the antihelmintic 4 [6] (Figure 1). We report herein the preparation of two

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• of the 3,5-disubstituted pyridine core of the antidyskinetic drug, 5-HT1A receptor agonist, dopamine D2 receptor ligand sarizotan 19 (Scheme 6). The pyridinyl-chroman sarizotan (also called EMD-128130) was originally developed by Merck KGaA in the late 1990’s [44] and was found to be a dual selective

• 5-HT1A receptor agonist and D2 receptor antagonist displaying a strong efficacy in the reduction of dyskinesia resulting from long-term antiparkinsonian treatment with levodopa [45][46][47][48][49][50]. Although its development was stopped by Merck KGaA in 2006 after analysis of data from Phase III

• starting N-allyl-ynamides. Intramolecular carbolithiation of N-allyl-ynamides to 1,4-dihydropyridines and pyridines. 2,3-Disubstituted pyridines by trapping of the intermediate metallated 1,4-dihydropyridine. Formal synthesis of the anti-dyskinesia agent, 5-HT1A receptor agonist, dopamine D2 receptor

trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT₂ receptor family

• Adam Pigott,
• Stewart Frescas,
• John D. McCorvy,
• Xi-Ping Huang,
• Bryan L. Roth and
• David E. Nichols

Beilstein J. Org. Chem. 2012, 8, 1705–1709, doi:10.3762/bjoc.8.194

• , however, were higher than for 1a. In particular, the introduction of the cyclopropane appears to increase significantly affinities at the 5-HT1A, 5HT1B, and 5-HT1D receptors. In that regard, although (−)-4 and (−)-5 have affinities at the 5-HT2A receptor somewhat higher than 1a, their selectivity over the

• 5-HT1A receptor is less than 100-fold. As shown in Table 1, both 4 and 5 are extremely potent ligands in vitro. Furthermore, as anticipated, it was the (−)-enantiomers that proved to have highest affinity. We included (+)-5 in Table 3 simply to illustrate the difference in affinity between the two

• would also need to be mindful that their selectivity for 5-HT2A over 5-HT1A is only about 70-fold. The most efficient approach appears to be the synthesis of the chiral cyclopropane carboxylic acids, followed by derivatization at the 4-position. This approach would be most appealing if a chiral

Marilones A–C, phthalides from the sponge-derived fungus Stachylidium sp.

• Celso Almeida,
• Stefan Kehraus,
• Miguel Prudêncio and
• Gabriele M. König

Beilstein J. Org. Chem. 2011, 7, 1636–1642, doi:10.3762/bjoc.7.192

• level against 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT5A, 5-HT6, 5-HT7, α1A, α1B, α1D, α2A, α2B, α2C, β1, β2, β3, BZP Rat Brain Site, D1, D2, D3, D4, D5, DAT, δ, κ, μ, GABAA, H1, H2, H3, H4, M1, M2, M3, M4, M5, NET, SERT, σ1, σ2) are fully described [39]. Secondary metabolites