13787-59-2Relevant articles and documents
Evaluation of Cyclic Amides as Activating Groups in N-C Bond Cross-Coupling: Discovery of N-Acyl-δ-valerolactams as Effective Twisted Amide Precursors for Cross-Coupling Reactions
Bisz, Elwira,Chen, Hao,Dziuk, B?a?ej,Ejsmont, Krzysztof,Lalancette, Roger,Pyle, Daniel J.,Rahman, Md. Mahbubur,Szostak, Michal,Szostak, Roman,Wang, Qi
, p. 10455 - 10466 (2021/07/31)
The development of efficient methods for facilitating N-C(O) bond activation in amides is an important objective in organic synthesis that permits the manipulation of the traditionally unreactive amide bonds. Herein, we report a comparative evaluation of a series of cyclic amides as activating groups in amide N-C(O) bond cross-coupling. Evaluation of N-acyl-imides, N-acyl-lactams, and N-acyl-oxazolidinones bearing five- and six-membered rings using Pd(II)-NHC and Pd-phosphine systems reveals the relative reactivity order of N-activating groups in Suzuki-Miyaura cross-coupling. The reactivity of activated phenolic esters and thioesters is evaluated for comparison in O-C(O) and S-C(O) cross-coupling under the same reaction conditions. Most notably, the study reveals N-acyl-δ-valerolactams as a highly effective class of mono-N-acyl-activated amide precursors in cross-coupling. The X-ray structure of the model N-acyl-δ-valerolactam is characterized by an additive Winkler-Dunitz distortion parameter ?(τ+χN) of 54.0°, placing this amide in a medium distortion range of twisted amides. Computational studies provide insight into the structural and energetic parameters of the amide bond, including amidic resonance, N/O-protonation aptitude, and the rotational barrier around the N-C(O) axis. This class of N-acyl-lactams will be a valuable addition to the growing portfolio of amide electrophiles for cross-coupling reactions by acyl-metal intermediates.
Discovery of potent IDO1 inhibitors derived from tryptophan using scaffold-hopping and structure-based design approaches
Zou, Yi,Wang, Yan,Wang, Fang,Luo, Minghao,Li, Yuezhen,Liu, Wen,Huang, Zhangjian,Zhang, Yihua,Guo, Wenjie,Xu, Qiang,Lai, Yisheng
, p. 199 - 211 (2017/07/03)
Indoleamine 2,3-dioxygenase 1 (IDO1) is frequently hijacked by tumors to escape the host immune response, and the enzyme is now firmly established as an attractive target for cancer immunotherapy. To identify novel IDO1 inhibitors suitable for drug development, a scaffold-hopping strategy combined with the average electrostatic potentials calculation was ultilized to design novel benzoxazolinone derivatives. Among these, compounds 7e, 7f and 9c exhibited the inhibitory potency in the low micromolar range and displayed negligible level of cytotoxicity against HeLa cells. Treatment with these three compounds promoted the proliferation of T lymphocyte and led to the dramatic decrease of regulatory T cells in the B16F1 cells and na?ve T cells co-culture system. Subsequent spectroscopic experiments suggested that these benzoxazolinones formed a coordinate bond with the heme iron to stabilize the complex. This study suggested that the benzoxazolinone was an interesting scaffold for discovering novel IDO1 inhibitors, and these compounds are attractive candidates for further development.
Benzo five-membered heterocyclic IDO1 (indoleamine 2,3-dioxygenase 1) inhibitor, preparation method thereof and application
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Paragraph 0169; 0170; 0171; 0172; 0173; 0174; 0175; 0176, (2017/07/22)
The invention belongs to the field of medicines, and particularly relates to a benzo five-membered heterocyclic compound or pharmaceutically acceptable salt of the compound, a preparation method of the compound and an application of the compound serving as an IDO1 (indoleamine 2,3-dioxygenase 1) inhibitor. Experimental results indicate that the compound has a remarkable inhibiting effect on activity of IDO1, T cell proliferation can be effectively promoted, differentiation of initial T cells into regulatory T cells is inhibited, IDO1-mediated immune inhibition is reversed, and the compound can be used for treating related diseases with pathological features of an IDO1-mediated kynurenine metabolic pathway, wherein the related diseases include cancer, virus infection, neurodegenerative diseases, cataract, organ transplant rejection, depression and autoimmune diseases.
