- 2-(Nitroaryl)benzothiazole and benzoxazole derivatives as fluorogenic substrates for the detection of nitroreductase activity in clinically important microorganisms
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A series of carboxy-substituted 2-(nitroaryl)benzothiazole derivatives and carboxy-substituted 2-(nitroaryl)benzoxazole derivatives were prepared and evaluated as potential nitroreductase substrates for the purpose of detecting clinically important microorganisms. Several of the substrates produced highly fluorescent colonies with the majority of a panel of 10 Gram-negative bacteria and also with two of a panel of 8 Gram-positive bacteria.
- Cellier, Marie,Gignoux, Amandine,James, Arthur L.,Orenga, Sylvain,Perry, John D.,Robinson, Shaun N.,Stanforth, Stephen P.,Turnbull, Graeme
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- AZABICYCLO AND DIAZEPINE DERIVATIVES FOR TREATING OCULAR DISORDERS
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The present invention provides in one aspect azabicycio and diazepine derivatives useful as modulators of muscarinic receptors. In another aspect, the present invention provides pharmaceutical compositions for treating ocular diseases, the compositions comprising at least one muscarinic receptor modulator. Formulae (I) & (II):
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Page/Page column 71
(2019/05/22)
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- An intestinal gastric pirenzepine hydrochloride is an important intermediate for simple synthesis process (by machine translation)
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The invention discloses an intestinal gastric pirenzepine hydrochloride is an important intermediate for simple and convenient synthetic process, against the 5, 11 - dihydro - 11 - chloracetyl - 6 H - pyrido [2.3 - b] [1, 4] benzodiazepine - 6 - one synthetic, develops a piece of raw materials are simple and easy, simple operation of the synthesis process, in order to O-nitro benzoic acid and 2 - chloro - 3 - aminopyridine as a main raw material, five-step synthesis of the target compound, low cost, high yield, high purity, the final drug has far-reaching practical significance. (by machine translation)
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Paragraph 0028; 0031
(2019/05/04)
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- THIAZOLOPYRIDINE SIRTUIN MODULATING COMPOUNDS
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Provided herein are novel sirtuin-modulating compounds of Structural Formula (Ia) and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
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Page/Page column 67
(2010/08/05)
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- SOLUBILIZED THIAZOLOPYRIDINES
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Provided herein are novel sirtuin-modulating compounds Structural Formula (I): and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benfit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
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Page/Page column 65
(2009/06/27)
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- MUSCARINIC ANTAGONISTS WITH PARP AND SIR MODULATING ACTIVITY AS CYTOPROTECTIVE AGENTS
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The present invention relates to generally to the cytoprotective activity of mixed muscarinic inhibition/PARP modulation and in particular to the use of dual inhibitors of M1 muscarinic receptor and poly(ADP-ribose) polymerase (PARP) as neuroprotective medicaments, particularly as medicaments for the prevention and/or treatment of neurological diseases. Particularly preferred compounds are condensed diazepinones, e.g. condensed benzodiazepinones such as pirenzepine or compounds which are metabolized to condensed benzodiazepinones such as olanzapine.
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Page/Page column 20
(2010/02/15)
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- Palladium-mediated approach to dibenzo[b,e][1,4]diazepines and benzopyrido-analogues. An efficient synthesis of tarpane
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An original synthetic route toward dibenzo[b,e][1,4]diazepin-11-ones and analogues pyridobenzodiazepinones has been developed. The method relies upon an intramolecular amination process between an (hetero)aryl halide and the appropriate aniline moiety. Graphical Abstract.
- Beccalli, Egle M.,Broggini, Gianluigi,Paladino, Giuseppe,Zoni, Caterina
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- Fluorescent pirenzepine derivatives as potential bitopic ligands of the human M1 muscarinic receptor
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Following a recent description of fluorescence resonance energy transfer between enhanced green fluorescent protein (EGFP)-fused human muscarinic M1 receptors and Bodipy-labeled pirenzepine, we synthesized seven fluorescent derivatives of this antagonist in order to further characterize ligand-receptor interactions. These compounds carry Bodipy [558/568], Rhodamine Red-X [560/580], or Fluorolink Cy3 [550/570] fluorophores connected to pirenzepine through various linkers. All molecules reversibly bind with high affinity to M1 receptors (radioligand and energy transfer binding experiments) provided that the linker contains more than six atoms. The energy transfer efficiency exhibits modest variations among ligands, indicating that the distance separating EGFP from the fluorophores remains almost constant. This also supports the notion that the fluorophores may bind to the receptor protein. Kinetic analyses reveal that the dissociation of two Bodipy derivatives (10 or 12 atom long linkers) is sensitive to the presence of the allosteric modulator brucine, while that of all other molecules (15-24 atom long linkers) is not. The data favor the idea that these analogues might interact with both the acetylcholine and the brucine binding domains.
- Tahtaoui, Chouaib,Parrot, Isabelle,Klotz, Philippe,Guillier, Fabrice,Galzi, Jean-Luc,Hibert, Marcel,Ilien, Brigitte
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p. 4300 - 4315
(2007/10/03)
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- New pyridobenzodiazepine derivatives as potential antipsychotics: Synthesis and neurochemical study
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The discovery of a new, safe, atypical antipsychotic remains an important challenge. To achieve this goal, a series of N-methylpiperazinopyrido[2,3- b][1,4]- and -[1,5]- and -pyrido[4,3-b][1,4]- and -[1,5]-benzodiazepines were synthesized. The dopaminergic (D1, D2), serotonergic (5-HT2), and cholinergic (M) affinities, frequently remarked in the action mechanisms of antipsychotic drugs, were determined using their respective in vitro receptor binding assays. All affinities were reduced for each compound. Optimal substituents were found to be in the 2- or 8-position for the retention of affinities, while substitution at the 5-position by acyl or alkyl groups dramatically diminished binding affinities. Pyridobenzodiazepine derivatives, such as clozapine, were found to be inactive or only weakly effective against apomorphine-mediated stereotypes in rats. In an original and complex behavioral model developed in dogs and successfully used to differentiate distinct classes of psychotropic drugs and to discriminate between typical and atypical neuroleptic drugs, 8-chloro-6-(4-methyl-1-piperazinyl)-11H- pyrido[2,3-b][1,4]benzodiazepine (9), 8-methyl-6-(4-methyl-1-piperazinyl)- 11H-pyrido[2,3-b][1,4]benzodiazepine (12), and 5-(4-methyl-1-piperazinyl)- 11H-pyrido[2,3-b][1,5]benzodiazepine (16) showed most of the behavioral characteristics previously described for neuroleptics. Their neurochemical profiles, particularly their 5-HT2/D2 pK(i) ratios, were compatible with an atypical antipsychotic effect. These compounds were selected for further investigation. The proposed modulations could lead to new possibilities for the pharmacochemistry of diarylazepines.
- Liegeois,Bruhwyler,Damas,Thuy Phuong Nguyen,Chleide,Mercier,Rogister,Delarge
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p. 2107 - 2114
(2007/10/02)
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- Process for the synthesis of oxazolopyridine compounds
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Process for the synthesis of compounds of formula (I): STR1 their pyridinium salts and N-oxides, in which formula: the nitrogen of the pyridine ring is situated in the α-, β-, γ- or δ-position with respect to the ring junction; R1 represents a halogen, a substituted or unsubstituted alkyl, a substituted or unsubstituted alkoxy or a nitro, substituted or unsubstituted amino, phenyl or cyano group; 0≤m≤2; R2 represents a lower alkyl or cycloalkyl group, a 5- or 6-membered heterocycle containing 1 or 2 hetero atoms, substituted or otherwise, or an aryl group STR2 such that: R3 represents a halogen, a substituted or unsubstituted alkyl, a substituted or unsubstituted alkoxy or a nitro, phenyl, substituted or unsubstituted sulfonyl, cyano, thioalkyl, substituted or unsubstituted amino, substituted or unsubstituted sulfinyl, mercapto, hydroxyl or ester group, 0≤n≤5 employing trimethylsilyl polyphosphate (PPSE) as a cyclization agent and enabling the compounds of formula (I) to be obtained in virtually quantitative yields. The compounds of formula I have anti-inflammatory, analgesic, and antipyretic activity.
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- A New Convenient Synthesis of 2-Aryl- and 2-Heteroaryloxazolopyridines
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Several 2-aryl- and 2-heteroaryloxazolopyridines were synthesized in high yields from 3-(arylcarbonylamino)-2-chloropyridines by heating in the presence of trimethylsilylpolyphosphate ester.
- Flouzant, Christine,Guillaumet, Gerald
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