ABSTRACT
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.
Subject(s)
Nucleoside Transport Proteins/metabolism , Osteoclasts/metabolism , Osteogenesis/drug effects , Small Molecule Libraries/pharmacology , Animals , Cell Line, Tumor , Female , Gene Expression Regulation/drug effects , Humans , Mice , Mice, Inbred ICR , Osteoclasts/drug effects , Osteogenesis/genetics , RANK Ligand/pharmacology , RAW 264.7 Cells , Signal Transduction/drug effects , Small Molecule Libraries/chemistry , Tritium/metabolismABSTRACT
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.
Subject(s)
Alkynes/chemistry , Indoles/chemical synthesis , Acetylene/chemistry , Carbohydrates/chemistry , Indoles/chemistry , Molecular Structure , StereoisomerismABSTRACT
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.
