- Synthesis and X-ray crystal structure of 1,4-dihydro-2,6-dimethyl-4-(2'-isopropylphenyl)-3,5-pyridine-dicarboxy lic acid dimethyl ester: A nifedipine analogue
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We report the synthesis and X-ray crystal structure of 1,4-dihydro-2,6-dimethyl-4-(2'-isopropylphenyl)-3,5-pyridine-dicarboxy lic acid dimethyl ester (4), an analogue of the 1,4-dihydropyridine calcium channel antagonist, nifedipine. Solution state NOE data indicate the presence of both rotameric forms. The solid state shows exclusively one rotamer of 4 (that in which the 2'-isopropyl substituents is syn with C4H, which is also the major solution state rotamer). The 3,5-methyl esters adopt an ap/sp orientation with respect to the dihydropyridine double bonds in the solid state.
- Palmer, Robert B.,Andersen, Niels H.
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- Bridged bicyclic 2,3-dioxabicyclo[3.3.1]nonanes as antiplasmodial agents: Synthesis, structure-activity relationships and studies on their biomimetic reaction with Fe(II)
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Despite recent advancements in its control, malaria is still a deadly parasitic disease killing millions of people each year. Progresses in combating the infection have been made by using the so-called artemisinin combination therapies (ACTs). Natural and synthetic peroxides are an important class of antimalarials. Here we describe a new series of peroxides synthesized through a new elaboration of the scaffold of bicyclic-fused/bridged synthetic endoperoxides previously developed by us. These peroxides are produced by a straightforward synthetic protocol and are characterized by submicromolar potency when tested against both chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains. To investigate their mode of action, the biomimetic reaction of the representative compound 6w with Fe(II) was studied by EPR and the reaction products were characterized by NMR. Rationalization of the observed structure-activity relationship studies was performed by molecular docking. Taken together, our data robustly support the hypothesized mode of activation of peroxides 6a-cc and led to the definition of the key structural requirements responsible for the antiplasmodial potency. These data will pave the way in future to the rational design of novel optimized antimalarials suitable for in vivo investigation.
- D'Alessandro, Sarah,Alfano, Gloria,Di Cerbo, Luisa,Brogi, Simone,Chemi, Giulia,Relitti, Nicola,Brindisi, Margherita,Lamponi, Stefania,Novellino, Ettore,Campiani, Giuseppe,Gemma, Sandra,Basilico, Nicoletta,Taramelli, Donatella,Baratto, Maria Camilla,Pogni, Rebecca,Butini, Stefania
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supporting information
(2019/06/13)
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- Transfer hydrogenation of aromatic and linear aldehydes catalyzed using Cp*Ir(pyridinesulfonamide)Cl complexes under base-free conditions
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Cp*Ir(pyridinesulfonamide)Cl (Cp*?=?pentamethylcyclopentadienyl) precatalysts 1–7 are active for the transfer hydrogenation of aryl, alkyl, and heterocyclic aldehydes. Catalysis is conducted under base-free conditions in air without dried or degassed substrates and solvents. These reductions occur rapidly in moderate to high conversion (39–100%). Benzaldehyde derivatives are reduced to alcohols within 30?min?at 85?°C using 1?mol% iridium precatalyst; reduction also occurs at lower temperatures and loadings (60?°C, 0.50?mol% precatalyst). Benzaldehyde derivatives that possess electron-rich and electron-poor substituents in the para position, including base-sensitive 4-hydroxybenzaldehyde, are readily reduced. Aryl aldehydes containing electron-poor groups are reduced faster than substrates possessing electron-rich moieties. Reduction of the positional isomers of methoxybenzaldehyde and isopropylbenzaldehyde shows highest reduction for the ortho isomer, followed by the meta isomer. Heterocyclic substrates, including biomass derived 5-hydroxymethylfurfural and 2-furfural, were reduced selectively to the alcohol. Decyl aldehyde was reduced to the linear alcohol; importantly self-condensation was not observed. Competition studies demonstrated selective reduction of aldehydes over ketones and a mercury poisoning experiment supports a homogeneous catalyzed pathway.
- Townsend, Tanya M.,Kirby, Christopher,Ruff, Andrew,O'Connor, Abby R.
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- Compounds of the menthane series. Synthesis of unsaturated primary alcohols with the o- and p-menthane skeletons
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Precursors to terpene alcohols of the o- and p-menthane series (o-cimen-7-ol and o- and p-cimen-9-ols) were synthesized, and their reduction with lithium in ethylenediamine was studied. The reduction of o- and p-cimen-9-ols in the presence of isopropyl alcohol selectively afforded the corresponding 1,4-dihydro derivatives. Under analogous conditions, o-cimen-7-ol was converted into a mixture of unsaturated hydrocarbons. The reduction with lithium in ethylenediamine in the absence of isopropyl alcohol in all cases gave mixtures of menthene alcohols.
- Fedorov,Fedorova,Sheverdov,Pavlov,Eremkin
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p. 806 - 812
(2016/07/30)
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- Nucleotides and nucleosides and methods for their use in DNA sequencing
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The present invention relates generally to labeled and unlabled cleavable terminating groups and methods for DNA sequencing and other types of DNA analysis. More particularly, the invention relates in part to nucleotides and nucleosides with chemically cleavable, photocleavable, enzymatically cleavable, or non-photocleavable groups and methods for their use in DNA sequencing and its application in biomedical research.
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Page/Page column 134; 135
(2015/12/18)
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- Novel phenyl-substituted imidazolidines, process for preparation thereof, medicaments comprising said compounds and use thereof
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The invention relates to compounds of formula (I) wherein the groups have stated meanings, and to their physiologically compatible salts. Said compounds are suitable, for example, as anti-obesity drugs and for treating cardiometabolic syndrome.
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Page/Page column 50
(2011/08/04)
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- Facile and efficient hydrolysis of organic halides, epoxides, and esters with water catalyzed by ferric sulfate in a PEG1000-DAIL[BF 4]/toluene temperature-dependent biphasic system
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An efficient and environmentally friendly procedure for the hydrolysis of organic halides, epoxides, and esters with water catalyzed by ferric sulfate in a PEG1000-DAIL[BF4]/toluene temperature-dependent biphasic system has been developed. The product can be easily isolated by a simple decantation, and the catalytic system can be recycled and reused without loss of catalytic activity.
- Hu, Yu Lin,Jiang, Hui,Zhu, Jie,Lu, Ming
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experimental part
p. 292 - 298
(2011/04/21)
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- MORPHOLINE DERIVATIVES AS NOREPINEPHRINE REUPTAKE INHIBITORS
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Compounds of the general formula (I) are inhibitors of the reuptake of norepinephrine. As such, they may be useful for the treatment of disorders of the central and/or peripheral nervous system.
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Page/Page column 40-41
(2008/06/13)
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- 5-Benzylidene-1,2-dihydrochromeno[3,4-f]quinolines as selective progesterone receptor modulators
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A series of 5-benylidene-1,2-dihydrochromeno[3,4-f]quinolines (4) were synthesized and tested in bioassays to evaluate their progestational activities, receptor- and tissue-selectivity profiles as selective progesterone receptor modulators (SPRMs). Most of the new analogues exhibited as highly potent progestins with more than 100-fold receptor selectivity over other steroid hormone receptors and LG120920 (7b) demonstrated tissue selectivity toward uterus and vagina versus breasts in a rodent model after oral administration.
- Zhi, Lin,Tegley, Christopher M.,Pio, Barbara,Edwards, James P.,Motamedi, Mehrnouch,Jones, Todd K.,Marschke, Keith B.,Mais, Dale E.,Risek, Boris,Schrader, William T.
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p. 4104 - 4112
(2007/10/03)
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- Process for producing cyclopropanecarboxylates
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There is disclosed a process process for producing a cyclopropanecarboxylate of formula (1): 1which process comprises reacting cyclopropanecarboxylic acid of formula (2): 2with a monohydroxy compound of formula (3): R6OH??(3),in the presence of a catalyst compound comprising an element of to Group 4 of the Periodic Table of Elements.
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- Electron-transfer-induced reductive cleavage of phthalans: Reactivity and synthetic applications
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The behavior of phthalan (1a) was investigated under conditions of electron transfer from alkali metals in aprotic solvents. Reaction with lithium in the presence of a catalytic amount of naphthalene in THF led to the reductive cleavage of an arylmethyl carbon-oxygen bond, with formation of a stable dilithium compound. Trapping of this intermediate with several electrophiles (alkyl halides, carbonyl derivatives, CO2) was successful. The extension of this procedure to several substituted phthalans (1b-i) was investigated, and the regiochemistry as well as the synthetic usefulness of these reactions are discussed.
- Azzena, Ugo,Demartis, Salvatore,Melloni, Giovanni
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p. 4913 - 4919
(2007/10/03)
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- Kinetics and Regioselectivity of the Autoxidation of o-Substituted Isopropyl Aromatics
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The relative chain propagation constants and the regioselectivities of the oxidations of o-cymene and 2-isopropyl-1,4-dimethylbenzene were determined by competitive oxidations of the hydrocarbons with cumene.As expected, the reactivity of the tertiary C-H bond of the isopropyl group is considerably decreased by o-methyl groups.Also in α-isopropylnaphthalene a considerable decrease in the reactivity of the tertiary C-H bond takes place.The decrease of the chain propagation constants effects a decrease of the oxidabilities of o-substituted isopropyl aromatics.In the case of the methyl isopropyl benzenes the increase of the chain termination constants by primary peroxy radicals must also be taken into consideration.This results in a decrease of the oxidabilities which can be observed even in p-cymene (in comparison with cumene).
- Heinze, Antje,Lauterbach, Gerlinde,Pritzkow, Wilhelm,Schmidt-Renner, Wolfgang,Voerckel, Volkmar,Zewegsuren, Nansadyn
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p. 439 - 446
(2007/10/02)
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- CONCERNING THE CHLOROMETHYLATION OF ALKYLBENZENES AND POLYSTYRENES BY CHLOROMETHYL METHYL ETHER
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Chloromethyl methyl ether-stannic chloride treatments of toluene, ethylbenzene, isopropylbenzene and tert-butyl benzene afforded respectively, 26.5, 16.8, 5.5 and 2.5percent orthoproducts.No meta-products could be detected (less than 0.5percent).Similar chloroalkylation of linear polystyrenes followed by conversion of the chloromethyl groups to hydroxylmethyl, yielded products possessing 5.0 +/- .3percent ortho-substitution.
- Pinnell, R. P.,Khune, G. D.,Khatri, N. A.,Manatt, S. L.
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p. 3511 - 3514
(2007/10/02)
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- Photochemistry of Cyclopropene Derivatives. 20. Deuterium Isotope Effects in the Triplet-Induced Photochemistry of Tetrasubstituted Cyclopropenes
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The photochemical behavior of a number of 3-(o-alkylphenyl)-substituted cyclopropenes which contain a benzylic hydrogen in the γ-position of the side chain has been studied in mechanistic detail.The results obtained indicate that the products of the direct and triplet-sensitized photolysis are completely different.The singlet states of these systems react by ?-bond cleavage of the ring to give products which are explicable in terms of the chemistry of vinyl carbenes.The triplet state, generated by sensitization techniques, undergoes hydrogen atom abstraction by mechanism analoqous to the well-known Norrish type II process of carbonyl compounds.Rate constants for hydrogen abstraction were obtained by plotting Φo/Φq vs. trans-stilbene at a constant quencher to cyclopropene ratio.In contrast to the symmetrically substituted 1,2-diphenylcyclopropenes, the quantum efficiency of hydrogen abstraction of the 1,3 isomers was found to depend on the concentration of starting material.The primary deuterium isotope effect encountered with the symmetrical 1,2-diphenylcyclopropene systems is significantly larger than any previously reported value for hydrogen transfer to an excited state (kH/kD ca. 20/1).A substantial tunnel effect is proposed to rationalize the results.In contrast to the results obtained with the symmetrical cyclopropenes, a much smaller effect on the quantum efficiency was observed with the unsymmetrical systems (kH/kD = 3.3/1).
- Padwa, Albert,Chou, Chuen S.,Rosenthal, Robert J.,Rubin, Byron
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p. 3057 - 3068
(2007/10/02)
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