C:Corrosive;104224-50-2Relevant articles and documents
Development of biotin-retinoid conjugates as chemical probes for analysis of retinoid function
Fujii, Shinya,Mori, Shuichi,Kagechika, Hiroyuki,Mendoza Parra, Marco Antonio,Gronemeyer, Hinrich
, p. 2442 - 2445 (2018)
Herein, we report the rational design, synthesis and biological evaluation of conjugates consisting of the synthetic retinoid Am580 and biotin connected via a linker moiety. We found that the linking substructure between the retinoid part and the biotin part is critical for retaining the biological activity. Conjugate 4 with a shorter linker showed similar potency to endogenous retinoid ATRA (1) and the parent compound Am580 (2) for neural differentiation of mouse embryotic carcinoma P19 cells, and showed the same pattern of induction of gene expression. It is expected to be useful as a probe for investigations of retinoid function. The design rationale and structure-activity relationship of the linker moiety are expected to be helpful for developing biotin conjugates of other nuclear receptor ligands.
Retinobenzaldehydes as proper-trafficking inducers of folding-defective P23H rhodopsin mutant responsible for Retinitis Pigmentosa
Ohgane, Kenji,Dodo, Kosuke,Hashimoto, Yuichi
, p. 7022 - 7028 (2010)
The Retinitis pigmentosa (RP)-causing mutant of rhodopsin, P23H rhodopsin, is folding-defective and unable to traffic beyond the endoplasmic reticulum (ER). This ER retention, and in some cases aggregation, are proposed to result in ER-stress and eventually cell death. The endogenous rhodopsin ligand 11-cis-retinal and its isomer 9-cis-retinal have been shown to act as pharmacological chaperones, promoting proper folding and trafficking of the P23H rhodopsin. In spite of this promising effect, the development of retinals and related polyenealdehydes as pharmacological agents has been hampered by their undesirable properties, which include chemical instability, photolability, and potential retinoidal actions. Here, we report the design and synthesis of a class of more stable nonpolyene-type rhodopsin ligands, structurally distinct from, and with lower toxicity than, retinals. A structure-activity relationship study was conducted using cell-surface expression assay to quantify folding/trafficking efficiency of P23H rhodopsin.
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
supporting information, p. 458 - 462 (2020/10/23)
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.
Synthetic method of retinoic acid derivative Am580
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Paragraph 0041-0043, (2021/03/13)
The invention discloses a synthetic method of retinoic acid derivative Am580, which comprises: stirring a solution of 2, 5-dimethyl hexane-2, 5-diol in concentrated HCl for 30 min, introducing HCl gasinto the system, carrying out a reaction for 3 h, performing stirring until the system becomes a two-phase mixture, performing cooling to a room temperature, performing filtering to obtain a light pink solid, washing the solid with water, performing recrystallizing in methanol, and performing filtering to obtain an intermediate 3 which is a white solid; dissolving 2, 5-dichloro-2, 5-dimethylhexane in an organic solvent, adding AlCl3 into the solution according to a molar ratio of the 2, 5-dichloro-2, 5-dimethylhexane to the AlCl3 of 1: 0.1-1: 0.2, performing heating to 100-120 DEG C, performing stirring for 16 hours, quenching the reaction by using 3M HCl, performing extracting by using normal hexane, and performing distilling under reduced pressure to remove the solvent to obtain a colorless oily matter intermediate 4. The method has the beneficial effects that the yield of each step is relatively high, the post-treatment is simple, and the industrial production is easier; reaction conditions and a solvent system are optimized for the Friedel-Crafts reaction and the oxidation reaction, and industrial production is better facilitated.
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
experimental part, 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.
THERAPEUTIC DRUG FOR ADULT T-CELL LEUKEMIA
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Page/Page column 8, (2011/08/02)
An object is to provide a novel therapeutic drug for adult T-cell leukemia having an ATL cell specific antitumor effect. The therapeutic drug for adult T-cell leukemia according to the invention is characterized by containing a compound represented by the formula I or a prodrug thereof, wherein R1 is H, OH, an alkoxy group, an acyl group, or a thioacyl group, R2 is an acyl group, a thioacyl group, CONR7R8, or CSNR7R8 (R7 and R8 being each independently H, an alkyl group containing 1 to 3 carbon atoms, or a phenyl group), or R1 and R2 together may form a ring, X1 and X2 may be the same or different and are each —CR3R4—, —SiR3R4— or oxygen, and R3 and R4 may be the same or different and are each an alkyl group containing 1 to 6 carbon atoms.
RETINOID PRODRUG COMPOUND
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Page/Page column 15, (2010/08/18)
A compound represented by the following general formula (I) : [R1 to R5 represent hydrogen atom, an alkyl group, or a trialkylsilyl group, X represents -NH-CO-, -CO-NH-, -N(COR6)-CO-, -CO-N(COR7)- (R6 and R7 represent a lower alkoxy group, or a carboxy-substituted phenyl group) etc.; and Z represents -Y-CH(R12)-COOH, -CHO, -CH-CH-COOH, or -COOR13 (Y represents a single bond, -CH2-, -CH(OH)-, -CO-, -CO-NH-, or -CO-NH-CH2-CO-NH-, R12 represents hydrogen atom or a lower alkyl group, and R13 represents hydrogen atom, -CH(R14)-COOH (R14 represents hydrogen atom, a lower alkyl group, or hydroxy group), -[CH2CH2-O]n-CH2-CH2-OH, CH2-O-[CH2CH2O]m-CH2-OH, or -[CH(CH3)-CO-O]p-CH(CH3)-COOH (m, n and p represent an integer of 1 to 100))], a salt thereof or an ester thereof, which has a property of being converted into a retinoid after absorption in vivo.
RETINOID PRODRUG COMPOUND
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Page/Page column 12-13, (2010/12/29)
A compound represented by the following general formula (I): [R1 to R5 represent hydrogen atom, an alkyl group, or a trialkylsilyl group, X represents —NH—CO—, —CO—NH—, —N(COR6)—CO—, —CO—N(COR7)— (R6 and R7 represent a lower alkoxy group, or a carboxy-substituted phenyl group) etc.; and Z represents —Y—CH(R12)—COOH, —CHO, —CH═CH—COOH, or —COOR13 (Y represents a single bond, —CH2—, —CH(OH)—, —CO—, —CO—NH—, or —CO—NH—CH2—CO—NH—, R12 represents hydrogen atom or a lower alkyl group, and R13 represents hydrogen atom, —CH(R14)—COOH(R14 represents hydrogen atom, a lower alkyl group, or hydroxy group), —[CH2CH2—O]n—CH2—CH2—OH, —CH2—O—[CH2CH2—O]m—CH2—OH, or —[CH(CH3)—CO—O]p—CH(CH3)—COOH (m, n and p represent an integer of 1 to 100))], a salt thereof or an ester thereof, which has a property of being converted into a retinoid after absorption in vivo.
Synthesis and antioxidant activity of new tetrahydro-naphthalene-indole derivatives as retinoid and melatonin analogs
Ates-Alagoz, Zeynep,Coban, Tulay,Buyukbingol, Erdem
, p. 193 - 200 (2007/10/03)
A number of retinoid-related compounds represent classes of antioxidative and proapoptotic agents with promising potential in the treatment of neoplastic diseases. Indeed, the synthetic retinoid amide fenretinide [N-(4-hydroxyphenyl) retinamide] induces apoptosis of cancer cells and acts as a chemotherapeutic drug in cancer therapy. In the present work, and as a continuation of our studies on retinoid-type compounds, the synthesis of melatonin retinamide derivatives was studied as a novel series of melatonin retinoids, using the condensation reaction sequence involving tetrahydrotetramethylnaphthalene carboxylic acid and appropriate melatonin-type moieties. Despite of the weak DPPH inhibition activity pattern of the synthesized compounds, some of them showed a strong inhibition on lipid peroxidation (IVa-b, Va, and VIIa-c, 88, 96, 90, 94, 93, and 86%, respectively at 10-4 M concentration) when melatonin (85% at 10-4 M concentration) was used as a reference compound.
Tricyclic hydroxamate and benzaminde derivatives, compositions and methods
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Page/Page column 12; 37, (2008/06/13)
The present invention relates to compounds and methods for inhibiting histone deacetylase enzymatic activity. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit histone deacetylases (HDACs), and in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, and also central nervous system diseases. It further deals with processes for preparing said compounds.
