- Tumor microenvironment and NIR laser dual-responsive release of berberine 9-: O -pyrazole alkyl derivative loaded in graphene oxide nanosheets for chemo-photothermal synergetic cancer therapy
-
A berberine 9-O-pyrazole alkyl derivative, a chemical compound (called B3) previously synthesized by our group, shows anti-cancer activity. However, B3 lacks targeting cytotoxicity to cancer cells, leading to obvious toxic side effects on normal cells. To solve this problem, here, we prepared a drug delivery system, namely, AS1411-GO/B3 for tumor targeting, in which nano-graphene oxide (GO) sheets were employed as the drug carrier, and the aptamer AS1411 was conjugated onto GO for tumor targeting. GO also had a photothermal effect, which helped the release of B3 from GO as well as the thermal cytotoxicity to cells. We found that the release of B3 could respond to acid conditions, indicating that the tumor intracellular environment could promote the release of B3, thus allowing it to perform chemotherapy effects. This system could also release B3 in response to photothermal heating, moreover, combined photothermal therapy and chemotherapy to improve the anticancer activity was achieved. This AS1411-GO/B3 platform with chemo-photothermal synergetic therapy provides a very promising treatment for tumors.
- Cai, Shundong,Du, Peifang,Liu, Yanfei,Liu, Zhenbao,Long, Shuo,Peng, Dongming,Wang, Yirong,Wen, Nachuan,Xiong, Hongjie,Yan, Jianhua
-
-
Read Online
- R4NHal/NOHSO4: A Usable System for Halogenation of Isoxazoles, Pyrazoles, and beyond
-
A new convenient and versatile halogenating system (R4NHal/NOHSO4), giving straightforward and general access to halogenated 3,5-diaryl- and alkylarylisoxazoles, pyrazoles and electron-rich benzenes from the corresponding scaffolds, is suggested. The method provides excellent regioselectivity, scalability to the gram scale, and a broad scope for both aromatics and halogens. A three-step, one-pot reaction protocol was developed, and a series of 3,5-diaryl-4-haloisoxazoles has been efficiently synthesized from 1,2-diarylcyclopropanes under suggested nitrosating-halogenating conditions.
- Bondarenko, Oksana B.,Karetnikov, Georgy L.,Komarov, Arseniy I.,Pavlov, Aleksandr I.,Nikolaeva, Svetlana N.
-
supporting information
p. 322 - 332
(2021/01/14)
-
- Identification of Isoform 2 Acid-Sensing Ion Channel Inhibitors as Tool Compounds for Target Validation Studies in CNS
-
Acid-sensing ion channels (ASICs) are a family of ion channels permeable to cations and largely responsible for the onset of acid-evoked ion currents both in neurons and in different types of cancer cells, thus representing a potential target for drug discovery. Owing to the limited attention ASIC2 has received so far, an exploratory program was initiated to identify ASIC2 inhibitors using diminazene, a known pan-ASIC inhibitor, as a chemical starting point for structural elaboration. The performed exploration enabled the identification of a novel series of ASIC2 inhibitors. In particular, compound 2u is a brain penetrant ASIC2 inhibitor endowed with an optimal pharmacokinetic profile. This compound may represent a useful tool to validate in animal models in vivo the role of ASIC2 in different neurodegenerative central nervous system pathologies.
- Bencheva, Leda Ivanova,De Matteo, Marilenia,Ferrante, Luca,Ferrara, Marco,Prandi, Adolfo,Randazzo, Pietro,Ronzoni, Silvano,Sinisi, Roberta,Seneci, Pierfausto,Summa, Vincenzo,Gallo, Mariana,Veneziano, Maria,Cellucci, Antonella,Mazzocchi, Nausicaa,Menegon, Andrea,Di Fabio, Romano
-
supporting information
p. 627 - 632
(2019/03/07)
-
- A mild halogenation of pyrazoles using sodium halide salts and Oxone
-
A mild, inexpensive, and operationally simple pyrazole halogenation method utilizing Oxone and sodium halide salts is reported. This work documents 17 examples of alkyl, aryl, allyl, and benzyl substituted 4-chloro and 4-bromopyrazoles, obtained in up to 93% yield. Reactions are performed in water under ambient conditions and generation of organic byproducts is avoided.
- Olsen, Kathryn L.,Jensen, Matthew R.,MacKay, James A.
-
supporting information
p. 4111 - 4114
(2017/09/29)
-
- Discovery of DS79182026: A potent orally active hepcidin production inhibitor
-
Hepcidin has emerged as the central regulatory molecule of systemic iron homeostasis. Inhibition of hepcidin could be a strategy favorable to treating anemia of chronic disease (ACD). We report herein the synthesis and structure-activity relationships (SARs) of a series of benzisoxazole compounds as orally active hepcidin production inhibitors. The optimization study of multi kinase inhibitor 1 led to a potent and bioavailable hepcidin production inhibitor 38 (DS79182026), which showed serum hepcidin lowering effects in a mouse IL-6 induced acute inflammatory model.
- Fukuda, Takeshi,Goto, Riki,Kiho, Toshihiro,Ueda, Kenjiro,Muramatsu, Sumie,Hashimoto, Masami,Aki, Anri,Watanabe, Kengo,Tanaka, Naoki
-
p. 3716 - 3722
(2017/07/27)
-
- A two-valence sulfonyl isoxazole derivatives and use thereof
-
The invention discloses a bi-titer sulfonyl isoxazole derivative in the technical field of organic compound weedicides, and application thereof. The bi-titer sulfonyl isoxazole derivative has a molecular structural formula shown as a general formula I. The invention further discloses a preparation method of the bi-titer sulfonyl isoxazole derivative. The bi-titer sulfonyl isoxazole derivative has very high activity of inhibiting weed growth and killing and removing weeds, and can be used in agricultural production, and is classified as a novel active component for weedicides.
- -
-
Paragraph 0060; 0068-0069
(2017/10/07)
-
- Synthesis and characterization of some symmetrical substituted 1-(2-chloroethyl)pyrazole-based chalcogenides
-
The present paper describes the synthesis of some symmetrical substituted 1-(2-chloroethyl) pyrazole-based dichalcogenides and monochalcogenides by reacting different 3,4,5-trisubstituted 1-(2-chloroethyl) pyrazole derivatives with in situ prepared Na2E2 (E = S, Se, Te) and sodium hydrogen selenide, respectively. All compounds were fully characterized by different spectroscopic techniques, namely, IR, 1H, 13C, 77Se nuclear magnetic resonance, and mass spectrometry. X-ray crystal structure determination of 1,2-bis(2-(4-bromo-3,5-dimethyl-1H-pyrazol-1-yl)ethyl)diselane (10b) reveals intermolecular Se·N·H interactions between two molecules.
- Pundir,Mehta,Mobin,Bhasin
-
-
- Synthesis of [1,2,4]triazolo[4,3-b]-s-tetrazines with incorporated furazan ring
-
Furazancarboxylic hydrazides can serve as nucleophiles to substitute for one dimethylpyrazole fragment in bis(3,5-dimethylpyrazol-1-yl)-s-tetrazine, giving the corresponding N-[6-(3,5-dimethylpyrazol-1-yl)-s-tetrazin-3-yl] -4-R-furazan-3-carbohydrazides i
- Sheremetev,Palysaeva,Suponitskii,Struchkova
-
p. 121 - 130
(2013/01/15)
-
- α-Substituted boron difluoride acetylacetonates
-
By treatment of α-substituted acetylacetone derivatives with boron trifluoride etherate a series of earlier unknown boron difluoride complexes is obtained. The series includes binuclear complexes containing boron in the chelate fragment connected via sulfur or selenium atom. Gas chromatographic and spectral characteristics of the obtained compounds were investigated. By means of chromato-mass spectrometry their reaction with hydrazine in acidic and alkaline media was studied.
- Svistunova,Fedorenko
-
body text
p. 1515 - 1523
(2009/06/28)
-
- N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase
-
Human neutrophil elastase (NE) plays an important role in the pathogenesis of pulmonary disease. Using high-throughput chemolibrary screening, we identified 10 N-benzoylpyrazole derivatives that were potent NE inhibitors. Nine additional NE inhibitors were identified through further screening of N-benzoylpyrazole analogues. Evaluation of inhibitory activity against a range of proteases showed high specificity for NE, although several derivatives were also potent inhibitors of chymotrypsin. Analysis of reaction kinetics and inhibitor stability revealed that N-benzoylpyrazoles were pseudoirreversible competitive inhibitors of NE. Structure-activity relationship (SAR) analysis demonstrated that modification of N-benzoylpyrazole ring substituents modulated enzyme selectivity and potency. Furthermore, molecular modeling of the binding of selected active and inactive compounds to the NE active site revealed that active compounds fit well into the catalytic site, whereas inactive derivatives contained substituents or conformations that hindered binding or accessibility to the catalytic residues. Thus, N-benzoylpyrazole derivatives represent novel structural templates that can be utilized for further development of efficacious NE inhibitors.
- Schepetkin, Igor A.,Khlebnikov, Andrei I.,Quinn, Mark T.
-
p. 4928 - 4938
(2008/03/13)
-
- Halogenation of pyrazoles using N-halosuccinimides in CCl4 and in water
-
Reaction of pyrazoles with N-halosuccinimides (NXS, X=Br, Cl) in either CCl4 or water gave 4-halopyrazoles in excellent yields. The reaction was carried out under mild conditions and did not require any catalysts or special precautions. The reaction provides an efficient method for 4-C halogenation of pyrazoles. Copyright Taylor & Francis Group, LLC.
- Zhao, Zhi-Gang,Wang, Zhong-Xia
-
p. 137 - 147
(2007/10/03)
-
- Organocatalysis in conjugate amine additions. Synthesis of β-amino acid derivatives
-
Conjugate addition of O-protected hydroxylamines to pyrazole-derived enoates proceeds with high efficiency and enantioselectivity when chiral thioureas are used as activators. A wide variety of substrates undergo conjugate amine addition providing access to enantioenriched β-amino acid derivatives. Structural requirements for the optimal thiourea catalyst have been established, and the results suggest that it operates as a bifunctional catalyst. Copyright
- Sibi, Mukund P.,Itoh, Kennosuke
-
p. 8064 - 8065
(2008/02/09)
-
- A mild and efficient method for halogenation of 3,5-dimethyl pyrazoles by ultrasound irradiation using N-halosuccinimides
-
The 4-halo-3,5-dimethyl pyrazoles have been synthetisized in good yields in short reaction times in the absence of a catalyst by reaction of 3,5-dimethyl pyrazoles with N-halosuccinimides (NBS, NCS and NIS) under ultrasound irradiation. Finally, the halogenation of pyrazoles with Br2, IC1 and I2 was showed in similar conditions.
- Stefani, Hélio A.,Pereira, Claudio M. P.,Almeida, Roberta B.,Braga, Rodolpho C.,Guzen, Karla P.,Cella, Rodrigo
-
p. 6833 - 6837
(2007/10/03)
-
- Enantioselective enol lactone synthesis under double catalytic conditions
-
(Chemical Equation Presented) The reaction of dimedone with 1-(2-alkenoyl)-4-bromo-3,5-dimethylpyrazoles in THF, catalyzed by catalytic amounts of both DBFOX/Ph-nickel-(II) perchlorate trihydrate and 2,2,6,6-tetramethylpiperidine, in the presence of acetic anhydride in THF produces the corresponding enol lactones in high enantioselectivities through enantioselective Michael additions followed by cyclization with removal of the pyrazole auxiliary. Other related nucleophile precursors can be successfully applied in the enantioselective enol lactone synthesis under the double catalytic conditions.
- Itoh, Kennosuke,Hasegawa, Masayuki,Tanaka, Junji,Kanemasa, Shuji
-
p. 979 - 981
(2007/10/03)
-
- An efficient method for the N-debenzylation of aromatic heterocycles
-
The treatment of N-benzylated heterocycles with potassium tert-butoxide/DMSO and oxygen at room temperature cleanly affords N-debenzylated products in high yield. This procedure can be utilized on a variety of functionalized nitrogen-containing heterocycles such as imidazoles, benzimidazoles, pyrazoles, indazoles, carbazoles, and indoles.
- Haddach, Aubrey A.,Kelleman, Audrey,Deaton-Rewolinski, Melissa V.
-
p. 399 - 402
(2007/10/03)
-
- Gas-chromatographic study of hydrazine reaction with metal β-diketonates
-
When treated with hydrazine, metal β-diketonates undergo decomposition to form the corresponding pyrazoles, irrespective of the kinetic stability of the chelates. With substituted metal chelates, the main reaction products are pyrazoles bearing in positio
- Svistunova,Shapkin,Nikolaeva
-
p. 899 - 900
(2007/10/03)
-
- Pyrazole as a leaving group in nucleophilic substitution in 3,6-bis(3,5-dimethyl-1-pyrazolyl)-1,2,4,5-tetrazines
-
Nucleophilic substitution by N-nucleophiles of the 3,5-dimethyl-1-pyrazolyl group in 3,6-bis-(3,5-dimethyl-1-pyrazolyl)-1,2,4,5-tetrazine is discussed.
- Latosh,Rusinov,Ganebnykh,Chupakhin
-
p. 1363 - 1371
(2007/10/03)
-
- Metal pyrazolate polymers. Part 3. Synthesis and study of Cu(I) and Cu(II) complexes of 4-Xdmpz (where X = H, Cl, Br, I, and CH3 for Cu(I) and X = H, Cl, Br, and CH3 for Cu(II); dmpz = 3,5-dimethylpyrazolate)
-
The copper(I) complexes 3 (where X = H, Cl, Br, I, and CH3; dmpz = 3,5-dimethylpyrazolate) and the copper(II) complexes x have been synthesized and characterized.Qualitative solubility, infrared spectroscopic, and differential scanning calorimetric studies are reported for all complexes.Mass spectra support trimeric formulations for the copper(I) complexes.Scanning electron micrographs and powder X-ray diffractograms have been reported for the copper(II) compounds.Electronic and EPR spectroscopic studies as well as magnetic susceptibilitystudies from 2 to 300 K are also reported for the copper(II) compounds, which are proposed to have polymeric chain structures.The magnetic data reveal strong antiferromagnetic interactions in all four copper(II) compounds.The data have been analysed employing an isotropic Heisenberg model for antiferromagnetic coupling in extended chain polymers.Values of the exchange coupling constant, J, are determined as -58, -61, -66, and -66 cm-1 for the X = H, CH3, Cl, and Br complexes respectively.The X = Cl compound exhibits an abrupt decrease in magnetic susceptibility below 40 K and possible causes of this anomalous behaviour are discussed.
- Ehlert, Martin K.,Storr, Alan,Thompson, Robert C.
-
p. 1121 - 1128
(2007/10/02)
-
- Polynuclear pyrazolate complexes of copper. Crystal and molecular structures of 3, 2Cu, and 2 (where mepz = methylpyrazolate, dmpz = dimethylpyrazolate, and tmpz = trimethylpyrazolate) and magnetic susceptibility studies...
-
The reaction of molten trimethylpyrazole (tmpzH) with copper metal shot in air yields a mixture of the trinuclear copper(I) complex 3, 1, and the trinuclear copper(I/II)complex a = 8.403(3), b = 22.453(2), c = 11.362(2) Angstroem, β = 95.83(2) deg, Z = 4, space group P21/c.Crystals of 2 are triclinic, a = 10.988(3), b = 11.009(2), c = 6.457(1) Angstroem, α = 103.13(2) deg, β = 103.02(2) deg, γ = 108.70(2) deg, Z = 1, space group .The reaction of molten 4-bromodimethylpyrazole (4-BrdmpzH) with copper metal shot in air gave the binuclear copper(II) complex 2, 3 (where mepz is methylpyrazolate).There are two crystalline forms of 3: 3a, triclinic, a = 10.152(3), b = 13.068(3), c = 10.033(3) Angstroem, α = 112.38(2) deg, β = 116.46(2) deg, γ = 70.29(2) deg, Z = 1, space group ; and 3b, monoclinic, a = 13.470(1), b = 16.005(2), c = 20.174(1) Angstroem, β = 98.142(6) deg, Z = 4, space group C2/c.Magnetic susceptibility studies on a bulk sample of 3 (2.0-300 K) revealed antiferromagnetic coupling between the double pyrazolate bridged copper centres and analysis of the data according to a Heisenberg model for coupled pairs of S = 1/2 metal ions gave -75.4 cm-1 for the value of the exchange coupling constant.J.The crystal structures of 1, 2, 3a, and 3b were solved by the Patterson method and were refined by full-matrix least squares procedures to final R values of 0.036, 0.056, 0.042, and 0.042 for 2265, 1764, 2011, and 2575 reflections with I 3?(I), respectively.
- Ehlert, Martin K.,Rettig, Steven J.,Storr, Alan,Thompson, Robert C.,Trotter, James
-
p. 2161 - 2173
(2007/10/02)
-
- Pyrazole Chemistry. Part 4. Directed Lithiation of 4-Bromo-1-phenylsulphonylpyrazole: a Convenient Approach to Vicinally Disubstituted Pyrazoles
-
4-Bromo-1-phenylsulphonylpyrazole (10), obtained from 4-bromopyrazole (5) and benzenesulphonyl chloride, can be metallated regioselectively by phenyl-lithium to give the 5-lithio derivative (15) which upon quenching with appropriate electrophiles leads to the 4-bromo-1-phenylsulphonyl-5-substituted pyrazoles (16)-(23), (25), and (26).Compounds (22), (23), and (25) were found to undergo isomerisation to afford the thermodynamically more stable 4-bromo-1-phenylsulphonyl-3-substituted pyrazoles (11), (24), and (13) under the reaction conditions applied.The phenylsulphonyl protecting group then can be removed readily under alkaline conditions to yield the corresponding 4-bromo-3(5)-substituted 1H-pyrazoles (6), (9), (28), (29), and (30).
- Heinisch, Gottfried,Holzer, Wolfgang,Pock, Sabine
-
p. 1829 - 1834
(2007/10/02)
-
- Reactions of N-Aminopyrazoles with Halogenating Reagents and Synthesis of 1,2,3-Triazines
-
Reactions of N-aminopyrazoles with halogenating reagents (Cl2, Br2, I2, BrCl, ICl, IBr, N-chlorosuccinimide, and N-bromosuccinimide) were examined.Some of these reagents preferentially lead to oxidation of the amino group to give the corresponding 1,2,3-triazines as major products, while others mainly gave either or both of 1-amino-4-halopyrazoles and 5-halo-1,2,3-triazines as the result of halogenation of the 4-position of the pyrazole ring prior to the oxidation of the amino group.In some cases, the oxidation of the amino group and the halogenation of the pyrazole ring proceeded concurrently to form not only the unhalogenated triazines but also the 1-amino-4-halopyrazoles and the 5-halotriazines.Various reagents and reaction conditions were explored to utilize the reaction for the synthesis of halogenated and unhalogenated 1,2,3-triazines.Keywords - 1,2,3-triazine; halo-1,2,3-triazine; pyrazole; 1-aminopyrazole; 1-aminohalopyrazole; synthesis; oxidation; halogenation; ring expansion
- Ohsawa, Akio,Kaihoh, Terumitsu,Itoh, Takashi,Okada, Mamiko,Kawabata, Chikako,et al.
-
p. 3838 - 3848
(2007/10/02)
-
