- Tryptanthrin from indigo: Synthesis, excited state deactivation routes and efficient singlet oxygen sensitization
-
The microwave-assisted synthesis of tryptanthrin from indigo in mild oxidation conditions, and a comprehensive study of the excited state properties of this compound in a variety of solvents with different polarity and viscosity values at room and low temperatures are reported. In contrast with indigo, emission of the triplet state of tryptanthrin is observed with a very efficient singlet oxygen sensitization quantum yield, indicating that the triplet state is efficiently populated. From time-resolved fluorescence and femtosecond transient absorption data, further supported with time-dependent density functional theory (TDDFT) calculations, two species, with S1 states with locally excited (LE) of π,π* nature and a charge transfer (CT) of n,π* characteristics, originated from an initially populated Frank-Condon S2 state (π,π*), are observed. The two electronically independent species are energetically nearly degenerate and inter-conversion is predicted (and rate constants determined) to occur between LE (S1) and CT (S1) species. Due to the low value of the fluorescence quantum yield (~10?3) and high triplet state yield (?T≥?Δ), the high stability of this compound is associated to the high efficiency of the radiationless deactivation processes which involve the formation of the CT state which efficiently converts, through S1 ~~> Tn intersystem crossing, to the T1 triplet state.
- Pinheiro, Daniela,Pineiro, Marta,Pina, Jo?o,Brand?o, Pedro,Galv?o, Adelino M.,Seixas de Melo, J. Sérgio
-
-
Read Online
- Is the 2,3-carbon-carbon bond of indole really inert to oxidative cleavage by Oxone?-Synthesis of isatoic anhydrides from indoles
-
A recent report has indicated that the oxidizing agent Oxone does not possess the ability to cleave the 2,3-carbon-carbon bond of indole. Work in our laboratory shows that this is not the case. Indole and a variety of aryl ring substituted derivatives readily react to form synthetically important isatoic anhydrides.
- Nelson, Amber C.,Kalinowski, Emily S.,Czerniecki, Nikolas J.,Jacobson, Taylor L.,Grundt, Peter
-
-
Read Online
- Synthesis, structure, and properties of N-(nitramino)phthalimide
-
N-(Nitramino)phthalimide R2N-NHNO2 (R2NH is phthalimide) was synthesized by nitration of N-aminophthalimide with nitronium tetrafluoroborate. The structure of this compound was established by X-ray diffraction and confirmed by 1H, 13C, and 14N NMR spectroscopy. The methylation of this compound with diazomethane affords a mixture of N-methyl (R2N-NMeNO2) and O-methyl (R2N-N=N(O)OMe) isomers. The latter compound contains the previously unknown high-nitrogen-oxygen fragment. The thermal decomposition of N-(nitramino)phthalimide in vacuo at 80-100 °C gives 2H-3,1-benzoxazine- 2,4(1H)-dione (isatoic anhydride) as the major product.
- Klenov,Churakov,Anikin,Strelenko,Fedyanin,Lyssenko,Tartakovsky
-
-
Read Online
- An unusual addition and ring-closure reaction of 1-(2-bromoethyl)-2,3-dihydro-3-propyl-1,3,2-benzo-diazaphosphorin-4(1H)-one 2-oxide with carbon disulfide for a new and convenient synthesis of the fused phosphorus heterocyclic compound
-
The reaction of 1-(2-bromoethyl)-2,3-dihydro-3-propyl-1,3,2- benzodiazaphosphorin-4(1H)-one 2-oxide with carbon disulfide takes an alternative pathway in the use of different bases. The sodium hydride mediated reaction leads to the formation of the tricyclic fused 1,2,3,4,4a,4b,5,6-octahydro-6-oxo-5-propyl-4-thia-3,4b,4a -thiazphosphaphenanthridine 4a-oxide via addition of H-P bond across the double bond of carbon disulfide followed by intramolecular cyclization. In the presence of triethylamine, refluxing a mixture of 1-(2-bromoethyl)-2,3-dihydro-3-propyl-1,3,2-benzodiazaphosphorin-4(1H)-one 2-oxide with carbon disulfide in benzene takes an unusual course with formation in excellent yield of the first example of fused phosphorus heterocyclic 4-[1′-(β-bromoethyl)-4′-oxo-3′-propyl-1′, 2′,3′,4′-tetrahydro-1,3,2-benzodiazaphosphorin-2′ -sulfide]-1,2,3,4,4a,4b,5,6-octahydro-6-oxo-5-propyl-3,4b, 4a- thiazphosphaphenanthridine 4a,2′-dioxide, which was confirmed by spectroscopic methods, microanalyses and single crystal X-ray structure determination.
- Huang, Jun-Min,Chen, Hui,Chen, Ru-Yu
-
-
Read Online
- Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: Preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives
-
A convenient two-step synthesis of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate derivatives has been developed starting from commercially available 2-aminobenzoic acids. In step 1, the anthranilic acids are smoothly converted to isatoic anhydrides using solid triphosgene in THF. In step 2, the anhydride electrophiles are reacted with the sodium enolate of ethyl acetoacetate, generated from sodium hydroxide, in warm N,N-dimethylacetamide resulting in the formation of substituted quinolines. A degradation–buildup strategy of the ethyl ester at the 3-position allowed for the construction of the α-hydroxyacetic acid residue required for the synthesis of key arylquinolines involved in an HIV integrase project.
- Jentsch, Nicholas G.,Hume, Jared D.,Crull, Emily B.,Beauti, Samer M.,Pham, Amy H.,Pigza, Julie A.,Kessl, Jacques J.,Donahue, Matthew G.
-
-
Read Online
- Switchable Access to 3-Carboxylate-4-quinolones and 1-Vinyl-3-carboxylate-4-quinolones via Oxidative Cyclization of Isatins and Alkynes
-
An efficient transition-metal-free oxidative cyclization reaction using isatins and alkynes for the facile synthesis of structurally diverse 4-quinolones has been developed. Intriguingly, switchable access to substituted 3-carboxylate-4-quinolones and 1-vinyl-3-carboxylate-4-quinolones could be achieved by choosing a different base in the reaction. The obtained products could undergo further transformations, increasing the application potential of the method in organic synthesis.
- Jiang, Shi-Fen,Xu, Cheng,Zhou, Zhi-Wen,Zhang, Qin,Wen, Xiao-Hui,Jia, Feng-Cheng,Wu, An-Xin
-
-
Read Online
- Green synthesis of novel phosphonate derivatives using ultrasonic irradiation
-
[Figure not available: see fulltext.] A novel and efficient procedure for the generation of quinazolinone phosphonate derivatives employing the reaction of euparin, isatin or its derivatives, primary amines, dialkyl acetylenedicarboxylates, trimethyl phosphite or triphenyl phosphite, and acidic solution of hydrogen peroxide in aqueous media at ambient temperature under ultrasonic irradiation was developed. Without ultrasonic irradiation, the reaction does not proceed and agitation of the reaction mixture is difficult. Some advantages of this procedure are: short time of reaction, high yields of products, easy isolation of products.
- Sharafian, Shirin,Hossaini, Zinatossadat,Rostami-Charati, Faramarz,Khalilzadeh, Mohammad A.
-
-
Read Online
- Facile synthesis of fluoroalkylated quinolones using fluoroalk-2-ynoates as fluorinated building blocks
-
In the presence of Na2CO3, a variety of fluoroalkylated quinolones were efficiently synthesized from isatins and fluoroalk-2-ynoates in good to excellent yields at room temperature. The reaction can proceed via two different ways with Michael adduct or isatoic anhydride as the key intermediate.
- Wu, Jun,Zhang, Hui,Ding, Xiao,Tan, Xuefei,Shen, Hong C.,Chen, Jie,He, Weimin,Deng, Hongmei,Song, Liping,Cao, Weiguo
-
-
Read Online
- TBHP-Mediated Oxidative Decarboxylative Cyclization in Water: Direct and Sustainable Access to Anti-malarial Polycyclic Fused Quinazolinones and Rutaecarpine
-
Polycyclic fused quinazolinones with anti-malarial activity were synthesized through tert-butyl hydroperoxide (TBHP)-mediated oxidative decarboxylative cyclization between commercially available isatins and cyclic amines in one step. The reaction proceeds smoothly in water without additional transition-metal catalyst, acid and base. The newly synthesized products were evaluated to exhibit moderate to good anti-malarial activity against chloroquine drug-sensitive Plasmodium falciparum 3D7 strain. Additionally, this method also provides direct approach to Rutaecarpine in good yield.
- Chen, Xingyu,Xia, Fei,Zhao, Yifan,Ma, Ji,Ma, Yue,Zhang, Dong,Yang, Lan,Sun, Peng
-
-
Read Online
- Recyclable (PhSe)2-catalyzed selective oxidation of isatin by H2O2: a practical and waste-free access to isatoic anhydride under mild and neutral conditions
-
After a series of careful conditional optimizations and catalyst screenings, a methodology to prepare isatoic anhydrides through organoselenium-catalyzed selective oxidation of isatins by H2O2 under mild and neutral conditions was developed. The reactions were very practical because of the recyclability of the catalyst and solvent and the convenient isolation procedures of the products. This work reports the organoselenium-catalyzed oxidation of heterocycles that greatly expands the application scopes of organoselenium catalysis. It also indicates that the organoselenium catalysts are robust enough to be recycled in industrial production if suitable isolation procedures are developed.
- Yu, Lei,Ye, Jianqing,Zhang, Xu,Ding, Yuanhua,Xu, Qing
-
-
Read Online
- Formation of tryptanthrin compounds upon Oxone-induced dimerization of indole-3-carbaldehydes
-
Tryptanthrin is a natural product with numerous important pharmacological properties. Tryptanthrin and its analogs are commonly prepared by condensation of isatoic anhydride and isatin. In this Letter we investigate the formation of tryptanthrin derivatives upon Oxone-induced oxidative dimerization of indole-3-carbaldehydes.
- Nelson, Amber C.,Kalinowski, Emily S.,Jacobson, Taylor L.,Grundt, Peter
-
-
Read Online
- Discovery of phthalazino[1,2-b]-quinazolinone derivatives as multi-target HDAC inhibitors for the treatment of hepatocellular carcinoma via activating the p53 signal pathway
-
In view of histone deacetylases (HDACs) as a promising target for cancer therapy, a series of phthalazino[1,2-b]-quinazolinone units were hybrided with ortho-aminoanilide or hydroxamic acid to serve as multi-target HDAC inhibitors for the treatment of solid tumors. Among the target compounds, 8h possessed nano-molar IC50 values toward the tested cancer cells and HDAC subtypes, which was more potent than the HDAC inhibitor SAHA (vorinostat). Mechanism study revealed that compound 8h could suppress the HepG2 cell proliferation via prompting the acetylation of histone 3 (H3) and α-tubulin, and activating the p53 signal pathway as designed. In addition, compound 8h exhibited much stronger in vivo antitumor efficacy than SAHA in the HepG2 xenograft tumor model with negligible toxicity. As a novel multi-target HDAC inhibitor, compound 8h deserves further development as a potential anticancer agent.
- Gou, Shaohua,Liu, Qingqing,Wang, Xinyi,Wang, Yuanjiang,Zhang, Bin
-
-
- Synthesis of α-Amino Acid N-Carboxyanhydrides
-
A simple phosgene- and halogen-free method for synthesizing α-amino acid N-carboxyanhydrides (NCAs) is described. The reaction between Boc-protected α-amino acids and T3P reagent gave the corresponding NCA derivatives in good yield and purity with no detectable epimerization. The process is safe, is easy-to-operate, and does not require any specific installation. It generates nontoxic, easy to remove byproducts. It can apply to the preparation of NCAs for the on-demand on-site production of either little or large quantities.
- Laconde, Guillaume,Amblard, Muriel,Martinez, Jean
-
p. 6412 - 6416
(2021/08/30)
-
- Preparation method of 4(3H)-quinazolinone compound
-
The invention discloses a preparation method of a 4(3H)-quinazolinone compound, and relates to the technical field of organic synthesis, 2,3-diketone indoline is used as a raw material, sodium hypochlorite or potassium hypochlorite is used as an oxidant, an oxidation reaction is carried out in a reaction solvent, and the 4(3H)-quinazolinone compound is prepared by a one-pot method. According to the method, 2,3-diketoindoline is used as a raw material, sodium hypochlorite or potassium hypochlorite which is easily available as the raw material is used as an oxidizing agent; the target product is prepared by a one-pot method, the reaction time is short, and the yield is high. The product is high in purity and is suitable for industrial application.
- -
-
Paragraph 0007; 0029-0042
(2021/05/01)
-
- MODIFIED PROTEINS AND PROTEIN DEGRADERS
-
Provided herein are compounds, pharmaceutical compositions, and methods for binding or degrading target proteins. Further provided herein are compounds having a DNA damage-binding protein 1 (DDB1) binding moiety. Some such embodiments include a linker. Some such embodiments include a target protein binding moiety. Further provided herein are ligand-DDB1 complexes. Further provided herein are in vivo modified DDB1 proteins.
- -
-
Paragraph 00455; 00458; 00459
(2021/12/08)
-
- METHOD OF SYNTHESIZING N-CARBOXYANHYDRIDE USING FLOW REACTOR
-
PROBLEM TO BE SOLVED: To provide a synthesis method that allows high-yield continuous production of a compound of interest in synthesis and production of N-carboxyanhydride (NCA) and the like using a flow reactor. SOLUTION: In a synthesis method using a flow reactor 100, a basic solution adjusted in advance to a pH of 7-14 becomes acidic with a pH of 0-7, or an acidic solution adjusted in advance to a pH of 0-7 becomes basic with a pH of 7-14, within 60 seconds after the start of mixture of at least two ingredient solutions. SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2020,JPOandINPIT
- -
-
Paragraph 0158-0160; 0188-0189
(2020/03/26)
-
- Benzoxazepine-Derived Selective, Orally Bioavailable Inhibitor of Human Acidic Mammalian Chitinase
-
Human acidic mammalian chitinase (hAMCase) is one of two true chitinases in humans, the function of which remains elusive. In addition to the defense against highly antigenic chitin and chitin-containing pathogens in the gastric and intestinal contents, AMCase has been implicated in asthma, allergic inflammation, and ocular pathologies. Potent and selective small-molecule inhibitors of this enzyme have not been identified to date. Here we describe structural modifications of compound OAT-177, a previously developed inhibitor of mouse AMCase, leading to OAT-1441, which displays high activity and selectivity toward hAMCase. Significantly reduced off-target activity toward the human ether-à-go-go-related gene (hERG) and a good pharmacokinetic profile make OAT-1441 a potential candidate for further preclinical development as well as a useful tool compound to study the physiological role of hAMCase.
- Andryianau, Gleb,Bartoszewicz, Agnieszka,Czestkowski, Wojciech,Dymek, Barbara,Dzwonek, Karolina,Golab, Jakub,Golebiowski, Adam,Gruza, Mariusz,Koralewski, Robert,Kowalski, Michal,Matyszewski, Krzysztof,Mazur, Marzena,Niedziejko, Piotr,Olczak, Jacek,Olejniczak, Sylwia,Piotrowicz, Michal C.,Pluta, Elzbieta,Rajkiewicz, Adam A.,Rymaszewska, Aleksandra,Salamon, Magdalena,Sklepkiewicz, Piotr L.,Stefaniak, Filip,Welzer, Mikolaj,Zagozdzon, Agnieszka
-
supporting information
p. 1228 - 1235
(2020/07/03)
-
- Synthesis and nematicidal activities of 1,2,3-benzotriazin-4-one containing 4,5-dihydrothiazole-2-thiol derivatives against Meloidogyne incognita
-
A series of novel 1,2,3-benzotriazin-4-one derivatives containing 4,5-dihydrothiazole-2-thiol were synthesized and characterized by 1H NMR, 13C NMR, 19F NMR and HRMS. The bioassay results showed that compounds 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-7-methoxybenzo[d][1–3]triazin-4(3H)-one, 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-6-nitrobenzo[d][1–3]triazin-4(3H)-one, 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one exhibited good control efficacy against the cucumber root-knot nematode disease caused by Meloidogyne incognita at the concentration of 10.0 mg L?1 in vivo. Compound 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one showed excellent nematicidal activity with inhibition 68.3% at a concentration of 1.0 mg L?1. It suggested that the structure of 1,2,3-benzotriazin-4-one containing 4,5-dihydro-thiazole-2-thiol could be optimized further.
- Chen, Xiulei,Zhou, Zhen,Li, Zhong,Xu, Xiaoyong
-
p. 194 - 200
(2019/09/13)
-
- Discovery of Evodiamine Derivatives as Highly Selective PDE5 Inhibitors Targeting a Unique Allosteric Pocket
-
Clinical use of phosphodiesterase-5 (PDE5) inhibitors is limited by several side effects due to weak isoform selectivity. Herein, a unique allosteric pocket of PDE5 is identified by molecular modeling and structural biology, which enables the discovery of highly selective PDE5 inhibitors from natural product evodiamine (EVO). The crystal structure of PDE5 with bound EVO derivative (S)-7e revealed that binding of (S)-7e to the novel allosteric pocket induced dramatic conformation changes in the H-loop with a maximum 24 ? movement of their Cα atoms. This movement directly blocks the binding of substrate/inhibitors to the PDE5 active site, which is different from all traditional PDE5 inhibitors such as sildenafil, tadalafil, and vardenafil. These derivatives showed >570-fold selectivity over PDE6C and PDE11A and achieved potent efficacy for the effective treatment of pulmonary hypertension in vivo.
- Zhang, Tianhua,Lai, Zengwei,Yuan, Suying,Huang, Yi-You,Dong, Guoqiang,Sheng, Chunquan,Ke, Hengming,Luo, Hai-Bin
-
p. 9828 - 9837
(2020/10/19)
-
- Hetero-substituted sulfonamido-benzamide hybrids as glucokinase activators: Design, synthesis, molecular docking and in-silico ADME evaluation
-
A series of hetero-substituted sulphonamido-benzamide derivatives which can activate glucokinase (GK) were synthesized and screened in-vitro using Human GK activation assay and in-vivo following oral glucose tolerance test (OGTT) assays. All the molecules were docked into the active site of 1V4S receptor grid by XP docking method utilizing Schrodinger software to assess the binding interactions. Compounds 12 (EC50 = 495 nM) and 15 (EC50 = 522 nM), revealed maximum in-vitro GK activation. Selected compounds were subjected for in-vivo OGTT assay. The data revealed that same compounds 12 (135 mg/dL) showed maximum reduction in blood glucose level followed by compound 15 (142 mg/dL) at 120 min. The docking results as glide score, binding energy and interactions were reported and compounds with maximum pharmacological activity were studied precisely. In-silico ADME parameters, pharmacokinetic properties and toxicity studies were carried out and all compounds were found to have good bioavailability and nontoxic. Overall, the series of hetero-substituted sulphonamido-benzamide hybrids are safe and could be explored further for better therapeutic efficacy as GK activators.
- Amnerkar, Nikhil D.,Charbe, Nitin B.,Chatpalliwar, Vivekanand A.,Dhote, Ashish M.,Dighole, Krushna S.,Khadse, Saurabh C.,Lokwani, Deepak K.,Patil, Vikas R.,Ugale, Vinod G.
-
-
- Carbene-Catalyzed Enantioselective Decarboxylative Annulations to Access Dihydrobenzoxazinones and Quinolones
-
A direct decarboxylative strategy for the generation of aza-o-quinone methides (aza-o-QMs) by N-heterocyclic carbene (NHC) catalysis has been discovered and explored. This process requires no stoichiometric additives in contrast with current approaches. Aza-o-QMs react with trifluoromethyl ketones through a formal [4+2] manifold to access highly enantioenriched dihydrobenzoxazin-4-one products, which can be converted to dihydroquinolones through an interesting stereoretentive aza-Petasis–Ferrier rearrangement sequence. Complementary dispersion-corrected density functional theory (DFT) studies provided an accurate prediction of the reaction enantioselectivity and lend further insight to the origins of stereocontrol. Additionally, a computed potential energy surface around the major transition structure suggests a concerted asynchronous mechanism for the formal annulation.
- Lee, Ansoo,Zhu, Joshua L.,Feoktistova, Taisiia,Brueckner, Alexander C.,Cheong, Paul H.-Y.,Scheidt, Karl A.
-
supporting information
p. 5941 - 5945
(2019/04/03)
-
- Cascade Knoevenagel and aza-Wittig reactions for the synthesis of substituted quinolines and quinolin-4-ols
-
A [4 + 2] annulation involving cascade Knoevenagel, aza-Wittig and dehydrofluorination reactions is developed for the synthesis of substituted quinolin-4-ols including analogs bearing CF2H, CF3, and C2F5 groups. This simple and highly efficient method is also applicable for the synthesis of substituted quinolines. A number of reported biologically active compounds can be readily prepared by this one-pot synthesis. Green chemistry metrics analysis of the new reaction processes provided favorable results.
- Zhang, Xiaofeng,Ma, Xiaoming,Qiu, Weiqi,Evans, Jason,Zhang, Wei
-
supporting information
p. 349 - 354
(2019/01/28)
-
- Synthesis and nematicidal evaluation of 1,2,3-benzotriazin-4-one derivatives containing piperazine as linker against Meloidogyne incognita
-
To explore new skeleton with nematicidal activity, a series of novel 1,2,3-benzotriazin-4-one derivatives containing piperazine as linker were synthesized and varied fragments were also introduced to increase structure diversity of the new skeleton. Their inhibitory activities in vivo were evaluated against Meloidogyne incognita. The newly prepared compounds A6, A8, A21, A28 and A38 exhibited more than 50% inhibition at the concentration of 20 mg/L. Especially compound A6 displayed 71.4% inhibition against Meloidogyne incognita at the concentration of 20 mg/L. The nematicidal activities varied significantly depending on the types and positions of the substituents, which provided guidance for further structure modification.
- Chen, Xiulei,Jia, Haowu,Li, Zhong,Xu, Xiaoyong
-
supporting information
p. 1207 - 1213
(2019/03/29)
-
- 4-hydroxy-2-quinolone-nitrogen-(4-quinazolinone)-3-formamide derivatives
-
The invention belongs to the technical field of antibacterial drugs and relates to 4-hydroxy-2-quinolone-nitrogen-(4-quinazolinone)-3-formamide derivatives as well as a preparation method and an application thereof as an antibacterial drug. The compounds are shown in a formula (I), wherein R1 is selected from hydrogen, trifluoromethyl, C1-C8 alkyl, C1-C8 alkoxy and halogen; R2 is selected from hydrogen, nitryl, C1-C8 alkyl, C1-C8 alkoxy and halogen; R3 is selected from C1-C8 alkyl and aryl methyl; R4 is selected from C1-C8 alkyl. The 4-hydroxy-2-quinolone-nitrogen-(4-quinazolinone)-3-formamidederivatives are first discovered antibacterial compounds of novel structures, the compounds have higher inhibition functions on gram-positive bacteria including staphylococcus aureus, staphylococcusepidermidis, enterococcus and the like, particularly, drug-resistant gram-positive bacteria (MRSA (methicillin-resistant staphylococcus aureus), MRSE (methicillin-resistant staphylococcus epidermidis)and VRE (vancomycin-resistant enterococci)) and can be used for following further modification and development.
- -
-
Paragraph 0074-0075
(2019/08/06)
-
- Catalytic Asymmetric Synthesis of Atropisomeric Quinolines through the Friedl?nder Reaction
-
A phosphoric acid catalyzed atroposelective Friedl?nder reaction was developed in which acetylacetone and a variety of 2′-substituted 2-Aminobenzophenones were successfully employed to give optically active biaryl quinolines in good yields and with high enantioselectivities.
- Hu, Xingena,Jiang, Jun,Lan, Yunjun,Li, Juan,Li, Xinhua,Liu, Hongxin,Wan, Junlin,Xiao, Hong-Ping
-
supporting information
p. 2198 - 2202
(2019/11/25)
-
- Eco-friendly decarboxylative cyclization in water: Practical access to the anti-malarial 4-quinolones
-
An environmentally benign decarboxylative cyclization in water has been developed to synthesize 4-quinolones from readily available isatoic anhydrides and 1,3-dicarbonyl compounds. Isatins are also compatible for the reaction to generate 4-quinolones in the presence of TBHP in DMSO. This protocol provides excellent yields under mild conditions for a broad scope of 4-quinolones, and has good functional group tolerance. Only un-harmful carbon dioxide and water are released in this procedure. Moreover, the newly synthesized products have also been selected for anti-malarial examination against the chloroquine drug-sensitive Plasmodium falciparum 3D7 strain. 3u is found to display excellent anti-malarial activity with an IC50 value of 33 nM.
- Ma, Yue,Zhu, Yongping,Zhang, Dong,Meng, Yuqing,Tang, Tian,Wang, Kun,Ma, Ji,Wang, Jigang,Sun, Peng
-
p. 478 - 482
(2019/02/14)
-
- Naphtho[d][1,3]oxazine-2,4(1H)-diketone derivatives and synthetic method and application thereof
-
The invention relates to benzoxazine diketone derivatives which simultaneously have inhibiting effects on acetylcholinesterase and phosphodiesterase V, and a synthetic method and application thereof,in particular to 2H-naphtho[d][1,3]oxazine-2,4(1H)-diketone derivatives in a structural general formula (I) and a synthetic method and application thereof. R1, R2, R3, R4, R5, R6, R7, R8 and R9 are asshown in limitations given in the description. The invention discloses compound structures and the synthetic method and an in vitro acetylcholinesterase and phosphodiesterase V inhibition activity thereof. The derivatives can be further developed into a medicament for treating the alzheimer disease. The formula is shown in the description.
- -
-
-
- Gold-Catalyzed Selective 6-exo-dig and 7-endo-dig Cyclizations of Alkyn-Tethered Indoles to Prepare Rutaecarpine Derivatives
-
An efficient method to synthesize rutaecarpine derivatives via the gold-catalyzed selective cyclization of alkyn-tethered indoles under mild conditions is described. The alkyn-tethered indole can undergo 6-exo-dig cyclization by oxidation and sequential gold catalysis, while it goes through 7-endo-dig cyclization by gold catalysis and sequential oxidation. Substrate scope studies reveal that the selectivity of cyclization was controlled by the substrates with sp3 and sp2 hybridization of carbon at the 2 position in quinazolinone. Furthermore, the rutaecarpine scaffold was prepared in 67% yield at gram scale easily in four steps from isatoic anhydride.
- Kong, Xiang-Fei,Zhan, Feng,He, Guo-Xue,Pan, Cheng-Xue,Gu, Chen-Xi,Lu, Ke,Mo, Dong-Liang,Su, Gui-Fa
-
p. 2006 - 2017
(2018/02/23)
-
- Palladium-Catalyzed Cyclization Reaction of o-Iodoanilines, CO2, and CO: Access to Isatoic Anhydrides
-
Isatoic anhydrides, a class of valuable synthetic intermediates and RNA structure probing reagents, are usually prepared with highly toxic phosgene or stoichiometric oxidants. Herein we report a highly selective palladium-catalyzed cyclization reaction for the efficient synthesis of isatoic anhydrides from readily available o-iodoanilines, CO2, and CO. The reaction proceeds under mild conditions and is redox-neutral. Both CO2 and CO are indispensable C1 building blocks for this catalytic reaction.
- Zhang, Wen-Zhen,Zhang, Ning,Sun, Yu-Qian,Ding, Yu-Wei,Lu, Xiao-Bing
-
p. 8072 - 8076
(2017/12/08)
-
- INHIBITORS OF IRES-MEDIATED PROTEIN SYNTHESIS
-
This disclosure relates to inhibitors of IRES-mediated protein synthesis, compositions comprising therapeutically effective amounts of these compounds, and methods of using those compounds and compositions in treating hyperproliferative disorders, e.g., cancers. This disclosure also relates to compositions comprising inhibitors of IRES-mediated protein synthesis and mTOR inhibitors, and to methods of treating cancer by conjoint administration of inhibitors of IRES-mediated protein synthesis and mTOR inhibitors.
- -
-
Page/Page column 38; 44
(2017/12/18)
-
- Mechanistic insights into a catalyst-free method to construct quinazolinones through multiple oxidative cyclization
-
A novel one-pot benign oxidative cyclization of alcohols with 2-aminobenzamides was successfully developed without catalyst to afford the quinazolinones under O2. This one-pot protocol involved oxidations and cyclizations to construct the skeleton of quinazolinones through possibly three kinds of distinct reaction mechanisms.
- Wang, Zhen-Zhen,Tang, Yu
-
p. 1330 - 1336
(2017/02/15)
-
- Investigation into the stability and reactivity of the pentacyclic alkaloid dehydroevodiamine and the benz-analog thereof
-
Limited synthetic approaches to obtain the biologically active alkaloid dehydroevodiamine (DHED) are known to date. Undesired demethylation in the most widely applied route was found to be a hampering side reaction for the benz-DHED derivative leading to a quinazolinone, which represents a benz-rutaecarpine derivative. For rutaecarpine, a related plant alkaloid, many different synthetic approaches have been described. Alternative reaction procedures to obtain DHED such as methylation of rutaecarpine and oxidation of evodiamine were investigated to make DHED more easily accessible and the latter method proved to be the most successful one. Furthermore, the remarkable equilibrium between the ring closed quinazolinium and the ring open form of the compounds was systematically investigated by UV-vis measurements. The ring open form and the quinazolinium salt, form the same species when incubated in buffer solution for 24 h. A better soluble form, i.e., 'hydroxyevodiamine', seems to represent the biologically active form that has not yet been described.
- Wehle, Sarah,Espargaró, Alba,Sabaté, Raimon,Decker, Michael
-
supporting information
p. 2535 - 2543
(2016/04/26)
-
- Isatoic anhydride and its process for synthesis of derivatives of
-
The invention discloses a synthesis method of isatoic anhydride and a derivative thereof, relating to the technical field of chemical synthesis. In the presence of catalysis of an organic selenium catalyst, isatin or a derivative thereof is oxidized by using hydrogen peroxide to prepare the isatoic anhydride and the derivative thereof. The synthesis method disclosed by the invention is simple and easily available in raw materials, low in cost, clean in oxidizing agent, free from a metal catalyst, and environmentally friendly, can be carried out in a neutral environment, and is small in corrosion to equipment.
- -
-
Paragraph 0014; 0015; 0016; 0017
(2017/01/12)
-
- METHOD OF PRODUCING NITROGEN-CONTAINING HETEROCYCLIC COMPOUND
-
PROBLEM TO BE SOLVED: To provide a chemical compound production method realizing easy and high-yield production of a nitrogen-containing heterocyclic compound useful as a synthetic intermediate and the like in many fields such as medicine, agriculture and synthetic resin additives. SOLUTION: In the production method, an ortho-substituted benzene azide derivative represented by formula (1) is reacted with carbon dioxide in the presence of a reductant to obtain a compound represented by formula (2). [R is H and/or a substituent; A is an intramolecular cyclizable group; and B is a divalent linking group of C, N and O. COPYRIGHT: (C)2016,JPOandINPIT
- -
-
Paragraph 0042-0045
(2016/10/08)
-
- Identification of degradation products of indigoids by tandem mass spectrometry
-
The study concerns identification of photodegradation products of indigotin, indirubin and isoindigo. Experimental methodology consists of degradation of standard solutions of indigoids in a solar box and analysis of samples taken at different aging time by using capillary high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometric and spectrophotometric detectors. Identification of the formed compounds was based on careful interpretation of the electrospray ionization MS/MS spectra. Apart from the well-known degradation products of indigoids: isatin, isatoic anhydride and anthranilic acid, another seven species were also identified, and their proposed structures were confirmed by high-resolution molecular masses measurements; according to the best knowledge of authors, they have not been reported so far. The obtained results formed the basis for postulating mechanism of the process. Moreover, the MRM (Multiple Reaction Monitoring) method was developed for the identification of natural dyes and their degradation products in textiles of historical value. Apart from such colorants as indigotin and flavonoids, also presence of degradation products of indigoids was confirmed.
- Witkos?, Katarzyna,Lech, Katarzyna,Jarosz, MacIej
-
p. 1245 - 1251
(2015/11/09)
-
- Identification of Multiple Structurally Distinct, Nonpeptidic Small Molecule Inhibitors of Protein Arginine Deiminase 3 Using a Substrate-Based Fragment Method
-
The protein arginine deiminases (PADs) are a family of enzymes that catalyze the post-translational hydrolytic deimination of arginine residues. Four different enzymologically active PAD subtypes have been characterized and exhibit tissue-specific expression and association with a number of different diseases. In this Article we describe the development of an approach for the reliable discovery of low molecular weight, nonpeptidic fragment substrates of the PADs that then can be optimized and converted to mechanism-based irreversible PAD inhibitors. The approach is demonstrated by the development of potent and selective inhibitors of PAD3, a PAD subtype implicated in the neurodegenerative response to spinal cord injury. Multiple structurally distinct inhibitors were identified with the most potent inhibitors having >10,000 min-1 M-1 kinact/KI values and ≥10-fold selectivity for PAD3 over PADs 1, 2, and 4. (Figure Presented).
- Jamali, Haya,Khan, Hasan A.,Stringer, Joseph R.,Chowdhury, Somenath,Ellman, Jonathan A.
-
supporting information
p. 3616 - 3621
(2015/03/30)
-
- Synthesis and Nematicidal Activities of 1,2,3-Benzotriazin-4-one Derivatives against Meloidogyne incognita
-
A series of novel 1,2,3-benzotriazin-4-one derivatives were synthesized by the reaction of 3-bromoalkyl-1,2,3-benzotriazin-4-ones with potassium salt of 2-cyanoimino-4-oxothiazolidine in the presence of potassium iodide. Nematicidal assays in vivo showed that some of them exhibited good control efficacy against the cucumber root-knot nematode disease caused by Meloidogyne incognita, up to 100% at the concentration of 10.0 mg L-1, which indicated that 1,2,3-benzotriazin-4-one derivatives might be potential for novel promising nematicides. The nematicidal activity was influenced by the combination of substituent type, substituted position, and linker length in the molecule. The inhibition rate data at the concentrations of 5.0 and 1.0 mg L-1 for the compounds with high inhibitory activities were also provided. When tested in vitro, none of them showed direct inhibition against M. incognita. The investigation of a significant difference between in vivo and in vitro data is in progress.
- Wang, Gaolei,Chen, Xiulei,Deng, Yayun,Li, Zhong,Xu, Xiaoyong
-
p. 6883 - 6889
(2015/08/18)
-
- One-pot synthesis of tryptanthrin by the Dakin oxidation of indole-3-carbaldehyde
-
A one-pot approach to indolo[2,1-b]quinazolines from indole-3-carbaldehydes through the Dakin oxidation was developed. It was shown that the reaction proceeded through the condensation of indole-3-carbaldehydes with isatoic anhydrides, derived in situ from indole-3-carbaldehydes by the Dakin oxidation, and further oxidation/cyclization steps.
- Abe, Takumi,Itoh, Tomoki,Choshi, Tominari,Hibino, Satoshi,Ishikura, Minoru
-
p. 5268 - 5270
(2015/01/09)
-
- Palladium-catalyzed carbonylation of o-iodoanilines for synthesis of isatoic anhydrides
-
A novel palladium-catalyzed oxidative double carbonylation of o-iodoanilines for the synthesis of isatoic anhydrides has been developed. The reaction employs readily available o-iodoanilines as the starting materials and proceeds under mild conditions. For extension, palladium-catalyzed oxidative carbonylation of anthranilic acids was developed for the synthesis of substituted isatoic anhydrides in high to excellent yields.
- Gao, Sha,Chen, Ming,Zhao, Mi-Na,Du, Wei,Ren, Zhi-Hui,Wang, Yao-Yu,Guan, Zheng-Hui
-
p. 4196 - 4200
(2014/05/20)
-
- QUINAZOLINE-2,4-DIONE DERIVATIVES
-
The invention relates to antibacterial compounds of formula (I), wherein R1 is H, halogen, (C1-C3)alkyl or (C1-C3)alkoxy; R2 is H, halogen, (C1-C3)alkyl, (C1-C3)alkoxy or pyrrolidin-1-yl; R3 is H, halogen, (C1-C3)alkyl, (C1-C3)alkoxy, vinyl or 2-methoxycarbonyvinyl or R2 and R3 together with the two carbon atoms which bear them form a phenyl ring; R4 is H, halogen, (C1-C3)alkyl or (C1-C3)alkoxy; and R5 is H, (C1-C3)alkyl or cyclopropyl, or R4 and R5 form together a —CH2CH2CH2— group; A is the divalent group —CH2—, —CH2CH2—, #—CH(OH)CH2—*, #—CH2N(R6)—* and —CH2NHCH2—, wherein # indicates the point of attachment to the optionally substituted (quinazoline-2,4-dione-3-yl)methyl residue and * represents the point of attachment to the substituted (oxazolidinon-4-yl)methyl residue; R6 is H or acetyl; Y is CH or N; and Q is O or S; and salts of such compounds.
- -
-
Page/Page column
(2014/06/25)
-
- Synthesis, biological evaluation and SAR of 3-benzoates of ingenol for treatment of actinic keratosis and non-melanoma skin cancer
-
Ingenol 3-benzoates were investigated with respect to chemical stability, pro-inflammatory effects, cell death induction and PKCδ activation. A correlation between structure, chemical stability and biological activity was found and compared to ingenol mebutate (ingenol 3-angelate) used for field treatment of actinic keratosis. We also provided further support for involvement of PKCδ for induction of oxidative burst and cytokine release. Molecular modeling and dynamics calculations corroborated the essential interactions between key compounds and C1 domain of PKCδ.
- Grue-Sorensen, Gunnar,Liang, Xifu,Mansson, Kristoffer,Vedso, Per,Dahl Sorensen, Morten,Soor, Anke,Stahlhut, Martin,Bertelsen, Malene,Engell, Karen Margrethe,Hoegberg, Thomas
-
-
- A simple heterocyclic fusion reaction and its application for expeditious syntheses of rutaecarpine and its analogs
-
In the search for new inhibitors of cholinesterases, a simple heterocyclic fusion reaction of isatoic anhydride 8 and 3,4-dihydroisoquinoline 22 was discovered which involves a spontaneous dehydrogenation upon heating. Applying the reaction, the bioactive natural alkaloid rutaecarpine and several substituted derivatives out of tryptamines and anthranilic acids or isatoic anhydrides, respectively, can be synthesized without tedious chromatographic purification. This provides simple and fast access to larger amounts of compounds with this privileged structure in medicinal chemistry.
- Huang, Guozheng,Roos, Dominika,Stadtmüller, Patricia,Decker, Michael
-
supporting information
p. 3607 - 3609
(2014/06/23)
-
- Discovery of tryptanthrin derivatives as potent inhibitors of indoleamine 2,3-dioxygenase with therapeutic activity in lewis lung cancer (LLC) tumor-bearing mice
-
Indoleamine 2,3-dioxygenase (IDO-1) is emerging as an important new therapeutic target for the treatment of cancer, neurological disorders, and other diseases that are characterized by pathological tryptophan metabolism. However, only a few structural classes are known to be IDO-1 inhibitors. In this study, a natural compound tryptanthrin was discovered to be a novel potent IDO-1 inhibitor by screening of indole-based structures. Three series of 13 tryptanthrin derivatives were synthesized, and the structure-activity analysis was undertaken. The optimization led to the identification of 5c, which exhibited the inhibitory activity at a nanomolar level. In vitro 5c dramatically augmented the proliferation of T cells. When administered to Lewis lung cancer (LLC) tumor-bearing mice, 5c significantly inhibited IDO-1 activity and suppressed tumor growth. In addition, 5c reduced the numbers of Foxp3 + regulatory T cells (Tregs), which are known to prevent the development of efficient antitumor immune responses.
- Yang, Shuangshuang,Li, Xishuai,Hu, Fangfang,Li, Yinlong,Yang, Yunyun,Yan, Junkai,Kuang, Chunxiang,Yang, Qing
-
p. 8321 - 8331
(2013/12/04)
-
- A phosgene and peroxide-free one-pot tandem synthesis of isatoic anhydrides involving anthranilic acid, boc anhydride and 2-chloro-N-methyl pyridinium iodide
-
A phosgene and peroxide-free approach for the synthesis of isatoic anhydrides has been described. The synthesis involves the carbamate formation with boc anhydride followed by in situ cyclization to afford the isatoic anhydride. The importance of this synthetic strategy is in the ease of operation, scalability and preparation from readily available raw materials.
- Verma, Chhaya,Sharma, Somesh,Pathak, Arunendra
-
supporting information
p. 6897 - 6899
(2019/04/10)
-
- Synthesis of novel series of 6-chloro-1,1-dioxo-1,4,2-benzodithiazine derivatives with potential biological activity
-
A series of 6′-chloro-1′,1′-dioxo-2′H- spiro[benzo[d][1,3,7]oxadiazocine-4,3′-(1,4,2-benzodithiazine)]-2,6(1H,5H) -dione derivatives 2a, 2b and 3a, 3b have been synthesized starting from 3-aminobenzodithiazines 1a, 1b and isatoic anhydride. Subsequent reactions of 2a with 3-chlorophenyl isocyanate gave condensation products 4 and 5. Compound 2a was also converted into 3-(2-aminobenzamido)-6-chloro-7-methyl-1,1-dioxo-1,4,2- benzodithiazine derivatives 6, 7, 8, 9, 10. The mechanisms of the reactions are discussed.
- Brzozowski, Zdzislaw,Slawinski, Jaroslaw
-
p. 1099 - 1107
(2013/10/21)
-
- Synthesis of pyridine-based 1,3,4-oxadiazole derivative as fluorescence turn-on sensor for high selectivity of Ag+
-
An oxadiazole derivative(OXD) containing symmetrical pyridine-2- formamidophenyl-binded moiety was synthesised as fluorescence turn-on sensor OA1. Its ultraviolet-visible(UV-vis) and fluorescent spectra(FS) gave prominent fluorescence enhancement only for monovalent silver ion(Ag+) in HEPES buffer solution (10 mM, pH = 7.0, DMF-H2O, 9:1, v/v), which indicated the photo-induced electron transfer(PET) occurred from the donor of pyridine-2-formamidophenyl group to oxadiazole fluorophore. The present study demonstrated that OA1 was a viable candidate as fluorescent receptor for a new Ag+ sensor. And the results of fluorescent spectral titration showed this sensor formed 1:1 complex with Ag+.
- Zheng, Chunling,Yuan, Ailin,Zhang, Zhengyu,Shen, Hong,Bai, Shuyuan,Wang, Haibo
-
p. 785 - 791
(2013/07/26)
-
- Oxidation of 2-arylindoles for synthesis of 2-arylbenzoxazinones with oxone as the sole oxidant
-
A novel and efficient method for the oxidation of 2-arylindoles to synthesize 2-arylbenzoxazinones utilizing oxone as the sole oxidant has been developed. The reaction tolerates a wide range of functional groups and allows quick and atom-economical assembly of a variety of valuable 2-arylbenzoxazinones in high yields.
- Lian, Xiao-Li,Lei, Hao,Quan, Xue-Jing,Ren, Zhi-Hui,Wang, Yao-Yu,Guan, Zheng-Hui
-
supporting information
p. 8196 - 8198
(2013/09/12)
-
- PYRAZOLE AMIDE COMPOUNDS AND USES THEREOF
-
Disclosed is a pyrazole amide compound having fungicidal activity, with a structure shown by the general formula (I): Each of the substituents of the compound being defined as in the description. The compound of the present invention has fungicidal activity, and excellent prevention and controlling effects on diseases, such as cucumber downy mildew, corn rust, wheat powdery mildew, rice blast, etc., and in particular, a better prevention and controlling effect on cucumber downy mildew and corn rust. Also disclosed is a process for preparing the compound, a fungicidal composition containing the compound of general formula (I) and the use thereof in preventing and controlling disease in crops.
- -
-
Paragraph 0213; 0214
(2013/09/12)
-
- PYRAZOLE AMIDE COMPOUND AND USE THEREOF
-
Disclosed is a pyrazole amide compound having fungicidal activity, with a structure shown by the general formula (I): Each of the substituents of the compound being defined as in the description. The compound of the present invention has fungicidal activity, and excellent prevention and controlling effects on diseases, such as cucumber downy mildew, corn rust, wheat powdery mildew, rice blast, etc., and in particular, a better prevention and controlling effect on cucumber downy mildew and corn rust. Also disclosed is a process for preparing the compound, a fungicidal composition containing the compound of general formula(I) and the use thereof in preventing and controlling disease in crops.
- -
-
Paragraph 0125; 0126
(2013/09/26)
-
- BISBENZOXAZINONE COMPOUND
-
It is an object of the present invention to provide a bisbenzoxazinone compound which does not substantially contain an alkali metal salt, has high purity and provides a resin composition having excellent resistance to hydrolysis when it is contained in a resin, a production method thereof, and a resin composition comprising the compound. The present invention is a bisbenzoxazinone compound represented by the following formula (4): (R1 and R2 are each independently a hydrogen atom, hydroxyl group, alkyl group having 1 to 3 carbon atoms, or the like), and has (i) a purity of 98% or more, (ii) a content of a compound represented by the following formula (7) of less than 0.15 wt %: (iii) a maximum peak in the measurement of the light reflectance at a visible range of its powder at 380 to 480 nm and a maximum light reflectance of 100 to 120%, (iv) a metal sodium content of less than 50 ppm and (v) a YI value of ?10 to 10.
- -
-
Page/Page column 14
(2012/10/08)
-
- BIS-BENZOXAZINONE COMPOUND
-
It is an object of the present invention to provide a bisbenzoxazinone compound which does not substantially contain an alkali metal salt, has high purity and provides a resin composition having excellent resistance to hydrolysis when it is contained in a resin, a production method thereof, and a resin composition comprising the compound. The present invention is a bisbenzoxazinone compound represented by the following formula (4): (R1 and R2 are each independently a hydrogen atom, hydroxyl group, alkyl group having 1 to 3 carbon atoms, or the like), and has (i) a purity of 98 % or more, (ii) a content of a compound represented by the following formula (7) of less than 0.15 wt%: (iii) a maximum peak in the measurement of the light reflectance at a visible range of its powder at 380 to 480 nm and a maximum light reflectance of 100 to 120 %, (iv) a metal sodium content of less than 50 ppm and (v) a YI value of -10 to 10.
- -
-
Page/Page column 22
(2012/10/18)
-
- New tricks for an Old natural product: Discovery of highly potent evodiamine derivatives as novel antitumor agents by systemic structure-activity relationship analysis and biological evaluations
-
Evodiamine is a quinazolinocarboline alkaloid isolated from the fruits of traditional Chinese herb Evodiae fructus. Previously, we identified N13-substituted evodiamine derivatives as potent topoisomerase I inhibitors by structure-based virtual screening and lead optimization. Herein, a library of novel evodiamine derivatives bearing various substitutions or modified scaffold were synthesized. Among them, a number of evodiamine derivatives showed substantial increase of the antitumor activity, with GI50 values lower than 3 nM. Moreover, these highly potent compounds can effectively induce the apoptosis of A549 cells. Interestingly, further computational target prediction calculations in combination with biological assays confirmed that the evodiamine derivatives acted by dual inhibition of topoisomerases I and II. Moreover, several hydroxyl derivatives, such as 10-hydroxyl evodiamine (10j) and 3-amino-10-hydroxyl evodiamine (18g), also showed good in vivo antitumor efficacy and low toxicity at the dose of 1 mg/kg or 2 mg/kg. They represent promising candidates for the development of novel antitumor agents.
- Dong, Guoqiang,Wang, Shengzheng,Miao, Zhenyuan,Yao, Jianzhong,Zhang, Yongqiang,Guo, Zizhao,Zhang, Wannian,Sheng, Chunquan
-
p. 7593 - 7613
(2012/10/29)
-