- New asymmetrical morpholinium- and 1,1-dioxidothiomorpholinium-based dicationic ionic liquid: structure, thermophysical and electrochemical properties of propylene carbonate solutions
-
A new asymmetrical 1,1-dioxidothiomorpholinium- and morpholinium-based dicationic ionic liquid (4-ethyl-4-[3-(4-ethyl-1,1-dioxidothiomorpholin-4-ium-4-yl)propyl]morpholin-4-ium tetrafluoroborate (EtDTMC3EtM·2BF4)) was synthesized in four stages and characterized by 1H, 13C, 1H,1H–COSY NMR, single X-ray diffraction, XPS spectroscopy and simultaneous thermal analysis. Electrical conductivities of several EtDTMC3EtM·2BF4 solutions in propylene carbonate (PC) were measured in the 298 – 368 K temperature range and analyzed using the Arrhenius, Litovitz, and Vogel–Fulcher–Tammann (VFT) equations.
- Arkhipova, Ekaterina A.,Ivanov, Anton S.,Levin, Mikhail M.,Maslakov, Konstantin I.,Kupreenko, Stepan Yu.,Lyssenko, Konstantin A.,Savilov, Serguei V.
-
-
- New pyrido[3,4-g]quinazoline derivatives as CLK1 and DYRK1A inhibitors: synthesis, biological evaluation and binding mode analysis
-
Cdc2-like kinase 1 (CLK1) and dual specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) are involved in the regulation of alternative pre-mRNA splicing. Dysregulation of this process has been linked to cancer progression and neurodegenerative diseases, making CLK1 and DYRK1A important therapeutic targets. Here we describe the synthesis of new pyrido[3,4-g]quinazoline derivatives and the evaluation of the inhibitory potencies of these compounds toward CDK5, CK1, GSK3, CLK1 and DYRK1A. Introduction of aminoalkylamino groups at the 2-position resulted in several compounds with low nanomolar affinity and selective inhibition of CLK1 and/or DYRK1A. Their evaluation on several immortalized or cancerous cell lines showed varying degree of cell viability reduction. Co-crystal structures of CLK1 with two of the most potent compounds revealed two alternative binding modes of the pyrido[3,4-g]quinazoline scaffold that can be exploited for future inhibitor design.
- Tazarki, Helmi,Zeinyeh, Wael,Esvan, Yannick J.,Knapp, Stefan,Chatterjee, Deep,Schr?der, Martin,Joerger, Andreas C.,Khiari, Jameleddine,Josselin, Béatrice,Baratte, Blandine,Bach, Stéphane,Ruchaud, Sandrine,Anizon, Fabrice,Giraud, Francis,Moreau, Pascale
-
p. 304 - 317
(2019/02/07)
-
- Highly Selective Butyrylcholinesterase Inhibitors with Tunable Duration of Action by Chemical Modification of Transferable Carbamate Units Exhibit Pronounced Neuroprotective Effect in an Alzheimer's Disease Mouse Model
-
In this study, the carbamate structure of pseudo-irreversible butyrylcholinesterase (BChE) inhibitors was optimized with regard to a longer binding to the enzyme. A set of compounds bearing different heterocycles (e.g., morpholine, tetrahydroisoquinoline, benzimidazole, piperidine) and alkylene spacers (2 to 10 methylene groups between carbamate and heterocycle) in the carbamate residue was synthesized and characterized in vitro for their binding affinity, binding kinetics, and carbamate hydrolysis. These novel BChE inhibitors are highly selective for hBChE over human acetycholinesterase (hAChE), yielding short-, medium-, and long-acting nanomolar hBChE inhibitors (with a half-life of the carbamoylated enzyme ranging from 1 to 28 h). The inhibitors show neuroprotective properties in a murine hippocampal cell line and a pharmacological mouse model of Alzheimer's disease (AD), suggesting a significant benefit of BChE inhibition for a disease-modifying treatment of AD.
- Hoffmann, Matthias,Stiller, Carina,Endres, Erik,Scheiner, Matthias,Gunesch, Sandra,Sotriffer, Christoph,Maurice, Tangui,Decker, Michael
-
p. 9116 - 9140
(2019/11/03)
-
- Two-photon fluorescent probe for detecting nitric oxide near cell membranes
-
A two-photon fluorescent probe for detecting nitric oxide near cell membranes belongs to the field of fine chemical engineering and is made by using naphthalimide as chromophores and introducing hydrophilic quaternary ammonium salt cations and hydrophobic fatty carbon chains. The amphiphilic phospholipid molecular structure provides cell membrane targeting function for probe molecules and allows the molecules to stay on the cell membranes quickly and stably, and enhancement of fluorescent signals indicate the presence of nitric oxide molecules near the cell membranes. The molecules of the two-photon fluorescent probe allow fluorescence imaging to be performed through single-photon laser excitation, is further suitable for fluorescence imaging for 690-950 nm two-photon laser, and is applicable to fluorescence detection inside cells and deep biological tissues; the molecules of the probe have stable solid stability, are easy to preserve, and may serve as a detection reagent to study nitric-oxide-related physiological process.
- -
-
Paragraph 0015
(2018/03/28)
-
- INHIBITORS OF BACTERIAL GLYCOSYL TRANSFERASES
-
Described herein are compounds of Formula (I'), Formula (IA), Formulae (I)-(VII), pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrug sthereof. The invention also provides pharmaceutical compositions of the compounds for human and veterinary use. Compounds of the present invention are useful for inhibiting bacterial growth and therefore are useful in treating and/or preventing bacterial infections. Methods of using the compounds for treating and/or preventing a bacterial infection in a subject are also described.
- -
-
Paragraph 00366; 00437-00438
(2016/12/22)
-
- Colloid and nanosized catalysts in organic synthesis: XII. Hydrogenation of carbonitriles catalyzed by nickel nanoparticles
-
Hydrogenation of carbonitriles catalyzed by nickel nanoparticles in isopropanol proceeds under atmospheric pressure of hydrogen within 6-15 h to yield mainly secondary amines. Hydrogenation of α-aminonitriles results in reductive decyanation. β-Aminonitriles undergo hydrogenolysis at the nitrogen-carbon bond.
- Mokhov,Popov,Shcherbakova
-
p. 273 - 280
(2016/04/20)
-
- Flavonoid derivatives as selective ABCC1 modulators: Synthesis and functional characterization
-
A series of chromones, bearing substituted amino groups or N-substituted carboxamide moieties in position 2, was synthesized and characterized in cellular assays for modulation of the ABC transporters ABCC1 (MDCKII-MRP1 cells), ABCB1 (Kb-V1 cells) and ABCG2 (MCF-7/Topo cells). The most potent ABCC1 modulators identified among these flavonoid-type compounds were comparable to the reference compound reversan regarding potency, but superior in terms of selectivity concerning ABCB1 and ABCG2 (2-[4-(Benzo[c][1,2,5]oxadiazol-5-ylmethyl)piperazin-1-yl]-5,7-dimethoxy-4H-chromen-4-one (51): ABCC1, IC50 11.3-1/4M; inactive at ABCB1 and ABCG2). Compound 51 was as effective as reversan in reverting ABCC1-mediated resistance to cytostatics in MDCKII-MRP1 cells and proved to be stable in mouse plasma and cell culture medium. Modulators, such as compound 51, are of potential value as pharmacological tools for the investigation of the (patho)physiological role of ABCC1.
- Obreque-Balboa, José Esteban,Sun, Qiu,Bernhardt, Günther,K?nig, Burkhard,Buschauer, Armin
-
supporting information
p. 124 - 133
(2016/01/20)
-
- HIV INTEGRASE INHIBITORS
-
The present invention features compounds that are HIV integrase inhibitors and therefore are useful in the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC.
- -
-
-
- Selectivity Optimization of Substituted 1,2,3-Triazoles as α7 Nicotinic Acetylcholine Receptor Agonists
-
Three series of substituted anti-1,2,3-triazoles (IND, PPRD, and QND), synthesized by cycloaddition from azide and alkyne building blocks, were designed to enhance selectivity and potency profiles of a lead α7 nicotinic acetylcholine receptor (α7-nAChR) agonist, TTIn-1. Designed compounds were synthesized and screened for affinity by a radioligand binding assay. Their functional characterization as agonists and antagonists was performed by fluorescence resonance energy transfer assay using cell lines expressing transfected cDNAs, α7-nAChRs, α4β2-nAChRs, and 5HT3A receptors, and a fluorescence cell reporter. In the IND series, a tropane ring of TTIn-1, substituted at N1, was replaced by mono- and bicyclic amines to vary length and conformational flexibility of a carbon linker between nitrogen atom and N1 of the triazole. Compounds with a two-carbon atom linker optimized binding with Kds at the submicromolar level. Further modification at the hydrophobic indole of TTIn-1 was made in PPRD and QND series by fixing the amine center with the highest affinity building blocks in the IND series. Compounds from IND and PPRD series are selective as agonists for the α7-nAChRs over α4β2-nAChRs and 5HT3A receptors. Lead compounds in the three series have EC50s between 28 and 260 nM. Based on the EC50, affinity, and selectivity determined from the binding and cellular responses, two of the leads have been advanced to behavioral studies described in the companion article (DOI: 10.1021/acschemneuro.5b00059).
- Arunrungvichian, Kuntarat,Fokin, Valery V.,Vajragupta, Opa,Taylor, Palmer
-
p. 1317 - 1330
(2015/09/01)
-
- COLORING AGENTS AND METHODS OF USE THEREOF
-
Dyes, compositions comprising dyes and methods for using the same are provided.
- -
-
-
- Synthesis and biological evaluation of 2,4-diaminoquinazoline derivatives as novel heat shock protein 90 inhibitors
-
Novel 2,4-diaminoquinazoline derivatives originating from a virtual screening approach were designed, synthesized and their biological activities as heat shock protein 90 (Hsp90) inhibitors were evaluated. The prepared compounds exhibited significant anti-proliferative activities against DU-145, HT-29, HCT-116, A375P and MCF-7 cancer cell lines. The selected compounds were tested against Her2, a client protein of Hsp90, and showed significant reduction in Her2 protein expression. Compound 6b was found the most potent, reduced Her2 protein expression levels and induced Hsp70 protein expression levels significantly.
- Thorat, Dhanaji Achyutrao,Doddareddy, Munikumar Reddy,Seo, Seon Hee,Hong, Tae-Joon,Cho, Yong Seo,Hahn, Ji-Sook,Pae, Ae Nim
-
scheme or table
p. 1593 - 1597
(2011/05/05)
-
- Sulfonamides having antiangiogenic and anticancer activity
-
Compounds having methionine aminopeptidase-2 inhibitory (MetAP2) are described. Also described are pharmaceutical compositions comprising the compounds, methods of treatment using the compounds, methods of inhibiting angiogenesis, and methods of treating cancer.
- -
-
-
- Phenyl derivatives
-
Novel compounds of the formula I in which W, X, Y, T, R1 and R2 are as defined in Patent claim 1, are inhibitors of coagulation factor Xa and can be employed for the prophylaxis and/or therapy of thromboembolic disorders.
- -
-
-
- Sulfonamides having antiangiogenic and anticancer activity
-
Compounds having methionine aminopeptidase-2 inhibitory (MetAP2) are described. Also described are pharmaceutical compositions comprising the compounds, methods of treatment using the compounds, methods of inhibiting angiogenesis, and methods of treating cancer.
- -
-
-
- Expedient protocol for solid-phase synthesis of secondary and tertiary amines
-
Equation presented. An expedient solid-phase synthetic approach to secondary and tertiary amines was developed. The protocol employs conversion of resin-bound amino alcohols to the corresponding iodides, followed by iodide displacement with primary or sec
- Olsen, Christian A.,Witt, Matthias,Jaroszewski, Jerzy W.,Franzyk, Henrik
-
p. 1935 - 1938
(2007/10/03)
-
- Tetracyclic benzimidazole derivatives and combinatorial libraries thereof
-
The present invention relates to novel tetracyclic benzimidazole derivative compounds of the following formula: wherein R1to R10have the meanings described in here. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing tetracyclic benzimidazole derivative compounds.
- -
-
-
- A new class of histamine H3-receptor antagonists: Synthesis and structure - Activity relationships of 7,8,9,10-Tetrahydro-6H-cyclohepta[b]quinolines
-
The synthesis and biological evaluation of novel cycloheptaquinoline antagonists of the human H3 receptor are described. Two series of compounds, bearing either an amino substituent or an alkyne linker at the 11-position, were investigated. Modifications of the amino substituents, optimization of chain length and the effect of conformational restraints are described. Several compounds with high affinity and selectivity for the H3 receptor were discovered.
- Turner, Sean C.,Esbenshade, Timothy A.,Bennani, Youssef L.,Hancock, Arthur A.
-
p. 2131 - 2135
(2007/10/03)
-
- 2-aminobenzoxazole derivatives and combinatorial libraries thereof
-
The present invention relates to novel 2-aminobenzoxazole derivative compounds of the following formula: wherein R1 to R4 and Z have the meanings provided herein. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing 2-aminobenzoxazole derivative compounds.
- -
-
-
- 2-aminopyridine derivatives and combinatorial libraries thereof
-
The present invention relates to novel 2-aminopyridine derivative compounds of the following formula: wherein R1to R5have the meanings provided herein. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing 2-aminopyridine derivative compounds.
- -
-
-
- Hair revitalizing tonic composition containing a 2,2-dimethylpropanediol compound and use thereof
-
Disclosed is a hair revitalizing tonic composition containing a dimethylpropanediol derivative of the formula: wherein R1and R2are each independently a C1-30hydrocarbon group which may be substituted, or a five- or six-membered heterocyclic group which contains1to4heteroatoms selected from oxygen, sulfur and nitrogen atoms and which may be substituted, R3is hydrogen atom, an alkyl group which may be substituted, an acyl group, an alkoxycarbonyl group, a phenoxycarbonyl group, or a carbamoyl group which may be substituted, and a and b are each 0 or 1, as well as a method for effecting hair growth promotion, hair growth stimulation, or hair loss prevention in mammals by using such a hair revitalizing tonic composition. Also disclosed is the use of a compound of formula (I) in the preparation of a hair revitalizing tonic composition. Thus, this invention can provide an excellent means of hair revitalization or hair loss prevention in mammals.
- -
-
-
- Design, synthesis and biological evaluation of 1,3-diaminopropanes: A new class of polyamine analogs as leishmanicidal agents
-
Analogs of 1,3-diaminopropane as inhibitors for the growth of Leishmania donovani have been synthesized and evaluated for their antileishmanial activity. Of the many active compounds, 1-(3-N,N-bis methoxycarbonyl guanidino)propyl-4- methylpiperidine piperazine (4e,f) exhibited significant in vivo inhibitory efficacy against L. donovani by oral and intraperitoneal route of administration.
- Kumar, Versha Vinay,Singh, Sudhir K.,Sharma,Bhaduri,Gupta, Suman,Zaidi, Alima,Tiwari, Suman,Katiyar
-
p. 675 - 680
(2007/10/03)
-
- NUCLEOPHILIC CLEAVAGE AND FORMATION OF SATURATED HETEROCYCLES. XII. REACTIVITY OF SMALL HETEROCYCLES TOWARD AMINOLYSIS AND HYDROLYSIS
-
The cleavage of four-membered saturated heterocycles proceeds via a more product-like transition state than that of three-membered rings.General acid catalysis is characteristic of oxygen heterocycles, but in the case of nitrogen heterocycles catalysis is specific.The reactivity of amines in the cleavage of azetidines is linearly dependent on their pKa values, primary and secondary amines comprising separate reaction series.
- Bobylev, V. A.,Veselkov, N. Yu.,Dalin, A. R.,Sharikov, F. Yu.
-
p. 1700 - 1713
(2007/10/02)
-
- 3-amino-5-methyl-1H-pyrazole-4-carboxylic acids and esters thereof as anticonvulsants, muscle relaxants and anxiolytics
-
A novel method of controlling epilepsy, muscle tension, muscular spasticity, and anxiety in living animal bodies by administering compounds of the formula: STR1 wherein: R1 is hydrogen, loweralkyl or a pharmaceutically acceptable cation; R2 and R3, same or different, are hydrogen, loweralkyl, aryl, cycloalkyl, loweralkenyl, 1-adamantyl, heterocyclicaminoalkyl, diloweralkylaminoloweralkyl, or R2 with R3 and adjacent nitrogen may form a heterocyclic ring structure; and the pharmaceutical acceptable acid salts, and tautomeric isomers thereof; and novel pharmaceutical compositions therefor are disclosed.
- -
-
-
- β-TRIMETHYLSILYLETHANESULFONYL CHLORIDE (SES-Cl): A NEW REAGENT FOR PROTECTION OF AMINES
-
The title compound, easily prepared in two steps from vinyltrimethylsilane, is a useful reagent for the protection of primary and secondary amines as their sulfonamides, which are cleaved by fluoride ion.
- Weinreb, Steven M.,Demko, Donald M.,Lessen, Thomas A.,Demers, James P.
-
p. 2099 - 2102
(2007/10/02)
-
- INTRAMOLECULAR GENERAL-BASE CATALYSIS OF SCHIFF-BASED HYDROLYSIS BY TERTIARY AMINO GROUPS.
-
Hydrolysis of a series of Schiff bases derived from benzophenone and various amines has been studied kineticlly in aqueous solution. A linear correlation of the log of the rate constants for the water reaction with the Schiff base pK//a (slope minus 0. 70) shows large positive deviations for Schiff bases derived from (2-aminoethyl)diethylamine, N-(2-aminoethyl)morpholine, N-(2-aminoethyl)piperazine and 2-(aminomethyl)pyridine (1i) but small deviations for Schiff bases from N-(3-aminopropyl)morpholine and 2-(2-aminoethyl)pyridine. The deviations found are attributed to intramolecular general-base catalysis of the water reaction by the internal tertiary amino groups. Magnitudes of the rate enhancement are correlated well with pK//a//l of the internal catalyst ( beta equals 0. 49). Effective concentrations of the internal bases are estimated to range from 340 (1e) to 40 M.
- Okuyama,Shibuya,Fueno
-
p. 730 - 736
(2007/10/02)
-
