111042-89-8Relevant articles and documents
One-pot approach to construct benzo[4,5]thieno[3,2-b]indoles, pyrido[3′,2’:4,5]thieno[3,2-b]indoles and pyrazino[2′,3’:4,5]thieno[3,2-b]indoles based on the Fischer indole synthesis
Irgashev, Roman A.,Steparuk, Alexander S.,Rusinov, Gennady L.
, (2020)
During this study, series of benzo[4,5]thieno[3,2-b]indoles, pyrido[3′,2’:4,5]thieno[3,2-b]indoles and pyrazino[2′,3’:4,5]thieno[3,2-b]indoles were efficiently synthesized from benzo- and pyrido- or pyrazino-fused 3-aminothiophene-2-carboxylates, respectively, using one-pot two-step strategy based on the Fischer indolization reaction. The essence of this synthetic approach is acid-promoted reaction of the 3-aminothiophene intermediates, in situ generated from the corresponding ring-fused 3-aminothiophene-2-carboxylates, with arylhydrazines to give arylhydrazones of thiophen-3(2H)-ones, followed by their indolization to afford thieno[3,2-b]indole-cored molecules.
Polysubstituted thieno[2,3-b]pyridine derivatives, and preparation method and application thereof
-
Paragraph 0117; 0118; 0121-0127; 0172, (2020/01/12)
The invention discloses polysubstituted thieno[2,3-b]pyridine derivatives, and a preparation method and an application thereof. The structural formula of the derivatives are represented by formula I shown in the description. A compound for inhibiting a urea transporter is screened by using an erythrocyte model. Experimental results show that the compounds (represented by formula I-1) can inhibit the permeation of a urea transporter UT-B mediated erythrocyte membrane to urea, and the effect of the compounds has a dose-dependent relationship; the compounds represented by the formula I-1 have nocytotoxic effect on MDCK cells within an effective dose range, so the effect of the compounds represented by the formula I-1 on inhibiting cell permeation urea is irrelevant to the cytotoxicity of thecompounds; the inhibition effect of the compounds represented by the formula I-1 on the urea transporter UT-B is gradually enhanced; the inhibiting effect of the compounds represented by the formulaI-1 on the UT-B is reversible; and in-vivo test results show that the compounds represented by the formula I-1 can significantly increase the urination volume of rats, reduce the concentration of ureain rat urine and reduce the osmotic pressure, so that the compounds represented by the formula I-1 generate a urea selective diuresis effect in vivo.
Synthesis and structure-activity relationship studies of 2-(1,3,4-oxadiazole-2(3H)-thione)-3-amino-5-arylthieno[2,3-b]pyridines as inhibitors of DRAK2
Leonczak, Piotr,Gao, Ling-Jie,Ramadori, Anna Teresa,Lescrinier, Eveline,Rozenski, Jef,De Jonghe, Steven,Herdewijn, Piet
, p. 2587 - 2601 (2015/04/22)
In recent years, DAPK-related apoptosis-inducing protein kinase 2 (DRAK2) has emerged as a promising target for the treatment of a variety of autoimmune diseases and for the prevention of graft rejection after organ transplantation. However, medicinal chemistry optimization campaigns for the discovery of novel small-molecule inhibitors of DRAK2 have not yet been published. Screening of a proprietary compound library led to the discovery of a benzothiophene analogue that displays an affinity constant (Kd) value of 0.25 μM. Variation of the core scaffold and of the substitution pattern afforded a series of 5-arylthieno[2,3-b]pyridines with strong binding affinity (Kd=0.008 μM for the most potent representative). These compounds also show promising activity in a functional biochemical DRAK2 enzyme assay, with an IC50 value of 0.029 μM for the most potent congener. Selectivity profiling of the most potent compounds revealed that they lack selectivity within the DAPK family of kinases. However, one of the less potent analogues is a selective ligand for DRAK2 and can be used as starting point for the synthesis of selective and potent DRAK2 inhibitors.
