17138-28-2Relevant articles and documents
Seven-membered fused ring compound and organic photovoltaic cell
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Paragraph 0043-0051, (2021/03/23)
The invention discloses a seven-membered fused ring compound shown as a formula (I) and an organic photovoltaic cell containing the seven-membered fused ring compound. When the seven-membered fused ring compound is used as a non-fullerene organic electron acceptor material, a relatively environment-friendly chlorine-free solvent can be used for coating in the manufacturing process of an organic photovoltaic cell, and meanwhile, the high energy conversion efficiency (PCE) of the organic photovoltaic cell can be maintained;.
Aryl phenol compound as well as synthesis method and application thereof
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Paragraph 0104-0107, (2021/05/12)
The invention discloses a synthesis method of an aryl phenol compound shown as a formula (3). All systems are carried out in an air or nitrogen atmosphere, and visible light is utilized to excite a photosensitizer for catalyzation. In a reaction solvent, ArNR1R2 as shown in a formula (1) and water as shown in a formula (2) are used as reaction raw materials and react under the auxiliary action of acid to obtain the aryl phenol compound as shown in a formula (3). The ArNR1R2 in the formula (1) can be primary amine and tertiary amine, can also be steroid and amino acid derivatives, and can also be drugs or derivatives of propofol, paracetamol, ibuprofen, oxaprozin, indomethacin and the like. The synthesis method has the advantages of cheap and easily available raw materials, simple reaction operation, mild reaction conditions, high reaction yield and good compatibility of substrate functional groups. The fluid reaction not only can realize amplification of basic chemicals, but also can realize amplification of fine chemicals, such as synthesis of drugs propofol and paracetamol. The invention has wide application prospect and use value.
L-Thyroxin and the Nonclassical Thyroid Hormone TETRAC Are Potent Activators of PPAR?
Gellrich, Leonie,Heitel, Pascal,Heering, Jan,Kilu, Whitney,Pollinger, Julius,Goebel, Tamara,Kahnt, Astrid,Arifi, Silvia,Pogoda, Werner,Paulke, Alexander,Steinhilber, Dieter,Proschak, Ewgenij,Wurglics, Mario,Schubert-Zsilavecz, Manfred,Chaikuad, Apirat,Knapp, Stefan,Bischoff, Iris,Fürst, Robert,Merk, Daniel
, p. 6727 - 6740 (2020/09/11)
Thyroid hormones (THs) operate numerous physiological processes through modulation of the nuclear thyroid hormone receptors and several other proteins. We report direct activation of the nuclear peroxisome proliferator-activated receptor gamma (PPAR?) and retinoid X receptor (RXR) by classical and nonclassical THs as another molecular activity of THs. The T4 metabolite TETRAC was the most active TH on PPARγwith nanomolar potency and binding affinity. We demonstrate that TETRAC promotes PPAR?/RXR signaling in cell-free, cellular, and in vivo settings. Simultaneous activation of the heterodimer partners PPARγand RXR resulted in high dimer activation efficacy. Compared to fatty acids as known natural ligands of PPARγand RXR, TETRAC differs markedly in its molecular structure and the PPAR?-TETRAC complex revealed a distinctive binding mode of the TH. Our observations suggest a potential connection of TH and PPAR signaling through overlapping ligand recognition and may hold implications for TH and PPAR pharmacology.
Method for continuously preparing pimavanserin by using micro-channel reactor
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Paragraph 0037-0038, (2020/11/09)
The invention discloses a method for continuously preparing pimavanserin by using a micro-channel reactor. The method comprises the following steps: dissolving a reaction substrate in an organic solvent, pumping the material solution into a micro-channel reactor by using a feeding pump, sufficiently mixing, and carrying out continuous Curtius rearrangement and addition reaction to obtain the pimavanserin. According to the invention, the micro-channel reactor is adopted for reaction, so that the mixing uniformity is good, the reaction time is shortened, and the operation is simple and safe; andthe environmental pollution is obviously reduced.
Design and Structural Optimization of Dual FXR/PPARδActivators
Schierle, Simone,Neumann, Sebastian,Heitel, Pascal,Willems, Sabine,Kaiser, Astrid,Pollinger, Julius,Merk, Daniel
supporting information, p. 8369 - 8379 (2020/08/12)
Nonalcoholic steatohepatitis (NASH) is considered as severe hepatic manifestation of the metabolic syndrome and has alarming global prevalence. The ligand-activated transcription factors farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR) δhave been validated as molecular targets to counter NASH. To achieve robust therapeutic efficacy in this multifactorial pathology, combined peripheral PPAR?-mediated activity and hepatic effects of FXR activation appear as a promising multitarget approach. We have designed a minimal dual FXR/PPARδactivator scaffold by rational fusion of pharmacophores derived from selective agonists. Our dual agonist lead compound exhibited weak agonism on FXR and PPARδand was structurally refined to a potent and balanced FXR/PPARδactivator in a computer-aided fashion. The resulting dual FXR/PPARδmodulator comprises high selectivity over related nuclear receptors and activates the two target transcription factors in native cellular settings.
Design potential selective inhibitors for human leukocyte common antigen-related (PTP-LAR) with fragment replace approach
Li, Hong-Lian,Li, Wei-Ya,Lu, Xin-Hua,Ma, Ying,Tang, Xue,Wang, Run-Ling,Wu, Jing-Wei,Zhang, Huan,Zheng, Zhi-Hui
, p. 5338 - 5348 (2019/12/24)
The overexpression of PTP-LAR could cause the insulin resistance, so PTP-LAR might be a promising target for treating diabetes. In this study, we applied the computer modeling methods with fragment replace approach to screen the fragment database by targeting PTP domain and site B with the aim to discover potent and selective PTP-LAR inhibitors. A series of novel 4-thiazolidone derivatives were gained. The results of their ADMET predictions indicated that these new compounds might become drug candidates. The series of these derivatives were synthesized. Subsequently, their PTP-LAR inhibitory activities were assayed. The compound7d showed highly selectivity for PTP-LAR (10.41 μM) over its close homolog PTP1B (IC50=44.40 μM), SHP2 (IC50>122.81 μM) and CDC25B (IC50>122.81 μM) and docking and molecular dynamics simulation were applied to propose the most likely binding mode of compound7d with PTP-LAR. Thus, our findings reported here may pave a way for discovering potential selective PTP-LAR inhibitors. AbbreviationsPTP-LAR Human leukocyte common antigen-relatedPTP Protein Tyrosine PhosphataseIR insulin receptorPTP1B Protein tyrosine phosphatase-1BLRP Lung resistance proteinADMET absorption, distribution, metabolism, excretion, toxicityPPB plasma protein bindingBBB blood brain barrier penetrationCYP450 cytochrome P450HIA human intestinal absorptionTLC thin-layer chromatographyUV Ultra VioletNMR nuclear magnetic resonanceTMS tetramethylsilaneMS mass spectrometryANM anisotropic network modePDB Protein Data BankDMF N,N-DimethylformamidepNPP para-nitrophenyl phosphateDTT dithiothreitolMD molecular dynamicRMSD root-mean-square deviationRMSF root-mean-square fluctuationSPC single-point chargePME Particle Mesh EwaldMM-PBSA molecular mechanics Poisson Boltzmann surface areaH bond, hydrogen bondVDW Van der Waals Communicated by Ramaswamy H. Sarma.
Structure activity relationship of 4-Amino-2-thiopyrimidine derivatives as platelet aggregation inhibitors
Bossi, Elena,Cacciari, Barbara,Cattaneo, Marco,Cheng, Chun Yan,Crepaldi, Pamela,Federico, Stephanie,Jacobson, Kenneth A.,Spalluto, Giampiero
, p. 863 - 872 (2020/01/28)
Background: Platelet aggregation plays a pathogenic role in the development of arterial thrombi, which are responsible for common diseases caused by thrombotic arterial occlusion, such as myocardial infarction and stroke. Much efforts are directed toward developing platelet aggregation inhibitors that act through several mechanisms: The main antiplatelet family of COXinhibitors, phosphodiesterase inhibitors, and thrombin inhibitors. Recently, the important role in the platelet aggregation of adenosine diphosphate (ADP)-activated P2Y12 and P2Y1 receptors, Gprotein coupled receptors of the P2 purinergic family, has emerged, and their inhibitors are explored as potential therapeutic antithrombotics. P2Y12 inhibitors, i.e. clopidogrel, prasugrel, ticagrelor, and cangrelor, are already used clinically to reduce coronary artery thrombosis risk and prevent acute coronary syndromes. The search for new P2Y12 inhibitors, with better risk-to-benefit profiles is still ongoing. Methods: Several years ago, our group prepared a series of 6-amino-2-thio-3H-pyrimidin-4-one derivatives that displayed an interesting platelet aggregation inhibiting activity. In order to probe the structure-activity relationships and improve their inhibitory effects of these compounds, we synthesized variously substituted 6-amino-2-thio-3H-pyrimidin-4-one derivatives and substituted 4-amino-2-thiopyrimidine-5-carboxylic acid analogues. All the synthesized compounds were tested by light trasmission aggregometry (LTA) as inducers or inhibitors of platelet aggregation in citrated platelet-rich plasma (PRP). Results: Among the 6-amino-2-thio-3H-pyrimidin-4-one derivatives, compounds 2c and 2h displayed marked inhibitory activity, with a capability to inhibit the ADP(10-6M)-induced platelet aggregation by 91% and 87% at 10-4M concentration, respectively. Selected 4-amino-2- thiopyrimidine-5-carboxylic acid derivatives were tested as P2Y12 and P2Y1 antagonists and found to display negligible activity. Conclusion: These negative findings demonstrated that this heterocyclic nucleus is not a useful common pharmacophore for developing P2Y-dependent inhibitors of platelet aggregation. Nevertheless, compounds 2c and 2h could represent a new chemotype to further develop inhibitors of platelet aggregation.
Carbene Transfer and Carbene Insertion Reactions Catalyzed by a Mixed-Ligand Copper(I) Complex
Brenna, Stefano,Ardizzoia, G. Attilio
, p. 3336 - 3342 (2018/07/13)
The catalytic activity of the mixed-ligand copper(I) complex [Cu(PPh3)2(κ2-O,O"-lact)] (1) {lact = l-(+)-lactate} has been investigated in carbene transfer and carbene insertion reactions. Complex 1 catalytically promoted the diastereoselective cyclopropanation of olefins in the presence of ethyl diazoacetate (EDA), under mild conditions, and with a low catalyst loading (1 mol-%). In the case of internal alkenes, a trans/cis ratio of up to 93:7 was reached. Moreover, compound 1 easily promoted the insertion of the carbene fragment deriving from the decomposition of ethyl diazoacetate into O–H (alcohols and phenols) and N–H (amine) bonds, with formation of the corresponding ethyl 2-alkoxyacetate, ethyl 2-phenoxyacetate, and ethyl 2-aminoacetate derivatives in good to high yields.
Facile synthesis of 2-aryl or β,γ-unsaturated esters via 1,2-Migration from aryl or α,β-unsaturated ketones using thallium(III) p-tosylate
Lee, Jae In
, p. 125 - 128 (2017/06/07)
The experiment reports that 2-aryl esters can be efficiently synthesized via 1,2-aryl migration from aryl ketones using thallium(III) p-tosylate in high yields. To determine optimum conditions for conversion of aryl ketones to 2-aryl esters, the effects of solvents were examined. An initial reaction of 4'-methoxypropiophenone and perchloric acid using thallium(III) p-tosylate in ethanol afforded ethyl 2-(4-methoxyphenyl)propanoate in only 10% yield after 24 h at room temperature. However, the corresponding reaction in ethanol/triethyl orthoformate (4/1) was completed in 1 h between 0 °C and room temperature to give ethyl 2-(4-methoxyphenyl)propanoate in 94% yield. The presence of triethyl orthoformate induced rapid ketalization of enol intermediate and facilitated 1,2-migration of the 4-methoxyphenyl group. The relative effectiveness of several metal salts was also examined for conversion of 2',4'-dimethoxypropiophenone to ethyl 2-(2,4-dimethoxyphenyl)propanoate. The solvents were evaporated off under reduced pressure, and the residue was dissolved in methylene chloride. The white precipitate was filtered off, and the resulting yellow solution was poured into saturated NaHCO3 solution and extracted with methylene chloride. The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified by vacuum distillation using a Kugelrohr apparatus to give 4g as a colorless liquid.
Modular Synthesis of Arylacetic Acid Esters, Thioesters, and Amides from Aryl Ethers via Rh(II)-Catalyzed Diazo Arylation
Best, Daniel,Jean, Micka?l,Van De Weghe, Pierre
, p. 7760 - 7770 (2016/09/12)
One-pot formation of arylacetic acid esters, thioesters, and amides via Rh(II)-catalyzed arylation of a Meldrum's acid-derived diazo reagent with electron-rich arenes is described. The methodology was used to efficiently synthesize an anticancer compound.
