- Hybrids of 4-hydroxy derivatives of goniothalamin and piplartine bearing a diester or a 1,2,3-triazole linker as antiproliferative agents
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A library of nine hybrids of 4-hydroxygoniothalamin (2), 4-hydroxypiplartine (4), monastrol (5) and oxo-monastrol (6) was prepared via a modular synthetic route with a diester or a 1,2,3-triazole as linkers. The compounds were assayed against a panel of h
- Grigolo, Thiago A.,Braga, Carolyne B.,Ornelas, Catia,Russowsky, Dennis,Ferreira-Silva, Guilherme A.,Ionta, Marisa,Pilli, Ronaldo A.
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supporting information
(2021/09/14)
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- CEPHEM COMPOUNDS WITH LATENT REACTIVE GROUPS AND METHODS OF USING AND MAKING SAME
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The present application provides novel cephem, penem, and monobactam compounds that exhibit antibiotic activity against both Gram-negative and Gram-positive bacteria, as well as compositions comprising these compounds and methods of using these compounds and compositions to treat bacterial infections.
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- NUCLEIC ACID-POLYPEPTIDE COMPOSITIONS AND USES THEREOF
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Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a modified polynucleic acid molecule and a polymer. Also described herein include methods for treating a cancer which utilize a composition or a
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Paragraph 0441
(2020/12/29)
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- Functionalised bicyclic tetramates derived from cysteine as antibacterial agents
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Routes to bicyclic tetramates derived from cysteine permitting ready incorporation of functionality at two different points around the periphery of a heterocyclic skeleton are reported. This has enabled the identification of systems active against Gram-positive bacteria, some of which show gyrase and RNA polymerase inhibitory activity. In particular, tetramates substituted with glycosyl side chains, chosen to impart polarity and aqueous solubility, show high antibacterial activity coupled with modest gyrase/polymerase activity in two cases. An analysis of physicochemical properties indicates that the antibacterially active tetramates generally occupy physicochemical space with MW of 300-600, clog D7.4 of -2.5 to 4 and rel. PSA of 11-22%. This work demonstrates that biologically active 3D libraries are readily available by manipulation of a tetramate skeleton.
- Panduwawala, Tharindi D.,Iqbal, Sarosh,Thompson, Amber L.,Genov, Miroslav,Pretsch, Alexander,Pretsch, Dagmar,Liu, Shuang,Ebright, Richard H.,Howells, Alison,Maxwell, Anthony,Moloney, Mark G.
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supporting information
p. 5615 - 5632
(2019/06/13)
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- SUBSTITUTED ISOXAZOLE AMIDE COMPOUNDS AS INHIBITORS OF STEAROYL-COA DESATURASE 1 (SCD1)
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The invention is concerned with a compound of formula (I) and pharmaceutically acceptable salts thereof. In addition, the present invention relates to methods of manufacturing and using the compound of formula (I) as well as pharmaceutical compositions containing such compounds. The compound of formula (I) are SCD1 inhibitors and may be useful in treating cancer.
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Page/Page column 32; 33
(2014/06/24)
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- Polyfluorinated bis-styrylbenzenes as amyloid-β plaque binding ligands
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Detection of cerebral β-amyloid (Aβ) by targeted contrast agents remains of great interest to aid the in vivo diagnosis of Alzheimer's disease (AD). Bis-styrylbenzenes have been previously reported as potential Aβ imaging agents. To further explore their potency as 19F MRI contrast agents we synthetized several novel fluorinated bis-styrylbenzenes and studied their fluorescent properties and amyloid-β binding characteristics. The compounds showed a high affinity for Aβ plaques on murine and human brain sections. Interestingly, competitive binding experiments demonstrated that they bound to a different binding site than chrysamine G. Despite their high logP values, many bis-styrylbenzenes were able to enter the brain and label murine amyloid in vivo. Unfortunately initial post-mortem 19F NMR studies showed that these compounds as yet do not warrant further MRI studies due to the reduction of the 19F signal in the environment of the brain.
- Nabuurs, Rob J.A.,Kapoerchan, Varsha V.,Metaxas, Athanasios,De Jongh, Sanne,De Backer, Maaike,Welling, Mick M.,Jiskoot, Wim,Windhorst, Albert D.,Overkleeft, Hermen S.,Van Buchem, Mark A.,Overhand, Mark,Van Der Weerd, Louise
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p. 2469 - 2481
(2014/05/06)
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- VIRAL REPLICATION INHIBITORS
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The present invention relates to a series of novel compounds, methods to prevent or treat viral infections in animals by using the novel compounds and to said novel compounds for use as a medicine, more preferably for use as a medicine to treat or prevent viral infections, particularly infections with RNA viruses, more particularly infections with viruses belonging to the family of the Flaviviridae, and yet more particularly infections with the Dengue virus. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the novel compounds, to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of viral infections. The invention also relates to processes for preparation of the compounds.
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- Synthesis of skeletally diverse alkaloid-like molecules: Exploitation of metathesis substrates assembled from triplets of building blocks
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A range of metathesis substrates was assembled from triplets of unsaturated building blocks. The approach involved the iterative attachment of a propagating and a terminating building block to a fluorous-tagged initiating building block. Metathesis cascade chemistry was used to "reprogram" the molecular scaffolds. Remarkably, in one case, a cyclopropanation reaction competed with the expected metathesis cascade process. Finally, it was demonstrated that the metathesis products could be derivatised to yield the final products. At each stage, purification was facilitated by the presence of a fluorous-tagged protecting group.
- Maurya, Sushil K.,Dow, Mark,Warriner, Stuart,Nelson, Adam
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p. 775 - 785
(2013/06/05)
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- Peroxisome proliferator-activated receptor agonists with phenethylphenylphthalimide skeleton derived from thalidomide-related liver X receptor antagonists: Relationship between absolute configuration and subtype selectivity
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Introduction of an alkylcarboxylic acid unit, which is a partial structure of endogenous peroxisome proliferator-activated receptor (PPAR) ligands, into a phenethylphenylphthalimide skeleton, which possesses liver X receptor (LXR) antagonistic activity, afforded novel PPAR ligands. The results of structure-activity relationship analysis and docking studies led us to the potent PPAR agonists 13c-e. The absolute configuration of 13c-e affects the PPAR subtype selectivity.
- Motoshima, Kazunori,Ishikawa, Minoru,Hashimoto, Yuichi,Sugita, Kazuyuki
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experimental part
p. 3156 - 3172
(2011/06/26)
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- PIPERAZINE AND AMINOPYRROLIDINE COMPOUNDS AS HISTAMINE H3 RECEPTOR ANTAGONISTS
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The invention relates to compounds of formula (I) wherein R1 to R3 and X0, X1, X2 have the meaning as cited in the description and the claims. Said compounds are useful as Histamine H3 receptor antago
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Page/Page column 48
(2010/12/18)
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- Deprotection of acetals and ketals in a colloidal suspension generated by sodium tetrakis(3,5-trifluoromethylphenyl)borate in water
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Deprotection of acetals and ketals can be achieved by using sodium tetrakis(3,5-trifluoromethylphenyl)borate (NaBArF4) as the catalyst in water at 30°C. For example, a quantitative conversion of 2-phenyl-1,3-dioxolane into benzaldehyde was accomplished within five minutes by using this sodium salt (0.1 mol%) in water. Georg Thieme Verlag Stuttgart.
- Chang, Chih-Ching,Liao, Bei-Sih,Liu, Shiuh-Tzung
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p. 283 - 287
(2007/10/03)
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- Vitamin D analogues
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The invention concerns novel bi-aromatic compounds having the formula: which are analogs of vitamin D, the process of preparing them, as well as their use in pharmaceutical compositions in human or veterinary medicine, particularly in dermatology, cancer treatment, treatment of auto-immune diseases, and in organ or tissue transplants. Cosmetic compositions and methods of use are also included.
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Page column 44
(2010/02/05)
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- CARBOXYLIC ACID DERIVATIVE AND SALT THEREOF
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The present invention provides a novel carboxylic acid compound, a salt thereof or a hydrate of them useful as an insulin sensitizer, and a medicament comprising the compound as an active ingredient. That is, the present invention provides a carboxylic acid compound represented by the following formula, a salt thereof, an ester thereof or a hydrate of them. Wherein R1 represents a hydrogen atom, hydroxyl group, halogen, carboxyl group, or a C1-6 alkyl group etc., each of which may have one or more substituents; L represents a single bond, or a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group, each of which may have one or more substituents; M represents a single bond, or a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group, each of which may have one or more substituents; T represents a single bond, or a C1-3 alkylene group, a C2-3 alkenylene group or a C2-3 alkynylene group, each of which may have one or more substituents; W represents a carboxyl group;- - - represents a single bond etc. ; X represents a single bond, oxygen atom, a group represented by -NRX1CQ1O- (wherein Q1 represents an oxygen atom or sulfur atom; and RX1 represents a hydrogen atom, formyl group, or a C1-6 alkyl group etc., each of which may have one or more substituents), -OCQ1NRX1- (wherein Q1 and RX1 are as defined above), -CQ1NRx1O- (wherein Q1 and RX1 are as def ined above), ONRX1CQ1- (wherein Q1 and RX1 are as defined above), - Q2SO2- (wherein Q2 is an oxygen atom or -NRX10- (wherein RX10 represents a hydrogen atom, formyl group, or a C1-6 alkyl group etc., each of which may have one or more substituents)) or -SO2Q2- (wherein Q2 is as defined above), (wherein, provided that RX2 and RX3, and/or RX4 and RX5 may together form a ring, Q3 and Q4 are the same as or different from each other and each represents an oxygen atom, (O)S(O) or NRX10 (wherein NRX10 is as defined above)); Y represents a 5- to 14-membered aromatic group etc., which may have one or more substituents and one or more hetero atoms; and the ring Z represents a 5-to 14-membered aromatic group which may have 0 to 4 substituents and one or more hetero atoms, and wherein part of the ring may be saturated.
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- Catalytic Conversions in Water. Part 23: Steric Effects and Increased Substrate Scope in the Palladium-Neocuproine Catalyzed Aerobic Oxidation of Alcohols in Aqueous Solvents
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The steric influence of substituents on the 2-and 9-positions of phenanthroline in the (2,9-R2-1,10-phenanthroline)palladium(II)- catalyzed aerobic oxidation of 2-hexanol was investigated by means of high throughput experimentation. (Neocuproine)Pd-(OAc)2 (R=CH 3) was found to be a highly active catalyst for alcohol oxidation in 1:1 water/DMSO mixtures. The catalyst is unique in that it tolerates water, polar co-solvents and a wide variety of functional groups in the alcohol. Turn-over frequencies of > 1500 h-1 were achieved and a series of alcohols was oxidised with 0.1 to 0.5 mol % of catalyst.
- Ten Brink, Gerd-Jan,Arends, Isabel W. C. E.,Hoogenraad, Marcel,Verspui, Goeran,Sheldon, Roger A.
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p. 1341 - 1352
(2007/10/03)
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- A simple and efficient chemoselective method for the catalytic deprotection of acetals and ketals using bismuth trifiate
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Bismuth triflate is a highly efficient catalyst (0.1-1 mol %) for the deprotection of acetals and ketals. The procedure is very facile and selective for acetals derived from ketones and conjugated aldehydes. tert-Butyldimethylsilyl ethers are stable to the reaction conditions. The highly catalytic nature of bismuth triflate and the use of a relatively nontoxic solvent system (THF/H2O) make this procedure particularly attractive for large-scale synthesis.
- Carrigan, Marc D.,Sarapa, Dusan,Smith, Russell C.,Wieland, Laura C.,Mohan, Ram S.
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p. 1027 - 1030
(2007/10/03)
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- Highly efficient aerobic oxidation of benzylic and allylic alcohols by a simple catalyst system of [RuCl2(p-cymene)]2/Cs2CO3
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A new catalyst system of [RuCl2(p-cymene)]2/Cs2CO3 has been disclosed for highly efficient aerobic oxidation of activated alcohols to the corresponding carbonyl compounds, which is characterized by its high selectivity and activity, operational simplicity, and low air and moisture sensitivity. (C) 2000 Elsevier Science Ltd.
- Lee,Chang
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p. 7507 - 7510
(2007/10/03)
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- N-benzylpyroglutamyl-L-phenylalanine derivatives as VCAM/VLA-4 antagonists
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A series of N-(N-benzylpyroglutamyl)-4-substituted-L-phenylalanine derivatives was prepared as VLA-4/VCAM antagonists. Analogues substituted by electron deficient benzoylamino groups bearing bulky ortho substituents had low-nM potency in an ELISA assay an
- Chen, Li,Tilley, Jefferson W.,Guthrie, Robert W.,Mennona, Francis,Huang, Tai-Nan,Kaplan, Gerry,Trilles, Richard,Miklowski, Dorota,Huby, Nicolas,Schwinge, Virginia,Wolitzky, Barry,Rowan, Karen
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p. 729 - 733
(2007/10/03)
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- Development of dual-acting agents for thromboxane receptor antagonism and thromboxane synthase inhibition. 2. Design, synthesis, and evaluation of a novel series of phenyl oxazole derivatives
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Synthesis and initial in vitro evaluation of a novel series of phenyl oxazole derivatives are described. An SAR study of the novel dual-acting TRA/TSI agent has revealed that the lipophilicity of the oxazole amide substituents greatly influences the TRA activity but not the TSI. The chain length of the alkenoic acid side chain affects both TRA and TSI. The optimal chain length for the combined activities was found to be n = 4 (heptenoic acid).
- Takeuchi, Kumiko,Kohn, Todd J.,Mais, Dale E.,True, Timothy A.,Wyss, Virginia L.,Jakubowski, Joseph A.
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p. 1943 - 1948
(2007/10/03)
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- 8-Fluoro-6-(methoxymethoxy)quinoline: Synthesis and Regioselective Functionalization via Reaction with Organolithium Compounds
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8-Fluoro-6-(methoxymethoxy)quinoline (1) was synthesized, and the reactivity of 1 against organolithium compounds was studied under different reaction conditions. With BuLi, directed ortho-metalation (DoM) was accompanied by 1,2-addition to the C=N bond.
- Stadlwieser, Josef,Barbier, Pierre,Taylor, Sven
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p. 1088 - 1094
(2007/10/03)
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- 2-Hydroxy-2,2-dimethylacetic acid ester derived heterobiaryl ethers containing 1,3,5-triazine substituents
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The 1,3,5-triazines 3 were obtained from methyl 4-formylbenzoate (4) in a multistep synthesis by first introducing the ester unit under Williamson conditions. Subsequently, the 1,3,5-triazine ring was synthesized by reaction of isocyanates with 1,3-diazadienes obtained from N-silylimines.
- Barluenga,Del Pozo,Olano
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p. 1529 - 1533
(2007/10/02)
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