- Lipid reducing activity of novel cholic acid (CA) analogs: Design, synthesis and preliminary mechanism study
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Bile acids, initially discovered as endogenous ligands of farnesoid X receptor (FXR), play a central role in the regulation of triglyceride and cholesterol metabolism and have recently emerged as a privileged structure for interacting with nuclear receptors relevant to a large array of metabolic processes. In this paper, phenoxy containing cholic acid derivatives with excellent drug-likeness have been designed, synthesized, and assayed as agents against cholesterol accumulation in Raw264.7 macrophages. The most active compound 14b reduced total cholesterol accumulation in Raw264.7 cells up to 30.5% at non-toxic 10 μM and dosage-dependently attenuated oxLDL-induced foam cell formation. Western blotting and qPCR results demonstrate that 14b reduced both cholesterol and lipid in Raw264.7 cells through (1) increasing the expression of cholesterol transporters ABCA1 and ABCG1, (2) accelerating ApoA1-mediated cholesterol efflux. Through a cell-based luciferase reporter assay and molecular docking analysis, LXR was identified as the potential target for 14b. Interestingly, unlike conventional LXR agonist, 14b did not increase lipogenesis gene SREBP-1c expression. Overall, these diverse properties disclosed herein highlight the potential of 14b as a promising lead for further development of multifunctional agents in the therapy of cardiovascular disease.
- Luo, Guoshun,Qian, Zhouyang,Qiu, Rongmao,You, Qidong,Xiang, Hua
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Read Online
- Ring-Opening Metathesis Polymerization of a Macrobicyclic Olefin Bearing a Sacrificial Silyloxide Bridge
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Ring-opening metathesis polymerization (ROMP) has been regarded as a powerful tool for sequence-controlled polymerization. However, the traditional entropy-driven ROMP of macrocyclic olefins suffers from the lack of ring strain and poor regioselectivity,
- Chen, Xu-Man,Huang, Shuai,Wang, Meng,Yang, Hong,Yu, Zhen
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supporting information
(2021/11/27)
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- NOVEL COMPOUND, PREPARATION METHOD THEREOF, AND USE THEREOF
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The present invention relates to a method for preparing a biomaterial having selectively functionalized tyrosine, a biomaterial having selectively functionalized tyrosine, and a pharmaceutical composition containing the same as an active ingredient. The method for preparing a biomaterial to which a compound represented by formula 2 is coupled, of the present invention, allows the compound represented by formula 2 to be selectively coupled, in a high yield in a biomaterial, to tyrosine, which is present on the surface of an aqueous solution such that the coupling thereof to amino acids other than tyrosine does not occur and, when only one tyrosine is present, heterogeneous mixtures are not present and the inherent activity of the biomaterial is maintained, and thus the compound can be effectively used as a pharmaceutical composition containing a biomaterial drug as an active ingredient. In addition, the method can selectively functionalize tyrosine, and thus can be effectively used for tyrosine functionalization in a biomaterial.
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Paragraph 852-856
(2021/07/24)
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- Double-target inhibitor targeting FGFR (fibroblast growth factor receptor) and HDAC (histone deacetylase) as well as preparation method and application thereof, pharmaceutical composition and medicament
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The invention discloses a double-target inhibitor targeting FGFR (fibroblast growth factor receptor) and HDAC (histone deacetylase) as well as a preparation method and application thereof, a pharmaceutical composition and a medicament, and belongs to the
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Paragraph 0429-0431; 0446-0448
(2021/06/09)
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- Piperazine benzamide derivative and application thereof
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The invention belongs to the field of medical chemistry, and particularly relates to a compound shown as a formula (I) and pharmaceutically acceptable salt thereof, which are applied to prevention andtreatment of depression.
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Paragraph 0042-0045
(2020/07/24)
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- Morpholine benzamide compound and application thereof
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The invention belongs to the field of medical treatment, and particularly relates to a morpholine benzamide compound and application thereof, the morpholine benzamide compound has a compound structureshown as a formula (A), and the compound can be applied
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Paragraph 0063-0065
(2020/07/24)
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- Self-assembly of nanoparticles by human serum albumin and photosensitizer for targeted near-infrared emission fluorescence imaging and effective phototherapy of cancer
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Photodynamic therapy (PDT) and photothermal therapy (PTT) are effective cancer treatments, and photosensitizers play the most important role in the treatment. However, photosensitizers are insufficient for in vivo tumor treatment. Herein, we develop a small molecule fluorophore Cy-HPT as a novel photosensitizer, which possesses the advantages of near-infrared (NIR) emission, high photothermal conversion efficiency and high singlet oxygen generation efficiency. Moreover, a nanoplatform of HSA@Cy-HPT was synthesized by self-assembly of Cy-HPT and human serum albumin (HSA) in aqueous solution. Compared to Cy-HPT, HSA@Cy-HPT possesses more stable spectral properties, enhances the effect of PDT/PTT, and exhibits more satisfactory in vivo metabolism. HSA@Cy-HPT demonstrates outstanding tumor targeting in subcutaneous tumor xenograft models owing to its enhanced permeability and retention in tumor tissue. Furthermore, HSA@Cy-HPT was successfully utilized in tumor xenograft models and tumor tissue growth was clearly inhibited without any regrowth, extending survival rate of the models. Also, no distinct damage of the normal tissue of tumor xenograft models was observed using hematoxylin & eosin staining. This study presents a promising therapeutic agent for the synergetic PDT and PTT cancer treatment.
- Huang, Yan,He, Na,Wang, Yunqing,Shen, Dazhong,Kang, Qi,Zhao, Rongfang,Chen, Lingxin
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supporting information
p. 1149 - 1159
(2019/02/20)
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- Transition-Metal-Free Borylation of Alkyl Iodides via a Radical Mechanism
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We describe an operationally simple transition-metal-free borylation of alkyl iodides. This method uses commercially available diboron reagents as the boron source and exhibits excellent functional group compatibility. Furthermore, a diverse range of prim
- Liu, Qianyi,Hong, Junting,Sun, Beiqi,Bai, Guangcan,Li, Feng,Liu, Guoquan,Yang, Yang,Mo, Fanyang
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supporting information
(2019/07/08)
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- Cytotoxic Activity and Structure–Activity Relationship of Triazole-Containing Bis(Aryl Ether) Macrocycles
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Cancer continues to be a worldwide health problem. Certain macrocyclic molecules have become attractive therapeutic alternatives for this disease because of their efficacy and, frequently, their novel mechanisms of action. Herein, we report the synthesis of a series of 20-, 21-, and 22-membered macrocycles containing triazole and bis(aryl ether) moieties. The compounds were prepared by a multicomponent approach from readily available commercial substrates. Notably, some of the compounds displayed interesting cytotoxicity against cancer (PC-3) and breast (MCF-7) cell lines, especially those bearing an aliphatic or a trifluoromethyl substituent on the N-phenyl moiety (IC501H-3,10-dioxa-6-aza-1(4,1)-triazola-4(1,3),9(1,4)-dibenzenacyclotridecaphane-5-carboxamide (12 f) was the most potent in this regard (22.7 % of apoptosis).
- Hernández-Vázquez, Eduardo,Chávez-Riveros, Alejandra,Romo-Pérez, Adriana,Ramírez-Apán, María Teresa,Chávez-Blanco, Alma D.,Morales-Bárcenas, Rocío,Due?as-González, Alfonso,Miranda, Luis D.
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p. 1193 - 1209
(2018/06/26)
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- Cholic acid derivatives and their preparation method and medical application
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The invention relates to the field of pharmaceutical chemistry and relates to cholic acid derivatives and their preparation method and medical application and particularly relates to cholic acid derivatives having the general formula (I), their preparation method, a pharmaceutical composition containing the compounds, medical application of the cholic acid derivatives, and medical application of the cholic acid derivatives as drugs for preventing or treating hyperlipidemia, obesity or type II diabetes.
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Paragraph 0098; 0099; 0100
(2017/07/21)
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- A nitric oxide donor nature of the benzofuran compounds (by machine translation)
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The invention discloses a benzofuran compound with nitrous oxide donor property. The benzofuran compound is a compound shown by a general formula (I) or a pharmaceutically acceptable salt thereof, wherein in the formula, R1 or R2 represents independent hy
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Paragraph 0097-0098
(2017/04/20)
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- Novel Pyrazolo[1,5-a]pyrimidines as Translocator Protein 18 kDa (TSPO) Ligands: Synthesis, in Vitro Biological Evaluation, [18F]-Labeling, and in Vivo Neuroinflammation PET Images
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A series of novel pyrazolo[1,5-a]pyrimidines, closely related to N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide (2, DPA-714), were synthesized and biologically in vitro evaluated for their potential to bind
- Damont, Annelaure,Médran-Navarrete, Vincent,Cacheux, Fanny,Kuhnast, Bertrand,Pottier, Géraldine,Bernards, Nicholas,Marguet, Frank,Puech, Frédéric,Boisgard, Rapha?l,Dollé, Frédéric
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p. 7449 - 7464
(2015/10/05)
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- PHENOXY-AZETIDINE DERIVATIVES AS SPHINGOSINE 1-PHOSPHATE (S1P) RECEPTOR MODULATORS
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The present invention relates to phenoxy-azetidine derivatives of Formula I, processes for preparing them, pharmaceutical compositions containing them, and their use as pharmaceuticals as modulators of sphingosine-1-phosphate receptors.
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Page/Page column 14; 15-16
(2015/06/18)
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- PHENOXY DERIVATIVES AS SPHINGOSINE 1-PHOSPHATE (S1P) RECEPTOR MODULATORS
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The present invention relates to phenoxy derivatives, processes for preparing them, pharmaceutical compositions containing them, and their use as pharmaceuticals as modulators of sphingosine-1-phosphate receptors.
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Page/Page column 14; 15-16
(2015/06/18)
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- Domino synthesis of 2-arylbenzo[b]furans by copper(II)-catalyzed coupling of o-iodophenols and aryl acetylenes
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A wide range of 2-arylbenzo[b]furans are synthesized through domino intermolecular C(aryl)-C(alkynyl) bond formation followed by intramolecular C(alkynyl)-O bond forming cyclization via copper(II)-catalyzed coupling of o-iodophenols and aryl terminal acetylenes. This method requires neither expensive palladium catalyst nor oxophilic phosphine ligands, can tolerate different functional groups. The methodology is successfully utilized in formal synthesis of β-amyloid aggregation inhibitor 5-chloro-3-[4-(3-diethylaminopropoxy)benzoyl]-2-(4-methoxyphenyl) benzofuran.
- Jaseer,Prasad,Sekar, Govindasamy
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experimental part
p. 2077 - 2082
(2010/04/29)
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- PYRROLOTRIAZINE KINASE INHIBITORS
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The present invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase activity of Trk receptors such as TrkA, TrkB, TrkC or Flt-3 thereby making them useful as antiproliferative agents.
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Page/Page column 39
(2008/06/13)
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- PYRROLIDINE DERIVATIVES AS HISTAMINE H3 RECEPTOR ANTAGONISTS
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The present invention discloses novel compounds of Formula (I) or pharmaceutically acceptable salts thereof which have histamine-H3 receptor antagonist or inverse agonist activity, as well as methods and intermediates for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula (I) as well as methods of using them to treat obesity, cognitive deficiencies, narcolepsy, and other histamine H3 receptor-related diseases.
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Page/Page column 31-32
(2008/06/13)
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- Synthesis and Pharmacological Evaluation of 1-Oxo-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinolines and Related Analogues as a New Class of Specific Bradycardic Agents Possessing If Channel Inhibitory Activity
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A series of 1-oxo-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinolines and related analogues were prepared and evaluated for their bradycardic activities in isolated right atrium and in anesthetized rats. (± )-6,7-Dimethoxy-2-{1- [3-(3,4-methylenedioxyphenoxy)propyl]-3-piperidyl}-1,2,3, 4-tetrahydroisoquinoline (4) was chosen as a lead, and structural modifications were performed on the tetrahydroisoquinoline ring and the terminal aromatic ring. The modifications on the tetrahydroisoquinoline ring revealed that the 1-oxo-1,2,3,4-tetrahydroisoquinoline ring system was optimum structure for both in vitro potency and in vivo efficacy. Furthermore, methoxy, ethoxy, and methoxycarbonyl groups were identified as preferable substituents on the terminal aromatic ring. One of the 1-oxo-1,2,3,4-tetrahydroisoquinoline derivatives, (R)-10a, was further evaluated for its bradycardic activity and inhibitory activity against If currents. Compound (R)-10a demonstrated potent bradycardic activity in rats with minimal influence on blood pressure after oral administration. The compound also showed inhibition of If currents (IC50 = 0.32 μM) in guinea pig pacemaker cells.
- Kubota, Hideki,Kakefuda, Akio,Watanabe, Toshihiro,Ishii, Noe,Wada, Koichi,Masuda, Noriyuki,Sakamoto, Shuichi,Tsukamoto, Shin-ichi
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p. 4728 - 4740
(2007/10/03)
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- Radical isomerization via intramolecular ipso substitution of aryl ethers: Aryl translocation from oxygen to carbon
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Bromopropyl aryl ethers an converted to 3-arylpropanols under standard radical generating conditions in the presence of tributylstannane and AIBN. This rearrangement involves intramolecular ipso attack of the alkyl radicals which generates spiro cyclohexadienyl radical intermediates.
- Lee, Eun,Lee, Chulbom,Tae, Jin Sung,Whang, Ho Sung,Li, Kap Sok
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p. 2343 - 2346
(2007/10/02)
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