- Effects of N-Substitutions on the Tetrahydroquinoline (THQ) Core of Mixed-Efficacy μ-Opioid Receptor (MOR)/δ-Opioid Receptor (DOR) Ligands
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N-Acetylation of the tetrahydroquinoline (THQ) core of a series of μ-opioid receptor (MOR) agonist/δ-opioid receptor (DOR) antagonist ligands increases DOR affinity, resulting in ligands with balanced MOR and DOR affinities. We report a series of N-substituted THQ analogues that incorporate various carbonyl-containing moieties to maintain DOR affinity and define the steric and electronic requirements of the binding pocket across the opioid receptors. 4h produced in vivo antinociception (ip) for 1 h at 10 mg/kg.
- Harland, Aubrie A.,Bender, Aaron M.,Griggs, Nicholas W.,Gao, Chao,Anand, Jessica P.,Pogozheva, Irina D.,Traynor, John R.,Jutkiewicz, Emily M.,Mosberg, Henry I.
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p. 4985 - 4998
(2016/06/13)
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- The modified trifluoromethylation protocol applicable to electronically deficient iodopyridinones
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Utilization of a mixed solvent system of DMF/HMPA=1/1 (v/v) to the KF/CuI/TMSCF3 reagent system proved to significantly affect the reaction, realizing convenient introduction of a trifluoromethyl (CF3) group not only to electron-deficient iodopyridinones with quite a few previous successful examples but also to aliphatic vinylic iodides.
- Kawasaki-Takasuka, Tomoko,Yamazaki, Takashi
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p. 6824 - 6831
(2015/08/24)
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- Reactive derivatives of sulforhodamine 101 with enhanced hydrolytic stability
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The invention describes reactive dyes having an alkyl spacer attached via a sulfonamide bond to a sulforhodamine 101 fluorophore, and a variety of useful conjugates prepared therefrom. The increased length of the covalent linkage due to the alkyl spacer results in dye-conjugates having a number of surprisingly advantageous properties relative to previous sulforhodamine 101-labeled conjugates, including enhanced solubility and increased fluorescence. The reactive dyes of the present invention are more stable than the known compound sulforhodamine 101 sulfonyl chloride. Novel reactive dyes are described for selective modification of groups other than amines, including thiols and photoreactive derivatives.
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- POLYHYDROXY BENZOIC ACID DERIVATIVES AND THEIR USE AS NEURAMINIDASE INHIBITORS
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The present invention is directed to compositions of the formula: wherein: R2 is H, or an alkyl group having 1 to 3 carbon atoms and 0 to 2 hydroxyls; R3 is H, or hydroxyl; R4 is H, or forms a hydrolyzable ester or amide with -C02-; R5 are H, or are taken together to form =NH; and R6 comprises an amine, or a group having 1 to 12 carbon atoms and 1 to 3 amine groups. The invention is also directed to methods of inhibiting the activity of neuraminidase using the compounds of the invention
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- Scavenger assisted combinatorial process for preparing libraries of tertiary amine compounds
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This invention relates to a novel solution phase process for the preparation of tertiary amine combinatorial libraries. These libraries have utility for drug discovery and are used to form wellplate components of novel assay kits.
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- Cephem compound, process for producing the compound, and antimicrobial composition containing the same
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The present invention provides a cephem compound having a high antimicrobial activity against various pathogenic bacteria. The cephem compound of the invention is represented by the formula STR1 wherein Q represents CH or N, R1 represents a carboxylate or the like, R2 represents a hydrogen atom, and R represents STR2 wherein R3 represents a group --(CH2)m --Y (wherein m is an integer of 1 to 5, and Y represents a quaternary ammonium group) or the like, n is an integer of 0 to 4, B- represents an anion, f is 0 or 1 when R1 represents a carboxylate, and 2 when R1 represents a carboxyl group, and the ring C represents a 5-membered heterocyclic group of not more than 4 nitrogen atoms, which may be substituted by a lower alkyl group.
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- Preparation process of aminoacetamide derivative
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Disclosed herein are novel processes for preparing aminoacetamide derivatives, wherein: (1) a secondary amine is reacted with a 2-haloacetamide in the presence or absence of at least one solvent selected from water, lower alcohols, aromatic solvents and acetic acid esters; (2) an N-benzylideneamine derivative is reacted with dimethyl sulfate or diethyl sulfate to form a secondary amine, and this secondary amine is then reacted with a 2-haloacetamide; and (3) a primary amine is reacted with benzaldehyde to form an N-benzylideneamine derivative, this product is then reacted with dimethyl sulfate or diethyl sulfate to form a secondary amine, and this secondary amine is further reacted with a 2-haloacetamide. The 2-aminoacetamide derivatives are useful as intermediates for the preparation of novel antibiotics.
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- Reactive derivatives of bapta used to make ion-selective chelators
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The invention relates to fluorescent and/or reactive derivatives of 1,2-bis-(2-aminophenoxyethane)-N,N,N',N'-tetraacetic acid (BAPTA) according to the formula: STR1 where at least one of W and X is a functional group, with or without a spacer, that terminates in an alcohol or phenol, a thiol, a haloacetamide, an alkyl halide, an amine or aniline, a carboxylic acid, an anhydride, an isocyanate, an isothiocyanate, a maleimide, or an activated ester. The BAPTA-like molecule may be further substituted, one or more times, by additional functional groups with or without spacers or by CH3, NO2, CF3, F, Cl, Br, I, or carboxylic acid derivatives or pharmaceutically acceptable salts thereof, or by indolyl or benzofuran fluorophores. The functional groups allow for subsequent covalent attachment of one or more oxygen heterocycle fluorophores (e.g. fluorescein, coumarin, rhodamine); or polymolecular assemblies (e.g. gel and resin polymers, polysaccharides, polypeptides, nucleic acids, and liposomes); or combinations thereof.
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- Long wavelength chemically reactive dipyrrometheneboron difluoride dyes and conjugates
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This invention relates to derivatives of dipyrrometheneboron difluoride fluorescent dyes that have an absorption maximum at wavelengths longer than about 525 nm, and are chemically reactive with nucleic acids, proteins, carbohydrates, and other biologically derived or synthetic chemical materials. The dyes generally have the structure: STR1 wherein at least one of the substituents R1 -R7, is a reactive functional group, and at least one of the substituents R1 -R7 contains a bathochromic moiety. The bathochromic moiety is an unsaturated organic group, preferably heteroaryl or alkenyl. The remaining substituents, which may be the same or different, are hydrogen, halogen, alkyl (containing 1-5 carbon atoms), aryl, arylalkyl, or sulfo. The dyes are used to make novel conjugates with members of specific binding pairs that are ligands or receptors.
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- Chemically reactive dipyrrometheneboron difluoride dyes
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Novel fluorescent dyes based on the dipyrrometheneboron difluoride structure are provided. The new reagents contain functional groups capable of forming a stable fluorescent product with functional groups typically found in biomolecules or polymers including amines, phenols, thiols, acids, aldehydes and ketones. Reactive groups in the dipyrrometheneboron difluoride dyes include activated esters, isocyanates, amines, hydrazines, sulfonyl halides, acids, aldehydes, alcohols and haloacetamides. The products are detected by their absorbance or fluorescence properties. The spectral properties of the fluorescent dyes are sufficiently similar in wavelengths and intensity to fluorescein as to permit use of the same euqipment. The dyes, however, have narrower spectral bandwidths than fluorescein, do not show appreciable sensitivity to pH, have higher solubility in non-polar solvents and have improved photostability.
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- 2-(Aminomethyl)phenols, a New Class of Saluretic Agents. 4. Effects of Oxygen and/or Nitrogen Substitution
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A series of oxygen and/or nitrogen substituted 2-(aminomethyl)phenols was synthesized and tested orally in rats for saluretic and diuretic effects.Intravenous dog data are included as supplementary material to demonstrate diuretic responses, or lack thereof, in a secon species.In general, substitution on nitrogen with groups other than lower alkyl or substitution on nitrogen and/or oxygen with groups resistant to hydrolysis substantially diminished or ablated saluretic effects.
- Stokker, G. E.,Deana, A. A.,deSolms, S. J.,Schultz, E. M.,Smith, R. L.,et al.
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p. 735 - 742
(2007/10/02)
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