- Direct Hydrogenation of a Broad Range of Amides under Base-free Conditions using an Efficient and Selective Ruthenium(II) Pincer Catalyst
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The ruthenium(II) complex, [fac-PNHN]RuH(η1-BH4)(CO) (B; PNHN=8-(2-diphenylphosphinoethyl)aminotrihydroquinoline), is a highly versatile and effective catalyst (loadings of 0.1–1 mol %) for the hydrogenation of a multitude of amides, which include primary, secondary, and tertiary amides, to give their corresponding alcohols and amines in high yields under base-free conditions. All products were confirmed by using GC and GC–MS.
- Wang, Zheng,Li, Yong,Liu, Qing-Bin,Solan, Gregory A.,Ma, Yanping,Sun, Wen-Hua
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p. 4275 - 4281
(2017/12/02)
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- Structurally simple inhibitors of lanosterol 14α-demethylase are efficacious in a rodent model of acute Chagas disease
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We report structure-activity studies of a large number of dialkyl imidazoles as inhibitors of Trypanosoma cruzi lanosterol-14α-demethylase (L14DM). The compounds have a simple structure compared to posaconazole, another L14DM inhibitor that is an anti-Chagas drug candidate. Several compounds display potency for killing T. cruzi amastigotes in vitro with values of EC 50 in the 0.4-10 nM range. Two compounds were selected for efficacy studies in a mouse model of acute Chagas disease. At oral doses of 20-50 mg/kg given after establishment of parasite infection, the compounds reduced parasitemia in the blood to undetectable levels, and analysis of remaining parasites by PCR revealed a lack of parasites in the majority of animals. These dialkyl imidazoles are substantially less expensive to produce than posaconazole and are appropriate for further development toward an anti-Chagas disease clinical candidate.
- Suryadevara, Praveen Kumar,Olepu, Srinivas,Lockman, Jeffrey W.,Ohkanda, Junko,Karimi, Mandana,Verlinde, Christophe L. M. J.,Kraus, James M.,Schoepe, Jan,Van Voorhis, Wesley C.,Hamilton, Andrew D.,Buckner, Frederick S.,Gelb, Michael H.
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experimental part
p. 3703 - 3715
(2010/04/24)
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- Direct Aromatic Amination by Azides: Reactions of Hydrazoic Acid and Butyl Azides with Aromatic Compounds in the Presence of Both Trifluoromethanesulfonic Acid and Trifluoroacetic Acid
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Reactions of hydrazoic acid with aromatic compounds in the presence of both trifluoromethanesulfonic acid (TFSA) and trifluoroacetic acid (TFA) efficiently gave primary arylamines without diamine contaminants.The reactions provide mainly the ortho- and para-monoamines wven for readily oxidised aromatic compounds such as cumene, mesitylene, durene, isodurene and anisole.The mechanistic investigation demonstrates that the reactions proceed via a concerted process involving both arene attack on a conjugate acid of the azide and elimination of N2 from the conjugate acid.The reaction of butyl azide with benzene and mesitylene in the presence of both TFSA and TFA produced N-butylarylamines in low yields together with high yields of butanal via a butylnitrenium ion intermediate; a similar reaction with tert-butyl azide gave no tert-butylarylamines.
- Takeuchi, Hiroshi,Adachi, Taki,Nishiguchi, Hideaki,Itou, Katsutaka,Koyama, Kikuhiko
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p. 867 - 870
(2007/10/02)
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- Kynurenic acid derivatives useful in the treatment of neurodegenerative disorders
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4-Oxo-1,4-dihydroquinoline compounds having a 2-acidic group or a group convertible thereto in vivo, and their pharmaceutically acceptable salts, are potent specific antagonists of N-methyl-D-aspartate (NMDA) receptors and are therefore useful in the treatment of neurodegenerative disorders. 4-Oxo-1,4-dihydroquinoline compounds having a 2-acidic group or a group convertible thereto in vivo, other than carboxy or C 1-6 alkoxycarbonyl, are novel compounds, as also are compounds of formula II STR1 wherein R 2 represents carboxy or a group convertible thereto in vivo, R 6 is hydrogen and R 5 and R 7 represent C 1-6 alkyl or halogen, provided that R 5 and R 7 are not simultaneously chlorine or simultaneously bromine; a process for preparing the novel compounds is described, as also are pharmaceutical compositions containing the novel compounds.
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- Intramolecular Selectivity of the Alkylation of Substituted Anilines by Gaseous Cations
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The intramolecular selectivity of the electrophilic reactions of Et(1+), i-Pr(1+), and Me2F(1+) cations with substituted anilines, including m-toluidine, m-anisidine, and m- and p-fluoroaniline, has been investigated in the dilute gas state at pressures ranging from 100 to 720 torr by a radiolytic technique, complemented by chemical ionization mass spectrometry.The results indicate an appreciable kinetic bias for the nitrogen atom, leading to predominant N-methylation by Me2F(1+).The reactivity of the carbenium ions is complicated by the simultaneous occurrence of proton transfer, in particular to the NH2 group, which increases the relative extent of ring alkylation.The positional selectivity is characterized, aside from the usual orienting effects of the substituents, by the enchanced reactivity of the ring positions ortho to an n-type substituent, irrespective of its activating or deactivating properties.The effect is traced to the preliminary formation of an electrostatic adduct between the aniline and the gaseous electrophile.
- Attina, Marina,Cacace, Fulvio,de Petris, Giulia
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p. 1556 - 1561
(2007/10/02)
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- Aromatic Substitution in the Gas Phase. Intramolecular Selectivity of the Reaction of Aniline with Charged Electrophiles
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The intramolecular selectivity of the electrophilic reactions of radiolytically formed C2H5+, i-C3H7+, t-C4H9+, (CH3)2F+, and CH3CO+ cations with aniline has been investigated in the gas phase at nearly atmospheric pressure.Under conditions of kinetic control of products, the reactivity of the N atom and of the aromatic ring is comparable, a mixture of ring- and N-substituted products being invariably formed in proportions that depend on the nature of the electrophile.The relative rate of N-substitution increases in the order: C2H5+ ca. i-C3H7++++.The positional selectivity of the gaseous electrophiles, except CH3CO+, is characterized by predominant ortho substitution.
- Attina, Marina,Cacace, Fulvio
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p. 1122 - 1126
(2007/10/02)
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- Quantitative Structure Activity Relationship in 3,4-Disubstituted Pyridines and 1-(3"-Amino-4"-pyridyl)-4-arylpiperazines
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In a study of the SAR in 3,4-disubstituted pyridines, it has been observed that both stimulant and anticonvulsant activities are confined to 1-(3'-amino-4'-pyridyl)-4-phenylpiperazines, and further the substitution in the phenyl ring can dissociate these activities of this prototype.In order to understand the relationship of electronic (?), hydrophobic (?) and stereo (Es) parameters of the substituents with anticonvulsant activity, a multi-parameter regression analysis of twelve compounds of this group has been carried out, which suggests that hydrophobic and electronic factors are more important and anticonvulsant activity can be enhanced by compounds having log P = 2.7- 3.1 0= 2.67 (Eq. 5) and (log P)0= 3.09 (Eq. 6)> with an electron withdrawing substituent in the phenyl ring.
- Saxena, Anil K.,Arunamurthy, V.,Patnaik, G. K.,Jain, Padam C.,Anand, Nitya
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p. 873 - 878
(2007/10/02)
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