Design, synthesis and biological activity of novel dimethyl-{2-[6-substituted-indol-1-yl]-ethyl}-amine as potent, selective, and orally-Bioavailable 5-HT 1D agonists

Isaac, Methvin; Slassi, Malik; Tao, Xin; Arora, Jalaj; O’Brien, Anne; Edwards, Louise; MacLean, Neil; Wilson, Julie M.; Demschyshyn, Lidia; Labrie, Phillipe; Naismith, Angela; Maddaford, Shawn P.; Papac, Damon I.; Harrison, Shuree; Wang, Hua; Draper, Stan; Tehim, Ashok

doi:10.1016/j.bmcl.2003.09.025

Cited by 7 publications

(2 citation statements)

References 11 publications

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“…NL1 is synthesized from 6-bromoindole in four steps by attaching the short peptide-like chain to the indole nitrogen atom (Figure 3). First, 6-bromoindole 4 is alkylated with bromoacetic ester and then hydrolyzed to yield 2-(6-bromo-1H-indol-1-yl) acetic acid 6 [9,10]. The subsequent reaction of the latter with glycine ester hydrochloride under peptide synthesis conditions creates an amide bond [11].…”

Section: Synthesis Of Nl1 Inhibitormentioning

confidence: 99%

Synthesis of the Indole-Based Inhibitors of Bacterial Cystathionine γ-Lyase NL1-NL3

et al. 2023

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Bacterial cystathionine γ-lyase (bCSE) is the main producer of H2S in pathogenic bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, etc. The suppression of bCSE activity considerably enhances the sensitivity of bacteria to antibiotics. Convenient methods for the efficient synthesis of gram quantities of two selective indole-based bCSE inhibitors, namely (2-(6-bromo-1H-indol-1-yl)acetyl)glycine (NL1), 5-((6-bromo-1H-indol-1-yl)methyl)- 2-methylfuran-3-carboxylic acid (NL2), as well as a synthetic method for preparation 3-((6-(7-chlorobenzo[b]thiophen-2-yl)-1H-indol-1-yl)methyl)- 1H-pyrazole-5-carboxylic acid (NL3), have been developed. The syntheses are based on the use of 6-bromoindole as the main building block for all three inhibitors (NL1, NL2, and NL3), and the designed residues are assembled at the nitrogen atom of the 6-bromoindole core or by the substitution of the bromine atom in the case of NL3 using Pd-catalyzed cross-coupling. The developed and refined synthetic methods would be significant for the further biological screening of NL-series bCSE inhibitors and their derivatives.

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Section: Synthesis Of Nl1 Inhibitormentioning

confidence: 99%

Synthesis of the Indole-Based Inhibitors of Bacterial Cystathionine γ-Lyase NL1-NL3

et al. 2023

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“…The model substrates 5-bromo-1-(triisopropylsilyl)-1H-indole (2a) and 1-(triisopropylsilyl)-1H-indole (4) were prepared according to literature procedures [18] [19]. The bromoindoles 2b [20] [21], 2c -d, 2e [18], 2h -j, 2k [22], and 2l were prepared by alkylation of the commercially available bromoindoles 1a -d using an appropriate alkylating agent and NaH as base. The reactions were performed at ambient temperature in 1,2-dimethoxyethane (DME) containing 10% of DMSO (Scheme 1).…”

mentioning

confidence: 99%

Convenient Synthesis of 1H‐Indol‐1‐yl Boronates via Palladium(0)‐Catalyzed Borylation of Bromo‐1H‐indoles with ‘Pinacolborane’

Stadlwieser

Dambaur

2006

Helvetica Chimica Acta

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An atom-economic Pd 0 -catalyzed synthesis of a series of pinacol-type indolylboronates 3 from the corresponding bromoindole substrates 2 and pinacolborane (pinBH) as borylating agent was elaborated. The optimal catalyst system consisted of a 1 : 2 mixture of [Pd(OAc) 2 ] and the ortho-substituted biphenylphosphine ligand L-3 (Scheme 4, Table). Our synthetic protocol was applied to the fast, preparative-scale synthesis of 1-substituted indolylboronates 3a -h in the presence of different functional groups, and at a catalyst load of only 1 mol-% of Pd.

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