117237-99-7Relevant articles and documents
Unexpected imidazoquinoxalinone annulation products in the photoinitiated reaction of substituted-3-methyl-quinoxalin-2-ones with N-phenylglycine
De La Fuente, Julio R.,Canete, Alvaro,Jullian, Carolina,Saitz, Claudio,Aliaga, Christian
, p. 1335 - 1345 (2013)
Photoinduced electron transfer between N-phenylglycine (NPG) and electronically excited triplets of 7-substituted-3-methyl-quinoxalin-2-ones in acetonitrile generate the respective ion radical pair, where by decarboxylation the phenyl-amino-alkyl radical, PhNHCH2?, is generated. This radical reacts with the 3-methyl-quinoxalin-2-ones ground states, leading to the product 2. Other, unexpected, 7-substituted-1,2,3,3a-tetrahydro-3a-methyl-2- phenylimidazo[1,5-a]quinoxalin-4(5H)-ones, annulation products, 3a-f, were generated; likely by the addition of two PhNHCH2? radicals, to positions 3 and 4 of the quinoxalin-2-ones. The reaction mechanism includes a photoinduced one electron transfer initiation step, propagation steps involving radical intermediates and NPG with radical chain termination steps that lead to the respective products 2a-f and 3a-f and NPG by-products. The proposed mechanism accounts for the strong dependency found for the initial photoconsumption quantum yields on the electron-withdrawing power of the substituent. Therefore, photolysis of common reactants widely used such as NPG and substituted quinoxalin-2-ones may provide a simple synthetic way to the unusual, unreported tetrahydro-imidazoquinoxalinones 3a-f.
In situ localization of alkaline phosphatase activity in tumor cells by an aggregation-induced emission fluorophore-based probes
Guan, Qinghua,Lu, Xinmiao,Su, Yue,Xu, Jichen,Liang, Xiaofei,Li, Peiyong,Zhu, Xinyuan
, (2020)
In situ detection of certain specific enzyme activities in cells is deeply attached to tumor diagnosis. Conventional enzyme-responsive fluorescent probes have difficulty detecting targeted enzymes in situ in cells due to the low detection accuracy caused by the spread of fluorescence probes. In order to solve this problem, we have designed and synthesized an enzyme-responsive, water-soluble fluorescent probe with AIE characteristics, which could aggregate and precipitate to produce in situ fluorescence when reacting with the targeted enzyme in cells. The AIE fluorophore (TPEQH) was utilized to design the enzyme-responsive, fluorescent probe (TPEQHA) by introducing a phosphate group on to it, which could be specifically decomposed by the targeted enzyme, namely alkaline phosphatase (ALP). In tumor cells, TPEQH was highly produced due to the interaction of phosphate on the TPEQHA and the overexpressed ALP. Water-insoluble TPEQH then precipitated and release fluorescence in situ, thereby successfully detecting the ALP. Furthermore, the expression level of ALP could be determined by the fluorescence intensity of TPEQH with higher accuracy due to the inhibition of TPEQH leak, which demonstrated a potential application of in suit ALP detection in both clinical diagnosis and scientific research of tumor.
Iron- or Zinc-Mediated Synthetic Approach to Enantiopure Dihydroquinoxalinones
Li, Dazhi,Ollevier, Thierry
, p. 1273 - 1280 (2019/01/04)
A general and efficient synthesis of enantiopure dihydroquinoxalinones has been developed using naturally occurring amino acids as starting materials. The reductive cyclization of N-(o-nitroaryl)amino esters was performed by using iron and zinc metal under mild conditions in a water/ethyl acetate mixture. The corresponding dihydroquinoxalinones were obtained in moderate to high yields and high enantiomeric purity, among which 7 new compounds were unprecedented in the literature.
Fluorescent probe based on quinoxalinone aryl sulfides as well as preparation method and application thereof
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Paragraph 0053; 0054; 0055; 0059; 0082, (2018/06/16)
The invention provides a fluorescent probe based on quinoxalinone aryl sulfides as well as a preparation method and application thereof. A chemical structure of a fluorescent probe molecule is shown in formula (I) (shown in the specification), wherein R is selected from allyl and derivatives thereof, benzyl and derivatives thereof, fatty acid ester groups with the carbon atom number of 1-8 or fatty acid with the carbon atom number of 1-8; R1 is selected from alkoxy with the carbon atom number of 1-8, halogen or alkyl with the carbon atom number of 1-8; and R2 is aryl sulfides. The fluorescentprobe molecule is obtained by cyclizing o-phenylenediamine and derivatives thereof, carrying out nucleophilic substitution and carrying out aldol condensation reaction. The quinoxalinone derivative compound turns red fluorescence into green fluorescene after thioether is oxidized into sulfoxide in the presence of up-regulated heme oxidase and active oxygen in ferroptosis cells. The fluorescent probe provided by the invention can be directly added into a culture medium, then acts on cells and carries out detection, and also can be directly injected intravenously or intratumorally and play a role of animal in vivo detection.
HEPATITIS C VIRUS NS3/4A PROTEASE INHIBITORS
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Paragraph 00191, (2019/01/11)
The invention provides novel classes of HCV therapeutics that are orally available, safe and effective HCV NS3/4A protease inhibitors and are less susceptible to drug resistance than existing therapeutics. The invention also relates to pharmaceutical composition of these compounds and methods of preparation and use thereof.
Hepatitis C Virus NS3/4A Protease Inhibitors Incorporating Flexible P2 Quinoxalines Target Drug Resistant Viral Variants
Matthew, Ashley N.,Zephyr, Jacqueto,Hill, Caitlin. J.,Jahangir, Muhammad,Newton, Alicia,Petropoulos, Christos J.,Huang, Wei,Kurt-Yilmaz, Nese,Schiffer, Celia A.,Ali, Akbar
supporting information, p. 5699 - 5716 (2017/07/22)
A substrate envelope-guided design strategy is reported for improving the resistance profile of HCV NS3/4A protease inhibitors. Analogues of 5172-mcP1P3 were designed by incorporating diverse quinoxalines at the P2 position that predominantly interact with the invariant catalytic triad of the protease. Exploration of structure-activity relationships showed that inhibitors with small hydrophobic substituents at the 3-position of P2 quinoxaline maintain better potency against drug resistant variants, likely due to reduced interactions with residues in the S2 subsite. In contrast, inhibitors with larger groups at this position were highly susceptible to mutations at Arg155, Ala156, and Asp168. Excitingly, several inhibitors exhibited exceptional potency profiles with EC50 values ≤5 nM against major drug resistant HCV variants. These findings support that inhibitors designed to interact with evolutionarily constrained regions of the protease, while avoiding interactions with residues not essential for substrate recognition, are less likely to be susceptible to drug resistance.
Hepatitis C virus inhibitors
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Page/Page column 593, (2017/01/23)
Hepatitis C virus inhibitors having the general formula (I) are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
TRIAZOLOPYRAZINE DERIVATIVES AND THEIR USE FOR TREATING NEUROLOGICAL AND PSYCHIATRIC DISORDERS
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Page/Page column 22, (2013/03/26)
The present invention is directed to triazolopyrazine compounds of Formula (I). Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds as therapeutic agents treating neurological and psychiatric disorders.
1-ARYL-4-METHYL-[1,2,4]TRIAZOLO[4,3-a]QUINOXALINE DERIVATIVES
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Page/Page column 60, (2013/03/26)
The present invention relates to novel l-aryl-4-methyl-[l,2,4]triazolo[4,3-a]- quinoxaline derivatives as inhibitors of phosphodiesterase 2 (PDE2) and to a lesser extent of phosphodiesterase 10 (PDE10) or as inhibitors of both, phosphodiesterases 2 and 10. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which PDE2 is involved, or disorders in which both PDE2 and PDE10 are involved, such as neurological and psychiatric disorders, and endocrinological or metabolic diseases. The present invention also relates to radiolabeled compounds which may be useful for imaging and quantifying the PDE2 enzyme in tissues, using positron- emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, to the use of such compounds and compositions for imaging a tissue, cells or a host, in vitro or in vivo and to precursors of said compounds.
COMPOUNDS FOR THE TREATMENT OF MULTI-DRUG RESISTANT BACTERIAL INFECTIONS
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Page/Page column 141, (2010/11/25)
The present invention relates to compounds that demonstrate antibacterial activity, processes for their preparation, pharmaceutical compositions containing them as the active ingredient, to their use as medicaments and to their use in the manufacture of medicaments for use in the treatment of bacterial infections in warm-blooded animals such as humans. In particular this invention relates to compounds useful for the treatment of bacterial infections in warm-blooded animals such as humans, more particularly to the use of these compounds in the manufacture of medicaments for use in the treatment of bacterial infections in warm-blooded animals such as humans.
