- Development of Acidic Imidazolium Ionic Liquids for Activation of Kraft Lignin by Controlled Oxidation: Comprehensive Evaluation and Practical Utility
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A novel, eco-friendly method for the activation of lignin by controlled oxidation was studied. The results obtained for six acidic imidazolium ionic liquids containing the hydrogen sulfate anion were compared. The key goal of this research was to increase the content of carbonyl groups in the lignin structure because these may play the main role in the transport of protons and electrons in active materials for electrochemical applications. By means of a variety of analytical techniques (FTIR, 13C CP/MAS NMR, and X-ray photoelectron spectroscopy; selected reactions to determine the presence of carbonyl groups; SEM; zeta-potential analysis; thermogravimetric analysis/differential thermogravimetric analysis; and porous structure analysis), it was determined that the product obtained after treatment with 3-cyclohexyloxymethy-1-methylimidazolium hydrogen sulfate had favorable properties, in terms of the target application. Electrochemical tests proved that the obtained materials could be used as anodes in lithium batteries. The results show that the activation of lignin with ionic liquids can increase its capacity and maintain stability.
- Klapiszewski, ?ukasz,Szalaty, Tadeusz J.,Kurc, Beata,Stanisz, Ma?gorzata,Zawadzki, Bartosz,Skrzypczak, Andrzej,Jesionowski, Teofil
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p. 361 - 374
(2018/06/04)
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- 6-Cyclohexylmethyl-3-hydroxypyrimidine-2,4-dione as an inhibitor scaffold of HIV reverase transcriptase: Impacts of the 3-OH on inhibiting RNase H and polymerase
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3-Hydroxypyrimidine-2,4-dione (HPD) represents a versatile chemical core in the design of inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (RT)-associated RNase H and integrase strand transfer (INST). We report herein the design, synthesis and biological evaluation of an HPD subtype (4) featuring a cyclohexylmethyl group at the C-6 position. Antiviral testing showed that most analogues of 4 inhibited HIV-1 in the low nanomolar to submicromolar range, without cytotoxicity at concentrations up to 100?μM. Biochemically, these analogues dually inhibited both the polymerase (pol) and the RNase H functions of RT, but not INST. Co-crystal structure of 4a with RT revealed a nonnucleoside RT inhibitor (NNRTI) binding mode. Interestingly, chemotype 11, the synthetic precursor of 4 lacking the 3-OH group, did not inhibit RNase H while potently inhibiting pol. By virtue of the potent antiviral activity and biochemical RNase H inhibition, HPD subtype 4 could provide a viable platform for eventually achieving potent and selective RNase H inhibition through further medicinal chemistry.
- Tang, Jing,Kirby, Karen A.,Huber, Andrew D.,Casey, Mary C.,Ji, Juan,Wilson, Daniel J.,Sarafianos, Stefan G.,Wang, Zhengqiang
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p. 168 - 179
(2017/02/15)
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- New compound for sequencing by synthesis
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The present invention provides deoxynucleoside tri - or tetraphosphate comprising a 3' nitrate and a detectable label covalently bound to the oxygen atom of a oxymethyl or oxyallyl or oxypropargyl substitution of a nucleobase. Such compounds provide new possibilities for future Sequencing by Synthesis technologies.
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Page/Page column
(2015/06/03)
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- The preparation of several 1,2,3,4,5-functionalized cyclopentane derivatives
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With the goal of eventually synthesizing [5]radialene (3), the still missing member of the parent radialene hydrocarbons, we have prepared the pentaacetates 21 and 31, the pentabromide 29 and the hexabromide 32. In principle these should be convertible by elimination reactions to the desired target molecule.
- Kelch, Andre S.,Jones, Peter G.,Dix, Ina,Hopf, Henning
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p. 1705 - 1712
(2013/10/22)
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- 6-Benzoyl-3-hydroxypyrimidine-2,4-diones as dual inhibitors of HIV reverse transcriptase and integrase
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N-3-Hydroxylation of pyrimidine-2,4-diones was recently found to yield inhibitors of both HIV-1 reverse transcriptase (RT) and integrase (IN). An extended series of analogues featuring a benzoyl group at the C-6 position of the pyrimidine ring was synthesized. Through biochemical studies it was found that these new analogues are dually active against both RT and IN in low micromolar range. Antiviral assays confirmed that these new inhibitors are active against HIV-1 in cell culture at nanomolar to low micromolar range, further validating 3-hydroxypyrimidine-2,4-diones as a viable scaffold for antiviral development.
- Tang, Jing,Maddali, Kasthuraiah,Dreis, Christine D.,Sham, Yuk Y.,Vince, Robert,Pommier, Yves,Wang, Zhengqiang
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supporting information; experimental part
p. 2400 - 2402
(2011/05/15)
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- 3-Hydroxypyrimidine-2,4-diones as an Inhibitor Scaffold of HIV Integrase
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Integrase (IN) represents a clinically validated target for the development of antivirals against human immunodeficiency virus (HIV). Inhibitors with a novel structure core are essential for combating resistance associated with known IN inhibitors (INIs). We have previously disclosed a novel dual inhibitor scaffold of HIV IN and reverse transcriptase (RT). Here we report the complete structure-activity relationship (SAR), molecular modeling, and resistance profile of this inhibitor type on IN inhibition. These studies support an antiviral mechanism of dual inhibition against both IN and RT and validate 3-hydroxypyrimidine-2,4-diones as an IN inhibitor scaffold.
- Tang, Jing,Maddali, Kasthuraiah,Metifiot, Mathieu,Sham, Yuk Y.,Vince, Robert,Pommier, Yves,Wang, Zhengqiang
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experimental part
p. 2282 - 2292
(2011/06/17)
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- 6-(AMINOALKYL)INDAZOLES
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6-(Aminoalkyl) indazoles of formula (I) and the salts thereof have renin-inhibiting properties and can be used as antihypertensive, and renal, cardiac and vascular protecting medicinally active ingredients.
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Page/Page column 45-46
(2010/11/28)
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- Practical synthesis of an orally active renin inhibitor aliskiren
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A convergent synthesis of aliskiren was accomplished via the use of Segment AB as the key intermediate, which was prepared via the coupling of the Grignard reagent derived from Segment B with Segment A, followed by subsequent oxidative lactonization.
- Dong, Hua,Zhang, Zhi-Liu,Huang, Jia-Hui,Ma, Rujian,Chen, Shu-Hui,Li, Ge
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p. 6337 - 6340
(2007/10/03)
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- Substituted tricyclics
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A class of novel tricyclics is disclosed together with the use of such compounds for inhibiting sPLA2mediated release of fatty acids for treatment of conditions such as septic shock.
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- Substituted tricyclics useful in sPLA2 induced diseases
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A class of novel tricyclics is diclosed of the formula (I) : is phenyl or pyridyl wherein the nitrogen is at the 5-, 6-, 7- or 8-position; one of B or D is nitrogen and the other is carbon; is cyclohexenyl, phenyl, pyridyl, wherein the nitrogen is at the 1 -, 2-, or 3position, or a 6-membered hetero-cyclic ring having one heteroatom selected from the group consisting of sulfur or oxygen at the 1-, 2- or 3-position, and nitrogen at the 1 -, 2-, 3- or 4-position; is a double or single bond; together with the use of such compounds for inhibiting SPLA2 mediated release of fatty acids for treatment of conditions such as septic shock.
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- A novel and efficient synthesis of a highly active analogue of clasto-lactacystin β-lactone
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Herein, we describe a new convergent synthesis of a more potent analogue of clasto-lactacystin β-lactone (2), PS-519 compound 4, which is currently in preclinical development for the treatment of ischemia-reperfusion injury in stroke and myocardial infarction. The synthetic strategy relies on building two intermediates (an oxazoline and an aldehyde) which are joined through a doubly diastereoselective aldol reaction, setting up the requisite unichiral centers in the final product (4). The facial selectivity and ultimate stereocontrol are achieved by employing a trivalent aluminum Lewis acid, Me2AlCl, in a chelation-induced reaction which yields a single aldol adduct. The efficiency of the synthetic approach has allowed for the preparation of multigram quantities of clinical grade material, which will support Phase I studies.
- Soucy, Francois,Grenier, Louis,Behnke, Mark L.,Destree, Antonia T.,McCormack, Teresa A.,Adams, Julian,Plamondon, Louis
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p. 9967 - 9976
(2007/10/03)
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- Synthesis of acyclic analogs of pyrimidine nucleosides with aromatic units in the side chain
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The synthesis of some pyrimidine acyclonucleotides with aromatic units in the side chain has been accomplished. Their physicochemical and spectroscopic properties have been studied. These compounds may be described as the substances with potential as antiviral and anticancer activity. 1996 Plenum Publishing Corporation.
- Novikov,Ozerov,Brel',Solodunova,Ozerova
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p. 328 - 332
(2007/10/03)
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- Amino acid protecting groups
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This invention relates to compounds of the formula a compound of the formula STR1 wherein X is O, CR7 R8, S or NR9 wherein R7 and R8 are independently hydrogen, or lower alkyl, and R9 is lower alkyl; n is 0 or 1; R1 and R2 are independently hydrogen, lower alkyl, monoorganosilyl, diorganosilyl, triorganosilyl, halogen, aryl, or nitro; R3 is hydrogen, lower alkyl, monoorganosilyl, diorganosilyl, triorganosilyl, halogen, 9-fluorenylalkyl, cycloalkyl, aryl or aralkyl; R4 and R5 are independently hydrogen, lower alkyl, or aryl or one of R4 and R5 is 9-fluorenyl; R6 is H or COZ wherein Z is an amino acid, a peptide residue or a leaving group; and with the provisos that when n is 0 and R3 is hydrogen, R1 and R2 are not hydrogen, halogen or nitro; that when n is 0 and R3 is lower alkyl, R1 and R2 are not hydrogen; and that when X is O or CR7 R8 wherein R7 and R8 are H, that R1, R2, R3, R4, R5, and R6 are not all simultaneously H. The compounds of the present invention are useful in peptide synthesis as blocking or protecting groups for reactive groups. The present invention is also directed to a method of protecting a reactive group of an organic molecule during a reaction which modifies a portion of the molecule other than the protected group.
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- STEROID DERIVATIVES USEFUL AS HYPOCHOLESTEROLEMICS
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Lanosterols substituted in the 14 and/or 15 position(s) which are active in inhibiting lanosta-8,24-dien-3β-ol 14α-methyl-demethylase activity, suppressing 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity, decreasing cholesterol s
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- Sulfonic and Phosphonic Acids Formed by Bisulfite and Phosphite Adduct Formation with Pyrimidinones
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By analogy with carbonyl compounds, ?-electron deficient 2-pyrimidinones form adducts with sodium bisulfite and phosphite esters.Both the 3,4- and 3,6-bisulfite adducts were found.The 3,4-isomer was often predominant and was obtained isomerically pure by selective precipitation from an aqueous solution.The adduct formation is reversible in aqueous solution.The adduct was also readily cleaved by trifluoroacetic acid.With tris(trimethylsilyl) phosphite, regiospecific formation of the 3,4-adduct was observed.The corresponding 3,4-dihydro-4-phosphonic acid was prepared by methanol cleavage of the silyl ester function.
- Benneche, Tore,Strande, Per,Undheim, Kjell
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p. 448 - 454
(2007/10/02)
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- An easy access to homopropargylic ethers
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Chloromethyl ethers, obtained from alcohols, formaldehyde and HCl, react regioselectively, as shown previously in one case by L.Miginiac, with allenyl aluminium reagents derived from propargyl bromides and aluminium, to give homopropargyl ethers.No evidence for the presence of allenyl ethers was obtained in the cases described.This condensation is used to obtain a protected acetylenic synthon 1, required for the synthesis of an ecdysteroid analogue (1).
- Guedin-Vuong, Denis,Nakatani, Yoichi
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p. 245 - 252
(2007/10/02)
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- Iron-tetraphenylporphine complex having phosphocholine group
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Disclosed is an iron-5,10,15,20-tetra(α, α, α, α-o-substituted phenyl)porphine complex having one or four substituents with a phosphocholine group at the terminal end thereof. The substituents are positioned ortho of the phenyl group or groups.
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- 10-Hydroxy PGC compounds
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10α-Hydroxy-11-desoxy-prostaglandin analogs of the PGE1 and PGE2 and PGF1α and PGF2α series, the 11-dehydro derivatives thereof as well as the 9,10-ketals in the PGF series, and methods of preparing same, 9-keto-10α,15α-dihydroxyprosta-13-trans-enoic or 5-cis,13-trans-dienoic acid, 9α,10α,15α-trihydroxyprosta-11,13-trans-dienoic or 5-cis, 11,13-trans-trienoic acid and 9α,10α-isopropyli-denedioxy-15α-hydroxyprosta-13-trans-enoic or 5-cis,13-trans-dienoic acid are representative of the class. Also included are the corresponding pharmaceutically acceptable, non-toxic esters, ethers and salts. These compounds possess prostaglandin-like activity and thus are useful in the treatment of mammals, where prostaglandins are indicated.
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- Substituted prostaglandin derivatives
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Prostaglandin analogs of the PGF2α, PGE2, PGF1α and PGE1 series substituted at C-10α by a hydroxyl group, the derivatives of the PGF1α and PGE1 series further substituted at C-5,6 by a methylene or dihalomethylene group, and the 10,11-ketals thereof and methods of preparing such compounds. 9α,15α-Dihydroxy-10α,11α-isopropylidenedioxyprosta-5,13-dienoic acid, 9-keto-10α,11α-isopropylidenedioxy-15α-hydroxyprosta-5,13-dienoic acid and 5,6-methylene-9α,15α-dihydroxy-10α,11α-isopropylidenedioxyprost-13-enoic acid are representative of the class. Also included are the corresponding esters, ethers, pharmaceutically acceptable salts and amides. These compounds possess prostaglandin-like activity and thus are useful in the treatment of mammals, where prostaglandins are indicated.
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