590417-96-2Relevant academic research and scientific papers
Discovery of (1 H-Pyrazolo[3,4- c]pyridin-5-yl)sulfonamide Analogues as Hepatitis B Virus Capsid Assembly Modulators by Conformation Constraint
Wang, Chunting,Pei, Yameng,Pei, Yameng,Wang, Lin,Li, Shuo,Jiang, Chao,Tan, Xu,Dong, Yi,Xiang, Ye,Ma, Yao,Liu, Gang
supporting information, p. 6066 - 6089 (2020/07/10)
Hepatitis B virus (HBV) capsid assembly modulators (CAMs) have been suggested to be effective anti-HBV agents in both preclinical and clinical studies. In addition to blocking HBV replication, CAMs could reduce the formation of covalently closed circular DNA (cccDNA), which accounts for the persistence of HBV infection. Here, we describe the discovery of (1H-indazole-5-yl)sulfonamides and (1H-pyrazolo[3,4-c]pyridin-5-yl)sulfonamides as new CAM chemotypes by constraining the conformation of the sulfamoylbenzamide derivatives. Lead optimization resulted in compound 56 with an EC50 value of 0.034 μM and good metabolic stability in mouse liver microsomes. To increase the solubility, the amino acid prodrug (65) and its citric acid salt (67) were prepared. Compound 67 dose dependently inhibited HBV replication in a hydrodynamic injection-based mouse model of HBV infection, while 56 did not show in vivo anti-HBV activity, likely owing to its suboptimal solubility. This class of compounds may serve as a starting point to develop novel anti-HBV drugs.
Compounds and their use in treatment on hepatitis B
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Paragraph 0373-0375, (2020/07/15)
The invention provides compounds, a pharmaceutical composition containing the compounds and an application of the compounds. The compound is a compound shown in a formula (I) or a stereoisomer, a tautomer, nitric oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug of the compound shown in the formula (I). The compound provided by the invention can interfere with the shell assembly process of hepatitis B virus, thereby inhibiting hepatitis B virus replication. Moreover, the compound has good absorption, relatively high biological activity and availability and low toxicity, particularly has relatively strong stability in vivo, is not easy to decompose and has long drug effect time, so that an effect of treating hepatitis B is achieved and the compound has a goodapplication prospect.
2,3-DISUBSTITUTED PYRIDINE COMPOUNDS AS TGF-BETA INHIBITORS AND METHODS OF USE
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Paragraph 0177, (2015/11/27)
The invention described herein comprises compounds of formula (IV) and a method of treating cancer comprising administering to a subject having cancer one of the compounds in conjunction with another therapeutic treatment of cancer. The compounds (IV) inhibit signaling by a member of the TGF-β superfamily such as Nodal or Activin.
The Suzuki reaction applied to the synthesis of novel pyrrolyl and thiophenyl indazoles
Migliorini, Antonella,Oliviero, Chiara,Gasperi, Tecla,Loreto, Maria Antonietta
experimental part, p. 4508 - 4521 (2012/07/27)
The paper describes the Suzuki cross-coupling of a variety of N and C-3 substituted 5-bromoindazoles with N-Boc-2-pyrrole and 2-thiopheneboronic acids. The reactions, performed in the presence of K2CO3, dimethoxyethane and Pd(dppf)Cl2 as catalyst, gave the corresponding adducts in good yields. The methodology allows the facile production of indazole-based heteroaryl compounds, a unique architectural motif that is ubiquitous in biologically active molecules.
HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Page/Page column 79-80, (2012/09/21)
Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
IMINOTHIADIAZINE DIOXIDE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE
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Page/Page column 88-89, (2011/04/26)
In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (a) and include tautomers, solvates, prodrugs, esters, and deuterates thereof, and pharmaceutically acceptable salts of said compounds, tautomers, solvates, prodrugs, esters, and deuterates, wherein each of R1, R2, R3, R4, R5, R9, ring A, ring B, ring C, m, n, p, q, -L1-, -L2-,L3-, and L4 - is selected independently and as defined herein. The compounds of the invention have, surprisingly and advantageously, improved solution stability. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Abeta) protein, including Alzheimers Disease, are also disclosed
Substituted phenylalkanoic acid derivatives and use thereof
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Page 151, (2008/06/13)
A compound represented by the formula (I) or a salt thereof: wherein n represents an integer of 1 to 3, R represents an alkyl group having 3 to 8 carbon atoms, a group represented by the following formula: R1(CH2)k— (wherein k represents 0 or an integer of 1 to 3; R1 represents a saturated cyclic alkyl group having 3 to 7 carbon atoms or a saturated condensed cyclic alkyl group having 6 to 8 carbon atoms, and the group R1 may be substituted with a lower alkyl group having 1 to 4 carbon atoms) and the like, and Ar represents a condensed bicyclic group such as naphthalen-1-yl group, which has suppressing action on prostaglandin and leukotriene production and is useful for prophylactic and/or therapeutic treatment of various inflammatory diseases and the like caused by these lipid mediators.
