- Synthesis, Antibacterial, and Anticancer Evaluation of Novel Spiramycin-Like Conjugates Containing C(5) Triazole Arm
-
Huisgen cycloaddition allowed obtaining of novel triazole-bridged antibiotics (6-16) with the reconstructed C(5) arm of spiramycin. 1H-1H NOESY couplings indicated the structure of novel derivatives in solution and demonstrated that
- Klich, Katarzyna,Pyta, Krystian,Kubicka, Marcelina M.,Ruszkowski, Piotr,Celewicz, Lech,Gajecka, Marzena,Przybylski, Piotr
-
-
Read Online
- ISOINDOLINE COMPOUND, AND PREPARATION METHOD, PHARMACEUTICAL COMPOSITION, AND APPLICATION OF ISOINDOLINE COMPOUND
-
The present invention relates to an isoindoline compound as represented by general formula (I) and used as a CRBN regulator, and a preparation method, a pharmaceutical composition, and an application of the isoindoline compound. Specifically, a class of polysubstituted isoindoline compound provided in the present invention, as a class of CRL4CRBN E3 ubiquitin ligase regulator having a novel structure, has good anti-tumor activity and immunoregulatory activity, and can be used for preparing drugs for treating diseases associated with a CRL4CRBN E3 ubiquitin ligase.
- -
-
Paragraph 0281-0282
(2021/10/22)
-
- Discovery and Characterization of 1 H-1,2,3-Triazole Derivatives as Novel Prostanoid EP4 Receptor Antagonists for Cancer Immunotherapy
-
The prostanoid EP4 receptor is one of the key receptors associated with inflammatory mediator PGE2-elicited immunosuppression in the tumor microenvironment. Blockade of EP4 signaling to enhance immunity-mediated tumor elimination has recently emerged as a promising strategy for cancer immunotherapy. In our efforts to discover novel subtype-selective EP4 antagonists, we designed and synthesized a class of 1H-1,2,3-triazole-based ligands that display low nanomolar antagonism activity toward the human EP4 receptor and excellent subtype selectivity. The most promising compound 59 exhibits single-digit nanomolar potency in the EP4 calcium flux and cAMP-response element reporter assays and effectively suppresses the expression of multiple immunosuppression-related genes in macrophage cells. On the basis of its favorable ADMET properties, compound 59 was chosen for further in vivo biological evaluation. Oral administration of compound 59 significantly inhibited tumor growth in the mouse CT26 colon carcinoma model accompanied by enhanced infiltration of cytotoxic T lymphocytes in the tumor tissue.
- Yang, Jun-Jie,Yu, Wei-Wei,Hu, Long-Long,Liu, Wen-Juan,Lin, Xian-Hua,Wang, Wei,Zhang, Qiansen,Wang, Pei-Li,Tang, Shuo-Wen,Wang, Xin,Liu, Mingyao,Lu, Weiqiang,Zhang, Han-Kun
-
p. 569 - 590
(2020/02/05)
-
- P-benzoquinone diazide core skeleton derivative as well as preparation method and application thereof
-
The invention relates to a p-benzoquinone diazide core skeleton derivative and a preparation method and application, thereof, belongs to. the field of organic chemistry, and can effectively treat-ovarian-ovarian cancer-carcinoma STAT3-ovarian, cancer-ATG4
- -
-
Paragraph 0046; 0182-0186
(2020/03/17)
-
- Visible-Light-Mediated Click Chemistry for Highly Regioselective Azide–Alkyne Cycloaddition by a Photoredox Electron-Transfer Strategy
-
Click chemistry focuses on the development of highly selective reactions using simple precursors for the exquisite synthesis of molecules. Undisputedly, the CuI-catalyzed azide–alkyne cycloaddition (CuAAC) is one of the most valuable examples of click chemistry, but it suffers from some limitations as it requires additional reducing agents and ligands as well as cytotoxic copper. Here, we demonstrate a novel strategy for the azide–alkyne cycloaddition reaction that involves a photoredox electron-transfer radical mechanism instead of the traditional metal-catalyzed coordination process. This newly developed photocatalyzed azide–alkyne cycloaddition reaction can be performed under mild conditions at room temperature in the presence of air and visible light and shows good functional group tolerance, excellent atom economy, high yields of up to 99 %, and absolute regioselectivity, affording a variety of 1,4-disubstituted 1,2,3-triazole derivatives, including bioactive molecules and pharmaceuticals. The use of a recyclable photocatalyst, solar energy, and water as solvent makes this photocatalytic system sustainable and environmentally friendly. Moreover, the azide–alkyne cycloaddition reaction could be photocatalyzed in the presence of a metal-free catalyst with excellent regioselectivity, which represents an important development for click chemistry and should find versatile applications in organic synthesis, chemical biology, and materials science.
- Wu, Zheng-Guang,Liao, Xiang-Ji,Yuan, Li,Wang, Yi,Zheng, You-Xuan,Zuo, Jing-Lin,Pan, Yi
-
supporting information
p. 5694 - 5700
(2020/04/24)
-
- 5-HETEROARYL SUBSTITUTED INDAZOLES AS KINASE INHIBITORS
-
The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein A, R1, R2, R3 and m, are defined in the description. The present invention relates also to methods of making said compounds, and compositions containing said compounds which are useful for inhibiting kinases such as Glycogen Synthase kinase 3 (GSK-3), Rho kinase (ROCK), Janus Kinases (JAK), AKT, PAK4, PLK, CK2, KDR, MK2, JNK1, aurora, pim 1 and nek 2.
- -
-
Page/Page column 88
(2009/01/24)
-