RESUMO
We screened small-molecule compounds that inhibit osteoclast differentiation to find new anti-osteoporosis agents and found that a novel compound, SUKU-1, suppressed osteoclastogenesis. We also synthesized 38 derivatives of SUKU-1 and discovered that nine of them had inhibitory effects on osteoclastogenesis and that SUKU-33 was the most potent inhibitor. Next, we investigated the mechanisms by which SUKU-33 suppressed osteoclast differentiation. By measuring the uptake of [(3) H]-uridine in cells, we found that SUKU-33 suppressed both equilibrative nucleoside transporters and concentrative nucleoside transporters. These results suggest that SUKU-33 inhibits osteoclast differentiation by suppressing nucleoside transporters.
Assuntos
Proteínas de Transporte de Nucleosídeos/metabolismo , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Linhagem Celular Tumoral , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos ICR , Osteoclastos/efeitos dos fármacos , Osteogênese/genética , Ligante RANK/farmacologia , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/química , Trítio/metabolismoRESUMO
Regioselectivity of Larock indole synthesis, a palladium-catalyzed heteroannulation between o-iodoaniline and internal acetylene, was estimated using acetylenes substituted with ester and/or Boc-protected amine at the homopropargylic position and with perbenzyl- and unprotected glucose. Low to moderate regioselectivities were observed in all the cases, indicating these functional groups do not exert good directing effects, in the Larock indole synthesis.
Assuntos
Alcinos/química , Indóis/síntese química , Acetileno/química , Carboidratos/química , Indóis/química , Estrutura Molecular , EstereoisomerismoRESUMO
Naturally occurring terphenyls and related compounds such as terferol and its corresponding quinone and phlebiarubrone were synthesized from 2,5-diphenyl-1,4-benzoquinone. According to the proposed biosynthetic pathway, chemical conversion of phlebiarubrone to ustalic acid, a toxic compound isolated from the poisonous mushroom, Tricholoma ustale, was examined to find a low-yield conversion to the ustalic acid dimethyl ester.
