Synthesis of novel 7-aryl and 7-spiropyrazolo[4′,3′:5,6]pyrido[2,3-<Emphasis Type="BoldItalic">d</Emphasis>]pyrimidine derivatives and their study as AChE inhibitors

An efficient route for the synthesis of novel 7-aryl and 7-spiropyrazolo[4\(^{\prime }\),3\(^{\prime }\):5,6]pyrido[2,3-d]pyrimidine derivatives is described. These compounds were obtained by a cyclocondensation reaction between pyrazolopyridinediamines 4 and aldehydes 5 or cyclic ketones 6 in the presence of acetic acid as catalyst. This procedure provides the desired compounds in good yields under a simple two-step methodology. The obtained compounds were evaluated as AChE inhibitors and showed weak AChe inhibition with \(\hbox {IC}_{50} = 115{-}470 \, \upmu \hbox {M}\).     

Synthesis and structure–behavior relationships of tetra-substituted imidazole derivatives of 1,3-diazabicyclo[3,1,0]hex-3-ene

Among photochromic compounds 1,3-diazabicyclo[3.1.0]hex-3-ene derivatives are currently the subject of intense research due to their photochromic behavior particularly in the crystalline state. In this work, the click syntheses of photochromic compounds containing tetrasubstituted imidazole moieties have been investigated. The structure?Cphotochromic behavior relationships of these compounds have been evaluated.     

2-[2-[4-[2-[2-[1,3-Dihydro-1,1-bis(4-hydroxyphenyl)-3-oxo-5-isobenzofuranthioureidyl]ethylaminocarbonyl]ethyl]phenyl] ethylamino]-5′-N-ethylcarboxamidoadenosine (FITC-APEC): A fluorescent ligand for A2a-adenosine receptors

The fluorescein conjugate, FITC-APEC (2-[2-[4-[2-[2-[1,3-dihydro-1,1-bis(4-hydroxyphenyl)-3-oxo-5-isobenzofuranthioureidyl]ethylaminocarbonyl]ethyl] phenyl]ethylamino]-5-N-ethylcarboxamidoadenosine), is a novel ligand derived from a series of functionalized congeners that act as selective A_2a-adenosine receptor agonists. The binding of FITC-APEC to bovine striatal A_2a-adenosine receptors measured by fluorescence techniques was saturable and of a high affinity, with aB _max of 2.3±0.3 pmol/mg protein andK _D of 57±2 nM. TheK _D value estimated by fluorescence was consistent with theK _i (11±0.3 nM) obtained by competition studies with [³H]CGS 21680. Additionally, theB _max value found by FITC-APEC measurement was in agreement withB _max values obtained using radioligand binding. FITC-APEC exhibited rapid and reversible binding to bovine striatum. The potencies of chemically diverse A_2a-adenosine receptor ligands estimated by inhibition of FITC-APEC binding were in good agreement with their potencies determined using radioligand binding techniques (r=0.97,P=0.0003). FITC-APEC binding was not altered by purine derivatives that do not recognize A_2a-adenosine receptors. These findings demonstrate that the novel fluorescent ligand FITC-APEC can be used in the quantitative characterization of ligand binding to A_2a-adenosine receptors.     

Stable green light-emission from poly[9,9-bis(4′-n-octyloxyphenyl)fluorenyl-2,7-vinylene] synthesized via the Gilch polymerization route

A new fluorene-containing poly(arylenevinylene) derivative, poly[9,9-bis(4-octyloxyphenyl)fluorenyl-2,7-vinylene] (PBOPFV), was synthesized via the Gilch polymerization route and its light-emission properties were characterized and compared with those of poly(9,9-di-n-octylfluorenyl-2,7-vinylene) (PFV). As is the case for poly(alkylfluorene)s, PFV exhibits a long-wavelength emission that is additional to its emission in the blue-green region after thermal annealing or the passage of current. We have successfully suppressed this long-wavelength emission by introducing an octyloxyphenyl group at the 9-position of the fluorene group. PBOPFV produces PL emission maxima at 478 and 510 nm and no significant changes were found in its PL emission spectrum even after thermal annealing at 150 °C for 2 h. Light-emitting devices were fabricated with ITO/PEDOT:PSS/polymer/LiF/Al configurations. The EL spectrum of the device constructed using PFV was found to undergo significant changes during device operation, whereas the EL spectrum of the device constructed using PBOPFV was found to be stable.     

New one-pot synthesis of spiro[furo[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidine-6,5′-pyrimidine]pentaones and their sulfur analogues

Reaction of barbituric acid (BA), 1,3-dimethyl barbituric acid (DMBA) and 2-thiobarbituric acid (TBA) with cyanogen bromide and various aldehydes in presence of triethylamine afforded a new class of heterocyclic stable 5-alkyl and/or 5-aryl-1H, 1′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]2,2′,4,4′,6′(3H,3′H,5H)-pentaones which are dimeric forms of barbiturate (uracil and thiouracil derivatives) at 0 °C to ambient temperatures. Structure elucidation is proved by X-ray crystallography, ¹H NMR, ¹³C NMR, FT-IR, CHN and mass analyses techniques. Mechanisms of the formations are discussed.     

Identification of furo[3′, 2′:3,4]naphtho[1,2-d]imidazole derivatives as orally active and selective inhibitors of microsomal prostaglandin E2 synthase-1 (mPGES-1)

This study describes the synthesis and anti-inflammatory effects of furo[3', 2':3,4]naphtho[1,2-d] imidazole derivatives. Among these furo[3', 2':3,4]naphtho[1,2-d]imidazole derivatives, 2-(4-methoxyphenyl)furo [3', 2':3,4]naphtho[1,2-d]imidazole (12) exhibited a strong inhibitory activity against LPS-induced PGE(2) production, with an IC(50) value of 47?nM. Compound 12 is then further examined for its inhibitory effects in the protein expression of COX-2 and microsomal prostaglandin E(2) synthase-1 (mPGES-1) in Raw 264.7 cells. Our results indicate that compound 12 was capable against inhibiting LPS-induced mPGES-1 protein expression at a concentration of 1.0?μM and no inhibitory effect in COX-2 expression. The sepsis-induced PGE(2) production in rat serum decreased ~250% by the pretreatment of 12 at 10?mg/kg. These results are especially important since compound 12 exhibited good oral bioavailability (72%) and was not cytotoxic at a concentration of 10.0?μM. Therefore, compound 12 is a highly selective mPGES-1 inhibitor that can serve as a lead for the development of novel oral anti-inflammatory drug candidates.     

Self-assembled structures of 4′-([2,2′:6′,2″-terpyridine]-4′-yl)-[1,1′-phenyl]-4-carboxylic acid molecules induced by metal atoms on ag(111) surface

The self-assembled supramolecular structures of 4′-([2,2′:6′,2″-terpyridine]-4′-yl)-[1,1′-phenyl]-4-carboxylic acid (Y) molecules on Ag(111) surface induced by metal elements have been studied by scanning tunneling microscopy. After annealing, the as-deposited monolayer of Y molecules shows four kinds of well-ordered structures due to the competition between dipole interaction, hydrogen bonding and Van der Waals interaction. Introduced Cu atoms drive ordered monolayer into a self-assembled supramolecular structure with bright spots. Deposited Ag atoms cause the monolayer change to a windmill shape self-assembled supramolecular structure. Though the Cu and Ag are in the same group of the periodic table, a Cu atom connects two COOH groups and an Ag atom trends to bind to three COOH groups during the formation of metal-organic bonding within both induced structures. Such result suggests that the self-assembled structures formed by metal-organic coordination bonding can be controlled by choosing the number of metal-organic coordination bonds, which can be helpful to design metal-organic molecular architectures comprising functional building blocks.     

Synthesis and Analytical Application of a Novel Fluorescent Hg2+ Probe 3′, 6′-Bis(Diethylamino)-2-((2,4-Dimethoxybenzylidene)Amino)Spiro[Isoindoline-1,9′-Xanthene]-3-Thione

A novel probe, 3′,6′ - bis(diethylamino) -2- ((2,4-dimethoxybenzylidene)amino) spiro [isoindoline-1,9′-xanthene]-3-thione (RBS), was designed and synthesized. Its structure was characterized with elemental analysis, IR spectra and ¹H NMR. The probe displayed highly selective and sensitive recognition of Hg²⁺. Reacting with mercury ions in aqueous solution, its fluorescence intensity was enhanced significantly, while its color was changed from colorless to pink. So, a new fluorescence method of detection of Hg²⁺ was proposed. Its dynamic response concentration range and detection limit for Hg²⁺ were 5.00?×?10^?9 M to 1.00?×?10^?6 M detected and 1.83?×?10^?9 M, respectively. Satisfying results were obtained when the probe was applied to detect spiked Hg²⁺ in samples.     

Structure of the product of intracomplex alkylation of target octanucleotide pd[TGTTTGGC] by means of 4-[N-methyl-N-(2-chloro-ethyl)-amino]benzyl-5′-phosphamido derivative of heptanucleotide pd[CCAAACA]: Two-dimensional1H-NMR spectroscopy and restrained molecular mechanics refinement

The spatial structure of a covalent adduct — the product of intracomplex alkylation at N-3-position of dC-8 nucleoside residue of target octanucleotide pd[TGTTTGGC] by means of 4-[N-methyl-N-(2-chloroethyl)amino]benzyl-5′-phosphamido derivative of heptanucleotide pd[CCAAACA] — has been investigated in aqueous solution by two-dimensional (2D)¹H-NMR spectroscopy and restrained molecular mechanics calculations. By using COSY, COSY-DQF and NOESY experiments the assignment of oligonucleotide protons as well as protons of modifying group was carried out. The correlation times of benzylamide fragment protons and those of neighbouring nucleotide residues dC-1 and dC-8 were shown to be equal and shorter thanτ _c of intraduplex nucleotides. The analysis of proton-proton coupling constants for H1′, H2′a, H2′b and H3′ protons showed all sugar residues to be in 2′-endo conformation. The distances between protons closed in the space were determined by means of a set of one-dimensional (1D) NOE experiments. The experimental distances were used as the constraints for energy minimization by molecular mechanics calculations. Eight conformations of benzylamide fragment of the covalent adduct differed with orientations of 4-N-methyl residue of the alkylating group and 1-methyleneamide linker function were constructed as starting structures in energy minimization procedure. Among of the resulting optimized structures only one S(Alk)8^* was found to satisfy both experimental data and energetic criteria. The benzylamide fragment in conformation S(Alk)8^* has been shown to localize in the region of lacked nucleoside residue of the duplex at the end of heptanucleotide chain less than 5 Å apart from the residues dC-1 and alkylated dC-8.     

Isotope Effects by Comparing 1H‐ and 2D‐NMR Spectra of 9,9′‐Bisbicyclo[4.3.0]‐cyclonona‐2,4,7‐triene

Abstract

Inverse secondary kinetic isotope effects are determined for the dimerization of all‐cis‐cyclononatetraenyl radical, 1, to its corresponding dimer, all‐cis‐9,9′‐bicyclonona‐1,3,5,7‐tetraene, 2, (step 1, k _H/k _D=0.5), and cyclization of the latter to 9,9′‐bisbicyclo[4.3.0]cyclonona‐2,4,7‐triene, 3 (step 2, k _H/k _D=0.75). These results are obtained by comparison of ¹H‐ and ²D‐NMR spectra of 3 and employment of a simple statistical method for acquiring kinetic data. This new strategy appears superior to conventional methods in being fast, simple, and less expensive.     

Molecular Orientation and Aggregation in the Langmuir-Blodgett Films of 4-[4′-(4″-Decyloxy Phenylazo) Naphthloxy] Butyl Trimethylammonium Dextran Sulfate Studied by Ultra-Violet and Infrared Spectroscopy

Infrared transmission, Reflectance-Absorption (RA) and Ultra-Violet (UV) spectra were measured for mono-and multi-layers Langmuir-Blodgett (LB) films of 4-[4′-(4″-decyIoxy phenylazo)naphthloxy] butyl trimethylammonium bromide formed with SDS to study the molecular orientation and aggregation. The results indicate that the compound do not aggregate in the LB films, and the alkyl tail is nearly perpendicular to the substrate surface and the chromorphore part adopts trans-zigzag conformation. These results also suggest that the molecular orientation and aggregation are not depend upon the number of monolayers The comparison of infrared transmission and RA spectra indicates that the hydrocarbon chain is nearly perpendicular to the substrate surface, but the two rings in the chromophore part are tilted considerably from the surface normal.