194490-18-1Relevant articles and documents
Synthesis method for preparing 2-substituted indole derivative
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Paragraph 0051-0054, (2019/05/28)
The invention relates to a synthesis method for preparing a 2-substituted indole derivative. The method includes the following steps: mixing aromatic amine compounds (I), ketone compounds (II) and a drying agent in an organic solvent; adding a palladium catalyst; and reacting in an aerobic weak acid environment to prepare the indole compounds (III). (I), (II) and (III) are as shown in the specification, wherein R1 is selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkanoyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, hydroxyl, substituted or unsubstituted amino, substituted or unsubstituted phenyl, pyridyl and heterocyclic aryl; (I) can be pyridylamine, pyrimidylamine, pyridazinam or pyrazinamide which may further be substituted or unsubstituted; and the substituents are selected fromone or more C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkanoyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, hydroxyl, amino; and R2 is selected from C1-C6 alkyl, formate groups or C1-C6 alkylamide groups.
Characterization of HERG potassium channel inhibition using CoMSiA 3D QSAR and homology modeling approaches
Pearlstein, Robert A.,Vaz, Roy J.,Kang, Jiesheng,Chen, Xiao-Liang,Preobrazhenskaya, Maria,Shchekotikhin, Andrey E.,Korolev, Alexander M.,Lysenkova, Ludmila N.,Miroshnikova, Olga V.,Hendrix, James,Rampe, David
, p. 1829 - 1835 (2007/10/03)
A data set consisting of twenty-two sertindole analogues and ten structurally diverse inhibitors, spanning a wide range in potency, was analyzed using CoMSiA. A homology model of HERG was constructed from the crystal structure of the open MthK potassium channel. A complementary relationship between our CoMSiA and homology models is apparent when the long inhibitor axis is oriented parallel to the longitudinal axis of the pore, with the tail region pointed toward the selectivity filter. The key elements of the pharmacophore, the CoMSiA and the homology model are: (1) The hydrophobic feature optimally consists of an aromatic group that is capable of engaging in π-stacking with a Phe656 side chain. Optionally, a second aromatic or hydrophobic group present in some inhibitors may contact an additional Phe656 side chain. (2) The basic nitrogen appears to undergo a π-cation interaction with Tyr652. (3) The pore diameter (12 A+), and depth of the selectivity loop relative to the intracellular opening, act as constraints on the conformation-dependent inhibitor dimensions.
Monocyte chemoattractant protein-1 inhibitor compounds
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, (2008/06/13)
The invention concerns the use of a compound of the formula (I) in which Z, X, T, A, R1, R2, p and q have any of the meanings defined herein, and their pharmaceutically acceptable salts or in vivo hydrolysable esters, in the treatment of a disease or condition mediated by monocyte chemoattractant protein-1 (MCP-1). Certain of the components of formula (I) are novel and are provided, together with pharmaceutical compositions thereof, as further features of the invention.