trans-2-Aryl-N,N-dipropylcyclopropylamines:  Synthesis and Interactions with 5-HT1A Receptors

Vallgårda, Jerk; Appelberg, Ulf; Arvidsson, L.-E.; Stephan, Holger; Svensson, Björn E.; Hacksell, Uli

doi:10.1021/jm9507136

Cited by 30 publications

(11 citation statements)

References 32 publications

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“…These values are consistent with the literature. 43 0, 110.9, 117.3, 119.8, 123.2, 124.3, 129.3, 158.3. These values are consistent with the literature.…”

Section: Methodsmentioning

confidence: 99%

Deprotonative Metalation of Five-Membered Aromatic Heterocycles Using Mixed Lithium−Zinc Species

et al. 2007

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Deprotonation of benzoxazole, benzothiazole, benzo[b]thiophene, benzo[b]furan, N-Boc-protected indole and pyrrole, and N-phenylpyrazole using an in situ mixture of ZnCl(2).TMEDA (0.5 equiv) and lithium 2,2,6,6-tetramethylpiperidide (1.5 equiv) in THF at room temperature is described. The reaction was evidenced by trapping with iodine, regioselectively giving the expected functionalized derivatives in 52-73% yields. A mixture of mono- and disubstituted derivatives was obtained starting from thiazole. Cross-coupling reactions of 2-metalated benzo[b]thiophene and benzo[b]furan with heteroaromatic chlorides proved possible under palladium catalysis. A reaction pathway where the lithium amide and zinc diamide present in solution behave synergically was proposed for the deprotonation reaction, taking account of NMR and DFT studies carried out on the basic mixture.

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“…These values are consistent with the literature. 43 0, 110.9, 117.3, 119.8, 123.2, 124.3, 129.3, 158.3. These values are consistent with the literature.…”

Section: Methodsmentioning

confidence: 99%

Deprotonative Metalation of Five-Membered Aromatic Heterocycles Using Mixed Lithium−Zinc Species

et al. 2007

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“…Based on these findings, Vallgårda et al synthesized N , N ‐di‐n‐propyl‐substituted derivatives of trans ‐2‐arylcyclopropylamine, (±) ‐ 63 , (±) ‐ 64 and (±)‐ 65 , by modification of the aryl ring of (±)‐ 61 (Fig. ).…”

Section: Introductionmentioning

confidence: 99%

An Overview of Phenylcyclopropylamine Derivatives: Biochemical and Biological Significance and Recent Developments

Khan

Suzuki

Miyata

2012

Medicinal Research Reviews

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trans-2-Phencylcyclopropylamine (2-PCPA), a potent, clinically used antidepressant, affects monoamine neurotransmitter levels by inhibiting the main metabolizing enzymes, monoamine oxidases (MAOs). However, the antidepressant action of this compound was not fully explained by its effects on MAOs due to its wide variety of biological effects. 2-PCPA also affects depression-associated pathophysiological pathways, and linked with increased levels of trace amines in brain, upregulation of GABAB receptors (where GABA is gamma amino butyric acid), modulation of phospholipid metabolism, and interference with various cytochrome P450 (CYP) enzymes. Consequently, despite its adverse effects and limited clinical applicability, 2-PCPA has attracted interest as a structural scaffold for the development of mechanism-based inhibitors of various enzymes, including lysine-specific demethylase 1 (LSD1), which is a possible target for cancer chemotherapy. In the recent years, many reports have appeared in the literature based on 2-PCPA scaffold and their potential medicinal implications. This review mainly focuses on the medicinal chemistry aspects including drug design, structure-activity relationships (SAR), biological and biochemical properties, and mechanism of actions of 2-PCPA and its derivatives. Furthermore, we also highlight recent advance in this area and discuss their future applications for beneficial therapeutic effects.

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“…We failed to use the simplest and most logical method for its preparation by cyclopropanation of styrylcyclopropane 4 . The double bond in this compound proved to be surprisingly non‐reactive and 4 did not undergo cyclopropanation, neither under conditions of catalytic or thermal cyclopropanation with diazomethane, nor under Simmons‐Smith cyclopropanation conditions . Therefore, we developed a scheme based on the traditional reaction sequence well proven for DACs: Knoevenagel condensation / Corey‐Chaykovsky cyclopropanation –.…”

Section: Resultsmentioning

confidence: 99%

1,1 ’-Bicyclopropyl-2,2-dicarboxylate and Cyclopropylmethylidenemalonate as Homovinylogs and Vinylogs of Donor-Acceptor Cyclopropanes

et al. 2016

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A new approach was suggested for the development of new carbon-based synthons on donor-acceptor cyclopropane (DAC) basis, that are more complex than the usual cyclopropane ring, while maintaining the principle of separation of donor and acceptor substituents in the molecule. This approach is based on expansion of the reactive cyclopropane ring system in DACs by inserting into the structure the additional reactive CÀC double bond or the second cyclopropane ring between donor and acceptor substituents. Within this approach and applying a set of procedures adopted in cyclopropane chemistry, the new (2-phenylcyclopropyl)methylidenemalonate (3) and related 2 '-phenylbicyclopropyl-1,1-dicarboxylate (2) were synthesized as vinylog and homovinylog of donor-acceptor cyclopropanes. Upon studying their reactivity, focusing on their transformations in the presence of various Lewis acids, the bicyclopropyl skeleton in 2 behaved as a single six-carbon synthon, in which both cyclopropane rings reacted in tandem furnishing various products with opening of the cyclopropane rings. On the other hand, the vinylcyclopropane 3 turned out to be much less reactive towards the same Lewis acids. Mechanistic aspects, further transformations of the ring-opened products and potential synthetic applications of these new reactions in organic synthesis are being discussed as well.

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trans-2-Aryl-N,N-dipropylcyclopropylamines: Synthesis and Interactions with 5-HT_1A Receptors

Cited by 30 publications

References 32 publications

Deprotonative Metalation of Five-Membered Aromatic Heterocycles Using Mixed Lithium−Zinc Species

Deprotonative Metalation of Five-Membered Aromatic Heterocycles Using Mixed Lithium−Zinc Species

An Overview of Phenylcyclopropylamine Derivatives: Biochemical and Biological Significance and Recent Developments

1,1 ’-Bicyclopropyl-2,2-dicarboxylate and Cyclopropylmethylidenemalonate as Homovinylogs and Vinylogs of Donor-Acceptor Cyclopropanes

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