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Novel quinazolinone based alpha-glucosidase inhibitors have been developed. For this purpose a virtual screening model has been generated and validated utilizing acarbose as a alpha-glucosidase inhibitor. Homology modeling, docking, and virtual screening were successfully employed to discover a set of structurally diverse compounds active against alpha-glucosidase. A search of a 3D database containing 22 500 small molecules using the structure based virtual model yielded ten possible candidates. All ten candidates were N-3-pyridyl-2-cyclopropyl quinazolinone-4-one derivatives, varying at the 6 position. This position was modified by Suzuki-Miyaura cross coupling with aryl, heteroaryl, and alkyl boronic acids. A catalyst screen was performed, and using the best optimal conditions, a series of twenty five compounds was synthesized. Notably, the C-C cross coupling reactions of the 6-bromo-2-cyclopropyl-3- (pyridyl-3-ylmethyl)quinazolin-4(3H)-one precursor have been accomplished at room temperature. A comparison of the relative reactivities of 6-bromo and 6-chloro-2,3-disubstituted quinazolinones with phenyl boronic acid was conducted. An investigation of pre-catalyst loading for the reaction of the 6-bromo-2-cyclopropyl-3-(pyridyl-3-ylmethyl)quinazolin-4(3H)-one substrate was also carried out. Finally, we submitted our compounds to biological assays against alpha-glucosidase inhibitors. Of these, three hits (compounds 4a, 4t and 4r) were potentially active as alpha-glucosidase inhibitors and showed activity with IC50 values <20 muM. Based on structural novelty and desirable drug-like properties, 4a was selected for structure-activity relationship study, and thirteen analogs were synthesized. Nine out of thirteen analogs acted as alpha-glucosidase inhibitors with IC50 values <10 muM. These lead compounds have desirable physicochemical properties and are excellent candidates for further optimization. Sometimes chemists are able to propose two or more mechanisms that are consistent with the available data. category: catalyst-palladium, If a proposed mechanism predicts the wrong experimental rate law, however, the mechanism must be incorrect.Welcome to check out more blogs about 95464-05-4, in my other articles.

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

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The reaction of [Pd(dtbpf)Cl2] (dtbpf = 1,1?-bis(di-tert- butylphosphino)ferrocene) with a chemical oxidant led unexpectedly to the formation of [Pd(dtbpf)Cl]+. Further study found that a variety of reagents could be used to abstract a chloride ligand from [Pd(dtbpf)Cl 2] to yield [Pd(dtbpf)Cl]+. The solid-state structure suggests the formation of an Fe-Pd interaction. The presence of the bulky tert-butyl groups is essential, as similar reactions with [Pd(PP)Cl2] (PP = other 1,1?-bis(phosphino)ferrocene ligands) results in the formation of [Pd(PP)(mu-Cl)]22+. The analogous platinum compounds have also been investigated and appear to behave in a similar manner. Similar compounds of the type [M?(PP)(PR3)]2+ (M? = Pd, Pt, R = Ph, Me) have been prepared, and a metal-metal interaction has also been observed. Steric and electronic effects dictate the formation of these compounds. X-ray crystal structures were obtained for eight of these compounds and were used as the basis for a computational analysis of the metal-metal interaction. DFT analysis indicates the presence of a weak, noncovalent interaction between the two metal centers. The electrochemical properties of these compounds were examined by cyclic voltammetry and typically show one oxidative wave and either one two-electron or two one-electron reductive waves.

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

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Cyclopropylidene lithium carbenoids reacted with bis-(pinacolato)diboron in THF/Et2O at -110C to give various 1,1-diborylated cyclopropanes in good yields. Treatment of the diborylated cyclopropanes with 3-chloro-1-lithio-3-methyl-1-butyne produced the corresponding diborylated allenylcyclopropanes, which underwent ring-expansion in the presence of a Rh catalyst to give 1,2-diborylated methylenecyclopentenes conveniently. Copyright

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

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Reported herein are the syntheses and properties of a series of multi-nuclear metallodithiolene complex oligomers (5, 6 and 7) and a homologous polymer (8). The Ni/Pd-dithiolene complexes 5, 6 and 7 are characterized by intense absorption in the spectral region of 1000-1800 nm with a high molar absorption coefficient (e.g., 105 M-1 cm-1 at 1257 nm for 7). Complex polymer 8 is readily soluble in common organic solvents and shows remarkably broad and intense absorption in the entire near- and mid-infrared spectral region (800 nm-25 I¼m). The films of these metallodithiolene materials exhibit good visual transparency or extremely weak absorption in the visible region, making them potentially useful as excellent colourless infrared absorbers.

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

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The reaction of (eta2-CH2=CHCHO)ML2 (M = Pd, Pt; L = PPh3, L2 = DPPF) with methyl triflate gave eta3-methoxyallyl complexes [(eta3-CH 3OCHCHCH2)ML2][OTf]. X-ray diffraction analysis on [(eta3-CH3OCHCHCH2)M(dppf)] [OTf] (M = Pd, Pt) showed a distorted eta3-allyl structure. The enone complexes (eta2-CH2=CHCOCH3)M(PPh 3)2 also reacted with methyl triflate to give [(eta 3-CH3OC(CH3)CHCH2)M(PPh 3)2] [OTf]. It was proposed that these complexes were formed by the direct electrophilic attack of methyl triflate at the carbonyl oxygen of the enal or enone ligand on the palladium and platinum. In fact, no insertion of acrolein into the platinum-methyl bond of the separately isolated methylplatinum complex proceeded. On the other hand, methyl iodide underwent oxidative addition with zerovalent enal or enone complexes to give methylmetal complexes concomitant with dissociation of an enal or enone molecule.

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

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Nickel and palladium complexes of the 1,1′-bis(diphenylphosphino)ferrocene ligand effectively catalysed the regioselective cross-coupling of allylic ethers with phenylmagnesium bromide; use of the nickel catalyst leads to carbon-carbon bond formation giving the terminal alkene while the palladium catalyst gives the non-terminal alkene.

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

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Nucleophilic addition of the heterometallic complex [Pd2(dppf)2(mu-S)2] [dppf = 1,1?-bis(diphenylphosphino)-ferrocene] to [AgCl(PPh3)] or AgCl gave [Ag2Pd2Cl2(dppf)2-(mu 3-S)2], the first example of a heteropolymetallic aggregate based on a {Pd2S2} core and whose crystal structure shows a planar {Pd2S2} ring with two protruding AgCl fragments.

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

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Complexes of 1,1′-bis(diphenylphosphino)ferrocene corresponding to the separate steps of cross-coupling have been identified and related to the catalytic cycle.

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

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The present invention provides a nitrogen-containing saturated heterocyclic compound of the formula [I]: wherein R1 is a cycloalkyl group and the like, R22 is an optionally substituted aryl and the like, R is a lower alkyl and the like, T is a carbonyl group, Z is -O- and the like, and R3 to R6 are the same or different and a hydrogen atom and the like; or a pharmaceutically acceptable salt, that is useful as a renin inhibitor.

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

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A class of 3-phenylimidazo[1,2-a]pyridine derivatives, substituted at the meta position of the phenyl ring by an optionally substituted aryl or heteroaryl group which is directly attached or bridged by an oxygen atom or a ?NH? linkage, are selective ligands for GABAA receptors, in particular having high affinity for the alpha2 and/or alpha3 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of disorders of the central nervous system, including anxiety and convulsions.

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