- TETRAZOLE DERIVATIVES AS TRPA1 INHIBITORS
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The present disclosure provides certain tetrazole derivatives that are inhibitors of transient receptor potential ankyrin 1 (TRPA1), and are therefore useful for the treatment of diseases treatable by inhibition of TRPA1. Also provided are pharmaceutical compositions containing the same, and processes for preparing said compounds.
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Paragraph 0302-0306
(2022/01/12)
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- Novel oxindole/benzofuran hybrids as potential dual CDK2/GSK-3β inhibitors targeting breast cancer: design, synthesis, biological evaluation, and in silico studies
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The serine/threonine protein kinases CDK2 and GSK-3β are key oncotargets in breast cancer cell lines, therefore, in the present study three series of oxindole-benzofuran hybrids were designed and synthesised as dual CDK2/GSK-3β inhibitors targeting breast cancer (5a–g, 7a–h, and 13a–b). The N1 -unsubstituted oxindole derivatives, series 5, showed moderate to potent activity on both MCF-7 and T-47D breast cancer cell lines. Compounds 5d–f showed the most potent cytotoxic activity with IC50 of 3.41, 3.45 and 2.27 μM, respectively, on MCF-7 and of 3.82, 4.53 and 7.80 μM, respectively, on T-47D cell lines, in comparison to the used reference standard (staurosporine) IC50 of 4.81 and 4.34 μM, respectively. On the other hand, the N1 -substituted oxindole derivatives, series 7 and 13, showed moderate to weak cytotoxic activity on both breast cancer cell lines. CDK2 and GSK-3β enzyme inhibition assay of series 5 revealed that compounds 5d and 5f are showing potent dual CDK2/GSK-3β inhibitory activity with IC50 of 37.77 and 52.75 nM, respectively, on CDK2 and 32.09 and 40.13 nM, respectively, on GSK-3β. The most potent compounds 5d–f caused cell cycle arrest in the G2/M phase in MCF-7 cells inducing cell apoptosis because of the CDK2/GSK-3β inhibition. Molecular docking studies showed that the newly synthesised N1 -unsubstituted oxindole hybrids have comparable binding patterns in both CDK2 and GSK-3β. The oxindole ring is accommodated in the hinge region interacting through hydrogen bonding with the backbone CO and NH of the key amino acids Glu81 and Leu83, respectively, in CDK2 and Asp133 and Val135, respectively, in GSK-3β. Whereas, in series 7 and 13, the N1 -substitutions on the oxindole nucleus hinder the compounds from achieving these key interactions with hinge region amino acids what rationalises their moderate to low anti-proliferative activity.
- Eldehna, Wagdy M.,Al-Rashood, Sara T.,Al-Warhi, Tarfah,Eskandrani, Razan O.,Alharbi, Amal,El Kerdawy, Ahmed M.
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p. 270 - 285
(2020/12/18)
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- Development of novel benzofuran-based SLC-0111 analogs as selective cancer-associated carbonic anhydrase isoform IX inhibitors
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In the present study, we describe the design of different series of benzofuran-based derivatives as potential carbonic anhydrase inhibitors (CAIs). The adopted design is based on bioisosteric replacement for the p-fluorophenyl SLC-0111 tail with the lipop
- Shaldam, Moataz,Eldehna, Wagdy M.,Nocentini, Alessio,Elsayed, Zainab M.,Ibrahim, Tamer M.,Salem, Rofaida,El-Domany, Ramadan A.,Capasso, Clemente,Abdel-Aziz, Hatem A.,Supuran, Claudiu T.
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- HDAC inhibitor and preparation method and application thereof
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The present invention discloses a compound represented by a formula I, a stereoisomer thereof, and a pharmaceutically acceptable salt thereof. The invention further relates to a pharmaceutical composition containing the compound shown in the formula I and application of the compound in preparation of HDAC inhibitor drugs. The compound or the pharmaceutical composition thereof can be used for treating cell proliferation diseases, autoimmune diseases, inflammation, neurodegenerative diseases or viral diseases.
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Paragraph 0197-0204
(2020/11/12)
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- Benzofuran-Based Carboxylic Acids as Carbonic Anhydrase Inhibitors and Antiproliferative Agents against Breast Cancer
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Pursuing our effort for developing effective inhibitors of the cancer-related hCA IX isoform, here we describe the synthesis of novel benzofuran-based carboxylic acid derivatives, featuring the benzoic (9a-f) or hippuric (11a,b) acid moieties linked to 2-
- Abdel-Aziz, Hatem A.,Al-Sanea, Mohammad M.,Al-Warhi, Tarfah,Aljaeed, Nada,Alotaibi, Ohoud J.,Eldehna, Wagdy M.,Elsayed, Zainab M.,Nocentini, Alessio,Supuran, Claudiu T.
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p. 1022 - 1027
(2020/06/27)
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- Synthesis and biological evaluation of novel shikonin-benzo[b]furan derivatives as tubulin polymerization inhibitors targeting the colchicine binding site
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A novel series of shikonin-benzo[b]furan derivatives were designed and synthesized as tubulin polymerization inhibitors, and their biological activities were evaluated. Most compounds revealed the comparable anti-proliferation activities against the cancer cell lines to that of shikonin and simultaneously low cytotoxicity to non-cancer cells. Among them, compound 6c displayed powerful anti-cancer activity with the IC50 value of 0.18 μM against HT29 cells, which was significantly better than that of the reference drugs shikonin and CA-4. What's more, 6c could inhibit tubulin polymerization and compete with [3H] colchicine in binding to tubulin. Further biological studies depicted that 6c can induce cell apoptosis and cell mitochondria depolarize, regulate the expression of apoptosis related proteins in HT29 cells. Besides, 6c actuated the HT29 cell cycle arrest at G2/M phase, and influenced the expression of the cell-cycle related protein. Moreover, 6c displayed potent inhibition on cell migration and tube formation that contributes to the antiangiogenesis. These results prompt us to consider 6c as a potential tubulin polymerization inhibitor and is worthy for further study.
- Kong, Ling-Yi,Leng, Jia-Fu,Lian, Bao-Ping,Shao, Yu-Ying,Xia, Yuan-Zheng,Yin, Yong
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- Tandem Synthesis of 2-Carboxybenzofurans via Sequential Cu-Catalyzed C-O Coupling and Mo(CO)6-Mediated Carbonylation Reactions
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A modular tandem synthesis of 2-carboxybenzofurans from 2-gem-dibromovinylphenols has been established based on a sequence of Cu-catalyzed intramolecular C-O coupling and Mo(CO)6-mediated intermolecular carbonylation reactions. This protocol allowed one-step access to a broad variety of functionalized benzofuran-2-carboxylic acids, esters, and amides in good to excellent yields under Pd- and CO gas-free conditions.
- Mo, Qinliang,Sun, Nan,Jin, Liqun,Hu, Baoxiang,Shen, Zhenlu,Hu, Xinquan
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p. 11490 - 11500
(2020/10/12)
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- Preparation method of 5-halo-benzofuran-2-formic ether compound
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The invention relates to a preparation method of a 5-halo-benzofuran-2-formic ether compound. The method specifically comprises the following steps that a compound of a formula I shown in the description and dibromoacetylene are subjected to a reaction in an organic solvent under the function of an alkaline reagent to generate a compound of a formula II, wherein R is selected from an optionally-substituted alkyl group, and X is halogen.
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Paragraph 0011-0013
(2018/10/19)
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- Cathepsin K inhibitor and application thereof
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The invention relates to a cathepsin K inhibitor and an application thereof, in particular to compounds (as shown in formula (I) in the specification) for treating or preventing cathepsin-dependent diseases. The compounds comprise but not limited to the cathepsin K inhibitor. The compounds and pharmaceutical composition of the compounds can be used as a bone resorption inhibitor in the treatment of related diseases.
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Paragraph 0216; 0217; 0218
(2017/08/28)
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- Imidazole-containing condensed tricyclic compound and application thereof
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The invention discloses an imidazole-containing condensed tricyclic compound adopting the structure as shown in the formula (I) or pharmaceutically acceptable salts, stereisomers or prodrug molecules thereof. The imidazole-containing condensed tricyclic compound has the IDO1 activity regulation function, can enhance T-cell activation through blocking immune checkpoints IDO1, is used for treating IDO1-mediated immunosuppression, and therefore, can become an effective medicine for treating malignant tumors. When used together with checkpoint protein anti-body drugs or other anti-cancer drugs, the imidazole-containing condensed tricyclic compound can enhance the anti-cancer effect. Meanwhile, the imidazole-containing condensed tricyclic compound has the potential of effectively treating IDO1 abnormity related immunosuppressive diseases and has a high application value.
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Paragraph 0473
(2018/03/01)
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- Aminostyrylbenzofuran derivatives as potent inhibitors for Aβ fibril formation
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The synthesis of a novel series of aminostyrylbenzofuran derivatives 1a-w and their inhibitory activities for Aβ fibril formation were described. All the synthesized compounds were evaluated by thioflavin T (ThT) assay and displayed potent inhibitory activities for Aβ fibril formation. Among them, compounds 1i and 1q exhibited excellent inhibitory activities (IC50 = 0.07 and 0.08 μM, respectively) than those of Curcumin (IC50 = 0.80 μM) and IMSB (IC50 = 8.00 μM) as reference compounds. Both compounds were selected as promising candidates for further biological evaluation.
- Byun, Ji Hun,Kim, HyeYun,Kim, YoungSoo,Mook-Jung, Inhee,Kim, Dong Jin,Lee, Won Koo,Yoo, Kyung Ho
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scheme or table
p. 5591 - 5593
(2009/06/18)
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- ANTIFUNGAL AGENT CONTAINING PYRIDINE DERIVATIVE
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The present invention provides an antifungal agent that has superior antifungal action and is also superior in terms of physical properties, safety and metabolic stability. The present invention discloses a compound represented by the formula (I): (wherein X represents an oxygen atom, a sulfur atom or -NH-, R1 represents a hydrogen atom, a halogen atom, a cyano group, an amino group or a substituent, and R2 and R3 independently represent a hydrogen atom, a halogen atom, a hydroxyl group or a substituent, except for a case in which R2 and R3 are both hydrogen atoms), and an antifungal agent containing the above compound.
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Page/Page column 48
(2008/06/13)
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- AGENT FOR CONTROLLING FUNCTION OF GPR34 RECEPTOR
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The present invention provides a GPR receptor function regulator comprising the compound represented by the formula: [wherein ring A is an optionally substituted isocyclic or heterocyclic ring, P is a bond or spacer, ring D is an optionally substituted monocyclic aromatic ring which may be condensed with a 5-to 7-membered ring, V is a bond or the group represented by the formula -CR14=CR15 - or - N=CR16- (wherein R14, R15 and R16 each represents a hydrogen atom or optionally substituted hydrocarbon group), Q is a bond or spacer, and W is a carboxyl or a group biologically equivalent to a carboxyl] or its salt or a prodrug thereof
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Page/Page column 86
(2010/11/28)
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- VITAMIN D RECEPTOR MODULATORS
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The present invention relates to novel, non-secosteroidal, phenyl-benzofuran compounds with vitamin D receptor (VDR) modulating activity that are less hypercalcemic than 1α,25 dihydroxy vitamin D3. These compounds are useful for treating bone disease and psoriasis.
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Page/Page column 115
(2008/06/13)
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- Alkyne compounds with MCH antagonistic activity and medicaments comprising these compounds
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The present invention relates to alkyne compounds of general formula I wherein the groups and residues A, B, W, X, Y, Z, R1 and R2 have the meanings given in claim 1. The invention further relates to pharmaceutical compositions containing at least one alkyne according to the invention. In view of their MCH-receptor antagonistic activity the pharmaceutical compositions according to the invention are suitable for the treatment of metabolic disorders and/or eating disorders, particularly obesity, bulimia, anorexia, hyperphagia and diabetes.
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- Benzofurylpyrone derivatives
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There is provided benzofuryl-α-pyrone derivative represented by the following structural formula (I): wherein R1represents a hydrogen atom or an alkyl group of 1 to 5 carbons; R2represents hydrogen, —CO—R5or —SO2/sub
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- Benzofuran and dihydrobenzofuran derivatives useful as beta-3 adrenoreceptor agonists
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This invention relates to novel benzofuran and dihydrobenzofuran compounds, pharmaceutical compositions containing such compounds, and methods of treating beta-3 adrenoreceptor-mediated conditions with such compositions.
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Page/Page column 31
(2010/01/31)
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- Alkoxycarbonylamino heteroaryl carboxylic acid derivatives as IP antagonists
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This invention relates to compounds which are IP receptor antagonists and which are represented by Formula (I): wherein G2 is a heteroaryl group containing one or two nitrogen atoms substituted with a carboxylic acid group, said heteroaryl ring
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- Alkoxycarbonylamino benzoic acid or alkoxycarbonylamino tetrazolyl phenyl derivatives as IP antagonists
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This invention relates to compounds which are generally IP receptor antagonists and which are represented by Formula I: wherein G1 is selected from the group consisting of a, b1, and b2 and A and G2 are as defin
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- Aromatic amidine derivatives useful as selective thrombin inhibitors
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The present invention relates to a novel thrombin inhibitor which is effective even when orally administered. More specifically, the present invention relates to an aromatic amidine derivative represented by formula (I) and the salts thereof, which show potent selective inhibitory activity for thrombin in which (a), R, R1, R2, R3, A, W, Y and n are defined as described in the specification.
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- P(MeNCH2CH2)3N: An efficient catalyst for the synthesis of substituted ethyl benzofuran-2-carboxylates
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A superior method for the synthesis of substituted ethyl benzofuran-2-carboxylates in 80-99% yields from substituted 2-formylphenoxy ethylcarboxylates using 0.4 equiv of commercially available P(MeNCH2CH2)3N at 70 °C for 3 hours is described.
- D'Sa, Bosco A.,Kisanga, Philip,Verkade, John G.
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p. 670 - 672
(2007/10/03)
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- Carboxylic acid derivatives as IP antagonists
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This invention relates to compounds which are generally IP receptor antagonists and which are represented by Formula I: wherein: R1, R2, and R3 are each independently in each occurrence aryl or heteroaryl; R4 is
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- Benzopyran derivatives having leukotriene-antagonistic action
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The present invention relates to novel 4-oxo-4H-1-benzopyran compounds containing benzyloxymethyl, 3-phenylpropyl, or other araliphatic substituents in their 8-position. These compounds show a leukotriene-antagonistic activity. The compounds are characterized by good oral adsorption. The compounds of the present invention may be used as anti-inflammatory and antiallergic medicaments, and in the treatment of cardiovascular diseases.
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- Inhibition of aromatase (P450Arom) by some 1-(benzofuran-2-ylmethyl)imidazoles.
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Studies of a series of 1-(benzofuran-2-ylmethyl)imidazoles, 1-5, previously proposed as potential agents for prostatic cancer by their inhibition of 17beta-hydroxylase:17,20-lyase (P450 17), have been extended to their selectivity against placental microsomal aromatase (P450(Arom)) in man. The compounds were 3-7-fold more potent than aminoglutethimide and had some selectivity for P450 17 as expressed by the ratio (IC50 P450(Arom))/(IC50 P450) 17)/17.0 (2), 10.3 (3), 34.6 (4) and 42.0 (5), where IC50 is the concentration resulting in 50% inhibition. The lower potency of 1-5 towards P450(Arom) compared with the racemic alpha-phenyl-substituted compounds (6, 80-1000 x aminoglutethimide) and some racemic alpha-methyl (8.5 and 12.2 x aminoglutethimide) and alpha-ethyl (12.1 and 32.9 x aminoglutethimide) analogues has been rationalized. This work selectively extends studies of the P450 17 inhibitor 5, a potential prostatic cancer agent, towards other cytochrome P450 enzymes in the steroidogenic pathway and provides a general method for determining the relative influence of chemical manipulation of a parent inhibitor towards two enzymes in the pathway using additional literature data.
- Owen,Nicholls,Smith,Whomsley
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p. 427 - 433
(2007/10/03)
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- The conformation and activity relationship of benzofuran derivatives as angiotensin II receptor antagonists
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We have synthesized various benzofuran derivatives to study the relationship between the conformation and the angiotensin II type I receptor antagonistic activity.
- Yoo, Sung-Eun,Lee, Seung-Heui,Kim, Soo-Kyung,Lee, Sung-Hou
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p. 445 - 459
(2007/10/03)
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