RESUMO
Exploration of alternative structures of the substituted piperidine or piperazine ring which are characteristic in most of the reported GPR119 agonists provided novel spirocyclic cyclohexane derivatives. The representative 17 with a high three-dimensionality exhibited potent agonistic activity (EC50â¯=â¯4â¯nM) with no CYP inhibitory activity (IC50 >10⯵M). Compound 17 also displayed hypoglycemic activity with insulin secretion dependent on glucose concentration in an intraperitoneal glucose tolerance test in rats.
Assuntos
Cicloexanos/farmacologia , Desenho de Fármacos , Hipoglicemiantes/farmacologia , Receptores Acoplados a Proteínas G/agonistas , Compostos de Espiro/farmacologia , Animais , Cicloexanos/síntese química , Cicloexanos/química , Relação Dose-Resposta a Droga , Glucose/administração & dosagem , Glucose/análise , Teste de Tolerância a Glucose , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Injeções Intraperitoneais , Insulina/metabolismo , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/metabolismo , Compostos de Espiro/síntese química , Compostos de Espiro/química , Relação Estrutura-AtividadeRESUMO
3-Allyl-1-silaindenes are synthesised from alkynes having an allylsilane moiety by a gold-catalysed intramolecular trans-allylsilylation reaction.
RESUMO
[reaction: see text] Silicon-bridged 1,6-diynes underwent [2 + 2 + 2] cycloaddition with alkynes in the presence of an iridium(I)-phosphine catalyst to afford densely substituted silafluorene derivatives. Extended silafluorene skeletons were constructed by the [2 + 2 + 2] cycloaddition of tetraynes.
RESUMO
Dihydrosilanes undergo double trans-hydrosilylation with 1,4-diarylbuta-1,3-diynes in the presence of a cationic ruthenium catalyst to afford 2,5-diarylsiloles: in particular, 9-silafluorene is a good hydrosilylating agent to produce spiro-type siloles in good yield.
RESUMO
A ring-closing metathesis reaction of allenynes occurred at room temperature in the presence of a molybdenum alkylidene complex to give ring-closed vinylallenes. The vinylallene skeletons were constructed by a metathesis-type reaction between the alkyne moiety and the proximal carbon-carbon double bond of the allene moiety. [reaction: see text]
RESUMO
Two structurally distinct carbocycles were selectively obtained by the reactions of 2-(o-styryl)cyclobutanones promoted by ytterbium salts. Treatment of the cyclobutanones with YbCl(3) in 1,4-dioxane at 100 degrees C afforded 2-(2-chloroethyl)naphthalenes. On the other hand, the reaction with Yb(OTf)(3) in chlorobenzene at 130 degrees C gave 9,10-dihydrobenzocycloocten-7(8H)-ones.
RESUMO
Reaction of triethylgermane and alkynes in the presence of a ruthenium catalyst occurred in a trans fashion. The ruthenium-catalyzed trans-hydrogermylation of 1,3-diynes with dihydrogermanes afforded 2,5-disubstituted germoles in good yield through a two fold addition process. The hydrogermylation reaction was successfully applied to synthesis of 2,2'-bigermole.