Phenylamino Group Research Articles

Synthesis, SAR, and Evaluation of 4-[2,4-Difluoro-5-(cyclopropylcarbamoyl)phenylamino]pyrrolo[2,1-f][1,2,4]triazine-based VEGFR-2 kinase inhibitors

Introduction of the 2,4-difluoro-5-(cyclopropylcarbamoyl)phenylamino group at the C-4 position of the pyrrolo[2,1-f][1,2,4] triazine scaffold led to the discovery of a novel sub-series of inhibitors of VEGFR-2 kinase activity. Subsequent SAR studies on the 1,3,5-oxadiazole ring appended to the C-6 position of this new sub-family of pyrrolotriazines resulted in the identification of low nanomolar inhibitors of VEGFR-2. Antitumor efficacy was observed with compound 37 against L2987 human lung carcinoma xenografts in athymic mice.

3-(5-Chloro-2-hydroxyanilino)isobenzofuran-1(3H)-one

The crystal structure of the title compound, C14H10ClNO3, is stabilized by inversion-related O—H...O and C—H...O intermolecular hydrogen bonds and also by C—H...π and π–π interactions (centroid-to-centroid distance 3.681 Å and plane-to plane separation 3.618 Å). The O—H...O and C—H...O hydrogen bonds generate edge-fused R 2 1(6)R 4 4(27)R 2 1(6) ring motifs. The phthalide part of the molecule is planar and is inclined at 76.8 (2)° to the benzene ring of the aminophenyl group.

Investigation of the UV/Visible Absorption Spectra of Merocyanine Dyes Using Time-Dependent Density Functional Theory

The visible spectral properties of a set of merocyanine dyes have been determined experimentally and compared to theoretical estimates calculated using time-dependent density functional theory. Three families of merocyanines have been investigated. The merocyanines of the first class contain the 4-thiazolidinone, 2-thioxo group in resonance with different donor groups. In the second family, they present a common pyrrolo[2,3-c]pyrazole-6-(2H)-acetic acid, the 4-[4-(dialkylamino)phenyl]-3,5-dihydro-3,5-dioxo-2-phenyl group with different substituents on the two phenyl rings, while in the third family, they are constituted of an isoxazolone group linked via a conjugated polyenic segment to an aminophenyl group. Two hybrid exchange-correlation functionals have been used, whereas solvent effects have been included using the integral equation formalism of the polarizable continuum model. Moreover, for one compound, the vibrational structure of the electronic transitions has been determined by calculating the Franck-Condon factors within the Born-Oppenheimer approximation. The calculations show that the dominant transitions present a pi-pi(*) character. This approach reproduces nicely the variations of excitation energies with the nature of the merocyanine so that least-squares fits can be used to correct for the major systematic errors of the computational scheme and to reach an accuracy of 0.09 eV or better. Part of these systematic errors is shown to originate from the description of the solvent effects, whereas vibronic effects can account for most of the remaining differences.

Characterization of cationic glycoporphyrins by electrospray tandem mass spectrometry

Novel cationic porphyrin derivatives having a galactose or a bis(isopropylidene)galactose unit linked directly to a pyridine or to an aminophenyl group were characterized by electrospray tandem mass spectrometry (ESI-MS/MS). The electrospray mass spectra (ESI-MS) show the M(+) ions, since these porphyrins are already monocharged in solution. The fragmentation of these ions under ESI-MS/MS conditions was studied and it was found that elimination of the sugar residue as a radical (-163 or -243 Da) is a common fragmentation pathway. Loss of the sugar unit as a neutral fragment (-162 or -242 Da) and cross-ring fragmentations typical of glyco-derivatives are also observed for the pyridinium glycoporphyrins, but they are absent in the case of ammonium glycoporphyrins. The cationic beta-pyridiniumvinyl porphyrins show an atypical fragmentation due to the cleavage of the C(5)-C(6) bond of the sugar unit. Overall, the different patterns of fragmentation observed in the ESI-MS/MS spectra of the sugar pyridinium porphyrins and of the sugar ammonium phenyl porphyrins can give important information about the type of spacer between the porphyrin and the sugar unit.

Synthesis of Silica−Gold Nanocomposites and Their Porous Nanoparticles by an In-Situ Approach

We demonstrate the one-step synthesis of a silica-gold nanocomposite by simultaneous hydrolysis and reduction of gold chloride. The aminophenyl group was used as a reducing agent, and the trimethoxy silane group acts a precursor for the formation of silica. The porous gold nanoparticles were formed by etching out the silica-gold nanocomposite by hydrofluoric acid. The electron diffraction of porous gold nanoparticles showed that the particle are polycrystalline with FCC structure. The silica-gold nanocomposite exhibited nonlinear current-voltage behavior, and the porous gold nanoparticles displayed linear current-voltage behavior.

Photophysical studies of tetratolylporphyrin photosensitizers for potential medical applications

A group of meso-substituted synthetic tetratolylporphyrins was investigated by the methods of absorption and fluorescence spectroscopies as well as steady-state and time-resolved photothermal spectroscopies. The experiments were carried out in the air, oxygen or nitrogen atmospheres, at two temperatures. The details concerning the fast and slow deactivation processes of excitation energy of the dyes were studied. The estimated quantum yield of fluorescence and the efficiency of (S 1–T 1) intersystem crossing process give a possibility to evaluate the population yield and quenching rate of the triplet state, important for the therapeutic application, mostly mediated by the T 1-state. For tetrapyrrole with the carboxyphenyl group substituted in meso-position, the triplet state yield was the highest, of 0.86–0.94, whereas the porphyrin with aminophenyl group seemed to be efficient singlet oxygen generators (0.81–0.99) with a high rate constant of its excited triplet state quenching by molecular oxygen.

Synthesis and Src Kinase Inhibitory Activity of 2-Phenyl- and 2-Thienyl-7-phenylaminothieno[3,2-b]pyridine-6-carbonitriles

2-phenyl-7-phenylaminothieno[3,2-b]pyridine-6-carbonitriles were recently reported to be inhibitors of Src kinase activity. In this study we present structure-activity relationships for additional thieno[3,2-b]pyridine-6-carbonitriles, modifying the substituents on the C-2 phenyl and C-7 phenylamino groups. Derivatives with various aminomethyl and aminoethyl substituents on the para position of the C-2 phenyl group retained the activity of the initial analogues. However, direct attachment of an amino group led to decreased activity. A 2,4-dichloro-5-methoxyphenylamino group at C-7 provided superior inhibition of Src enzymatic activity. Replacement of the C-2 phenyl group with a 3,5-substituted thiophene led to improved Src inhibitory activity compared to the parent compound, but other thiophene isomers were less active. One of the analogues reported here exhibited in vivo activity comparable to that of SKI-606, a related 3-quinolinecarbonitrile currently in clinical trials.

(1-Naphthyl)phenylamino functionalized three-coordinate organoboron compounds: syntheses, structures, and applications in OLEDs

New three-coordinate organoboron compounds functionalized by a (1-naphthyl)phenylamino group, B(mes)2(dbp-NPB) (1), B(db-NPB)3 (2), and B(dbp-NPB)3 (3), have been synthesized. A variable temperature 1H NMR study showed that the aryl groups around the boron center in these compounds have a rotation barrier ∼70 kJ mol−1. The new boron compounds are amorphous solids with Tg being 110 °C, 171 °C and 173 °C, respectively. The electronic properties of the new boron compounds were investigated by cyclic voltammetry and UV–visible spectroscopy. All three boron compounds are blue emitters in the solid state. In solution the emission spectra of the boron compounds shift toward a longer wavelength with increasing solvent polarity. In CH2Cl2, the emission quantum efficiency of the three compounds was determined to be 0.22, 0.27 and 0.23, respectively. Several series of electroluminescent (EL) devices where compounds 1–3 are used as either an emitter/electron transport material, a hole transport material, or a hole injection material have been fabricated and their performance has been compared to the corresponding devices of BNPB, a previously investigated molecule, NPB, a commonly used hole transport material, and CuPc, a commonly used hole injection material. The EL results indicate that the new boron compounds are not suitable as emitters/electron transport materials, but they are promising as hole transport and hole injection materials in EL devices.

Novel 3‐Arylamino‐ and 3‐Cycloalkylamino‐5,6‐diphenyl‐pyridazines Active as ACAT Inhibitors.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Efficient Synthesis of 8‐Substituted Pyrazolo[1,5‐a]‐1,3,5‐triazines by Regioselective Acylation.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Novel 3-arylamino- and 3-cycloalkylamino-5, 6-diphenyl-pyridazines active as ACAT inhibitors.

A new series of pyridazine derivatives, structurally related to the previously reported ACAT inhibitors 3-(cyclo)alkylamino-5, 6-diphenyl-pyridazines, were synthesized and tested for their inhibitory properties. Substitution of the 3-alkylamino chain with a phenylamino group maintains activity. In contrast, the presence of either substituents on the phenylamino group or aliphatic rings having more or less than six carbon atoms lowers it.

Imaging Characteristics of Diazo Resin with a Dialkylamino Group for Screen Printing

When photolysis of diazo compounds with dialkylamino groups is compared with photolysis of diazo compounds with other substituents, quantum yields Φ are larger and thermal decomposition rates are slower than for the other substituents, respectively. These properties are suitable for sensitivity and thermal stability for diazo resins. In this study, the imaging characteristics of a diazo resin with dialkylamino groups (MDR) are reported and compared with the conventional diazo resin with the phenylamino group (DPR) for screen printing. The photosensitive diazo compounds with the dialkylamino group, p-N, N bis(3-aryloxy-2-hydroxy-propyl) amino benzene diazo compound (MD), has λmax at 382 nm, and shows little absorption in the visible region. The transmittance of the diazo resin MDR based on MD in PVA film at 400 nm after exposure with a high pressure mercury lamp was 10 % higher than that of DPR which is a condensation product between p-diazodiphenylamine (DPD) and formaldehyde. Molar extinction coefficient (ε) and quantum yield (Φ) of MD at 365 nm were similar to those of p-dimethylaminobenzene diazo compounds (DED). The values of ε and Φ were 1.3 times and 1.2 times as large as those of DPD, respectively. The degradation temperature (TD) by thermogravimetric analysis of MDR was 5°C lower than that of DPR, but the storage stability of MDR was superior. We propose that the high photosensitivity, the bleaching characteristics, and the superior storage stability should make MDR a useful thick resist layer for screen printing.

The redox properties of ferrocenyl-substituted aryl azines

A series of ferrocenyl substituted azines (1-Fc/Ar, where Ar = 4-NO2C6H4, 4-CNC6H4, 4-OCH3C6H4, C5H4N, ferrocene, anthracene, and pyrene) were investigated by electrochemical and photochemical techniques. All the 1-Fc/Ar exhibited oxidation waves within 60 mV of each other, consistent with the expected oxidation of the ferrocene moiety. The reduction properties of 1-Fc/Ar is governed by the nature of the Ar substituent. The standard reduction potentials suggest that ferrocene has comparable electron donating abilities as a 4-methoxyphenyl and 4-dimethyl aminophenyl group. The anthracenyl azines exhibit one-electron reversible reduction followed by dimerization of the radical anion resulting in dimerization rate constants (kd) between 5.1 × 104 and 1.5 × 105 M–1 s–1. 1-Fc/Anth and related azines undergo photochemical E/Z isomerization of the C=N bonds to produce E/Z and Z/Z isomers from the thermodynamically most stable E/E form. Fluorescence at 77 K, was observed for these compounds only after long- wavelength irradiation to produce a mixture of E/E, E/Z, and Z/Z isomers. Fluorescence quantum yields of 0.042, 0.090, and 0.176 were determined for 2-Anth/H, 2-Anth/Anth, and 1-Fc/Anth, respectively. The electrochemical, photochemical, and X-ray data suggest that the azine unit is a conjugation "limiter" and may be a general characteristic of azine molecules.Key words: azines, electrochemistry, cyclic voltammetry, reduction, electron transfer.

Direct Phenylamination of 6-Aminonaphthacenequinones Promoted by Metal Salts

6-Amino-5,12- and -5,11-naphthacenequinones react with aniline in the presence of cobalt, copper, and manganese salts, resulting in replacement of hydrogen in the peri-position with respect to the carbonyl group by phenylamino group and formation of 11- and 12-phenylamino-6-amino(phenylamino)-5,12- and -5,11-naphthacenequinones.

Histamine H 1 receptor ligands : Part II. Synthesis and in vitro pharmacology of 2-[2-(phenylamino)thiazol-4-yl]ethanamine and 2-(2-benzhydrylthiazol-4-yl)ethanamine derivatives

New 2-[2-(phenylamino)thiazol-4-yl]ethanamine and 2-(2-benzhydrylthiazol-4-yl)ethanamine derivatives were prepared and tested in vitro as H 1 receptor antagonists. The compounds with 2-phenylamino substitution with meta-halide substituents at the phenyl ring, showed weak H 1-antagonistic activity (pA 2: 4.62–5.04) and this activity was completely lost in the case of meta-methyl substituent (pA 2<4). When the phenylamino group was replaced by benzhydryl groups of classic antihistamines, the resulting compounds exhibited slightly improved H 1-antagonistic activity (at the meta-position pA 2: 6.38–6.15; at the para-position pA 2: 6.04–5.87).

Synthesis and Characterization of Dendritic Poly(ether imide)s

New dendritic poly(ether imide)s were synthesized by the convergent growth approach, using 1-(4-aminophenyl)-1,1-bis(4-hydroxyphenyl)ethane, as the building block. The aromatic nucleophilic substitution of the building block with 3-nitro-N-phenylphthalimide led to the first-generation dendron with aminophenyl group at the focal point, which was subsequently reacted with 3-nitrophthalic anhydride to yield the dendritic wedge containing an activated nitro group. The resulting nitro functionality was allowed to react with the building block to give the second-generation dendron, which was then condensed with 3-nitrophthalic anhydride, followed by ring closure to re-form the phthalimide ring and restore a reactive nitro group. Through an aromatic nucleophilic substitution, the dendritic wedges with an activated nitro group were coupled to the polyfunctional core to form the dendritic macromolecules. Structures of the ether−imide dendrimers were fully characterized by use of a combination of techniques including 1H NMR, 13C NMR, IR, and mass spectrometry. The glass transition temperature of the dendrimers increased with molecular weight, and the variation was consistent with theoretical calculations. These dendritic poly(ether imide)s are soluble in various organic solvents and had a thermal stability comparable to linear poly(aryl ether imide)s.

Investigation of poly(arylenevinylene)s, 42. Synthesis of PPV-based copolymers containing alkyldiphenylamine and triphenylamine in the main chain

PPV-based copolymers carrying in-chain tertiary amino groups have been synthesized by Horner-type polycondensation of arylamine dialdehydes and alkoxy-substituted xylylene bis(phosphonate)s: [-NR-C 6 H 4 -CH=CH-C 6 H 2 (OAlkyl) 2 -CH=CH-C 6 H 4 -] n 6. Several compounds with the general structure 6 and containing methylamino, cyclohexylamino, and phenylamino groups have been prepared and analyzed. Incorporation of electron-rich amino groups into the PPV backbone does not interrupt the main-chain conjugation but has the effect of reducing the oxidation potential, thus transforming these polymers into highly photoconducting and hole injecting/hole transporting materials. These new polymers were evaluated using photoluminescence and cyclic voltammetry methods and characterized by gel-permeation chromatography (GPC) and DSC. The chemical structure was confirmed by NMR- and UV/VIS absorption spectroscopy. The polymers 6 are well-defined, completely soluble materials of high molecular weight (M w > 20000). They possess all-trans vinylene units and exhibit a strong green photoluminescence (Φ PL 70%). Solution-cast solid films show an outstanding photoconductivity in the UV/VIS range.

Synthesis and tyrosine kinase inhibitory activity of a series of 2-amino-8H-pyrido[2,3-d]pyrimidines: identification of potent, selective platelet-derived growth factor receptor tyrosine kinase inhibitors.

Screening of a compound library led to the identification of 2-amino-6-(2,6-dichlorophenyl)-8-methylpyrido[2,3-d]pyrimidine (1) as a inhibitor of the platelet-derived growth factor receptor (PDGFr), fibroblast growth factor receptor (FGFr), and c-src tyrosine kinases (TKs). Replacement of the primary amino group at C-2 of 1 with a 4-(N,N-diethylaminoethoxy)phenylamino group yielded 2a, which had greatly increased activity against all three TKs. In the present work, variation of the aromatic group at C-6 and of the alkyl group at N-8 of the pyrido[2,3-d]pyrimidine core provided several analogues that retained potency, including derivatives that were biased toward inhibition of the TK activity of PDGFr. Analogues of 2a with a 3-thiophene or an unsubstituted phenyl group at C-6 were the most potent inhibitors. Compound 54, which had IC50 values of 31, 88, and 31 nM against PDGFr, FGFr, and c-src TK activity, respectively, was active in a variety of PDGF-dependent cellular assays and blocked the in vivo growth of three PDGF-dependent tumor lines.

The Role of the 2,4,6‐Tris(trifluoromethyl)phenylamino Group in Stabilizing New Phosphorus‐, Arsenic‐, and Germanium‐Containing Main‐Group Compounds and Transition‐Metal Derivatives

AbstractThe reactions of potassium Rf‐amide [Rf = tris(trifluoromethyl)phenyl](2) with PCl3, AsC13, and GeC12 · dioxane yield new four‐membered inorganic heterocycles [RfNPCl]2 (3), [RfNAsC1]2 (4), and [RfNGe]2 (5), respectively. On the other hand, the reaction of Rf‐amide 2 with two equivalents of RfPCl2 leads to the formation of the imino‐γ3‐phosphane RfN=PRf (6) and the diamino‐γ3‐phosphane (RfNH)2PRf (7). The iminophosphane 6 reacts with Ni(CO)2(PPh3)2 and forms the complex [Ni(PPh3)2(RfN=PRf)] (9), in which the imino‐ phosphane coordinates to the metal through the phosphorus lone pair. Treatment of lithium amide 2 with transition metal chlorides ZnCl2 and FeCl2 yields the imido/amido spirocyclic metal derivatives 9 and 10, respectively. Compounds 3–10 have been extensively characterized by their analytical and mass, IR, and NMR (1H, 19F, and 31P) spectroscopy. Further, the molecular structures of all the compounds have been unambiguously determined by single‐crystal X‐ray diffraction studies. The diazadigermetidine 5 crystallizes in a fluorescent‐yellow orthorhombic and a yellow monoclinic crystal modification. The results obtained reveal the role of Rf, group in stabilizing new multiple bonded systems and inorganic heterocycles. A skeletal rearrangment of the Rf ligand is observed in the reactions leading to compounds 9 and 10. Moreover, the preparation of compounds 9 and 10 indicates the limitation of the use of this ligand in the preparation of new metal‐amide systems, especially where the metal atoms have a strong tendency for the formation of strong MF bonds.

Highly sensitive spectrophotometric determination of nitrite ion using 5,10,15,20-tetrakis(4-aminophenyl)porphine for application to natural waters

A water-soluble porphyrin having the aminophenyl group, 5,10,15,20-tetrakis(4-aminophenyl)porphine, reacts with nitrite ion, and produces a large spectral change ( Δε = 3.0 × 10 5 l mol −1 cm −1, 434 nm). There are few interfering substances and it is easy to establish the reaction conditions because the spectral change mechanism is based only on diazotization. A highly sensitive spectrophotometric determination of nitrite was developed on this basis. The calibration graph was linear in the range 0 to 4.0 × 10 −7 mol l −1 (0–18 ng ml −1). The detection limit { S N = 3} was 4.0 / sx 10 −9 mol l −1 (0.18 ng ml −1), and the relative standard deviation was 1.0% (at 2.0 × 10 −7 mol l −1 nitrite, 10 determinations). This method has been applied to the determination of nitrite in rain, tap and spring water without any pretreatment.