130403-84-8Relevant academic research and scientific papers
BETA-LACTONE COMPOUNDS
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Page/Page column 11, (2009/05/28)
The present invention provides compounds having the general structure A, or a pharmaceutically acceptable derivatives thereof: wherein R is an alkyl group, and R1 comprises at least one moiety selected from a group consisting of an alkyl, an alkenyl, an aryl, a heterocycle, hydroxyl, ester, amido, aldehyde, and a halogen.
Synthesis of novel &β-lactone inhibitors of fatty acid synthase
Richardson, Robyn D.,Knowles, Lynn M.,Cieplak, Piotr,Smith, Jeffrey W.,Ma, Gil,Oyola, Yatsandra,Zancanella, Manuel,Romo, Daniel
scheme or table, p. 5285 - 5296 (2010/04/02)
Fatty acid synthase (FAS) is necessary for growth and survival of tumor cells and is a promising drug target for oncology. Here, we report on the syntheses and activity of novel inhibitors of the thioesterase domain of FAS. Using the structure of orlistat as a starting point, which contains a β-lactone as the central pharmacophore, 28 novel congeners were synthesized and examined. Structural features such as the length of the α- and β-alkyl chains, their chemical composition, and amino ester substitutions were altered and the resulting compounds explored for inhibitory activity toward the thioesterase domain of FAS. Nineteen congeners show improved potency for FAS in biochemical assays relative to orlistat. Three of that subset, including the natural product valilactone, also display an increased potency in inducing tumor cell death and improved solubility compared to orlistat. These findings support the idea that an orlistat congener can be optimized for use in a preclinical drug design and for clinical drug development.
Discovery of a new chemical lead for a matrix metalloproteinase inhibitor
Ikura, Masahiro,Nakatani, Shingo,Yamamoto, Shingo,Habashita, Hiromu,Sugiura, Tsuneyuki,Takahashi, Kanji,Ogawa, Koji,Ohno, Hiroyuki,Nakai, Hisao,Toda, Masaaki
, p. 4241 - 4252 (2007/10/03)
A series of N-benzoyl γ-aminobutyric hydroxamic acids were synthesized and evaluated as matrix metalloproteinase inhibitors. First, we focused on chemical modification of the N-benzoyl residue. Introduction of electron-rich para-substituents was effective
Design and synthesis of novel metalloproteinase inhibitors
Nakatani, Shingo,Ikura, Masahiro,Yamamoto, Shingo,Nishita, Yoshitaka,Itadani, Satoshi,Habashita, Hiromu,Sugiura, Tsuneyuki,Ogawa, Koji,Ohno, Hiroyuki,Takahashi, Kanji,Nakai, Hisao,Toda, Masaaki
, p. 5402 - 5422 (2007/10/03)
A series of N-benzoyl 4-aminobutyric acid hydroxamate analogs were synthesized and evaluated as matrix metalloproteinase inhibitors. Synthetic work was focused on the chemical modification of the 4-aminobutyric acid part using easily available starting materials. As such, chemical modification was carried out using commercially available starting materials such as 4-aminobutyric acid, (+)- and (-)-malic acid, and d- and l-glutamic acid derivatives. Among the compounds tested, N-[4-(benzofuran-2-yl)benzoyl] 4-amino-4S-hydroxymethylbutyric acid hydroxamates derived from l-glutamic acid demonstrated more potent inhibitory activity against MMP-2 and MMP-9 compared with the corresponding 2S-hydroxy analogs or 3S-hydroxy analogs, respectively, which were derived from (-)-malic acid. Structure-activity relationship study is presented.
Total synthesis and comparative analysis of orlistat, valilactone, and a transposed orlistat derivative: Inhibitors of fatty acid synthase
Ma, Gil,Zancanella, Manuel,Oyola, Yatsandra,Richardson, Robyn D.,Smith, Jeffrey W.,Romo, Daniel
, p. 4497 - 4500 (2007/10/03)
Concise syntheses of orlistat (Xenical), a two-carbon transposed orlistat derivative, and valilactone are described that employ the tandem Mukaiyama aldol-lactonization (TMAL) process as a key step. This process allows facile modification of the α-side chain. Versatile strategies for modifying the δ-side chain are described, involving cuprate addition and olefin metathesis. Comparative antagonistic activity of these derivatives toward a recombinant form of the thioesterase domain of fatty acid synthase is reported along with comparative activity-based profiling.
A facile synthesis of (S)-4-hydroxypyrrolidin-2-one from (S)-malic acid
Seki, Masahiko,Kondo, Kazuhiko
, p. 745 - 747 (2007/10/03)
The chiral diol methyl 3,4-dihydroxybutanoate 4b obtained from (S)- malic acid dimethyl ester (3b) was subjected to regioselective tosylation to give the tosylate 6 in good yield. Subsequent treatment of 6 with aqueous ammonia afforded (S)-4hydroxypyrrolidin-2-one (1) through three steps in 32% overall yield from 3b.
The first total synthesis of (-)-lipstatin
Pommier,Pons,Kocienski
, p. 7334 - 7339 (2007/10/03)
A key step in the first total synthesis of the potent pancreatic lipase inhibitor (-)-lipstatin (1) is a diastereoselective Lewis acid-promoted [2 + 2] cycloaddition reaction between n-hexyl(trimethylsilyl)ketene (4) and (R)-(-)-(Z,Z)-3-[(tert-butyldimethylsilyl)oxy]-5,8-tetradecadienal (3), which is prepared from dimethyl (S)-(-)-malate.
Enantiospecific Synthesis of 17- and 18-Hydroxyeicosatetraenoic Acids, Cytochrome P450 Arachidonate Metabolites
Falck, J. R.,Lumin, Sun,Lee, Sang-Gyeong,Heckmann, Bertrand,Mioskowski, Charles,et al.
, p. 4893 - 4896 (2007/10/02)
The title bioactive eicosanoids were prepared from dimethyl L-malate by a convergent strategy exploiting the differential reactivity of ethereal dialkylcuprates towards tosylates versus bromides.
