- 4-AMINOBUT-2-ENAMIDE DERIVATIVES AND SALTS THEREOF
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The present invention provides an antitumor agent comprising a compound or a pharmaceutically acceptable salt thereof that covalently binds to GTP-bound KRASG12C as an active ingredient.
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Paragraph 0412
(2021/05/07)
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- Thiazole ring-containing amide compounds as well as preparation method and application thereof
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The invention discloses thiazole ring-containing amide compounds as well as a preparation method and application thereof, and belongs to the field of chemical technologies and pesticides. According to the present invention, p-phenylenediamine is adopted as a raw material to synthesize a series of the thiazole ring-containing amide compounds, and the synthesized thiazole ring-containing amide compounds have good inhibition effects on Xanthomonas oryzae pv.Oryza (Xoo), Xanthomonas oryzae pv.Oryzcola (Xoc) and Xanthomonas axonophora pv.Citri (Xac) in agricultural diseases and insect pests, and can be used for preparing the anti-plant bacterium agent.
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Paragraph 0044; 0051; 0058; 0061; 0122; 0127; 0206; 0211
(2021/06/23)
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- Polysubstituted Ligand Framework for Color Tuning Phosphorescent Iridium(III) Complexes
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A series of ligands have been synthesized based upon a polysubstituted 2-phenylquinoxaline core structure. These ligands introduce different combinations of fluorine and methyl substituents on both the phenyl and quinoxaline constituent rings. The resultant investigation of these species as cyclometalating agents for Ir(III) gave cationic complexes of the form [Ir(C^N)2(bipy)]PF6 (where C^N = cyclometalating ligand; bipy = 2,2′-bipyridine). X-ray crystallographic studies were conducted on four complexes and each revealed the expected distorted octahedral geometry based upon a cis-C,C and trans-N,N ligand arrangement at Ir(III). Supporting computational studies predict that each of the complexes share the same general descriptions for the frontier orbitals. TD-DFT calculations suggest MLCT contributions to the lowest energy absorption and a likely MLCT/ILCT/LLCT nature to the emitting state. Experimentally, the complexes display tunable luminescence across the yellow-orange-red part of the visible spectrum (λem = 579-655 nm).
- Beames, Joseph M.,Coles, Simon J.,Elgar, Christopher E.,Fitzgerald, Sophie A.,Horton, Peter N.,Otaif, Haleema Y.,Pope, Simon J. A.,Sawicka, Natalia
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p. 15467 - 15484
(2021/10/20)
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- Novel BuChE-IDO1 inhibitors from sertaconazole: Virtual screening, chemical optimization and molecular modeling studies
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In our effort towards the identification of novel BuChE-IDO1 dual-targeted inhibitor for the treatment of Alzheimer's disease (AD), sertaconazole was identified through a combination of structure-based virtual screening followed by MM-GBSA rescoring. Preliminary chemical optimization was performed to develop more potent and selective sertaconazole analogues. In consideration of the selectivity and the inhibitory activity against target proteins, compounds 5c and 5d were selected for the next study. Further modification of compound 5c led to the generation of compound 10g with notably improved selectivity towards BuChE versus AChE. The present study provided us with a good starting point to further design potent and selective BuChE-IDO1 inhibitors, which may benefit the treatment of late stage AD.
- Zhou, You,Lu, Xin,Du, Chenxi,Liu, Yijun,Wang, Yifan,Hong, Kwon Ho,Chen, Yao,Sun, Haopeng
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-
- BuChE-IDO1 inhibitor as well as preparation method and application thereof
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The invention relates to the field of medicines, and particularly discloses a BuChE-IDO1 inhibitor as well as a preparation method and application thereof. The 7-chlorine-3-substituted benzothiophene part of sertaconazole is chemically modified, the influence of the 7-chlorine-3-substituted benzothiophene part of sertaconazole on the in-vitro inhibitory activity of AChE, BuChE and IDO1 is explored, the target compound is further optimized, and the technical problems that an existing BuChE-IDO1 inhibitor is poor in pertinence and safety are solved. What is explored is that an appropriate substituent group introduced to a 2-benzothiazole ring can form additional interaction with surrounding amino acids and heme iron, so that the binding affinity of the analogue with BuChE and IDO1 is increased, and a new idea is broadened for more efficient and targeted treatment of advanced AD diseases.
- -
-
Paragraph 0070-0072; 0090-0091
(2021/04/26)
-
- Microwave-assisted synthesis and luminescent activity of imidazo[1,2-a]pyridine derivatives
-
In this work, a series of phenacyl bromide derivatives was synthesized and employed as key intermediate for the synthesis of substituted imidazo[1,2-a]pyridines. First, phenacyl bromide molecules were obtained from the bromination reaction of acetophenones assisted by microwave irradiation, obtaining the products 4a-v in a 15 minutes reaction with yields in the range of 50% to 99%. Subsequently, the conjugation of these molecules with 2-aminopyridine conduced to the production of imidazo[1,2-a]pyridine derivatives (7a-v) in a 60-second reaction with yields of 24% to 99%. Improved yields were determined with respect to those obtained with more tedious methodologies like thermally and mechanically assisted routes. Intense luminescence emissions in the purple and blue regions of the electromagnetic spectra were observed under UV excitation according to the nature of the substituents. This environmentally friendly methodology is expected to constitute an important class of organic compounds for the development of biomarkers, photochemical sensors, and medicinal applications.
- Rodríguez, Juan C.,Maldonado, Rony A.,Ramírez-García, Gonzalo,Díaz Cervantes, Erik,de la Cruz, Fabiola N.
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p. 2279 - 2287
(2020/03/16)
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- Usnic Acid Enaminone-Coupled 1,2,3-Triazoles as Antibacterial and Antitubercular Agents
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(+)-Usnic acid, a product of secondary metabolism in lichens, has displayed a broad range of biological properties such as antitumor, antimicrobial, antiviral, anti-inflammatory, and insecticidal activities. Interested by these pharmacological activities and to tap into its potential, we herein present the synthesis and biological evaluation of new usnic acid enaminone-conjugated 1,2,3-triazoles 10-44 as antimycobacterial agents. (+)-Usnic acid was condensed with propargyl amine to give usnic acid enaminone 8 with a terminal ethynyl moiety. It was further reacted with various azides A1-A35 under copper catalysis to give triazoles 10-44 in good yields. Among the synthesized compounds, saccharin derivative 36 proved to be the most active analogue, inhibiting Mycobacterium tuberculosis (Mtb) at an MIC value of 2.5 μM. Analogues 16 and 27, with 3,4-difluorophenacyl and 2-acylnaphthalene units, respectively, inhibited Mtb at MIC values of 5.4 and 5.3 μM, respectively. Among the tested Gram-positive and Gram-negative bacteria, the new derivatives were active on Bacillus subtilis, with compounds 18 [3-(trifluoromethyl)phenacyl] and 29 (N-acylmorpholinyl) showing inhibitory concentrations of 41 and 90.7 μM, respectively, while they were inactive on the other tested bacterial strains. Overall, the study presented here is useful for converting natural (+)-usnic acid into antitubercular and antibacterial agents via incorporation of enaminone and 1,2,3-triazole functionalities.
- Bangalore, Pavan K.,Vagolu, Siva K.,Bollikanda, Rakesh K.,Veeragoni, Dileep K.,Choudante, Pallavi C.,Misra, Sunil,Sriram, Dharmarajan,Sridhar, Balasubramanian,Kantevari, Srinivas
-
supporting information
p. 26 - 35
(2020/01/03)
-
- Synthesis and Antibacterial Evaluation of N-phenylacetamide Derivatives Containing 4-Arylthiazole Moieties
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A series of new N-phenylacetamide derivatives containing 4-arylthiazole moieties was designed and synthesized by introducing the thiazole moiety into the amide scaffold. The structures of the target compounds were confirmed by 1H-NMR, 13C-NMR and HRMS. Their in vitro antibacterial activities were evaluated against three kinds of bacteria-Xanthomonas oryzae pv. Oryzae (Xoo), Xanthomonas axonopodis pv. Citri (Xac) and X.oryzae pv. oryzicola (Xoc)-showing promising results. The minimum 50% effective concentration (EC50) value of N-(4-((4-(4-fluoro-phenyl)thiazol-2-yl)amino)phenyl)acetamide (A1) is 156.7 μM, which is superior to bismerthiazol (230.5 μM) and thiodiazole copper (545.2 μM). A scanning electron microscopy (SEM) investigation has confirmed that compound A1 could cause cell membrane rupture of Xoo. In addition, the nematicidal activity of the compounds against Meloidogyne incognita (M. incognita) was also tested, and compound A23 displayed excellent nematicidal activity, with mortality of 100% and 53.2% at 500 μg/mL and 100 μg/mL after 24 h of treatment, respectively. The preliminary structure-activity relationship (SAR) studies of these compounds are also briefly described. These results demonstrated that phenylacetamide derivatives may be considered as potential leads in the design of antibacterial agents.
- Jin, Linhong,Lu, Hui,Wang, Lei,Zhou, Xia
-
-
- Development of triazolothiadiazine derivatives as highly potent tubulin polymerization inhibitors: Structure-activity relationship, in vitro and in vivo study
-
Based on our prior work, we reported the design, synthesis, and biological evaluation of fifty-two new triazolothiadiazine-based analogues of CA-4 and their preliminary structure-activity relationship. Among synthesized compounds, Iab was found to be the most potent derivative possessing IC50 values ranging from single-to double-digit nanomolar in vitro, and also exhibited excellent selectivity over the normal human embryonic kidney HEK-293 cells (IC50 > 100 μM). Further mechanistic studies revealed that Iab significantly blocked tubulin polymerization and disrupted the intracellular microtubule network of A549 cells. Moreover, Iab induced G2/M cell cycle arrest by regulation of p-cdc2 and cyclin B1 expressions, and caused cell apoptosis through up-regulating cleaved PARP and cleaved caspase-3 expressions, and down-regulating of Bcl-2. Importantly, in vivo, Iab effectively suppressed tumor growth of A549 lung cancers in a xenograft mouse model without obvious signs of toxicity, confirming its potential as a promising candidate for cancer treatment.
- Ma, Weifeng,Chen, Peng,Huo, Xiansen,Ma, Yufeng,Li, Yanhong,Diao, Pengcheng,Yang, Fang,Zheng, Shengquan,Hu, Mengjin,You, Wenwei,Zhao, Peiliang
-
-
- Discovery of novel potent GPR40 agonists containing imidazo[1,2-a]pyridine core as antidiabetic agents
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Free fatty acid receptor 1 (FFA1 or GPR40) has been studied for many years as a target for the treatment of type 2 diabetes mellitus. In order to increase potency and reduce hepatotoxicity, a series of novel compounds containing imidazo[1,2-a]pyridine sca
- Ye, Zhiwen,Liu, Chunxia,Zou, Feng,Cai, Yan,Chen, Bin,Zou, Yuxing,Mo, Jiaxian,Han, Ting,Huang, Wenlong,Qiu, Qianqian,Qian, Hai
-
-
- Diaryl-containing imidazole compound and preparation method and medical application thereof
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The invention discloses a diaryl-containing imidazole compound. The invention further discloses application of the diaryl-containing imidazole compound to preparation of drugs for preventing or treating Alzheimer's disease. The inventor screens butyrylcholine esterase and IDO1 as carriers for inhibiting the activity to evaluate the effect of the diaryl imidazole compound to treat Alzheimer's disease, and finds that the diaryl imidazole compound has good in vitro activity, and can be further developed as a precursor substance for performing the Alzheimer's disease resistant effect by inhibitingthe activity of cholinesterase. (The formula is shown in the description).
- -
-
Paragraph 0066; 0067; 0068
(2019/02/21)
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- Novel arylimino thiazole compound, preparation method and uses thereof
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The present invention relates to a compound with antibacterial synergy activity, a preparation and uses thereof, particularly to a novel arylimino thiazole compound, a preparation method and uses thereof, and specifically discloses a class of compounds represented by a formula (I) or optical isomers, cis-trans isomers or pharmaceutically acceptable salts thereof, a preparation method and uses thereof. The invention further discloses a pharmaceutical composition containing the compound. The compound of the present invention can effectively enhance the antibacterial activity of antibiotics, andcan be used for treating antibiotic-resistant bacteria. The formula (I) is defined in the specification.
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Paragraph 0162; 0166; 0167; 0168
(2018/03/28)
-
- Antibacterial synergist, preparation method and uses thereof
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The present invention relates to an antibacterial synergist, a preparation method and uses thereof, and specifically discloses a compound represented by a formula (I) and having antibacterial synergyactivity, or an optical isomer, a cis-trans isomer or a pharmaceutically acceptable salt thereof, and a preparation method thereof. The present invention further discloses a medical composition containing the compound, and uses thereof. According to the present invention, the compound can effectively enhance the antibacterial activity of polymyxin B against Acinetobacter baumannii and Klebsiella pneumoniae, and can be used for the antibacterial treatment of pathogenic bacteria insensitive to polymyxin or having low bacterial inhibition activity. The formula (I) is defined in the specification.
- -
-
Paragraph 0219; 0220; 0221; 0222
(2018/03/28)
-
- Halides Held by Bifurcated Chalcogen-Hydrogen Bonds. Effect of μ(S,N-H)Cl Contacts on Dimerization of Cl(carbene)PdII Species
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The reaction of cis-[PdCl2(CNCy)2] (1) with thiazol-2-amines (2-10) leads to the C,N-chelated diaminocarbene-like complexes [PdCl{C(N(H)4,5-R2-thiazol-2-yl)NHCy}(CNCy)] (11-14; 82-91%) in the case of 4,5-R2-thiazol-2-amines (R, R = H, H (2), Me, Me (3), -(CH2)4- (4)) and benzothiazol-2-amine (5) or gives the diaminocarbene species cis-[PdCl2{C(N(H)Cy)N(H)4-R-thiazol-2-yl}(CNCy)] (15-19; 73-93%) for the reaction with 4-aryl-substituted thiazol-2-amines (R = Ph (6), 4-MeC6H4 (7), 4-FC6H4 (8), 4-ClC6H4 (9), 3,4-F2C6H3 (10)). Inspection of the single-crystal X-ray diffraction data for 15-17 and 19 suggests that the structures of all these species exhibit previously unrecognized bifurcated chalcogen-hydrogen bonding μ(S,N-H)Cl and also PdII···PdII metallophilic interactions. These noncovalent interactions collectively connect two symmetrically located molecules of 15-17 and 19, resulting in their solid-state dimerization. The existence of the μ(S,N-H)Cl system and its strength (6-9 kcal/mol) were additionally verified/estimated by a Hirshfeld surface analysis and DFT calculations combined with a topological analysis of the electron density distribution within the formalism of Bader's theory (AIM method) and NBO analysis. The observed noncovalent interactions are jointly responsible for the dimerization of 15-19 not only in the solid phase but also in CHCl3 solutions, as predicted theoretically by DFT calculations and confirmed experimentally by FTIR, HRESI-MS, 1H NMR, and diffusion coefficient NMR measurements. Available CCDC data were processed under the new moiety angle, and the observed μ(S,E-H)Cl systems were classified accordingly to E (E = N, O, C) type atoms.
- Mikherdov, Alexander S.,Novikov, Alexander S.,Kinzhalov, Mikhail A.,Boyarskiy, Vadim P.,Starova, Galina L.,Ivanov, Alexander Yu.,Kukushkin, Vadim Yu.
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supporting information
p. 3420 - 3433
(2018/03/25)
-
- Synthesis and bioevaluation of N,4-diaryl-1,3-thiazole-2-amines as tubulin inhibitors with potent antiproliferative activity
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A series of N,4-diaryl-1,3-thiazole-2-amines containing three aromatic rings with an amino linker were designed and synthesized as tubulin inhibitors and evaluated for their antiproliferative activity in three human cancer cell lines. Most of the target compounds displayed moderate antiproliferative activity, and N-(2,4-dimethoxyphenyl)-4-(4-methoxyphenyl)-1,3-thiazol-2-amine (10s) was determined to be the most potent compound. Tubulin polymerization and immunostaining experiments revealed that 10s potently inhibited tubulin polymerization and disrupted tubulin microtubule dynamics in a manner similar to CA-4. Moreover, 10s effectively induced SGC-7901 cell cycle arrest at the G2/M phase in both concentrationand time-dependent manners. The molecular docking results revealed that 10s could bind to the colchicine binding site of tubulin.
- Sun, Maolin,Xu, Qile,Xu, Jingwen,Wu, Yue,Wang, Yueting,Zuo, Daiying,Guan, Qi,Bao, Kai,Wang, Jian,Wu, Yingliang,Zhang, Weige
-
-
- Substituted imidazole-1-vinyl compound and use thereof
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The invention relates to a substituted imidazole-1-ethylene compound as well as a preparation and an application thereof. The substituted imidazole-1-ethylene compound is a compound shown as a formula I, or salts thereof formed with medicinal acids or bases. According to the antifungal activity test performed on eight clinical fungi by the compound provided in the invention, a good fungus killing effect is achieved. The compound can serve as a novel broad-spectrum antifungal activity compound and is developed into antifungal medicines, disinfectants or feed additives.
- -
-
Paragraph 0051; 0198-0201
(2016/10/27)
-
- HEPATITIS B ANTIVIRAL AGENTS
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The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: [in-line-formulae]X-A-Y-Z-L-R1??(I)[/in-line-formulae] which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
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Paragraph 0205
(2016/12/12)
-
- Synthesis, activity, and docking study of phenylthiazole acids as potential agonists of PPARγ
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Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-mediated transcription factor playing key roles in glucose and lipid homeostasis, and PPARγ ligands possess therapeutic potential in these as well as other areas. In this study, a series of phenylthiazole acids have been synthesized and evaluated for agonistic activity by a convenient fluorescence polarization-based PPARγ ligand screening assay. Compound 4t, as a potential PPARγ agonist with half maximal effective concentration (EC50) 0.75±0.20 μM, exhibited in vitro potency comparable with a 0.83±0.14 μM of the positive control rosiglitazone. Molecular docking and molecular dynamics simulations indicated that phenylthiazole acid 4t interacted with the amino acid residues of the active site of the PPARγ complex in a stable manner, consistent with the result of the in vitro ligand assay.
- Ma, Liang,Wang, Taijin,Shi, Min,Ye, Haoyu
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p. 1807 - 1815
(2016/06/09)
-
- Synthesis and antimicrobial activity evaluation of new dithiocarbamate derivatives bearing thiazole/benzothiazole rings
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The synthesis of 2-(substituted phenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A1-A24) derivatives and 2-(4-substituted thiazol-2-ylamino)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (B1-B14) derivatives was undertaken starting from the potassium salt of 4-(2-pyrimidinyl)piperazine dithiocarbamate. The structures of the obtained compounds were elucidated by1H NMR,13C NMR, MS spectral data, and elemental analysis. The antimicrobial activity of the thirty eight newly synthesized compounds were tested against 12 microorganism strains using the microdilution technique. Compounds 2-(4-ethoxycarbonylthiazol-2-ylamino)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (B12), 2-(3-fluorophenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A18) and 2-(3,4-difluorophenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A21) were determined to possess high antimicrobial activity.
- Yurtta?, Leyla,?zkay, Yusuf,Duran, Murat,Turan-Zitouni, Gülhan,?zdemir, Ahmet,Cantürk, Zerrin,Kü?üko?lu, Kaan,Kaplanc?kl?, Zafer As?m
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p. 1166 - 1173
(2016/07/27)
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- Synthesis and in-vitro evaluation of 2-amino-4-arylthiazole as inhibitor of 3D polymerase against foot-and-mouth disease (FMD)
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Foot-and-mouth disease (FMD) is a highly contagious vesicular disease of livestock caused by a highly variable RNA virus, foot-and-mouth disease virus (FMDV). One of the targets to suppress expansion of and to control FMD is 3D polymerase (FMDV 3Dpol). In this study, 2-amino-4-arylthiazole derivatives were synthesized and evaluated for their inhibitory activity against FMDV 3Dpol. Among them, compound 20i exhibited the most potent functional inhibition (IC50 = 0.39μM) of FMDV 3D polymerase and compound 24a (EC50=13.09 μM) showed more potent antiviral activity than ribavirin (EC50=1367 μM) and T1105 (EC50=347 μM) with IBRS-2 cells infected by the FMDV O/SKR/2010 strain.
- Jeong, Kwi-Wan,Lee, Jung-Hun,Park, Sun-Mi,Choi, Joo-Hyung,Jeong, Dae-Youn,Choi, Dong-Hwa,Nam, Yeonju,Park, Jong-Hyeon,Lee, Kwang-Nyeong,Kim, Su-Mi,Ku, Jin-Mo
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p. 387 - 397
(2015/09/01)
-
- Design, Synthesis and Biological Evaluation of Imidazo[1,2-a]pyridine Derivatives as Novel DPP-4 Inhibitors
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A new series of DPP-4 inhibitors with imidazo[1,2-a]pyridine scaffold were designed by exploiting scaffold hopping strategy and docking study. Based on docking binding model, structural modifications of 2-benzene ring and pyridine moieties of compound 5a led to the identification of compound 5d with 2, 4-dichlorophenyl group at the 2-position as a potent (IC50 = 0.13 μm), selective (DPP-8/DPP-4 = 215 and DPP-9/DPP-4 = 192) and in vivo efficacious DPP-4 inhibitor. Further, molecular docking revealed that compound 5d could retain key binding features of DPP-4 with the pyridine moiety of imidazo[1,2-a]pyridine ring providing an additional π-π interaction with Phe357 of DPP-4. Compound 5d might be a promising lead for further development of novel DPP-4 inhibitor treating T2DM.
- Li, Qing,Zhou, Muxing,Han, Li,Cao, Qing,Wang, Xinning,Zhao, Leilei,Zhou, Jinpei,Zhang, Huibin
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p. 849 - 856
(2015/10/06)
-
- Discovery of functionalized bisimidazoles bearing cyclic aliphatic-phenyl motifs as HCV NS5A inhibitors
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This Letter describes the discovery of a number of functionalized bisimidazoles bearing a cyclohexylphenyl, piperidylphenyl, or bicyclo[2,2,2]octylphenyl motif as HCV NS5A inhibitors. Compounds 2c, 4b and 6 have demonstrated low single-digit nM potency in gt-1a replicon and double-digit pM potency in gt-1b replicon, respectively. Moreover, both 4b and 6 have, respectively, exhibited good oral bioavailability in rats with a favorable liver/plasma ratio of the drug concentration.
- Zhong, Min,Peng, Eric,Huang, Ningwu,Huang, Qi,Huq, Anja,Lau, Meiyen,Colonno, Richard,Li, Leping
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p. 5731 - 5737
(2015/01/08)
-
- Synthesis and initial biological evaluation of substituted 1-phenylamino-2-thio-4,5-dimethyl-1H-imidazole derivatives
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In this work, some new 2-[(4,5-dimethyl-1-(arylamino)-1H-imidazol-2-yl) thio]-1-(aryl)ethanone derivatives were synthesized and investigated for their antibacterial, antifungal and anticancer activities. Toxicity of the most effective compounds was established by performing Brine-Shrimp lethality assay. Antifungal activity of the compounds was found to be higher than antibacterial and anticancer activities of the compounds.
- Yurttas, Leyla,Duran, Murat,Demirayak, Seref,Gencer, Huelya Karaca,Tunali, Yagmur
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supporting information
p. 6764 - 6768
(2014/01/06)
-
- Design, synthesis and biological evaluation of thiazole- and indole-based derivatives for the treatment of type II diabetes
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Present studies have shown that the lipid carrier has a significant role in several aspects of metabolic syndrome in A-FABP/ap2-deficient mice, including type 2 diabetes and atherosclerosis. 38 Thiazole- and indole-based derivatives were synthesized and investigated for their inhibitory effects on the production of LPS-stimulated TNF-α. Among them, 12b exhibited an excellent inhibitory efficiency compared to BMS309403 (95% vs. 85%) at the concentration of 10 μM and a binding affinity for ap2 with the apparent Ki values 33 nM. Oral administration of 12b at a dosage of 50 mg/kg effectively reduced the levels of plasma blood glucose, triglycerides, insulin, total cholesterol and alanine aminotransferase in high-fat/diet-induced obesity model. The results highlighted that 12b was a potent anti-diabetic agent.
- Xu, Qinyuan,Huang, Li,Liu, Juan,Ma, Liang,Chen, Tao,Chen, Jinying,Peng, Fei,Cao, Dong,Yang, Zhuang,Qiu, Neng,Qiu, Jingxiang,Wang, Guangcheng,Liang, Xiaolin,Peng, Aihua,Xiang, Mingli,Wei, Yuquan,Chen, Lijuan
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experimental part
p. 70 - 81
(2012/07/30)
-
- Synthesis, spectral characterization and biological evaluation of a novel series of 6-arylsubstituted-3-[2-(4-substitutedphenyl)propan-2-yl]-7H-[1,2,4] triazolo[3,4-b][1,3,4]thiadiazines
-
On account of the reported anticancer activity of triazolothiadiazines, we have synthesized a novel series of 6-arylsubstituted-3-[2-(4-substitutedphenyl) propan-2-yl]-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines and tested for in-vitro cytotoxicity by trypan blue exclusion and MTT assay. These compounds were also evaluated for their in-vivo anthelmintic activity, as well as in-vitro antimicrobial studies. Amongst the tested compounds, the compound 7j was the most promising cytotoxic agent with IC50 value of 10.54 μM in MCF-7 cells. The compounds 7l and 7q exhibited excellent anthelmintic activity. The compounds 7d, 7f, 7j, 7l, 7o, 7p and 7r showed good antibacterial activity, whereas compounds 7e and 7k exhibited excellent antifungal activity. The structures of newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR and LCMS analysis.
- Puthiyapurayil, Pushpan,Poojary, Boja,Chikkanna, Chandrashekhar,Buridipad, Sunil Kumar
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p. 407 - 416
(2013/01/15)
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- PYRIMIDINE-2,4,6-TRIONES FOR USE IN THE TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS
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The present invention relates to the identification of inventive pyrimidine-2,4,6- triones (PYT compounds) and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the inventive PYT compounds.
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Page/Page column 109
(2010/11/18)
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- Aryl-and heteroaryl-substituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine and serotonin
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The present invention relates to a method of treating disorders by administering to a patient in need of such treatment a therapeutically effective amount of a compound of formula (I): wherein R1-R8 are as described herein, R4 being aryl or heteroaryl.
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Page/Page column 16
(2008/06/13)
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- 4-Phenyl substituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine and serotonin
-
The present invention relates to a method of treating disorders by administering a compound of the formulae IA-IF. These compounds are tetrahydroisoquinolines of the following structure: wherein R1-R8 for compounds of each of the formulae IA, IB, IC, ID, IE and IF are as described herein.
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Page/Page column 24-25
(2010/11/08)
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- 2-Arylimino-2,3-dihydrothiazoles, and their use thereof as somatostatin receptor ligands
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The invention concerns novel 2-arylimino-2,3-dihydrothiazole derivatives of general formula (I), their preparation methods and their use as medicines, in particular for treating pathological conditions or diseases wherein one (or several) somatostatin receptors is/are involved. Said pathological conditions include in particular acromegaly, pituitary adenoma or endocrine gastroenteropanceatic tumors including the carcinoid syndrome, and gastrointestinal bleeding. In general formula (I), R1 represents in particular an alkyl, aralkyl, cyclohexyl radical optionally substituted by an amino radical or R1 represents a —C(R11)(R12)—CO—R10 radical wherein R11 represents H, R12 represents in particular H, carbocyclic or heterocyclic alkyl, cycloalkyl or aralkyl and R10 represents in particular an aminoalkylamino radical; R2 represents a carcyclic or heterocyclic aryl radical optionally substituted; R3 represents in particular COR5 or a carbocyclic or heterocyclic alkyl, adamantyl, aryl radical optionally substituted, carbocyclic or heterocyclic aralkyl optionally substituted on the aryl group; and R5 represents a radical fixed by a nitrogen atom to the group CO.
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Page column 47
(2010/02/06)
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- Antifungal amine derivatives and processing for producing the same
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Novel amine derivatives having an excellent antimycotic effect represented by general formula (1) below and salts thereof are provided. [in the formula (1, R1represents a C1-5alkyl group which may be halogenated, R2represents 4-(1,1-dimethylalkyl)benzyl group, 4-(1-methyl-phenylethyl)benzyl group, 1-or 2-naphthylmethyl group, or a hydrocarbon group having 3,3-dimethyl-1-butynyl group or a phenyl group at its terminal and 1 to 3 double bonds; R3represents oxygen atom or a methylene group which may be substituted by a C1-4alkyl group; and R4represents 1-or 2 naphthyl group or a phenyl group which may be substituted.
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-
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- Diarylspiro[2.4]heptenes as orally active, highly selective cyclooxygenase-2 inhibitors: Synthesis and structure-activity relationships
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A novel series of 5,6-diarylspiro[2.4]hept-5-enes was shown to provide highly potent and selective cyclooxygenase-2 (COX-2) inhibitors. A study of structure-activity relationships in this series suggests that 3,4- disubstituted phenyl analogs are generally more selective than 4-substituted phenyl analogs and that replacement of the methyl sulfone group on the 6- phenyl ring with a sulfonamide moiety results in compounds with superior in vivo pharmacological properties, although with lower COX-2 selectivity. Several compounds have been shown to possess promising pharmacological properties in adjuvant-induced arthritis and edema analgesia models. The absence of gastrointestinal (GI) toxicity at 200 mpk of several selected compounds in rats and mice corresponds well with the weak potency for inhibition of COX-1 observed in the enzyme assay. Methyl sulfone 55 and sulfonamide 24 were shown to have superior in vivo pharmacological profiles, low GI toxicity, and good oral bioavailability and duration of action.
- Huang, Horng-Chih,Li, James J.,Garland, Danny J.,Chamberlain, Timothy S.,Reinhard, Emily J.,Manning, Robert E.,Seibert, Karen,Koboldt, Carol M.,Gregory, Susan A.,Anderson, Gary D.,Veenhuizen, Amy W.,Zhang, Yan,Perkins, William E.,Burton, Earl G.,Cogburn, J. Nita,Isakson, Peter C.,Reitz, David B.
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p. 253 - 266
(2007/10/03)
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- Potential antiarthritic agents. II. Benzoylacetonitriles and β-aminocinnamonitriles
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Benzoylacetonitrile and β-aminocinnamonitrile are shown to possess potent intiinflammatory activity in the rat adjuvant arthritis model. In a series of phenyl-substituted analogues, only o-, m-, and p-fluorobenzoylacetonitrile and m- and p-fluoro-β-aminocinnamonitrile retained activity. Additionally, β-amino-2- and β-amino-3-thiopheneacrylonitrile and β-oxo-2- and β-oxo-3-thiophenepropionitrile exhibited similar activity. These agents are not believed to be acting via prostaglandin synthetase inhibition. The metabolic profile of benzoylacetonitrile is also described.
- Ridge,Hanifin,Harten,Johnson,Menschik,Nicolau,Sloboda,Watts
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p. 1385 - 1389
(2007/10/09)
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- Cis-2-benzoyl-3-hydroxy-2-alkenonitriles as anti-inflammatory agents
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This disclosure describes new compounds and compositions of matter useful as anti-inflammatory agents and as inhibitors of the progressive joint deterioration characteristic of arthritic disease and the methods of meliorating inflammation and of inhibiting joint deterioration in mammals therewith, the novel active ingredients of said compositions of matter being certain substituted cis-2-benozyl-3-hydroxy-2-alkenonitriles and/or the pharmacologically acceptable cationic salts thereof.
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