- Design and synthesis of acetaminophen probe APAP-P1 for identification of the toxicity targets thioredoxin reductase-1 in HepaRG cells
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Drug-induced liver injury is one of the main causes of drug non-approval and drug withdrawal by the Food and Drug Administration (FDA). Acetaminophen (APAP) is a widely used non-steroidal anti-inflammatory drug for treating fever and headache. APAP is con
- Wang, Shan,Tian, Yu,Lu, Shan,Wang, Ruiying,Shang, Hai,Zhang, Xuelian,Zhang, Chenyang,Sun, Guibo,Xu, Xudong,Sun, Xiaobo
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Read Online
- A Fluorescent Probe for Early Detection of Melanoma and Its Metastasis by Specifically Imaging Tyrosinase Activity in a Mouse Model
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Melanoma is a type of highly malignant and metastatic skin cancer, and early detection of melanoma by analyzing the level of its biomarker may decrease the likelihood of mortality. In this study, a fluorescent probe called NBR-AP for detecting tyrosinase
- Zhan, Chenyue,Cheng, Jiatian,Li, Bowen,Huang, Shuailing,Zeng, Fang,Wu, Shuizhu
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Read Online
- A GENERAL PROCEDURE FOR THE CATALYTIC HYDROGENOLYSIS OF N-BENZYLAMINES UNDER EXTREMELY MILD CONDITIONS.
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A general procedure for debenzylation of N-benzylamines, which contain acid sensitive functional groups, by the catalytic hydrogenolysis using 20percent Pd(OH)2-C is reported.
- Yoshida, Kiyoshi,Nakajima, Shigekazu,Wakamatsu, Takeshi,Ban, Yoshio,Shibasaki, Masakatsu
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Read Online
- POLYAROMATIC UREA DERIVATIVES AND THEIR USE IN THE TREATMENT OF MUSCLE DISEASES
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The current invention provides urea derivatives, in particular compounds having the core structure heteroaryl-NH-CO-NH-aryl-O- heteroaryl, for use in treating, ameliorating, delaying, curing and/ or preventing a disease or condition associated with muscle cells and/or satellite cells, such as Duchenne muscular dystrophy, Becker muscular dystrophy, cachexia or sarcopenia.
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Page/Page column 113
(2021/01/29)
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- METHODS AND COMPOUNDS FOR THE TREATMENT OF GENETIC DISEASE
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The present disclosure relates to compounds and methods for modulating the expression of dmpk, and treating diseases and conditions in which dmpk plays an active role. The compound can be a transcription modulator molecule having a first terminus, a second terminus, and oligomeric backbone, wherein: a) the first terminus comprises a DNA-binding moiety capable of noncovalently binding to a nucleotide repeat sequence CAG or CTG; b) the second terminus comprises a protein-binding moiety binding to a regulatory molecule that modulates an expression of a gene comprising the nucleotide repeat sequence CAG or CTG; and c) the oligomeric backbone comprising a linker between the first terminus and the second terminus.
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Paragraph 00616; 00618; 00635; 00636
(2021/08/13)
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- AMPK agonist compound or pharmaceutically acceptable salt or ester or solvate thereof and application thereof
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The invention discloses an AMPK agonist compound with structures shown as I and II or pharmaceutically acceptable salt or ester or solvate thereof and application thereof. Benzyloxy aryl amide and piperidine urea compounds have strong AMPK agonist activit
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Paragraph 0054-0057
(2021/07/17)
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- Probe for determining gamma-glutamyltranspeptidase as well as synthesis method and application thereof
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The invention discloses a fluorescent probe for determining gamma-glutamyltranspeptidase. The structural formula of the fluorescent probe is shown in the specification; and the fluorescent probe can realize the conversion of a fluorescence signal from wea
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Paragraph 0053-0057; 0071; 0074; 0079; 0082
(2021/09/04)
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- Synthesis of Substituted Anilines from Cyclohexanones Using Pd/C-Ethylene System and Its Application to Indole Synthesis
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The synthesis of anilines and indoles from cyclohexanones using a Pd/C-ethylene system is reported. A simple combination of NH4OAc and K2CO3 under nonaerobic conditions was found to be the most suitable to perform this reaction. Hydrogen transfer between cyclohexanone and ethylene generates the desired products. The reaction tolerates a variety of substitutions on the starting cyclohexanones.
- Maeda, Katsumi,Matsubara, Ryosuke,Hayashi, Masahiko
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supporting information
p. 1530 - 1534
(2021/03/08)
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- Selective primary aniline synthesis through supported Pd-catalyzed acceptorless dehydrogenative aromatization by utilizing hydrazine
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By utilizing hydrazine (N2H4) as the nitrogen source in the presence of a hydroxyapatite-supported Pd nanoparticle catalyst (Pd/HAP), various primary anilines can be selectively synthesized from cyclohexanonesviaacceptorless dehydrogenative aromatization. The strong nucleophilicity of N2H4and the stability of the hydrazone intermediates can effectively suppress the formation of the undesired secondary aniline byproducts.
- Lin, Wei-Chen,Yatabe, Takafumi,Yamaguchi, Kazuya
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supporting information
p. 6530 - 6533
(2021/07/07)
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- Fluorescent probe as well as preparation method and application thereof in tyrosinase detection (by machine translation)
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The invention belongs to the technical field of analysis and detection and discloses a fluorescent probe and a preparation method and application thereof in tyrosinase detection. The fluorescence probe system is named 3, 3' - ({5 - [3 - (4 - hydroxyphenyl
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Paragraph 0046-0047; 0054-0055; 0060-0061
(2020/08/09)
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- Small molecule compounds, and application thereof in preparation of anti-tumor metastasis drugs
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The invention belongs to the technical field of medicines, and particularly relates to small molecule compounds, and application thereof in preparation of anti-tumor metastasis drugs. The preparationmethod comprises the following steps: preparing an inter
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Paragraph 0059; 0060; 0061
(2020/08/30)
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- BIFUNCTIONAL SUBSTITUED PYRIMIDINES AS MODULATORS OF FAK PROTEOLYSE
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The present disclosure relates to bifunctional compounds, which find utility as modulators of focal adhesion kinase (FAK) or protein tyrosine kinase 2 (PTK2). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 00406
(2020/02/16)
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- Discovery of AdipoRon analogues as novel AMPK activators without inhibiting mitochondrial complex I
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Activation of AMPK emerges as a potential therapeutic approach to metabolic diseases. AdipoRon is claimed to be an adiponectin receptor agonist that activates AMPK through adiponectin receptor 1 (AdipoR1). However, AdipoRon also exhibits moderate inhibition of mitochondrial complex I, leading to increased risk of lactic acidosis. In order to find novel AdipoRon analogues that activate AMPK without inhibition of complex I, 27 analogues of AdipoRon were designed, synthesized and biologically evaluated. As results, benzyloxy arylamide B10 was identified as a potent AMPK activator without inhibition of complex I. B10 dose-dependently improved glucose tolerance in normal mice, and significantly lowered fasting blood glucose level and ameliorated insulin resistance in db/db diabetic mice. More importantly, unlike the pan-AMPK activator MK-8722, B10 did not cause cardiac hypertrophy, probably owing to its selective activation of AMPK in the muscle tissue but not in the heart tissue. Together, B10 represents a novel class of AMPK activators with promising therapeutic potential against metabolic disease.
- Chen, Caiping,Cheng, Keguang,Cheng, Yalong,Dai, Liang,Li, Haobin,Qian, Ming,Sun, Geng,Wang, Pengfei,Wen, Xiaoan,Xu, Qing-Long,You, Yanping,Yuan, Haoliang,Zhou, Xinyu
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supporting information
(2020/06/08)
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- Microballs Containing Ni(0)Pd(0) Nanoparticles for Highly Selective Micellar Catalysis in Water
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Both Ni(0) complexes and nanoparticles (NPs) are unstable in water, which poses a significant hindrance to their application in aqueous synthetic catalysis. To overcome these barriers, ligated Ni(0) nanoparticles (diameter 1 nm) containing a minimum amount of Pd(0) in the microballs formed of amphiphile PS-750-M are developed and applied in the highly selective carbamate cleavage. Selectivity and functional group tolerance are thoroughly investigated. Control experiments revealed the importance of an individual component of the nanocatalyst. Use of our proline-based amphiphile PS-750-M is critical for achieving microball architecture, the stability of nanoparticles, and desired catalytic activity. Once formed, microballs can be isolated and stored at ambient temperature. Catalyst is thoroughly characterized by X-ray photoelectron spectroscopy, scanning electron microscopy, high-resolution transmission electron microscopy, thermogravimetric analysis, infrared, and cyclic voltammetry. For selective catalysis, zero oxidation state of both Ni and Pd is crucial. On the basis of catalyst characterization and control experiments, the plausible reaction mechanism is proposed.
- Bihani, Manisha,Bora, Pranjal P.,Nachtegaal, Maarten,Jasinski, Jacek B.,Plummer, Scott,Gallou, Fabrice,Handa, Sachin
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p. 7520 - 7526
(2019/08/15)
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- INHIBITORS OF DIHYDROCERAMIDE DESATURASE FOR TREATING DISEASE
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Disclosed herein are dihydroceramide desaturase 1 (Des1) inhibitor compounds and compositions, which are useful in the treatment of diseases, such as metabolic disorders, where inhibition of Des1 is expected to be therapeutic to a patient. Methods of inhibition of Des1 activity in a human or animal subject are also provided.
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Paragraph 0435; 0436; 0437
(2019/08/20)
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- Analysis of chain length, substitution patterns, and unsaturation of AM-404 derivatives as 20S proteasome stimulators
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Proteasome-mediated degradation of proteins is a vital cellular process and is performed by the ubiquitin-dependent proteasome system (UPS) and the ubiquitin-independent proteasome system (UIPS). While both systems are necessary to maintain healthy cell function, many disease states are characterized by reduced activity of the UPS, and the UIPS cannot by itself maintain proper protein levels. It has been suggested that the 20S core particle (20S CP), the isoform of the proteasome in the UIPS that can degrade proteins without a ubiquitin tag, can be stimulated with a small molecule to assist the 20S CP to accept and hydrolyze substrates more rapidly. Several small molecule stimulators of the 20S CP have since been discovered, including AM-404, an arachidonic acid derivative. AM-404 has previously been shown to inhibit fatty acid amide hydrolase activity. We wished to evaluate what structural components of AM-404 are required to stimulate the 20S CP with the long-term goal of using this information to design a stimulator with better drug-like qualities. We synthesized numerous derivatives of AM-404, varying the chain length, substitutions, and degree of unsaturation. Through this endeavor, we obtained several molecules capable of stimulating the 20S CP to various degrees. We discovered that though chain length is important, the presence of a cis-alkene in a specific location in the aliphatic chain has the greatest impact on the ability to stimulate the 20S CP. Two of the derivatives maintain modest stimulatory activity, and have improved toxicity over AM-404.
- Coleman, Rachel A.,Muli, Christine S.,Zhao, Yizhou,Bhardwaj, Atul,Newhouse, Timothy R.,Trader, Darci J.
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supporting information
p. 420 - 423
(2019/01/04)
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- Selective Synthesis of Primary Anilines from NH3 and Cyclohexanones by Utilizing Preferential Adsorption of Styrene on the Pd Nanoparticle Surface
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Dehydrogenative aromatization is one of the attractive alternative methods for directly synthesizing primary anilines from NH3 and cyclohexanones. However, the selective synthesis of primary anilines is quite difficult because the desired primary aniline products and the cyclohexanone substrates readily undergo condensation affording the corresponding imines (i.e., N-cyclohexylidene-anilines), followed by hydrogenation to produce N-cyclohexylanilines as the major products. In this study, primary anilines were selectively synthesized in the presence of supported Pd nanoparticle catalysts (e.g., Pd/HAP, HAP=hydroxyapatite, Ca10(PO4)6(OH)2) by utilizing competitive adsorption unique to heterogeneous catalysis; in other words, when styrene was used as a hydrogen acceptor, which preferentially adsorbs on the Pd nanoparticle surface in the presence of N-cyclohexylidene-anilines, various structurally diverse primary anilines were selectively synthesized from readily accessible NH3 and cyclohexanones. The Pd/HAP catalyst was reused several times though its catalytic performance gradually declined.
- Koizumi, Yu,Jin, Xiongjie,Yatabe, Takafumi,Miyazaki, Ray,Hasegawa, Jun-ya,Nozaki, Kyoko,Mizuno, Noritaka,Yamaguchi, Kazuya
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supporting information
p. 10893 - 10897
(2019/07/12)
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- Synthesis and in vitro evaluation of diverse heterocyclic diphenolic compounds as inhibitors of DYRK1A
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Dual-specificity tyrosine phosphorylation-related kinase 1A (DYRK1A) is a dual-specificity protein kinase that catalyses phosphorylation and autophosphorylation. Higher DYRK1A expression correlates with cancer, in particular glioblastoma present within the brain. We report here the synthesis and biological evaluation of new heterocyclic diphenolic derivatives designed as novel DYRK1A inhibitors. The generation of these heterocycles such as benzimidazole, imidazole, naphthyridine, pyrazole-pyridines, bipyridine, and triazolopyrazines was made based on the structural modification of the lead DANDY and tested for their ability to inhibit DYRK1A. None of these derivatives showed significant DYRK1A inhibition but provide valuable knowledge around the importance of the 7-azaindole moiety. These data will be of use for developing further structure-activity relationship studies to improve the selective inhibition of DYRK1A.
- Zhou, Qingqing,Reekie, Tristan A.,Abbassi, Ramzi H.,Indurthi Venkata, Dinesh,Font, Josep S.,Ryan, Renae M.,Munoz, Lenka,Kassiou, Michael
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p. 5852 - 5869
(2018/11/10)
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- Addressing Kinase-Independent Functions of Fak via PROTAC-Mediated Degradation
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Enzymatic inhibition has proven to be a successful modality for the development of many small-molecule drugs. In recent years, small-molecule-induced protein degradation has emerged as an orthogonal therapeutic strategy that has the potential to expand the druggable target space. Focal adhesion kinase (Fak) is a key player in tumor invasion and metastasis, acting simultaneously as a kinase and a scaffold for several signaling proteins. While previous efforts to modulate Fak activity were limited to kinase inhibitors with low success in clinical studies, protein degradation offers a possibility to simultaneously block Fak's kinase signaling and scaffolding capabilities. Here, we report the development of a selective and potent Fak degrader, PROTAC-3, which outperforms a clinical candidate, defactinib, with respect to Fak activation as well as Fak-mediated cell migration and invasion. These results underline the potential that PROTACs offer in expanding the druggable space and controlling protein functions that are not easily addressed by traditional small-molecule therapeutics.
- Cromm, Philipp M.,Samarasinghe, Kusal T. G.,Hines, John,Crews, Craig M.
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supporting information
p. 17019 - 17026
(2019/01/04)
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- INHIBITORS OF DIHYDROCERAMIDE DESATURASE FOR TREATING DISEASE
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Disclosed herein are dihydroceramide desaturase 1 (Des1) inhibitor compounds and compositions, which are useful in the treatment of diseases, such as metabolic, cardiovascular, fibrotic, autoimmune/chronic inflammatory diseases, cystic fibrosis, various cancers, neurodegenerative diseases, lipid storage disorders, and ischemia/reperfusion injury, where inhibition of Des1 is expected to be therapeutic to a patient. Methods of inhibition of Des1 activity in a human or animal subject are also provided.
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Paragraph 00250
(2018/09/11)
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- Metal-free deoxygenation and reductive disilylation of nitroarenes by organosilicon reducing reagents
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A metal-free deoxygenation and reductive disilylation of nitroarenes was achieved using N,N’-bis(trime-thylsilyl)-4,4’-bipyridinylidene (1) under mild and neutral reaction conditions, and a broad functional group tolerance was possible in this reaction. Mono-deoxygenation, giving a synthetically valuable N,O-bis(trimethylsilyl)phe-nylhydroxylamine (7a) as a readily available and safe phenylnitrene source from nitrobenzene, and double-deoxy-genation, giving N,N-bis(trimethylsilyl)anilines 8, were easily controlled by varying the amounts of 1 and reaction temperature as well as adding dibenzothiophene (DBTP). Reaction of 2-arylnitrobenzenes with 1 resulted in the formation of the corresponding carbazoles 14 via in situ-gen-erated phenylnitrene species derived by thermolysis of N,O-bis(trimethylsilyl)phenylhydroxylamines 7, followed by their subsequent intramolecular C H insertion. In addition, the intramolecular N N coupling reaction proceeded in the reduction of 2,2’-dinitrobiphenyl derivatives by 1, giving the corresponding benzo[c]cinnolines.
- Bhattacharjee, Argha,Hosoya, Hiromu,Ikeda, Hideaki,Nishi, Kohei,Tsurugi, Hayato,Mashima, Kazushi
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supporting information
p. 11278 - 11282
(2018/10/20)
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- Multicomponent, fragment-based synthesis of polyphenol-containing peptidomimetics and their inhibiting activity on beta-amyloid oligomerization
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A new and short fragment-based approach towards artificial (but "natural-based") complex polyphenols has been developed, exploiting the Ugi multicomponent reaction of phenol-containing simple substrates. The resulting library of compounds has been tested
- Lambruschini, Chiara,Galante, Denise,Moni, Lisa,Ferraro, Francesco,Gancia, Giulio,Riva, Renata,Traverso, Alessia,Banfi, Luca,D'Arrigo, Cristina
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p. 9331 - 9351
(2017/11/22)
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- Structural Optimization and Pharmacological Evaluation of Inhibitors Targeting Dual-Specificity Tyrosine Phosphorylation-Regulated Kinases (DYRK) and CDC-like kinases (CLK) in Glioblastoma
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The DYRK family contains kinases that are up-regulated in malignancy and control several cancer hallmarks. To assess the anticancer potential of inhibitors targeting DYRK kinases, we developed a series of novel DYRK inhibitors based on the 7-azaindole scaffold. All compounds were tested for their ability to inhibit DYRK1A, DYRK1B, DYRK2, and the structurally related CLK1. The library was screened for anticancer efficacy in established and stem cell-like glioblastoma cell lines. The most potent inhibitors (IC50 ≤ 50 nM) significantly decreased viability, clonogenic survival, migration, and invasion of glioblastoma cells. Target engagement was confirmed with genetic knockdown and the cellular thermal shift assay. We demonstrate that DYRK1A’s thermal stability in cells is increased upon compound treatment, confirming binding in cells. In summary, we present synthesis, structure-activity relationship, and efficacy in glioblastoma-relevant models for a library of novel 7-azaindoles.
- Zhou, Qingqing,Phoa, Athena F.,Abbassi, Ramzi H.,Hoque, Monira,Reekie, Tristan A.,Font, Josep S.,Ryan, Renae M.,Stringer, Brett W.,Day, Bryan W.,Johns, Terrance G.,Munoz, Lenka,Kassiou, Michael
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p. 2052 - 2070
(2017/03/17)
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- Preparation and optoelectronic behaviours of novel electrochromic devices based on triphenylamine-containing ambipolar materials
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Two new triphenylamine-containing ambipolar electrochromic materials with ether linkages, 1-(2-(4-(bis(4-methoxyphenyl)amino)phenoxy)ethyl)-1′-ethyl-[4,4′-bipyridine]-1,1′-diium tetrafluoroborate (TPA-Vio) and 2-(4-(bis(4-methoxyphenyl)amino)phenoxy)anthracene-9,10-dione (TPA-OAQ), were successfully synthesized and fabricated into novel electrochromic devices. These devices demonstrated interesting and much higher performance than devices derived from TPA-3OMe with respect to driving voltage, switching time, and electrochromic stability.
- Huang, De-Cheng,Wu, Jung-Tsu,Fan, Yang-Ze,Liou, Guey-Sheng
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supporting information
p. 9370 - 9375
(2017/09/29)
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- NOVEL COMPOSITIONS FOR LABELING BIOMOLECULES AND METHODS USING SAME
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The present invention includes novel compounds useful for labeling biomolecules. The present invention further includes a novel method of labeling a biomolecule using a compound of the invention. The present invention further includes a novel method of im
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- BICYCLIC HETEROCYCLE DERIVATIVES AS BROMODOMAIN INHIBITORS
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The invention relates to novel bicyclic heterocycle derivatives of formula (I) wherein Cy1,Cy2, R1,R2 and L have the meaning given in the specification, and pharmaceutically acceptable salts thereof. The compounds of formula (I) are usefulas bromodomain inhibitors in the treatment or prevention of diseases or disorders where bromodomain inhibition is desired.
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Page/Page column 39
(2017/01/23)
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- Fe-Catalyzed Amination of (Hetero)Arenes with a Redox-Active Aminating Reagent under Mild Conditions
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A novel and efficient Fe-catalyzed direct C?H amination (NH2) of arenes is reported using a new redox-active aminating reagent. The reaction is simple, and can be performed under air, mild, and redox-neutral conditions. This protocol has a broad substrate scope and could be used in the late-stage modification of bioactive compounds. Mechanistic studies demonstrate that a radical pathway could be involved in this transformation.
- Liu, Jianzhong,Wu, Kai,Shen, Tao,Liang, Yujie,Zou, Miancheng,Zhu, Yuchao,Li, Xinwei,Li, Xinyao,Jiao, Ning
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supporting information
p. 563 - 567
(2017/01/18)
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- Fatty Acid Amide Hydrolase (FAAH), Acetylcholinesterase (AChE), and Butyrylcholinesterase (BuChE): Networked Targets for the Development of Carbamates as Potential Anti-Alzheimer's Disease Agents
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The modulation of the endocannabinoid system is emerging as a viable avenue for the treatment of neurodegeneration, being involved in neuroprotective and anti-inflammatory processes. In particular, indirectly enhancing endocannabinoid signaling to therapeutic levels through FAAH inhibition might be beneficial for neurodegenerative disorders such as Alzheimer's disease, effectively preventing or slowing the progression of the disease. Hence, in the search for a more effective treatment for Alzheimer's disease, in this paper, the multitarget-directed ligand paradigm was applied to the design of carbamates able to simultaneously target the recently proposed endocannabinoid system and the classic cholinesterase system, and achieve effective dual FAAH/cholinesterase inhibitors. Among the two series of synthesized compounds, while some derivatives proved to be extremely potent on a single target, compounds 9 and 19 were identified as effective dual FAAH/ChE inhibitors, with well-balanced nanomolar activities. Thus, 9 and 19 might be considered as new promising candidates for Alzheimer's disease treatment.
- Montanari, Serena,Scalvini, Laura,Bartolini, Manuela,Belluti, Federica,Gobbi, Silvia,Andrisano, Vincenza,Ligresti, Alessia,Di Marzo, Vincenzo,Rivara, Silvia,Mor, Marco,Bisi, Alessandra,Rampa, Angela
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supporting information
p. 6387 - 6406
(2016/07/26)
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- NOVEL AROMATIC COMPOUND AND USE THEREOF
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Provided is a compound showing a bone formation promoting action (and/or bone resorption suppressive action). A compound of the formula (I) or a pharmacologically acceptable salt: [wherein each substituent is as defined in the DESCRIPTION], has low toxicity, shows good pharmacokinetics, has an action to promote bone formation, and is useful for the prophylaxis or To treatment of metabolic bone diseases (osteoporosis, fibrous osteitis (hyperparathyroidism), osteomalacia, Paget's disease that influences the systemic bone metabolism parameter etc.) associated with a decrease in the bone formation ability as compared to the bone resorption capacity.
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Paragraph 0592-0594
(2016/08/17)
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- An efficient and chemoselective deprotection of aryl tert-butyldimethylsilyl (TBDMS) ethers by NaCN
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Phenolic tert-butyldimethylsilyl (TBDMS) ethers can be deprotected to yield phenols in excellent yield using sodium cyanide (NaCN) as catalyst in ethanol. The deprotectation of various phenolic TBDMS ethers were found to be very convenient, fast, high yielding and chemoselective.
- Qiao, Xue-Jun,Hou, Xiao,Fang, Wu-Hong,Bao, Xue-Fei,Chen, Guo-Liang
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p. 899 - 904
(2016/05/19)
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- INDOLE AND PYRROLE COMPOUNDS, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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Compounds of formula (I): wherein Ra, Rb, Rc, Rd, R3, R4, R5, A1, A2, T and W are as defined in the description. Medicinal products containing the same whic
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Paragraph 0199-0201
(2016/06/28)
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- Novel derivatives of indole and pyrrole, method for the production thereof and pharmaceutical compositions containing same
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The invention relates to compounds of formula (I), wherein Ra, Rb, Rc, Rd, R3, R4, R5, A1, A2, T and W are as defined in the description. The invention also relates to drugs containing same.
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Paragraph 0278; 0279; 0280; 0281; 0282
(2016/10/09)
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- PHOSPHATE COMPOUNDS, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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Compounds of formula (I): wherein X, Y, A1, A2, Ra, Rb, Rc, Rd, R3, R4, T and R5 are as defined in the description. Medicinal products containing the same which are useful in treating pathologies involving a deficit in apoptosis, such as cancer, auto-immune diseases, and diseases of the immune system.
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Paragraph 0155-0157
(2015/02/19)
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- PYRROLE COMPOUNDS, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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Compounds of formula (I): wherein A1, A2, Ra, Rb, Rc, Rd, R3, R4, R5 and T are as defined in the description. Medicinal products containing the same which are useful in treating pathologies involving a deficit in apoptosis, such as cancer, auto-immune diseases, and diseases of the immune system.
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Paragraph 0258; 0259; 0260
(2015/02/19)
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- Site-selective arene C-H amination via photoredox catalysis
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Over the past several decades, organometallic cross-coupling chemistry has developed into one of the most reliable approaches to assemble complex aromatic compounds from preoxidized starting materials. More recently, transition metal-catalyzed carbon-hydrogen activation has circumvented the need for preoxidized starting materials, but this approach is limited by a lack of practical amination protocols. Here, we present a blueprint for aromatic carbon-hydrogen functionalization via photoredox catalysis and describe the utility of this strategy for arene amination. An organic photoredox-based catalyst system, consisting of an acridinium photooxidant and a nitroxyl radical, promotes site-selective amination of a variety of simple and complex aromatics with heteroaromatic azoles of interest in pharmaceutical research. We also describe the atom-economical use of ammonia to form anilines, without the need for prefunctionalization of the aromatic component.
- Romero, Nathan A.,Margrey, Kaila A.,Tay, Nicholas E.,Nicewicz, David A.
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p. 1326 - 1330
(2015/10/12)
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- Preparation of nano silica supported sodium hydrogen sulfate: As an efficient catalyst for the trimethyl, triethyl and t-butyldimethyl silylations of aliphatic and aromatic alcohols in solution and under solvent-free conditions
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Nano silica supported sodium hydrogen sulfate has been prepared by mixing NaHSO4 with activated Nano silicagel. We wish to report a new method for the synthesis of trimethyl (TMS), triethyl (TES) and t-butyldimethyl silyl (TBS) ethers from benzylic, allylic, propargylic alcohols, phenols, naphtholes and some of phenolic drugs in the solution and under solvent-free conditions.
- Abri, Abdolreza,Ranjdar, Somayeh
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p. 929 - 934
(2014/10/16)
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- Synthesis of 5-methyl phenanthridium derivatives: A new class of human DOPA decarboxylase inhibitors
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DOPA decarboxylase (DDC) is responsible for the decarboxylation of l-DOPA and related aromatic amino acids and correlates closely with a number of clinical disorders. Sanguinarine, a natural quaternary benzophenanthridine alkaloid (QBA), was reported to b
- Cheng, Pi,Zhou, Jie,Qing, Zhixing,Kang, Weisong,Liu, Sheng,Liu, Wei,Xie, Hongqi,Zeng, Jianguo
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supporting information
p. 2712 - 2716
(2014/06/09)
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- Synthesis of 5-methyl phenanthridium derivatives: A new class of human DOPA decarboxylase inhibitors
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DOPA decarboxylase (DDC) is responsible for the decarboxylation of l-DOPA and related aromatic amino acids and correlates closely with a number of clinical disorders. Sanguinarine, a natural quaternary benzophenanthridine alkaloid (QBA), was reported to b
- Cheng, Pi,Zhou, Jie,Qing, Zhixing,Kang, Weisong,Liu, Sheng,Liu, Wei,Xie, Hongqi,Zeng, Jianguo
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supporting information
p. 2712 - 2716
(2015/02/19)
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- β-Lactam estrogen receptor antagonists and a dual-targeting estrogen receptor/tubulin ligand
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Twelve novel β-lactams were synthesized and their antiproliferative effects and binding affinity for the predominant isoforms of the estrogen receptor (ER), ERα and ERβ, were determined. β-Lactams 23 and 26 had the strongest binding affinities for ERα (IC
- O'Boyle, Niamh M.,Pollock, Jade K.,Carr, Miriam,Knox, Andrew J. S.,Nathwani, Seema M.,Wang, Shu,Caboni, Laura,Zisterer, Daniela M.,Meegan, Mary J.
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p. 9370 - 9382
(2015/01/09)
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- A synthetic and mechanistic investigation into the cobalt(i) catalyzed amination of aryl halides
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Employing first-row transition metals in catalytic two-electron transformations remains a synthetic challenge. In order to overcome the common and often deleterious single-electron reactivity, an electron rich ligand was targeted on cobalt. Herein, we report the Co(i) catalyzed amination of aryl halides with lithium hexamethyldisilazide. This transformation features (PPh3)3CoCl (1) as the catalyst and affords structurally diverse and electronically varied primary arylamines in good chemical yields, with the scope of the reaction featuring arylamines that cannot be synthesized via traditional metal-catalyzed amination routes, including 4-aminophenylboronic acid pinacol ester. Stoichiometric reactivity revealed that (PPh3)2CoN(SiMe3)2 (2) is likely generated within the catalytic cycle and could be independently synthesized from the reaction of (PPh3)3CoCl with LiN(SiMe3)2. Catalytic reactivity featuring the Co-amide complex, (PPh3)2CoN(SiMe3)2, showed that it is a competent catalyst, implying that the (PPh3)3CoCl may be serving as a pre-catalyst in the reaction. Both stoichiometric and kinetic studies support the catalytic cycle involving a Co(i) complex. Catalytic reactions featuring Co(ii) complexes resulted in undesired biaryl formation, a product that is not observed under standard catalytic conditions and any productive catalytic reactivity likely arises from an in situ reduction of Co(ii) to Co(i). A Hammett study was carried out to differentiate between a closed-shell or radical mechanism, the results of which are consistent with the proposed closed-shell mechanism. Initial studies indicate that this reactivity may be expanded to other bulky nucleophiles. This journal is
- Brennan, Marshall R.,Kim, Dongyoung,Fout, Alison R.
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p. 4831 - 4839
(2015/02/19)
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- Chemoselective hydrogenation catalyzed by Pd on spherical carbon
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We have developed a highly chemoselective hydrogenation method using a novel palladium catalyst supported on spherical carbon (0.5 % Pd/SC). The 0.5 % Pd/SC exhibited a novel catalytic activity and could achieve the chemoselective hydrogenation of alkynes, alkenes, azides, nitro groups, and aliphatic O-tert-butyldimethylsilyl (TBS) ethers without hydrogenolysis of benzyl esters, benzyl ethers, nitriles, aromatic ketones, N-carbobenzyloxy (N-Cbz) protective groups, and aromatic O-TBS ethers. Highly selective spheres: The chemoselective hydrogenation of C-C multiple bonds, azides, nitro groups, and aliphatic O-tert-butyldimethylsilyl (TBS) ethers is achieved in the presence of benzyl esters, benzyl ethers, nitriles, aromatic ketones, N-carbobenzyloxy (Cbz) protective groups, and aromatic O-TBS ethers by a novel heterogeneous palladium catalyst supported on spherical carbon (0.5 % Pd/SC). Copyright
- Esaki, Hiroyoshi,Hattori, Tomohiro,Tsubone, Aya,Mibayashi, Satoko,Sakata, Takao,Sawama, Yoshinari,Monguchi, Yasunari,Yasuda, Hidehiro,Nosaka, Kazuto,Sajiki, Hironao
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p. 3629 - 3635
(2014/01/06)
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- A mild and highly efficient method for the preparation of silyl ethers using Fe(HSO4)3/Et3N by chlorosilanes
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Avery efficient and mild procedure for preparation of silyl ethers from benzylic, allylic, propargilic alcohols, phenols, naphtoles and some of phenolic drugs with trimethylsilylchloride (TMSCl), triethylsilylchloride (TESCl) and t-buthyldimethylsilyl chloride (TDSCl) ethers in the presence of Fe(HSO 4)3/Et3N in roomtemperature in excellent yields is reported. This procedure also allows the excellent selectivity for silylation of alcohols and phenols.
- Abri, Abdolreza,Assadi, Mohammad Galeh,Pourreza, Samira
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p. 1449 - 1454
(2013/03/13)
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- THERAPEUTIC AGENT FOR HEPATITIS C
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This invention provides a therapeutic agent for hepatitis C comprising, as an active ingredient, a compound having anti-HCV activity useful in treatment of hepatitis C. The therapeutic agent for hepatitis C comprises, as an active ingredient, a compound represented by formula (I) or a pharmaceutically acceptable salt thereof.
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- Highly selective reduction of nitroarenes by iron(0) nanoparticles in water
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Highly selective reduction of nitroarenes has been achieved using iron metal nanoparticles in water at room temperature. A wide spectrum of reducible functionalities remained inert under the reaction conditions. During the reaction a change in shape of Fe nanoparticles was observed.
- Dey, Raju,Mukherjee, Nirmalya,Ahammed, Sabir,Ranu, Brindaban C.
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supporting information; experimental part
p. 7982 - 7984
(2012/09/08)
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- TRYCYCLIC COMPOUNDS AND PBK INHIBITORS CONTAINING THE SAME
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Trycyclic compounds are provided. These compounds are PBK inhibitors, and are useful for the treatment of PBK related diseases, including cancer.
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Page/Page column 229
(2011/10/13)
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- Gold catalysis: Tandem reactions of diyne-diols and external nucleophiles as an easy access to tricyclic cage-like structures
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Different diyne-diols composed of two terminal homopropargylic alcohol groups were prepared by bi-directional synthesis. Subjection of the syn diastereomers to NAC-gold catalysts (NAC=nitrogen acyclic carbene) in the presence of external nucleophiles such
- Hashmi, A. Stephen K.,Buehrle, Miriam,Woelfle, Michael,Rudolph, Matthias,Wieteck, Marcel,Rominger, Frank,Frey, Wolfgang
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supporting information; experimental part
p. 9846 - 9854
(2010/11/04)
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- Discovery of novel quinolinone adenosine A2B antagonists
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A novel series of quinolinone-based adenosine A2B receptor antagonists was identified via high throughput screening of an encoded combinatorial compound collection. Synthesis and assay of a series of analogs highlighted essential structural features of the initial hit. Optimization resulted in an A2B antagonist (2i) which exhibited potent activity in a cAMP accumulation assay (5.1 nM) and an IL-8 release assay (0.4 nM).
- McGuinness, Brian F.,Ho, Koc-Kan,Stauffer, Tara M.,Rokosz, Laura L.,Mannava, Neelima,Kultgen, Steven G.,Saionz, Kurt,Klon, Anthony,Chen, Weiqing,Desai, Hema,Rogers, W. Lynn,Webb, Maria,Yin, Juxing,Jiang, Yan,Li, Tailong,Yan, Hao,Jing, Konghua,Zhang, Shengting,Majumdar, Kanak Kanti,Srivastava, Vikash,Saha, Samiran
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scheme or table
p. 7414 - 7420
(2011/02/23)
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- THIAZOLIDINONE COMPOUNDS, AND METHODS OF MAKING AND USING SAME
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Provided herein are thiazolidinone compounds, and methods of making and using the same. Such compounds may be used in inflammatory or immune-mediated disorders. The disclosure provides for treating respiratory or ocular disorders, treating arthritis, or may be used to treat cancer, such as prostate or breast cancer, or multiple myeloma.
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Page/Page column 64-65
(2009/04/25)
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- Palladium-catalyzed silane/siloxane reductions in the one-pot conversion of nitro compounds into their amines, hydroxylamines, amides, sulfonamides, and carbamates
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A combination of palladium(II) acetate, aqueous potassium fluoride, and polymethylhydrosiloxane (PMHS) facilitates the room-temperature reduction of aromatic nitro compounds to anilines. These reactions tend to be quick (30 min), high-yielding, and tolerate a range of other functional groups. Replacement of PMHS/KF with triethylsilane allows for the reduction of aliphatic nitro compounds to their corresponding hydroxylamines. Depending on the substrate, both conditions can allow for the in situ conversion of the product amines into amides, sulfonamides, and carbamates. Georg Thieme Verlag Stuttgart.
- Rahaim Jr., Ronald J.,Maleczka Jr., Robert E.
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p. 3316 - 3340
(2008/09/17)
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- New prodrugs derived from 6-aminodopamine and 4-aminophenol as candidates for melanocyte-directed enzyme prodrug therapy (MDEPT)
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Two novel tyrosinase mediated drug delivery pathways have been investigated for the selective delivery of cytotoxic units to melanocytes from urea and thiourea prodrugs. The synthesis of these prodrugs is reported, as well as oximetry data that illustrate that the targets are substrates for tyrosinase. The stability of each of the prodrugs in (i) phosphate buffer and (ii) bovine serum is discussed, and the urea prodrugs are identified as lead candidates for further studies. Finally, HPLC studies and preliminary cytotoxicity studies in a melanotic and an amelanotic cell line, that illustrate the feasibility of the approach, are presented. The Royal Society of Chemistry 2005.
- Knaggs, Sarah,Malkin, Hugh,Osborn, Helen M.I.,Williams, Nana Aba O.,Yaqoob, Parveen
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p. 4002 - 4010
(2007/10/03)
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- Novel steroid mimics directed towards the estradiol skeleton
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A series of non-symmetrical tri- and tetra-substituted ureas have been prepared to mimic the rigid tetracyclic core of estradiol. Tetra-substituted ureas were prepared by a five-step protocol, involving activation and displacement of a carbonyldiimidazole
- Bridgeman, Eve,Cavill, Julie L.,Schofield, Daniel J.,Wilkins, Derek S.,Tomkinson, Nicholas C. O.
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p. 8521 - 8524
(2007/10/03)
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