- Synthesis, inhibition properties against xanthine oxidase and molecular docking studies of dimethyl N-benzyl-1H-1,2,3-triazole-4,5-dicarboxylate and (N-benzyl-1H-1,2,3-triazole-4,5-diyl)dimethanol derivatives
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This study focused on synthesis various dimethyl N-benzyl-1H-1,2,3-triazole-4,5-dicarboxylate and (N-benzyl-1H-1,2,3-triazole-4,5-diyl)dimethanol derivatives under the conditions of green chemistry without the use of solvent and catalysts. Their inhibition properties were also investigated on xanthine oxidase (XO) activity. All dimethanol and dicarboxylate derivatives exhibited significant inhibition activities with IC50 values ranging from 0.71 to 2.25 μM. Especially, (1-(3-bromobenzyl)-1H-1,2,3-triazole-4,5-diyl)dimethanol (5c) and dimethyl 1-(4-chlorobenzyl)-1H-1,2,3-triazole-4,5-dicarboxylate (6 g) compounds were found to be the most promising derivatives on the XO enzyme inhibition with IC50 values 0.71 and 0.73 μM, respectively. Moreover, the double docking procedure was to evaluate compound modes of inhibition and their interactions with the protein (XO) at atomic level. Surprisingly, the docking results showed a good correlation with IC50 [correlation coefficient (R2 = 0.7455)]. Also, the docking results exhibited that the 5c, 6f and 6 g have lowest docking scores ?4.790, ?4.755, and ?4.730, respectively. These data were in agreement with the IC50 values. These results give promising beginning stages to assist in the improvement of novel and powerful inhibitor against XO.
- Yagiz, Güler,Noma, Samir Abbas Ali,Altundas, Aliye,Al-khafaji, Khattab,Taskin-Tok, Tugba,Ates, Burhan
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- BORON CONTAINING COMPOUNDS AND THEIR USES
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The present disclosure contemplates novel boron-containing compounds and their uses as active agents that exhibit pesticidal activity such as antimicrobial, insecticidal, arachnicidal, and/or anti parasitic activity. An agrochemical composition containing such a compound and its use in, animal health, agriculture, or horticulture is also contemplated. A method for promoting plant performance and/or controlling, reducing, preventing, ameliorating, or inhibiting microbes, insects, arachnids, and/or parasites on or in an animal, a plant, a plant part, plant propagation material, and/or harvested fruits or vegetables is also contemplated.
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Paragraph 0305; 0306
(2020/03/29)
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- Novel indole and triazole based hybrid molecules exhibit potent anti-adipogenic and antidyslipidemic activity by activating Wnt3a/β-catenin pathway
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Obesity and dyslipidemia is the two facet of metabolic syndrome, which needs further attention. Recent studies indicate triazole and indole derivatives have remarkable anti-obesity/antidyslipidemic activity. To harness the above-mentioned potential, a series of novel triazole clubbed indole derivatives were prepared using click chemistry and evaluated for anti-adipogenic activity. Based on the structure-activity relationship, essential functional groups which potentiate anti-adipogenic activity were identified. The lead compound 13m exhibited potent anti-adipogenic activity compared to its parent compounds with the IC-50 value of 1.67 μM. Further evaluation of anti-adipogenic activity was conducted in different cell lines such as C3H10T1/2 and hMSC with positive result. The anti-adipogenic effect of compound 13m was most prominent in the early phase of adipogenesis, which is driven by the G1 to S phase cell cycle arrest during mitotic clonal expansion. The mechanistic study suggests that compound 13m exhibit anti-adipogenic property by activating Wnt3a/β-catenin pathway, a known suppressor of key adipogenic genes PPARγ and C/EBPα. It is noteworthy that the compound 13m also reduced serum triglyceride, LDL and total cholesterol in Syrian Golden hamster model of dyslipidemia. The anti-adipogenic activity of compound 13m can also be correlated with decreased expression of PPARγ and increased expression of β-catenin in epididymal white adipose tissue (eWAT) in vivo. The compound 13m also increased the expression of genes involved in reverse cholesterol transport (RCT) such as PPARα and LXR1α indicating another mechanism by which compound 13m ameliorates dyslipidemia in Syrian Golden hamster model. Overall this study provides a unique perspective into the anti-adipogenic/antidyslipidemic property of triazole and indole hybrids molecules with further scope to increase the anti-adipogenic potency for therapeutic intervention of obesity and metabolic syndrome.
- Rajan, Sujith,Puri, Surendra,Kumar, Durgesh,Babu, Madala Hari,Shankar, Kripa,Varshney, Salil,Srivastava, Ankita,Gupta, Abhishek,Reddy, M. Sridhar,Gaikwad, Anil N.
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p. 1345 - 1360
(2017/11/20)
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- O-alkylhydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1
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Indoleamine 2,3-dioxygenase-1 (IDO1) is a promising therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. Recently important advances have been made in understanding IDO1's catalytic mechanism. Although much remains to be discovered, there is strong evidence that the mechanism proceeds through a heme-iron bound alkylperoxy transition or intermediate state. Accordingly, we explored stable structural mimics of the alkylperoxy species and provide evidence that such structures do mimic the alkylperoxy transition or intermediate state. We discovered that O-benzylhydroxylamine, a commercially available compound, is a potent sub-micromolar inhibitor of IDO1. Structure-activity studies of over forty derivatives of O-benzylhydroxylamine led to further improvement in inhibitor potency, particularly with the addition of halogen atoms to the meta position of the aromatic ring. The most potent derivatives and the lead, O-benzylhydroxylamine, have high ligand efficiency values, which are considered an important criterion for successful drug development. Notably, two of the most potent compounds demonstrated nanomolar-level cell-based potency and limited toxicity. The combination of the simplicity of the structures of these compounds and their excellent cellular activity makes them quite attractive for biological exploration of IDO1 function and antitumor therapeutic applications.
- Malachowski, William P.,Winters, Maria,DuHadaway, James B.,Lewis-Ballester, Ariel,Badir, Shorouk,Wai, Jenny,Rahman, Maisha,Sheikh, Eesha,LaLonde, Judith M.,Yeh, Syun-Ru,Prendergast, George C.,Muller, Alexander J.
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supporting information
p. 564 - 576
(2016/01/09)
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- The selective activation of a C-F bond with an auxiliary strong Lewis acid: a method to change the activation preference of C-F and C-H bonds
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The selective activation of the C-F bonds in substituted (2,6-difluorophenyl)phenylimines (2,6-F2H3C6-(C=NH)-n′-R-C6H4 (n′ = 2, R = H (1); n′ = 2, R = Me (2); n′ = 4, R = tBu (3))) by Fe(PMe3)4 with an auxiliary strong Lewis acid (LiBr, LiI, or ZnCl2) was explored. As a result, iron(ii) halides ((H5C6-(C=NH)-2-FH3C6)FeX(PMe3)3 (X = Br (8); Cl (9)) and (n-RH4C6-(C=NH)-2′-FH3C6)FeX(PMe3)3 (n = 2, R = Me, X = Br (11); n = 4, R = tBu, X = I (12))) were obtained. Under similar reaction conditions, using LiBF4 instead of LiBr or ZnCl2, the reaction of (2,6-difluorophenyl)phenylimine with Fe(PMe3)4 afforded an ionic complex [(2,6-F2H3C6-(C=NH)-H4C6)Fe(PMe3)4](BF4) (10) via the activation of a C-H bond. The method of C-F bond activation with an auxiliary strong Lewis acid is appropriate for monofluoroarylmethanimines. Without the Lewis acid, iron(ii) hydrides ((2-RH4C6-(C=NH)-2′-FH3C6)FeH(PMe3)3 (R = H (13); Me (14))) were generated from the reactions of Fe(PMe3)4 with the monofluoroarylmethanimines (2-FH4C6-(C=NH)-2′-RC6H4 (R = H (4); Me (5))); however, in the presence of ZnCl2 or LiBr, iron(ii) halides ((2-RH4C6-(C=NH)-H4C6)FeX(PMe3)3 (R = H, X = Cl (15); R = Me, X = Br (16))) could be obtained through the activation of a C-F bond. Furthermore, a C-F bond activation with good regioselectivity in (pentafluorophenyl)arylmethanimines (F5C6-(C=NH)-2,6-Y2C6H3 (Y = F (6); H (7))) could be realized in the presence of ZnCl2 to produce iron(ii) chlorides ((2,6-Y2H3C6-(C=NH)-F4C6)FeCl(PMe3)3 (Y = F (17); H (18))). This series of iron(ii) halides could be used to catalyze the hydrosilylation reaction of aldehydes. Due to the stability of iron(ii) halides to high temperature, the reaction mixture was allowed to be heated to 100 °C and the reaction could finish within 0.5 h.
- Wang, Lin,Sun, Hongjian,Li, Xiaoyan,Fuhr, Olaf,Fenske, Dieter
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p. 18133 - 18141
(2016/11/25)
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- Imine Nitrogen Bridged Binuclear Nickel Complexes via N-H Bond Activation: Synthesis, Characterization, Unexpected C,N-Coupling Reaction, and Their Catalytic Application in Hydrosilylation of Aldehydes
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The reactions of NiMe2(PMe3)3 with 2,6-difluoroarylimines were explored. As a result, a series of binuclear nickel complexes (5-8, 11) were synthesized. Meanwhile, from the reactions of NiMe2(PMe3)3 with [2-CH3C6H4-C(=NH)-2,6-F2C6H3] (9) and [2,6-(CH3)2C6H3-C(=NH)-2,6-F2C6H3] (10), two unexpected C,N-coupling products (12 and 13) were obtained. It is believed that these coupling reactions underwent activation of the N-H and C-F bonds. The binuclear nickel complexes showed excellent catalytic activity in the hydrosilylation of aldehydes. The mechanism of the reaction was studied through stoichiometric reactions, and the double-(η2-Si-H)-NiII intermediate was detected by in situ 1H NMR spectroscopy, which may be the key point in the catalytic cycle.
- Wang, Lin,Sun, Hongjian,Li, Xiaoyan
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p. 5175 - 5182
(2015/11/09)
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- Synthesis of iron hydrides by selective C-F/C-H bond activation in fluoroarylimines and their applications in catalytic reduction reactions
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The reactions of Fe(PMe3)4 with different 2,6-diflurophenylarylimines 1-5 were explored. Fluoroarylimines 1-3, the aryl rings of which are substituted with electron-withdrawing groups, reacted with Fe(PMe3)4 to afford the C-H activation products 6-8. However, if the aryl rings of the fluoroarylimines were substituted with electron-donating groups, the iron hydrides 9 and 10 were obtained from the reactions of the fluoroarylimines with Fe(PMe3)4 through C-F bond activation. In a further study, silanes, especially triethoxysilane, were found to benefit the reactions and improve the yields of the hydridoiron complexes. The three-component reaction of Fe(PMe3)4, a fluoroarylimine, and a silane could also be utilized in reactions involving 2,6-(CH3)2C6H3-C(=NH)-2,6-F2C6H3 (13) and 2,6-F2C6H3-C(=NH)-C6F5 (16) to synthesize iron hydrides (15 and 18). The hydridoiron complexes could be utilized as efficient catalysts in the hydrosilylation of aldehydes and ketones. Furthermore, cinnamaldehydes were selectively reduced to the corresponding cinnamyl alcohols in high yields. The mechanism of the catalytic reduction reaction was studied extensively through operando IR spectroscopy.
- Wang, Lin,Sun, Hongjian,Li, Xiaoyan
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p. 2732 - 2743
(2015/06/22)
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- 2,3-DIHYDROIMIDAZOL[1,2-C]PYRIMIDIN-5(1H)-ONE BASED LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 (LP-PLA2) INHIBITORS
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The present invention relates to novel compounds that inhibit Lp-PLA2 activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases associated with the activity of Lp-PLA2, for example atherosclerosis, Alzheimer's disease.
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Page/Page column 26
(2014/08/07)
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- COMPOUNDS
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The present invention relates to novel compounds that inhibit Lp-PLA2 activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases associated with the activity of Lp-PLA2, for example atherosclerosis, Alzheimer's disease.
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Paragraph 0167; 0168; 0169; 0221; 0222; 0223
(2014/08/07)
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- METALLOENZYME INHIBITOR COMPOUNDS
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The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.
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Page/Page column 26
(2013/02/28)
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- A simple reduction of methyl aromatic esters to alcohols using sodium borohydride-methanol system
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Several aromatic esters were reduced to the corresponding alcohol by using sodium borohydride-methanol system. The reduction was completed within 2.0-4.0h after refluxing in THF. The alcohol products were isolated after aqueous workup in good yields (88-97%).
- Boechat, Núbia,Santos Da Costa, Jorge Carlos,De Souza Mendon?a, Jorge,Mello De Oliveira, Pedro Santos,Nora De Souza, Marcus Vinícius
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p. 6021 - 6022
(2007/10/03)
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