- Regioselective Biomimetic Synthesis of Dimeric Oxyresveratrol Derivatives
-
Oxyresveratrol and its methylated derivative as coupling precursors were efficiently prepared in four steps, with Wittig reactions and subsequent isomerization reactions as the key steps. The coupling reactions of oxyresveratrol under various oxidative conditions gave a complex and inseparable mixture of coupling products. The oxidative dimerizations of methylated oxyresveratrols catalyzed by horseradish peroxidase-H 2O 2or FeCl 3·6H 2O in an acetone system predominantly produced the 8-5-coupled and 8-10-coupled dihydrobenzofuran-type dimers, respectively. This regioselective biomimetic strategy might be useful in synthesizing other dimeric oxyresveratrol derivatives.
- Ran, Lu,Li, Hongpeng,Chao, Ge,Kang, Xiaodong,Lei, Tian,Li, Wenling
-
-
Read Online
- A facile synthesis of biogenetic precursor, puerarone, isolated from Pueraria sp
-
Puerarone was synthesized using chalcone oxidation with thallium (III) trinitrate and chromenation of the resulting isoflavone using 3-hydroxyisovaleraldehyde dimethylacetal. The key demethylation step was achieved with boron tribromide.
- Khan,Kapil
-
-
Read Online
- Synthesis and characterisation of novel tricyclic and tetracyclic furoindoles: Biological evaluation as SAHA enhancer against neuroblastoma and breast cancer cells
-
The dihydropyranoindole structures were previously identified as promising scaffolds for improving the anti-cancer activity of histone deacetylase inhibitors. This work describes the synthesis of related furoindoles and their ability to synergize with suberoylanilide hydroxamic acid (SAHA) against neuroblastoma and breast cancer cells. The nucleophilic substitution of hydroxyin-dole methyl esters with α-haloketones yielded the corresponding arylether ketones, which were subsequently cyclized to tricyclic and tetracyclic furoindoles. The furoindoles showed promising individual cytotoxic efficiency against breast cancer cells, as well as decent SAHA enhancement against cancer cells in select cases. Interestingly, the best IC50 value was obtained with the non-cyclized intermediate.
- Arndt, Greg M.,Bingul, Murat,Black, David Stc.,Cheung, Belamy B.,Kumar, Naresh,Marshall, Glenn M.
-
-
- Preparation method of 4-butyl resorcinol
-
The invention belongs to the field of chemical synthesis and fine chemical manufacturing, and particularly discloses a preparation method of 4-butyl resorcinol, which comprises the following steps: byusing cheap and accessible 2, 4-dihydroxy benzaldehyde as a starting raw material and benzyl halide as an alkylation reagent, carrying out double O-benzylation under alkaline conditions to obtain 2,4-dibenzyloxy benzaldehyde; by taking triphenylpropyl phosphine halide as a reagent, carrying out Wittig alkenylation to prepare 2, 4-dibenzyloxy phenyl butene; and carrying out metal catalytic hydrogenation, and simultaneously completing alkenyl reduction and debenzylation to prepare the 4-butyl resorcinol in one pot. According to the method disclosed by the invention, a Friedel-Crafts acylationreaction and a reduction deketonization reaction which are necessary for a traditional method are abandoned, the use of excessive high-pollution reagents such as zinc chloride and hydrochloric acid isavoided, and the emission of three wastes is greatly reduced; the catalyst is reusable, free of by-products, simple and convenient to operate and suitable for large-scale production; the yield is increased, the cost is reduced, and the green upgrading of the industrial production technology of the 4-butylresorcinol is completed.
- -
-
Paragraph 0045-0047
(2020/12/05)
-
- Potent human dihydroorotate dehydrogenase inhibitory activity of new quinoline-4-carboxylic acids derived from phenolic aldehydes: Synthesis, cytotoxicity, lipophilicity and molecular docking studies
-
A series of novel 2-substituted quinoline-4-carboxylic acids was synthesized by Doebner reaction starting from freely available protocatechuic aldehyde and vanillin precursors. Human dihydroorotate dehydrogenase (hDHODH) was recognised as a clear molecular target for these heterocycles. All compounds were also tested for their antiproliferative potential against three cancer cells (MCF-7, A549, A375) and one normal cell line (HaCaT) to evaluate the selective cytotoxicity. Quinoline derivatives 3f and 3g were identified as potent hDHODH inhibitors while 3k and 3l demonstrated high cytotoxic activity against MCF-7 and A375 cells and good selectivity. In addition, the logD7.4 values obtained by the experimental method were found to be in the range from ?1.15 to 1.69. The chemical structures of all compounds were confirmed by IR, NMR and elemental analysis. The compounds pharmacology on the molecular level was revealed by means of molecular docking, highlighting the structural differences that distinguish highly active from medium and low active hDHODH inhibitors.
- Petrovi?, Milena M.,Roschger, Cornelia,Chaudary, Sidrah,Zierer, Andreas,Mladenovi?, Milan,Jakovljevi?, Katarina,Markovi?, Violeta,Botta, Bruno,Joksovi?, Milan D.
-
-
- RESORCINOL DERIVATIVE AND TYROSINASE ACTIVITY INHIBITOR CONTAINING THE SAME
-
PROBLEM TO BE SOLVED: To provide a compound showing high tyrosinase inhibitory activity. SOLUTION: The present invention provides resorcinol derivatives represented by formula I and II and a tyrosinase activity inhibitor containing one of them, where n is
- -
-
Paragraph 0034-0035
(2020/09/30)
-
- Identification of Interleukin-8-Reducing Lead Compounds Based on SAR Studies on Dihydrochalcone-Related Compounds in Human Gingival Fibroblasts (HGF-1 cells) in Vitro
-
Background: In order to identify potential activities against periodontal diseases, eighteen dihydrochalcones and structurally related compounds were tested in an established biological in vitro cell model of periodontal inflammation using human gingival fibroblasts (HGF-1 cells). Methods: Subsequently to co-incubation of HGF-1 cells with a bacterial endotoxin (Porphyromonas gingivalis lipopolysaccharide, pgLPS) and each individual dihydrochalcone in a concentration range of 1 μM to 100 μM, gene expression of interleukin-8 (IL-8) was determined by qPCR and cellular interleukin-8 (IL-8) release by ELISA. Results: Structure–activity analysis based on the dihydrochalcone backbone and various substitution patterns at its aromatic ring revealed moieties 20,4,40,60-tetrahydroxy 3-methoxydihydrochalcone (7) to be the most effective anti-inflammatory compound, reducing the pgLPS-induced IL-8 release concentration between 1 μM and 100 μM up to 94%. In general, a 2,4,6-trihydroxy substitution at the A-ring and concomitant vanilloyl (4-hydroxy-3-methoxy) pattern at the B-ring revealed to be preferable for IL-8 release inhibition. Furthermore, the introduction of an electronegative atom in the A,B-linker chain led to an increased anti-inflammatory activity, shown by the potency of 4-hydroxybenzoic acid N-vanillylamide (13). Conclusions: Our data may be feasible to be used for further lead structure designs for the development of potent anti-inflammatory additives in oral care products.
- Hans, Joachim,Ley, Jakob P.,Pfeiffer, Stefanie,Schueller, Katharina,Somoza, Veronika,Walker, Jessica
-
-
- Synthesis of cinnamic amide derivatives and their anti-melanogenic effect in α-MSH-stimulated B16F10 melanoma cells
-
Of the three enzymes that regulate the biosynthesis of melanin, tyrosinase and its related proteins TYRP-1 and TYRP-2, tyrosinase is the most important because of its ability to limit the rate of melanin production in melanocytes. For treating skin pigmentation disorders caused by an excess of melanin, the inhibition of tyrosinase enzyme is by far the most established strategy. Cinnamic acid is a safe natural product with an (E)-β-phenyl-α,β-unsaturated carbonyl motif that we have previously shown to play an important role in high tyrosinase inhibition. Since cinnamic acid is relatively hydrophilic, which hinders its absorption on the skin, fifteen less hydrophilic cinnamic amide derivatives (1–15) were designed as safe and more potent tyrosinase inhibitors and were synthesized through a Horner-Wadsworth-Emmons reaction. The use of conc-HCl and acetic acid for debenzylation of the O-benzyl-protected cinnamic amides 40–54 produced the following three results. 1) Cinnamic amides 43, 48, and 53 with a 2,4-dibenzyloxyphenyl group, irrespective of the amine type of the amides, produced complex compounds with high polarity. 2) Cinnamic amides 40–42, 44, 50–52, and 54 with a benzylamino, or diethylamino group produced the desired debenzylated cinnamic amides 1–3, 5, 10–13, and 15. 3) Cinnamic amides 45–47, and 49 with an anilino moiety provided 3,4-dihydroquinolinones 16–19 through intramolecular Michael addition of the anilide group. Notably, the use of BBr3 as an alternative debenzylating agent for debenzylation of cinnamic amides 45–49 with the anilino moiety provided our desired cinnamic amides 6–10 without inducing the intramolecular Michael addition. Debenzylation of cinnamic amides 43, 48, and 53 with a 2,4-dibenzyloxyphenyl group was also successfully accomplished using BBr3 to give 4, 9, and 14. Among the nine compounds that inhibited mushroom tyrosinase more potently at 25 μM than kojic acid, four cinnamic amides 4, 5, 9, and 14 showed 3-fold greater tyrosinase inhibitory activity than kojic acid. The docking simulation using tyrosinase indicated that these four cinnamic amides (?6.2 to ?7.9 kcal/mol) bind to the active site of tyrosinase with stronger binding affinity than kojic acid (?5.7 kcal/mol). All four cinnamic amides inhibited melanogenesis and tyrosinase activity more potently than kojic acid in α-MSH-stimulated B16F10 melanoma cells in a dose-dependent manner without cytotoxicity. The strong correlation between tyrosinase activity and melanin content suggests that the anti-melanogenic effect of cinnamic amides is due to tyrosinase inhibitory activity. Considering that the cinnamic amides 4, 9, and 14, which exhibited strong inhibition on mushroom tyrosinase and potent anti-melanogenic effect in B16F10 cells, commonly have a 2,4-dihydroxyphenyl substituent, the 2,4-dihydroxyphenyl substituent appears to be essential for high anti-melanogenesis. These results support the potential of these four cinnamic amides as novel and potent tyrosinase inhibitors for use as therapeutic agents with safe skin-lightening efficiency.
- Ullah, Sultan,Kang, Dongwan,Lee, Sanggwon,Ikram, Muhammad,Park, Chaeun,Park, Yujin,Yoon, Sik,Chun, Pusoon,Moon, Hyung Ryong
-
-
- RESORCINOL DERIVATIVES FOR THEIR COSMETIC USE
-
The invention relates to resorcinol-based compounds of formula (I), to the salts, solvates, optical and/or geometrical isomers thereof, to the use thereof as active agents for depigmenting, lightening and/ or bleaching keratin materials, and/or for preven
- -
-
Page/Page column 18
(2019/04/26)
-
- Tyrosinase inhibition and anti-melanin generation effect of cinnamamide analogues
-
Abnormal melanogenesis results in excessive production of melanin, leading to pigmentation disorders. As a key and rate-limiting enzyme for melanogenesis, tyrosinase has been considered an important target for developing therapeutic agents of pigment disorders. Despite having an (E)-β-phenyl-α,β-unsaturated carbonyl scaffold, which plays an important role in the potent inhibition of tyrosinase activity, cinnamic acids have not attracted attention as potential tyrosinase inhibitors, due to their low tyrosinase inhibitory activity and relatively high hydrophilicity. Given that cinnamic acids’ structure intrinsically features this (E)-scaffold and following our experience that minute changes in the chemical structure can powerfully affect tyrosinase activity, twenty less hydrophilic cinnamamide derivatives were designed as potential tyrosinase inhibitors and synthesised using a Horner-Wadsworth-Emmons reaction. Four of these cinnmamides (4, 9, 14, and 19) exhibited much stronger mushroom tyrosinase inhibition (over 90% inhibition) at 25 μM compared to kojic acid (20.57% inhibition); crucially, all four have a 2,4-dihydroxy group on the β-phenyl ring of the scaffold. A docking simulation using tyrosinase indicated that the four cinnamamides exceeded the binding affinity of kojic acid, and bound more strongly to the active site of tyrosinase. Based on the strength of their tyrosinase inhibition, these four cinnamamides were further evaluated in B16F10 melanoma cells. All four cinnamamides, without cytotoxicity, exhibited higher tyrosinase inhibitory activity (67.33 – 79.67% inhibition) at 25 μM than kojic acid (38.11% inhibition), with the following increasing inhibitory order: morpholino (9) = cyclopentylamino (14) cyclohexylamino (19) N-methylpiperazino (4) cinnamamides. Analysis of tyrosinase activity and melanin content in B16F10 cells showed that the four cinnamamides dose-dependently inhibited both cellular tyrosinase activity and melanin content and that their inhibitory activity at 25 μM was much better than that of kojic acid. The results of melanin content analysis well matched those of the cellular tyrosinase activity analysis, indicating that tyrosinase inhibition by the four cinnamamides is a major factor in the reduction of melanin production. These results imply that these four cinnamamides with a 2,4-dihydroxyphenyl group can act as excellent anti-melanogenic agents in the treatment of pigmentation disorders.
- Ullah, Sultan,Park, Chaeun,Ikram, Muhammad,Kang, Dongwan,Lee, Sanggwon,Yang, Jungho,Park, Yujin,Yoon, Sik,Chun, Pusoon,Moon, Hyung Ryong
-
-
- Design, synthesis and anti-melanogenic effect of cinnamamide derivatives
-
Pigmentation disorders are attributed to excessive melanin which can be produced by tyrosinase. Therefore, tyrosinase is supposed to be a vital target for the treatment of disorders associated with overpigmentation. Based on our previous findings that an (E)-β-phenyl-α,β-unsaturated carbonyl scaffold can play a key role in the inhibition of tyrosinase activity, and the fact that cinnamic acid is a safe natural substance with a scaffolded structure, it was speculated that appropriate cinnamic acid derivatives may exhibit potent tyrosinase inhibitory activity. Thus, ten cinnamamides were designed, and synthesized by using a Horner-Emmons olefination as the key step. Cinnamamides 4 (93.72% inhibition), 9 (78.97% inhibition), and 10 (59.09% inhibition) with either a 2,4-dihydroxyphenyl, or 4-hydroxy-3-methoxyphenyl substituent showed much higher mushroom tyrosinase inhibition at 25 μM than kojic acid (18.81% inhibition), used as a positive control. Especially, the two cinnamamides 4 and 9 having a 2,4-dihydroxyphenyl group showed the strongest inhibition. Docking simulation with tyrosinase revealed that these three cinnamamides, 4, 9, and 10, bind to the active site of tyrosinase more strongly than kojic acid. Cell-based experiments carried out using B16F10 murine skin melanoma cells demonstrated that all three cinnamamides effectively inhibited cellular tyrosinase activity and melanin production in the cells without cytotoxicity. There was a close correlation between cellular tyrosinase activity and melanin content, indicating that the inhibitory effect of the three cinnamamides on melanin production is mainly attributed to their capability for cellular tyrosinase inhibition. These results imply that cinnamamides having the (E)-β-phenyl-α,β-unsaturated carbonyl scaffolds are promising candidates for skin-lighting agents.
- Ullah, Sultan,Park, Yujin,Ikram, Muhammad,Lee, Sanggwon,Park, Chaeun,Kang, Dongwan,Yang, Jungho,Akter, Jinia,Yoon, Sik,Chun, Pusoon,Moon, Hyung Ryong
-
p. 5672 - 5681
(2018/10/24)
-
- RESORCINOL DERIVATIVES FOR THEIR COSMETIC USE
-
The invention relates to resorcinol derivatives of formula (I) and also the salts thereof, the solvates thereof and the optical and/or geometrical isomers thereof, including enantiomers and diastereoisomers, and the racemic mixtures thereof, alone or as a mixture. The invention also relates to a cosmetic process for depigmenting, lightening and/or bleaching keratin materials, especially the skin, using these compounds (I).
- -
-
Page/Page column 15-18; 22-29
(2018/12/13)
-
- Total Synthesis of Two Glycosylated Stilbenes, Oxyresveratrol 2-O-β- d -Glucopyranoside and 2,3,5,4′-Tetrahydroxystilbene 2-O-β- d -Glucopyranoside
-
Glycosylated stilbenes are biologically active secondary metabolites of plants and have the potential to alleviate a broad range of human diseases. However, some of these compounds are not naturally abundant, and thus the synthesis of such molecules is de
- Kumar, Sunil,Lee, Hsueh-Yun,Liou, Jing-Ping
-
p. 1294 - 1301
(2017/05/31)
-
- Tyrosinase inhibitor
-
PROBLEM TO BE SOLVED: To provide a new resorcinol derivative, and further, to provide a new tyrosinase activity inhibitor composed of the resorcinol derivative. SOLUTION: There are provided the resorcinol derivative, represented by formula 1, and th
- -
-
Paragraph 0062; 0063; 0064
(2019/04/02)
-
- IRE-1α INHIBITORS
-
PROBLEM TO BE SOLVED: To provide compounds which directly inhibit inositol requiring enzyme 1 (IRE-1α activity) in vitro, prodrugs, and pharmaceutically acceptable salts thereof. SOLUTION: The present invention provides a compound represented by formula (A) [R3 and R4 are H or the like; Q5-Q8, together with the benzene ring to which they are attached, form a benzofused ring, where at least one of Q5-Q8 is a heteroatom selected from N, O, and S. COPYRIGHT: (C)2016,JPOandINPIT
- -
-
Paragraph 1145; 1146
(2016/10/07)
-
- Coumarin moiety can enhance abilities of chalcones to inhibit DNA oxidation and to scavenge radicals
-
Coumarin and chalcone are naturally occurring compounds, and coumarin as a functional group was combined with chalcone in this work, aiming to test the inhibitory effects of coumarin-substituted chalcones on the oxidation of DNA and on scavenging radicals. It was found that the antioxidant activity of hydroxyl group attaching to coumarin can be increased by hydroxyl groups attaching to chalcone. The double hydroxyl groups at adjacent position exhibited high abilities to inhibit Cu2+/glutathione-induced oxidation of DNA and to trap 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+) as well as 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH). Especially, the double hydroxyl groups in chalcone were able to protect DNA against 2,2′-azobis(2-amidinopropanehydrochloride) (AAPH)-induced oxidation significantly. On the other hand, the hydroxyl group attaching to coumarin exhibited high ability to inhibit OH-induced oxidation of DNA. Therefore, coumarin-appended chalcones exhibited higher antioxidant effectiveness with only single or double phenolic hydroxyl groups contained.
- Xi, Gao-Lei,Liu, Zai-Qun
-
p. 8397 - 8404
(2015/03/04)
-
- Antioxidant effectiveness generated by one or two phenolic hydroxyl groups in coumarin-substituted dihydropyrazoles
-
A cascade operation was designed to synthesize nine coumarin-substituted dihydropyrazoles with only one or two phenolic hydroxyl groups contained. Antioxidant abilities of the obtained compounds were evaluated by inhibiting 2,2′-azobis(2-amidinopropanehydrochloride) (AAPH)-, Cu2+/ glutathione (GSH)-, and .OH-induced oxidation of DNA. It was found that less phenolic hydroxyl groups can enhance the abilities of coumarin-substituted dihydropyrazoles to protect DNA against the oxidation. Moreover, these coumarin-substituted dihydropyrazoles were employed to scavenge 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+.), 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical, respectively. It was found that double phenolic hydroxyl groups were more beneficial for enhancing the abilities of coumarin-substituted dihydropyrazoles to quench the aforementioned radicals. Therefore, dihydropyrazole linked with coumarin exhibited powerful antioxidant effectiveness even in the case of less phenolic hydroxyl groups involved.
- Xi, Gao-Lei,Liu, Zai-Qun
-
p. 385 - 393
(2013/10/01)
-
- Multidimensional optimization of promising antitumor xanthone derivatives
-
A promising antitumor xanthone derivative was optimized following a multidimensional approach that involved the synthesis of 17 analogues, the study of their lipophilicity and solubility, and the evaluation of their growth inhibitory activity on four human tumor cell lines. A new synthetic route for the hit xanthone derivative was also developed and applied for the synthesis of its analogues. Among the used cell lines, the HL-60 showed to be in general more sensitive to the compounds tested, with the most potent compound having a GI50 of 5.1 μM, lower than the hit compound. Lipophilicity was evaluated by the partition coefficient (Kp) of a solute between buffer and two membrane models, namely liposomes and micelles. The compounds showed a log Kp between 3 and 5 and the two membrane models showed a good correlation (r2 = 0.916) between each other. Studies concerning relationship between solubility and structure were developed for the hit compound and 5 of its analogues.
- Azevedo, Carlos M.G.,Afonso, Carlos M.M.,Sousa, Diana,Lima, Raquel T.,Helena Vasconcelos,Pedro, Madalena,Barbosa, Jo?o,Corrêa, Arlene G.,Reis, Salette,Pinto, Madalena M.M.
-
p. 2941 - 2959
(2013/07/05)
-
- Synthesis and antibacterial evaluation of anziaic acid and its analogues as topoisomerase i inhibitors
-
Naturally occurring anziaic acid has very recently been reported as a topoisomerase I inhibitor with antibacterial activity. Herein total synthesis of anziaic acid and its structural analogues is described and the preliminary structure-activity relationship (SAR) has been developed based on topoisomerase inhibition and whole cell antibacterial activity.
- Lin, Hao,Annamalai, Thirunavukkarasu,Bansod, Priyanka,Tse-Dinh, Yuk-Ching,Sun, Dianqing
-
supporting information
p. 1613 - 1618
(2013/12/04)
-
- COMPOUNDS AND METHODS FOR PREPARATION OF DIARYLPROPANES
-
Compounds of structure (I): including stereoisomers, tautomers and salts thereof, wherein R1, R2, R3, R4, R5, R6, X, Y and Z are as defined herein. Such compounds are useful for the preparation of diarylpropane compounds. Methods for the preparation of compounds of structure (I) are also disclosed, as are methods employing compounds of structure (I) for the preparation of diarylpropanes.
- -
-
Page/Page column 16
(2012/10/08)
-
- AGONISTS OF GPR40
-
The present invention relates to compounds that have the ability to modulate the activity of GPR40 and are there-fore useful in the treatment of GPR40 related disorders. In addition the invention relates to the compounds, methods for their preparation, pharmaceutical compositions containing the compounds and the uses of these compounds in the treatment of certain disorders related to GPR40 activity.
- -
-
Page/Page column 160
(2012/02/05)
-
- Lead identification of β-lactam and related imine inhibitors of the molecular chaperone heat shock protein 90
-
Heat shock protein 90 is an emerging target for oncology therapeutics. Inhibitors of this molecular chaperone, which is responsible for the maintenance of a number of oncogenic proteins, have shown promise in clinical trials and represent a new and exciting area in the treatment of cancer. Heat shock protein 90 inhibitors have huge structural diversity, and here we present the lead identification of novel inhibitors based on β-lactam and imine templates. β-Lactam 5 and imines 12 and 18 exhibit binding to heat shock protein 90-α with IC50 values of 5.6 μM, 14.5 μM, and 22.1 μM, respectively. The binding affinity displayed by these compounds positions them as lead compounds for the design of future inhibitors of heat shock protein 90 based on the β-lactam and imine templates.
- O'Boyle, Niamh M.,Knox, Andrew J.S.,Price, Trevor T.,Williams, D. Clive,Zisterer, Daniela M.,Lloyd, David G.,Meegan, Mary J.
-
experimental part
p. 6055 - 6068
(2011/11/06)
-
- Design, synthesis and SAR study of hydroxychalcone inhibitors of human β-secretase (BACE1)
-
According to the structural characteristics of isoliquiritigenin from Glycyrrhiza uralensis, a series of hydroxychalcones has been designed, synthesized and evaluated for their in vitro inhibitory activities of β-secretase (BACE1). Structure-activity relationship study suggested that inhibitory activity against BACE1 was governed to a greater extent by the hydroxyl substituent on A-and B-ring of the chalcone, and the most active compound was substituted with four hydroxyl group (17, IC50=0.27 μM).
- Ma, Lei,Yang, Zhengyi,Li, Chenjing,Zhu, Zhiyuan,Shen, Xu,Hu, Lihong
-
experimental part
p. 643 - 648
(2012/04/10)
-
- Synthesis and evaluation of C-ring aromatized analogues of phenanthridone alkaloids
-
Phenanthridone alkaloids are envisaged as an attractive lead for the development of anticancer agents. We have prepared a series of aromatized analogues on the basis of the structure of this class of alkaloids with the hope of finding the simplified compounds with comparable activities. The obtained analogues were evaluated for their cytotoxic effect against several cancer cell lines and found to be virtually inactive. These observations together with molecular modeling studies strongly suggest that the stereochemistries of hydroxyl groups in C-ring of phenanthridone alkaloids are crucial to biological effects.
- Lee, Seokwoo,Hwang, Soonho,Yu, Shuai,Jang, Wonyoung,Lee, Yun Mi,Kim, Sanghee
-
scheme or table
p. 1065 - 1070
(2012/07/14)
-
- Novel thiazolidinedione derivatives with anti-obesity effects: Dual action as PTP1B inhibitors and PPAR-γ activators
-
Benzylidene-2,4-thiazolidinedione derivatives with substitutions at both the ortho and para-positions of the phenyl group were synthesized as PTP1B inhibitors with IC50 values in a low micromolar range. Compound 18l, the lowest, bore an IC50 of 1.3 μM. In a peroxisome proliferator-activated receptor-γ (PPAR-γ) promoter reporter gene assay, 18l was found to activate the transcription of the reporter gene with potencies comparable to those of troglitazone, rosiglitazone, and pioglitazone. In vivo efficacy of 18l as an anti-obesity and hypoglycemic agent was evaluated in a mouse model system. Compound 18l significantly suppressed weight gain and significantly improved blood parameters such as TG, total cholesterol and NEFA without overt toxic effects.
- Bhattarai, Bharat Raj,Kafle, Bhooshan,Hwang, Ji-Sun,Ham, Seung Wook,Lee, Keun-Hyeung,Park, Hwangseo,Han, Inn-Oc,Cho, Hyeongjin
-
supporting information; experimental part
p. 6758 - 6763
(2010/12/20)
-
- Synthetic access to optically active isoflavans by using allylic substitution
-
A general approach to the (S)- and (R)-isoflavans was invented, and efficiency of the method was demonstrated by the synthesis of (S)-equol ((S)-3), (R)-sativan ((R)-4), and (R)-vestitol ((R)-5). The key step is the allylic substitution of (S)-6a (Ar1=2,4-(MeO)2C6H3) and (R)-6b (Ar1=2,4-(BnO)2C6H3) with copper reagents derived from CuBr·Me2S and Ar2-MgBr (7a, Ar2=4-MeOC6H4; 7b, 2,4-(MeO)2C6H3; 7c, 2-MOMO-4-MeOC6H3), furnishing anti SN2′ products (R)-8a and (S)-8b,c with 93-97% chirality transfer in 60-75% yields. The olefinic part of the products was oxidatively cleaved and the Me and Bn groups on the Ar1 moieties was then removed. Finally, phenol bromide 9a and phenol alcohols 9b,c underwent cyclization with K2CO3 and the Mitsunobu reagent to afford (S)-3 and (R)-4 and -5, respectively.
- Takashima, Yuji,Kaneko, Yuki,Kobayashi, Yuichi
-
experimental part
p. 197 - 207
(2010/03/03)
-
- The total large-scale synthesis of argiopine
-
The total large-scale synthesis of a natural toxin argiopine, a polymethylenepolyamine derivative, was developed. It consisted of 26 stages and included three key block schemes. Most of the stages proceeded quantitatively, which excluded the necessity of using the chromatographic separation of intermediates.
- Formanovsky,Popova,Mikhura
-
experimental part
p. 752 - 758
(2010/07/15)
-
- A new structural class of S-adenosylhomocysteine hydrolase inhibitors
-
Effective inhibitors of S-adenosylhomocysteine hydrolase hold promise towards becoming useful therapeutic agents. Since most efforts have focused on the development of nucleoside analog inhibitors, issues regarding bioavailability and selectivity have bee
- Kim, Byung Gyu,Chun, Tae Gyu,Lee, Hee-Yoon,Snapper, Marc L.
-
supporting information; experimental part
p. 6707 - 6714
(2009/12/06)
-
- Hydroxy-Substituted Diphenylazetidinones for the Treatment of Hyperlipidemia
-
The present invention comprises compounds and compositions for the treatment of metabolic disorders and more particularly, those insulin-related metabolic disorders of the blood such as hyperlipidemia, diabetes, insulin-resistance and the like comprising diphenylazetidinones compounds which have an additional hydroxy function in the 2″ position and their salts. The invention therefore relates to compounds of formula I: in which the meanings R1, R2, R3, R4, R5, R6 are defined herein.
- -
-
Page/Page column 27
(2008/12/08)
-
- Practical synthesis of lespedezol A1
-
A practical formal synthesis of lespedezol A1 (1) was accomplished in 33% yield for four steps starting from formation of the substituted chalcone. Of particular note is a useful protocol for reduction of the 2-ene bond in the isoflavone intermediate. A significant improvement in the final ring closure when water was scavenged from the reaction is also noteworthy. The ready availability of lespedezol A1 will provide material for further pharmacological evaluation and for exploration of the pterocarpene nucleus as a potential entry into various 6a-hydroxypterocarpans.
- Khupse, Rahul S.,Erhardt, Paul W.
-
p. 275 - 277
(2008/12/23)
-
- Thienopyrrole compound and use thereof as HCV polymerase inhibitor
-
The present invention relates to a thienopyrrole compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable a salt thereof, and a hepatitis C virus (HCV) polymerase inhibitor and a therapeutic agent for hepatitis C containing this compound as an active ingredient. The compound of the present invention shows an anti-HCV activity based on the HCV polymerase inhibitory activity, and useful as an agent for the prophylaxis or treatment of hepatitis C.
- -
-
Page/Page column 155
(2008/06/13)
-
- PHENYLAZETIDINONE DERIVATIVES
-
Various azetidinone derivatives are described, as are pharmaceutical compositions containing these compounds and methods of treatment of diseases using these compounds. Other embodiments are also described.
- -
-
Page/Page column 246-247
(2008/06/13)
-
- DIPHENYLHETEROCYCLE CHOLESTEROL ABSORPTION INHIBITORS
-
Various azetidinone, pyrrolidine, imidazolidine, and oxazolidine derivatives are described, as are pharmaceutical compositions containing these compounds and methods of treatment of diseases using these compounds. Other embodiments are also described.
- -
-
Page/Page column 250-252; 280-281
(2008/06/13)
-
- Biological activities of α-mangostin derivatives against acidic sphingomyelinase
-
Deprenyl and benzofenone-type congeners of α-mangostin 1 have been synthesized to understand their role for the inhibitory activity against sphingomyelinase (SMase). While removal of the prenyl group of the right side (11 and 12) caused loss of the selectivity between ASMase (acidic sphingomyelinase) and NSMase (neutral sphingomyelinase), the prenyl group of the left side appeared to increase the inhibitory activities (16 and 17).
- Hamada, Motoko,Iikubo, Kazuhiko,Ishikawa, Yuichi,Ikeda, Aya,Umezawa, Kazuo,Nishiyama, Shigeru
-
p. 3151 - 3153
(2007/10/03)
-
- Synthesis of constrained raloxifene analogues by complementary use of Friedel-Crafts and directed remote metalation reactions
-
New constrained heterocyclic analogues, 2a,b and 3, of Raloxifene (1) have been prepared by complementary Directed remote Metalation (DreM)/Friedel-Crafts cyclization approaches. Utilization of a benzylidene-thiolactone rearrangement was successfully impl
- Kalinin, Alexey V.,Reed, Mark A.,Norman, Bryan H.,Snieckus, Victor
-
p. 5992 - 5999
(2007/10/03)
-
- The first direct synthesis of α-mangostin, a potent inhibitor of the acidic sphingomyelinase
-
A total synthesis of α-mangostin 1a has been achieved. The key cyclization reaction to construct the xanthone framework was undertaken by employing the PPh3-CCl4 conditions. The inhibitory activities of 1a and the benzophenone intermediate 16 against the acidic sphingomyelinase were discussed.
- Iikubo, Kazuhiko,Ishikawa, Yuichi,Ando, Noritaka,Umezawa, Kazuo,Nishiyama, Shigeru
-
p. 291 - 293
(2007/10/03)
-
- Substituted phenyl compounds
-
Compounds of formula (I) are described wherein R1is hydrogen, -(lower alkyl)q(CO2R6or OH), —CN, —C(R7)═NOR8, NO2, —O(lower alkyl)R9, —C≡C—R10, —CR11═C(R12)(R13), —C(═O)CH2C(═O)CO2H, —CO(R14), alkylthio, alkylsulphinyl, alkylsulphonyl, carbamoyl, thiocarbamoyl, substituted carbamoyl, substituted thiocarbamoyl, sulphamoyl or an optionally substituted nitrogen-containing ring, m, n, o and p are independently zero or 1 and R2, R3, R4and R5are various groups; and physiologically acceptable salts, N-oxides and prodrugs thereof. The compounds have endothelin antagonist activity and are useful as pharmaceuticals.
- -
-
-
- 2-Azetidinone cholesterol absorption inhibitors: Increased potency by substitution of the C-4 phenyl ring
-
SAR studies directed towards the optimization of 2-azetidinone cholesterol absorption inhibitors led to the discovery of 11a, the most potent cholesterol absorption inhibitor yet identified. Copyright (C) 1998 Elsevier Science Ltd.
- Vaccaro, Wayne D.,Sher, Rosy,Davis Jr., Harry R.
-
p. 1429 - 1437
(2007/10/03)
-
- Selective endothelin A receptor ligands. 1. Discovery and structure-activity of 2,4-disubstituted benzoic acid derivatives
-
This paper describes the discovery of a new non-peptide endothelin A (ET(A)) selective ligand, 2,4-dibenzyloxybenzoic acid 3, which inhibits the binding of [125I]ET-1 to ET(A) receptors with an IC50 of 9 μM (ET-1 = endothelin-1). Optimisation of 3 resulted in compound 52 which had an IC50 of 1 μM. One of the analogues of 3, compound 15, was examined in a functional assay and shown to antagonise ET-1-induced contraction of rat aorta. The identification of 3 was made through the application of ChemDBS-3D searching of our corporate database. The 3D query, using an aromatic ring to a carboxylic acid group separated by 10.2 ± 1.1 A, was derived from an examination of common pharmacophoric distances found in the low energy conformations of two known ET(A) antagonists, the cyclic pentapeptide BQ 123 1 and myriceron caffeoyl ester 2.
- Astles,Brown,Handscombe,Harper,Harris,Lewis,Lockey,McCarthy,McLay,Porter,Roach,Smith,Walsh
-
p. 409 - 423
(2007/10/03)
-
- The regioselecttve 4-benzylation of 2,4-dihydroxybenzaldehyde
-
A regioselective mono-benzylation of the 4-hydroxyl group of 2,4-dihydroxybenzaldehyde (2) to produce 1 under extremely mild basic conditions (NaHCO3 or KF) has been developed. This approach gives improved regioselectivity relative to earlier methods.
- Mendelson, Wilford L.,Holmes, Monica,Dougherty, Jack
-
p. 593 - 601
(2007/10/03)
-
- N-heterocyclic amides
-
A compound of the formula: STR1 wherein STR2 represents a cyclic amino group, A represents a methylene group or a carbonyl group, m represents an integer of 1 to 3, n represents an integer of 0 to 4 and p represents an integer of 1 to 2, or a salt thereof, which has glutamate receptor inhibiting activity is provided.
- -
-
-
- Synthesis of a Proposed Isomer of F420 having α-Glutamyl Bonding.
-
A proposed isomer of redox coenzyme F420 having α-glutamyl bonding, has been synthesized from 8-benzyloxy-10-D-ribityl-5-deazaflavin and α-L-glutamyl-L-glutamic acid moiety, by the phosphite triester approach followed by deprotection procedures.
- Kimachi, Tetsutaro,Tanaka, Kiyoshi,Yoneda, Fumio
-
p. 439 - 443
(2007/10/02)
-
- Amide compounds, their production and use
-
A compound is provided which has the formula STR1 wherein m is an integer of 1 to 3; n is an integer of 1 or 2; p is an integer of 1 or 2; q is an integer of 1 to 6; x is an integer of 2 to 6; Ph is phenylene or a pharmceutically acceptable salt thereof. Also provided is a method for glutamate receptor inhibition which comprises administering to a mammal in need thereof an effective amount of said compound or a pharmaceutically acceptable salt thereof. Compositions for glutamate receptor inhibition are provided which contain an effective amount of said compound to provide a glutamate receptor inhibition effect, together with at least one pharmaceutically acceptable carrier, dilient or excipient therefor.
- -
-
-
- Glutamate receptor inhibitor and insecticidal composition
-
A compound of the formula STR1 wherein R' is hydrogen atom or an alkyl group, m is an integer of 1 to 3, p is 1 or 2, x is an integer of 2 to 6, and y is an integer of 1 to 3, or a salt thereof, which has glutamate receptor inhibitor activity, a process for preparing the same and an insecticidal composition containing the same are provided.
- -
-
-
- SYNTHESIS OF SPIDER TOXIN (JSTX-3) AND ITS ANALOGS
-
One of the active principles isolated from spider venom, JSTX-3, and its analogs of the polyamine part were synthesized.
- Hashimoto, Yuichi,Endo, Yasuyuki,Shudo, Koichi,Aramaki, Yoshio,Kawai, Nobufumi,Nakajima, Terumi
-
p. 3511 - 3514
(2007/10/02)
-