- Compound with glucose-reducing and lipid-regulating effects as well as preparation and application thereof
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The invention discloses a compound with glucose-reducing and lipid-regulating effects as well as a preparation and application thereof. The compound with glucose-reducing and lipid-regulating effectsis a compound with structures as shown in a formula I and a formula II and a pharmaceutically acceptable salt, wherein the structures as shown in the formula I and the formula II are specifically shown in the specification. The preparation is a tablet, a capsule, powder, a pill or an injection prepared by adding pharmaceutically acceptable auxiliary materials into the compound with the glucose-reducing and lipid-regulating effects. The application is the application of the compound with the glucose-reducing and lipid-regulating effects in preparing an FFA1/PPARdelta dual agonist. The application is the application of the compound with the glucose-reducing and lipid-regulating effects in preparation of drugs for preventing and/or treating glucose metabolic disorder and/or lipid metabolic disorder diseases. The compound and the medicinal salt thereof can be potentially used for treating or preventing diabetes, hyperlipidemia, fatty liver and other related metabolic syndromes, and have wide development prospects.
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- Synthesis and preliminary evaluation of benzofuran-oxadiazole conjugates as potential antitubercular agents
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In the present study, a series of benzofuran-oxadiazole conjugates 7(a-o) was designed, synthesized and characterized through IR,1H NMR,13C NMR and mass spectral data. All the compounds were screened for preliminary antitubercular activity against Mycobacterium phlei and Mycobacterium tuberculosis H37RV. Among all the target compounds, the compound possessing chlorine (7k, MIC 1.56 μg/mL) and bromine (7m, MIC 1.56 μg/mL) on 6th position of benzofuran showed highest activity against Mycobacterium phlei. Whereas, bromine on either 5th position (7l, MIC 3.125 μg/mL) or 6th position (7m MIC 3.125 μg/mL) on benzofuran exhibited highest activity for Mycobacterium tuberculosis (H37 RV).
- Negalurmath, Veerabhadrayya S.,Kotresh, Obelannavar,Basanagouda, Mahantesha
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p. 965 - 970
(2019/03/07)
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- The Fragment-Based Development of a Benzofuran Hit as a New Class of Escherichia coli DsbA Inhibitors
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A fragment-based drug discovery approach was taken to target the thiol-disulfide oxidoreductase enzyme DsbA from Escherichia coli (EcDsbA). This enzyme is critical for the correct folding of virulence factors in many pathogenic Gram-negative bacteria, and small molecule inhibitors can potentially be developed as anti-virulence compounds. Biophysical screening of a library of fragments identified several classes of fragments with affinity to EcDsbA. One hit with high mM affinity, 2-(6-bromobenzofuran-3-yl)acetic acid (6), was chemically elaborated at several positions around the scaffold. X-ray crystal structures of the elaborated analogues showed binding in the hydrophobic binding groove adjacent to the catalytic disulfide bond of EcDsbA. Binding affinity was calculated based on NMR studies and compounds 25 and 28 were identified as the highest affinity binders with dissociation constants (KD) of 326 ± 25 and 341 ± 57 μM respectively. This work suggests the potential to develop benzofuran fragments into a novel class of EcDsbA inhibitors.
- Duncan, Luke F.,Wang, Geqing,Ilyichova, Olga V.,Scanlon, Martin J.,Heras, Bego?a,Abbott, Belinda M.
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- Biphenyl heterocyclic derivatives, their preparation and their use as medicaments (by machine translation)
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The present invention relates to a novel biphenyl heterocyclic derivative represented by a general formula (I) and a preparation method thereof and use of a pharmaceutical composition containing the derivative for preparation of a drug for treating diabetes. The biphenyl heterocyclic derivative has extremely excellent hypoglycemic activity in vivo, and excellent in vivo safety and low liver toxicity risk of the compound having such a structure are unexpectedly found, and the novel biphenyl heterocyclic derivative may be used for preventing or treating diabetes.
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- (S) - 2 - (2,3-dihydrobenzo-furan-3-yl) acetic acid derivatives, its preparation process and its use in medicine
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The invention relates to an (S)-2-(2,3-dihydrobenzofuran-3-radical) acetic acid derivative, a preparation method of the derivative, a medicine composition containing the derivative and the application of the derivative serving as a therapeutic agent, particularly GPR40/FFA1, and particularly provides the (S)-2-(2,3-dihydrobenzofuran-3-radical) acetic acid derivative shown in a general formula (I), and pharmaceutically acceptable salts of the derivative or a prodrug of the derivative. The compound is an agonist of a GPR40/FFA1 receptor and has a good preventive and therapeutic effect on lots of GPR40-mediated diseases, especially diabetes mellitus. The invention also provides a preparation method of the compound.
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Paragraph 0116-0118
(2016/10/08)
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- Novel oxime ether derivative and preparation method thereof and application of derivative by serving as drug
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The invention relates to a novel oxime ether derivative shown as a general formula (I) (please see the formula in the description) and a preparation method thereof and application of a pharmaceutical composition containing the derivative in preparation of a drug for treating diabetes and a metabolic syndrome. The oxime ether derivative has the excellent in-vivo hypoglycemic activity and can be used for preventing or treating the diabetes.
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- Aromatic polycyclic carboxylic acid derivatives
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The invention belongs to the field of medicine technology, and specifically relates to an aromatic polycyclic carboxylic acid derivative GPR40 receptor agonist with a general formula (I), a pharmaceutically acceptable salt thereof, and an ester or stereoi
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- Novel nitrogen-containing heterocyclic derivative and preparation method thereof and application of derivative by serving as drug
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The invention relates to a novel nitrogen-containing heterocyclic derivative shown as a general formula (I) (please see the formula in the description) and a preparation method thereof and application of a pharmaceutical composition containing the derivative in preparation of a drug for treating diabetes and a metabolic syndrome. The nitrogen-containing heterocyclic derivative has the excellent in-vivo hypoglycemic activity and can be used for preventing or treating the diabetes.
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- Efficient and Convenient Method for Synthesis of Benzofuran-3-acetic Acids and Naphthafuran-acetic Acids
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Herein, we report an efficient and convenient method for synthesis of benzofuran-3-acetic acids and naphthafuran-acetic acids 5a-p by the reaction of substituted-4-bromomethylcoumarins with aqueous sodium hydroxide at refluxing temperature. The obtained products are characterized by infrared, 1H NMR, 13C NMR, and mass spectral data. Structures 5a and 5e are confirmed by their single x-ray diffraction studies. The advantages of this method are good yields, easy workup, and no chromatographic purifications.
- Basanagouda, Mahantesha,Narayanachar,Majati, Iranna B.,Mulimani, Shiddappa S.,Sunnal, Satish B.,Nadiger, Rohit V.,Ghanti, Ashok S.,Gudageri, Siddeshwar F.,Naik, Ravi,Nayak, Akshata
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supporting information
p. 2195 - 2202
(2015/09/22)
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- AGONISTS OF GPR40
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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.
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- Identification of fused-ring alkanoic acids with improved pharmacokinetic profiles that Act as G protein-coupled receptor 40/free fatty acid receptor 1 agonists
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The G protein-coupled receptor 40 (GPR40)/free fatty acid receptor 1 (FFA1) has emerged as an attractive target for a novel insulin secretagogue with glucose dependency. We previously identified phenylpropanoic acid derivative 1 (3-{4-[(2′,6′-dimethylbiphenyl-3-yl)methoxy]-2-fluorophenyl} propanoic acid) as a potent and orally available GPR40/FFA1 agonist; however, 1 exhibited high clearance and low oral bioavailability, which was likely due to its susceptibility to β-oxidation at the phenylpropanoic acid moiety. To identify long-acting compounds, we attempted to block the metabolically labile sites at the phenylpropanoic acid moiety by introducing a fused-ring structure. Various fused-ring alkanoic acids with potent GPR40/FFA1 activities and good PK profiles were produced. Further optimizations of the lipophilic portion and the acidic moiety led to the discovery of dihydrobenzofuran derivative 53 ((6-{[4′-(2-ethoxyethoxy)-2′,6′-dimethylbiphenyl-3-yl]methoxy} -2,3-dihydro-1-benzofuran-3-yl)acetic acid), which acted as a GPR40/FFA1 agonist with in vivo efficacy during an oral glucose tolerance test (OGTT) in rats with impaired glucose tolerance.
- Negoro, Nobuyuki,Sasaki, Shinobu,Ito, Masahiro,Kitamura, Shuji,Tsujihata, Yoshiyuki,Ito, Ryo,Suzuki, Masami,Takeuchi, Koji,Suzuki, Nobuhiro,Miyazaki, Junichi,Santou, Takashi,Odani, Tomoyuki,Kanzaki, Naoyuki,Funami, Miyuki,Tanaka, Toshimasa,Yasuma, Tsuneo,Momose, Yu
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p. 1538 - 1552
(2012/04/10)
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- PRODUCTION METHOD OF OPTICALLY ACTIVE DIHYDROBENZOFURAN DERIVATIVE
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Provided is a production method of an optically active dihydrobenzofuran derivative. A production method of an optically active form of a compound represented by the formula: wherein each symbol is as defined in the specification, or a salt thereof and the like.
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- Bicyclic derivatives of the potent dual aromatase-steroid sulfatase inhibitor 2-bromo-4-{[(4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl} phenylsulfamate: Synthesis, SAR, crystal structure, and in vitro and in vivo activities
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The design and synthesis of a series of bicyclic ring containing dual aromatase-sulfatase inhibitors (DASIs) based on the aromatase inhibitor (AI) 4-[(4-bromobenzyl)(4H-1,2,4-triazol-4-yl)amino] benzonitrile are reported. Biological evaluation with JEG-3 cells revealed structure-activity relationships. The X-ray crystal structure of sulfamate 23 was determined, and selected compounds were docked into the aromatase and steroid sulfatase (STS) crystal structures. In the sulfamate-containing series, compounds containing a naphthalene ring are both the most potent AI (39, IC50AROM=0.25 nm) and the best STS inhibitor (31, IC50STS=26 nm). The most promising DASI is 39 (IC50AROM= 0.25 nm, IC50STS=205 nm), and this was evaluated orally in vivo at 10 mgkg-1, showing potent inhibition of aromatase (93%) and STS (93%) after 3 h. Potent aromatase and STS inhibition can thus be achieved with a DASI containing a bicyclic ring system; development of such a DASI could provide an attractive new option for the treatment of hormone-dependent breast cancer.
- Wood, Paul M.,Woo, L. W. Lawrence,Labrosse, Jean-Robert,Thomas, Mark P.,Mahon, Mary F.,Chander, Surinder K.,Purohit, Atul,Reed, Michael J.,Potter, Barry V. L.
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scheme or table
p. 1577 - 1593
(2011/12/01)
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- FUSED CYCLIC COMPOUNDS
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The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the description, or a salt thereof. The compound or a salt thereof or a prodrug thereof has a GPR40 receptor function modulating action and is useful as an insulin secretagogue or an agent for the prophylaxis or treatment of diabetes and the like.
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Page/Page column 87
(2008/06/13)
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- Synthesis and SAR of selective benzothiophene, benzofuran, and indole-based peroxisome proliferator-activated receptor δ agonists
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Recent literature has suggested the benefit of selective PPARδ agonists for the treatment of atherosclerosis and other disease states associated with the metabolic syndrome. Herein we report the synthesis and structure-activity relationships of a series of novel and selective PPARδ agonists. Our search began with identification of a novel benzothiophene template which was modified by the addition of various thiazolyl, isoxazolyl, and benzyloxy-benzyl moieties. Further elucidation of the SAR led to the identification of benzofuran and indole based templates. During the course of our research, we discovered three new chemical templates with varying degrees of affinity and potency for PPARδ versus the PPARα and PPARγ subtypes.
- Filzen, Gary F.,Bratton, Larry,Cheng, Xue-Min,Erasga, Noe,Geyer, Andrew,Lee, Chitase,Lu, Gina,Pulaski, Jim,Sorenson, Roderick J.,Unangst, Paul C.,Trivedi,Xu, Xiangyang
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p. 3630 - 3635
(2008/02/08)
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- A CONVENIENT SYNTHESIS OF BENZOFURAN-3-ACETIC ACIDS
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We describe a two-step synthesis of benzofuran-3-acetic acids (1) from phenols (2) involving alkali-mediated rearrangement of 4-halomethylcoumarins (3) via α,β-unsaturated acids (4).Electron-donating substituents at the meta position of the phenol favour high yields of the coumarin, which in all cases rearranges to afford benzofuran-3-acetic acids in near quantitative yields.
- Fall, Yagamare,Santana, Lourdes,Teijeira, Marta,Uriarte, Eugenio
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p. 647 - 650
(2007/10/02)
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