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S(+)-4-(1-phenylethylamino)quinazolines as inhibitors of human immunoglobuline E synthesis: Potency is dictated by stereochemistry and atomic point charges at N-1

Since the pathogenesis of allergic diseases is associated with elevated levels of immunoglobulin E (IgE), we developed a high throughput reporter gene assay in a human B-cell line to screen for low molecular weight IgE inhibitory compounds. Monitoring the IL-4 driven IgE-germline promoter activity (IgE-GLP), we discovered 4-(1-phenylethylamino)qinazolines as potent inhibitors of IgE-germline gene expression. Testing of the individual enantiomers (1, 2) revealed that only the S(+) enantiomer 1 was active. A cell viability assay done in the same cell line in parallel discriminated the dose-dependent inhibition from a general antiproliferative effect. The observed correlation of the inhibitory potencies found in the reporter gene assay with those measured by IgE-ELISA in primary human splenocytes provided evidence that the blockade of IgE synthesis is the direct consequence of IgE-germline gene inhibition, thereby validating the reporter gene assay. Parallel synthesis in solution rapidly provided a series of analogues of compound I with modifications in the phenethylamine side chain and the quinazoline core for SAR studies. Increasing the lipophilicity of the arylalkylamine moiety yielded S(+)-4-(1-(2-naphthyl)ethylamino)quinazoline (6) as the most potent inhibitor (IC50 of 14 nM) while the R(-) enantiomer was again found to be inactive. Within the set of S enantiomers, quantum mechanical calculations revealed that the IgE inhibitory activity can be quantitatively described by the charge at N-1 of the heterocyclic core and to a lesser extent by the molar refractivity. These results demonstrate the importance of electron-deficient fused 4-aminopyrimidines and lipophilic side chains for biological activity. The strong preference for the S configuration of the phenethylamine side chain is remarkable insofar as biological activity for fused 4-(1-phenylethylamino)pyrimidines has been published for the R enantiomers only (EGFR tyrosine kinase inhibition).

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Preparation of substituted 2-chloropyridines

A process for the preparation of a substituted 2-chloropyridine derivatives of the formula STR1 in which R1, R2, R3 and R4 represent hydrogen or various other radicals, which comprises reacting a pyridine-1-oxide of the formula STR2 with an aromatic carbonyl chloride in the presence of an inert organic solvent and in the presence of an acid acceptor at a temperature between about -20 C. and 200 C.

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19493-44-8, The reaction rate of a catalyzed reaction is faster than the reaction rate of the uncatalyzed reaction at the same temperature.19493-44-8, Name is 1-Chloroisoquinoline, molecular formula is C9H6ClN. In a Article, authors is Shigeno, Masanori£¬once mentioned of 19493-44-8

Organic Superbase t-Bu-P4 Catalyzes Amination of Methoxy(hetero)arenes

We report that the organic superbase t-Bu-P4 efficiently catalyzes the amination of methoxy(hetero)arenes with amine nucleophiles such as aniline, indoline, and aminopyridine derivatives. This catalytic reaction is effective for the transformation of electron-deficient methoxyarenes possessing diverse functionalities (carbonyl, cyano, nitro, and halogen) as well as methoxyheteroarenes, including pyrazine, quinoline, isoquinoline, and pyridine derivatives. Intramolecular reactions provide six- and seven-membered ring cyclic amine products.

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19493-44-8, Because a catalyst decreases the height of the energy barrier, its presence increases the reaction rates of both the forward and the reverse reactions by the same amount.19493-44-8, Name is 1-Chloroisoquinoline, molecular formula is C9H6ClN. In a article£¬once mentioned of 19493-44-8

Design and optimisation of potent gp120-CD4 inhibitors

The synthesis and structure-activity relationship of a series of novel gp120-CD4 inhibitors are described. Pharmacokinetic studies and antiviral spectrum assessment of lead compounds led to the identification of compound 36, a potent gp120-CD4 inhibitor which exhibited antiviral potency across a spectrum of 25 clade B isolates.

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Iron catalyzed cross coupling reactions of aromatic compounds

A process for the production of compounds Ar?R1 by means of a cross-coupling reaction of an organometallic reagent R1?M with an aromatic or heteroaromatic substrate Ar?X catalyzed by one or several iron salts or iron complexes as catalysts or pre-catalysts, present homogeneously or heterogeneously in the reaction mixture. This new invention exhibits substantial advantages over established cross coupling methodology using palladium- or nickel complexes as the catalysts. Most notable aspects are the fact that (i) expensive and/or toxic nobel metal catalysts are replaced by cheap, stable, commercially available and toxicologically benign iron salts or iron complexes as the catalysts or pre-catalysts, (ii) commercially attractive aryl chlorides as well as various aryl sulfonates can be used as starting materials, (iii) the reaction can be performed under ?ligand-free? conditons, and (iv) the reaction times are usually very short.

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Chemistry can be defined as the study of matter and the changes it undergoes. 19493-44-8. You¡¯ll sometimes hear it called the central science because it is the connection between physics and all the other sciences, starting with biology.19493-44-8, Name is 1-Chloroisoquinoline, molecular formula is C9H6ClN, introducing its new discovery.

Saturated red iridium(iii) complexes containing a unique four-membered Ir-S-C-N backbone: Mild synthesis and application in OLEDs

A series of new iridium(iii) cyclometalated complexes (4tfmpiq)2Ir(tiptha), (4tfmpiq)2Ir(phdiptha), (4tfmpiq)2Ir(fphdiptha) and (4tfmpiq)2Ir(ipdptha) (4tfmpiq = 4-(4-(trifluoromethyl)phenyl)isoquinoline, tiptha = 1,1,3-triisopropylthiourea, phdiptha = 1,1-diisopropyl-3-phenylthiourea, fphdiptha = 3-(4-fluorophenyl)-1,1-diisopropylthiourea, ipdptha = 3-isopropyl-1,1-diphenylthiourea) containing a unique four-membered ring Ir-S-C-N backbone were facilely synthesized under mild conditions. By introducing different substituents such as isopropyl, phenyl, 4-fluorophenyl, diisopropylamine and diphenylamine on the thiourea ancillary ligands, not only the S-C-N ligands can be extensively derived, but also the emission colors (lambdapeak = 627-636 nm) and photoluminescence quantum efficiencies (PhiP = 38.0-42.0%) can be regulated. Employing these complexes as emitters, the organic light emitting diodes (OLEDs) exhibited good performances with a maximum external quantum efficiency (EQEmax) of 13.1% for saturated red emission with CIE coordinates of (0.68, 0.32). These results demonstrate the great potential of the S-C-N ancillary ligands for developing new Ir(iii) complexes towards OLED applications.

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The Chemistry of 5-Oxodihydroisoxazoles. Part 23. Photochemical and Thermal Reactions of Isoxazol-5(2H)-ones Substituted at C-3 or C-4 with Nitrogen, Oxygen or Sulfur

The photolysis of 2,3-dimethyl-4-phenoxy- and 4-thiophenoxyisoxazol-5(2H)-one in methanol has been re-examined, but no new products were isolated. Flash vacuum pyrolysis of the former gave a novel product, phenyl N-methylpropenimidate, from rearrangement of the intermediate carbene. Irradiation of the 3-hydroxy-2-phenyl-4-carboxylate gave two products which arise from the 3-hydroxy and 5-hydroxy tautomers. By contrast, the 3-hydroxy-4-acetyl isoxazolone reacted exclusively as one tautomer giving the expected loss of CO2 to form the carbene which was captured by methanol on photolysis, or underwent methyl migration and cyclisation to 3-methylazetidine-1,3-dione on pyrolysis. 3-Amino and 3-phenylamino substituted isoxazolones also gave photolysis and pyrolysis products characteristic of discrete tautomers.

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19493-44-8, Name is 1-Chloroisoquinoline, belongs to isoquinoline compound, is a common compound. 19493-44-8In an article, authors is Al-Awadi, Nouria, once mentioned the new application about 19493-44-8.

The Mechanism of Thermal Eliminations. Part 21. Rate Data for Pyrolysis of 2-Ethoxyquinoline, 1-and 3-Ethoxyisoquinoline, and 1-Ethoxythiazole: Correlation of Reactivities with ?-Bond Order of the C=N Bond

We have measured the rates of thermal elimination of ethylene from the title compounds between 587.3 and 722.9 K.The reactivities relative to 2-ethoxypyridine at 650 K are: 3-ethoxyisoquinoline (0.21), 2-ethoxyquinoline (3.13), 1-ethoxyisoquinoline (6.47), 2-ethoxythiazole (63.1).These reactivities parallel the ?-bond order of the C=N bond, though the exceptional reactivity of 2-ethoxythiazole is attributed to additional acceleration through +M electron release from sulphur to nitrogen.This emphasizes the greater relative importance of nucleophilic attack by the nitrogen upon the beta-hydrogen atom as compared with the analogous mechanism for pyrolysis of esters.Because of semi-concentrated nature of the reaction, interruption of aromaticity is much less significant than in, for example, electrophilic aromatic substitution.Thus retention of the benzenoid character of the ring not involved in the elimination is not an important rate-determining feature, as shown by the lower reactivity of 3-ethoxyisoquinoline relative to 2- ethoxypyridine.The unimportance of the interruption of aromaticity of the benzenoid ring means that conjugative effects are better relayed to nitrogen in the beta-naphthalene-like position (isoquinoline) than in the alpha-naphthalene-like position (quinoline).This is the reverse of the familiar pattern for reactions of naphthalene-like systems where full charges are involved, and may be an additional factor contributing to the higher reactivity of 1-ethoxyisoquinoline than of 2-ethoxyquinoline, as may also be the -I effect of the benzo substiutent.The conclusions are used to predict elimination rates for alkoxyheterocycles not yet studied.

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