RESUMO
The P2X3 receptor is an attractive target for the treatment of pain and chronic coughing, and thus P2X3 antagonists have been developed as new therapeutic drugs. We previously reported selective P2X3 receptor antagonists by derivatization of hit compound 1. As a result, we identified hit compound 3, the structure of which was similar to hit compound 1. On the basis of SAR studies of hit compound 1, we modified hit compound 3 and compound 42 was identified as having analgesic efficacy by oral administration.
Assuntos
Antagonistas do Receptor Purinérgico P2X/química , Antagonistas do Receptor Purinérgico P2X/farmacologia , Pirazolonas/química , Pirazolonas/farmacologia , Receptores Purinérgicos P2X3/metabolismo , Descoberta de Drogas , Humanos , Simulação de Acoplamento Molecular , Pirróis/química , Pirróis/farmacologia , Receptores Purinérgicos P2X3/química , Relação Estrutura-AtividadeRESUMO
The oxidation of non-phenolic alkanoic acid derivatives to oxygen heterocycles was investigated; a new oxidative route to dienone lactones has been developed using a combination of hypervalent iodine(III) reagent, phenyliodine(III) bis(trifluoroacetate)(PIFA), and heteropoly acid (HPA).
Assuntos
Fluoracetatos , Iodo/química , Lactonas/química , Ciclização , Compostos Heterocíclicos/síntese química , Compostos Heterocíclicos/química , Indicadores e Reagentes , Iodobenzenos , Oxirredução , Ácido Trifluoracético/químicaRESUMO
The combination of the water-soluble radical initiator, 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (VA-044), and surfactant, cetyltrimethylammonium bromide (CTAB), was found to be the most suitable condition for the effective direct synthesis of useful active thioesters (pentafluorophenyl thioesters) in water.
RESUMO
The reaction of 1-(p-hydroxyaryl)cyclobutanols and phenyl iodide(III) diacetate in hexafluoroisopropanol and water produced spiro cyclohexadienone lactones via a domino reaction.
Assuntos
Cicloexenos/síntese química , Iodo/química , Lactonas/síntese química , Compostos de Espiro/síntese química , Cicloexenos/química , Lactonas/química , Compostos de Espiro/químicaRESUMO
The domino reaction of 2,3-epoxy-1-alcohol derivatives, namely tetrasubstituted 2,3-epoxy-1-alcohols and 2- or 3-alkyl trisubstituted 2,3-epoxy-1-alcohols, with PhI(OCOCF(3))(2) in the presence of H(2)O is described in detail. In this reaction, several types of lactol derivatives can be directly obtained from the 2,3-epoxy-1-alcohol derivatives in a single operation. The obtained lactols were successively converted into the corresponding lactones. This reaction is applicable to the construction of optically active lactone compounds. The asymmetric total synthesis of (+)-tanikolide, an antifungal marine natural product, has been effectively achieved by using this reaction.
Assuntos
Álcoois/química , Antifúngicos/síntese química , Produtos Biológicos/síntese química , Compostos de Epóxi/química , Iodo/química , Lactonas/síntese química , Biologia Marinha , Modelos Químicos , Estereoisomerismo , Água/químicaRESUMO
The combination of the water-soluble radical initiator, 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (VA-044) and the surfactant, cetyltrimethyl-ammonium bromide (CTAB), was found to be the most suitable condition for the effective and direct synthesis of useful active thioesters (pentafluorophenyl thioesters) in water. In addition, the direct amidation of aldehydes was achieved by the addition of the amines to the thioesterification reaction mixture in water.
Assuntos
Aldeídos/química , Amidas/síntese química , Ésteres/síntese química , Cetrimônio , Compostos de Cetrimônio , Indicadores e Reagentes , Espectrofotometria Infravermelho , Espectroscopia de Infravermelho com Transformada de Fourier , Água/químicaRESUMO
The non-phenolic coupling reaction of benzyltetrahydroisoquinolines (laudanosine derivatives) by using a hypervalent iodine(III) reagent is described. In general, chemical oxidation of laudanosine gives glaucine. In contrast to general chemical oxidizing reagent systems, the novel use of reagent combination of phenyliodine bis(trifluoroacetate) (PIFA), and heteropoly acid (HPA) afforded morphinandienone alkaloids in excellent yields. In order to achieve the coupling reaction with simple reaction procedure, the use of HPA supported on silica gel instead of HPA was demonstrated and sufficient yield was exerted again. The present reagent system, PIFA/HPA, was also applied to the oxidation of other non-phenolic benzyltetrahydroisoquinolines and the high yield conversion to morphinandienones was accomplished.
Assuntos
Ácidos/química , Alcaloides/química , Iodo/química , Morfinanos/química , Isoquinolinas/química , Estrutura Molecular , OxirreduçãoRESUMO
Intramolecular oxidative coupling reaction of N-protected benzyltetrahydroisoquinoline derivatives using hypervalent iodine(III) reagents was investigated. The use of remarkable combination of phenyliodine bis (trifluoroacetate) (PIFA) and heteropoly acid (HPA) in wet acetonitrile smoothly afforded morphinandienone alkaloids, while neospirinedienone alkaloids were obtained in high yield under anhydrous conditions.