- CONJUGATED TLR7 AND/OR TLR8 AND TLR2 AGONISTS
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A conjugated compound of formula Q-Z—R4 wherein Q is a TLR7 and/or TLR8 agonist and Z—R4 is a TLR2 agonist, and the uses thereof in the treatment of infection, cancer or immune disorders or for use in vaccines.
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Page/Page column
(2015/07/22)
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- Vicarious nucleophilic amination of nitroquinolines by 1,1,1- trimethylhydrazinium iodide
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(Chemical Equation Presented) The amination of 3-, 5-, 6-, 7- and 8-nitroquinoline via the vicarious nucleophilic substitution of hydrogen (VNS) with 1,1,1-trimethylhydrazinium iodide (TMHI) in the presence of t-BuOK in DMSO was studied. The amination occurs regioselectively giving ortho or ortho and para isomers relative to the nitro group with a high yield (95-86%). 2-Nitroquinoline does not undergo vicarious amination but displacement of the labile nitro group by an amino group occurs and then transformation to an imine compound and hydrolysis gives 2(1H)-quinolinone.
- Grzegozek, Maria
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experimental part
p. 1879 - 1882
(2009/06/18)
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- Vicarious nucleophilic amination of Nitroquinolines with 4-amino-1,2,4-triazole
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3-, 5-. 6-, 7- and 8-Nitroquinolines react with 4-amino-l,2,4-triazole in basic medium (potassium tert-butoxide-dimethyl sulfoxide) giving amino products of the vicarious nucleophilic substitution (VNS) of hydrogen, predominantly at ortho position to the nitro group, except 8-nitroquinoline, which reacts at para position. Additionally, furazano[3,4-f]- and furazano[3,4-zh]quinoline were obtained in the case of 5- and 8- nitroquinoline, respectively. 2-Nitroquinoline was aminated to 2-quinolino(l,2,4-triazol-4-yl)amine in these conditions.
- Szpakiewicz, Barbara,Grzegozek, Maria
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p. 682 - 685
(2008/09/21)
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- A3 ADENOSINE RECEPTOR ALLOSTERIC MODULATORS
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The present invention relates to allosteric modulation of A3 adenosine receptor (A3AR) and provides for the use of an A3 adenosine receptor modulator (A3RM),for the preparation of pharmaceutical compositions for
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Page/Page column 21
(2008/06/13)
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- Structure-activity relationships of new 1H-imidazo[4,5-c]quinolin-4-amine derivatives as allosteric enhancers of the A3 adenosine receptor
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1H-Imidazo[4,5-c]quinolin-4-amine derivatives have been synthesized as allosteric modulators of the human A3 adenosine receptor (AR). Structural modifications were made at the 4-amino and 2 positions. The compounds were tested in both binding and functional assays, and many were found to be allosteric enhancers of the action of A3AR agonists by several different criteria. First, a potentiation of the maximum efficacy of the agonist C1-IB-MECA was observed for numerous derivatives. Also, a number of these compounds decreased the rate of dissociation of the agonist [ 125I]I-AB-MECA from the A3AR. Most prominently, compound 43 (LUF6000) was found to enhance agonist efficacy in a functional assay by 45% and decrease dissociation rate similarly without influencing agonist potency. The structural requirements for allosteric enhancement at the A3AR were distinct from the requirements to inhibit equilibrium binding. Thus, we have prepared allosteric enhancers of the human A3AR that have an improved allosteric effect in comparison to the inhibition of equilibrium binding at the orthosteric site.
- G?bly?s, Anikó,Gao, Zhan-Guo,Brussee, Johannes,Connestari, Roberto,Santiago, Sabrina Neves,Ye, Kai,Ijzerman, Adriaan P.,Jacobson, Kenneth A.
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p. 3354 - 3361
(2007/10/03)
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- Synthesis and structure-activity relationships of fused imidazopyridines: A new series of benzodiazepine receptor ligands
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2-Arylimidazo[4,5-c]quinolines and analogous fused imidazopyridines were synthesized and evaluated as benzodiazepine receptor ligands. Affinity to the receptors was greatly affected by the bulkiness of the aryl group at the 2- position, compared to the pyrazoloquinolines such as CGS-9896. Derivatives with an isoxazole moiety at the 2-position showed high binding affinity and in vivo activity. In the imidazo[4,5-c]quinoline series, substitution at the 6-position decreased or abolished activity. Most derivatives with an unsubstituted isoxazolyl group showed antagonist or inverse agonist activity except for the 7-halo analogues, which exhibited agonist activity. On the other hand, 5-methylisoxazol-3-yl or 3-methylisoxazol-5-yl derivatives generally exhibited agonist activity. A similar substitution effect on the isoxazole moiety was observed in the imidazopyridines fused with a nonaromatic ring. From the detailed pharmacological evaluation, S-8510, 2- (3-isoxazolyl)-3,6,7,9-tetrahydroimidazo[4,5-d]pyrano[4,3-b]pyridine monophosphate, possessing weak inverse agonist activity was selected as a therapeutic candidate for the treatment of some symptoms of senile dementia.
- Takada, Susumu,Sasatani, Takashi,Chomei, Nobuo,Adachi, Makoto,Fujishita, Toshio,Eigyo, Masami,Murata, Shunji,Kawasaki, Kazuo,Matsushita, Akira
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p. 2844 - 2851
(2007/10/03)
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- Oxidative Methylamination of Nitroquinolines
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3-, 5-, 6-, 7- and 8-nitroquinoline as well as 5,7- and 6,8-dinitroquinoline are methylaminated with a liquid methylamine solution of potassium permanganate (LMA/PP) to the corresponding mono- and bis(methylamino)-substituted compounds. 2-Nitroquinoline is aminated with LMA/PP to 2-(methylamino)quinoline.The intermediate methylamino ?-adducts of 3-nitro- and 5,7- and 6,8-dinitroquinoline are detected by 1H-NMR spectroscopy.Quantum chemical calculations for the mononitroquinolines suggest that the experimentally observed regioselectivity of the methylamination is controlled by an interaction of frontal molecular orbitals (FMO) of the reagents. Key Words: Methylaminations / ?-Adducts, methylamino / Calculations, FMO / Quinolines / Aminations
- Wozniak, Marian,Grzegozek, Maria
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p. 823 - 830
(2007/10/02)
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- 1H-Imidazoquinolin-4-amines: Novel Non-Xanthine Adenosine Antagonists
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On the basis of a model we recently developed for the antagonist binding site of the adenosine A1 receptor (J.Med.Chem. 1990, 33, 1708-1713), it was predicted that 1H-imidazoquinolin-4-amines would be antagonists of the A1 rec
- Galen, Philip J. M. van,Nissen, Peter,Wijngaarden, Ineke van,IJzerman, Adriaan P.,Soudijn, Willem
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p. 1202 - 1206
(2007/10/02)
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- On the Chichibabin Amination of Quinoline and some Nitroquinolines
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Quinoline is aminated into 2-aminoquinoline (55-60percent) when treated with potassium amide/liquid ammonia/potassium permanganate at -65 deg C.When the amination is carried out by allowing the solution of quinoline in potassium amide/liquid ammonia to raise from -60 deg C to +15 deg C before addition of potassium permanganate, the main product is 4-aminoquinoline.Using as reagent liquid ammonia/potassium permanganate (thus without the presence of potassium amide) 3-nitroquinoline is exclusively aminated at -40 deg C into 4-amino-3-nitroquinoline.Using the same conditions, from 4-nitroquinoline 3-amino-4-nitroquinoline is obtained.The mechanism of these amination reactions is discussed.
- Tondyz, Hanna,Plas, Henk C. van der,Wozniak, Marian
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p. 353 - 355
(2007/10/02)
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