72544-16-2Relevant articles and documents
Design and synthesis of rho kinase inhibitors (III)
Iwakubo, Masayuki,Takami, Atsuya,Okada, Yuji,Kawata, Takehisa,Tagami, Yoshimichi,Sato, Motoko,Sugiyama, Terumi,Fukushima, Kayoko,Taya, Shinichiro,Amano, Mutsuki,Kaibuchi, Kozo,Iijima, Hiroshi
, p. 1022 - 1033 (2007/10/03)
The structure-activity relationship of Rho kinase inhibitors bearing an isoquinoline scaffold was studied. N-(1-Benzyl-3-pyrrolidyl)-N-(5-isoquinolyl)amine analogues were optimized with respect to their inhibitory potencies for the enzyme and for chemotaxis. The potent analogues were further evaluated by an ex vivo test in which the selected compounds were orally administered to rats, and the Rho kinase inhibitory potency observed in the rat serum was evaluated 3 h after the administration. Compound 23g showed a high level of Rho kinase inhibitory activity in the rat serum and was stable in an in vitro metabolic test using a microsomal cytochrome preparation. The (R)-isomer of 23g displayed a higher level of inhibitory potency than the (S)-isomer in a cell-free kinase assay and in the cell migration assay (IC50ENZ = 25 nM and IC50MCP = 1 μ M). The (R)-isomer successfully inhibited the phosphorylation of MBS (myosin-binding subunit) in cells.
Novel 1,4 substituted piperidine derivatives. Synthesis and correlation of antioxidant activity with structure and lipophilicity
Alexidis,Rekka,Demopoulos,Kourounakis
, p. 131 - 137 (2007/10/02)
A series of novel piperidine derivatives was prepared and their lipophilicity was determined (as R(M) values). These compounds as well as two intermediate α-keto-esters were tested for antioxidant activity. It was found that the cysteamine derivatives were efficient antioxidants, i.e. they could inhibit lipid peroxidation, act as hydroxyl radical scavengers and interact with 2,2-diphenyl-1-picrylhydrazyl radicals. This interaction could be attributed to the free SH group and this activity seemed to be favoured by increased lipophilicity. Replacement of SH by NH2 or OH resulted in a decreased antioxidant activity of the compounds. However, the described activities seem not to be connected with any O2- scavenging ability, at least under the experimental conditions applied. Furthermore, cysteamine derivatives seem to induce O2- generation, a phenomenon often observed with thiol compounds. The antioxidant activity of the intermediate α-keto-esters varied and is probably mediated by different mechanisms.