- COMPOSITIONS AND METHODS OF MODULATING THE IMMUNE RESPONSE BY ACTIVATING ALPHA PROTEIN KINASE 1
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The disclosure provides compositions and methods related to activating alpha-kinase 1 (ALPK1) for modulating an immune response and treating or preventing cancer, infection, inflammation and related diseases and disorders as well as potentiating an immune response to a target antigen. The disclosure also provides heterocyclic compounds of formula (I) as agonists of alpha protein kinase 1 (ALPK1) and their use in activating ALPK1, modulating an immune response and treating diseases such as cancer, wherein A1, A2, L1, L2, L3, Z1, Z2, W1, W2, R1, R2, R3, R4, R5, R6 and R7 are defined herein.
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Paragraph 246; 247
(2019/05/15)
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- Tricyclanos: Conformationally constrained nucleoside analogues with a new heterotricycle obtained from a d-ribofuranose unit
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A novel type of nucleoside analogue in which the sugar part is replaced by a new tricycle, 3,7,10-trioxa-11-azatricyclo[5.3.1.05,11]undecane has been prepared by substrate-controlled asymmetric synthesis. 1,5-Dialdehydes obtained from properly protected or unprotected uridine, ribothymidine, cytidine, inosine, adenosine and guanosine by metaperiodate oxidation reacted readily with tris(hydroxymethyl)aminomethane to provide the corresponding tricyclic derivatives with three new stereogenic centers. Through a double cyclisation cascade process the tricyclic compounds were obtained in good to high yields, with very high diastereoselectivity. Formation of one stereoisomer, out of the eight possible, was observed in all cases. The absolute configuration of the new stereotriad-containing tricyclic systems was aided by conventional NMR experiments followed by chemical shift calculations using an X-ray crystal structure as reference that was in good agreement with H-H distances obtained from a new ROESY NMR method. The synthesis was compatible with silyl, trityl and dimethoxytrityl protecting groups. A new reagent mixture containing ZnCl2, Et3SiH and hexafluoroisopropanol was developed for detritylation of the acid-sensitive tricyclano nucleosides.
- Kicsák, Máté,Mándi, Attila,Varga, Szabolcs,Herczeg, Mihály,Batta, Gyula,Bényei, Attila,Borbás, Anikó,Herczegh, Pál
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supporting information
p. 393 - 401
(2018/02/06)
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- CYCLIC DINUCLEOTIDES AS STING AGONISTS
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Disclosed are compounds, compositions and methods for treating of diseases, syndromes, or disorders that are affected by the modulation of STING. Such compounds are represented by Formula (I) as follows: wherein R, R1B, R1C, R2B
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Page/Page column 130; 132
(2018/08/20)
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- Design, synthesis and anti flaviviridae activity of N6-, 5′,3′-O- and 5′,2′-O-substituted adenine nucleoside analogs
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During a random screening of representative libraries of nucleoside analogues we discovered that the adenine derivatives FEVB28 and FEG118 were Flaviviridae inhibitors endowed with potency comparable, if not superior, to that of ribavirin. Those studies prompted us to design a new class of protected nucleoside analogs, reported herein, which displays interesting anti-bovine viral diarrhea virus (BVDV) activity and low cytotoxicity in cell-based assays (4, 23, 29 EC50: 14, 11, 26 μM respectively, CC50 > 100 μM) and appreciable activity in enzyme assays against the RNA dependent RNA polymerase (RdRp) of BVDV (4, 23, 29, RdRp inhibition activity 27, 16, 15 μM respectively). A molecular modeling study was also carried out to highlight the possible interactions between this compounds class and the corresponding hepatitis C virus (HCV) enzyme.
- Angusti, Angela,Manfredini, Stefano,Durini, Elisa,Ciliberti, Nunzia,Vertuani, Silvia,Solaroli, Nicola,Pricl, Sabrina,Ferrone, Marco,Fermeglia, Maurizio,Loddo, Roberta,Secci, Barbara,Visioli, Anna,Sanna, Tiziana,Collu, Gabriella,Pezzullo, Margherita,La Colla, Paolo
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experimental part
p. 423 - 432
(2009/04/11)
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- First synthesis of 2'-deoxyfluoropuromycin analogues: Experimental insight into the mechanism of the staudinger reaction
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The N6, N6-dedimethyl-2'-deoxyfluoro analogue of puromycin (= 3'-deoxy-N6, N6-dimethyl-3'- [Omethyltyrosylamido]adenosine), its 2',3'-regioisomer and a 3'-cytidyl-5'-(2'deoxyfluoro)puromycyl dinucleotide analogu
- Charafeddine, Adib,Dayoub, Wissam,Chapuis, Hubert,Strazewski, Peter
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p. 5566 - 5584
(2008/02/12)
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- Synthetic Approaches towards Nucleocidin and Selected Analogues; anti-HIV Activity in 4'-Fluorinated Nucleoside Derivatives
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Nucleocidin 1 has been synthesised from the adenosine derivative 4 via the intermediacy of the dihalogeno compound 9.The latter compound showed slight but significant activity against HIV-infected cells while the isomer 10 and the monohalogeno compound 60 were inactive.Synthetic approaches towards other 4'-fluorinated nucleoside derivatives are also described.The epimeric 4'-fluorinated nucleosides 26 and 27 displayed similar activity against HIV-infected cells to that observed for the dihalogenated compound 9.
- Maguire, Anita R.,Meng, Wei-dong,Roberts, Stanley M.,Willetts, Andrew J.
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p. 1795 - 1808
(2007/10/02)
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