- Design, synthesis, and biological evaluation of 2,4-diamino pyrimidine derivatives as potent FAK inhibitors with anti-cancer and anti-angiogenesis activities
-
A series of 2,4-diamino pyrimidine (DAPY) derivatives were designed, synthesized, and evaluated as inhibitors of focal adhesion kinase (FAK) with antitumor and anti-angiogenesis activities. Most compounds effectively suppressed the enzymatic activities of
- Wang, Shan,Zhang, Rong-Hong,Zhang, Hong,Wang, Yu-Chan,Yang, Dan,Zhao, Yong-Long,Yan, Guo-Yi,Xu, Guo-Bo,Guan, Huan-Yu,Zhou, Yan-Hua,Cui, Dong-Bing,Liu, Ting,Li, Yong-Jun,Liao, Shang-Gao,Zhou, Meng
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-
- Trifluoroacetic Acid Hydroxylamine System as Organocatalyst Reagent in a One-Pot Salt Free Process for the Synthesis of Caprolactam and Amides of Industrial Interest
-
In this work we studied the reactivity of the Trifluoroacetic acid hydroxylamine system in the one step salt free synthesis of amides from ketones. A particular regards was paid to the caprolactam synthesis because of its industrial relevance. Synthesis, reactivity and characterization of the hydroxylamine trifluoroacetate is given. Fast oximation reaction of several ketones was gained at room temperature (1?h of reaction quantitative conversion for several ketones). In the same reactor, by raising the temperature at 383?K, the Beckmann rearrangement of the so obtained oximes is easily accomplished in the presence of three equivalent of TFA. The possibility of obtaining the trifluoroacetate of the hydroxylamine with a modified nitric acid hydrogenation reactions was verified, too. Reuse of solvent and trifluoroacetic acid is easily achieved by distillation. Graphical abstract: Salt free one-pot caprolactam and amides process catalyzed by CF3COOH, in the presence of NH2OH TFA as the oximation agent.[Figure not available: see fulltext.].
- Manente,Pietrobon,Ronchin,Vavasori
-
p. 3543 - 3549
(2021/03/30)
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- 2-(4-methanoyl) anilino-4-aminopyrimidine derivatives and application thereof
-
The invention belongs to the technical field of chemical medicines, and particularly relates to 2-(4-methanoyl) anilino-4-aminopyrimidine derivatives and application thereof. According to the invention, nitryl, carboxyl, cyano and the like are adopted to
- -
-
Paragraph 0031-0036
(2021/04/03)
-
- A Convenient One-Pot Synthesis of 1,5-Disubstituted Tetrazoles Containing an Amino or a Carboxy Group
-
Abstract: A convenient method is proposed for constructing the tetrazole ring by a one-pot reaction of amides with phosphorus oxychloride and sodium azide. A series of 1,5-disubstituted tetrazoles containing an amino or a carboxy group, which present interest as buildings blocks for the synthesis of biologically active substances, were obtained.
- Obushak, M. D.,Pokhodylo, N. T.,Shyyka, O. Ya.
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p. 802 - 812
(2020/07/03)
-
- 4, 6-disubstituted pyridine [3, 2-d] pyrimidine compound as well as preparation and application thereof
-
The invention belongs to the technical field of medicines. The invention relates to the field of pharmaceutical chemistry, in particular to a 4, 6-disubstituted pyridine [3, 2-d] pyrimidine compound and pharmaceutically acceptable salt thereof, a preparation method of the compound, a pharmaceutical composition taking the compound as an active ingredient, and application of the compound in preparation of an MNK inhibitor and drugs for treating and/or preventing various cancers and/or metabolic diseases. The present invention relates to compounds represented by formulas I, II, III or IV, and pharmaceutically acceptable salts, hydrates, solvates and metabolites thereof, wherein the variables are described in the claims and the description.
- -
-
Paragraph 0403-0406
(2020/04/02)
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- Chemoselective Synthesis of Aryl Ketones from Amides and Grignard Reagents via C(O)-N Bond Cleavage under Catalyst-Free Conditions
-
Conversion of a wide range of N-Boc amides to aryl ketones was achieved with Grignard reagents via chemoselective C(O)-N bond cleavage. The reactions proceeded under catalyst-free conditions with different aryl, alkyl, and alkynyl Grignard reagents. α-Ketoamide was successfully converted to aryl diketones, while α,β-unsaturated amide underwent 1,4-addition followed by C(O)-N bond cleavage to provide diaryl propiophenones. N-Boc amides displayed higher reactivity than Weinreb amides with Grignard reagents. A broad substrate scope, excellent yields, and quick conversion are important features of this methodology.
- Sureshbabu, Popuri,Azeez, Sadaf,Muniyappan, Nalluchamy,Sabiah, Shahulhameed,Kandasamy, Jeyakumar
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p. 11823 - 11838
(2019/10/02)
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- Nickel-catalyzed aminocarbonylation of aryl halides with carbamoylsilanes: efficient synthesis of secondary (primary) aromatic amides
-
A nickel-catalyzed aminocarbonylation of aryl halides using carbamoylsilane as an amide source leading to corresponding secondary or primary aromatic amides has been developed, in which the methoxymethyl and benzyl were used as amino protecting group. The protocol tolerates a broad range of aryl halides bearing different functional groups to afford good yields of aryl amides under mild reaction conditions. The types and the relative positions of substituents on the aryl ring make a notable impact on the coupling efficiency. The plausible mechanism of nickel-catalyzed aminocarbonylation has been suggested.
- Chen, Jianxin,Chen, Wenwen,Wen, Xueping
-
-
- Selective N-Monoalkylation of Amide Derivatives with Trialkyl Phosphates
-
A highly selective and easily handled monoalkylation of primary amide derivatives by using trialkyl phosphates as alkylating reagents in cyclopentyl methyl ether (CPME) was developed. Various monoalkylated amide derivatives were efficiently synthesized by changing the alkyl moiety (e.g., methyl, ethyl, butyl, or benzyl) of the trialkyl phosphate. These phosphate reagents are relatively stable and easily available, and CPME is a useful solvent in process chemistry.
- Asai, Shota,Ban, Kazuho,Monguchi, Yasunari,Sajiki, Hironao,Sawama, Yoshinari
-
supporting information
p. 322 - 325
(2017/10/31)
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- Palladium-Catalyzed Direct C-H Trifluoroethylation of Aromatic Amides
-
A simple and direct C-H trifluoroethylation of aromatic amides has been developed. The protocol is applicable to a variety of aromatic amides, including ones derived from amino acids. The developed method can be used for further modifications of peptides. Preliminary mechanistic studies have been done by isolating the reaction intermediate.
- Maraswami, Manikantha,Pankajakshan, Sreekumar,Chen, Gang,Loh, Teck-Peng
-
supporting information
p. 4223 - 4226
(2017/08/23)
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- Synthesis of Secondary Aromatic Amides via Pd-Catalyzed Aminocarbonylation of Aryl Halides Using Carbamoylsilane as an Amide Source
-
Using N-methoxymethyl-N-organylcarbamoyl(trimethyl)silanes as secondary amides source, the direct transformation of aryl halides into the corresponding secondary aromatic amides via palladium-catalyzed aminocarbonylation is described. The reactions tolerated a broad range of functional groups on the aryl ring except big steric hindrance of substituent. The types and the relative position of substituents on the aryl ring impact the coupling efficiency.
- Tong, Wenting,Cao, Pei,Liu, Yanhong,Chen, Jianxin
-
p. 11603 - 11608
(2017/11/10)
-
- Nickel-catalyzed aminocarbonylation of aryl halides using carbamoylsilane as an amide source
-
The nickel-catalyzed aminocarbonylation of aryl halides using carbamoylsilane as an amide source is developed. The procedure can prepare both tertiary and secondary amides, and is applicable to various carbamoylsilanes and aryl halides containing differen
- Wen, Xue-Ping,Han, Yu-Ling,Chen, Jian-Xin
-
p. 45107 - 45112
(2017/10/13)
-
- Cobalt(III)-Catalyzed Directed C-H Allylation
-
The cobalt(III)-catalyzed allylation was developed for amide-directed C-H activation of arenes, heteroarenes, and olefins. A variety of allyl sources can be employed to introduce this useful functional group.
- Gensch, Tobias,Vásquez-Céspedes, Suhelen,Yu, Da-Gang,Glorius, Frank
-
supporting information
p. 3714 - 3717
(2015/08/18)
-
- Reductive N-O cleavage of Weinreb amides by sodium in alumina and silica gels: synthetic and mechanistic studies
-
The use of sodium in alumina and silica gels for the reductive cleavage of the N-O bond of N-methoxy-N-methylamides, commonly referred to as Weinreb amides, has been investigated. This method reduces a diverse set of Weinreb amides with different function
- Jackson, James E.,O'Brien, Brittany N.,Kedzior, Sonya K.,Fryz, Gage R.,Jalloh, Fatmata S.,Banisafar, Arash,Caldwell, Michael A.,Braun, Max B.,Dunyak, Bryan M.,Dye, James L.
-
supporting information
p. 6227 - 6230
(2015/10/20)
-
- Efficient synthesis of N-methylamides and amines via 4-(alkylamino)benzyl- N-methylamine as a new protecting group
-
4-(Alkylamino)benzyl-N-methylamine is a good protecting group for the synthesis of N-methylamides and amines. The N-debenzylation of N-methylamides and amines can be carried out selectively and efficiently under condition using trifluoroacetic acid (TFA).
- Lee, Sang-Hak,Mu, Yu,Kim, Gun-Woo,Kim, Jin-Seok,Park, Seok-Hwi,Jin, Tian,Lee, Kee-Young,Ham, Won-Hun
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p. 1749 - 1764
(2013/09/12)
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- Copper-catalyzed N-methylation of amides and O-methylation of carboxylic acids by using peroxides as the methylating reagents
-
The copper-catalyzed N-methylation of amides and O-methylation of carboxylic acids by using peroxides as the methylating reagent are described. Various amides and carboxylic acids were methylated affording N-substituted amides and esters. Tentative mechanistic studies suggest that this reaction is likely to involve a radical process.
- Xia, Qinqin,Liu, Xiaolong,Zhang, Yuejiao,Chen, Chao,Chen, Wanzhi
-
supporting information
p. 3326 - 3329
(2013/07/26)
-
- Transition metal-free one-pot synthesis of 2-substituted 3-carboxy-4-quinolone and chromone derivatives
-
A novel one-pot synthesis of the 2-substituted 3-carboxy-4-quinolone/ chromone derivatives from readily available 3-oxo-3-arylpropanoates and amides/acyl chlorides is reported, without any transition metal aid. The Royal Society of Chemistry 2013.
- Lin, Jian-Ping,Long, Ya-Qiu
-
supporting information
p. 5313 - 5315
(2013/06/27)
-
- DERIVATIVES OF QUINOLINE-3-CARBOXYLIC ACID AND THEIR MEDICAL USE
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A compound of formula (I) as well as pharmaceutically acceptable salts thereof and pharmaceutical compositions comprising a therapeutically effective amount of the compounds. The compounds are useful in treatment of cancer, diabetic retinopathy, age-related macular degeneration, inflammation, stroke, ischemic myocardium, atherosclerosis, macular edema or psoriasis.
- -
-
Page/Page column 29-30
(2010/12/18)
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- A simple and highly efficient one-pot procedure for the synthesis of amides via beckmann rearrangements using 1-tosylimidazole (TsIm)
-
A facile and highly efficient method for one-pot Beckmann rearrangement of ketoximes into N-substituted amides using N-(p-toluenesulfonyl)imidazole (TsIm) is described. In this method, ketoximes are refluxed with TsIm and Cs2CO3 in the presence of SiO2 as a recyclable catalyst in DMF affording the corresponding amides in high yields. This methodology is highly efficient and regioselective for various structurally diverse ketoximes including symmetrical and unsymmetrical as well as cyclic oximes. The results of quantum mechanical studies used to rationalize the experimental outcomes are discussed. Copyright Taylor & Francis Group, LLC.
- Rad, Mohammad Navid Soltani,Khalafi-Nezhad, Ali,Behrouz, Somayeh,Amini, Zohreh,Behrouz, Marzieh
-
experimental part
p. 1658 - 1671
(2010/09/09)
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- NOVEL PIPERAZINE DERIVATIVES AS INHIBITORS OF STEAROYL-CoA DESATURASE
-
The present invention relates to piperazine derivatives that act as inhibitors of stearoyl-CoA desaturase. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.
- -
-
Page/Page column 24
(2009/10/01)
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- Establishment of heterolytic and homolytic Y-NO2 bond dissociation energy scales of nitro-containing compounds in acetonitrile: Chemical origin of NO2 release and capture
-
(Chemical Equation Presented) The first heterolytic and homolytic N(O)-NO2 bond dissociation energy scales of three types Y-nitro (Y = N, O) compounds and corresponding radical anions in acetonitrile were established by using titration calorimetry combined with relevant electrochemical data through proper thermodynamic cycles.
- Li, Xin,Zhu, Xiao-Qing,Zhang, Fan,Wang, Xiao-Xiao,Cheng, Jin-Pei
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p. 2428 - 2431
(2008/09/20)
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- Room-temperature debenzylation of N-benzylcarboxamides by N-bromosuccinimide
-
A simple and highly efficient method has been developed with which to cleave the N-benzyl group on N-mono- or disubstituted carboxamides using N-bromosuccinimide (NBS) at room temperature. All the 31 substrates examined showed moderate to excellent deprotection yields. Our study also indicated that the debenzylation may involve an oxygen/light initiated free radical mechanism. Georg Thieme Verlag Stuttgart.
- Kuang, Liping,Zhou, Jing,Chen, Sheng,Ding, Ke
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p. 3129 - 3134
(2008/03/28)
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- Comparative studies on the pyrolysis of N-arylideneaminoamides: Kinetic and mechanistic studies
-
Rates of thermal decomposition of title compounds have been measured using a static reaction system. They undergo a unimolecular first-order elimination to give arylnitrile and the corresponding substituted amides. The decomposition parallels that of N-arylidenamino cyclic amide. The relative elimination rates at 600 K were calculated. The kinetic data reveal that the electronic effects of substituents, such as methyl, phenyl, benzyl, and allyl groups, are associated with the opposing directions in which the lone pair of electrons on the nitrogen atom of the arylidene moiety is being delocalized.
- Al-Awadi, Nouria A.,Ibrahim, Yehia A.,Patel, Mehul,George, Bobby J.,Al-Etiabi, Alya M.
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-
- P2O5/SiO2-catalyzed one-pot synthesis of amides from ketones via schmidt reaction under microwave irradiation in dry media
-
A facile and efficient method for the preparation of amides from ketones by the Schmidt reaction is described for the first time using P 2 O 5 /SiO 2 and sodium azide under solvent-free microwave irradiation. Advantages of this procedure are selectivity, good yields, a simple operation, short reaction time, and solvent-free conditions. Copyright Taylor & Francis Group, LLC.
- Eshghi, Hossein,Hassankhani, Asadollah
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p. 2211 - 2216
(2007/10/03)
-
- Discovery of CC chemokine receptor-3 (CCR3) antagonists with picomolar potency
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Starting with our previously described20 class of CC chemokine receptor-3 (CCR3) antagonist, we improved the potency by replacing the phenyl linker of 1 with a cyclohexyl linker and by replacing the 4-benzylpiperidine with a 3-benzylpiperidine. The resulting compound, 32, is a potent and selective antagonist of CCR3. SAR studies showed that the 3-acetylphenyl urea of 32 could be replaced with heterocyclic ureas or heterocyclic-substituted phenyl ureas and still maintain the potency (inhibition of eotaxin-induced chemotaxis) of this class of compounds in the low-picomolar range (IC50 = 10-60 pM), representing some of the most potent CCR3 antagonists reported to date. The potency of 32 for mouse CCR3 (chemotaxis IC50 = 41 nM) and its oral bioavailability in mice (20% F) were adequate to assess the efficacy in animal models of allergic airway inflammation. Oral administration of 32 reduced eosinophil recruitment into the lungs in a dose-dependent manner in these animal models. On the basis of its overall potency, selectivity, efficacy, and safety profile, the benzenesulfonate salt of 32, designated DPC168, entered phase I clinical trials.
- De Lucca, George V.,Ui, Tae Kim,Vargo, Brian J.,Duncia, John V.,Santella III, Joseph B.,Gardner, Daniel S.,Zheng, Changsheng,Liauw, Ann,Wang, Zhang,Emmett, George,Wacker, Dean A.,Welch, Patricia K.,Covington, Maryanne,Stowell, Nicole C.,Wadman, Eric A.,Das, Anuk M.,Davies, Paul,Yeleswaram, Swamy,Graden, Danielle M.,Solomon, Kimberly A.,Newton, Robert C.,Trainor, George L.,Decicco, Carl P.,Ko, Soo S.
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p. 2194 - 2211
(2007/10/03)
-
- Oxidation of tertiary benzamides by 5,10,15,20-tetraphenyl- porphyrinatoironIII chloride-tert-butylhydroperoxide
-
Tertiary benzamides are oxidized by the 5,10,15,20- tetraphenylporphyrinatoiron(III) chloride-ButOOH system at the α-position of the N-alkyl groups. The major products are N-acylamides, although small amounts of secondary amides, the products of dealkylation, are also formed. Plots of initial rate versus initial substrate concentration for these reactions are curved, suggesting formation of an oxidant-substrate complex. The reaction rates are almost insensitive to the substituent in the benzamide moiety, but there is a kinetic deuterium isotope effect of 5.6 for the reaction of the N,N-(CH3)2 and N,N-(CD3) 2 compounds. Comparison of the reaction products from N-alkyl-N-methylbenzamides reveals that, for all compounds studied except N-cyclopropyl-N-methylbenzamide, oxidation of the alkyl group is preferred, strongly so (by a factor of ca. 8) for N-allyl-N-methylbenzamide. In contrast to microsomal oxidation, there is no steric hindrance to oxidation of an isopropyl group. Thus, we propose that these reactions proceed via hydrogen atom abstraction to form an α-carbon-centred radical and we attribute the observed diminished reactivity of the N-cyclopropyl group to its known reluctance to form a cyclopropyl radical. Oxidation of N-methyl-N-(2,2,3,3- tetramethylcyclopropyl)methylbenzamide provides preliminary evidence for rearrangement of an intermediate radical. While it remains unclear how these reactions proceed directly to the N-acyl products, we have established that N-hydroxymethyl, N-alkoxymethyl and N-alkylperoxymethyl intermediates are not involved.
- Constantino, Luis,Iley, Jim
-
p. 1894 - 1900
(2007/10/03)
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- N-ureidoalkyl-piperidines as modulators of chemokine receptor activity
-
The present application describes modulators of CCR3 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.
- -
-
-
- N-ureidoalkyl-piperidines as modulators of chemokine receptor activity
-
The present application describes modulators of CCR3 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.
- -
-
-
- Piperidine amides as modulators of chemo kine receptor activity
-
The present application describes modulators of CCR3 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.
- -
-
-
- A rapid and convenient synthesis of amides from aromatic acids and aliphatic amines in dry media under microwave irradiation
-
The synthesis of amides 2 from the corresponding aromatic acids and aliphatic amines in the presence of catalytic amount of p-toluenesulfonic acid has been reported. The reactions are accelerated with microwave irradiation under solvent-free conditions to afford a high yielding synthesis of amides.
- Hajipour,Ghasemi
-
p. 504 - 507
(2007/10/03)
-
- A convenient and efficient one-pot conversion of ketones into amides under microwave irradiation using silica gel supported NaHSO4 catalyst
-
A simple and rapid conversion of ketones into the corresponding amides in high yields has been developed by treatment with hydroxylamine hydrochloride under microwave irradiation in the presence of silica gel supported NaHSO4 catalyst.
- Das,Ravindranath,Venkataiah,Madhusudhan
-
p. 482 - 483
(2007/10/03)
-
- First N-alkyl heterolysis of tertiary benzamides in neutral conditions
-
Tertiary benzamides 1-4 bearing a tricyclopropylmethyl substituent were synthesized and found to undergo rapid alkyl-nitrogen heterolysis at pH 7. X-Ray diffraction structural data for these amides revealed that their ability to give N-alkyl fission was not induced by the pyramidalization of the nitrogen atom, in contrast to what has been observed in the case of N-acyl cleavage (hydrolysis). (C) 2000 Elsevier Science Ltd.
- Auzeil, Nicolas,Tomas, Alain,Fleury, Maurice-Bernard,Largeron, Martine
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p. 8781 - 8785
(2007/10/03)
-
- Substituent effect on acidity of substituted 2-(4-nitrobenzoylamino)alkanamidesin methanol-dimethyl sulfoxide mixtures
-
The dissociation constants of substituted 2-(4-nitrobenzoylamino)alkanamides, N-[2-(4-nitrobenzoylamino)aikanoyl]pyrrolidines, and N-alkyl-4-nitrobenzamides have been measured spectrophotometrically in 60 and 80% v/v DMSO. The pKA values of these N-acids are discussed from the point of view of substituents at the acetamide a-carbon atom.
- Mitas, Petr,Sedlak, Milos,Kavalek, Jaromir
-
-
- N-methylation of substituted benzonitriles with methyl fluorosulfonate
-
Substituted benzonitriles ArCN treated at 20-70°C with methyl fluorosulfonate yield the corresponding N-methylbenzamides ArCONHMe. Compounds with two cyano groups afford N,N′-methylated diamides.
- Salfetnikova,Vasil'ev,Rudenko
-
p. 838 - 844
(2007/10/03)
-
- Triazene Drug Metabolites. Part 13. The Decomposition of 3-Acyl-3-alkyl-1-aryltriazenes in Aqueous Sulfuric Acid
-
The hydrolysis of 1-aryl-3-acyl-3-methyltriazenes in aqueous sulfuric acid si described.The 3-formyl derivative undergoes an acid-catalysed deacylation reaction, characterised by a monotonic rise in the pseudo-first-order rate constant ko with increasing acidity, solvent deuterium isotope effects, kH2SO4/kD2SO4, of 0.9 (at 0.95 mol dm-3 H2SO4) and 0.8 (at 2.85 mol dm-3 H2SO4) and an entropy of activation of -80 J mol-1 K-1.The 3-alkanoyl derivatives also undergo acid-catalysed decomposition involving cleavage of either the N3-C acyl bond or the N2-N3 triazene bond.Below 3 mol dm-3 H2SO4, only acyl bond cleavage is observed.At higher acidities the extent of N2-N3 bond cleavage increases.The reaction is characterised by (i) solvent deuterium isotope effects of ca. 0.6 at 2 and 5 mol dm-3 H2SO4 and ca. 0.4 at 8 mol dm-3 H2SO4, (ii) ΔS(excit.) values of -6.7 and 51 J mol-1 K-1 at 2 and 6.1 mol dm-3 H2SO4, respectively, (iii) Hammett ρ values for the substituent in the triazene N-aryl ring of -0.7 and -0.9 at 3 and 9 mol dm-3 H2SO4, respectively, and (iv) an increase in reactivity with electron donating ability of the alkyl substituent of the acyl group.The 3-trifluoroacetyl triazenes are subject to solvolysis of the neutral, as well as the protonated, substrate.The hydrolysis of the neutral substrate involves N-acyl bond cleavage and is characterised by a solvent deuterium isotope effect, kH2O/kD2O, of 2.4, and a Hammett ρ value of +0.8 for the substituent in the N-aryl ring.The reactivity of the neutral substrate diminishes with increasing acidity until 6 mol dm-3 H2SO4, beyond which acid-catalysed N-acyl bond cleavage predominates, for which the solvent isotope effect, kH2SO4/kD2SO4, is 0.8 and the Hammett ρ value -0.5.The 3-aroyl substrates suffer acid-catalysed decomposition, the extent of the N2-N3 bond cleavage process being greater than for the N-alkanoyl counterparts.The reactions are rationalised in terms of a process that involves pre-equilibrium protonation of the substrate either at the N1 triazene atom or the amide oxygen atom, followed by subsequent decomposition of the protonated substrate via either N3-C bond cleavage, involving attack of water at the amide carbonyl, or unimolecular N2-N3 bond cleavage.The relative extents of the N3-C and N2-N3 bond cleavage processes depend on the reactivity of the acyl group and the water acitivity; the higher the water activity and the more reactive the acyl group, the more deacylation is favoured.
- Carvalho, Emilia,Iley, Jim,Rosa, Eduarda
-
p. 865 - 870
(2007/10/02)
-
- Acyloxymethyl as a Drug Protecting Group. Kinetics and Mechanism of the Hydrolysis of N-Acyloxymethylbenzamides
-
Acyloxymethyl derivatives of secondary and tertiary amides undergo hydrolysis via acid-catalysed, base-catalysed and pH-independent processes.The pH-independent pathway involves rate-limiting iminium ion formation and is characterised by the following: a Hammett ρ value for the substituent in the benzamide moiety of ca. -1.2 for both types of substrate; the absence of general-base or nucleophilic catalysis; a common benzoate ion effect; a solvent deuterium isotope effect, kobsH2O/kobsD2O, of ca. 1.6; Σ(excit.) values of -4 and -12 J k-1 mol-1 for secondary and tertiary substrates respectively; and higher reactivity of the tertiary amides over their secondary counterparts.The acid-catalysed process involves protonation of the substrate followed by iminium ion formation, and is characterised by the following: a Hammett ρ value of ca. -1.5 for the substitutent effect of the benzamide moiety; a solvent deuterium isotope effect of ca. 0.4; a monotonic rise in the pseudo-first-order rate constant kobs with increasing ; ΔS(excit.) values > 0 J K-1 mol-1; higher reactivity of the tertiary substrates over their secondary counterparts; and a value of 0.85 for the Bronsted coefficient, βlg, for the carboxylate nucleofuge.The base-catalysed hydrolysis of tertiary substrates involves normal ester hydrolysis via acyl-oxygen bond cleavage, and is characterised by a Hammett ρ value of +0.38, a solvent deuterium isotope effect, kOH-/kOD-, of 0.85, and a ΔS(excit.) balue of -96 J K-1 mol-1.The corressponding base-catalysed process for the secondary substrates involves imine formation via an E2 elimination reaction.The secondary acyloxymethylamides are some 7 * 104 times more reactive than their tertiary counterparts in the base-catalysed region.Hammett ρ values of +1.1 and +0.6 are obtained for the substituents in the base-catalysed region.Hammett ρ values of +1.1 and +0.6 are obtained for the substituents in the ester and amide moieties, respectively.Buffer catalysis is observed, and the value of ca. 0.5 for the Bronsted β coefficient identifies the amide proton as approximately 50percent transferred to the buffer species in the transition state.Heats of formation, ΔHf, calculated using the AM1 SCF MO package reveal that iminium ion formation is thermodynamically equi-energetic for cyclic and acyclic systems.Iminium ion formation from tertiary substrates is favoured by ca. 25 kJ mol-1 over the corresponding secondary analogues.
- Iley, Jim,Moreira, Rui,Rosa, Eduarda
-
p. 563 - 570
(2007/10/02)
-
- Metalloporphyrin-promoted rearrangement of 2-alkyloxaziridines
-
Transformation of 2-alkyloxaziridines to the corresponding amides is efficiently catalyzed by high-valent metalloporphyrins. This novel rearrangement was used to create a peptide bond and the precursor of a dipeptide ''aspartame'' was obtained in good yield.
- Suda,Umehara,Hino
-
p. 839 - 841
(2007/10/02)
-
- Electrochemical Models for Cytochrome P-450. N-Demethylation of Tertiary Amides by Anodic Oxidation
-
Anodic oxidation of N,N-dimethylamides in acetonitrile/water (95:5) containing NaClO4 gives the corresponding N-methylamides in high yields.N-Methyl-N-(hydroxymethyl)benzamide was isolated as an intermediate in the electrochemical N-demethylation of N,N-d
- Hall, Larry R.,Iwamoto, Reynold T.,Hanzlik, Robert P.
-
p. 2446 - 2451
(2007/10/02)
-
- Polymer-Bound Mixed Carboxylic Dithiocarbamic Anhydrides. A New Class of Selective and Recyclable Solid-Phase Acylating Reagents
-
Polymer-supported mixed carboxylic dithiocarbamic anhydrides are a new class of regenerable solid-phase reagents for acylating amino groups specifically.The resins were prepared by a four-step synthesis from cross-linked poly(chloromethylstyrene) (Merrifield's resin).The chloromethyl groups were converted to aminomethyl groups by the Gabriel synthesis, and reaction of the aminomethyl resin with carbon disulfide and aqueous sodium hydroxide gave a dithiocarbamate resin.Treatment of this resin with an acyl chloride gave the mixed carboxylic dithiocarbamic anhydride resin.These insoluble anhydrides transfer the acyl group to amines or amino acids in solution at room temperature, yielding a solution of the corresponding amide or peptide.The spent polymeric reagent can be regenerated to the carboxylic dithiocarbamic anhydride by treatment with carbon disulfide and sodium hydroxide followed by acylation.
- Haridasan, V. K.,Ajayaghosh, A.,Pillai, V. N. Rajasekharan
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p. 2662 - 2665
(2007/10/02)
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- Anticonvulsant activity of some 4-aminobenzamides
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A series of 4-aminobenzamides of some simple primary and secondary amines were prepared and evaluated for anticonvulsant effects. The compounds were tested in mice against seizures induced by electroshock and pentylenetetrazole (metrazole) and in the rotorod assay for neurologic deficit. For those N-alkyl amides tested, 4-amino-N-amylbenzamide was the most potent against maximal electroshock seizures (MES): ED50=42.98 mg/kg; however, the N-cyclohexylbenzamide showed the greatest protective index (PI=TD50/ED50), 2.8. The introduction of a second aromatic ring produced more potent compounds, with d,l-4-amino-N-(α-methylbenzyl)-benzamide showing the highest level of activity. This compound has an anti-MES ED50 of 18.02 mg/kg in mice when administered intraperitoneally (ip) and a TD50 of 170.78 mg/kg (PI=9.5) in the same species. These data compare quite favorably with those for phenobarbital and phenytoin in the same assays.
- Clark,Wells,Sansom,et al.
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p. 779 - 782
(2007/10/02)
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- Mesoionic Six-Membered Heterocycles, V. Reactions of 6-Oxo-6H-1,3-oxazin-3-ium-4-olates with o-Quinones and Heterocumulenes
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Mesoionic 6-oxo-6H-1,3-oxazine-3-ium-4-olates (1, 7) react with o-quinones (2, 4) to give compounds 3, 5, which may result from a primary cycloaddition and subsequent loss of carbon dioxide.Phenyl isocyanate and phenylisothiocyanate react with 1h and
- Friedrichsen, Willy,Kujath, Eckard,Liebezeit, Gerd
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p. 222 - 233
(2007/10/02)
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- Anodic Oxidation of Carboxamides. Part 3. The Mechanism of Anodic Cyclization of N-Methylcarbanilides
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Anodic oxidation in methanol of N-methylcarbanilides with an alkoxy-group para to the nitrogen atom (I) gives the intramolecular cyclization products, N-methylbenzoxazolium perchlorates: no cyclization product is obtained in the electrolysis of the anilides in acetonitrile.The process of cyclization was investigated by cyclic voltammetry, controlled potential electrolysis, and open circuit relaxation experiments using an optically transparent glassy carbon electrode.In spectroelectrochemical experiments on 4'-methoxy-N-methylbenzanilides (Ib-d) in methanol, accumulation of a metastable intermediate has been demonstrated.A possible reaction sequence for the formation of the benzoxazolium salts is discussed.
- Ohmori, Hidenobu,Ueda, Chihiro,Nobusue, Yasuhiro,Saitou, Naoko,Yokota, Tomoko,Masui, Masaichiro
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p. 1599 - 1605
(2007/10/02)
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- 11a-Methano-TXA compounds
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The present invention provides novel 11a-methano-TXA compounds and intermediates and processs for their preparation. Further provided are methods for using these novel TXA analogs as inhibitors of thromboxane synthetase, rendering these analogs useful for a variety of pharmacological purposes. These pharmacological uses include anti-inflammatory, anti-thromobitc, and anti-asthma indications.
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