- 2,3,5-substituted biphenyls useful in the treatment of insulin resistance and hyperglycemia
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This invention provides compounds of Formula I having the structure wherein:B, C, D, and R1 are as defined hereinbefore in the specification, or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.
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- Zwitterionic sulfobetaine inhibitors of squalene synthase
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A substantial number of sulfobetaines (e.g., 10) have been synthesized and evaluated as inhibitors of squalene synthase (SS) on the basis of the idea that their zwitterionic structure would have properties conducive both to binding in the active site and to passage through cell membranes. When the simple sulfobetaine moiety is incorporated into compounds containing hydrophobic portions like those in farnesyl diphosphate (1) or presqualene diphosphate (2), inhibition of SS in a rat liver microsomal assay was indeed observed. For example, farnesylated sulfobetaine 10 has IC50 = 10 μM and aromatic derivative 35 has IC50 = 2 μM for SS inhibition. A wide variety of structural modifications, exemplified by compounds 43, 52, 76, 85, 91, 99, 111, and 115, was investigated. Unfortunately, no inhibitors in the submicromolar range were discovered, and exploration of a different type of zwitterion seems necessary if this appealing approach to inhibition of SS is going to provide a potential antihypercholesterolemic agent.
- Spencer, Thomas A.,Onofrey, Thomas J.,Cann, Reginald O.,Russel, Jonathon S.,Lee, Laura E.,Blanchard, Daniel E.,Castro, Alfredo,Gu, Peide,Jiang, Guojian,Shechter, Ishaiahu
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p. 807 - 818
(2007/10/03)
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- Processes and intermediates for the preparation of 2-substituted benzaldehydes
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Processes for preparing 2-substituted benzaldehydes of general formula (I), wherein: R1 is CH2 CH2 --(L1)p --(CH2)q --(L2)r --CH2 --(T)2/su
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- Synthesis of long chain ω-aralkylbromides
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1-Iodo-4-acetoxybutane is a useful 4 carbon synthon which reacts selectively with Grignards under copper catalysis. The immediate products are converted to bromides.
- Forth,Smith
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p. 951 - 959
(2007/10/02)
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- Unusually Long Lifetimes of the Singlet Derived from 4-Azido-2,3,5,6-tetrafluorobenzamides
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Laser flash photolysis (308 nm, 20 ns, 150 mJ) of 4-azido-2,3,5,6-tetrafluorobenzamides, esters, and thioesters generate singlet nitrenes which can be intercepted with pyridine to produce strongly absorbing ylides.It was possible to resolve the rate of formation of the ylides as a function of pyridine concentration.This has lad to direct measurements of the absolute rate constants of (a) the reaction of the nitrene with pyridine, (b) ring expansion of the nitrene to a ketenimine, and (c) singlet to triplet nitrene intersystem crossing.
- Marcinek, Andrzej,Platz, Matthew S.,Chan, Stephen Y.,Floresca, Rey,Rajagopalan, Krishnan,et al.
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p. 412 - 419
(2007/10/02)
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- 5-(phenylalkoxy)primaquine compounds and their use for treatment of malaria
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Improvement in the treatment of malaria has been demonstrated with 5-arylalkoxy primaquine compounds of the formula STR1 wherein R2 represents H or methyl, R represents an alkylene group having from about 2 to about 12 carbon atoms, R' represents a substituted or non-substituted aryl moiety, such as phenyl and napthyl, and pharmaceutically acceptable salts thereof, wherein the salt forming acid may be organic or inorganic in nature. These primaquine related compounds are effective in malarial chemotherapy, by exerting plasmodicidal activity on malarial parasites present in both the blood and formed tissues of the mammalian host. The 5-arylalkoxy primaquine compounds of the invention are at least as effective in malarial treatment as the prior art 5-alkoxy primaquine compounds, but are not as toxic as the 5-alkoxy compounds at higher dosage ranges.
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- Synthesis of Malabaricone-A - Confirmation of its Structure
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Wittig reaction of 7-phenylheptyl bromide (I) with 2,6-dimethoxyphenylglyoxal (II) affords 1-(2,6-dimethoxybenzoyl)-8-phenyl-oct-1-ene (III).III on hydrogenation over Pd/C catalyst followed by demethylation with pyridine hydrobromide yields malabaricone-A
- Parthasarathy, M. R.,Gupta, Sushma
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