- NUCLEOSIDE ANALOGUES FOR THE TREATMENT OF PARASITIC INFECTIONS
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The present invention relates to novel nucleoside analogues and compositions containing said nucleoside analogues. Moreover, the present invention provides processes for the preparation of the disclosed compounds, as well as methods of using them, for instance as a medicine, in particular for the diagnosis, prevention and/or treatment of parasitic infections, more specifically for use in the diagnosis, prevention and/or treatment of a Trypanosoma infection.
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Page/Page column 40
(2019/05/10)
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- SYNTHESIS AND STRUCTURE OF HIGH POTENCY RNA THERAPEUTICS
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This invention provides expressible polynucleotides, which can express a target protein or polypeptide. Synthetic mRNA constructs for producing a protein or polypeptide can contain one or more 5′ UTRs, where a 5′ UTR may be expressed by a gene of a plant. In some embodiments, a 5′ UTR may be expressed by a gene of a member of Arabidopsis genus. The synthetic mRNA constructs can be used as pharmaceutical agents for expressing a target protein or polypeptide in vivo.
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- ADENOSINE ANALOG AND ITS USE IN REGULATING THE CIRCADIAN CLOCK
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Provided are a kind of nucleoside analogue compounds, and compositions comprising these compounds and pentostatin, their use for modulating circadian rhythm, preferably, for shifting circadian phase, and methods for modulating circadian rhythm, preferably, for shifting circadian phase via these compounds or the compositions.
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Paragraph 0191; 0198; 0199
(2018/08/12)
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- CYCLIC DINUCLEOTIDES AS AGONISTS OF STIMULATOR OF INTERFERON GENE DEPENDENT SIGNALLING
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Disclosed herein are new cyclic dinucleotide compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of modulation of immune response to disease, and induce Stimulator of Interferon Genes (STING) dependent type I interferon production and co-regulated genes in a human or animal subject are also provided for the treatment diseases such as cancer, particularly metastatic solid tumors and lymphomas, inflammation, allergic and autoimmune disease, infectious disease, and for use as anti-viral agents and vaccine adjuvants.
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Paragraph 0278
(2018/09/26)
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- Glycosylation of Pyrrolo[2,3- d]pyrimidines with 1- O-Acetyl-2,3,5-tri- O-benzoyl-β- d -ribofuranose: Substituents and Protecting Groups Effecting the Synthesis of 7-Deazapurine Ribonucleosides
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Glycosylation of nonfunctionalized 6-chloro-7-deazapurine with commercially available 1-O-acetyl-2,3,5-tri-O-benzoyl-β-d-ribofuranose (45%) followed by amination and deprotection gave tubercidin in only two steps. Similar conditions applied for the synthe
- Ingale, Sachin A.,Leonard, Peter,Seela, Frank
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p. 8589 - 8595
(2018/06/25)
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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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- Antibacterial Agents
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The invention provides compounds of formula (I) and salts thereof: R1-L-R2—B wherein R1, L, R2, and B have any of the values defined herein, as well as compositions comprising such compounds, and therapeutic methods comprising the administration of such compounds or salts. The compounds block siderophore production in bacteria and are useful as antibacterial agents.
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Page/Page column 54
(2009/01/20)
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- A facile and improved synthesis of tubercidin and certain related pyrrolo[2,3-d]pyrimidine nucleosides by the stereospecific sodium salt glycosylation procedure [1]
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A simple synthesis of tubercidin, 7-deazaguanosine and 2'-deoxy-7-deazaguanosine has been accomplished using the sodium salt glycosylation procedure. Reaction of the sodium salt of 4-chloro- and 2-amino-4-chloro-pyrrolo[2,3-d]pyrimidine, 3 and 4, respectively, with 1-chloro-2,3-O-isopropylidene,5-O-(t-butyl)dimethylsilyl-α-D-ribofur nose gave the corresponding protected nucleosides 6 and 7 with β-anomeric configuration. Deprotection of 6 provided 8, which on heating with methanolic ammonia gave tubercidin in excellent yield. Functional group transformation of 7, followed by deisopropylidenation gave 2-aminotubercidin and 2-amino-7-β-ribofuranosylpyrrolo[2,3-d]pyrimidine-4(3H)-thione. Treatment of 7 with 1N sodium methoxide followed by exposure to aqueous trifluoroacetic acid, and ether cleavage furnished 7-deazaguanosine. 2'-Deoxy-7-deazaguanosine and 2'-deoxy-7-deaza-6-thioguanosine were also prepared by using similar sequence of reactions employing 4 and 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranose.
- Ramasamy,Imamura,Robins,Revankar
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p. 1893 - 1898
(2007/10/02)
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- Anomers of Tubercidin Derivatives with 2-Methylthio and N4-(Δ2-Isopentenyl) Residues
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Starting with the chloronucleosides 3a and 4a the anomers 1 and 2 of 2-(methylthio)tubercidin were prepared.They are desulfurized to tubercidin (3c) and its α-anomer 4c.Desulfurization of the N4-(Δ2-isopentenyl) compounds 3b and 4b yields 3d and 4d; due to hydrogenation the by-products 3e and 4e are formed.Isopentylation of tubercidin followed by Dimroth rearrangement also gives N4-(Δ2-isopentenyl)tubercidin (3d).From the 1J(C,H) coupling constants of the glyconic moiety the sequence of the 13C signals of the α-anomer 2 was deduced.The 3J(C-6,1'-H) couplings of tubercidins gave the torsion angle χ which is found to be in the anti region.
- Seela, Frank,Bussmann, Werner
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p. 1972 - 1980
(2007/10/02)
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- 2' AND 3'-KETONUCLEOSIDES AND THEIR ARABINO AND XYLO REDUCTION PRODUCTS CONVENIENT ACCESS VIA SELECTIVE PROTECTION AND OXIDATION OF RIBONUCLEOSIDES
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A number of 2',5'- or 3',5'-diprotected ribonucleosides and 5'-protected 2'- or 3'-deoxy-β-D-erythro-pentofuranosyl nucleosides have been oxidized to the corresponding 3' or 2'-ketonucleoside derivatives using chromium trioxide/pyridine/acetic anhydride or dimethyl sulfoxide/acetic anhydride.Reduction of the carbonyl functions with sodium borohydride gave the inverted arabino, xylo, or deoxy-threo isomers as predominant products by attack at the less hindered α-face of the sugar ring.Parallel reductions using sodium borodeuteride corroborated the epimeric ratios by demonstrating that complete oxidation of the original hydroxyl groups had occured.The deuterium labeling also aided in making NMR spectral assignments.
- Hansske, Fritz,Madej, Danuta,Robins, Morris J.
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p. 125 - 135
(2007/10/02)
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