- Tumor immunity compound and application thereof
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Disclosed are a tumor immunity compound and an application thereof. The invention discloses a compound as shown in the formula (I), optical isomers thereof, and pharmaceutically acceptable salts thereof, and an application of the compound as an STING agonist.
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Paragraph 0384; 0390-0394
(2020/07/14)
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- Synthesis and evaluation of analogs of 5′-(((Z)-4-amino-2-butenyl)methylamino)-5′-deoxyadenosine (MDL 73811, or AbeAdo) – An inhibitor of S-adenosylmethionine decarboxylase with antitrypanosomal activity
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We describe our efforts to improve the pharmacokinetic properties of a mechanism-based suicide inhibitor of the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (AdoMetDC), essential for the survival of the eukaryotic parasite Trypanosoma brucei responsible for Human African Trypanosomiasis (HAT). The lead compound, 5′-(((Z)-4-amino-2-butenyl)methylamino)-5′-deoxyadenosine (1, also known as MDL 73811, or AbeAdo), has curative efficacy at a low dosage in a hemolymphatic model of HAT but displayed no demonstrable effect in a mouse model of the CNS stage of HAT due to poor blood–brain barrier permeation. Therefore, we prepared and evaluated an extensive set of analogs with modifications in the aminobutenyl side chain, the 5′-amine, the ribose, and the purine fragments. Although we gained valuable structure–activity insights from this comprehensive dataset, we did not gain traction on improving the prospects for CNS penetration while retaining the potent antiparasitic activity and metabolic stability of the lead compound 1.
- Brockway, Anthony J.,Volkov, Oleg A.,Cosner, Casey C.,MacMillan, Karen S.,Wring, Stephen A.,Richardson, Thomas E.,Peel, Michael,Phillips, Margaret A.,De Brabander, Jef K.
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supporting information
p. 5433 - 5440
(2017/10/06)
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- Design and synthesis of fluorescent 7-deazaadenosine nucleosides containing π-extended diarylacetylene motifs
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C-modified 7-deazaadenosines containing a diphenylacetylene moiety have been synthesised using cross-coupling approaches. The C-modified nucleosides exhibit remarkable fluorescence properties, including high quantum yields. Solvatochromic studies show a n
- De Ornellas, Sara,Slattery, John M.,Edkins, Robert M.,Beeby, Andrew,Baumann, Christoph G.,Fairlamb, Ian J. S.
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supporting information
p. 68 - 72
(2015/02/02)
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- COMPOUNDS, COMPOSITIONS AND METHODS FOR TREATING VIRAL INFECTION
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The present invention describes compounds of formulae I and II and methods for treating viral infection, such as Flaviviridae virus infection, including Hepatitis C infection (HCV).
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Page/Page column 131
(2010/12/18)
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- TRICYCLIC-NUCLEOSIDE COMPOUNDS FOR TREATING VIRAL INFECTIONS
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Disclosed are tricyclic nucleoside compounds of formula (I), and methods thereof for treating viral infections mediated at least in part by a Flaviviridae family virus.
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Page/Page column 39
(2009/03/07)
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- 7-Functionalized 7-deazapurine β-d and β-l-ribonucleosides related to tubercidin and 7-deazainosine: glycosylation of pyrrolo[2,3-d]pyrimidines with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-d or β-l-ribofuranose
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Several 7-functionalized 7-deazapurine ribonucleosides were prepared. Glycosylation of 7-halogenated 6-chloro-7-deazapurines with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-d-ribofuranose or 1-O-acetyl-2,3,5-tri-O-benzoyl-β-l-ribofuranose gave the protected β-d-nuc
- Seela, Frank,Ming, Xin
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p. 9850 - 9861
(2008/02/11)
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- Study on the synthesis and PKA-I binding activities of 5-alkynyl tubercidin analogues
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5-Alkynyl tubercidin analogues were synthesized and their biologica activities were evaluated. It was found that protein kinase A could be activated by 5-alkynyl tubercidin (9a) and cAMP- binding ability to PKA-I was selectively inhibited by it. Molecular
- Zhang, Liangren,Zhang, Yunlong,Li, Xianghui,Zhang, Lihe
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p. 907 - 912
(2007/10/03)
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- Adenosine kinase inhibitors. 1. Synthesis, enzyme inhibition, and antiseizure activity of 5-iodotubercidin analogues
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Adenosine receptor agonists produce a wide variety of therapeutically useful pharmacologies. However, to date they have failed to undergo successful clinical development due to dose-limiting side effects. Adenosine kinase inhibitors (AKIs) represent an alternative strategy, since AKIs may raise local adenosine levels in a more site- and event-specific manner and thereby elicit the desired pharmacology with a greater therapeutic window. Starting with 5-iodotubercidin (IC50 = 0.026 μM) and 5'-amino-5'- deoxyadenosine (IC50 = 0.17 μM) as lead inhibitors of the isolated human AK, a variety of pyrrolo[2,3-d]pyrimidine nucleoside analogues were designed and prepared by coupling 5-substituted-4-chloropyrrolo[2,3-d]pyrimidine bases with ribose analogues using the sodium salt-mediated glycosylation procedure. 5'-Amino-5'-deoxy analogues of 5-bromo- and 5-iodotubercidins were found to be the most potent AKIs reported to date (IC50s 0.001 μM). Several potent AKIs were shown to exhibit anticonvulsant activity in the rat maximal electric shock (MES) induced seizure assay.
- Ugarkar, Bheemarao G.,DaRe, Jay M.,Kopcho, Joseph J.,Browne III, Clinton E.,Schanzer, Juergen M.,Wiesner, James B.,Erion, Mark D.
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p. 2883 - 2893
(2007/10/03)
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