Heteroaromatic Analogues Research Articles

Heteroaromatic Analogs of Curcumin: Design, Synthesis, and Cytotoxic Activities

Heteroaromatic Analogs of Curcumin: Design, Synthesis, and Cytotoxic Activities

ChemInform Abstract: Sequential Protocol for C(sp3)—H Carboxylation with CO2: Transition‐Metal‐Catalyzed Benzylic C—H Silylation and Fluoride‐Mediated Carboxylation.

AbstractA new method to prepare arylacetic acid esters and some heteroaromatic analogues is reported.

Heteroaromatic analogues of 1,5-diarylpyrazole class as anti-inflammatory agents

A novel series of heteroaromatic analogues of known anti-inflammatory (AI) drug celecoxib replacing the benzenesulfonamide moiety with 6-sulfonamidobenzothiazol-2-yl moiety was synthesized. Regioselective synthesis of the target compounds 2a–i having 1,5-diaryl relationship was achieved by exploring reaction conditions. All the newly synthesized compounds (2a–i and 8) were screened for their in vivo AI activity using carrageenan-induced rat paw edema assay. Five compounds (2c–f and 2i) were found to possess good AI activity (≥60% inhibition), 3 h after the carrageenan injection when compared to that of standard drug indomethacin (78%), whereas the remaining four compounds (2a–b and 2g–h) with 1,5-diaryl relationship have shown moderate activity with 49–56% inhibition after 3 h. However, pyrazole 8 having 1,3-diaryl relationship failed to show appreciable AI activity.

Nouveaux traceurs TEMP : exemple des traceurs des protéoglycanes et de la mélanine

The majority of research program on new radiopharmaceutics turn to tracers used for positron emission tomography (PET). Only a few teams work on new non fluorine labeled tracers. However, the coming of SPECT/CT gamma cameras, the arrival of semi-conductors gamma cameras should boost the development of non-PET tracers. We exhibit in this article the experience acquired by our laboratory in the conception and design of two new non fluorine labelled compounds. The 99mTc-NTP 15-5 which binds to proteoglycans could be used for the diagnosis and staging of osteoarthritis and chondrosarcoma. The iodobenzamides, specific to the melanin, are nowadays compared to 18F-fluorodeoxyglucose in a phase III clinical trial for the diagnosis and detection of melanoma metastasis. Our last development focus on BZA heteroaromatic analogues usable for melanoma treatment.

Iodine-Mediated Electrophilic Cyclization of 2-Alkynyl-1-methylene Azide Aromatics Leading to Highly Substituted Isoquinolines and Its Application to the Synthesis of Norchelerythrine

The reaction of 2-alkynyl-1-methylene azide aromatics 1 with iodine and/or other iodium donors, such as the Barluenga reagent (Py2IBF4/HBF4) and NIS, gave highly substituted cyclization products, namely, the 1,3-disubstituted 4-iodoisoquinolines 2, in good to high yields. Not only simple 2-alkynyl benzyl azides 1a-j and their substituted analogues 1k-u and 6 but also heteroaromatic analogues, including pyridine 8, pyrroles 10a-c, furane 10d, and thiophenes 10e-g, gave the corresponding isoquinoline derivatives in excellent to allowable yields. Electron-donating and electron-accepting substituents on the aromatic ring were equally tolerated, and either acidic or basic (or even neutral) reaction conditions, depending on the reactivity of the substrate, could be applied to smoothly convert the azide starting materials into the desired isoquinoline products in moderate to good yields. Limits were found only in connection with the substituent at the alkyne terminus, where electron-neutral or electron-donating substituents are clearly favored. The iodine-mediated electrophilic cyclization of 1 most probably proceeds through the iodonium ion intermediate 4 followed by nucleophilic cyclization of the azide and subsequent elimination of N2. This new methodology was successfully applied to the short synthesis of norchelerythrine.

A New Strategy for the Synthesis of Optically Active Benzylic Fluorides and Corresponding Five‐Membered Heteroaromatic Analogues.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

A new strategy for the synthesis of optically active benzylic fluorides and corresponding five-membered heteroaromatic analogues

Benzylic fluorides, as well as five-membered heterocycles, have been obtained in high ee’s through cycloaddition reactions starting from easily accessible optically active propargylic fluorides.

Molecular polarizability of organic compounds and their complexes: XLIX. Molar volumes of polyaryl systems in solutions, extrapolated to infinite dilution, their additivity, and steric structure of the molecules

Molar volumes of a number of polyaryls and of several model systems at infinite dilution in carbon tetrachloride and benzene were determined. The molar volumes of the compounds under study are additive by bonds, groups, and molecular fragments. The dipole moments and Kerr molar constants of the compounds under study can be found by a simplified additive method. As follows from the additive analysis of the molar volumes of diphenyl, para-substituted diphenyls, heteroaromatic analogs, and a number of polyaryls, the molecules of these compounds are acoplanar in the solutions, and the degree of their acoplanarity is the same as in diphenyl.

Heteroaromatic side-chain analogs of pregabalin

A series of heteroaromatic analogs of pregabalin has been identified that possess anticonvulsant activity in the DBA/2 mouse model. The methods of synthesis and preliminary pharmacology are discussed herein.

New Triple‐Helix DNA Stabilizing Agents.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Highly Efficient Catalytic Aerobic Oxidations of Benzylic Alcohols in Water.

For Abstract see ChemInform Abstract in Full Text.

Highly Efficient Catalytic Aerobic Oxidations of Benzylic Alcohols in Water

A highly efficient catalytic system without transition metals in water has been developed for aerobic oxidations of benzylic alcohols. The newly developed catalyst system could oxidize benzylic alcohols and heteroaromatic analogues with 1 mol % TEMPO as a catalyst and with a catalytic amount of 1,3-dibromo-5,5-dimethylhydantoin and NaNO2 as cocatalysts. Under the optimal conditions, various alcohols could be converted into their corresponding aldehydes or ketones in high yields.

New triple-helix DNA stabilizing agents

Several substituted quinolin-4-amines and heteroaromatic analogs were synthesized and evaluated for interaction with triplex polydA·2polydT and duplex polydA·polydT by using UV-thermal melting experiments. Excellent triple-helix DNA ligands with high affinity toward T·A·T triplets and triple/duplex selectivity were designed through a rational approach.

Regio/diastereo-controls of the Bingel-type biscyclopropanation of [60]fullerene by using bismalonates with a Tröger base analogue-derived tether

Four kinds of bismalonates tethered with a Tröger base derivative were synthesized and used for the double Bingel reaction of [60]fullerene. The regio/diastereoselectivities of the reaction were highly influenced by the structure of the Tröger base derivatives. Heteroaromatic analogues of the Tröger base were found to be applicable as the core of the tether.

A synthesis of heteroaromatic analogues of 1-methyl-1,2,3,4-tetrahydroisoquinoline using the Pummerer-type cyclization reaction: observation of tandem cyclization reaction.

The sulfoxides 7b and 7d carrying thiophene or benzothiophene as heteroaromatic nucleophiles, when treated with trifluoroacetic anhydride at room temperature (Pummerer reaction), underwent an intramolecular alkylation in an exclusive manner to yield 4,5,6,7-tetrahydro-7-methyl-4-phenylsulfanylthieno[2,3-c]pyridine-6-carbaldehyde (10) and the corresponding benzothiophene derivative (12b) in high yields, respectively. Thus, this route provides biologically interesting nitrogen heterocycles (1b) and (2b). On the other hand, the sulfoxide (7c) carrying benzofuran as a nucleophile on reaction with TFAA yielded not only the Pummerer-type cyclization product (12a), but also the diastereoisomeric tandem cyclization products (13) and (14) having a noble 11-aza-2-oxa-7-thiatricyclo[4.3.3.0(1,5)]dodecane ring system (B). The formation of these products can be readily rationalized by the intervention of the oxonium ion intermediate (21).

Synthesis of heteroaromatic analogues of (2-aryl-1-cyclopentenyl-1-alkylidene)-(arylmethyloxy)amine COX-2 inhibitors: effects on the inhibitory activity of the replacement of the cyclopentene central core with pyrazole, thiophene or isoxazole ring

Several heteroaromatic analogues of (2-aryl-1-cyclopentenyl-1-alkylidene)-(arylmethyloxy)amine COX-2 inhibitors, in which the cyclopentene moiety was replaced by pyrazole, thiophene or isoxazole ring, were synthesized, in order to verify the influence of the different nature of the central core on the COX inhibitory properties of these kinds of molecules. Among the compounds tested, only the 3-( p-methylsulfonylphenyl) substituted thiophene derivatives 17 and 22, showed a certain COX-2 inhibitory activity, accompanied by an appreciable COX-2 versus COX-1 selectivity. Only one of the 1-( p-methylsulfonylphenyl)pyrazole compounds ( 16) displayed a modest inhibitory activity towards both type of isoenzymes, while the pyrazole 1-( p-aminosulfonylphenyl) substituted 12 proved to be significantly active only towards COX-1. All the isoxazole derivatives were inactive on both COX isoforms.

Synthesis and Antiaggregant Properties of Stabilized Analogues of Polyunsaturated Fatty Acid Metabolites.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and antiaggregant properties of Stabilized analogues of polyunsaturated fatty acid metabolites

New aromatic and heteroaromatic analogues of polyunsaturated fatty acid metabolites have been prepared using short and versatile strategies. Preliminary studies of their activity as inhibitors of platelet aggregation are reported.

N-Hydroxyphthalimide/Cobalt(II) Catalyzed Low Temperature Benzylic Oxidation Using Molecular Oxygen

A variety of (substituted) aryl glyoxylates is formed in good to excellent yield under very mild conditions by direct oxidation of the corresponding arylacetic esters or mandelic acid esters with molecular oxygen and N-hydroxyphthalimide/cobalt(II) acetate as catalyst. Heteroaromatic analogs are more difficult to oxidize with this system. The effect of substitution in the aromatic ring of N-hydroxyphthalimide on the oxidation of ethylbenzene has been studied. Electron withdrawing substituents accelerate the oxidation of ethylbenzene and promote the formation of acetophenone. Electron donating substituents lead to decreased rates of oxidation and enhance the selectivity for 1-phenylethanol.

Heterocyclic congeners of PD 128,907 with a partially hydrogenated benzomorpholine moiety as potential dopamine D 3-receptor ligands

With a straightforward seven-step synthesis, racemic perhydro[1,4]benzoxazin-6-on was synthesized in overall good yields via regioselective epoxid ring-opening to the corresponding β-aminoalcohol. The oxazine derivative was the key intermediate for the preparation of heteroaromatic analogues of the dopamine D 3-receptor preferring agonist PD 128,907. The morpholine moiety of PD 128,907 was incorporated in diazole and diazine compounds obtained by different ring closure reactions. The target compounds obtained were structurally related to non-ergot heteroaromatic dopamine agonists which display preferential activity at the D 3 receptor, e.g., quinpirole, quinerolane, or pramipexole. The five membered aminothiazole, aminoselenazole, and pyrazole derivatives showed at least one order of magnitude higher binding at the human D 3 receptor than that at the D 2L receptor. Although the novel compounds displayed K i values only in the micromolar concentration range, the most active ones showed full agonist activity in a functional assay on mitogenesis.