109482-86-2

A cascade strategy to synthesise gem-difluorinated 2H-furans from reactions of BrCF2CO2Et with enaminones has been described. The reactions tolerate a wide variety of functional groups under metal-free conditions. An active aminocyclopropane is proposed to be a key intermediate through the cyclopropanation of difluorocarbene with enaminones, which further triggers a regioselective C-C bond cleavage in situ to afford the corresponding gem-difluorinated 2H-furans.

By removing 5-methyl and 6-acetyl groups in our previously reported compound 3, we designed a series of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine derivatives as potential tubulin polymerization inhibitors. Among them, compound 5e displayed low nanomolar antiproliferative efficacy on HeLa cells which was 166-fold higher than the lead analogue 3. Interestingly, 5e displayed significant selectivity in inhibiting cancer cells over HEK-293 (normal human embryonic kidney cells). In addition, 5e dose-dependently arrested HeLa in G2/M phase through the alterations of the expression levels of p-cdc2 and cyclin B1, and caused HeLa cells apoptosis by regulation of expressions of cleaved PARP. Further evidence demonstrated that 5e effectively inhibited tubulin polymerization and was 3-fold more powerful than positive control CA-4. Moreover, molecular docking analysis indicated that 5e overlapped well with CA-4 in the colchicine-binding site. These studies demonstrated that 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine skeleton might be used as the leading unit to develop novel tubulin polymerization inhibitors as potential anticancer agents.

A series of ruthenium (II) complexes derived from the reaction between cis-bis (2,2′-bipyridine) dichloro ruthenium (II) dihydrate and enaminone derivatives of ciprofloxacin were synthesized and fully characterized using elemental analysis, cyclic voltammetry and different spectroscopic techniques (Uv–vis, FTIR, NMR, mass spectroscopy, and X-ray photoelectron spectrometry (XPS)). The isolated compounds were tested for their antibacterial and antifungal activities against gram-negative and gram-positive bacteria. The FTIR data revealed that ciprofloxacin derivatives act as bidentate ligands through the pyridone carbonyl and the carboxylate oxygen atom. The UV–visible data showed that the charge transfer CT band is blue shifted upon the coordination of the ciprofloxacin derivatives compared to the CT band of the parent complex. The XPS results revealed the characteristic peaks of Ru3p3/2 and Ru3p1/2 as well as Ru3d5/2 and Ru3d3/2, which confirmed the assembly of the ruthenium (II) ciprofloxacin derivative complexes. Cyclic voltammetry data showed that the ciprofloxacin enaminone derivatives have a similar reduction potential for the Ru (II)/Ru (III) redox couple, and it revealed that the coordination of the ruthenium (II) ion altered the redox property of the ligands and enhanced their electron transfer rate. The electrochemical and the UV–visible results suggest that the ciprofloxacin derivative ligands are (Formula presented.) -acceptor ligands. Further, the complexes showed higher antibacterial activities than the parent ciprofloxacin antibiotic and did not show antifungal activities among the tested fungi strains.

A straightforward strategy for synthesis of highly functionalized trifluoromethyl 2H-furans is described. The copper catalyzed method relies on a cascade cyclic reaction between enaminones and N-tosylhydrazones. This method allows the synthesis of 2-amino

Novel 6(3-1H-1,2,4-triazol-1-yl)-3-phenylquinazoline-2,4(1H,3H)-diones (7a-e) were synthesized from different enaminones (6a-e) with 6-hydrazinyl-3-phenylquinazoline-2,4(1H,3H)-dione. 2,6(4-2-Substituted-1,3,5-triazin-1(2H)-yl)-3-phenylquinazoline-2,4(1H,3H)-diones (8a-k) were synthesized from the reaction of 1-(2,4-dioxo-3-phenyl-1,2,3,4-tetrahydroquinazolin-6-yl)thiourea, urea, or guanidine (3a-c) with enaminones (6a-e), and a series from 3-substituted-2-imino-1,3,5-triazin-1(2H)-yl-sulfonyl-phenyl-1-methylquinazoline-2,4(1H,3H)-dione (12a-j) were obtained from the reaction of N-(diaminomethylene)-4-(1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)benzenesulfonamide (11) with the enaminone (6a-j). The antitumor activity of the synthesized compounds was evaluated against two human cell lines: human colon carcinoma HCT116 and human hepatocellular carcinoma HEP-G2. Some of the tested compounds showed significant potency compared to the reference drug staurosporin.

A highly site-selective acyloxylation of stable enamines with PhI(OAc)2 under metal-free conditions to afford (E)-vinyl acetate derivatives in good to excellent yields is described. Depending on the judicious choice of the solvent system, either the α- or β-site-selective product could be obtained with high selectivity. For the α-site-selective product, the rearranged amide compound is obtained as the major product. This reaction proceeds under mild reaction conditions (room temperature, metal-free, and open-flask) and features a broad substrate scope.

A novel TBAI-catalyzed radical sulfonylation of readily available N,N-dimethylenaminones with sulfonylhydrazides to afford functionalized β-keto-sulfones has been developed. Various functional groups were tolerated well under the present oxidative conditions and the corresponding β-keto-sulfone compounds were obtained in moderate to good yields. Importantly, this transformation offered the first protocol for Csp3–S bond formation by oxidative Csp2–Csp2 bond cleavage in one step.

An efficient method to construct functionalized 1,4-ketoaldehydes bearing all-carbon α-quaternary centers via regioselective C-C bond activation has been described. The cyclopropanation of bench-stable enaminones with in situ generated diazo reagents from

A direct and regiocontrolled thiolation method to access β-amino sulfides through the palladium-catalyzed C(sp2)–H functionalization of stable enamines was described. The reaction was realized under mild conditions by adding an external phosphi

Enaminoketones undergo unexpected self condensation in acetic acid to produce a wide range of 2,3,6-trisubstituted pyridine derivatives in excellent yields in the presence of NH4OAc. This is the first Letter on the synthesis of 2,6-diarylnicoti

1-Methylimidazole exhibits an unusually high efficiency in promoting the reaction of aryl methyl ketones with DMF-DMA to form (2E)-1-aryl-3- dimethylamino-2-propenones which lacks correlation between the catalytic efficiency and the basicity of 1-methylim

A cascade organocatalysis is reported for the nucleophilic and electrophilic dual activation taking place in the reaction of methyl ketones or active methylene compounds with DMF-DMA (N,N-dimethylformamide dimethyl acetal). L-Proline serves as an efficient organocatalyst in the covalent and noncovalent synchronous mode for the ambiphilic activation of various aryl, heteroaryl, and styryl methyl ketones, cyclic ketones, and 1,3-diketones with DMF-DMA to achieve the convenient syntheses of the versatile synthons (2E)-1-aryl/ heteroaryl/styryl-3-(dimethylamino)-2-propen-1-ones, (E)-α- [(dimethylamino)formylidene]cycloalkanones, and (E)-2-(dimethylamino) formylidene-1,3-diketones in high yields under solvent-free conditions.

A novel organocatalytic dual activation strategy is reported for an efficient synthesis of the versatile synthons (2E)-1-aryl/heteroaryl/styryl-3- (dimethylamino)prop-2-en-1-ones and -(E)-[(dimethylamino)methylene] cycloalkanones. 2-Guanidinoacetic acid (10 mol%) serves as an ambifunctional organocatalyst for the reaction of various aryl/heteroaryl/styryl methyl ketones and cyclic ketones having an -methylene moiety with N,N-dimethylformamide dimethyl acetal at 100 C for 1-3 hours under solvent-free conditions to afford the corresponding (2E)-3-(dimethylamino)prop-2-en-1-ones in 72-95% yields. Georg Thieme Verlag Stuttgart - New York.

The anti-inflammatory activities of a prepared isoegomaketone 3a and its derivatives 3b-3f were evaluated in RAW 264.7 cells. Among these, the compound 3d was displayed the most potent inhibitory activities against production of nitric oxide, monocyte chemoattractant protein- 1 and interleukin-6. Based on these results, the abilities of compounds 3a-3f to modulate NF-κB and AP-1-mediated gene transcription using a luciferase reporter assay were investigated. The transcriptional activities of NF-κB and AP-1 decreased when pretreated with 3a- 3f. Interestingly, at 10 μM, compound 3d markedly suppressed the lipopolysaccharide-induced NF-κB and activator protein-1 DNA binding activities. Some preliminary structure-activity relationships were proposed that may provide a direction for further study.

Microwave-assisted [2+2] cycloaddition of (E)-3-dimethylamino-1-heteroaryl-prop-2-en-1-ones to dimethyl acetylenedicarboxylates gives (2E,3E)-dimethyl-2-[(dimethylamino)methylene]-3-(substituted)succinates in 8-91% yield. In the case of a 4,5-dihydrothiazoline derivative, cycloaddition also took place at the endocyclic C{double bond, long}N double bond.

The present invention provides 6-substituted 2,3,4,5-tetrahydro-1H-benzo[d]azepines of Formula I as selective 5-HT2C receptor agonists for the treatment of 5-HT2C associated disorders including obesity, obsessive/compulsive disorder, depression, and anxiety: Formula (I) where: R6 is selected from the group consisting of (a, b, c, d, e) and other substituents are as defined in the specification.

(Chemical Equation Presented) The regioselective synthesis of 3- and 5-substituted-isoxazoles from the reaction of β-dimethylaminovinyl ketones [R-C(O)CH=CH-NMe2, where R = Ph, MeO-4-C6H4, F-4-C6H4, C

The reaction of methyl ketones 1a-g with dimethylformamide dimethylacetal (DMFDMA) afforded the enaminones 2a-g, which were coupled with diazotized aromatic amines 3a,b to give the corresponding aryl hydrazones 6a-h. Condensation of compounds 6a-h with so

(Chemical Equation Presented) The reaction between 3-(dimethylamino)/3,3- bis(methylthio)-1-(substituted)prop-2-en-1-ones and 4-substituted-5-amino-1H- pyrazoles afforded new pyrazole[1,5-a]pyrimidines structurally related to Zaleplon. The chemical modifications introduced at the 3-, 5-, and 7-positions of the bicyclic structure revealed new promising candidates for the treatment of sleep disorders.

A novel series of antiproliferative agents containing pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides, selective for p21-deficient cells, were identified by high-throughput screening. Exploration of the SAR relationships in the headpiece, core, and tailpiece

The present invention provides 2-aminopyridine compound having an excellent adenosine receptor (A1, A2a, A2b receptors) antagonism, which is represented by the following formula: (wherein, R1 represents cyano gr

The synthesis of heterocyclic appended vinylogous iminium salts is described along with their conversion to heterocyclic appended pyrimidines, triazolopyrimidines, and pyrroles.

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Several new 6-substituted-3-acylamino-2H-pyran-2-ones 6 a-j are prepared from the reaction of the enaminones 4 a-f with N-acyl- and N-benzoyl-glycines. The enaminones 4 a-c react with malononitrile in ethanol solution and in presence of a base to yield th

Vinylogous hydroxamic acids (3-N-hydroxy-N-alkylamino)-2-propen-1-ones, VHA) were prepared as antiinflammatory agents.The synthesis, chemical properties, and in vitro biological activities of these relatively unexplored compounds are described.The VHAs were prepared by condensation of the appropriate N-substituted hydroxylamine with any of the three reagents: a 1,3-dicarbonyl compound (method A); a vinylogous amide (method B); or an alkynone (method C).The VHAs exist as one or more tautomers in solution with the relative proportions of each being dependent upon the structure of the VHA, solvent, and pH.VHAs undergo some of the typical reactions of hydroxamic acids as well as those of vinylogous amides.VHAs are active as inhibitors of 5-lipoxygenase and of IL-1 biosynthesis in vitro, which do not inhibit other enzymes of the arachidonic acid cascade.They have been shown by ESR studies to bring about inhibition of soybean type 1 15-lipoxygenase by reduction of the active site iron.

The invention provides a novel process for producing N-[3-(1H-imidazol-1-yl)phenyl]-4-(substituted)-2 pyrimidinamine compounds in which the substituent is a 2-pyridinyl, 3-pyrindinyl, 4-pyridinyl, 2-furanyl or 2-thienyl group. The process includes the steps of (1) reacting a 3-(1H-imidazol-1-yl)benzamine with cyanamide and a halogen acid while controlling the pH of the reaction between pH about 2 to abourt 3.5 and recovering a [3-(1H-imidazol-1-yl)phenyl] guanidine dihydrohalide and (2) reacting the [3-(1H-imidazol-1-yl)phenyl] guanidine dihydrohalide so recovered with an appropriately substituted 3-dimethylamino-1-(substituted)-2-propen-1-one and a base at a pH of from about 10.5 to about 11.5 and recovering the N-[3-(1H-imidazol-1-yl)phenyl-4-(substituted)-2-pyrimidamine compound so produced. The novel process provides improved yield and purity by adhering to the stated crucial pH ranges.

Novel pyrimidine compounds are disclosed of the class represented by the formula: STR1 wherein R1 is selected from the class consisting essentially of hydrogen, chloro, bromo, cyano (--CN), carbamoyl (--CO--NH2), carboxyl (--COOH), and lower alkoxycarbonyl (--CO--O--R3, where R3 is a lower alkyl radical having 1-4 carbon atoms), and wherein R2 is a monovalent radical selected from the class consisting essentially of furyl, thienyl, 3-pyridyl and 3-pyridyl-N-oxide, either of said pyridyl radicals optionally being substituted with an alkyl radical having from 1 to 4 carbon atoms. Processes of preparing such compounds are disclosed. The novel compounds are useful as anxiolytic agents in ameliorating anxiety in a mammal.