- An activated coumarin-enamine Michael acceptor for CN-
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Two coumarin-enamine chemodosimeters have been synthesized in three steps. They have been shown to selectively detect the cyanide ion with a fluorescent response (t1/2 = 20 s) and a limit of detection approximately 4.2 ppb in DMSO. The X-ray crystal structure of the thermodynamically stable E-(keto) enamine isomer of one compound was obtained and exhibited offset π-stacking. This journal is
- Davis, Aaron B.,Lambert, Rachel E.,Fronczek, Frank R.,Cragg, Peter J.,Wallace, Karl J.
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Read Online
- Detection of chemical warfare simulants by phosphorylation of a coumarin oximate
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The detection of chemical warfare simulants is attained by the PET mechanism that gives an "off-on" fluorescent response with a half-life of approximately 50 ms upon phosphorylation of a reactive oximate functionality; the X-ray crystal structure of the oximate was also obtained and is discussed. The Royal Society of Chemistry 2006.
- Wallace, Karl J.,Fagbemi, Ruth I.,Folmer-Andersen, Frantz J.,Morey, Jeroni,Lynth, Vincent M.,Anslyn, Eric V.
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- Discovery of 9-(1-anilinoethyl)-2-morpholino-4-oxo-pyrido[1,2-a]pyrimidine- 7-carboxamides as PI3Kβ/δ inhibitors for the treatment of PTEN-deficient tumours
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Starting from TGX-221, we designed a series of 9-(1-anilinoethyl)-2- morpholino-4-oxo-pyrido[1,2-a]pyrimidine-7-carboxamides as potent and selective PI3Kβ/δ inhibitors. Structure-activity relationships and structure-property relationships around the aniline and the amide substituents are discussed. We identified compounds 17 and 18, which showed profound pharmacodynamic modulation of phosphorylated Akt in the PC3 prostate tumour xenograft, after a single oral dose. Compound 17 also gave significant inhibition of tumour growth in the PC3 prostate tumour xenograft model after chronic oral dosing.
- Barlaam, Bernard,Cosulich, Sabina,Degorce, Sébastien,Fitzek, Martina,Giordanetto, Fabrizio,Green, Stephen,Inghardt, Tord,Hennequin, Laurent,Hancox, Urs,Lambert-Van Der Brempt, Christine,Morgentin, Rémy,Pass, Sarah,Plé, Patrick,Saleh, Twana,Ward, Lara
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- A novel dual-emission fluorescent probe for the simultaneous detection of H2S and GSH
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A novel chlorinated coumarin-malononitrile fluorescent probe with three potential reaction sites, which exhibited highly selective, rapid response, low detection limit, and was capable of the simultaneous detection of H2S (λex/em = 515/564 nm) and GSH (λex/em = 430/517 nm), was first proposed. The probe was successfully applied to dual-channel imaging H2S and GSH in MCF-7 cells.
- Li,Peng,Feng,Wang,Chen,Wang,Li,Li,Wang,Zhang
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- Design and synthesis of a novel colorimetric fluorescent probe for the selective detection of sulfur dioxide in SH-SY5Y neuroblastoma cells and its applications in traditional Chinese medicines
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Sulfur fumigation has attracted extensive attention as one of the important post-harvest processing methods for some traditional Chinese medicines (TCMs) in the last decade. However, sulfur fumigation has recently emerged as a controversial topic due to its potential detrimental effects on the safety and efficacy of TCMs as some sulfur-fumigated TCMs contain numerous sulfur dioxide derivatives; moreover, high levels of sulfur dioxide derivatives can cause some diseases and dangerous environmental pollution. In this study, a DTCC probe with a fast response time, low limit of detection and a high fluorescence quantum yield was designed and synthesized to detect SO2 derivatives based on the coumarin-thiophene dye, which was fused with a coumarin moiety and 2-thiophenecarboxaldehyde. The probe DTCC exhibited a fast response time (less than 10 s), satisfactory selectivity for SO2 derivatives in the presence of other ROS and excellent sensitivity for SO2 derivatives with a low limit of detection (0.23 μM) as well as a wide linear range (0-100 μM). Furthermore, the probe DTCC was successfully applied in fluorescence imaging in SH-SY5Y neuroblastoma cells with excellent membrane permeability and stability. It was also employed in monitoring the total SO2 derivatives in several real TCM samples. These results illustrate that the probe DTCC has an excellent capability for monitoring SO2 derivatives in living cells and real TCM samples.
- Yang, Lili,Liu, Mofan,Sheng, Kangjia,Li, Xiaolu,Du, Junli,Ning, Yaoyao,Wang, Xiaoqing,Li, Jianli,Zhang, Yongmin,Wu, Shaoping
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Read Online
- Dithioacetal-containing pyridopyrimidone derivative as well as preparation and application thereof
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The invention relates to a dithioacetal-containing pyridopyrimidone derivative as well as preparation and application thereof. The compound disclosed by the invention has a structure as shown in a formula (I) in the specification, has excellent insecticidal activity on sogatella furcifera, broad bean aphids and the like, and has a relatively good prevention and treatment effect on potato Y viruses at the same time. The compound can be used for preventing and treating hemiptera pests such as rice planthoppers and aphids, and also can be used for preventing and treating plant viruses such as potato Y viruses. The structure and the preparation process are simple, and the production cost is low.
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Paragraph 0047; 0050-0051
(2021/09/04)
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- SUBSTITUTED BICYCLE HETEROCYCLIC DERIVATIVES USEFUL AS ROMK CHANNEL INHIBITORS
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Disclosed are compounds of Formula (I) or a salt thereof, wherein R1 is (II) or (III); each W is independently NR1b or O; Z is a bond or CHR1d; and R1, R2, Rd, R3, L1, L2, R1a, R1b, R1c, and n are define herein. Also disclosed are methods of using such compounds as inhibitors of ROMK, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating cardiovascular diseases.
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Page/Page column 152
(2018/06/06)
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- SUBSTITUTED NITROGEN CONTAINING COMPOUNDS
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Disclosed are compounds of Formula (I): or a salt thereof, Formula (II) wherein R1 is: or; each W is independently NR1b or O; Z is a bond or CHR1d; and R1, R2, Rd, R3a, R3b, L1, B, V, Y, and n are defined herein. Also disclosed are methods of using such compounds as inhibitors of ROMK, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating cardiovascular diseases.
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Page/Page column 264
(2019/01/05)
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- Deep red emitting triphenylamine based coumarin-rhodamine hybrids with large Stokes shift and viscosity sensing: Synthesis, photophysical properties and DFT studies of their spirocyclic and open forms
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We designed and synthesized triphenylamine based and coumarin fused rhodamine hybrid dyes and characterized using 1H, 13C NMR and HR-LCMS analysis. Both the newly synthesized hybrid dyes were found to show red shifted absorption as well as emissions and large Stokes shift (40–68 nm) as compared to the small Stokes shift (25–30 nm) of reported dyes Rhodamine B and 101. Photophysical properties of these dyes were studied in different solvents and according to the solvents acidity or basicity they preferred to remain in their spirocyclic or open form in different ratio. We studied the spirocyclic as well as open form derivatives of these dyes for their viscosity sensitivity in three different mixture of solvents i.e. polar-protic [EtOH-PEG 400], polar-aprotic [toluene-PEG 400] and non-polar-aprotic [toluene-paraffin]. They are found to show very high viscosity sensitivity in polar-protic mixture of solvents [EtOH-PEG 400] and hence concluded that both polarity as well as viscosity factor worked together for the higher emission enhancement rather than only viscosity factor. As these dyes showed very high viscosity sensitivity in their spirocyclic as well as open form, they can be utilized as viscosity sensors in visible as well as deep red region. We also correlated our experimental finding theoretically by using Density Functional theory computations.
- Kothavale, Shantaram,Jadhav, Amol G.,Sekar, Nagaiyan
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p. 329 - 341
(2016/11/23)
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- Used for the prevention and treatment of cardiovascular diseases
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The invention relates to compounds that can be used for adjusting the expression of apolipoprotein A-I (ApoA-I) and usage of the compounds in treating and preventing cardiovascular diseases and related diseases, including the disorder related to cholesterol or lipids such as atherosclerosis.
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Paragraph 0402-0405
(2016/10/08)
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- Synthesis of 6-oxopyrimidin-1(6H)-yl benzamide derivatives and evaluation of their antibacterial and cytotoxic activity
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A series of novel 2-alkylamino and 2, 4-dialkyl amino 6-oxopyrimidin-1(6H)-yl) benzamide derivatives were prepared in good yields from a base-catalyzed ring opening of oxadiazolo[3,2-a]pyrimidin-5-one and evaluated for their antibacterial and cytotoxicity. Most of the compounds exhibited antibacterial activity. In particular, compounds 5b and 5k exhibited considerable antibiotic activity against Klebsiella pneumonia and Bacillus cereus. In addition, compounds 5g and 5i also inhibited the growth of two human tumor cell lines (A549 and H460) at micromolar concentrations.
- Devarasetty, Kiran,Tharikoppula, Giri,Sridhar, Tailor,Eppakayala, Laxminarayana,Kyasani, Mahesh,Arumugam, Premkumar,Pusuluri, Srinivas
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p. 263 - 274
(2016/03/09)
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- Diarylvinylene similar structure compound and its preparation method and application
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The invention discloses a group of diarylethene structure similar compounds as well as a preparation method and application thereof. The provided compounds have a structure of a general formula I. Moreover, the invention further provides medicinal compositions containing the compounds serving as active ingredients. Researches discover that the compounds have pharmacological activities of resisting influenza viruses, Coxsackie B3 viruses, AIDS viruses, hepatitis B viruses, hepatitis C viruses and the like. Therefore, the invention further provides the application of the compounds and the medicinal compositions containing the compounds serving as active ingredients in preparation of anti-virus medicaments. The invention lays a foundation for deeply researching and developing the application of the compounds as clinical medicaments. The general formula I is as shown in the specification.
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Paragraph 0603; 0604
(2016/10/09)
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- Exploring the isoform selectivity of TGX-221 related pyrido[1,2-a]pyrimidinone-based Class IA PI 3-kinase inhibitors: Synthesis, biological evaluation and molecular modelling
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A novel series of TGX-221 analogues was prepared and tested for their potency against the p110α, p110β, and p110δ isoforms of the PI3K enzyme, and in two cellular assays. The biological results were interpreted in terms of a p110β comparative model, in order to account for their selectivity towards this isoform. A CH2NH type linker is proposed to allow binding into the specificity pocket proposed to accommodate the high p110β-selectivity of TGX-221, although there was limited steric tolerance for substituents on the pendant ring with the 2-position most favourable for substitution.
- Marshall, Andrew J.,Lill, Claire L.,Chao, Mindy,Kolekar, Sharada V.,Lee, Woo-Jeong,Marshall, Elaine S.,Baguley, Bruce C.,Shepherd, Peter R.,Denny, William A.,Flanagan, Jack U.,Rewcastle, Gordon W.
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supporting information
p. 3796 - 3808
(2015/07/27)
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- TREATMENT OF DISEASES BY EPIGENETIC REGULATION
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The present disclosure provides non-naturally occurring polyphenol compounds that inhibit the bromodomain and extra terminal domain (BET) proteins. The disclosed compositions and methods can be used for treatment and prevention of cancer, including NUT midline carcinoma, Burkitt's Lymphoma, Acute Myelogenous Leukemia, and Multiple Myeloma; autoimmune or inflammatory diseases or conditions, and sepsis.
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Paragraph 0450; 0465
(2013/11/05)
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- Facile synthesis of novel pyrimido[1,2-a]pyrimidin-4-ones from highly reactive malonates
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A very simple and efficient procedure for the synthesis of novel 2-hydrox.y-4H-pyrimido[1,2-a]pyrimidin-4-ones is described. Title compounds were obtained from the room temperature reaction of 2-aminopyrimidine and its substituted derivatives with bis(2,4,6-trichlorophenyl) malonates. High product yields were observed under optimized conditions. Applicability and reactivity of a range of substituted and unsubstituted phenyl malonates were also investigated. Structural identification of all new compounds was accomplished by spectroscopic methods and elemental analysis.
- Guellue, Mustafa,Dincsoenmezl, Ali,Oezyavas, Oeznur
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experimental part
p. 2113 - 2120
(2010/06/15)
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- A Gorge-spanning, High-affinity cholinesterase inhibitor to explore β-amyloid plaques
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Cholinesterases are involved in the pathological formation of β-amyloid plaques. To investigate this pathohistological hallmark of Alzheimer's disease we prepared a high-affinity, fluorescent cholinesterase inhibitor. Its fluorescence intensity was significantly enhanced upon binding to cholinesterases. Using this probe, brain samples from mice and humans affected by Alzheimer's disease were successfully analyzed for β-amyloid plaques. Unexpectedly, it was discovered, by competition experiments, that the compound binds to amyloid structures, rather than to cholinesterases inside of the plaques.
- Elsinghorst, Paul W.,Haertig, Wolfgang,Goldhammer, Simone,Grosche, Jens,Guetschow, Michael
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supporting information; experimental part
p. 3940 - 3946
(2009/12/05)
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- COMPOUNDS FOR THE PREVENTION AND TREATMENT OF CARDIOVASCULAR DISEASES
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The present disclosure relates to compounds, which are useful for regulating the expression of apolipoprotein A-I (ApoA-I), and their use for treatment and prevention of cardiovascular disease and related disease states, including cholesterol- or lipid-related disorders, such as, for example, atherosclerosis.
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Page/Page column 26-27; 29-30; 40-41; 50-51
(2008/12/07)
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- COMPOUNDS FOR THE PREVENTION AND TREATMENT OF CARDIOVASCULAR DISEASES
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The present disclosure relates to compounds, which are useful for regulating the expression of apolipoprotei? A-I (ApoA-l), and their use for the treatment and prevention of cardiovascular disease and related disease states, including cholesterol- or lipid-related disorders, such as, for example, atherosclerosis.
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Page/Page column 60-63
(2008/12/07)
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- PHARMACEUTICAL COMPOSITIONS FOR THE PREVENTION AND TREATMENT OF COMPLEX DISEASES AND THEIR DELIVERY BY INSERTABLE MEDICAL DEVICES
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The present invention relates to polyphenol-like compounds that are useful for inhibiting VCAM-1 expression, MCP-1 expression and/or SMC proliferation in a mammal. The disclosed compounds are useful for regulating markers of inflammatory conditions, including vascular inflammation, and for treatment and prevention of inflammatory and cardiovascular diseases and related disease states.
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Page/Page column 94; 101-103
(2008/06/13)
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- 3-SUBSTITUTED-6-ARYL PYRIDINES
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3-substituted-6-aryl pyridines of Formula (I) are provided: Formula (I) wherein R1, R2, R3, R8, R9, A and Ar are defined herein. Such compounds are ligands of C5a receptors. Preferred compounds of Formula (I) bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse agonist activity at C5a receptors. The present invention also relates to pharmaceutical compositions comprising such compounds, and to the use of such compounds in treating a variety of inflammatory, cardiovascular, and immune system disorders. In addition, the present invention provides labeled 3-substituted-6-aryl pyridines, which are useful as probes for the localization of C5a receptors.
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- A novel orally active inhibitor of HLE
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Human leukocyte elastase (HLE) is a serine proteinase, capable of degrading a variety of structural matrix proteins. SSR69071 2-[(4-isopropyl-6-methoxy-1,1-dioxido-3-oxo-1,2-benzisothiazol-2( 3H)-yl) methoxy]-9-(2-piperidin-1-ylethoxy)-4H-pyrido[1,2-a]pyrimidin-4-o ne was selected as a novel orally active HLE inhibitor for treatment of chronic obstructive pulmonary diseases, asthma, emphysema, cystic fibrosis and several inflammatory diseases (WO 01/44245 A1) (J. Pharm. Exp. Ther., submitted for publication).
- Varga, Marton,Kapui, Zoltan,Batori, Sandor,Nagy, Lajos T.,Vasvari-Debreczy, Lelle,Mikus, Endre,Urban-Szabo, Katalin,Aranyi, Peter
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p. 421 - 425
(2007/10/03)
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