- Synthesis, Structure-Activity Relationships, and Antiviral Activity of Allosteric Inhibitors of Flavivirus NS2B-NS3 Protease
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Flaviviruses, including Zika, dengue, and West Nile viruses, are important human pathogens. The highly conserved NS2B-NS3 protease of Flavivirus is essential for viral replication and therefore a promising drug target. Through compound screening, followed by medicinal chemistry studies, a novel series of 2,5,6-trisubstituted pyrazine compounds are found to be potent, allosteric inhibitors of Zika virus protease (ZVpro) with IC50 values as low as 130 nM. Their structure-activity relationships are discussed. The ZVpro inhibitors also inhibit homologous proteases of dengue and West Nile viruses, and their inhibitory activities are correlated. The most potent compounds 47 and 103 potently inhibited Zika virus replication in cells with EC68 values of 300-600 nM and in a mouse model of Zika infection. These compounds represent novel pharmacological leads for drug development against Flavivirus infections.
- Nie, Shenyou,Yao, Yuan,Wu, Fangrui,Wu, Xiaowei,Zhao, Jidong,Hua, Yuanda,Wu, Jingyu,Huo, Tong,Lin, Yi-Lun,Kneubehl, Alexander R.,Vogt, Megan B.,Ferreon, Josephine,Rico-Hesse, Rebecca,Song, Yongcheng
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Read Online
- IMIDAZO[1,2-A]PYRAZINE MODULATORS OF THE ADENOSINE A2A RECEPTOR
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The present invention relates to the compound of formula (I) and salts, stereoisomers, tautomers, isotopologues,or N-oxides thereof. The present invention is further concerned with the use of such a compound or salt, stereoisomer, tautomer, isotopologues,or N-oxide thereof as medicament and a pharmaceutical composition comprising said compound.
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Page/Page column 93
(2019/01/17)
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- Concise Synthesis of v-Coelenterazines
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A novel synthetic method for v-coelenterazine (v-CTZ), which is a vinylene-bridged analog of native CTZ with a large red-shifted luminescence property, is described. The synthesis was achieved in a concise way through the use of three sequential cross-cou
- Hosoya, Takamitsu,Iimori, Rie,Yoshida, Suguru,Sumida, Yuto,Sahara-Miura, Yuiko,Sato, Jun-Ichi,Inouye, Satoshi
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supporting information
p. 3888 - 3891
(2015/08/18)
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- Method of manufacturing terazine compd. v-
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PROBLEM TO BE SOLVED: To provide a method for producing a v-coelenterazine compound.SOLUTION: There is provided a method for producing a v-coelenterazine compound represented by the general formula (II), the method comprising: (1) a step of reacting a compound represented by the general formula (VIII) with a methyltriphenylphosphonium salt in the presence of a base to obtain a compound represented by general formula (IX); (2) a step of performing a ring-closing metathesis reaction on any one selected from the group consisting of the compound represented by general formula (IX) and a compound represented by the general formula (X) in which the amino of the compound represented by the general formula (IX) is protected with Rand then deprotecting R4 and R5 when present to obtain a v-coelenteramine compound represented by the general formula (XIV); and (3) a step of reacting the compound represented by the general formula (XIV) with a compound represented by the general formula (XV) to obtain a compound represented by the general formula (II).
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Paragraph 0180; 0181
(2016/10/10)
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- PYRROLO[2,3-B]PYRAZINES AS SYK INHIBITORS
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The present invention relates to the use of novel pyrrolo[2,3- b]]pyrazines wherein all variable substituents are defined as described herein, which are SYK inhibitors and are useful for the treatment of auto-immune and inflammatory diseases.
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Page/Page column 88
(2014/03/25)
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- IP RECEPTOR AGONIST HETEROCYCLIC COMPOUNDS
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The present invention provides heterocyclic derivatives which activate the IP receptor, processes for preparing them, pharmaceutical compositions comprising said derivatives and uses thereof. Activating the IP receptor signaling pathway is useful to treat
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Paragraph 0359; 0360
(2013/07/25)
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- PROCESS FOR PRODUCING v-COELENTERAZINE COMPOUNDS
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A simple process for producing v-coelenterazine compounds has been desired. Described is a process for producing a v-coelenterazine compound represented by general formula (II) comprising (1) the step of reacting a compound of general formula (VIII) with a methyltriphenylphosphonium salt in the presence of a base to give a compound represented by general formula (IX), (2) the step of performing a ring-closing metathesis reaction on any one selected from the group consisting of the compound represented by general formula (IX) and a compound of general formula (X) which is the compound of general formula (IX) wherein the amino is protected with R5, and then deprotecting R4 and, if any, R5 to give a v-coelenteramine compound represented by general formula (XIV), and (3) the step of reacting the compound of general formula (XIV) with a compound represented by general formula (XV) to give the compound of general formula (II).
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Page/Page column 18
(2012/09/22)
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- IP RECEPTOR AGONIST HETEROCYCLIC COMPOUNDS
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The present invention provides heterocyclic derivatives which activate the IP receptor. Activating the IP receptor signaling pathway is useful to treat many forms of PAH, pulmonary fibrosis and exert beneficial effects in fibrotic conditions of various organs in animal models and in patients. Pharmaceutical compositions comprising such derivatives are also encompassed.
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Page/Page column 144; 145
(2012/02/02)
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- SULPHONAMIDE COMPOUNDS THAT MODULATE CHEMOKINE RECEPTOR ACTIVITY (CCR4)
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The invention relates to sulphonamide compounds, processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in therapy.
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