- 4,6-Substituted-1H-Indazoles as potent IDO1/TDO dual inhibitors
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Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are constitutively overexpressed in many types of cancer cells and exert important immunosuppressive functions. In this article, a series of 4,6-substituted-1H-indazole derivatives were synthesized and evaluated the inhibitory activities against IDO1 and TDO, as well as their structure-activity relationships (SARs). Among these, compound 35 displayed the most IDO1 inhibitory potency with an IC50 value of 0.74 μM in an enzymatic assay and 1.37 μM in HeLa cells. Quantitative analysis of the Western blot results indicated that 35 significantly decreased the INFγ-induced IDO1 expression in a concentration-dependent manner. In addition, 35 showed promising TDO inhibition with an IC50 value of 2.93 μM in the enzymatic assay and 7.54 μM in A172 cells. Moreover, compound 35 exhibited in vivo antitumor activity in the CT26 xenograft model. These findings suggest that 1H-indazole derivative 35 is a potent IDO1/TDO dual inhibitor, and has the potential to be developed for IDO1/TDO-related cancer treatment.
- Yang, Lingling,Chen, Yang,He, Junlin,Njoya, Emmanuel Mfotie,Chen, Jianjun,Liu, Siyan,Xie, Congqiang,Huang, Wenze,Wang, Fei,Wang, Zhouyu,Li, Yuzhi,Qian, Shan
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Read Online
- Novel 6-amino acid heteroaryldihydropyrimidines for the treatment and prophylaxis of hepatitis B virus infection
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The invention provides novel compounds having the general formula: wherein R1, R2, R3, R4 and A are as described herein, compositions including the compounds and methods of using the compounds.
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Paragraph 0439; 0440
(2015/02/19)
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- 6-AMINO ACID HETEROARYLDIHYDROPYRIMIDINES FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION
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The invention provides novel compounds having the general formula:, wherein R1, R2, R3, R4 and A are as described herein, compositions including the compounds and methods of using the compounds.
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Page/Page column 125
(2014/03/26)
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- Assembly of the nosiheptide A-ring: A fruitful lesson
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The synthesis of a 28-membered thiopeptide macrocycle is described. Key steps are mild aza-Wittig thiazole ring closures, a scandium(III)-mediated regioselective ester hydrolysis, and a highly efficient macrolactam formation with its 3-hydroxypyridine nucleus orthogonally protected. Georg Thieme Verlag Stuttgart, New York.
- Lu, Jin-Yong,Riedrich, Matthias,Wojtas, K.Philip,Arndt, Hans-Dieter
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supporting information
p. 1300 - 1311
(2013/07/04)
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- Substituted hydantoins
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The present invention relates to compounds of the formula which are useful in treating diseases characterized by the hyperactivity of MEK. Accordingly the compounds are useful in the treatment of diseases, such as, cancer, cognative and CNS disorders and inflammatory/autoimmune diseases.
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Page/Page column 28
(2008/06/13)
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- Synthesis of methyl 2-acetylamino-5-(1,3-dithian-2-yl)thiazole-4-carboxylate
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The synthesis of methyl 2-acetylamino-5-(1,3-dithian-2-yl)thiazole-4-carboxylate (4) by formylation of a 4-substituted thiazole and then reaction with 1,3-propanedithiol are described. The utility of different ortho-directing groups (ODGs) for the lithiation of the thiazole 4-position has been studied.
- Feliu, Lidia,Ajana, Wadi,Joule, John A.,Lopez-Calahorra, Francisco,Alvarez, Mercedes
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p. 1299 - 1308
(2007/10/03)
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