- PROCESS AND INTERMEDIATES FOR PREPARING GPR40 AGONISTS
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The present invention relates to compounds of formula I wherein RS denotes F or CF3, Ra denotes H or C1-4-alkyl and Z denotes a leaving group or an optionally substituted or protected hydroxyl group, suitable as
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Paragraph 0327
(2015/03/31)
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- PROCESS AND INTERMEDIATES FOR PREPARING INDANYLOXYDIHYDROBENZOFURANYL ACETIC ACID DERIVATIVES AS GPR40 AGONISTS
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The present invention relates to compounds of formula (I) werein Rs denotes F or CF3, Ra denotes H or C1-4-alkyl and Z denotes a leaving group or an optionally substituted or protected hydroxyl group, suitable a
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Page/Page column 85; 86
(2015/04/15)
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- Use of xanthine derivatives for reducing the pathological hyperreactivity of eosinophilic granulocytes, novel xanthine compounds and process for their preparation
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Use of xanthine derivatives for reducing the pathological hyperreactivity of eosinophilic granulocytes, novel xanthine compounds and process for their preparation. Tertiary 1-(hydroxyalkyl)-4-alkylxanthines are suitable for the production of pharmaceuticals for the treatment of disorders which is associated with a pathologically increased reactivity of eosinophilic granulocytes. Novel xanthine derivatives and process for their preparation are described.
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- ON THE THERMAL DECOMPOSITION OF 2,5-DIHYPOCHLORO-2,5-DIMETHYLHEXANE
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The title compound was prepared, characterized, and on thermal decomposition at 100 deg C in the presence of a chlorine atom trap was found to give acetone, 1,2-dichloroethane, and 4-chloro-2-methyl-2-butanol.
- Sanabia, J. Arce de,Cardenas, L. M. De,Mendez, N. Quiros
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p. 4027 - 4030
(2007/10/02)
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- Mechanistic and Preparative Studies on the Regio- and Stereoselective Paraffin Hydroxylation with Peracids
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Reactions of more than 20 hydrocarbons with p-nitro- or, e.g., 3,5-dinitroperbenzoic acid in chloroform show regioselectivities of Rst = 90 (relative rates of attack at tertiary and secondary C-H bonds, after statistical correction) to 500 and configurational retention, if applicable, of typically 97-99.7percent.Radical side reactions are recognized by concomitant formation of, e.g., nitrobenzene and are responsible for a decrease in regio- and stereoselectivity.Steric effects are observed in attack at axial tertiary C-H bonds and at bridgehead positions.Electronegative and hydrogen-bonding substituents in the alkane diminish, and alkyl groups enhance the rates; the observed Taft ρ* value of -2.2 indicates substantial positive charge accumulation in the transition state in agreement with the high regioselectivity.A Hammett reaction constant of +0.63 is obtained from substituted perbenzoic acids; activation parameters of ΔH* = 15-19 kcal mol-1 and ΔS* = -22 to -29 eu with three alkanes of different flexibility and an isotope effect of kH/kD = 2.2 with methylcyclohexane are measured.Aromatic rings are usually not attacked but lead to deactivation of the peracid even at remote alkane C-H positions; similar deactivation is found in hydrogen-bonding solvents.Androstanes yield preferentially 9α- and 5α-hydroxy products, if, e.g., a 17β-acetoxy substituent is used to steer the reaction.Diols usually are only observed as a result of a proximity effect of a peracid associated at the first formed hydroxy group.The results point to relatively late and oxenoid transition states with substantial charge separation in the substrate.Attempts to achieve selective oxidations using macrocyclic azacyclophanes with attached carboxylic functions were not successful, although the host compounds showed selective complexation of hydrocarbons.
- Schneider, Hans-Joerg,Mueller, Walter
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p. 4609 - 4615
(2007/10/02)
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- 22-Hydroxycholesterol Derivatives as HMG CoA Reductase Suppressors and Serum Cholesterol Lowering Agents
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A series of 22-hydroxycholesterol derivatives with a modified side chain terminus was prepared.These agents were evaluated in vitro and in vivo for their ability to suppress HMG CoA reductase, the rate-limiting enzyme of cholesterol biosynthesis.In tissue culture assays, 22-hydroxycholesterol as well as the side chain modified analogues were potent inhibitors of HMG CoA reductase.However, only those sterols with a modified side chain terminus were effective suppressors of liver reductase whene administered ig to rats. 22-Hydroxy-25-methylcholesterol (4a) and 25-fluoro-22-hydroxycholesterol (15a) significantly lowered serum cholesterol levels when administered ig to primates; 25-chloro-22-hydroxycholesterol (15b) and the analogue with a cyclopropyl terminus, 20b, were ineffective.The cholesterol-lowering sterols did not significantly alter lipoprotein levels; however, the two compounds have been shown to inhibit acyl-coenzyme A:cholesterol-transferase (ACAT) in tissue culture studies
- Chorvat, Robert J.,Desai, Bipin N.,Radak, Suzanne Evans,McLaughlin, Kathleen T.,Miller, James E.,et al.
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p. 194 - 200
(2007/10/02)
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- 25-Halocholest-5-ene-3β,22-diols and esters thereof
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25-Halocholest-5-ene-3β,22-diols and esters thereof which inhibit the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and inhibit the formation of serum cholesterol and their preparation from 3α,5-cyclo-6β-methoxy-23,24-dinor-5α-cholan-20-al are disclosed.
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