55581-41-4Relevant academic research and scientific papers
Structure-based design and biological evaluation of novel 2-(indol-2-yl) thiazole derivatives as xanthine oxidase inhibitors
Song, Jeong Uk,Jang, Jae Wan,Kim, Tae Hun,Park, Heuisul,Park, Wan Su,Jung, Sang-Hun,Kim, Geun Tae
, p. 950 - 954 (2016/05/24)
Inhibition of xanthine oxidase (XO) has obviously been a central concept for controlling hyperuricemia, which causes serious and painful inflammatory arthritis disease such as gout. We discovered a series of novel 2-(indol-2-yl)thiazole derivatives as XO inhibitors at the level of nanomolar activity. Structure-guided design using molecular modeling program (Accelrys Software program) provided an excellent basis for optimization of 2-(indol-2-yl)thiazole compounds. Structure-activity relationship indicated that hydrophobic alkoxy group (isopropoxy, cyclopentoxy) at 5-position and hydrogen binding acceptor (NO2, CN) at 7-position of indole ring appear as critical functional groups. Among the compounds, 2-(7-nitro-5-isopropoxy-indol-2-yl)-4-methylthiazole-5-carboxylic acid (9m) exhibits the most potent XO inhibitory activity (IC50value: 5.1 nM) and the excellent uric acid lowering activity in potassium oxonate induced hyperuricemic rat model.
Continuous flow thermolysis of azidoacrylates for the synthesis of heterocycles and pharmaceutical intermediates
O'Brien, Alexander G.,Levesque, Francois,Seeberger, Peter H.
supporting information; experimental part, p. 2688 - 2690 (2011/04/25)
An efficient, safe and scalable procedure for the continuous flow thermolysis of azidoacrylates to yield indoles has been developed and was applied to the synthesis of related heterocycles. The scalability of the process was demonstrated in the continuous flow synthesis of a precursor to the DAAO inhibitor 4H-furo[3,2-b]pyrrole-5-carboxylic acid.
Structural necessity of indole C5-O-substitution of seco-duocarmycin analogs for their cytotoxic activity
Choi, Taeyoung,Ma, Eunsook
experimental part, p. 7971 - 7984 (2011/03/22)
A series of racemic indole C5-O-substituted seco-cyclopropylindole (seco-CI) compounds 1-5 were prepared by coupling in the presence of EDCI of 1-(tertbutyloxycarbonyl)- 3-(chloromethyl)indoline (seg-A) with 5-hydroxy-, 5-O-methylsulfonyl, 5-O-aminosulfonyl, 5-O-(N,N-dimethylaminosulfonyl)- and 5-O-benzyl-1H-indole-2- carboxylic acid as seg-B. Compounds 1-5 were tested for cytotoxic activity against four human cancer cell lines (COLO 205, SK-MEL-2, A549, and JEG-3) using a MTT assay. Compounds 2 and 3 with small sized sulfonyl substituents like 5-O-methylsulfonyl and 5- O-aminosulfonyl exhibit a similar level of activity as doxorubicin against all cell lines tested.
Tandem palladium-catalyzed N,C-coupling/carbonylation sequence for the synthesis of 2-carboxyindoles
Vieira, Tiago O.,Meaney, Laura A.,Shi, Yong-Ling,Alper, Howard
supporting information; experimental part, p. 4899 - 4901 (2009/05/31)
(Chemical Equation Presented) Tandem palladium-catalyzed N,C-coupling/carbonylation, under 10 aim of carbon monoxide and at 110 °C, is a novel and efficient method for the preparation of 2-carboxyindoles. The catalyst system tolerates a variety of functional groups, and the noted indoles were obtained in good isolated yields.
Probing the subpockets of factor Xa reveals two binding modes for inhibitors based on a 2-carboxyindole scaffold: A study combining structure-activity relationship and X-ray crystallography
Nazaré, Marc,Will, David W.,Matter, Hans,Schreuder, Herman,Ritter, Kurt,Urmann, Matthias,Essrich, Melanie,Bauer, Armin,Wagner, Michael,Czech, J?rg,Lorenz, Martin,Laux, Volker,Wehner, Volkmar
, p. 4511 - 4525 (2007/10/03)
Structure-activity relationships within a series of highly potent 2-carboxyindole-based factor Xa inhibitors incorporating a neutral P1 ligand are described with particular emphasis on the structural requirements for addressing subpockets of the factor Xa enzyme. Interactions with the subpockets were probed by systematic substitution of the 2-carboxyindole scaffold, in combination with privileged P1 and P4 substituents. Combining the most favorable substituents at the indole nucleus led to the discovery of a remarkably potent factor Xa inhibitor displaying a Ki value of 0.07 nM. X-ray crystallography of inhibitors bound to factor Xa revealed substituent-dependent switching of the inhibitor binding mode and provided a rationale for the SAR obtained. These results underscore the key role played by the P1 ligand not only in determining the binding affinity of the inhibitor by direct interaction but also in modifying the binding mode of the whole scaffold, resulting in a nonlinear SAR.
