- Approaches to open fullerenes: Synthesis and kinetic stability of Diels-Alder adducts of substituted isobenzofurans and C60
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(Chemical Equation Presented) We have examined the reactions of 1,3-disubstituted isobenzofurans with the fullerene C60 in the context of an approach to open a large orifice on the fullerene framework. A variety of substituted isobenzofurans (6a-h), generated from the reaction of 1,4-substituted 1,4-epoxynaphthalenes 3a-h with 3,6-bis(2-pyridyl)-1,2,4,5- tetrazine (4a) or 1,2,4,5-tetrazine (4b), were added to C60 to afford the Diels-Alder adducts 7a-h. The thermal stability of these adducts toward retro-Diels-Alder fragmentation differs greatly in solution from that in the solid state. In solution, the relatively facile retro-Diels-Alder fragmentation of monoadducts 7a and 7c, to give C60 and the free isobenzofurans 6a and 6c, have rate constants (and activation barriers) of k = 9.29 × 10-5 s-1 at 70°C (Ea = 32.6 kcal mol -1) and k = 1.36 × 10-4 s-1 at 40°C (Ea = 33.7 kcal mol-1), respectively, indicating that the addition of isobenzofurans to C60 is readily reversible at those temperatures. In the solid state, thermogravimetric analysis of adduct 7a indicates that its decomposition occurs only within the temperature range of 220-300°C. As a result, these compounds can be stored at room temperature in the solid state for several weeks without significant decomposition but have to be handled within several hours in solution.
- Chuang, Shih-Ching,Sander, Michael,Jarrosson, Thibaut,James, Scott,Rozumov, Eugene,Khan, Saeed I.,Rubin, Yves
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- One-Pot and Two-Chamber Methodologies for Using Acetylene Surrogates in the Synthesis of Pyridazines and Their D-Labeled Derivatives
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Acetylene surrogates are efficient tools in modern organic chemistry with largely unexplored potential in the construction of heterocyclic cores. Two novel synthetic paths to 3,6-disubstituted pyridazines were proposed using readily available acetylene surrogates through flexible C2 unit installation procedures in a common reaction space mode (one-pot) and distributed reaction space mode (two-chamber): (1) an interaction of 1,2,4,5-tetrazine and its acceptor-functionalized derivatives with a CaC2?H2O mixture performed in a two-chamber reactor led to the corresponding pyridazines in quantitative yields; (2) [4+2] cycloaddition of 1,2,4,5-tetrazines to benzyl vinyl ether can be considered a universal synthetic path to a wide range of pyridazines. Replacing water with D2O and vinyl ether with its trideuterated analog in the developed procedures, a range of 4,5-dideuteropyridazines of 95–99% deuteration degree was synthesized for the first time. Quantum chemical modeling allowed to quantify the substituent effect in both synthetic pathways.
- Ananikov, Valentine P.,Ledovskaya, Maria S.,Polynski, Mikhail V.
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p. 2286 - 2297
(2021/07/20)
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- Synthesis of novel 7-azaindole derivatives containing pyridin-3-ylmethyl dithiocarbamate moiety as potent PKM2 activators and PKM2 nucleus translocation inhibitors
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Multiple lines of evidence have indicated that pyruvate kinase M2 (PKM2) is upregulated in most cancer cells and it is increasingly recognized as a potential therapeutic target in oncology. In a continuation of our discovery of lead compound 5 and SAR study, the 7-azaindole moiety in compound 5 was systematically optimized. The results showed that compound 6f, which has a difluoroethyl substitution on the 7-azaindole ring, exhibited high PKM2 activation potency and anti-proliferation activities on A375 cell lines. In a xenograft mouse model, oral administration of compound 6f led to significant tumor regression without obvious toxicity. Further mechanistic studies revealed that 6f could influence the translocation of PKM2 into nucleus, as well as induction of apoptosis and autophagy of A375 cells. More importantly, compound 6f significantly inhibited migration of A375 cells in a concentration-dependent manner. Collectively, 6f may serve as a lead compound in the development of potent PKM2 activators for cancer therapy.
- Liu, Bin,Yuan, Xia,Xu, Bo,Zhang, Han,Li, Ridong,Wang, Xin,Ge, Zemei,Li, Runtao
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- Efficient synthesis of pyrazine boronic esters via palladium-catalyzed Miyaura borylation
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A facile and efficient protocol for palladium-catalyzed Miyaura borylation reaction of chloropyrazines with B2pin2has been developed. A certain range of difficult-to-access pyrazine boronic esters can be easily prepared from the corresponding chloropyrazines in moderate to good yields.
- Lu, Hongtao,Wang, Shengqiang,Li, Jingya,Zou, Dapeng,Wu, Yusheng,Wu, Yangjie
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supporting information
p. 839 - 842
(2017/02/10)
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- METHODS OF INCORPORATING AN AMINO ACID COMPRISING A BCN GROUP INTO A POLYPEPTIDE USING AN ORTHOGONAL CODON ENCODING IT AND AN ORTHORGONAL PYLRS SYNTHASE
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The invention relates to a polypeptide comprising an amino acid having a bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN) group, particularly when said BCN group is present as: a residue of a lysine amino acid. The invention also relates to a method of producing a polypeptide comprising a BCN group, said method comprising genetically incorporating an amino acid comprising a BCN group into a polypeptide. The invention also relates to an amino acid comprising bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN), particularly and amino acid which is bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN) lysine. In addition the invention relates to a PylRS tRNA synthetase comprising the mutations Y271M, L274G and C313A.
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Page/Page column
(2015/06/03)
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- ALPHA-HELIX MIMETIC WITH FUNCTIONALIZED PYRIDAZINE
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The synthesis of new α-helix scaffolds mimicking i, i+3 or i+4, i+7 residues, was accomplished. The common pyridazine heterocycle originates from the easily available dimethyl pyridazine-3,6-dicarboxylate building block. These scaffolds may be thought of as synthetic counterparts of amphiphilic α-helices having a hydrophilic face along one side and a hydrophobic face along the other side of the helix.
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- Experimental and theoretical characterization of the valence isomerization of Bi-2H-azirin-2-yls to diazabenzenes
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3,4-Diazidocyclobutenes 16 were prepared from the corresponding dihalides. Some of these diazides, such as parent compound 16 d and phenyl-substituted derivatives 16c,f, underwent spontaneous stereoselective electrocyclic ring opening below room temperature, whereas the tetraalkyl derivatives of 16 had to be heated to force the same reaction. In most cases, the resulting 1,4-diazidobuta-1,3-dienes 8 were isolated to study their photochemical transformation into bi-2Hazirin-2-yls 9 via intermediate monoazirines 17. Except for starting materials with a low number of substituents such as 9d and 9f, title compounds 9 underwent a thermal valence isomerization which led exclusively to pyridazines 18 at surprisingly low temperatures. Based on quantum-chemical calculations for the parent bi-2H-azirinyl 2-yl 9d at the UB3LYP/6-31+G(d) and MR-MP2/TZV(2df,2p) levels, the valence isomerization process is best explained by simultaneous homolytic cleavage of both C-N single bonds of 9 to generate energetically favorable N,N′ diradicals 26, which cyclize to 18. The theoretical studies indicate also that one stereoisomer of 9, namely, the rac compound, should undergo valence isomerization more easily than the other, which is in conformity with different rates of these rearrangement reactions found experimentally. For the tetramethyl-bi-2H-azirin-2-yls 9g, which are better models for the experimentally studied compounds, simultaneous homolytic cleavage of both C-N single bonds is also predicted by the calculations, although the intermediate diradicals 26 g are significantly higher in energy than those of the parent system 9d.
- Banert, Klaus,Grimme, Stefan,Herges, Rainer,Hess, Kirsten,Koehler, Frank,Mueck-Lichtenfeld, Christian,Wuerthwein, Ernst-Ulrich
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p. 7467 - 7481
(2007/10/03)
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- Inhibitors of protein kinase for the treatment of disease
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The present invention is directed in part towards methods of modulating the function of protein kinases with phenol- and hydroxynaphthalene-based compounds. The methods incorporate cells that express a protein kinase. In addition, the invention describes methods of preventing and treating protein kinase-related abnormal conditions in organisms with a compound identified by the invention. Furthermore, the invention pertains to phenol- and hydroxynaphthalene-based compounds and pharmaceutical compositions comprising these compounds.
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- Trisubstituted heterocyclic compounds and their use as fungicides
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Compounds of general formula (I): in which:Het represents a five or six membered saturated, partially unsaturated or aromatic ring containing between one and six heteroatoms of the group N, O, S, in which the heterocycle is substituted in an adjacent manner with -P-Q1-T-Q2, -GZ and Y, such that the substituant -GZ is adjacent to both. the other substituants being as defined in the description,process for preparing these compounds,fungicidal compositions comprising these compounds,processes for treating plants by applying these compounds or compositions.
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- Novel compounds
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The present invention is directed to novel pyridazine compounds of the formula I as well as pharmaceutically and pharmacologically acceptable salts, and hydrates thereof; to a process for their preparation, their use and pharmaceutical compositions comprising said novel compounds. These novel compounds are useful in therapy, particularly for the treatment of type 2 diabetes mellitus.
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- Heterocyclic compounds and medical use thereof
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The present invention provides an AP-1 activation inhibitor, a NF-kappaB activation inhibitor, an inflammatory cytokine production inhibitor, a production inhibitor for matrix metalloprotease or an inflammatory cell adhesion factor expression inhibitor, which contains a heterocyclic compound or a pharmaceutically acceptable salt thereof as an active ingredient.
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- SUBSTITUTED 6,5-HETERO-BICYCLIC DERIVATIVES
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This invention relates to compounds of the formula wherein A, B, D, E K, I, G, R3 and R5 are defined as in the specification, and to the pharmaceutically acceptable salts of such compounds.
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- Hydrazinecarboxylic acids
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Disclosed are certain 3-phenylpyridazines, compositions thereof which are herbicidal and methods of using such compositions for controlling undesired plants. Intermediates useful in preparing the 3-phenylpyridazines are disclosed.
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- 1-arylsulphonyl, arylcarbonyl and 1-arylphosphonyl-3-phenyl-1,4,5,6-tetrahydropyridazines
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Disclosed are progestin agonists having the following formula: STR1 W is absent or --CH=CH--; R1 are independently selected from the group consisting of halogen, --CF3, and NO2, or both R1 may be joined to form a bi-radical which is --CH=CHCH=CH--; R3 are independently selected from the group consisting of hydrogen, C1-6 branched or linear alkyl, halogen and --CF3, with the proviso that R3 at the 3-position must be H where R3 at the 4-position is H, or both R3 may be joined to form a bi-radical selected from the group consisting of --CH=CHCH=CH--, --C(NC1-4 alkyl2)=CHCH=CH-- and --(CH2)4 --; R5 is selected from the group consisting of H and Me; with the proviso that only one of R1 and R3 forms the fused bi-radical; and the stereoisomers.
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- Antihypercholesterolemic compounds and related pharmaceutical compositions and methods of use
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Novel antihypercholesterolemic agents are provided. An exemplary group of compounds has the structural formula (I) STR1 wherein R is a C-17 side chain, R1 is --OH, =O, or the like, and X and Y are N, N→O, CH, C--OH, C--OCH3 or C--Z. Methods of using the compound of formula (I) or other novel oxysterol analogs to treat hypercholesterolemia are provided, as are pharmaceutical compositions containing the compounds.
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- HYDROXAMIC ACID AND CARBOXYLIC ACID DERIVATIVES, PROCESS FOR THEIR PREPARATION AND USE THEREOF
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This disclosure relates to a novel class of hydroxamic and carboxylic acid based matrix metalloproteinase inhibitor derivatives. The disclosure further relates to pharmaceutical compositions containing such compounds and to the use of such compounds and compositions in the treatment of matrix metalloproteinase induced diseases.
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- Gas-phase reactions of benzene and derivatives triggered by hydrazine/ozone; hydroxylation vs. degradation
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The reactions of benzene derivatives C6H5X (X = H, Cl, CH3 and CF3) with hydrazine and ozone in the dark (a source of OH radicals) have been studied in a flow reactor at ambient temperature. (Substituted) phenols were formed, but these were relatively unimportant compared to N-heterocyclic compounds (condensation products of cis-butenedial and analogues with hydrazine) and other (degradation) products.Benzene and (trifluoromethyl)benzene follow a similar path as toluene, also with oxidative ring opening as major reactions.
- Sol, Veronica M.,Mulder, Peter,Louw, Robert
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p. 577 - 582
(2007/10/02)
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- Theory and Experimental Illustration of Preparative Electrochemistry Using Redox Catalysis of Electron Transfer Initiated Radical Chain Reactions. Application to the Cross-Coupling between Aryl Halides and Phenoxide Ions
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A general equation predicting the yield of electron transfer initiated radical chain reaction (SRN1 and related mechanisms) under preparative electrochemical conditions is given for situations where the electron-transfer activation of the chain is performed by means of a redox mediator.Simple tests, allowing for the choice of proper redox mediator, are given, and their origins established and discussed.The validity and application of this simple model is shown and discussed for the case of the SRN1-like reaction involving di-tert-butylphenoxide as a nucleophile, to afford biaryls of interest for their properties in nonlinear optics.
- Alam, N.,Amatore, C.,Combellas, C.,Thiebault, A.,Verpeaux, J. N.
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p. 6347 - 6356
(2007/10/02)
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- An N.M.R. Study of Electron Donor-Electron Acceptor Interaction Between Aromatic Hydrocarbons and Diazines
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Equilibrium constants have been measured by n.m.r. spectroscopy for the electron donor-electron acceptor interaction between a number of aromatic hydrocarbons and diazines.The values obtained have shown that the interaction is weak, and that the aromatic hydrocarbon acts as the electron donor and the diazine as the electron acceptor in the systems studied.Chemical-shift data have provided evidence for the relative positioning of the donor and acceptor components within the various complexes.The effect of temperature on the equilibrium constant for complex formation between (2H6)benzene and pyrazine has shown that the enthalpy of format ion is close to zero.
- Hurst, Derek T.,Thakrar, Usha B.,Wells, Clifford H. J.,Wyer, John
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p. 1313 - 1319
(2007/10/02)
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- FLASH VACUUM PYROLYSIS OF PYRIDAZINE N-OXIDES
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Flash vacuum pyrolysis of 6-unsubstituted pyridazine 1-oxides afforded nitriles and pyrroles. 6-Phenylpyridazine 1-oxides gave 2-phenyloxazole together with nitriles and pyrroles. 6-Methylpyridazine 1-oxide and 3,6-dimethylpyridazine 1-oxide afforded naphthalene and benzene, respectively, together with other products.The formation mechanism of these products was speculated.
- Ohsawa, Akio,Itoh, Takashi,Igeta, Hiroshi
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p. 2677 - 2681
(2007/10/02)
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- 3,4-DIAZABENZVALENE, THE AZOALKANE PRECURSOR TO TETRAHEDRANE. SYNTHESIS AND REACTIVITY.
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The title diazene 1 has been synthesized and shown to decompose thermally to cyclobutadiene over a surprisingly small barrier.
- Kaisaki, David A.,Dougherty, Dennis A.
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p. 5263 - 5266
(2007/10/02)
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- Azo Bridges from Azines, III. Unexpected Formation of a Compound with Parallel C = C and N = N Bonds
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Dialdehyde 5 reacts with hydrazine at pH > 7 to form the trimeric azine 6Tr, at pH 4, however, to yield unexpectedly 8, which contains parallel C = C and N = N bonds in close proximity.The complex reaction is clarified. 8 is characterized by structure proving reactions and its spectroscopic data.
- Berning, Wilfried,Huenig, Siegfried,Prokschy, Frank
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p. 1455 - 1464
(2007/10/02)
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- NEW ROUTES TO γ-KETOESTERS, β-HYDROXY-δ-KETOESTERS, α,β-UNSATURATED γ-KETOALDEHYDES, AND ACETALS. SYNTHESIS OF CYCLOPENTENONES
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New methodology, based on the chemistry of silyl nitronates, nitrile oxides (hydroxamic acid chlorides), and derived 2-isoxazolines, is developed for the preparation of the title compounds.
- Sharma, K. K.,Torssell, K. B. G.
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p. 1085 - 1089
(2007/10/02)
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- N-Substituted 1,4-dihydropyridazines and pharmaceutical compositions
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Compounds of the formula: STR1 which are useful as antihypertensive agents are disclosed.
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- 3-(1-Pyrazolyl)-pyridazine derivatives and hypotensive compositions thereof
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The invention relates to compounds of general formula STR1 wherein R1 stands for a hydrogen atom or a C1-6 alkyl-, a C2-4 hydroxyalkyl, a C3-6 cycloalkyl or a phenyl group, R2 stands for a hydrogen, fluorine, chlorine or bromine atom or a C1-6 alkyl, a C2-4 hydroxyalkyl, a nitro or an --NR5 R6 group, wherein R5 and R6 may have the same or different meaning and stand each for a hydrogen atom or a C1-4 alkyl or a C2-4 hydroxyalkyl group, R3 stands for a hydrogen atom or a C1-6 alkyl, a C2-4 hydroxyalkyl, a C3-6 cycloalkyl or a phenyl group, a chlorine atom or a hydroxyl, amino or methoxy group, R4 stands for a carbamoyl, a cyano or an --NR7 --NHR8 group, wherein R7 and R8 may have the same or different meaning and stand each for a hydrogen atom or a C1-4 alkyl, a C2-4 hydroxyalkyl, a C1-4 alkoxycarbonyl or an --NR9 R10 group, wherein R9 and R10 may have the same or different meaning and stand each for a hydrogen atom or a C1-5 alkyl, a C2-4 hydroxyalkyl, a C3-6 cycloalkyl, a phenyl or a benzyl group, or --NR9 R10 may represent a morpholine, piperidine or piperazine ring, and their pharmaceutically acceptable acid-addition salts. Furthermore, the invention relates to a process for preparing these compounds. The novel compounds of general formula I have valuable pharmacological properties. Thus they show a considerable hypotensive effect and are capable to inhibit enzymes regulating the catabolism of prostaglandins.
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