- Discovery of Hydroxyamidine Derivatives as Highly Potent, Selective Indoleamine-2,3-dioxygenase 1 Inhibitors
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In this study, a series of novel hydroxyamidine derivatives were identified as potent and selective IDO1 inhibitors by structure-based drug design. Among them, compounds 13-15 and 18 exhibited favorable enzymatic and cellular activities. Compound 18 showed improved bioavailability in mouse, rat, and dog (F% = 44%, 58.8%, 102.1%, respectively). With reasonable in vivo pharmacokinetic properties, compound 18 was further evaluated in a transgenic MC38 xenograft mouse model. The combination of compound 18 with PD-1 monoclonal antibody showed a synergistic antitumor effect. These data indicated that compound 18 as a potential cancer immunotherapy agent should warrant further investigation.
- Jin, Fangfang,Hu, Qiyue,Fei, Hongbo,Lv, Hejun,Wang, Shenglan,Gui, Bin,Zhang, Junzhen,Tu, Wangyang,Zhang, Yun,Zhang, Lei,Wan, Hong,Zhang, Limin,Hu, Bin,Yang, Fanglong,Bai, Chang,He, Feng,Zhang, Lianshan,Tao, Weikang
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supporting information
p. 195 - 201
(2021/02/06)
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- Site-selective conversion of azido groups at carbonyl α-positions into oxime groups leading triazide to a triple click conjugation scaffold
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This paper reports the selective conversion of alkyl azido groups at the carbonyl α-position into oximes through β-elimination of dinitrogen, followed by transoximation. With this method and diazo conversion, a triazido molecule was transformed into a triple click conjugation scaffold allowing one-pot four-component coupling.
- Yokoi, Taiki,Ueda, Tomomi,Tanimoto, Hiroki,Morimoto, Tsumoru,Kakiuchi, Kiyomi
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supporting information
p. 1891 - 1894
(2019/05/02)
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- Arylglyoxal oximes as putative C-nucleophiles in eliminative nucleophilic substitution process
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Reaction of arylglyoxal oximes ArCOCH=NOH (Ar = 4-MeOC6H4, Ph) with 5-arylfurazanopyrazines proceeds as vicarious nucleophilic substitution of hydrogen in pyrazine ring with the elimination of hyponitrous acid, affording 5-(aroylmethylidene)-6-aryl-4H-furazano[3,4-b]pyrazines. Structure of the product was confirmed by X-ray diffraction.
- Tsyganov, Dmitry V.,Samet, Alexander V.,Dorovatovskii, Pavel V.,Khrustalev, Victor N.,Semenov, Victor V.
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p. 296 - 298
(2019/06/13)
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- The synthesis and characterization of (MSalen/salophen/saldeta/salpy) [M=Fe(III) or Cr(III)] capped heteromultinuclear schiff bases-dioxime Ni(II) complexes: Their thermal and magnetic behaviours
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Chlorophenylglyoxime and Ligand Complexes ([M(Salen/Salophen)]2O, [M(Saldeta/Salpy)Cl] shortened as LC, M = Fe(III) or Cr(III)) have been synthesized. 3,5-dicarboxyanilinophenylglyoxime (5) and 4-carboxyphenylhydrazinophenylglyoxime (6) have been synthesized with the reaction of chlorophenylglyoxime and 5-aminoisophtalalic acid or 4-hydrazinobenzoic acid. [M(Salen/Salophen/Saldeta/Salpy)-3,5-dicarboxyanilinophenyl-glyoxime)] (7–14) or [M(Salen/Salophen)-4-carboxyphenylhydrazinophenylglyoxime)] (15–22) have been synthesized from (5) or (6) and LCs. The new heterotrinuclear and pentanuclear complexes (23–38) have been obtained from (7–22) and Ni(II) salt. Then, heteronuclear and BF2 + capped vic-dioxime complexes (39–54) have been synthesized. The complexes have been characterized as low-spin (S = 1/2) distorted octahedral [FeIII(Salen/Salophen)], high-spin (S = 5/2) distorted octahedral [FeIII(Saldeta/Salpy)] and (S = 3/2) distorted octahedral [CrIII(Salen/Salophen/Saldeta/Salpy)] bridged by COO? groups. The structure of all ligand and complexes were identified by using elemental analysis, thermal analyses, magnetic susceptibility, LC-MS, ICP-AES, 1H-NMR and FT-IR spectral data.
- Uysal, ?aban,Erdem Ko?, Ziya
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- Hydroheteroarylation of Unactivated Alkenes Using N-Methoxyheteroarenium Salts
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We report the first reductive coupling of unactivated alkenes with N-methoxy pyridazinium, imidazolium, quinolinium, and isoquinolinium salts under hydrogen atom transfer (HAT) conditions, and an expanded scope for the coupling of alkenes with N-methoxy pyridinium salts. N-Methoxy pyridazinium, imidazolium, quinolinium, and isoquinolinium salts are accessible in 1-2 steps from the commercial arenes or arene N-oxides (25-99%). N-Methoxy imidazolium salts are accessible in three steps from commercial amines (50-85%). In total 36 discrete methoxyheteroarenium salts bearing electron-donating, electron-withdrawing, alkyl, aryl, halogen, and haloalkyl substituents were prepared (several in multigram quantities) and coupled with 38 different alkenes. The transformations proceed under neutral conditions at ambient temperature, provide monoalkylation products exclusively, and form a single alkene addition regioisomer. Preparatively useful and complementary site selectivities in the addition of secondary and tertiary radicals to pyidinium salts are documented: harder secondary radicals favor C-2 addition (2->10:1), while softer tertiary radicals favor bond formation to C-4 (4.7->29:1). A diene possessing a 1,2-disubstituted and 2,2-disubstituted alkene undergoes hydropyridylation at the latter exclusively (61%) suggesting useful site selectivities can be obtained in polyene substrates. The methoxypyridinium salts can also be employed in dehydrogenative arylation, borono-Minisci, and tandem arylation processes. Mechanistic studies support the involvement of a radical process.
- Ma, Xiaoshen,Dang, Hester,Rose, John A.,Rablen, Paul,Herzon, Seth B.
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supporting information
p. 5998 - 6007
(2017/05/04)
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- Single-Step Modular Synthesis of Unsaturated Morpholine N-Oxides and Their Cycloaddition Reactions
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A single-flask procedure for the generation of α-keto-N-alkenylnitrones through a Chan–Lam coupling and subsequent spontaneous 6π electrocyclization of these intermediates for the synthesis of 2H-1,4-oxazine N-oxides has been developed for a variety of α-ketooximes and alkenylboronic acids. This transformation provides a new approach to C-substituted unsaturated morpholine derivatives that are poised to undergo further functionalization for the preparation of a diverse array of novel heterocyclic structures. The scope of the new method for the synthesis of 2H-1,4-oxazine N-oxides is discussed, in addition to initial studies describing the cycloaddition reactivity of these new heterocyclic intermediates.
- Son, Jongwoo,Kim, Ki Hwan,Mo, Dong-Liang,Wink, Donald J.,Anderson, Laura L.
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supporting information
p. 3059 - 3063
(2017/03/14)
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- Water-Assisted Nitrile Oxide Cycloadditions: Synthesis of Isoxazoles and Stereoselective Syntheses of Isoxazolines and 1,2,4-Oxadiazoles
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Conventional methods generate nitrile oxides from oxime halides in organic solvents under basic conditions. However, the present work revealed that water-assisted generation of nitrile oxides proceeds under mild acidic conditions (pH 4-5). Cycloadditions of nitrile oxides with alkynes and alkenes easily occurred in water without using catalysts, thus yielding isoxazoles and isoxazolines, respectively, with excellent stereoselectivity toward five- and six-membered cyclic alkenes. A double stereoselective cycloaddition of two units of a nitrile oxide with cyclohexene was also achieved, thus yielding 1,2,4-oxadiazole derivatives having a unique hybrid isoxazoline-oxadiazole skeleton. Enantiomerically pure isoxazolines were prepared from monoterpenes with a ring strain. In one case, the isoxazoline with a butterfly-like structure was simply prepared, and it might be used as a ligand in asymmetric catalysis.
- Kesornpun, Chatchai,Aree, Thammarat,Mahidol, Chulabhorn,Ruchirawat, Somsak,Kittakoop, Prasat
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supporting information
p. 3997 - 4001
(2016/03/19)
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- Regioselective Synthesis of V-Shaped Bistriazinyl-phenanthrolines
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A new, regioselective synthesis of V-shaped 2,9-bis(6-(4-halophenyl)-1,2,4-triazin-3-yl)-1,10-phenanthrolines (4XPhBTPhen) ligands was developed, creating access to a simple and reliable synthesis of precursors for future supramolecular actinide complexing systems. Described is a reactant-directed regioselective synthetic method, which was found to be high yielding and reliable and yields exclusively 6,6′-phenyl BTPhen derivatives (including 4-chloro and 4-bromo) in five simple steps. Molecular and crystal structures of PhBTP and PhBTPhen products are fully determined and both were found to be in space group C2/c. Additionally, molecular and crystal structures of Z and E isomers of 2-hydrazono-2-phenylacetaldehyde oxime, a reagent in the synthetic route, reveal existence of strong intramolecular N-H?O hydrogen bonding in the Z isomer explaining its lower solubility in water.
- Coogan, Niall T.,Chimes, Michael A.,Raftery, James,Mocilac, Pavle,Denecke, Melissa A.
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p. 8684 - 8693
(2015/09/15)
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- Copper-catalyzed direct amination of 1,2,3-triazole N-oxides by C-H activation and C-N coupling
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An efficient approach for the synthesis of 4-amino-2-aryl- 1,2,3-triazole derivatives has been developed through the copper-catalyzed direct C-H amination of 2-aryl-1,2,3-triazole N-oxides under mild reaction conditions. Various amines, including primary and secondary aliphatic and aromatic amines, can be employed as effective coupling partners. The general performance of our method was also demonstrated by the oxidative amination of thiazole and imidazole N-oxides.
- Zhu, Jiayi,Kong, Yubo,Lin, Feng,Wang, Baoshuang,Chen, Zhengwang,Liu, Liangxian
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supporting information
p. 1507 - 1515
(2015/03/04)
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- Green and highly selective protocol for the synthesis of oximes
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A green and efficient protocol has been developed for the synthesis of either exclusively a monoxime or exclusively a dioxime from a host of 1,2-dicarbonyl compounds on silica.
- Ghosh, Pranab,Subba, Raju
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p. 529 - 532
(2013/11/06)
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- NOVEL COELENTERAZINE SUBSTRATES AND METHODS OF USE
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An isolated polynucleotide encoding a modified luciferase polypeptide and novel coelenterazine-based substrates. The OgLuc variant polypeptide has at least 60% amino acid sequence identity to SEQ ID NO: 1 and at least one amino acid substitution at a position corresponding to an amino acid in SEQ ID NO: 1. The OgLuc variant polypeptide has at least one of enhanced luminescence, enhanced signal stability, and enhanced protein stability relative to the corresponding polypeptide of the wild-type Oplophorus luciferase.
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- Nitrite ionic liquids (IL-ONO and [bmim]NO2) as effective nitrosonium sources for the synthesis of α-oximinoketones under mild heterogeneous conditions
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Ketones and β-diketones were nitrosated and converted to their corresponding α-oximinoketones using task-specific ionic liquids, 1-(4-nitritobutyl)-3-methylimidazolium chloride, IL-ONO, and 1-butyl-3-methylimidazolium nitrite at room temperature. The results from two ionic liquids are comparable and showed that these IL's are effective nitrosonium sources for the preparation of oximinoketones. The protocol is rapid, the yields are excellent, and the method is simple. Copyright
- Valizadeh,Shomali,Gholipour
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experimental part
p. 163 - 166
(2012/03/10)
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- Asymmetric reduction of α-keto aldoxime o -ethers
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The catalytic asymmetric reduction of -keto aldoxime O-methyl, O-benzyl, and O-trityl ethers, derived from substituted acetophenones, with borane/oxazaborolidines, by transfer hydrogenation, and with yeast, was studied. The reduction with borane/oxazaborolidines produced the corresponding -hydroxy oxime ethers, -hydroxy hydroxylamine ethers, and -amino alcohols in 39-78% yields and up to 77% ee. The carbonyl group was selectively reduced by transfer hydrogenation with formic acid-triethylamine catalyzed by RhCl[(R,R)-TsDPEN](Ce, and also with yeast, producing -hydroxy oxime ethers, up to 75% ee and 93% ee, respectively. Georg Thieme Verlag Stuttgart New York.
- Bosiak, Mariusz J.,Pakulski, Marcin M.
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experimental part
p. 316 - 324
(2011/03/18)
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- A rapid synthesis of quinoxalines starting from ketones
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A fast and general synthesis of quinoxalines, performed in two stages or as a one-pot reaction, starting from ketones via their α-hydroxylimino ketone derivatives, and condensation of the latter with 1,2-diaminobenzene under microwave irradiation, is described.
- Padmavathy,Nagendrappa, Gopalpur,Geetha
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experimental part
p. 544 - 547
(2011/03/18)
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- A novel reaction of α-carbonyl oxime and amido alcohol: Synthesis, characterization, crystal structure, and thermal studies of an amido alcohol, a new oximino alcohol ligand, and its metal complexes
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In this study, a novel reaction was observed between isonitrosoacetophenone and 1-phenylethanol amine. Acetophenone was used as a starting material to synthesize isonitrosoacetophenone by reaction of acetophenone with n-butyl nitrite in the presence of sodium ethoxide and to synthesize 1-phenylethanol amine by reduction of isonitrosoacetophenone with LiAlH4 in diethyl ether. When the isonitrosoacetophenone reacted with 1-phenylethanol amine, (3E)-3-aza-5-(hydroxyimino)-1,4-diphenylpent-3-en-1-ol monohydrate, a new oximino alcohol ligand and amido alcohol were obtained as associated product interestingly. Four complexes were prepared by treatment of oximino alcohol with metal salts such as CuII, NiII, ZnII, and CoII. Amido alcohol was characterized by single-crystal X-ray diffraction, and all complexes were characterized by using spectroscopic techniques and thermogravimetric analysis (TGA). Copyright Taylor &Francis Group, LLC.
- Kaya, Yunus,Irez, Gazi,Mutlu, Hasene,Buyukgungor, Orhan
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experimental part
p. 754 - 762
(2011/10/05)
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- Metal nitrite: A powerful oxidizing reagent
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An efficient and simple source of nitroso reagents and their oxidation reactions are described. The combination of a Lewis acid and a metal nitrite was applied to the oxidation of silyl enol ethers. Amino acid and peptide derivatives were easily accessed through in situ C-C bond cleavage of fully substituted silyl enol ethers upon oxidation.
- Baidya, Mahiuddin,Yamamoto, Hisashi
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p. 13880 - 13882
(2011/10/09)
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- Synthesis and characterization of a new dioxime: Thermal and magnetic behavior of its heterotrinuclear BF+2-capped complexes
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New heterotrinuclear complexes have been obtained from dinuclear Fe(III) oxygen-bridged N,N'-bis(salicylidene)ethylenediamine (salenH2) and bis(salicylidene)-o-phenylenediamine (salophH2) and Co(II), Ni(II), Cu(II) salts. Then, heterotrinuclear vic-dioxime complexes containing [image omitted] caps have been synthesized. The complexes have been characterized as low-spin distorted octahedral Fe(III) bridged by COO- groups. The structure of dioxime and its complexes were identified by using elemental analysis, magnetic susceptibility, thermal analysis, ICP-AES, 1H-NMR, and IR spectral data.
- Uysal, Saban
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scheme or table
p. 2370 - 2378
(2010/12/24)
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- Synthesis and biological activities of 2,4-diaminopteridine derivatives
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Substituted 2,4-diaminopteridine derivatives 10a-10l were prepared in moderate to good yield. Their structures were confirmed by 1H-NMR and MS spectroscopy, as well as by elemental analysis. Their inhibitory properties against inducible nitric oxide synthase (iNOS) were evaluated in vitro. Biological tests indicated that compound 10a, 10d, 10e, 10h, 10i, and 10l showed potent inhibitory activities similar to that of methotrexate (MTX), while the activities of compound 10b, 10c, 10f, 10g, 10j, and 10k are stronger than MTX. Two compounds, i. e., 10b (IC50 = 18.85 μM) and 10i (IC 50 = 24.08 μM) were further studied for their effect on septic shock in rats and immunologically liver injured mice (in vivo). The results demonstrated that 10b and 10i had the capacity to increase the blood pressure in septic shock and showed notable protective activities on immunological hepatic injury.
- Ma, Fei,Lue, Gang,Zhou, Wei-Fen,Wang, Qiu-Juan,Zhang, Yi-Hua,Yao, Qi-Zheng
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experimental part
p. 274 - 280
(2009/09/06)
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- Beckmann rearrangement of α-oximinoketones
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The Beckmann rearrangement of α-oximinoketones gives benzoic acids as chief isolable products. Both first order and second order Beckmann rearrangements have been observed. The occurrence of first order Beckmann rearrangement in these oximinocarbonyl compounds is confirmed through the identification of the products obtained.
- Kumar, B. N. Hitesh,Prakasam,Srinivasan,Arabindoo, Bhanumathi,Ramana
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p. 963 - 965
(2008/12/23)
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- Synthesis of benzoylformic acid
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A new route for preparing benzoylformic acid (phenylglyoxylic acid) was studied by benzene as the starting material after Friedel-Crafts reaction with acetic anhydride, oximation by isopropyl nitrite, then hydrolysis by hydrochloric acid and sodium nitrite. Calculated on the basis of acetophenone, the final yield is 57.5%. The suitable experimental conditions were also discussed.
- Li, Gui-Yin,Jiang, Yu-Ren,Huang, Ke-Long,Liu, Zuo-Zhou,Ding, Ping
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experimental part
p. 552 - 554
(2009/07/18)
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- CASPASE INHIBITORS CONTAINING DICARBONYLAMINO-ISOXAZOLINE
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The present invention relates to a dicarbonylamino-isoxazoline derivative as an inhibitor against various caspases and a therapeutic composition for preventing inflammation and apoptosis comprising the same.
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Page/Page column 17
(2010/10/20)
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- An efficient route to 5-(hetero)aryl-2,4′- and 2,2′-bipyridines through readily available 3-pyridyl-1,2,4-triazines
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A new route to substituted bipyridines based on a new method for the synthesis of substituted 3-pyridyl-1,2,4-triazines and their aza-Diels-Alder reactions is shown to be an efficient strategy for the preparation of structurally diverse bipyridine ligands.
- Kozhevnikov, Valery N.,Kozhevnikov, Dmitry N.,Shabunina, Olga V.,Rusinov, Vladimir L.,Chupakhin, Oleg N.
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p. 1791 - 1793
(2007/10/03)
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- An efficient route to 5,5″-diaryl-2,2′:6′,2″- terpyridines through 2,6-bis(1,2,4-triazin-3-yl)pyridines
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A new route to substituted 2,2′:6′,2″-terpyridines based on a new method for the synthesis of substituted 2,6-bis(1,2,4-triazin-3-yl) pyridines and their inverse electron demand Diels-Alder reaction is shown to be an efficient strategy for the synthesis of structurally diverse terpyridine ligands.
- Kozhevnikov, Valery N.,Kozhevnikov, Dmitry N.,Shabunina, Olga V.,Rusinov, Vladimir L.,Chupakhin, Oleg N.
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p. 1521 - 1523
(2007/10/03)
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- One-pot synthesis of 3-amino-4-aryl- and 3-amino-4-hetarylfurazans
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A "one pot" method for the synthesis of 3-amino-4-aryl- and 3-amino-4-hetarylfurazans from β-aryl- and 4-β-hetaryl-β-oxo acid esters was developed.
- Sheremetev
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p. 1057 - 1059
(2007/10/03)
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- A remarkably simple α-oximation of ketones to 1,2-dione monooximes using the chlorotrimethylsilane-isoamyl nitrite combination
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Ketones undergo α-oximation by NOCl formed in situ from Me3SiCl and isoamyl nitrite, either in solution or under solvent-free conditions, to produce 1,2-dione monooximes in excellent yields. The oximation is regiospecific in appropriate cases.
- Mohammed, Abdulkarim H.A.,Nagendrappa, Gopalpur
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p. 2753 - 2755
(2007/10/03)
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- Electrical conductivity of chloro(phenyl)glyoxime and its Co(II), Ni(II) and Cu(II) complexes
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Chloro(phenyl)glyoxime, a vicinal dioxime, and its Ni(II), Cu(II) and Co(II) complexes were prepared. XRD patterns of the complexes point to similar crystal structures. IR and elemental analysis data revealed the 1:2 metal-ligand ratio in the complexes. The Co(II) complex is a dihydrate. Temperature dependence of electrical conductivity of the solid ligand and its complexes was measured in the temperature range 25-250°C; it ranged between 10-14-10-6 Ω-1 cm-1 and increased with rising temperature. The activation energies were between 0.61-0.80 eV. The Co(II) complex has lower electric conductivity than the Ni(II) and Cu(II) complexes. This difference in the conductivity has been attributed to differences in the stability of the complexes.
- Turkoglu, Orhan,Soylak, Mustafa,Belenli, Ibrahim
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p. 1233 - 1242
(2007/10/03)
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- Tandem oxidation processes: The direct conversion of activated alcohols into oximes; synthesis of citaldoxime
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The direct conversion of primary alcohols into oximes is reported using manganese dioxide and alkoxylamines/hydroxylamine as their hydrochloride salts or supported on Amberlyst 15. This transformation has been applied to a range of benzylic, allylic and propargylic alcohols and utilised to prepare the natural product citaldoxime.
- Kanno, Hisashi,Taylor, Richard J. K.
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p. 1287 - 1290
(2007/10/03)
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- A new and general method for the synthesis of quinoxalines
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A new and general synthetic method for the preparation of 2,3-disubstituted quinoxalines is described. Treatment of ?-phenylenediamine with α-ketoaldoximes in ethanol affords 2,3-disubstituted quinoxalines in one-step reaction.
- Tajbakhsh,Bakooie,Ghassemzadeh,Beheshtiha,Heravi
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p. 1232 - 1233
(2007/10/03)
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- Ozonolysis Of Substituted Isoxazoles
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The ozonolysis of substituted isoxazoles was investigated.The ozonolysis rates and the products were dependent on the site of the substituent group on isoxazole ring.The reaction mechanism of the ozonolysis of isoxazoles was also proposed.
- Kashima, Choji,Takahashi, Katsumi,Hosomi, Akira
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p. 1075 - 1082
(2007/10/02)
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- The Oxidation of 6- and 7-Aryl-4(3H)-pteridinones by Immobilized Arthrobacter M-4 Cells Containing Xanthine Oxidase
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The preparation of 6- and 7-(pX-phenyl)-4(3H)-pteridinones (X = H, CH3, OCH3) is described.The oxidation of these compounds by (immobilized) Arthrobacter M-4 cells containing xanthine oxidase has been studied.The oxidation monitored by uv spectroscopy usually goes fast, except for 7-(pX-phenyl)-4(3H)-pteridinones (X = CH3, OCH3), which are slowly oxidized.With bacterial cells immobilized in gelatine crosslinked with glutaraldehyde small laboratory-scale oxidations were carried out.Based on spectral data the products of the oxidation reactions are 6- and 7-aryllumazines.
- Meester, Johan W. G. De,Plas, Henk C. van der,Middelhoven, Wouter J.
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p. 441 - 451
(2007/10/02)
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