- Two polymorphic forms of 2,5-bis-(4-methoxycarbonylphenyl)-1,3,4-oxadiazole
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The title compound [systematic name: dimethyl 4,4′-(1,3,4-oxadiazole-2,5-diyl)diphenylenedicarboxylate], C18H14N2O5, crystallizes under similar conditions in two different orthorhombic crystalline forms. In both
- Reck, Guenter,Orgzall, Ingo,Schulz, Burkhard,Dietzel, Birgit
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- AROMATIC RING OR HETEROAROMATIC RING COMPOUNDS, PREPARATION METHOD THEREFOR AND MEDICAL USE THEREOF
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The present invention relates to aromatic ring or heteroaromatic ring compounds, a preparation method therefor and a medical use thereof. Particularly, the present invention relates to a compound as shown in general formula (I) and a preparation method th
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- Discovery of Novel Small-Molecule Inhibitors of NF-κB Signaling with Antiinflammatory and Anticancer Properties
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Excessive NF-κB activation contributes to the pathogenesis of numerous diseases. Small-molecule inhibitors of NF-κB signaling have significant therapeutic potential especially in treating inflammatory diseases and cancers. In this study, we performed a ce
- Zhang, Lei,Shi, Lei,Soars, Shafer Myers,Kamps, Joshua,Yin, Hang
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p. 5881 - 5899
(2018/06/13)
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- Antifungal benzo[b]thiophene 1,1-dioxide IMPDH inhibitors exhibit pan-assay interference (PAINS) profiles
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Fungi cause serious life-threatening infections in immunocompromised individuals and current treatments are now complicated by toxicity issues and the emergence of drug resistant strains. Consequently, there is a need for development of new antifungal drugs. Inosine monophosphate dehydrogenase (IMPDH), a key component of the de novo purine biosynthetic pathway, is essential for growth and virulence of fungi and is a potential drug target. In this study, a high-throughput screen of 114,000 drug-like compounds against Cryptococcus neoformans IMPDH was performed. We identified three 3-((5-substituted)-1,3,4-oxadiazol-2-yl)thio benzo[b]thiophene 1,1-dioxides that inhibited Cryptococcus IMPDH and also possessed whole cell antifungal activity. Analogs were synthesized to explore the SAR of these hits. Modification of the fifth substituent on the 1,3,4-oxadiazole ring yielded compounds with nanomolar in vitro activity, but with associated cytotoxicity. In contrast, two analogs generated by substituting the 1,3,4-oxadiazole ring with imidazole and 1,2,4-triazole gave reduced IMPDH inhibition in vitro, but were not cytotoxic. During enzyme kinetic studies in the presence of DTT, nucleophilic attack of a free thiol occurred with the benzo[b]thiophene 1,1-dioxide. Two representative compounds with substitution at the 5 position of the 1,3,4-oxadiazole ring, showed mixed inhibition in the absence of DTT. Incubation of these compounds with Cryptococcus IMPDH followed by mass spectrometry analysis showed non-specific and covalent binding with IMPDH at multiple cysteine residues. These results support recent reports that the benzo[b]thiophene 1,1-dioxides moiety as PAINS (pan-assay interference compounds) contributor.
- Kummari, Lalith K.,Butler, Mark S.,Furlong, Emily,Blundell, Ross,Nouwens, Amanda,Silva, Alberto B.,Kappler, Ulrike,Fraser, James A.,Kobe, Bostjan,Cooper, Matthew A.,Robertson, Avril A.B.
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p. 5408 - 5419
(2018/10/20)
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- Discovery of highly selective and potent monoamine oxidase B inhibitors: Contribution of additional phenyl rings introduced into?2-aryl-1,3,4-oxadiazin-5(6H)-one
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Monoamine oxidase B (MAO-B) is a flavin adenine dinucleotide (FAD)-containing enzyme that plays a major role in the oxidative deamination of biogenic amines and neurotransmitters. Inhibiting MAO-B activity is a promising approach in the treatment of neuro
- Lee, Jungeun,Lee, Yeongcheol,Park, So Jung,Lee, Joohee,Kim, Yeong Shik,Suh, Young-Ger,Lee, Jeeyeon
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p. 365 - 378
(2017/03/10)
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- PYRROL-1 -YL BENZOIC ACID DERIVATES USEFUL AS MYC INHIBITORS
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The present invention provides compounds of Formula (I-A), (I-B), and (I-C), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting Myc (e.g., c-Myc) activity. The p
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- IMIDAZO-OXADIAZOLE AND IMIDAZO-THIADIAZOLE DERIVATIVES
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The present invention provides compounds of Formula (I) used as Amyloid beta lowering agent for the treatment of neurodegenerative diseases.
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- Discovery of histone deacetylase 8 selective inhibitors
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We have developed an efficient method for synthesizing candidate histone deacetylase (HDAC) inhibitors in 96-well plates, which are used directly in high-throughput screening. We selected building blocks having hydrazide, aldehyde and hydroxamic acid functionalities. The hydrazides were coupled with different aldehydes in DMSO. The resulting products have the previously identified 'cap/linker/biasing element' structure known to favor inhibition of HDACs. These compounds were assayed without further purification. HDAC8-selective inhibitors were discovered from this novel collection of compounds.
- Tang, Weiping,Luo, Tuoping,Greenberg, Edward F.,Bradner, James E.,Schreiber, Stuart L.
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supporting information; experimental part
p. 2601 - 2605
(2011/06/22)
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- Substituted Benzo-Pyrido-Triazolo-Diazepine Compounds
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The present invention relates to substituted benzo-pyrido-triazolo-diazepine compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted benzo-pyrido-triazolo-diazepine compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds or pharmaceutical compositions to subjects in need thereof.
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Page/Page column 95
(2011/10/13)
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- 1,2,4-TRIAZOLE CARBOXYLIC ACID DERIVATIVES AS MODULATORS OF MGLUR5
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The present invention is directed to novel compounds, to a process for their preparation, their use in therapy and pharmaceutical compositions comprising the novel compounds.
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Page/Page column 10
(2009/05/29)
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- Fluorous-based small-molecule microarrays for the discovery of histone deacetylase inhibitors
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(Figure Presented) Noncovalent immobilization is an attractive method for identifying inhibitors of histone deacetylases (HDACs). Fluorous-based small-molecule microarrays were validated as an effective method. Three enzymes and three assays (microarray, biochemical activity, and surface plasmon resonance) were used to identify inhibitors of HDACs and to compare them.
- Vegas, Arturo J.,Bradner, James E.,Tang, Weiping,McPherson, Olivia M.,Greenberg, Edward F.,Koehler, Angela N.,Schreiber, Stuart L.
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p. 7960 - 7964
(2008/09/19)
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- 3-ALKYLIDENEHYDRAZINO SUBSTITUTED HETEROARYL COMPOUNDS AS THROMBOPOIETIN RECEPTOR ACTIVATORS
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A compound represented by the formula (1): wherein A is a nitrogen atom or CR4, B is an oxygen atom, a sulfur atom or NR9 (provided that when A is a nitrogen atom, B is not NH), R1 is a C2-14; aryl group, L1 is a bond, CR10R11, an oxygen atom, a sulfur atom or NR12, X is OR13, SR13 or NR14NR15, R2 is a hydrogen atom, a formyl group, a C1-10; alkyl group or the like, L2 is a bond or the like, L3 is a bond, CR17R18, an oxygen atom, a sulfur atom or NR19, L4 is a bond, CR20R21, an oxygen atom, a sulfur atom or NR22, Y is an oxygen atom, a sulfur atom or NR23, and R3 is a C2-14; aryl group, a tautomer, prodrug or pharmaceutically acceptable salt of the compound or a solvate thereof.
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Page 547-548
(2008/06/13)
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- PYRAZOLONE COMPOUNDS AND THROMBOPOIETIN RECEPTOR ACTIVATOR
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A preventive, therapeutic or improving agent for diseases against which activation of the thrombopoietin receptor is effective or a platelet increasing agent, which contains a thrombopoietin receptor activator represented by the formula (1): wherein A is
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