38750-13-9Relevant articles and documents
Synthesis and Biological Evaluation of Pyrroloindolines as Positive Allosteric Modulators of the α1β2γ2 GABAAReceptor
Blom, Annet E. M.,Su, Justin Y.,Repka, Lindsay M.,Reisman, Sarah E.,Dougherty, Dennis A.
supporting information, p. 2204 - 2211 (2020/12/17)
γ-Aminobutyric acid type A (GABAA) receptors are key mediators of central inhibitory neurotransmission and have been implicated in several disorders of the central nervous system. Some positive allosteric modulators (PAMs) of this receptor prov
A catalytic N-deacylative alkylation approach to hexahydropyrrolo[2,3-b]indole alkaloids
Kumar, Nivesh,Maity, Arindam,Gavit, Vipin R.,Bisai, Alakesh
supporting information, p. 9083 - 9086 (2018/08/21)
A versatile unprecedented strategy to diversely functionalized hexahydropyrrolo[2,3-b]indole alkaloids is described in high chemical yields. The synthesis features a key Pd(0)-catalyzed deacylative alkylation of N-acyl 3-substituted indoles using only 1 mol% of Pd(PPh3)4. The scope of this methodology is further defined in the asymmetric synthesis of pyrroloindolines using a diastereoselective approach.
Synthesis and evaluation of oxindoles as promising inhibitors of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1
Paul, Saurav,Roy, Ashalata,Deka, Suman Jyoti,Panda, Subhankar,Srivastava, Gopal Narayan,Trivedi, Vishal,Manna, Debasis
, p. 1640 - 1654 (2017/08/22)
Indoleamine 2,3-dioxygenase 1 (IDO1) is considered as an important therapeutic target for the treatment of cancer, chronic infections and other diseases that are associated with immune suppression. Recent developments in understanding the catalytic mechanism of the IDO1 enzyme revealed that conversion of l-tryptophan (l-Trp) to N-formylkynurenine proceeded through an epoxide intermediate state. Accordingly, we synthesized a series of 3-substituted oxindoles from l-Trp, tryptamine and isatin. Compounds with C3-substituted oxindole moieties showed moderate inhibitory activity against the purified human IDO1 enzyme. Their optimization led to the identification of potent compounds, 6, 22, 23 and 25 (IC50 = 0.19 to 0.62 μM), which are competitive inhibitors of IDO1 with respect to l-Trp. These potent compounds also showed IDO1 inhibition potencies in the low-micromolar range (IC50 = 0.33-0.49 μM) in MDA-MB-231 cells. The cytotoxicity of these potent compounds was trivial in different model cancer (MDA-MB-231, A549 and HeLa) cells and macrophage (J774A.1) cells. Stronger selectivity for the IDO1 enzyme (124 to 210-fold) over the tryptophan 2,3-dioxygenase (TDO) enzyme was also observed for these compounds. These results suggest that the oxindole moiety of the compounds could mimic the epoxide intermediate state of l-Trp. Therefore, the structural simplicity and low-micromolar inhibition potencies of these 3-substituted oxindoles make them quite attractive for further investigation of IDO1 function and immunotherapeutic applications.
