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Methylation of aromatic amines and imines using formic acid over a heterogeneous Pt/C catalyst

We describe here a commercially available Pt/C catalyst capable of catalyzing the methylation of anilines and aromatic imines with formic acid in the presence of a hydrosilane reductant. Both primary aniline and secondary aniline can be methylated. The advantage of this newly described method includes operational simplicity, high TON, ready availability of the catalyst, and also good functional group compatibility.

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A N – methyl anisidine preparation method (by machine translation)

The invention discloses a N – methyl anisidine preparation method, to anisidine and methanol as the reactant, a composite metal oxide A a B as catalyst, the reaction temperature 200 – 350 o C, the liquid volume airspeed is 0.1 – 2.0 h- 1 , N2 Under the condition of the gas as the carrier gas in a fixed bed continuous flow reactor reaction to obtain N – methyl-P-anisidine; composite metal oxide A a B A representative in the catalyst active component CuO – ZnO – NiO or CuO – ZnO – Cr2 O3 , The representative Al B surface coating2 O3 , SiO2 , TiO2 Or a material in the C; Cu and Zn molar ratio of 0.1 – 10:1, cu with Ni molar ratio of 0.1 – 10:1, cu with Cr molar ratio of 0.1 – 10:1; Al the surface coating2 O3 , SiO2 , TiO2 Or C material accounts for the total amount of catalyst 1 – 10 wt %. The invention has simple operation, mild condition, catalyst performance is stable, high yield, low cost, low pollution. (by machine translation)

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Photoinduced and N-bromosuccinimide-mediated cyclization of 2-azido-N-phenylacetamides

An efficient synthesis of quinoxalin-2(1H)-ones or spiro[cyclohexene-1, 2?-imidazol]-4?-ones has been achieved in moderate to high yields by the visible light-induced and N-bromosuccinimide-mediated cyclization reaction of 2-azido-N-phenylacetamides at ambient temperature. Both the regioselectivity and the speed of cyclization are affected by the substituents attached to the phenyl ring. For example, quinoxalin-2-ones are produced as the main products when the substrates bear electron-withdrawing groups at the para-position of the phenyl ring; in contrast, spiro[cyclohexene-1,2?-imidazol]-4?-ones are obtained as the main products when the substrates bear electron-donating groups at the para-position.

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Identification of novel 2-(benzo[d]isoxazol-3-yl)-2-oxo-N-phenylacetohydrazonoyl cyanide analoguesas potent EPAC antagonists

Two series of novel EPAC antagonists are designed, synthesized and evaluated in an effort to develop diversified analogues based on the scaffold of the previously identified high-throughput (HTS) hit 1 (ESI-09). Further SAR studies reveal that the isoxazole ring A of 1 can tolerate chemical modifications with either introduction of flexible electron-donating substitutions or structurally restrictedly fusing with a phenyl ring, leading to identification of several more potent and diversified EPAC antagonists (e.g., 10 (NY0617), 14 (NY0460), 26 (NY0725), 32 (NY0561), and 33 (NY0562)) with low micromolar inhibitory activities. Molecular docking studies on compounds 10 and 33 indicate that these two series of compounds bind at a similar site with substantially different interactions with the EPAC proteins. The findings may serve as good starting points for the development of more potent EPAC antagonists as valuable pharmacological probes or potential drug candidates.

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Palladium-catalyzed amination of chloromethylnaphthalene and chloromethylanthracene derivatives with various amines

Palladium-catalyzed amination of chloromethylnaphthalene and chloromethylanthracene derivatives to produce naphthylamines and anthrylamines in satisfactory to good yields has been developed. The unprecedented amination reactions proceeded smoothly under mild conditions in the presence of Pd(PPh3)4 as a catalyst.

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6-Substituted 2,4-diaminopyrido[3,2-d]pyrimidine analogues of piritrexim as inhibitors of dihydrofolate reductase from rat liver, Pneumocystis carinii, and Toxoplasma gondii and as antitumor agents

The synthesis and biological activity are reported for 21 6-substituted 2,4-diaminopyrido[3,2-d]pyrimidine analogues (4-24) of piritrexim (PTX) as inhibitors of dihydrofolate reductase (DHFR) and as antitumor agents. Recombinant DHFR from Pneumocystis carinii (pc) and native DHFR from Toxoplasma gondii (tg) were the target enzymes tested; these organisms are responsible for fatal opportunistic infections in AIDS patients. Rat liver (rl) DHFR served as the mammalian reference enzyme to determine selectivity for the pathogenic DHFR. The synthesis of S9-bridged compounds 4-6 was achieved by aryl displacement of 2,4-diamino-6-chloropyrido[3,2-d]pyrimidine (27) with thiol nucleophiles. Oxidation of 4-6 with hydrogen peroxide in glacial acetic acid afforded the corresponding sulfone analogues 7-9. The N9- bridged compounds 10-24 were synthesized from their precursor 3-amino-6- (arylamino)-2-pyridinecarbonitriles via a thermal cyclization with chloroformamidine hydrochloride. Unlike the S9-bridged compounds, the arylamino side chains of the N9-bridged analogues were introduced prior to the formation of the 2,4-diaminopyrido[3,2-d]pyrimidine nucleus. A reversed two-atom-bridged analogue (25) was also synthesized using a synthetic strategy similar to that utilized for compounds 10-24. The IC50 values of these compounds against pcDHFR ranged from 0.0023 x 10-6 M for 2,4-diamino- 6-(N-methyl-3′,4′-dimethoxyanilino)pyrido[3,2-d]pyrimidine (21), which was the most potent, to 90.4 x 10-6 M for 2,4-diamino-6-(4′-methoxyanilino)- pyrido[3,2-d]pyrimidine (12), which was the least potent. The three S9- bridged compounds tested were more potent than the corresponding sulfone- bridged compounds for all three DHFRs. N9-Methylation increased the potency by as much as 17 000-fold (compounds 15 and 21). None of the analogues were selective for pcDHFR. Against tgDHFR the most potent analogue was again 21 with an IC50 value of 0.00088 x 10-6 M and the least potent was 12 with an IC50 of 2.8 x 10-6 M. N9-Methylation afforded an increase in potency of up to 770-fold (compound 15 NH vs 21 N-CH3) compared to the corresponding N9-H analogue. In contrast to pcDHFR, several analogues had a greater selectivity ratio for tgDHFR compared to trimetrexate (TMQ) or PTX, most notably 2,4-diamino-6-[(3′,4′-dimethoxyphenyl)thio]pyrido[3,2-d]pyrimidine (4), 2,4-diamino-6-[(2′-methoxyphenyl)sulfonyl]pyrido[3,2-d]pyrimidine (7), and 2,4-diamino-6-(2′,5′-dimethoxyanilino)pyrido[3,2-d]pyrimidine (14) which combined relatively high potency at 10-7-10-8 M along with selectivity ratios of 3.97, 6.67, and 4.93, respectively. Several analogues synthesized had better selectivity ratios than TMQ or PTX for both pcDHFR and tgDHFR, and the potencies of the N9-methylated compounds were comparable to or greater than that of TMQ or PTX. Selected compounds were evaluated as inhibitors of the growth of a variety of tumor cells in culture. The N9-CH3 analogues were, in general, highly potent with GI50 values in the nanomolar range. The N9-H and S9 analogues were less potent with GI50 values in the millimolar to micromolar range.

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IMIDAZOL- OR 1,2,4-TRIAZOL-DERIVATIVES AND THEIR USE

The present invention is directed to novel compounds of formula (I), pharmaceutically acceptable salts or solvates thereof, and their use.

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Intramolecular annulation of aromatic rings with N-sulfonyl 1,2,3-triazoles: Divergent synthesis of 3-methylene-2,3-dihydrobenzofurans and 3-methylene-2,3-dihydroindoles

The controllable synthesis of 3-methylene-2,3-dihydrobenzofurans 2 and 3-methylene-2,3-dihydroindoles 5 has been developed through Rh-catalyzed intramolecular annulation of aromatic rings with azavinyl carbenes. This journal is

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Functionalized diarylisoxazoles inhibitors of ciclooxygenase

The present invention refers to isoxazole derivatives, in particular diarylisoxazole derivatives inhibitors of cyclooxygenase (COX), in particular cyclooxygenase-1 (COX-1), to their pharmaceutical compositions, the process for their preparation and their use for the chemoprevention and treatment of inflammatory syndromes and in the prevention and treatment of carcinomas, in particular intestinal, ovarian and cutaneous carcinomas, in the treatment of pain syndromes, in particular after surgery, and in the cardiovascular field as antithrombotics/vasoprotectives/cardioprotectives.

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Nucleophilic substitution of halogen in 4-halogenated derivatives of glutamic acid 2. Structural effects of arylamine as nucleophile

Kinetics of nucleophilic substitution of halogen in diastereomeric dimethyl 4-bromo- and 4-iodoglutamates with ortho-, meta-, and para-substituted anilines was studied by HPLC.The threo-diastereomers of the halogenated derivatives react 3-5 times faster than the erythro ones.The structure of the transition state is discussed. – Key words: glutamic acid; diastereoselectivity; nucleophilic substitution; rate constant; arylamine.

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