- Structure-activity relationships for vitamin D3-based aromatic a-ring analogues as hedgehog pathway inhibitors
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A structure-activity relationship study for a series of vitamin D3-based (VD3) analogues that incorporate aromatic A-ring mimics with varying functionality has provided key insight into scaffold features that result in potent, selective Hedgehog (Hh) pathway inhibition. Three analogue subclasses containing (1) a single substitution at the ortho or para position of the aromatic A-ring, (2) a heteroaryl or biaryl moiety, or (3) multiple substituents on the aromatic A-ring were prepared and evaluated. Aromatic A-ring mimics incorporating either single or multiple hydrophilic moieties on a six-membered ring inhibited the Hh pathway in both Hh-dependent mouse embryonic fibroblasts and cultured cancer cells (IC50 values 0.74-10 μM). Preliminary studies were conducted to probe the cellular mechanisms through which VD3 and 5, the most active analogue, inhibit Hh signaling. These studies suggested that the anti-Hh activity of VD3 is primarily attributed to the vitamin D receptor, whereas 5 affects Hh inhibition through a separate mechanism.
- Deberardinis, Albert M.,Madden, Daniel J.,Banerjee, Upasana,Sail, Vibhavari,Raccuia, Daniel S.,De Carlo, Daniel,Lemieux, Steven M.,Meares, Adam,Hadden, M. Kyle
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p. 3724 - 3736
(2014/05/20)
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- A simple method for chemoselective phenol alkylation
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A simple and effective method for chemoselective alkylation of phenol over carboxylic acid using a 40% aqueous solution of tetrabutylphosphonium hydroxide that affords the desired phenyl ethers in 82-99% yield is described.
- Liu, Pingli,Huang, Liang,Faul, Margaret M.
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p. 7380 - 7382
(2008/03/13)
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- NOVEL DICARBOXYLIC ACID DERIVATIVES WITH PHARMACEUTICAL PROPERTIES
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The present invention relates to the use of compounds of the formula (I) and to their salts and stereoisomers, for the preparation of medicaments for the treatment of cardiovascular disorders.
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Page/Page column 49
(2010/02/14)
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- Intramolecular Photocycloaddition of 2-Pyridines Tethered by a Three-Carbon Chain: Studies on the Formation of Cycloadducts and Control of Stereogenesis. 3
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Irradiation of a pair of 2-pyridones tethered at the 3- and 6'-positions by a three-carbon chain initiates an efficient cycloaddition to produce a densely functionalized, fused 5-8 carbocyclic ring system with the trans isomer predominant.An asymmetric center on the tether influences stereogenesis at the four new tetrahedral centers.This effect was probed with an alcohol substituent and its silyl ether as a function of solvent.A combination of inter- and intramolecular hydrogen-bonding can account for the observed levels of selectivity.Some of the cis products are unstable and undergo Cope rearrangement, yielding cyclobutane isomers.
- Sieburth, Scott McN.,Hiel, Gary,Lin, Chao-Hsiung,Kuan, Dora P.
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