- Benzothiazolyl ureas are low micromolar and uncompetitive inhibitors of 17Β-HSD10 with implications to Alzheimer’s disease treatment
-
Human 17β-hydroxysteroid dehydrogenase type 10 is a multifunctional protein involved in many enzymatic and structural processes within mitochondria. This enzyme was suggested to be involved in several neurological diseases, e.g., mental retardation, Parkinson’s disease, or Alzheimer’s disease, in which it was shown to interact with the amyloid-beta peptide. We prepared approximately 60 new compounds based on a benzothiazolyl scaffold and evaluated their inhibitory ability and mechanism of action. The most potent inhibitors contained 3-chloro and 4-hydroxy substitution on the phenyl ring moiety, a small substituent at position 6 on the benzothiazole moiety, and the two moieties were connected via a urea linker (4at, 4bb, and 4bg). These compounds exhibited IC50 values of 1–2 μM and showed an uncompetitive mechanism of action with respect to the substrate, acetoacetyl-CoA. These uncompetitive benzothiazolyl inhibitors of 17β-hydroxysteroid dehydrogenase type 10 are promising compounds for potential drugs for neurodegenerative diseases that warrant further research and development.
- Aitken, Laura,Benek, Ondrej,Chribek, Matej,Dolezal, Rafael,Gunn-Moore, Frank,Hrabinova, Martina,Hroch, Lukas,Jun, Daniel,Kralova, Vendula,Kuca, Kamil,Lycka, Antonin,Musilek, Kamil,Prchal, Lukas,Schmidt, Monika,Vinklarova, Lucie,Zemanova, Lucie
-
-
- Hyperbranched Poly(ester-enamine) from Spontaneous Amino-yne Click Reaction for Stabilization of Gold Nanoparticle Catalysts
-
Hyperbranched polymers have garnered much attention due to attractive properties and wide applications, such as drug-controlled release, stimuli-responsive nano-objects, photosensitive materials and catalysts. Herein, two types of novel hyperbranched poly(ester-enamine) (hb-PEEa) were designed and synthesized via the spontaneous amino-yne click reaction of A2 monomer (1, 3-bis(4-piperidyl)-propane (A2a) or piperazine (A2b)) and B3 monomer (trimethylolpropanetripropiolate). According to Flory's hypothesis, gelation is an intrinsic problem in an ideal A2+B3 polymerization system. By controlling the polymerization conditions, such as monomer concentration, molar ratio and rate of addition, a non-ideal A2+B3 polymerization system can be established to avoid gelation and to synthesize soluble hb-PEEa. Due to abundant unreacted alkynyl groups in periphery, the hb-PEEa can be further functionalized by different amino compounds or their derivates. The as-prepared amphiphilic PEG-hb-PEEa copolymer can readily self-assemble into micelles in water, which can be used as surfactant to stabilize Au nanoparticles (AuNPs) during reduction of NaBH4 in aqueous solution. As a demonstration, the as-prepared PEG-hb-PEEa-supported AuNPs demonstrate good dispersion in water, solvent stability and remarkable catalytic activity for reduction of nitrobenzene compounds.
- Yang, Dong,Liu, Pei,Lin, Wanran,Sui, Shanglin,Huang, Long-Biao,Xu, Ben Bin,Kong, Jie
-
supporting information
p. 2499 - 2504
(2020/07/13)
-
- 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
-
-
- HMOX1 inducers
-
The present invention is related to compounds of structure (I) as heme oxygenase 1 (HMOX 1) inducers. The present invention is also related a method of controlling the activity or the amount, or both the activity and the amount, of heme-oxygenase 1 in a mammalian subject. The definitions of the variables are provided herein.
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-
Page/Page column 62; 94
(2020/09/18)
-
- SUBSTITUTED 2-AZABICYCLO[3.1.1]HEPTANE AND 2-AZABICYCLO[3.2.1]OCTANE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS
-
There is provided a compound of formula (I), wherein L1 to L3, R1 to R4, X, A and B have meanings given in the description, and pharmaceutically acceptable salts, solvates and prodrugs thereof, which compounds are useful as antagonists of the orexin-1 and orexin-2 receptors or as selective antagonists of the orexin-1 receptor, and thus, in particular, in the treatment or prevention of inter alia substance dependence, addiction, anxiety disorders, panic disorders, binge eating, compulsive disorders, impulse control disorders, cognitive impairment and Alzheimer's disease.
- -
-
Page/Page column 131
(2019/03/17)
-
- 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
-
-
- Constructing magnetic Si-C-Fe hybrid microspheres for room temperature nitroarenes reduction
-
In this work, we present, for the first time, the synthesis and characterization of magnetic Si-C-Fe hybrid microspheres and their catalytic performance in room temperature reduction of 4-nitrophenol as a representative sustainable process for converting environmental pollutants to fine chemicals. The ferrocene-modified polydivinylbenzene (Fc-PDVB) precursor was synthesized by Pt-catalyzed hydrosilylation between the residual vinyl groups on the PDVB surface and 1,1′-bis (dimethylsilyl)ferrocene, where further pyrolysis led to the formation of Fe nanocrystal-containing Si-C-Fe hybrid microspheres. The precursor and hybrid microspheres were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), BET surface area/porosity, powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), magnetic properties and MAS solid-state NMR measurements. The ultimate microspherical catalyst exhibited nano- and meso-pores, a high specific surface area (i.e., 347.9 m2 g-1) and good ferromagnetic properties. Efficient catalytic activity (TOF: 0.163 s-1), 100% selectivity (to 4-aminophenol) and excellent reusability (with easy separation) have been delivered. The achieved microspheres outperform a number of nanomaterials such as supported noble metal particles, composites, monoliths and sheets. We have confirmed by DFT calculations that the activation of 4-nitrophenol via its weak non-covalent interaction with the sp2 carbon domain of Si-C-Fe hybrid microspheres contributed to the superior performance which can be extended to a range of nitrobenzenes.
- Zhang, Xiaofei,Chen, Lixin,Yun, Jin,Wang, Xiaodong,Kong, Jie
-
p. 10986 - 10997
(2017/07/11)
-
- Synthesis of 7 - fluoro - 6 - amino - 2 H - 1, 4 - benzoxazine - 3 (4 H) - one method (by machine translation)
-
The invention discloses a method for synthesizing 7 - fluoro - 6 - amino - 2 H - 1, 4 - benzoxazine - 3 (4 H) - one method, in order to 2, 4 - difluoroaniline as raw materials, through the substituted by hydroxyl, ether, nitration, hydrogenation reduction reaction to obtain the 7 - fluoro - 6 - amino - 2 H - 1, 4 - benzoxazine - 3 (4 H) - ketone (methylacetylene comprising diflufenican intermediate). Synthesis method of the invention, in order to 2, 4 - difluoroaniline as raw materials, cheap and easy to obtain, to a certain extent reduces the production cost; intermediate 1 without going through the high-pressure hydrogenation reaction can be with the chloroethyl acetate reaction ring, reduce the risk of the reaction; the nitration reaction is easy to control, decreasing the reaction, little impurity, raise the yield; hydrogenation reaction catalyst can be recovered, recycled, and reducing the cost; in addition the raw material is cheap, mild reaction, simple operation, facilitates large scale production. (by machine translation)
- -
-
Paragraph 0036; 0037; 0044; 0045
(2018/04/01)
-
- Comprehensive Analysis of Structure-Activity Relationships of α-Ketoheterocycles as sn-1-Diacylglycerol Lipase α Inhibitors
-
Diacylglycerol lipase α (DAGLα) is responsible for the formation of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the central nervous system. DAGLα inhibitors are required to study the physiological role of 2-AG. Previously, we identified the α-ketoheterocycles as potent and highly selective DAGLα inhibitors. Here, we present the first comprehensive structure-activity relationship study of α-ketoheterocycles as DAGLα inhibitors. Our findings indicate that the active site of DAGLα is remarkably sensitive to the type of heterocyclic scaffold with oxazolo-4N-pyridines as the most active framework. We uncovered a fundamental substituent effect in which electron-withdrawing meta-oxazole substituents increased inhibitor potency. (C6-C9)-acyl chains with a distal phenyl group proved to be the most potent inhibitors. The integrated SAR data was consistent with the proposed binding pose in a DAGLα homology model. Altogether, our results may guide the design of future DAGLα inhibitors as leads for molecular therapies to treat neuroinflammation, obesity, and related metabolic disorders.
- Janssen, Freek J.,Baggelaar, Marc P.,Hummel, Jessica J. A.,Overkleeft, Herman S.,Cravatt, Benjamin F.,Boger, Dale L.,Van Der Stelt, Mario
-
p. 9742 - 9753
(2016/01/12)
-
- ANTI-TRICHOPHYTIC ADHESIVE PATCH
-
According to the present invention, a patch for nail and/or skin having antifungal activity against dermatophytes, and having higher nail permeability can be provided. The patch for nail and/or skin for prevention or treatment of dermatophytosis comprises in a pressure sensitive adhesive layer a compound represented by the formula: wherein R1 represents a hydrogen atom, C1-6 alkyl, or trifluoromethyl; R2 represents a hydrogen atom, C1-6 alkyl, halogen, -COO(C1-6 alkyl), or (CH2)1-3COOR (R represents a hydrogen atom or C1-6 alkyl); R3 represents a hydrogen atom, C1-6 alkyl, amino, trifluoromethyl, or OR (R represents a hydrogen atom or C1-6 alkyl); R4 represents a hydroxyl group; R5 represents a hydrogen atom, C1-6 alkyl, a hydroxyl group, or halogen; R6 represents a hydrogen atom, C1-6 alkyl, trifluoromethyl, halogen, amino, -NRaRb, nitro, hydroxy-C1-6 alkyl, -CONRaRb, -COO(C1-6 alkyl), -COOH, -(CH2)1-3COOR, or ORa (R represents a hydrogen atom or C1-6 alkyl, Ra and Rb may be the same or different from each other, and each represent a hydrogen atom, C1-6 alkyl, or C1-6 acyl); R7 represents a hydrogen atom, C1-6 alkyl, -OR (R represents a hydrogen atom or C1-6 alkyl), or halogen; and R8 represents a hydrogen atom, C1-6 alkyl, a hydroxyl group, amino, or nitro, or a salt thereof.
- -
-
Paragraph 0152; 0195
(2015/06/17)
-
- PATCH FOR ANTI-DERMATOPHYTOSIS
-
A patch for nails or skin for prevention or treatment of dermatophytosis, containing a layer including a pressure sensitive adhesive layer and a compound represented by the formula: wherein R1 represents hydrogen, C1-16 alkyl, or trifluoromethyl; R2 represents hydrogen, C1-6 alkyl, halogen, —COO(C1-6 alkyl), or (CH2)1-3COOR; R3 represents hydrogen, C1-6 alkyl, amino, trifluoromethyl, or OR; R4 represents hydroxyl; R5 represents hydrogen, C1-6 alkyl, hydroxyl, or halogen; R6 represents hydrogen, C1-6 alkyl, trifluoromethyl, halogen, amino, —NRaRb, nitro, hydroxy-C1-6 alkyl, —CONRaRb, —COO(C1-6 alkyl), —COOH, —(CH2)1-3COOR, or ORa (Ra and Rb each represents hydrogen, C1-6 alkyl, or C1-6 acyl); R7 represents hydrogen, C1-6 alkyl, —OR, or halogen; R8 represents hydrogen, C1-6 alkyl, hydroxyl, amino, or nitro; and R represents hydrogen or C1-6 alkyl; or a salt thereof.
- -
-
Paragraph 0170-0172; 0298-0300
(2015/08/04)
-
- 2-Aminobenzoxazole ligands of the hepatitis C virus internal ribosome entry site
-
2-Aminobenzoxazoles have been synthesized as ligands for the hepatitis C virus (HCV) internal ribosome entry site (IRES) RNA. The compounds were designed to explore the less basic benzoxazole system as a replacement for the core scaffold in previously discovered benzimidazole viral translation inhibitors. Structure-activity relationships in the target binding of substituted benzoxazole ligands were investigated.
- Rynearson, Kevin D.,Charrette, Brian,Gabriel, Christopher,Moreno, Jesus,Boerneke, Mark A.,Dibrov, Sergey M.,Hermann, Thomas
-
supporting information
p. 3521 - 3525
(2014/07/22)
-
- TOPICAL LIQUID AGENT FOR THE TREATMENT OF DERMATOPHYTOSIS
-
A topical liquid agent for a nail and/or skin for prevention or treatment of dermatophytosis comprises a film-forming agent and a compound represented by the formula: wherein R1 represents hydrogen, C1-6 alkyl, or trifluoromethyl, R2 represents hydrogen, C1-6 alkyl, halogen, —COO(C1-6 alkyl), or (CH2)1-3COOR where R represents hydrogen or C1-6 alkyl, R3 represents hydrogen, C1-6 alkyl, amino, trifluoromethyl, or OR where R represents hydrogen or C1-6 alkyl, R4 represents hydroxyl, R5 represents hydrogen, C1-6 alkyl, hydroxyl, or halogen, R6 represents hydrogen, C1-6 alkyl, trifluoromethyl, halogen, amino, —NRaRb, nitro, hydroxy-C1-6 alkyl, —CONRaRb, —COO(C1-6 alkyl), —COOH, —(CH2)1-3COOR, or ORa where R represents hydrogen or C1-6 alkyl, Ra and Rb each represent hydrogen, C1-6 alkyl, or C1-6 acyl, R7 represents hydrogen, C1-6 alkyl, —OR where R represents hydrogen or C1-6 alkyl, or halogen, R8 represents hydrogen, C1-6 alkyl, hydroxyl, amino, or nitro, or a salt thereof.
- -
-
Paragraph 0140; 0141; 0142; 0268; 0269; 0270
(2014/02/16)
-
- Herbicidal Compositions
-
The present invention relates to a herbicidal composition comprising: A) at least one benzoxazinone compound of the formula I wherein the variables are as defined as given in the specification; and a safener of formula II as defined in the specification.
- -
-
Paragraph 0533-0535
(2013/10/22)
-
- TOPICAL ANTIFUNGAL AGENT
-
An anti-fungal agent for tinea comprising as active ingredient a compound having the skeleton of 2-(1H-pyrazol-1-yl)phenol represented by the following formula (I) or (II) or a salt thereof is provided
- -
-
Paragraph 0327; 0328; 0329
(2013/12/04)
-
- HERBICIDAL BENZOXAZINONES
-
The present invention provides benzoxazinones of formula I wherein R1 is hydrogen or halogen; R2 is hydrogen, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, C3/
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-
Page/Page column 77
(2012/04/17)
-
- HERBICIDAL COMPOSITIONS
-
The present invention relates to a herbicidal composition comprising: A) at least one benzoxazinone compound of the Formula (I), wherein the variables are as defined as given in the specification; and a safener of formula II as defined in the specificatio
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-
Page/Page column 69
(2012/06/30)
-
- High-efficiency tris(8-hydroxyquinoline)aluminum (Alq3) complexes for organic white-light-emitting diodes and solid-state lighting
-
Combinations of electron-withdrawing and -donating substituents on the 8-hydroxyquinoline ligand of the tris(8-hydroxyquinoline)aluminum (Alq 3) complexes allow for control of the HOMO and LUMO energies and the HOMO-LUMO gap responsible for emission from the complexes. Here, we present a systematic study on tuning the emission and electroluminescence (EL) from Alq3 complexes from the green to blue region. In this study, we explored the combination of electron-donating substituents on C4 and C6. Compounds 1-6 displayed the emission tuning between 478 and 526 nm, and fluorescence quantum yield between 0.15 and 0.57. The compounds 2-6 were used as emitters and hosts in organic light-emitting diodes (OLEDs). The highest OLED external quantum efficiency (EQE) observed was 4.6 %, which is among the highest observed for Alq3 complexes. Also, the compounds 3-5 were used as hosts for red phosphorescent dopants to obtain white light-emitting diodes (WOLED). The WOLEDs displayed high efficiency (EQE up to 19 %) and high white color purity (color rendering index (CRI≈85). Whiter than white: Electron-withdrawing and -donating substituents on the tris(8-hydroxyquinoline) AlIII (Alq3) complexes allow for control of the emission and electroluminescence from green (526 nm) to the blue region (487 nm), and of the fluorescence quantum yield (0.15-0.57). The compounds used as emitters in OLEDs show a maximum external quantum efficiency (EQE) of 4.6 %, which is among the highest observed for Alq3 complexes. The complexes were used in white-light emitting OLEDs achieving high efficiency (EQE ≈19 %) and high white color purity (CRI≈85).
- Perez-Bolivar, Cesar,Takizawa, Shin-Ya,Nishimura, Go,Montes, Victor A.,Anzenbacher, Pavel
-
supporting information; experimental part
p. 9076 - 9082
(2011/10/01)
-
- 3-(3,4-DIHYDRO-2H-BENZO [1,4]OXAZIN-6-YL)-1H-PYRIMIDIN-2,4-DIONE COMPOUNDS AS HERBICIDES
-
The present invention relates to uracils of formula (I) wherein the variables are defined according to the description, processes and intermediates for preparing the uracils of the formula (I), compositions comprising them and their use as herbicides, i.e
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Page/Page column 67
(2011/06/16)
-
- QU1NOLINE DERIVATIVES AND THEIR USES FOR RHINITIS AND URTICARIA
-
The present invention relates to compounds of formula (I) and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various diseases, such as allergic rhinitis.
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Page/Page column 46
(2010/09/17)
-
- Highly chemo- and regioselective reduction of aromatic nitro compounds catalyzed by recyclable copper(II) as well as cobalt(II) phthalocyanines
-
Copper/cobalt phthalocyanines were established for the first time as catalysts for the very efficient chemo- and regioselective reduction of aromatic nitro compounds to generate the corresponding amines. The selective reduction of nitro compounds was observed in the presence of a large range of functional groups such as aldehyde, keto, acid, amide, ester, halogen, lactone, nitrile and heterocyclic functional groups. Furthermore, the present method was found to be highly regioselective towards the reduction of aromatic dinitro compounds in a short time with high yields. In most of the cases the conversion and selectivity were >99% as monitored by GC-MS. The reduction mechanism was elucidated by UV-vis and electrospray ionization quadrupole time-of-flight tandem mass spectrometry.
- Sharma, Upendra,Kumar, Praveen,Kumar, Neeraj,Kumar, Vishal,Singh, Bikram
-
experimental part
p. 1834 - 1840
(2010/10/21)
-
- COMPOUND HAVING 11 ?-HSD1 INHIBITORY ACTIVITY
-
The present invention provides compounds having excellent 11β-HSD1 inhibitory activity. A compound represented by the following formula (I): [wherein X1 represents an oxygen atom, or the formula -(CR11R12)p-, etc., Y1 represents a hydrogen atom, a hydroxyl group, etc., Z1 represents an oxygen atom or the formula -(NR14)-, R1 represents a hydrogen atom, a halogen atom, a cyano group, a C1-4 alkyl group, a C1-4 alkyl group substituted with 1 to 3 halogen atoms, a C1-4 alkoxy group, a C1-4 alkoxycarbonyl group, a carboxyl group, a carbamoyl group, or an amino group, and m represents an integer of 1 or 2, and R2 represents a hydrogen atom or a C1-4 alkyl group, and n represents an integer of 1 or 2].
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Page/Page column 14-15
(2010/04/25)
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- HERBICIDAL BENZOXAZINONES
-
The present invention relates to benzoxazinones of the general formula (I) wherein the variables are defined according to the description, processes and intermediates for preparing the benzoxazinones of the formula (I), compositions comprising them and th
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-
Page/Page column 87; 88
(2010/12/31)
-
- SUBSTITUTED ACIDS FOR THE TREATMENT OF RESPIRATORY DISEASES
-
The invention relates to substituted acids of formula (I), where T,W,X,Y,Z, R1 and R2 as defined in the claims, as useful pharmaceutical compounds for treating asthma and rhinitis, pharmaceutical compositions containing them, and a processes for their preparation.
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Page/Page column 41
(2010/02/15)
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- PYRIDINAMIDE DERIVATIVE AS KINASE INHIBITORS
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The invention relates to substituted arylamide derivatives of formula (I), to the production and use thereof for the production of a medicament for the treatment of diseases, in particular tumours and/or diseases which are provoked, transmitted and/or propagated by angiogenesis. Compounds of formula (I) are active inhibitors of tyrosine kinases, in particular TIE-2 and VEGFR, and the Raf-kinases.
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Page/Page column 53
(2010/02/14)
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- NOVEL ALKYNYL DERIVATIVES AS MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
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The present invention relates to novel compounds of formula (I) wherein W, n, X and W’ are defined in the description; invention compounds are modulators of metabotropic glutamate receptors - subtype 5 (“mGluR5”) which are useful for the treatment of central nervous system disorders as well as other disorders modulated by mGluR5 receptors.
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Page/Page column 121-122
(2008/06/13)
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- IL-8 RECEPTOR ANTAGONISTS
-
The present invention relates to novel compounds and a novel use of phenyl ureas in the treatment of disease states mediated by the chemokine Interleukin-8 (IL-8).
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-
-
- Fused thiophene compounds and medicinal use thereof
-
A condensed thiophene compound of the formula (I) wherein each symbol is as defined in the specification, a pharmaceutically acceptable salt thereof and hydrates thereof. The compound of the formula (I) of the present invention is useful as a novel antipsychotic agent which is effective for both positive symptoms and negative symptoms of schizophrenia, which is associated with less side effects such as extrapyramidal motor disorder and the like and which is less associated with serious side effects such as agranulocytosis and the like. In addition, this compound is also useful as a therapeutic agent of Alzheimer's disease and manic-depressive illness.
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-
- Pyrazole derivatives and COX inhibitors containing them
-
PCT No. PCT/JP98/01664 Sec. 371 Date Oct. 7, 1999 Sec. 102(e) Date Oct. 7, 1999 PCT Filed Apr. 10, 1998 PCT Pub. No. WO98/46594 PCT Pub. Date Oct. 22, 1998The purpose is to provide anti-inflammatory agents which have potent pharmacological actions and exert a selective inhibitory activity on COX-2, thereby being expected to reduce adverse effects such as disorders in gastric mucosa. The present invention encompasses a compound of the formula (1): wherein R1 is hydrogen or halogen, R2 and R3 are each independently hydrogen, halogen, lower alkyl, lower alkoxy, hydroxy or lower alkanoyloxy, R4 is lower haloalkyl or lower alkyl, X is sulfur, oxygen or NH, and Y is lower alkylthio, lower alkylsulfonyl or sulfamoyl, which exerts superior anti-inflammatory activity, and highly inhibits COX-2 induced in inflamed sites, with less inhibitory action on COX-1 present in stomach, kidney, etc. Pharmaceutical agents comprising the compound of the present invention are provided as selective COX-2 inhibitors, and anti-inflammatory agents rarely accompanying adverse actions including attacks on gastric mucosa.
- -
-
-
- IL-8 RECEPTOR ANTAGONISTS
-
This invention relates to the novel use of phenyl ureas in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).
- -
-
-
- IL-8 RECEPTOR ANTAGONISTS
-
This invention relates to novel compounds and a novel use of phenyl ureas in the treatment of disease scates mediated by the chemokine, Interleukin-8 (IL-8). In particular, this invention relates to the novel compounds of Formula (Ia) and their use in treating chemokine mediated diseases wherein the chemokine binds to an IL-8 a or b receptor. Compounds of Formula (Ia) are represented by the structure: STR1 wherein interalia, X is oxygen or sulfur;Rb is NR 6 R. sub.7, alkcyl, aryl, arylC 1-4 alkyl, aryl C 2-4 alkenyl, heteroaryl, heteroarylC 1-4 alkyl, heteroarylC 2-4 alkenyl, heterocyclic or heterocyclic C 1-4 alkyl, or a heterocyclic C 2-4 alkenyl moiety, camphor, all of which may be optionally substituted; R 1 is independently selected from hydrogen; halogen; nitro; cyano; C 1-10 alkyl; halosubstituted C 1-10 alkyl; C 2-10 alkoxy; halosubstituted C 1-10 alkoxy; azide; (CR. sub.8 R 8)q S(O) t R 4 ; hydroxy; hydroxy substituted C 1-4 alkyl; aryl; aryl C 1-4 alkyl; aryl C 2-10 alkenyl; aryloxy; aryl C 1-4 alkyloxy; heteroaryl; heteroarylalkyl; heteroaryl C 2-10 alkenyl; heteroaryl C 1-4 alkyloxy; heterocyclic; heterocyclic C 1-4 alkyl; heterocyclicC 1-4 alkyloxy; heterocyclic C 2-10 alkenyl; q is 0 or an integer having a value of 1 to 10; n is an integer having a value of 1 to 3;m is an integer having a value of 1 to 3; Y is hydrogen; halogen; nitro; cyano; halosubstituted C 1-10 alkyl; C 1-10 alkyl; C 2-10 alkenyl C. sub.1-10 alkoxy; halosubstituted C 1-10 alkoxy; azide; (CR 8 R. sub.8)qS(O) t R 4, (CR 8 R 8)qOR 4 ; hydorxy; hydroxy substituted C. sub.1-4 alkyl; aryl; aryl C 1-4 alkyl; aryloxy; arylC. sub.1-4 alkyloxy; aryl C 2-10 alkenyl; heteroaryl; heteroarylalkyl; heteroaryl C 1-4 alkyloxy; heteroaryl C 2-10 alkenyl; heterocyclic, heterocyclic C 1-4 alkyl; heterocyclicC 2-10 alkenyl;or a pharmaceutically acceptable salt thereof.
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-
-
- Herbicidal glutarimides
-
This invention relates to glutarimide compounds exhibiting herbicidal activity having the structure STR1 wherein A is carbonyl, thiocarbonyl or methylene, A1 is carbonyl or methylene, Q is O or (CH2)n where n is 0 or 1, D is CH or N and R, R1, R2, T, X, Y and Z are as defined within, compositions containing these compounds and methods of using these compounds as herbicides and algicides.
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-
-
- Herbicidal glutaramic acids and derivatives
-
This invention relates to glutaramic acids and derivatives exhibiting herbicidal activity having the structure STR1 wherein A is a carboxylic acid or a derivative thereof, D is CH or N, and R, R1, R2, T, X, Y, and Z are as defined within, compositions containing these compounds and methods of controlling weeds with these compounds.
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-
-
- Acid-catalyzed amino-migration of O-phenylhydroxylamines
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The mechanism of amino-migration of O-phenylhydroxylamine (1a) was studied. It was found that 1 rearranges to give 2-aminophenol (50%) and 4-aminophenol (7%) in trifluoroacetic acid (TFA). The predominance of the ortho rearrangement of 1 clearly distinguishes this process from the Bamberger rearrangement. From cross-coupling experiments employing stable isotopes, it was clarified that the ortho rearrangement proceeds intramolecularly and the para rearrangement involves both intra- and intermolecular processes. Good first-order kinetics were obtained for the rearrangement. The Hammett plot (σ+) with a large negative slope (ρ = -7.8) indicates that initial heterolytic N-O bond cleavage of 1 occurs and generates a positive charge on the oxygen atom with considerable delocalization into the aromatic ring. An ion-molecule pair involving a phenoxenium ion and an ammonia molecule as an intermediate rationalizes all of the results. In this pair, intramolecular combination to the ortho position proceeds preferentially over that to the para position. Formation of catechol and hydroquinone can be explained in terms of nucleophilic attack of TFA on the phenoxenium ion in a solvent-separated pair.
- Haga, Naoki,Endo, Yasuyuki,Kataoka, Ken-Ichiro,Yamaguchi, Kentaro,Shudo, Koichi
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p. 9795 - 9806
(2007/10/02)
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