- Design, synthesis and biological evaluation of benz-fused five-membered heterocyclic compounds as tubulin polymerization inhibitors with anticancer activities
-
A series of benz-fused five-membered heterocyclic compounds were designed and synthesized as novel tubulin inhibitors targeting the colchicine binding site. Among them, compound 4d displayed the highest antiproliferative activity against four cancer cell lines with an IC50 value of 4.9?μM in B16-F10 cells. Compound 4d effectively inhibited tubulin polymerization in vitro (IC50 of 13.1?μM). Further, 4d induced cell cycle arrest in G2/M phase. Finally, 4d inhibited the migration of cancer cells in a dose-dependent manner. In summary, these results suggest that compound 4d represents a new class of tubulin inhibitors deserving further investigation.
- Komuraiah, Buduma,Ren, Yichang,Xue, Mingming,Cheng, Binbin,Liu, Jin,Liu, Yao,Chen, Jianjun
-
p. 1109 - 1116
(2021/03/16)
-
- METHODS AND COMPOSITIONS FOR MODULATING SPLICING
-
Described herein are small molecule splicing modulator compounds that modulate splicing of mRNA, such as pre-mRNA, encoded by genes, and methods of use of the small molecule splicing modulator compounds for modulating splicing and treating diseases and conditions.
- -
-
Paragraph 0620; 0654; 0754
(2020/08/22)
-
- Synthesis, docking, 3-D-qsar, and biological assays of novel indole derivatives targeting serotonin transporter, dopamine D2 receptor, and mao-a enzyme: In the pursuit for potential multitarget directed ligands
-
A series of 27 compounds of general structure 2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-{4-[3-(1H-3indolyl)-propyl]-1-piperazinyl}-ethanamides, Series I: 7(a-o) and (2-{4-[3-(1H-3-indolyl) -propyl]-1-piperazinyl}-acetylamine)-N-(2-morfolin-4-yl-ethyl)-fluorinated benzamides Series II: 13(a-l) were synthesized and evaluated as novel multitarget ligands towards dopamine D2 receptor, serotonin transporter (SERT), and monoamine oxidase-A (MAO-A) directed to the management of major depressive disorder (MDD). All the assayed compounds showed affinity for SERT in the nanomolar range, with five of them displaying Ki values from 5 to 10 nM. Compounds 7k, Ki = 5.63 ± 0.82 nM, and 13c, Ki = 6.85 ± 0.19 nM, showed the highest potencies. The affinities for D2 ranged from micro to nanomolar, while MAO-A inhibition was more discrete. Nevertheless, compounds 7m and 7n showed affinities for the D2 receptor in the nanomolar range (7n: Ki = 307 ± 6 nM and 7m: Ki = 593 ± 62 nM). Compound 7n was the only derivative displaying comparable affinities for SERT and D2 receptor (D2/SERT ratio = 3.6) and could be considered as a multitarget lead for further optimization. In addition, docking studies aimed to rationalize the molecular interactions and binding modes of the designed compounds in the most relevant protein targets were carried out. Furthermore, in order to obtain information on the structure-activity relationship of the synthesized series, a 3-D-QSAR CoMFA and CoMSIA study was conducted and validated internally and externally (q2 = 0.625, 0.523 for CoMFA and CoMSIA and r2ncv = 0.967, 0.959 for CoMFA and CoMSIA, respectively).
- Alarcón-Espósito, Jazmín,Araya-Maturana, Ramiro,Cabezas, David,Cerda-Cavieres, Christopher,Chung, Hery,Iturriaga-Vásquez, Patricio,Mella-Raipán, Jaime,Ojeda-Gómez, Claudia,Pessoa-Mahana, Carlos D.,Pessoa-Mahana, Hernán,Quiroz, Gabriel,Reyes-Parada, Miguel,Rodríguez-Lavado, Julio,Saitz, Claudio
-
-
- Structure-Activity Relationship Studies of Tolfenpyrad Reveal Subnanomolar Inhibitors of Haemonchus contortus Development
-
Recently, we have discovered that the registered pesticide, tolfenpyrad, unexpectedly and potently inhibits the development of the L4 larval stage of the parasitic nematode Haemonchus contortus with an IC50 value of 0.03 μM while displaying good selectivity, with an IC50 of 37.9 μM for cytotoxicity. As a promising molecular template for medicinal chemistry optimization, we undertook anthelmintic structure-activity relationships for this chemical. Modifications of the left-hand side (LHS), right-hand side (RHS), and middle section of the scaffold were explored to produce a set of 57 analogues. Analogues 25, 29, and 33 were shown to be the most potent compounds of the series, with IC50 values at a subnanomolar level of potency against the chemotherapeutically relevant fourth larval (L4) stage of H. contortus. Selected compounds from the series also showed promising activity against a panel of other different parasitic nematodes, such as hookworms and whipworms.
- Le, Thuy G.,Kundu, Abhijit,Ghoshal, Atanu,Nguyen, Nghi H.,Preston, Sarah,Jiao, Yaqing,Ruan, Banfeng,Xue, Lian,Huang, Fei,Keiser, Jennifer,Hofmann, Andreas,Chang, Bill C. H.,Garcia-Bustos, Jose,Wells, Timothy N. C.,Palmer, Michael J.,Jabbar, Abdul,Gasser, Robin B.,Baell, Jonathan B.
-
p. 1036 - 1053
(2019/01/14)
-
- Iguratimod intermediate and synthesis method thereof
-
The invention belongs to the technical field of chemical drug synthesis, and particularly relates to an Iguratimod key intermediate and a synthesis method thereof. The synthesis method comprises the following steps: carrying out reduction on 4-methoxy-2-n
- -
-
Paragraph 0034; 0037; 0040
(2019/05/15)
-
- Design, synthesis and characterization of potent microtubule inhibitors with dual anti-proliferative and anti-angiogenic activities
-
Microtubule has been an important target for anticancer drug development. Here we report the discovery and characterization of a series of fused 4-aryl-4H-chromene-based derivatives as highly potent microtubule inhibitors. Among a total of 37 derivatives synthesized, 23 exhibited strong in vitro anti-proliferative activities against A375 human melanoma cells. The relationship between the biological activities of these microtubule inhibitors and their chemical structure variations was analyzed. Studies of compounds 27a, 19a and 9a in parallel with colchicine as the positive control compound in a panel of biological assays revealed that these compounds blocked cell cycle progression, increased apoptosis, and inhibited HUVEC capillary tube formation at low nanomolar concentrations. The most potent compound 27a was also tested in eight additional cancer cell lines besides A375 cells and two non-cancer cells and showed potent and selective activity on these cancer cells. To understand the molecular and structure mechanism of action of these compounds, tubulin polymerization and molecular docking studies were carried out for 27a as the representative. The results were consistent with the mechanism by which 27a interacts with the colchicine binding site on tubulin and disrupts tubulin polymerization. With potent dual actions of microtubule destabilization and vascular disruption described above, this small molecule can serve as a valuable research probe of the function and role of microtubules in human diseases and promising lead for developing new therapeutic agents.
- Zhang, Huijun,Fang, Xiong,Meng, Qian,Mao, Yujia,Xu, Yan,Fan, Tingting,An, Jing,Huang, Ziwei
-
supporting information
p. 380 - 396
(2018/08/17)
-
- Synthesis and biological evaluation of potential acetylcholinesterase inhibitors based on a benzoxazine core
-
With the purpose of expanding the structural variety of chemical compounds available as pharmacological tools for the treatment of Alzheimer's disease, we synthesized and evaluated a novel series of indole-benzoxazinones (Family I) and benzoxazine-arylpiperazine derivatives (Family II) for potential human acetylcholinesterase (hAChE) inhibitory properties. The most active compounds 7a and 7d demonstrated effective inhibitory profiles with Ki values of 20.3 ± 0.9 μM and 20.2 ± 0.9 μM, respectively. Kinetic inhibition assays showed non-competitive inhibition of AChE by the tested compounds. According to our docking studies, the most active compounds from both series (Families I and II) showed a binding mode similar to donepezil and interact with the same residues.
- Méndez-Rojas, Claudio,Quiroz, Gabriel,Faúndez, Mario,Gallardo-Garrido, Carlos,Pessoa-Mahana, C. David,Chung, Hery,Gallardo-Toledo, Eduardo,Saitz-Barría, Claudio,Araya-Maturana, Ramiro,Kogan, Marcelo J.,Zú?iga-López, María C.,Iturriaga-Vásquez, Patricio,Valenzuela-Gutiérrez, Carla,Pessoa-Mahana, Hernán
-
-
- Suzuki Cross-Coupling for Post-Complexation Derivatization of Non-Racemic Bis-Cyclometalated Iridium(III) Complexes
-
A straightforward method for post-complexation derivatizations of diastereo- and enantiomerically pure bis-cyclometalated benzoxazole and benzothiazole iridium(III) complexes is reported. Triflate- and bromine-functionalized iridium(III) complex dimers, r
- Mietke, Thomas,Cruchter, Thomas,Winterling, Erik,Tripp, Matthias,Harms, Klaus,Meggers, Eric
-
supporting information
p. 12363 - 12371
(2017/09/14)
-
- Catalytic application of 1,3,5-triazine-pentaethylenehexamine polymer-supported palladium nanoparticles in the convenient reduction of nitroarenes with sodium borohydride or hydrazine
-
The catalytic activity of 1,3,5-triazine-pentaethylenehexamine (TAPEHA) polymer-supported Pd nanoparticles was investigated in the reduction of nitro arenes to the corresponding amines by NaBH4 or N2H4 .H2 O. Optimized reaction conditions for both systems were successfully tested on 20 nitroarenes with different characteristics. Considerably high yields (80%-98% in NaBH4 and 85%-98% in N2H4) were obtained in a short time and at ambient temperature. In addition to these methods being selective against other reducible functionalities such as -CN, -Br, -Cl, and -I, the catalyst can be recovered easily and reused more than ten times.
- Gen?, Hayriye,Zengin, Mustafa,Kü?ükislamo?lu, Mustafa,Imamoglu, Mustafa,Toplan, Hüseyin ?zkan,Arslan, Mustafa
-
p. 784 - 792
(2017/11/20)
-
- HEMOGLOBIN MODIFIER COMPOUNDS AND USES THEREOF
-
Described herein are compounds, including pharmaceutically acceptable salts thereof, methods of making such compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat, prevent or diagnose blood-based diseases, disorders or conditions.
- -
-
Paragraph 00435
(2018/02/28)
-
- Design and synthesis of novel benzoxazole analogs as Aurora B kinase inhibitors
-
A novel series of benzoxazole analogs was designed and synthesized, and their inhibitory activities against Aurora kinases were evaluated. Some of the tested compounds exhibited a promising activity with respect to the inhibition of Aurora B kinase. A structure-activity relationship study indicated that linker length, regiochemistry, and halogen substitution play important roles in kinase inhibitory potency. The binding modes between representative compounds and Aurora kinases were interpreted through a molecular docking study to explain the inhibitory activity and selectivity for Aurora A and B kinases. Compounds 13l and 13q also show an antiproliferative effect on the human tumor cell lines in a dose-dependent manner. The most potent 13q demonstrated good efficacy in the prostate cancer PC-3 tumor xenograft model.
- An, Ying,Lee, Eun,Yu, Yeongji,Yun, Jieun,Lee, Myeong Youl,Kang, Jong Soon,Kim, Woo-Young,Jeon, Raok
-
supporting information
p. 3067 - 3072
(2016/06/13)
-
- INHIBITORS OF HIF PROLYL HYDROXYLASE
-
The present invention concerns compounds of formula I or pharmaceutically acceptable salts thereof, which inhibit HIF prolyl hydroxylase, their use for enhancing endogenous production of erythropoietin, and for treating conditions associated with reduced endogenous production of erythropoietin such as anemia and like conditions, as well as pharmaceutical compositions comprising such a compound and a pharmaceutical carrier.
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Page/Page column 156
(2016/04/20)
-
- BICYCLIC HETEROCYCLIC DERIVATIVES AS BROMODOMAIN INHIBITORS
-
The present disclosure provides bicyclic heterocyclic derivatives of formula (I), which may be therapeutically useful, more particularly as bromodomain inhibitors; (I), in which R1, R2, R3, R4, L1, L2, Cy1, Cy2, X, n, and dotted line have the same meaning given in the specification, and pharmaceutically acceptable salts or pharmaceutically acceptable stereoisomers thereof that are useful in the treatment and prevention of diseases or disorders, in particular their use in diseases or disorders associated as bromodomain inhibitors. The present disclosure also provides preparation of compounds and pharmaceutical formulations comprising at least one of bicyclic heterocyclic derivatives of formula (I), together with a pharmaceutically acceptable carrier, diluent, or excipient.
- -
-
Paragraph 0134
(2017/04/04)
-
- IRE-1α INHIBITORS
-
PROBLEM TO BE SOLVED: To provide compounds which directly inhibit inositol requiring enzyme 1 (IRE-1α activity) in vitro, prodrugs, and pharmaceutically acceptable salts thereof. SOLUTION: The present invention provides a compound represented by formula (A) [R3 and R4 are H or the like; Q5-Q8, together with the benzene ring to which they are attached, form a benzofused ring, where at least one of Q5-Q8 is a heteroatom selected from N, O, and S. COPYRIGHT: (C)2016,JPOandINPIT
- -
-
Paragraph 1338; 1339
(2016/10/07)
-
- Efficient reductions of various nitroarenes with scrap automobile catalyst and NaBH4
-
The effect of scrap automobile catalyst (SAC), a waste material, was investigated as a catalyst for the reduction of nitroarenes to the corresponding amines with sodium borohydride in aqueous ethanol at 5-25 °C. Along with the observed high conversions, the SAC and NaBH4 combination also exhibits a selectively catalyzed reduction in compounds containing other reducible functionalities, such as CN, Br, Cl and I. Recycling automobile wastes into a catalyst for organic reactions will offer both environmental protection and economic advantages. As a result, an effective, easy to use, low-priced and reliable method has been developed.
- Genc, Hayriye
-
-
- BICYCLIC HETEROCYCLIC DERIVATIVES AS BROMODOMAIN INHIBITORS
-
The present invention provides bicyclic heterocyclic derivatives of formula (I), which may be therapeutically useful, more particularly as bromodomain inhibitors; (I), in which R1, R2, R3, R4, L1, L2, Cy1, Cy2, X, n and dotted line are have the same meaning given in the specification, and pharmaceutically acceptable salts or pharmaceutically acceptable stereoisomers thereof that are useful in the treatment and prevention of diseases or disorder, in particular their use in diseases or disorder associated as bromodomain inhibitors. The present invention also provides preparation of the compounds and pharmaceutical formulations comprising at least one of bicyclic heterocyclic derivatives of formula (I), together with a pharmaceutically acceptable carrier, diluent or excipient therefor.
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Page/Page column 27
(2015/07/23)
-
- Two-chamber hydrogen generation and application: Access to pressurized deuterium gas
-
Hydrogen and deuterium gas were produced and directly applied in a two-chamber system. These gaseous reagents were generated by the simple reaction of metallic zinc with HCl in water for H2 and DCl in deuterated water for D2. The setup proved efficient in classical Pd-catalyzed reductions of ketones, alkynes, alkenes, etc. in near-quantitative yields. The method was extended to the synthesis and isotope labeling of quinoline and 1,2,3,4-tetrahydroquinoline derivatives. Finally, CX-546 and Olaparib underwent efficient Ir-catalyzed hydrogen isotope exchange reactions.
- Modvig, Amalie,Andersen, Thomas L.,Taaning, Rolf H.,Lindhardt, Anders T.,Skrydstrup, Troels
-
p. 5861 - 5868
(2014/07/08)
-
- NEW CYCLOHEXYL AND QUINUCLIDINYL CARBAMATE DERIVATIVES HAVING BETA2 ADRENERGIC AGONIST AND M3 MUSCARINIC ANTAGONIST ACTIVITY
-
The present invention relates to novel compounds having β2 adrenergic agonist and M3 muscarinic antagonist dual activity, to pharmaceutical compositions containing them, to the process for their preparation and to their use in respiratory therapies.
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-
Page/Page column 124
(2014/07/08)
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- Synthesis of substituted 2-heteroarylbenzazol-5-ol derivatives as potential ligands for estrogen receptors
-
Exposure to estrogen is associated with increased risk of breast and other types of human cancer. One therapeutic goal would be the creation of new molecules that would retain hormonal potency while incorporating features to retard or prevent quinone toxicity. Hence, new structures closely related to ERB-041, a known ERβ selective agonist, were synthesized whereas the phenol ring is substituted with non-quinone forming rings such as pyrazole, 2-pyrimidine-2(1H)-one or pyridine-2(1H)-one. 2-Methyl-5-methoxy-1,3- benzoxazoles (or 1,3-benzothiazole) are key intermediates for the production of the pyrazole and pyrimidine-2(1H)-one analogs. The required 1,3-benzoxazoles were synthesized starting from reduction of 2-nitro-4-methoxyphenols, followed by condensation with trimethyl orthoacetate. Then, the diiminium perchlorate intermediates were prepared from the latter compounds by Vilsmeier-Haack reaction. The reaction of the resulting intermediates with hydrazine hydrate and guanidium chloride afforded the title pyrazole and pyrimidine-2(1H)-ones, respectively. The pyridine analogs were synthesized starting from the reaction of 2-amino-4-methoxyphenols with 6-bromopyridine-3-carboxaldehyde followed by oxidation with DDQ to afford bromopyridines. These compounds were next treated with benzyl alcohol in the presence of potassium tert-butoxide to afford 2-benzyloxypyridine, which in subsequent dealkylation with boron tribromide produced the title pyridine-2-(1H)-ones.
- Rezazadeh, Sina,Navidpour, Latifeh,Shafiee, Abbas
-
p. 6076 - 6082
(2013/07/19)
-
- Synthesis and evaluation of novel 18f labeled 2-pyridinylbenzoxazole and 2-pyridinylbenzothiazole derivatives as ligands for positron emission tomography (PET) imaging of β-amyloid plaques
-
A series of fluoro-pegylated (FPEG) 2-pyridinylbenzoxazole and 2-pyridinylbenzothiazole derivatives were synthesized and evaluated as novel β-amyloid (Aβ) imaging probes for PET. They displayed binding affinities for Aβ1-42 aggregates that varied from 2.7 to 101.6 nM. Seven ligands with high affinity were selected for 18F labeling. In vitro autoradiography results confirmed the high affinity of these radiotracers. In vivo biodistribution experiments in normal mice indicated that the radiotracers with a short FPEG chain (n = 1) displayed high initial uptake into and rapid washout from the brain. One of the 2-pyridinylbenzoxazole derivatives, [18F]-5-(5-(2-fluoroethoxy)benzo[d]oxazol-2-yl)-N- methylpyridin-2-amine ([18F]32) (Ki = 8.0 ± 3.2 nM) displayed a brain2min/brain60min ratio of 4.66, which is highly desirable for Aβ imaging agents. Target specific binding of [ 18F]32 to Aβ plaques was validated by ex vivo autoradiographic experiment with transgenic model mouse. Overall, [18F]32 is a promising Aβ imaging agent for PET and merits further evaluation in human subjects.
- Cui, Mengchao,Wang, Xuedan,Yu, Pingrong,Zhang, Jinming,Li, Zijing,Zhang, Xiaojun,Yang, Yanping,Ono, Masahiro,Jia, Hongmei,Saji, Hideo,Liu, Boli
-
p. 9283 - 9296
(2013/01/15)
-
- Novel 18F-labeled benzoxazole derivatives as potential positron emission tomography probes for imaging of cerebral β-amyloid plaques in alzheimers disease
-
Two radiofluoro-pegylated phenylbenzoxazole derivatives, 4-(5-(2-(2-(2-[18F]fluoroethoxy)ethoxy)ethoxy)benzo[d]oxazol-2-yl)-N- methylaniline ([18F]24) and 4-(5-(2-(2-(2-[18F] fluoroethoxy)ethoxy)ethoxy)benzo[d]oxazol-2-yl)
- Cui, Mengchao,Ono, Masahiro,Kimura, Hiroyuki,Ueda, Masashi,Nakamoto, Yuji,Togashi, Kaori,Okamoto, Yoko,Ihara, Masafumi,Takahashi, Ryosuke,Liu, Boli,Saji, Hideo
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p. 9136 - 9145
(2013/01/15)
-
- Design and synthesis of 5,6-fused heterocyclic amides as Raf kinase inhibitors
-
Two scaffolds based on 5,6-fused heterocyclic backbones were designed and synthesized as Raf kinase inhibitors. The scaffolds were assessed for in vitro pan-Raf inhibition, activity in cell proliferation and target modulation assays, and pharmacokinetic p
- Ramurthy, Savithri,Aikawa, Mina,Amiri, Payman,Costales, Abran,Hashash, Ahmad,Jansen, Johanna M.,Lin, Song,Ma, Sylvia,Renhowe, Paul A.,Shafer, Cynthia M.,Subramanian, Sharadha,Sung, Leonard,Verhagen, Joelle
-
supporting information; experimental part
p. 3286 - 3289
(2011/06/24)
-
- HARMFUL ARTHROPOD CONTROL COMPOSITION, AND FUSED HETEROCYCLIC COMPOUND
-
Disclosed is a harmful arthropod control composition comprising, as an active ingredient, a fused heterocyclic compound represented by formula (1) [wherein A1 and A2 independently represent a nitrogen atom or the like; R1 and R4 independently represent a halogen atom or the like; R2 and R3 independently represent a halogen atom or the like; R5 and R6 independently represent a linear C1-C6 hydrocarbon group which may be substituted, or the like (provided that both R5 and R6 cannot represent a hydrogen atom simultaneously); and n represents 0 or 1]. The harmful arthropod control composition has an excellent efficacy to control harmful arthropods.
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Page/Page column 120
(2011/02/18)
-
- HARMFUL ARTHROPOD CONTROL COMPOSITION, AND FUSED HETEROCYCLIC COMPOUND
-
Disclosed is a harmful arthropod control composition comprising, as an active ingredient, a fused heterocyclic compound represented by formula (1) [wherein A1 and A2 independently represent a nitrogen atom or the like; R1 and R4 independently represent a halogen atom or the like; R2 and R3 independently represent a halogen atom or the like; R5 and R6 independently represent a linear C1-C6 hydrocarbon group which may be substituted, or the like (provided that both R5 and R6 cannot represent a hydrogen atom simultaneously); and n represents 0 or 1]. The harmful arthropod control composition has an excellent efficacy to control harmful arthropods.
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Page/Page column 75
(2011/04/13)
-
- A facile pathway to enantiomerically enriched 3-hydroxy-2-oxindoles: Asymmetric intramolecular arylation of α-keto amides catalyzed by a palladium-DifluorPhos complex
-
Less metal wastes: The first catalytic, enantioselective intramolecular aryl-transfer reaction of aryl triflates to ketones has been developed (see scheme; R1=R2=aromatic and aliphatic). This method features overall practicality, inc
- Yin, Liang,Kanai, Motomu,Shibasaki, Masakatsu
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supporting information; body text
p. 7620 - 7623
(2011/09/30)
-
- COMPOSITION AND METHOD FOR CONTROLLING ARTHROPOD PESTS
-
The present invention provides: an arthropod pests control composition comprising, as active ingredients, a condensed heterocyclic compound and a neonicotinoid compound; a method for controlling arthropod pests which comprises applying effective amounts of a condensed heterocyclic compound and a neonicotinoid compound to the arthropod pests or a locus where the arthropod pests inhabit; and so on.
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Page/Page column 199-200
(2011/04/25)
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- COMPOSITION AND METHOD FOR CONTROLLING ARTHROPOD PESTS
-
The present invention provides: an arthropod pests control composition comprising, as active ingredients, a condensed heterocyclic compound and pyriproxyfen; a method for controlling arthropod pests which comprises applying effective amounts of a condensed heterocyclic compound and pyriproxyfen to the arthropod pests or a locus where the arthropod pests inhabit; and so on.
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Page/Page column 199
(2011/05/06)
-
- COMPOSITION AND METHOD FOR CONTROLLING ARTHROPOD PESTS
-
The present invention provides: an arthropod pests control composition comprising, as active ingredients, a condensed heterocyclic compound and a pyrethroid compound; a method for controlling arthropod pests which comprises applying effective amounts of a condensed heterocyclic compound and a pyrethroid compound to the arthropod pests or a locus where the arthropod pests inhabit; and so on.
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Page/Page column 200
(2011/05/06)
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- COMPOSITION AND METHOD FOR CONTROLLING ARTHROPOD PESTS
-
The present invention provides: an arthropod pests control composition comprising, as active ingredients, a condensed heterocyclic compound and pyridalyl; a method for controlling arthropod pests which comprises applying effective amounts of a condensed heterocyclic compound and pyridalyl to the arthropod pests or a locus where the arthropod pests inhabit; and so on.
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Page/Page column 199
(2011/05/06)
-
- COMPOSITION AND METHOD FOR CONTROLLING ARTHROPOD PESTS
-
The present invention provides: an arthropod pests control composition comprising, as active ingredients, a condensed heterocyclic compound and a diamide compound; a method for controlling arthropod pests which comprises applying effective amounts of a condensed heterocyclic compound and a diamide compound to the arthropod pests or a locus where the arthropod pests inhabit; and so on.
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Page/Page column 203
(2011/05/06)
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- 2-OXO-3-BENZYLBENZOXAZOL-2-ONE DERIVATIVES AND RELATED COMPOUNDS AS MET KINASE INHIBITORS FOR THE TREATMENT OF TUMOURS
-
Compounds of the formula (I), in which R1, R2, R3, R3′, R4, R4′, E, E′, E″ and E′″ have the meanings indicated in Claim 1, are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for the treatment of tumours.
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Page/Page column 18-19
(2010/12/29)
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- Pharmaceutical Compositions Comprising Nitrogen-Containing Fused Ring Coumpounds
-
[Problems] The present invention provides pharmaceutical composition which is effective for the prophylaxis or treatment of pathology showing involvement of uric acid (hyperuricemia, gouty tophus, acute gout arthritis, chronic gout arthritis, gouty kidney, urolithiasis, renal function disorder, coronary arterial disease, ischemic heart disease and the like) and the like, and is superior in the time-course stability and dissolution property (disintegration property). [Solving Means] The pharmaceutical composition of the present invention is a pharmaceutical composition comprising a nitrogen-containing fused ring compound represented by the following formula [1] or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable additives, wherein the nitrogen-containing fused ring compound or a pharmaceutically acceptable salt thereof is not in contact with a basic additive: wherein each symbol is as described in the specification.
- -
-
-
- Production Method of Nitrogen-Containing Fused Ring Compounds
-
[Problems] The present invention provides a superior production method and a superior purification method of compounds effective for the treatment or prophylaxis of pathology showing involvement of uric acid, such as hyperuricemia, gouty tophus, acute gouty arthritis, chronic gouty arthritis, gouty kidney, urolithiasis, renal function disorder, coronary artery disease, ischemic heart disease and the like. [Means] A compound represented by the following formula [2] or a pharmaceutically acceptable salt thereof can be produced by reacting a compound represented by the following formula [3] or a salt thereof with a compound represented by the following formula [4], a salt thereof or a reactive derivative thereof. Moreover, crystallization of a compound represented by the formula [2] can be performed with industrially superior workability, and high quality crystals of a compound represented by the formula [2] can be obtained. wherein each symbol is as defined in the description.
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Page/Page column 49
(2010/11/30)
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- Regulatory molecules for the 5-HT3 receptor ion channel gating system
-
Substituted benzoxazole derivatives which possess a nitrogen-containing heterocycle at C2 are selective partial agonists of the 5-HT3 receptor. Alteration of substituents on the benzoxazole nucleus affords both agonist-like and antagonist-like compounds, and uniquely modifies the function of the 5-HT3 receptor ion channel gating system. SAR and corroborative computational docking study for these partial agonists successfully explained structure and function of the 5-HT3 receptor.
- Yoshida, Satoshi,Watanabe, Takashi,Sato, Yasuo
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p. 3515 - 3523
(2008/02/07)
-
- CYANOISOQUINOLINE COMPOUNDS AND METHODS OF USE THEREOF
-
The present invention relates to cyanoisoquinoline compounds suitable for use in treating hypoxia inducible factor-mediated and/or erythropoietin-associated conditions. The cyanoisoquinoline compounds of the invention have the following structure: Formula (I).
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Page/Page column 85-86
(2008/06/13)
-
- Nitrogen-containing fused ring compounds and use thereof
-
A URAT1 activity inhibitor containing a nitrogen-containing fused ring compound represented by the following formula [1]: wherein each symbol is as defined in the description. The present invention is useful for the prophylaxis or treatment of pathology showing involvement of uric acid, such as hyperuricemia, gouty tophus, acute gouty arthritis, chronic gouty arthritis, gouty kidney, urolithiasis, renal function disorder, coronary artery disease, ischemic heart disease and the like.
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Page/Page column 85-86
(2010/11/25)
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- NOVEL MOLECULAR PROBES
-
The present invention relates to novel molecular probes having the formula (I) (I) useful for the characterization, detection, localization and isolation of the γ-secretase enzyme.
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Page/Page column 29
(2008/06/13)
-
- Indole derivative having piperidine ring
-
The present invention relates to a compound represented by the following formula, a pharmacologically acceptable salt thereof, or a use thereof as a pharmaceutical: wherein R1 and R2 are substituents adjacent to each other, and together with two carbon atoms to each of which they attach, form a 5- to 7-membered non-aromatic carbocyclic group or the like, which may be substituted by 1 to 4 substituents selected from (1) an oxo group, (2) a hydroxyl group, and the like; R3 represents a hydrogen atom or the like; and R6 represents a hydrogen atom or the like. It is an object of the present invention to discover an agent for treating or preventing lower urinary tract symptoms, and particularly symptoms regarding urinary storage, which has a superior strength of binding to a 5-HT1A receptor and an antagonism to the receptor.
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Page/Page column 60
(2008/06/13)
-
- Heteroaryl alkyl piperazine derivatives
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Novel compounds of the general formula: and pharmaceutically acceptable acid addition salts thereof, wherein the compounds are useful in therapy to protect skeletal muscles against damage resulting from trauma or to protect skeletal muscles subsequent to muscle or systemic diseases such as intermittent claudication, to treat shock conditions, to preserve donor tissue and organs used in transplants, in the treatment of diabetes, in the treatment of cardiovascular diseases including atrial and ventricular arrhythmias, Prinzmetal's (variant) angina, stable angina, and exercise induced angina, congestive heart disease, and myocardial infarction.
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- One step hair coloring compositions using salts
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A hair coloring composition comprising the following two compositions which are mixed just prior to application to the hair: (a) a composition comprising a water-soluble peroxygen oxidizing agent; and (b) a composition comprising one or more oxidative hair coloring agents selected from the group consisting of an aromatic diamine, an amino phenol, a naphthol, a polyhydric phenol, a catechol and mixtures thereof; wherein the composition comprising one or more oxidative hair coloring agents further comprises al least one water soluble carbonate releasing salts; and optionally a water soluble ammonium salt, is described.
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- Novel 5-HT7 receptor inverse agonists. Synthesis and molecular modeling of arylpiperazine- and 1,2,3,4-tetrahydroisoquinoline-based arylsulfonamides.
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A series of arylpiperazine- and 1,2,3,4-tetrahydroisoquinoline-based arylsulfonamides was synthesized and evaluated for their interactions with the constitutively active 5-HT7 receptor. Effects on basal adenylate cyclase activity were measured using HEK-293 cells expressing the rat 5-HT7. All ligands produced a decrease of adenylate cyclase activity, indicative of their inverse agonism. Additionally, computational studies with a set of 22 inverse agonists, including these novel inverse agonists and inverse agonists known from literature, resulted in a pharmacophore model and a CoMFA model (R2 = 0.97, SE = 0.18). Docking of inverse agonists at the binding site of a model of the helical parts of the 5-HT7 receptor, based on the alpha carbon template for 7-TM GPCRs, revealed interesting molecular interactions and a possible explanation for observed structure-activity relationships.
- Vermeulen, Erik S,van Smeden, Marjan,Schmidt, Anne W,Sprouse, Jeffrey S,Wikstroem, Hakan V,Grol, Cor J
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p. 5451 - 5466
(2007/10/03)
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- SUBSTITUTED HETEROCYCLIC COMPOUNDS
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Disclosed are novel heterocyclic derivatives, useful for the treatment of various disease states, in particular cardiovascular diseases such as atrial and ventricular arrhythmias, intermittent claudication, Prinzmetal's (variant) angina, stable and unstable angina, exercise induced angina, congestive heart disease, and myocardial infarction. The compounds are also useful in the treatment of diabetes.
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- Substituted benzazoles and methods of their use as inhibitors of Raf kinase
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New substituted benz-azole compounds, compositions and methods of inhibition of Raf kinase activity in a human or animal subject are provided. The new compounds compositions may be used either alone or in combination with at least one additional agent for the treatment of a Raf kinase mediated disorder, such as cancer.
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- Novel synthesis of benzoxazoles from o-nitrophenols and amines
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o-Nitrophenols and o-nitroaniline were reacted with amines at 210-215°C to produce the corresponding benzoxazoles and benzimidazoles, respectively, in moderate yields. The reactions between o-nitrophenols containing a CO2Me or OMe group on their benzene rings and N,N-diethylaniline were examined to investigate the effects of the position and electronic character of these substituents on the formation of the oxazole ring.
- Nishioka, Hiromi,Ohmori, Yukiko,Iba, Yumiko,Tsuda, Eri,Harayama, Takashi
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p. 193 - 198
(2007/10/03)
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- Transition metal complexes as dye forming catalysts in hair coloring compositions
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A hair coloring composition comprising a first composition which comprises: (a) a dye forming transition metal salt or complex; which is first applied to the hair; and a second composition which comprises the following two compositions which are mixed just prior to application to the hair: (a) a composition comprising a water-soluble peroxygen oxidizing agent; and (b) a composition comprising one or more oxidative hair coloring agents selected from the group consisting of an aromatic diamine, an aminophenol, a polyhydric phenol a catechol and mixtures thereof.
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- Enhanced color deposition for hair with sequestering agents
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Hair coloring compositions which comprise: (A) non-nitrogenous chelating agents from the group consisting of polyphosphate; phosphonates; hydroxycarboxylates; polyacrylates; zeolite; and mixtures thereof; (B) an oxidative dye primary intermediate; and (C) an oxidative dye coupler; (D) and water are described. The present invention also relates to a method for coloring hair which comprises contacting said hair with a hair coloring composition as described above.
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- Amidine derivatives, their preparation and application as medicines and pharmaceutical compositions containing same
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Amidine compounds of the formula wherein the substituents are defined as in the application useful as NO-synthase enzyme inhibitors.
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Page/Page column 48
(2008/06/13)
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- Heteroaryl alkyl piperazine derivatives
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Novel compounds of the general formula: and pharmaceutically acceptable acid addition salts thereof, wherein the compounds are useful in therapy to protect skeletal muscles against damage resulting from trauma or to protect skeletal muscles subsequent to muscle or systemic diseases such as intermittent claudication, to treat shock conditions, to preserve donor tissue and organs used in transplants, in the treatment of cardiovascular diseases including atrial and ventricular arrhythmias, Prinzmetal's (variant) angina, stable angina, and exercise induced angina, congestive heart disease, and myocardial infarction.
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- Heteroaryl alkyl piperazine derivatives
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Novel compounds of the general formula: and pharmaceutically acceptable acid addition salts thereof, wherein the compounds are useful in therapy to protect skeletal muscles against damage resulting from trauma or to protect skeletal muscles subsequent to muscle or systemic diseases such as intermittent claudication, to treat shock conditions, to preserve donor tissue and organs used in transplants, in the treatment of diabetes, in the treatment of cardiovascular diseases including atrial and ventricular arrhythmias, Prinzmetal's (variant) angina, stable angina, and exercise induced angina, congestive heart disease, and myocardial infarction.
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- Synthesis of novel bis(benzoxazole) derivatives by tandem Claisen rearrangement and their fluorescence behavior
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Novel bis(benzoxazole) derivatives were easily synthesized from isobutenyl bis(amide-ether)s by tandem Claisen rearrangement and subsequent intramolecular cyclization of the amide-phenol intermediates. The yields of the bis(benzoxazole)s depended on wheth
- Koyama, Emiko,Yang, Gang,Tsuzuki, Seiji,Hiratani, Kazuhisa
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p. 1996 - 2006
(2007/10/03)
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