- Regioselective Synthesis of Angular Isocoumarinselenazoles: A Benzoselenazole-directed, Site-specific, Ruthenium-catalyzed C(sp2)-H Activation
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The synthesis of new, angular isocoumarinselenazoles is described, which involves the construction of 2-amino benzoselenazoles and their regioselective C2N-alkylation and alkyne insertion. An expeditious and metal-free synthesis of 2-aminobenzoselenazoles
- Dhole, Sandip,Liao, Jen-Yu,Kumar, Sunil,Salunke, Deepak B.,Sun, Chung-Ming
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Read Online
- PGDH INHIBITORS AND METHODS OF MAKING AND USING
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Disclosed herein are compounds that can inhibit 15-hydroxyprostaglandin dehydrogenase. Such compounds may be administered to subjects that may benefit from modulation of prostaglandin levels.
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Paragraph 0271; 0278-0279
(2021/07/31)
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- Preparation method of 3-acetylindole BRPF1 inhibitor and use of 3-acetylindole BRPF1 inhibitor
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The invention relates to a 3-acetylindole compound of a novel structure shown in a formula (I), a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate or a solvate thereof, a preparation method of the compound, a pharmaceutical composition containing a therapeutically effective dose of the compound, and use thereof as a protein tyrosine kinase inhibitor, especially as a bromine-containing area PHD zinc finger protein 1 (BRPF1) inhibitor, in the prevention or treatment of disease benefited from the inhibition of BRPF1.
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Paragraph 0077-0080; 0134-0136
(2020/03/03)
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- Benzimidazole derivatives as potent and isoform selective tumor-associated carbonic anhydrase IX/XII inhibitors
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We describe the synthesis of a series of 2-arylbenzimidazole derivatives bearing sulfonamide functionality (4a–d, 7a–c and 10) as well as hydroxamic acid (15a–b), carboxylic acid (16a–b), carboxamide (17a–b) and boronic acid (22a–b and 26) functionalities, which act as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors. The newly synthesized benzimidazole derivatives were evaluated against 4 physiologically relevant CA isoforms (hCA I, II, IX, and XII), and especially the sulfonamide-containing benzimidazoles demonstrated intriguing inhibitory activity against tumor associated CA IX and XII with KI values in the range of 5.2–29.3 nM and 9.9–41.7 nM, respectively. Notably, compound 4c was the most potent and selective CA IX (KI = 6.6 nM) and XII (KI = 9.9 nM) inhibitor with a significant selectivity ratio over cytosolic CA I and II isoforms in the range of 3.4–25.2. In addition, compounds having hydroxamic acid (15a-b) or carboxylic acid (16a-b) functionalities resulted in greater selectivity ratios for CA IX/XII over CAI/II in the range of 4.1–121.5 although with KI values in lower micromolar potency (KIs = 0.36–0.85 μM for CA IX/XII).
- ?al??kan, Burcu,Banoglu, Erden,Gür Maz, Tu??e,Nocentini, Alessio,Supuran, Claudiu T.,Uslu, Azize Gizem
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supporting information
(2020/01/08)
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- EXON SKIPPING OLIGOMER CONJUGATES FOR MUSCULAR DYSTROPY
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Antisense oligomers complementary to a selected target site in the human dystrophin gene to induce exon 50 skipping are described. In various aspects, antisense oligomers are described according to Formula (I): or a pharmaceutically acceptable salt thereo
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Paragraph 0379
(2020/07/07)
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- EXON SKIPPING OLIGOMER CONJUGATES FOR MUSCULAR DYSTROPHY
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Antisense oligomer conjugates complementary to a selected target site in the human dystrophin gene to induce exon 52 skipping are described.
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- Substituent effects on the isomerization of hydrazone switches driven by the intramolecular hydrogen bond
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In this work, the substituent effects on hydrogen bonding in one kind of hydrazone-based switch are revealed. The E/Z isomerization ratios of these hydrazones and their intramolecular hydrogen bond strengths in the Z form were evaluated using NMR technique. Linear correlations between these parameters and Hammett empirical values for substituent effects are explored as well.
- Lu, Chaocao,Htan, Bu,Fu, Shitao,Ma, Chunmiao,Gan, Quan
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p. 4010 - 4016
(2019/07/03)
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- PROCESSES FOR PREPARING PHOSPHORODIAMIDATE MORPHOLINO OLIGOMERS VIA FAST-FLOW SYNTHESIS
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Provided herein are processes for preparing an oligomer (e.g., a morpholino oligomer). The synthetic processes described herein may be advantageous to scaling up oligomer synthesis while maintaining overall yield and purity of a synthesized oligomer.
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Page/Page column 80-81
(2019/04/16)
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- MODULATORS OF ORPHAN NUCLEAR RECEPTORS FOR NASH AND OTHER METABOLIC DISORDERS
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Compounds, compositions and methods for modulating retinoic acid receptor-like orphan receptors (ROR) and associated diseases. Methods for treatment or prophylaxis of metabolic disorders, liver disorders or diseases, including NASH, immune disorders, cent
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Page/Page column 58-60
(2019/11/19)
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- Oridonin derivatives as potential anticancer drug candidates triggering apoptosis through mitochondrial pathway in the liver cancer cells
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The biological function of the natural ent-kaurene diterpenoid isolated from genus Isodon, oridonin, has been intensively studied. However, its mechanism studies and clinical applications were hampered by its moderate biological activities. In order to en
- Luo, Dongdong,Yi, Yujiao,Peng, Kai,Liu, Tangrong,Yang, Jiayu,Liu, Shan,Zhao, Wanzhou,Qu, Xianjun,Yu, Wengong,Gu, Yuchao,Wan, Shengbiao
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p. 365 - 379
(2019/06/17)
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- SUBSTITUTED 2-AMINOBENZIMIDAZOLES ANALOGS AS ANTIBIOFILM AGENTS
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In one aspect, the disclosure relates to compositions and methods for dispersing exiting Salmonella biofilms and inhibiting formation of Salmonella biofilms. In various aspects, the disclosed compositions can be used in methods of treating a persistent Sa
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Paragraph 0225; 0226; 0237
(2019/10/29)
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- EXON SKIPPING OLIGOMER CONJUGATES FOR MUSCULAR DYSTROPHY
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Antisense oligomer conjugates complementary to a selected target site in the human dystrophin gene to induce exon 51 skipping are described.
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Paragraph 0342; 0343
(2018/07/15)
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- EXON SKIPPING OLIGOMER CONJUGATES FOR MUSCULAR DYSTROPHY
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Antisense oligomer conjugates complementary to a selected target site in the human dystrophin gene to induce exon 53 skipping are described.
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Page/Page column 94; 95
(2018/07/22)
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- EXON SKIPPING OLIGOMER CONJUGATES FOR MUSCULAR DYSTROPHY
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Antisense oligomer conjugates complementary to a selected target site in the human dystrophin gene to induce exon 45 skipping are described.
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Page/Page column 94
(2018/07/29)
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- NOVEL SUBSTITUTED BENZIMIDAZOLE DERIVATIVES AS D-AMINO ACID OXIDASE (DAAO) INHIBITORS
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The present invention provides novel substituted benzimidazole derivatives used as DAAO inhibitors and for treatment and/or prevention of neurological disorders.
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Paragraph 00220
(2018/04/13)
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- 2-Aminobenzimidazoles as antibiofilm agents against Salmonella enterica serovar Typhimurium
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Serovars within the species Salmonella enterica are some of the most common food and water-borne pathogens worldwide. Some S. enterica serovars have shown a remarkable ability to persist both inside and outside the human body. Salmonella enterica serovar
- Huggins, William M.,Vu Nguyen,Hahn, Nicholas A.,Baker, James T.,Kuo, Laura G.,Kaur, Darpan,Melander, Roberta J.,Gunn, John S.,Melander, Christian
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supporting information
p. 1547 - 1552
(2018/10/02)
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- An expedient synthesis of CMF-019: (s)-5-methyl-3-{1-(pentan-3-yl)-2-(thiophen-2-ylmethyl)-1h-benzo[d]imidazole-5-carboxamido}hexanoic acid, a potent apelin receptor (APJ) agonist
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Background: Apelin receptor (APJ) is a G protein-coupled receptor (GPCR) activated by the endogenous peptide apelin. The apelin–APJ system has emerged as an important regulator of cardiovascular homeostasis. Recently, a potent benzimidazole-derived apelin
- Trifonov, Lena,Afri, Michal,Korshin, Edward E.,Gruzman, Arie,Palczewski, Krzysztof
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p. 688 - 694
(2018/11/21)
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- PROCESSES FOR PREPARING OLIGOMERS
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Provided herein are processes for preparing an oligomer (e.g., a morpholino oligomer). The synthetic processes described herein may be advantageous to scaling up oligomersynthesis while maintaining overall yield and purity of a synthesized oligomer.
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Page/Page column 154-155
(2017/12/29)
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- Microwave synthesis, biological evaluation and docking studies of 2-substituted methyl 1-(4-fluorophenyl)-1H-benzimidazole-5-carboxylates
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A library of 22 novel 2-substituted fluorinated benzimidazoles (5a-v) was synthesized under microwave conditions in yields of between 85–96% and tested for their antimicrobial and antioxidant activity. Two trioxygenated derivatives 5p and 5r had minimum bactericidal concentration values ranging between 14.5–115.7 μM (5p) and 25.6–74.3 μM (5r) against S. aureus, E. coli, P. aeruginosa and K. pneumoniae. The benzimidazole 5e with a CF3 substituent had the best antifungal activity at 94.3 μM against C. albicans. Compounds 5p and 5r also showed good antioxidant activities of 386.6 and 306.7 μM respectively, comparable to that of ascorbic acid. Docking studies of 5 h and 5r into the active site of topoisomerase II DNA-gyrase indicated that interaction with the Mn2+ ion in the active site of the enzyme was crucial for antibacterial activity.
- Shintre, Suhas A.,Ramjugernath, Deresh,Singh, Parvesh,Mocktar, Chunderika,Koorbanally, Neil A.
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p. 484 - 498
(2017/01/28)
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- Synthesis of Aminofuran-Linked Benzimidazoles and Cyanopyrrole-Fused Benzimidazoles by Condition-Based Skeletal Divergence
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A condition-based skeletal divergent synthesis was explored to achieve skeletal diversity in two component condensation reaction. Cyanomethyl benzimidazole was reacted with α-bromoketone under thermal conditions to furnish 2-aminofuranyl-benzimidazoles, w
- Hsu, Wei-Shun,Tsai, Min-Huan,Barve, Indrajeet J.,Yellol, Gorakh S.,Sun, Chung-Ming
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p. 492 - 499
(2017/07/15)
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- Structure-based design of ester compounds to inhibit MLL complex catalytic activity by targeting mixed lineage leukemia 1 (MLL1)–WDR5 interaction
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WDR5 is an essential protein for enzymatic activity of MLL1. Targeting the protein–protein interaction (PPI) between MLL1 and WDR5 represents a new potential therapeutic strategy for MLL leukemia. Based on the structure of reported inhibitor WDR5-0103, a
- Li, Dong-Dong,Wang, Zhi-Hui,Chen, Wei-Lin,Xie, Yi-Yue,You, Qi-Dong,Guo, Xiao-Ke
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p. 6109 - 6118
(2016/11/09)
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- Cardiac action of the first G protein biased small molecule apelin agonist
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Apelin peptide analogues displaying bias towards G protein signalling pathways have beneficial cardiovascular actions compared with the native peptide in humans in vivo. Our aim was to determine whether small molecule agonists could retain G protein bias.
- Read, Cai,Fitzpatrick, Christopher M.,Yang, Peiran,Kuc, Rhoda E.,Maguire, Janet J.,Glen, Robert C.,Foster, Richard E.,Davenport, Anthony P.
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- Rhodium-Catalyzed Regioselective Synthesis of Isocoumarins through Benzothiadiazine-Fused Frameworks
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An unprecedented two-step, one-pot synthesis of benzimidazothiadiazine 5,5-dioxides is presented. Reaction condition based regioselectivity has been achieved where fused benzimidazo[1,2-b][1,2,4]thiadiazines are exclusively formed under thermal conditions
- Dalvi, Prashant B.,Lin, Kuang-Ling,Kulkarni, Manohar V.,Sun, Chung-Ming
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supporting information
p. 3706 - 3709
(2016/08/16)
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- Stable and easily accessible functional dyes: Dihydrotetraazaanthracenes as versatile precursors for higher acenes
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Abstract A series of new dihydrotetraazaanthracenes and one new dihydrotetraazatetracene as substances for applications in organoelectronic devices and as suitable building blocks for higher azaacenes was synthesised. The condensation of aromatic diamines with dichlorodicyanopyrazine led to these tricyclic/tetracyclic compounds. Syntheses of N-substituted phenylenediamines were developed to enable the introduction of multiple functional groups such as ester, amino, or nitro groups on the chromophoric system. Relationships between the structure and the spectroscopic properties could be derived from UV/Vis absorption and fluorescence spectroscopy, as well as by DFT and TD-DFT calculations of molecular and aggregate structures. The absorption spectra are dominated by π-π transitions of the single molecules, whereas aggregation needs to be taken into account to obtain reasonable agreement between theory and experiment in certain cases. Single-crystal X-ray analyses were carried out to examine the morphology and solid packing effects. Finally, a dihydrotetraazaanthracene was used as a building-block to create a mesoionic octaazapentacene. Dihydroazaacenes: A series of dihydrotetraazaanthracenes and one new dihydrotetraazatetracene as substances for applications in organoelectronic devices and as suitable building blocks for higher azaacenes was synthesised. Single-crystal X-ray analyses were carried out to examine the morphology and solid packing effects. Finally, a dihydrotetraazaanthracene was used as a building-block to create a mesoionic octaazapentacene.
- Gampe, Dominique Mario,Kaufmann, Martin,Jakobi, D?rthe,Sachse, Torsten,Presselt, Martin,Beckert, Rainer,G?rls, Helmar
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p. 7571 - 7581
(2015/05/13)
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- 2-(4-ARYL-1H-IMIDAZOL-1-YL)ANILINE COMPOUNDS
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The present invention provides compounds that are useful as vaccine adjuvants and/or antitumor agents and methods for producing and using the same. In one particular aspect of the invention, compounds of the invention are of the formula (I) where R1, R2, R3 and Ar1 are those defined herein.
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Paragraph 0106
(2015/11/27)
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- Heterocyclic derivative and pharmaceutical composition comprising the same
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The present invention provides novel compounds having a P2X3 and/or P2X2/3 receptor antagonistic effect. A pharmaceutical composition having a P2X3 and/or P2X2/3 receptor antagonistic effect comprising a compoun
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Page/Page column 251
(2016/01/10)
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- Synthesis and biological evaluation of bivalent cannabinoid receptor ligands based on hCB2R selective benzimidazoles reveal unexpected intrinsic properties
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The design of bivalent ligands targeting G protein-coupled receptors (GPCRs) often leads to the development of new, highly selective and potent compounds. To date, no bivalent ligands for the human cannabinoid receptor type 2 (hCB2R) of the end
- Nimczick, Martin,Pemp, Daniela,Darras, Fouad H.,Chen, Xinyu,Heilmann, Joerg,Decker, Michael
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supporting information
p. 3938 - 3946
(2014/08/18)
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- BENZOIMIDAZOLE-CARBOXYLIC ACID AMIDE DERIVATIVES AS APJ RECEPTOR MODULATORS
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The present invention relates to benzoimidazole-carboxylic acid amide compounds of the formula I, in which R', R", R"', R1, R2, R3, R4, R5, R6 and Z are defined as indicated below. The comp
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Page/Page column 349; 350
(2014/04/04)
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- BENZOIMIDAZOLE-CARBOXYLIC ACID AMIDE DERIVATIVES AS APJ RECEPTOR MODULATORS
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The present invention relates to benzoimidazole-carboxylic acid amide compounds of the formula I, in which R′, R″, R′″, R1, R2, R3, R4, R5, R6 and Z are defined as indicated below. The comp
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Paragraph 1938-1940
(2014/04/17)
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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds of Formula IIa: and compositions thereof, and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Paragraph 0235; 0253; 0254
(2014/05/20)
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- NOVEL HETEROCYCLIC COMPOUND, AND COMPOSITION FOR TREATING INFLAMMATORY DISEASES USING SAME
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Provided are heterocyclic compounds, having effects of treating and preventing inflammatory diseases and treating skin wounds, and particularly, exhibiting effects of recovering disrupted skin barriers, mitigating inflammation, and pruritus. Also, a compo
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Paragraph 0035
(2013/07/25)
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- NOVEL HETEROCYCLIC COMPOUND, AND COMPOSITION FOR TREATING INFLAMMATORY DISEASES USING SAME
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Provided are heterocyclic compounds, having effects of treating and preventing inflammatory diseases and treating skin wounds, and particularly, exhibiting effects of recovering disrupted skin barriers, mitigating inflammation, and pruritus. Also, a compo
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Paragraph 0062; 0063
(2013/06/28)
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- From bead to flask: Synthesis of a complex β-amido-amide for probe-development studies
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A concise synthesis of benzimidazole-substituted β-amido-amide LLW62 is presented. The original synthesis of compounds related to LLW62 was developed on Rink resin as part of a "one-bead, one-compound" combinatorial approach for on-bead screening purposes. The current synthesis is carried out in solution and is amenable to scale-up for follow-up studies on LLW62 and investigations of related structures. The key step involves the use of a β-amino acid-forming three-component reaction (3CR), the scope of which defines its role in the synthetic strategy.
- Martin, Kevin S.,Soldi, Cristian,Candee, Kellan N.,Wettersten, Hiromi I.,Weiss, Robert H.,Shaw, Jared T.
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supporting information
p. 260 - 264
(2013/03/29)
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- NOVEL HETEROCYCLIC DERIVATIVES AND PHARMACEUTICAL COMPOSITION CONTAINING SAME
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The present invention provides novel compounds having a P2X3 and/or P2X2/3 receptor antagonistic effect. A pharmaceutical composition having a P2X3 and/or P2X2/3 receptor antagonistic effect comprising a compoun
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Paragraph 0417; 0418
(2013/06/28)
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- COMPOUNDS AND COMPOSITIONS AS PDGFR KINASE INHIBITORS
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The invention provides compounds and pharmaceutical compositions thereof, which are useful as protein kinase inhibitors, as well as methods for using such compounds to treat, ameliorate or prevent a condition associated with abnormal or deregulated kinase
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Page/Page column 67-68; 75
(2013/03/28)
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- N-BENZYLBENZIMIDAZOLE MODULATORS OF PPARG
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The invention provides molecular entities that bind with high affinity to PPARG (PPAR?), inhibit cdk5-mediated phosphorylation of PPARG, but do not exert an agonistic effect on PPARG. Compounds of the invention can be used for treatment of conditions in patients wherein PPARG plays a role, such as diabetes or obesity. Methods of preparation of the compounds, bioassay methods for evaluating compounds of the invention as non-agonistic PPARG binding compounds, and pharmaceutical compositions are also provided.
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Page/Page column 66
(2013/06/06)
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- Multicomponent solvent-free synthesis of benzimidazolyl imidazo[1,2-a]-pyridine under microwave irradiation
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A novel one-pot, three-component reaction employing variously substituted benzimidazole-linked amino pyridines, aldehydes, and isonitriles catalyzed by scandium(III) triflate under solvent-free conditions were accomplished. This new synthetic methodology
- Maiti, Barnali,Chanda, Kaushik,Selvaraju, Manikandan,Tseng, Chih-Chung,Sun, Chung-Ming
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p. 291 - 297
(2013/07/25)
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- A concise synthesis of 2-(2-aminothiophene)-benzimidazoles by one-pot multicomponent reaction
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A one-pot synthesis of 2-aminothiophene linked benzimidazoles was achieved by utilizing 2-cyanomethyl benzimidazoles in a modified Gewald multicomponent reaction. The synthetic strategy of the reaction involved treatment of 2-(cyanomethyl)-benzimdazole wi
- Chen, Li-Hsun,Chuang, Ying-Sheng,Narhe, Bharat D.,Sun, Chung-Ming
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p. 13934 - 13943
(2013/08/23)
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- On the antitumor properties of novel cyclometalated benzimidazole Ru(ii), Ir(iii) and Rh(iii) complexes
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Smart design and efficient synthesis of benzimidazole Ru, Ir and Rh cyclometalated complexes are reported with promising cytotoxic activity against HT29, T47D, A2780 and A2780cisR cancer cell lines. Their apoptosis, accumulation, cell cycle arrest, protei
- Yellol, Gorakh S.,Donaire, Antonio,Yellol, Jyoti G.,Vasylyeva, Vera,Janiak, Christoph,Ruiz, Jose
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p. 11533 - 11535
(2013/12/04)
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- Design and synthesis of new biprivileged molecular scaffolds: Indolo-fused benzodiazepinyl/quinoxalinyl benzimidazoles
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The present article describes the design and synthesis of new biprivileged molecular scaffolds with diverse structural features. Commercially available, simple heterocyclic building blocks such as 4-fluoro-3-nitrobenzoic acid, 2-chloro-3-nitrobenzoic acid
- Barve, Indrajeet J.,Chen, Chan-Yu,Salunke, Deepak B.,Chung, Wen-Sheng,Sun, Chung-Ming
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experimental part
p. 1684 - 1690
(2012/08/08)
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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Page/Page column 32
(2012/07/27)
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- Discovery of a Plasmodium falciparum Glucose-6-phosphate Dehydrogenase 6-phosphogluconolactonase Inhibitor (R,Z)-N-((1-Ethylpyrrolidin-2-yl)methyl)-2- (2-fluorobenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide (ML276) that reduces parasite growth in vitro
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A high-throughput screen of the NIH's MLSMR collection of ~340000 compounds was undertaken to identify compounds that inhibit Plasmodium falciparum glucose-6-phosphate dehydrogenase (Pf G6PD). PfG6PD is important for proliferating and propagating P. falciparum and differs structurally and mechanistically from the human orthologue. The reaction catalyzed by glucose-6-phosphate dehydrogenase (G6PD) is the first, rate-limiting step in the pentose phosphate pathway (PPP), a key metabolic pathway sustaining anabolic needs in reductive equivalents and synthetic materials in fast-growing cells. In P. falciparum, the bifunctional enzyme glucose-6-phosphate dehydrogenase-6- phosphogluconolactonase (Pf GluPho) catalyzes the first two steps of the PPP. Because P. falciparum and infected host red blood cells rely on accelerated glucose flux, they depend on the G6PD activity of PfGluPho. The lead compound identified from this effort, (R,Z)-N-((1-ethylpyrrolidin-2-yl)methyl)-2-(2- fluorobenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carbox-amide, 11 (ML276), is a submicromolar inhibitor of PfG6PD (IC50 = 889 nM). It is completely selective for the enzyme's human isoform, displays micromolar potency (IC50 = 2.6 μM) against P. falciparum in culture, and has good drug-like properties, including high solubility and moderate microsomal stability. Studies testing the potential advantage of inhibiting Pf G6PD in vivo are in progress.
- Preuss, Janina,Malone, Patrick,Peddibhotla, Satyamaheshwar,Hedrick, Michael P.,Hershberger, Paul,Gosalia, Palak,Milewski, Monika,Li, Yujie Linda,Sugarman, Eliot,Hood, Becky,Suyama, Eigo,Nguyen, Kevin,Vasile, Stefan,Sergienko, Eduard,Mangravita-Novo, Arianna,Vicchiarelli, Michael,McAnally, Danielle,Smith, Layton H,Roth, Gregory P.,Diwan, Jena,Chung, Thomas D.Y.,Jortzik, Esther,Rahlfs, Stefan,Becker, Katja,Pinkerton, Anthony B.,Bode, Lars
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supporting information
p. 7262 - 7272
(2012/11/07)
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- When inhibitors do not inhibit: Critical evaluation of rational drug design targeting chorismate mutase from mycobacterium tuberculosis
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Tuberculosis (TB) is a devastating disease that claims millions of lives every year. Hindered access or non-compliance to medication, especially in developing countries, led to drug resistance, further aggravating the situation. With current standard ther
- Munack, Steffi,Leroux, Vincent,Roderer, Kathrin,?kvist, Mats,Van Eerde, André,Gundersen, Lise-Lotte,Krengel, Ute,Kast, Peter
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p. 2507 - 2527
(2013/01/16)
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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Page/Page column 32
(2012/09/21)
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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Page/Page column 14
(2012/09/11)
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- Synthesis of novel 1,2,5-trisubstituted benzimidazoles as potential antitumor agents
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Novel methyl 1-(5-tert-butyl-1H-pyrazol-3-yl)-2-(aryl)-1H-benzo[d] imidazole-5-carboxylates 11 were synthesized by following a four-step strategy involving a nucleophilic aromatic displacement (SNAr) and a solvent free approach as key steps for the formation of the desired products. Structure of intermediates and products were confirmed by X-ray diffraction as well as the tautomeric rearrangement suffered by the pyrazole moiety during the curse of the final cyclization process. Several of the obtained compounds were screened by the US National Cancer Institute (NCI) for their ability to inhibit 60 different human tumor cell lines. Products 11b and 11n exhibited the highest activity against a range of cancer cell lines with remarkable values in panels of Non-Small Cell Lung Cancer, Melanoma and Leukemia, with GI50 range of 1.15-7.33 μM and 0.167-7.59 μM, respectively, and suitable LC 50 with values greater than 100 μM.
- Abonia, Rodrigo,Cortes, Edwar,Insuasty, Braulio,Quiroga, Jairo,Nogueras, Manuel,Cobo, Justo
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experimental part
p. 4062 - 4070
(2011/11/12)
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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Page/Page column 44
(2011/04/14)
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- Discovery of GSK1997132B a novel centrally penetrant benzimidazole PPARγ partial agonist
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The peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated nuclear receptor, thought to play a role in energy metabolism, glucose homeostasis and microglia-mediated neuroinflammation. A novel benzimidazole series of centrally penetrant PPARγ partial agonists has been identified. The optimization of PPARγ activity and in vivo pharmacokinetics leading to the identification of GSK1997132B a potent, metabolically stable and centrally penetrant PPARγ partial agonist, is described.
- Sime, Mairi,Allan, Amanda C.,Chapman, Paul,Fieldhouse, Charlotte,Giblin, Gerard M.P.,Healy, Mark P.,Lambert, Millard H.,Leesnitzer, Lisa M.,Lewis, Ann,Merrihew, Raymond V.,Rutter, Richard A.,Sasse, Rosemary,Shearer, Barry G.,Wilson, Timothy M.,Xu, Robert X.,Virley, David J.
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scheme or table
p. 5568 - 5572
(2011/10/09)
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- A novel potential therapeutic avenue for autism: Design, synthesis and pharmacophore generation of SSRIs with dual action
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Autism symptoms are currently modulated by Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs slow onset of action limits their efficiency. The established synergistic activity of SSRIs and 5HT1B/1D autoreceptors antagonists motivated us to incorporate SSRIs and 5HT1B/1D antagonists in one 'hybrid' molecule. A library of virtual 'hybrid' molecules was designed using the tethering technique. A pharmacophore model was generated derived from 16 structurally diverse SSRIs (Ki = 0.013-5000 nM) and used as 3D query. Compounds with fit values (≥2) were chosen for synthesis and subsequent in vitro biological evaluation. Our pharmacophore model is a promising milestone to a class of SSRIs with dual action.
- Ghoneim, Ola M.,Ibrahim, Diaa A.,El-Deeb, Ibrahim M.,Lee, So Ha,Booth, Raymond G.
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scheme or table
p. 6714 - 6723
(2011/12/21)
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- AUTOTAXIN INHIBITORS
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The present invention relates to compounds according to formula (I) as autotaxin inhibitors and the use of such compounds for the treatment and/or prophylaxis of physiological and/or pathophysiological conditions, which are caused, mediated and/or propaga
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Page/Page column 69
(2010/11/03)
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