162510-56-7Relevant articles and documents
2-carboxyl piperazine linked tacrine-8-amino(hydroxyl) quinoline derivative as well as preparation and application
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, (2019/08/06)
The invention relates to the technical field of chemical synthesis, and specifically relates to a 2-carboxyl piperazine linked tacrine-8-amino(hydroxyl) quinoline derivative as well as preparation andapplication. The 2-carboxyl piperazine linked tacrine-8-amino(hydroxyl) quinoline derivative is a chemical compound shown in a formula I (the formula I is shown in the description) or a pharmaceutically acceptable salt thereof, and a solvent chemical compound, an enantiomer, a diastereoisomer, a tautomer or a mixture in any proportion of the chemical compound shown in the formula I or the pharmaceutically acceptable salt thereof, and includes a racemic mixture. Confirmed by a pharmacological test, the kind of chemical compound has an inhibiting effect on the activity of acetylcholinesterase(AChE) and butyrylcholinesterase(BuChE), and belongs to a cholinesterase inhibitor; the chemical compound also has an inhibiting effect on self-aggregation of beta-amyloid protein, and has delayed action on hydrolysis of acetylcholine and self-aggregation of the beta-amyloid protein, thereby improving the effect of the acetylcholine on a synapse, and finally realizing the purpose of effectively treating alzheimer's disease (AD).
Design and synthesis of imidazoline derivatives active on glucose homeostasis in a rat model of type ii diabetes. 2. Syntheses and biological activities of 1,4-dialkyl-, 1,4-dibenzyl, and 1-benzyl-4-alkyl-2-(4',5'- dihydro-1'H-imidazol-2'-yl)piperazines and isosteric analogues of imidazoline
Le Bihan, Ga?lle,Rondu, Frédéric,Pelé-Tounian, Agnès,Wang, Xuan,Lidy, Sandrine,Touboul, Estéra,Lamouri, Aazdine,Dive, Georges,Huet, Jack,Pfeiffer, Bruno,Renard, Pierre,Guardiola-Lema?tre, Béatrice,Manéchez, Dominique,Pénicaud, Luc,Ktorza, Alain,Godfroid, Jean-Jacques
, p. 1587 - 1603 (2007/10/03)
Piperazine derivatives have been identified as new antidiabetic compounds. Structure-activity relationship studies in a series of 1-benzyl- 4-alkyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)piperazines resulted in the identification of 1-methyl-4-(2',4'-dichlorobenzyl)-2-(4',5'-dihydro-1'H- imidazol-2'-yl)piperazine, PMS 812 (S-21663), as a highly potent antidiabetic agent on a rat model of diabetes, mediated by an important increase of insulin secretion independently of α2 adrenoceptor blockage. These studies were extended to find additional compounds in these series with improved properties. In such a way, substitution of both piperazine N atoms was first optimized by using various alkyl, branched or not, and benzyl groups. Second, some modifications of the imidazoline ring and its replacement by isosteric heterocycles were carried out, proceeding from PMS 812, to evaluate their influence on the antidiabetic activity. The importance of the distance between the imidazoline ring and the piperazine skeleton was studied third. Finally, the influence of the N-benzyl moiety was also analyzed compared to a direct N-phenyl substitution. The pharmacological evaluation was performed in vivo using glucose tolerance tests on a rat model of type II diabetes. The most active compounds were 1,4-diisopropyl-2-(4',5'-dihydro-1'H-imidazol-2'- yl)piperazine (41a), PMS 847 (S-22068), and 1,4-diisobutyl-2-(4',5'-dihydro- 1'H-imidazol-2'-yl)piperazine (41b), PMS 889 (S-22575), which strongly improved glucose tolerance without any side event or hypoglycemic effect. More particularly, PMS 847 proved to be as potent after po (100 μmol/kg) as after ip administration and appears as a good candidate for clinical investigations.