64507-05-7Relevant academic research and scientific papers
Enantiopure Benzofuran-2-carboxamides of 1-Aryltetrahydro-β-carbolines Are Potent Antimalarials In Vitro
Almolhim, Hanan,Bremers, Emily K.,Butler, Joshua H.,Butschek, Grant J.,Carlier, Paul R.,Cassera, Maria B.,Ding, Sha,Merino, Emilio F.,Rizopoulos, Zaira,Slebodnick, Carla,Totrov, Maxim
supporting information, p. 371 - 376 (2022/03/15)
The tetrahydro-β-carboline scaffold has proven fertile ground for the discovery of antimalarial agents (e.g., MMV008138 (1) and cipargamin (2)). Similarity searching of a publicly disclosed collection of antimalarial hits for molecules resembling 1 drew our attention to N2-acyl tetrahydro-β-carboline GNF-Pf-5009 ((±)-3b). Compound purchase, “analog by catalog”, and independent synthesis of hits indicated the benzofuran-2-yl amide portion was required for in vitro efficacy against P. falciparum. Preparation of pure enantiomers demonstrated the pharmacological superiority of (R)-3b. Synthesis and evaluation of D- and F-ring substitution variants and benzofuran isosteres indicated a clear structure-activity relationship. Ultimately (R)-3b was tested in Plasmodium berghei-infected mice; unfavorable physicochemical properties may be responsible for the lack of oral efficacy.
Synthesis of Indolo[2,3- c]quinolin-6(7 H)-ones and Antimalarial Isoneocryptolepine. Computational Study on the Pd-Catalyzed Intramolecular C-H Arylation
Szabó, Tímea,Papp, Marcell,Németh, Dóra Rita,Dancsó, András,Volk, Balázs,Milen, Mátyás
supporting information, p. 128 - 145 (2020/12/22)
The synthesis of variously substituted indolo[2,3-c]quinolin-6(7H)-ones was developed via Pd-catalyzed intramolecular C-H arylation. This method highlights a strategy for preparing indoloquinoline precursors bearing versatile functional groups and provide
Indole substituted amide compound, and preparation method and application thereof
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Paragraph 0069-0073, (2021/10/11)
The invention relates to an indole substituted amide compound, and a preparation method and application thereof. The chemical structural general formula of the indole substituted amide compound is shown as a formula VI or VII. The invention discloses a structural general formula, a synthetic route and the preparation method of the indole substituted amide compound and the application of the indole substituted amide compound as a bactericide, and also relates to application of the compound in preventing and controlling agricultural, forestry and gardening diseases in combination with agriculturally acceptable auxiliaries or synergists and commercial bactericides.
Drug Design and Synthesis of First in Class PDZ1 Targeting NHERF1 Inhibitors as Anticancer Agents
Coluccia, Antonio,La Regina, Giuseppe,Naccarato, Valentina,Nalli, Marianna,Orlando, Viviana,Biagioni, Stefano,De Angelis, Maria Laura,Baiocchi, Marta,Gautier, Candice,Gianni, Stefano,Di Pastena, Fiorella,Di Magno, Laura,Canettieri, Gianluca,Coluccia, Addolorata Maria Luce,Silvestri, Romano
supporting information, p. 499 - 503 (2019/04/25)
Targeted approaches aiming at modulating NHERF1 activity, rather than its overall expression, would be preferred to preserve the normal functions of this versatile protein. We focused our attention on the NHERF1/PDZ1 domain that governs its membrane recruitment/displacement through a transient phosphorylation switch. We herein report the design and synthesis of novel NHERF1 PDZ1 domain inhibitors. These compounds have potential therapeutic value when used in combination with antagonists of β-catenin to augment apoptotic death of colorectal cancer cells refractory to currently available Wnt/β-catenin-targeted agents.
Iron(III)-Catalyzed (4 + 2)-Cycloannulation of 2-Hydroxy Ketoxime Ethers with Indol-2-ylamides: Synthesis of Indole-Fused 2-Piperidinones
Schlegel, Marcel,Schneider, Christoph
, p. 5886 - 5892 (2019/04/25)
A highly regio- and diastereoselective (4 + 2)-cycloannulation process of indanone-derived 2-hydroxy ketoxime ethers with 1,4-bisnucleophilic indol-2-ylamides has been developed. In the presence of 5 mol % FeCl3, densely functionalized 2-piperidinones containing two new σ-bonds and two vicinal quaternary stereogenic centers were formed under mild reaction conditions in a one-pot operation. Moreover, most of the products directly precipitated out of the solution and were isolated by simple filtration without purification by column chromatography.
Novel inhibitors of Staphylococcus aureus RnpA that synergize with mupirocin
Lounsbury, Nicole,Eidem, Tess,Colquhoun, Jennifer,Mateo, George,Abou-Gharbia, Magid,Dunman, Paul M.,Childers, Wayne E.
supporting information, p. 1127 - 1131 (2018/02/21)
We recently discovered RnpA as a promising new drug discovery target for methicillin-resistant S. aureus (MRSA). RnpA is an essential protein that is thought to perform two required cellular processes. As part of the RNA degrasome Rnpa mediates RNA degradation. In combination with rnpB it forms RNase P haloenzymes which are required for tRNA maturation. A high throughput screen identified RNPA2000 as an inhibitor of both RnpA-associated activities that displayed antibacterial activity against clinically relevant strains of S. aureus, including MRSA. Structure-activity studies aimed at improving potency and replacing the potentially metabotoxic furan moiety led to the identification of a number of more potent analogs. Many of these new analogs possessed overt cellular toxicity that precluded their use as antibiotics but two derivatives, including compound 5o, displayed an impressive synergy with mupirocin, an antibiotic used for decolonizing MSRA whose effectiveness has recently been jeopardized by bacterial resistance. Based on our results, compounds like 5o may ultimately find use in resensitizing mupirocin-resistant bacteria to mupirocin.
Effect of H4R antagonist N-(2-aminoethyl)-5-chloro-1H-indol-2-carboxamides and 5-chloro-2-(piperazin-1-ylmethyl)-1H-benzimidazole on histamine and 4-methylhistamine-induced mast cell response
Nagarajan, Gomathi,Mariappanadar, Vairamani,Tamizh, Muthu,Kaliappan, Ilango,Elden, Berla Thangam
, p. 304 - 313 (2017/03/30)
Context: The histamine plays a decisive role in acute and chronic inflammatory responses and is regulated through its four types of distinct receptors designated from H1 to H4. Recently histamine 4 receptor (H4R) antagonists have been reported to possess various pharmacological effects against various allergic diseases. Objective: To investigate the inhibitory effect of N-(2-aminoethyl)-5-chloro-1H-indol-2-carboxamide (Compound A) and 5-chloro-2-(piperazin-1-ylmethyl)-1H-benzimidazole (Compound L) on H4R-mediated calcium mobilization, cytokine IL-13 production, ERK1/2, Akt and NF-κB activation in human mastocytoma cells-1 (HMC-1). Materials and methods: Compounds A and L were synthesized chemically and their inhibitory effect on intracellular calcium release was analyzed by Fluo-4 calcium assay, cytokine measurement through ELISA and activation of signaling molecules by western blot. Results: Pre-treatment with compounds A and L significantly reduced the H4R-mediated intracellular calcium release. Histamine and 4-methylhistamine (4-MH) induced Th2 cytokine IL-13 production in HMC-1 cells, was inhibited by compound A (77.61%, 74.25% at 1 μM concentration) and compound L (79.63%, 81.70% at 1 μM concentration). Furthermore, histamine induced the phosphorylation of ERK1/2, Akt and NF-κB was suppressed by compounds A and L at varying levels, ERK1/2 (88%, 86%), Akt (88%, 89%) and NF-κB (89%, 87%) in HMC-1 cells. Discussion and conclusions: Taken together these data demonstrate that compound A and compound L may block H4R-mediated downstream signaling events.
Synthesis of heteroarylogous 1H-indole-3-carboxamidines via a three-component interrupted Ugi reaction
La Spisa, Fabio,Meneghetti, Fiorella,Pozzi, Beatrice,Tron, Gian Cesare
, p. 489 - 496 (2015/02/19)
A novel one-pot multicomponent synthesis of heteroarylogous 1H-indole-3-carboxamidines starting from readily available N-alkyl-N-(1H-indol-2-ylmethyl)amines, isocyanides, and carbonyl compounds is reported. The strategy exploits the ability of the indole nucleus to interrupt the classical Ugi reaction, by intercepting the nascent nitrilium ion.
Antihyperlipidemic properties of novel N-(benzoylphenyl)-5-substituted-1H- indole-2-carboxamides in Triton WR-1339-induced hyperlipidemic rats
Al-Hiari, Yusuf,Shattat, Ghassan,Al-Qirim, Tariq,El-Huneidi, Waseem,Sheikha, Ghassan Abu,Hikmat, Suhair
experimental part, p. 8292 - 8304 (2011/12/14)
In the search for new potential antihyperlipidemic agents, the present study focuses on the synthesis of novel N-(benzoylphenyl)-5-substituted-1H- indole-2-carboxamides (compounds 8-12, 15, 16, 18) and investigating their antihyperlipidemic activity using
Indol-2-yl ethanones as novel indoleamine 2,3-dioxygenase (IDO) inhibitors
Dolusic, Eduard,Larrieu, Pierre,Blanc, Sebastien,Sapunaric, Frederic,Norberg, Bernadette,Moineaux, Laurence,Colette, Delphine,Stroobant, Vincent,Pilotte, Luc,Colau, Didier,Ferain, Thierry,Fraser, Graeme,Galeni, Moreno,Frre, Jean-Marie,Masereel, Bernard,Van Den Eynde, Benoit,Wouters, Johan,Frederick, Raphael
experimental part, p. 1550 - 1561 (2011/03/22)
Indoleamine 2,3-dioxygenase (IDO) is a heme dioxygenase which has been shown to be involved in the pathological immune escape of diseases such as cancer. The synthesis and structure-activity relationships (SAR) of a novel series of IDO inhibitors based on the indol-2-yl ethanone scaffold is described. In vitro and in vivo biological activities have been evaluated, leading to compounds with IC50 values in the micromolar range in both tests. Introduction of small substituents in the 5- and 6-positions of the indole ring, indole N-methylation and variations of the aromatic side chain are all well tolerated. An iron coordinating group on the linker is a prerequisite for biological activity, thus corroborating the virtual screening results.
