Xi:Irritant;103031-30-7Relevant articles and documents
Development of Selective TGR5 Ligands Based on the 5,6,7,8-Tetrahydro-5,5,8,8-tetramethylnaphthalene Skeleton
Terui, Ryusei,Yanase, Yuta,Yokoo, Hidetomo,Suhara, Yoshitomo,Makishima, Makoto,Demizu, Yosuke,Misawa, Takashi
, p. 458 - 462 (2021)
TGR5, a G-protein-coupled receptor (GPCR), plays an important role in several physiological functions. TGR5 activation through bile acids induces an increase in energy expenditure. Therefore, synthetic TGR5 ligands could be useful for the treatment of obesity or dyslipidemia. In this study, we designed and synthesized a set of TGR5 ligands with a 5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene (TMN) skeleton, and evaluated their TGR5 agonistic activity. We also investigated the selectivity of the synthesized compounds for TGR5 relative to the farnesoid X receptor (FXR) and retinoic acid receptor (RAR). Our results show that compound 4 b [N-(2-chlorophenyl)-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenecarboxamide] exhibited potent TGR5 agonist activity with an IC50 value of 8.4 nM without significant cytotoxicity. In addition, compound 4 b showed only slight agonistic activity toward FXR and RAR at 1 μM treatment. These data indicate that compound 4 b is a selective TGR5 agonist, and could be a promising therapeutic agent for dyslipidemia.
Synthesis and effects of some novel tetrahydronaphthalene derivatives on proliferation and nitric oxide production in lipopolysaccharide activated Raw 264.7 macrophages
Gurkan, A. Selen,Karabay, Arzu Z.,Buyukbingol, Zeliha,Buyukbingol, Erdem
, p. 468 - 479 (2011/03/19)
In this study, novel N-(3,5,5,8,8-pentamethyl-5,6,7,8- tetrahydronaphthalene-2-yl)-carboxamide (6-15) and 5,5,8,8-tetramethyl-5,6,7,8- tetrahydronaphthalene-2-carboxamide (16-32) derivatives were synthesized and their in vitro effects at 5 μM and 50 μM concentrations on proliferation and nitric oxide (NO) production in lipopolysaccharide (LPS) activated RAW 264.7 macrophage cells were determined. Compounds 12, 17, 24 and 26 were found to decrease nitrite levels in a dose-dependent manner in LPS-activated cells. At the tested concentrations, these compounds did not exhibit cytotoxic effects. Interestingly, compound 27 which contains nitroxide free radical was the most active compound in this series showing 59.2% nitrite inhibition in LPS-activated macrophage cells.
Discovery of tetrahydrotetramethylnaphthalene analogs as adult T-cell leukemia cell-selective proliferation inhibitors in a small chemical library constructed based on multi-template hypothesis
Nakamura, Masahiko,Hamasaki, Takayuki,Tokitou, Maiko,Baba, Masanori,Hashimoto, Yuichi,Aoyama, Hiroshi
experimental part, p. 4740 - 4746 (2009/10/10)
Adult T cell leukemia (ATL), caused by infection of human T-lymphotropic virus type 1 (HTLV-1), has a poor prognosis and curative therapy is unavailable, so it is important to find or design superior lead compounds for the drug treatment of ATL. We used our micro-reversed fragment-based drug design hypothesis and multi-template hypothesis to extract the tetrahydrotetramethylnaphthalene (TMN) skeleton from tamibarotene, a useful medicament for the treatment of acute promyelocytic leukemia (APL). Structural development of TMN yielded highly ATL cell-selective growth inhibitors, including 2-acetyl-3-hydroxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene (6). Structure-activity relationship analysis suggests the existence of a specific target molecule for ATL cell-selective inhibition of proliferation through G2 arrest.
