7511-14-0Relevant academic research and scientific papers
INDOLE AND AZAINDOLE HALOALLYLAMINE DERIVATIVE INHIBITORS OF LYSYL OXIDASES AND USES THEREOF
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Paragraph 0355, (2017/09/05)
The present invention relates to novel compounds which are capable of inhibiting certain amine oxidase enzymes. These compounds are useful for treatment of a variety of indications, e.g., fibrosis, cancer and/or angiogenesis in human subjects as well as i
Substrate-Controlled Transformation of Azobenzenes to Indazoles and Indoles via Rh(III)-Catalysis
Cai, Shangjun,Lin, Songyun,Yi, Xiangli,Xi, Chanjuan
, p. 512 - 520 (2017/04/26)
Rh(III)-catalyzed substrate-controlled transformation of azobenzenes to indazoles and 2-acyl (NH) indoles is achieved via C-H functionalization. Generally, good functional groups tolerance, satisfying yields, and excellent regio-selectivity are achieved in this reaction. Mechanistically, the reaction with acrylates undergoes β-hydride elimination, while the reaction with vinyl ketones or acrylamides undergoes nucleophilic addition. Copper acetate was supposed to play different roles in the β-hydride elimination to furnish indazoles and nucleophilic addition of C-Rh bond to deliver 2-acyl (NH) indoles.
Discovery of a Novel Class of Negative Allosteric Modulator of the Dopamine D2 Receptor Through Fragmentation of a Bitopic Ligand
Mistry, Shailesh N.,Shonberg, Jeremy,Draper-Joyce, Christopher J.,Klein Herenbrink, Carmen,Michino, Mayako,Shi, Lei,Christopoulos, Arthur,Capuano, Ben,Scammells, Peter J.,Lane, J. Robert
, p. 6819 - 6843 (2015/09/22)
Recently, we have demonstrated that N-((trans)-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652) (1) adopts a bitopic pose at one protomer of a dopamine D2 receptor (D2R) dimer to negatively modulate the binding of dopamine at the other protomer. The 1H-indole-2-carboxamide moiety of 1 extends into a secondary pocket between the extracellular ends of TM2 and TM7 within the D2R protomer. To target this putative allosteric site, we generated and characterized fragments that include and extend from the 1H-indole-2-carboxamide moiety of 1. N-Isopropyl-1H-indole-2-carboxamide (3) displayed allosteric pharmacology and sensitivity to mutations of the same residues at the top of TM2 as was observed for 1. Using 3 as an "allosteric lead", we designed and synthesized an extensive fragment library to generate novel SAR and identify N-butyl-1H-indole-2-carboxamide (11d), which displayed both increased negative cooperativity and affinity for the D2R. These data illustrate that fragmentation of extended compounds can expose fragments with purely allosteric pharmacology.
Synthesis and evaluation of N1-alkylindole-3-ylalkylammonium compounds as nicotinic acetylcholine receptor ligands
Perez, Edwin G.,Cassels, Bruce K.,Eibl, Christoph,Guendisch, Daniela
supporting information; experimental part, p. 3719 - 3727 (2012/08/08)
In this study thirty-three novel indole derivatives were designed and synthesized based on the structure of deformylflustrabromine B (1), a metabolite isolated from the marine bryozoan Flustra foliacea L. The syntheses were carried out using standard methodologies and in good yields. The molecules were tested for their affinities for the α4β2*, α3β 4*, α7* and (α1)2β1γδ nicotinic acetylcholine receptor (nAChR) subtypes. Binding assays showed that, among these ligands, compound 7c exhibited the highest affinity with K i = 136.1, 93.9 and 862.4 nM for the α4β2*, α3β4*, and α7* nAChRs subtypes, respectively. These results indicated that the indole core might be a useful scaffold for the development of new potent and selective nAChR ligands.
Synthesis and characterization of the aqueous solution chemistry of the food-derived carcinogen model N-acetoxy-N-(1-methyl-5H-pyrido[4,5-b]indol-3-yl)acetamide and its N-pivaloyloxy analogue
Rajagopal, Sridharan,Brooks, Michael E.,Nguyen, Thach-Mien,Novak, Michael
, p. 8003 - 8010 (2007/10/03)
We report the synthesis of N-acetoxy-N-(1-methyl-5H-pyrido[4,5-b]indol-3-yl)acetamide, 7, its N-pivaloyloxy analogue, 9, and improved synthesis of indole-2-acetonitrile, 3 (70% in five steps from indole-2-carboxylic acid), the carcinogenic amine Trp-P-2, 4 (40% from 3), and the nitro compound, 5 (40% from 4 by oxidation with H2O2 using Mo(CO)6 catalyst). In aqueous solution at neutral pH, 7 primarily undergoes C-O bond cleavage to yield the hydroxamic acid, 8, but under the same conditions the sterically hindered 9 decomposes predominately by N-O bond cleavage with a pH independent rate constant that is 7.5-fold smaller than that for 7. In the pH range 0.5-7.0 three different processes for the decomposition of 9 were detected by kinetics. Only the process that dominates at neutral pH generates a nitrenium species that can be trapped by N3-.
Nucleophilic Addition of 2-Indolylacyl Anion Equivalents to N-Alkylpyridinium Salts
Bennasar, M.-Lluisa,Zulaica, Ester,Bosch, Joan
, p. 2835 - 2841 (2007/10/02)
The reactions of the anions derived from dithioacetals 1-3 and α-amino nitriles 4 toward pyridinium salts 5 are studied.Depending on the nucleophile used, 2-(dihydropyridylmethyl)indoles 6 and 7, which can be cyclized to tetracyclic methanoazocinindole systems 10 and 11, respectively, or 2-substituted 3-(dihydropyridyl)indoles 8 and 9 are formed.
The N-tert-butylcarbamoyl directed metalation group for the regiospecific synthesis of 2-substituted pyrroles and indoles
Gharpure,Stoller,Bellamy,Firnau,Snieckus
, p. 1079 - 1082 (2007/10/02)
The N-tert-butylcarbamoyl serves as a useful, readily removable (LiOH/MeOH/THF) new directed metalation group for the synthesis of 2-substituted pyrroles and indoles.
