- Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders
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Muscarinic agonists might be useful in the treatment of neurological disorders, including Alzheimer's disease, schizophrenia, chronic pain, and drug abuse. Previous studies identified a series of bis-1,2,5-thiadiazole derivatives of 1,2,5,6-tetrahydropyridine with high activity and selectivity for muscarinic receptors. To develop compounds with improved central nervous system penetration, several new derivatives were synthesized and characterized for muscarinic receptor binding and activity. One ligand (11) exhibited agonist activity at M1, M2, and M4 receptors, a selectivity profile suggesting potential utility in the treatment of schizophrenia.
- Cao, Yang,Zhang, Minjia,Wu, Cindy,Lee, Selina,Wroblewski, Mary Elizabeth,Whipple, Trisha,Nagy, Peter I.,Takács-Novák, Krisztina,Balázs, Attila,Tor?s, Szilárd,Messer Jr., William S.
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- Inhibition of secretory phospholipase A2. 2-Synthesis and structure-activity relationship studies of 4,5-dihydro-3-(4-tetradecyloxybenzyl) -1,2,4-4H-oxadiazol-5-one (PMS1062) derivatives specific for group II enzyme
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We have recently reported the discovery of a series of specific inhibitors of human group IIA phospholipase A2 (hGIIA PLA2) to display promising in vitro and in vivo properties. Here we describe the influence of different structural modifications on the specificity and potency against hGIIA PLA2 versus porcine group IB PLA2. The SAR results, as well as the log P and pKa values of oxadiazolone determined in this work, provide important information towards the comprehension of the mode of action of this kind of compounds.
- Dong, Chang-Zhi,Ahamada-Himidi, Azali,Plocki, Stephanie,Aoun, Darina,Touaibia, Mohamed,Meddad-Bel Habich, Nadia,Huet, Jack,Redeuilh, Catherine,Ombetta, Jean-Edouard,Godfroid, Jean-Jacques,Massicot, France,Heymans, Francoise
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p. 1989 - 2007
(2007/10/03)
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- Formation of macrocyclic ethers by free radical cyclization: Effects of chain length, substituents, and solvents
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Free radical reduction by tributylstannane of w-iodopolyoxaalkyl acrylates derived from tri-, tetra-, penta-, hexa-, and heptaethylene glycols gives mixtures of uncyclized reduction products and macrocyclic ethers formed by endo cyclization. The rate constants for cyclization of the intermediate radicals at 80 °C in benzene were determined under carefully defined conditions to be 15 × 104,13 ×104,5.1 × 104,10 × 104 and 3.6 × 104 s-1, for formation of the 12-, 15-, 18-, 21- and 24-membered rings, respectively. These values indicate that the presence of oxygen atoms in the chains increases the rate by a factor of 10-30 by comparison with the previously reported cyclization of alkenyl species. The rate constants at 80 °C in benzene and the endo/exo ratio for reductive cyclizations of the methacrylate, crotonate, cinnamate, maleate, and fumarate esters of 8-iodo-3,6-dioxaoctanol have been determined. The reduction of the 8-iodo-3,6-dioxaoctyl acrylate in solvents of varying polarity indicated that the cyclization rate has a relatively low solvent dependence.
- Philippen, Annie,Degueil-Castaing, Marie,Beckwith, Athelstan L. J.,Maillard, Bernard
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p. 6814 - 6819
(2007/10/03)
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- Veretherungen von Diolen, Triolen und Hydroxycarbonsaeurederivaten ueber Thallium(I)-alkoholate. Eine neue Variante der Williamson-Reaktion
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The etherifications listed in tables 1 and 2 are achieved by converting hydroxy-derivatives, which contain additional oxygen functions, into thallium(I) alkoxides with thallium ethoxide, and treatment with haloalkanes.The scope and limitations of the method are discussed.
- Kalinowski, Hans-Otto,Crass, Gerhard,Seebach, Dieter
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p. 477 - 487
(2007/10/02)
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- Hydrophilic Lipids
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The new triesters of glycerol 1-8 with different oligoethylene glycol carboxylic acids ("hydrophilic lipids") have been synthesized and their complexation with alkali and alkaline earth metal cations has been investigated.
- Heimann, Ulrich,Voegtle, Fritz
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p. 858 - 862
(2007/10/02)
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