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POLYCYCLIC DERIVATIVES, PREPARATION METHOD AND MEDICAL USES THEREOF

Disclosed in the present invention are polycyclic derivatives as represented by general formula (I), the preparation method thereof, pharmaceutical compositions containing the derivatives and uses thereof as therapeutical agents, especially the GPR40 agonist and in preparation of drugs for treating diseases like diabetes and metabolic disorders, etc., wherein each substituent in the general formula (I) has the same definition as in the description.

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Synthesis and structural characterisation of [Pd2(mu-Br)2(PBut3)2], an example of a palladium(I)-palladium(I) dimer

The syntheses, spectroscopic characterisation and in one case (X = Br) the single-crystal structure of the novel PdI-PdI dimers [Pd2(mu-X)2(PBut3)2] (X = Br or I) have been determined; preliminary results on their reactions with CO, H2, CNC6H3Me2 and C2H2 have also been obtained.

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Aligning Potency and Pharmacokinetic Properties for Pyridine-Based NCINIs

Optimization of pyridine-based noncatalytic site integrase inhibitors (NCINIs) based on compound 2 has led to the discovery of molecules capable of inhibiting virus harboring N124 variants of HIV integrase (IN) while maintaining minimal contribution of enterohepatic recirculation to clearance in rat. Structure-activity relationships at the C6 position established chemical space where the extent of enterohepatic recirculation in the rat is minimized. Desymmetrization of the C4 substituent allowed for potency optimization against virus having the N124 variant of integrase. Combination of these lessons led to the discovery of compound 20, having balanced serum-shifted antiviral potency and minimized excretion in to the biliary tract in rat, potentially representing a clinically viable starting point for a new treatment option for individuals infected with HIV.

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

Discovery of Bis(tri-tert-butylphosphine)palladium

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Toward an Improved Understanding of the Unusual Reactivity of Pd 0/Trialkylphosphane Catalysts in Cross-Couplings of Alkyl Electrophiles: Quantifying the Factors That Determine the Rate of Oxidative Addition

What a difference a ligand makes! The reactivity of Pd 0/trialkylphosphane complexes is of great interest because of their unusual effectiveness as cross-coupling catalysts for alkyl electrophiles [Eq. (1)]. This study sheds light on various aspects of the critical oxidative-addition step of the catalytic cycle.

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Diverse N-Heterocyclic Ring Systems via Aza-Heck Cyclizations of N-(Pentafluorobenzoyloxy)sulfonamides

Aza-Heck cyclizations initiated by oxidative addition of Pd0-catalysts into the N?O bond of N-(pentafluoro-benzoyloxy)sulfonamides are described. These studies, which encompass only the second class of aza-Heck reaction developed to date, provide direct access to diverse N-heterocyclic ring systems.

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Diastereoselective synthesis of 2-vinylpyrrolidines and 2-vinylpiperidines by the palladium-catalysed cyclization of amino-allylic carbonates containing a chiral protecting group

An efficient diastereoselective synthesis of pyrrolidine-and piperidine-type N-heterocycles is reported, by the intramolecular Pd(0)-catalysed cyclization of amino carbonates containing chiral protecting group. The use of chiral auxiliary in the cyclization gave the corresponding heterocyclic derivatives in excellent yields and with good dr values.

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Modulation of ambipolar charge transport characteristics in side-chain polystyrenes as host materials for solution processed OLEDs

A series of side-chain polystyrenes was developed as ambipolar hosts for solution processed organic light emitting diodes (OLEDs). The series was derived from the hole-only transport host molecule 1,3-Bis(N-carbazolyl)benzene (mCP). Electron transport ability was incorporated into the host polymers by the introduction of electron-poor heterocycles (pyridine or triazine) and extending delocalization of the lowest unoccupied molecular orbital (LUMO). The materials were tested in Ir-based green OLED devices with all organic layers processed from solution. Devices with the polymer combining triazine and carbazole on its side-chain exhibited a low luminance on-set voltage of 3.0?V and a current efficacy of 28.9?cd/A, which was more than 10 times higher than for devices with the mCP-based polymer (1.6?cd/A). The increase in performance is most likely due to an improvement of charge balance in the emissive layer, showing that our ambipolar polymers are good candidates for further wet-process optoelectronic applications.

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Synthesis, complexation and spectrofluorometric studies of a new NS 3 anthracene-containing macrocyclic ligand

A new fluorescent device for detecting protons and metal ions, 11-(9-anthracenylmethyl)-1,4,7-trithia-11-azacyclotetradecane (L), has been synthesised. In addition, the photophysical properties of both the free and protonated species have been examined by absorption and fluorescence titrations of dichloromethane solutions of L with methanesulfonic acid. The coordinating properties of L toward PdII, ZnII, NiII and CoII have been studied both in solution and in the solid state. Different behaviours have been observed in the absorption and fluorescence titrations of L with the above-mentioned transition-metal ions. To evaluate whether these differences were due to the existence of equilibria between protonated and complexed species, such titrations have been repeated in the presence of an equivalent amount of acid. The structure of the [Pd(L)](BF 4)2 complex has been solved by X-ray crystallography. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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The expedient synthesis of 4,2?-difluoro-5?-(7- trifluoromethylimidazo[1,2-a]pyrimidin-3-yl)biphenyl-2-carbonitrile, a GABA alpha2/3 agonist

An expedient regioselective synthesis of a GABA alpha2/3 agonist 1 is described. The key step is an efficient regioselective palladium-catalyzed coupling of 7-trifluoromethylimidazo[1,2-a]pyrimidine (5) to 5?-chloro-4,2?-difluorobiphenyl-2-carbonitrile (15). The efficiency of this step was affected by the choice of solvent, ligand, and tetrabutylammonium salt additive.

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Solution processable truxene based blue emitters: Synthesis, characterization and electroluminescence studies

Truxene (10,15-dihydro-5H-diindeno[1,2-a;1?,2?-c]fluorene) derived blue emitting materials were designed and developed utilizing Suzuki and Buchwald-Hartwig type cross-coupling reactions. The target molecules T1, T2 and T3 bearing N-carbazolyl, 1-pyrenyl and N-phenyl-N-(pyren-1-yl) substituents, respectively at 2,7,12- positions, were synthesized under mild conditions by palladium-catalyzed reactions in good yields. To improve the solution processability of the material, n-hexyl chains were used as substituents at 5,5?-, 10,10?-, 15,15?- positions. From UV?vis measurements, the absorption maxima were found to be at 330 nm for T1, 356 nm for T2 and 412 nm for T3. The materials were found to be blue emitting with their emission maxima at 385 nm, 425 nm and 490 nm for T1, T2 and T3, respectively. The excited state lifetimes were investigated using time correlated single photon counting and were found to be 10 ns, 1.4 ns and 5.4 ns for T1, T2 and T3, respectively. The highest photoluminescence quantum yield was observed in the case of T2 corresponding to a value of 0.97. The compounds T2 and T3 were used as active materials for the fabrication of solution processed, single layer blue light emitting diodes, with low turn-on voltage (2?3.3 V) and Commission Internationale de l’eclairage (CIE) coordinates corresponding to (0.16, 0.23) and (0.17, 0.36) for T2 and T3, respectively.

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method