- A simple and efficient process for the preparation of 1,6- dimethoxynaphthalene
-
1,6-Dimethoxynaphthalene (1,6-DMN) was prepared by the O-dimethylation of 1,6-dihydroxynaphthalene (1,6-DHN) with dimethyl sulfate (DMS) in the presence of sodium hydroxide and additives in different solvents. The main reaction determining factors were divided into three categories with respect to yield and purity of 1,6-DMN: (1) Type of solvents and adding methods of NaOH had the highest effect on the results. (2) Amount of DMS and concentration of NaOH were less important. (3) Reaction time and temperature were the least important factors. The best reductant was Na2S2O4, and it was only under N2 atmosphere that yield and purity were also good. The improved process provides more than 99% yield, which considerably reduces the cost of 1,6-DMN, and more than 98% purity eliminates the purification process in the follow-up industrial production.
- Zhang, Tianyong,Yang, Qiusheng,Shi, Huixian,Chi, Lifeng
-
-
Read Online
- QUENCHER
-
A quencher is disclosed having a compound represented by the following general formula (1): wherein R5 each independently represent a halogen atom, an alkyl group, an alkoxy group, an alkylthio group, an amino group having a substituent or not having a substituent, a hydroxy group, an aryl group, an aryloxy group, or an arylalkyl group; R6 represents a group having a polymerizable unsaturated group, a hydroxy group, or the like; Y1 represents an oxygen atom, or the like; An? represents an anion; Ar1 represents a specific ring structure; * and ** represent binding positions; Ar2 represents a benzene ring, a naphthalene ring, or an anthracene ring; n1 represents a specific integer; and the following structure (1-10) in the general formula (1) is an asymmetric structure; (wherein R5, Y1, Ar1, Ar2, n1, * and ** are the same as described above.).
- -
-
Paragraph 0643
(2018/01/04)
-
- Optical Control of Dopamine Receptors Using a Photoswitchable Tethered Inverse Agonist
-
Family A G protein-coupled receptors (GPCRs) control diverse biological processes and are of great clinical relevance. Their archetype rhodopsin becomes naturally light sensitive by binding covalently to the photoswitchable tethered ligand (PTL) retinal. Other GPCRs, however, neither bind covalently to ligands nor are light sensitive. We sought to impart the logic of rhodopsin to light-insensitive Family A GPCRs in order to enable their remote control in a receptor-specific, cell-type-specific, and spatiotemporally precise manner. Dopamine receptors (DARs) are of particular interest for their roles in motor coordination, appetitive, and aversive behavior, as well as neuropsychiatric disorders such as Parkinson's disease, schizophrenia, mood disorders, and addiction. Using an azobenzene derivative of the well-known DAR ligand 2-(N-phenethyl-N-propyl)amino-5-hydroxytetralin (PPHT), we were able to rapidly, reversibly, and selectively block dopamine D1 and D2 receptors (D1R and D2R) when the PTL was conjugated to an engineered cysteine near the dopamine binding site. Depending on the site of tethering, the ligand behaved as either a photoswitchable tethered neutral antagonist or inverse agonist. Our results indicate that DARs can be chemically engineered for selective remote control by light and provide a template for precision control of Family A GPCRs.
- Donthamsetti, Prashant C.,Winter, Nils,Sch?nberger, Matthias,Levitz, Joshua,Stanley, Cherise,Javitch, Jonathan A.,Isacoff, Ehud Y.,Trauner, Dirk
-
p. 18522 - 18535
(2018/01/08)
-
- Au(i)-catalyzed triple bond alkoxylation/dienolether aromaticity-driven cascade cyclization to naphthalenes
-
A novel strategy for the synthesis of multisubstituted naphthalenes was developed via a Au(i)-catalyzed alkyne alkoxylation/dienolether aromaticity-driven cascade cyclization using 1,5-enyne substrates. The functional group toleration was examined by synthesizing a series of substrates and the mechanism was also studied based on intermediates isolated through deuterium labeling experiments. This journal is the Partner Organisations 2014.
- Liu, Yongxiang,Guo, Jia,Liu, Yang,Wang, Xiaoyu,Wang, Yanshi,Jia, Xinyu,Wei, Gaofei,Chen, Lizhu,Xiao, Jianyong,Cheng, Maosheng
-
supporting information
p. 6243 - 6245
(2014/06/09)
-
- Synthesis and biological evaluation of 1-benzylidene-3,4-dihydronaphthalen- 2-one as a new class of microtubule-targeting agents
-
A series of 1-benzylidene-3,4-dihydronaphthalen-2-one derivatives were designed and synthesized, and their biological activities in vitro and in vivo were evaluated. The results showed a number of the title compounds exhibiting potent nanomolar activity in several human cancer cell lines. Of these, compound 22b showed the strongest inhibitory activity against human CEM, MDA-MBA-435, and K562 cells (IC50 = 1 nM), displayed in vitro inhibition of tubulin polymerization (IC50 = 3.93 μM), and significantly induced cell cycle arrest in G2/M phase. In addition, compound 22b could inhibit the tumor growth in colon nude mouse xenograft tumor model significantly and seemed safer than CA-4 when achieving a similar tumor suppression. This study provided a new molecular scaffold for the further development of antitumor agents that target tubulin.
- Liu, Jia,Zheng, Can-Hui,Ren, Xiao-Hui,Zhou, Feng,Li, Wei,Zhu, Ju,Lv, Jia-Guo,Zhou, You-Jun
-
scheme or table
p. 5720 - 5733
(2012/07/30)
-
- Adenosine A2A receptor-antagonist/dopamine D2 receptor-agonist bivalent ligands as pharmacological tools to detect A 2A-D2 receptor heteromers
-
Adenosine A2A (A2AR) and dopamine D2 (D2R) receptors mediate the antagonism between adenosinergic and dopaminergic transmission in striatopallidal GABAergic neurons and are pharmacological targets for the treatment of Parkinson's disease.Here, a family of heterobivalent ligands containing a D2R agonist and an A 2AR antagonist linked through a spacer of variable size was designed and synthesized to study A2AR-D2R heteromers. Bivalent ligands with shorter linkers bound to D2R or A2AR with higher affinity than the corresponding monovalent controls in membranes from brain striatum and from cells coexpressing both receptors. In contrast, no differences in affinity of bivalent versus monovalent ligands were detected in experiments using membranes from cells expressing only one receptor. These findings indicate the existence of A2AR-D2R heteromers and of a simultaneous interaction of heterobivalent ligands with both receptors. The cooperative effect derived from the simultaneous interaction suggests the occurrence of A2AR-D2R heteromers in cotransfected cells and in brain striatum. The dopamine/adenosine bivalent action could constitute a novel concept in Parkinson's disease pharmacotherapy.
- Soriano, Aroa,Ventura, Ruben,Molero, Anabel,Hoen, Rob,Casado, Vicent,Corte, Antoni,Fanelli, Francesca,Albericio, Fernando,Lluís, Carmen,Franco, Rafael,Royo, Miriam
-
supporting information; experimental part
p. 5590 - 5602
(2010/03/24)
-
- Synthesis and antifungal activities of novel 2-aminotetralin derivatives
-
Novel 2-aminotetralin derivatives were synthesized as antifungal agents. The 2-aminotetralin scaffold was chemically designed to mimic the tetrahydroisoquinoline ring of the lead molecule described before. Their antifungal activities were evaluated in vitro by measuring the minimal inhibitory concentrations (MICs). Compounds 10a, 12a, 12c, 13b, and 13d are more potent than fluconazole against seven testing human fungal pathogens. Compound 10b exhibits much higher antifungal activities against all of the four fluconazole-resistant clinic Candida albicans strains than the control drugs including amphotericin B, terbinafine, ketoconazole, and itraconazole. The mode of action of some compounds to the potential receptor lanosterol 14α-demethylase (CYP51) was investigated by molecular docking. The studies presented here provide a new structural type for the development of novel antifungal compounds. Furthermore, 10b was evaluated in vivo by a rat vaginal candidiasis model, and it was found that 10b significantly decreases the number of fungal colony counts.
- Yao, Bin,Ji, Haitao,Cao, Yongbin,Zhou, Youjun,Zhu, Jü,Lü, Jiaguo,Li, Yaowu,Chen, Jun,Zheng, Canhui,Jiang, Yuanying,Liang, Rongmei,Tang, Hui
-
p. 5293 - 5300
(2008/03/18)
-
- An unexpected double-bond isomerization catalyzed by Crabtree's iridium(I) catalyst
-
The first iridium-catalyzed isomerization of an exocyclic into an endocyclic double bond is described. A mechanism is proposed for this reaction. Crabtree's catalyst thus allows the migration of a double bond that does not occur under classical conditions. Georg Thieme Verlag Stuttgart.
- Krel, Michael,Lallemand, Jean-Yves,Guillou, Catherine
-
p. 2043 - 2046
(2007/10/03)
-
- Bicyclic aromatic compounds as therapeutic agents
-
Compounds of formula I STR1 and pharmaceutically acceptable salts thereof in which A is methylene or --O--; B is methylene or --O--; and g is 0, 1, 2, 3 or 4; R1, R2, R3, R4, U, Q and T are defined in claim 1. The compounds have utility in the treatment of central nervous system disorders, for example depression, anxiety, psychoses (for example schizophrenia), tardive dyskinesia, Parkinson's disease, obesity, hypertension, Tourette's syndrome, sexual dysfunction, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, senile dementia, obsessive-compulsive behaviour, panic attacks, eating disorders and anorexia, cardiovascular and cerebrovascular disorders, non-insulin dependent diabetes mellitus, hyperglycaemia, constipation, arrhythmia, disorders of the neuroendocrine system, stress, prostatic hypertrophy, and spasticity.
- -
-
-
- The preparation and biological activity of lactam-based, non-steroidal, inhibitors of human type-1 steroid 5α-reductase
-
A Beckmann rearrangement of cis- and trans-fused 3,4,4a,9,10,10a-hexahydrophenanthren-1(2H)-one oximes has yielded three azepines. An in vitro assay of the azepines and (3aSR,9bSR)-6-methoxy-3-methyl-1,3,3a,4,5,9b-hexahydro-2H-benz[e]indol-2-one, prepared in four steps from naphthalene-1,6-diol, against human type-1 steroid 5α-reductase, revealed the tricyclic five-membered lactam to be a potent inhibitor (IC50 733 nM).
- Abell, Andrew D.,Phillips, Andrew J.,Budhia, Sangeeta,McNulty, Ann M.,Neubauer, Blake L.
-
p. 389 - 396
(2007/10/03)
-
- Regioselective Monomethylation of Unsymmetrical Naphthalenediols with Methanolic HCl
-
Treatment of naphthalene-1,3-diol and naphthalene-1,7-diol with methanol containing dry hydrogen chloride at room temperature gives exclusively 3-methoxy-1-naphthol and 7-methoxy-1-naphthol, respectively.Of the other two unsymmetrical naphthalenediols, the 1,2-isomer was unreactive and the 1,6-isomer gave a mixture of regioisomers under the same conditions.Two symmetrical diols (the 1,5- and 2,7-isomers) examined by the same procedure gave the monomethyl ethers in 60-70percent yields.
- Bell, Kevin H.,McCaffery, Leslie F.
-
p. 731 - 737
(2007/10/02)
-
- 2-Amido-8-methoxytetralins: A Series of Nonindolic Melatonin-like Agents
-
A series of unsubstituted and methoxy-substituted 2-amidotetralins (4a-q) was prepared and evaluated for their ability to complete for 2-iodomelatonin binding to chicken retinal membranes and for their potency to inhibit the calcium-dependent release of dopamine from rabbit retina.The lead compound, 2-acetamido-8-methoxytetralin (4j), showed a moderate affinity (Ki = 46 nM) and potency (IC50 = 1.4 nM) at the melatonin receptor.The structural requirements necessary for optimal agonistic activity at the melatonin receptor are as follows.First, the amido group, which should have a small, nonbranched alkyl group, is essential for affinity, and second, the methoxy substituent at the 8-position of the 2-amidotetralin ring is essential for optimal agonistic activity at the melatonin receptor.We concluded that this series of unsubstituted and methoxy-substituted 2-amidotetralins constitutes a class of nonindolic melatonin-like agents that can be used as pharmacological tools to further characterize melatonin receptors and to elucidate the mode of action of melatonin.
- Copinga, Swier,Tepper, Pieter G.,Grol, Cor J.,Horn, Alan S.,Dubocovich, Margarita L.
-
p. 2891 - 2898
(2007/10/02)
-
- Method for detecting dopaminergic diseases using fluorine-18 radiolabelled D2 dopamine receptor ligands
-
Abnormalitites in the distribution of a dopamine D 2 receptors in humans and other mammals are detected by(1) administering to a human or other mammal an amount of a 18 F-radiolabelled compound sufficient to be detected by a positron emission sensitive means for imaging, said compound having affinity for said receptors selected from the group consisting of optically active or racemic compounds represented by the general formula: STR1 (2) forming at least one image showing the distribution of the radiolabelled compound within the human or other mammal using a positron emission-sensitive means for imaging; and(3) determining normality of the concentrations or distribution by comparing the image with an image showing the normal concentrations and distribution of the receptors in humans or mammals of the same species wherein R1-R4, n and m- are as set forth in the specification.
- -
-
-
- Syntheses of 5-, 7-, and 8-Methoxy-3-methyl-2-tetralone
-
Two efficient syntheses of 5-methoxy- and 8-methoxy-3-methyl-2-tetralone and the synthesis of the 7-methoxy isomer via a different route are described.Also reported is the synthesis of 8-methoxy-3,3-dimethyl-2-tetralone.The regioselectivity of lithium carbanion formation in 1,6-, 1,7-, and 2,7-dihydroxynaphthalene is discussed.The latter compound undergoes dimetalation more easily than the other isomers.
- Johansson, Anette M.,Mellin, Charlotta,Hacksell, Uli
-
p. 5252 - 5258
(2007/10/02)
-
