19165-29-8Relevant academic research and scientific papers
Substituent effects on energetics of peptide-carboxylate hydrogen bonds as studied by 1H NMR spectroscopy: Implications for enzyme catalysis
Emenike, Bright U.,Liu, Albert Tianxiang,Naveo, Elsy P.,Roberts, John D.
, p. 11765 - 11771 (2014/01/06)
Substituent effects in N-H···O hydrogen bonds were estimated by comparing the acidities of two series of model compounds: N-benzoylanthranilic acids (A) and 4-benzoylamidobenzoic acids (B). Intramolecular N-H···O hydrogen bonds were found to be present in the A series of compounds, while B acids were used as control models. The respective pKa values for A and B acids were determined experimentally in DMSO solution using proton NMR spectroscopy. With X = H, the pKa for A and B acids were observed to be 7.6 and 11.6, respectively, a difference of 4.0 units (ΔpKa). However, with X = p-NO 2, the ΔpKa value between A and B acids increased to 4.7 units: the pKa values for A and B acids were determined as 6.7 and 11.4, respectively. The ΔpKa values between A and B acids as a function of the X substituents were studied in 10 other examples. The effects of X substituents in A acids could be predicted on the basis of the observed linear Hammett correlations, and the sensitivity of each substituent effect was found to be comparable to those observed for the ionization of substituted benzoic acids (ρ = 1.04 for A acids, and ρ = 1.00 for benzoic acids).
Contribution of intramolecular NH...O hydrogen bonds to magnesium-carboxylate bonds
Okamura, Taka-Aki,Nakagawa, Junko
, p. 10812 - 10824 (2013/10/22)
A series of magnesium carboxylate complexes containing intramolecular NH...O hydrogen bonds were synthesized. Their molecular structures were determined by X-ray analysis. A direct NH...O hydrogen bond to the coordinated oxygen atom elongated the Mg-O bond, while a hydrogen bond to the carbonyl group shortened the Mg-O bond. Double NH...O hydrogen bonds significantly lowered the basicity of the carboxylate anion and prevented coordination to the Mg ion in a trans configuration; however, a cis-dicarboxylate complex was successfully obtained. Strong coordination of water to the Mg2+ ion stabilizes the weak Mg-carboxylate bond at the trans position. In contrast, a weak Mg-carboxylate bond strengthens the Mg-O(water) bond, probably increasing the acidity. Based on the experimental results and theoretical calculations, a new switching mechanism is proposed. In the proposed mechanism, the acidity of the coordinated water on magnesium is controlled during catalytic hydrolysis in endonuclease.
The multicomponent approach to N-methyl peptides: Total synthesis of antibacterial (-)-viridic acid and analogues
Neves Filho, Ricardo A. W.,Stark, Sebastian,Westermann, Bernhard,Wessjohann, Ludger A.
supporting information, p. 2085 - 2090 (2013/02/22)
Two syntheses of natural viridic acid, an unusual triply N-methylated peptide with two anthranilate units, are presented. The first one is based on peptide-coupling strategies and affords the optically active natural product in 20% overall yield over six steps. A more economical approach with only four steps leads to the similarly active racemate by utilizing a Ugi four-component reaction (Ugi-4CR) as the key transformation. A small library of viridic acid analogues is readily available to provide first SAR insight. The biological activities of the natural product and its derivatives against the Gram-negative bacterium Aliivibrio fischeri were evaluated.
Synthesis leading to novel 2,4,6-trisubstituted quinazoline derivatives, their antibacterial and cytotoxic activity against thp-1, hl-60 and a375 cell lines
Chandrika, P Mani,Yakaiah,Narsaiah,Sridhar,Venugopal,Rao, J Venkateshwara,Kumar, K Pranay,Murthy,Rao, A Raghu Ram
experimental part, p. 840 - 847 (2009/12/24)
A series of novel 2,4,6-trisubstituted quinazoline derivatives 6 have been synthesized from anthranilic acids 1 in five steps via benzoxazinones 2, N-benzoyl benzamides 3, quinazol-4-ones 4, 4-chloroquinazolines 5. Products 6 have been screened for antibacterial and cytotoxic activity, promising compounds have been identified.
Synthesis of simple analogues of methyllycaconitine - An efficient method for the preparation of the N-substituted anthranilate pharmacophore
Barker, David,Brimble, Margaret A.,McLeod, Malcolm D.
, p. 5953 - 5963 (2007/10/03)
The synthesis of several A and AE ring analogues of the alkaloid methyllycaconitine is reported. The key 2-(2″-methylsuccinimido)benzoate ester pharmacophore is introduced using an efficient two step procedure. Esterification of the alcohol precursors with N-(trifluoroacetyl)anthranilic acid under Steglich conditions followed by sodium borohydride mediated cleavage of the trifluoroacetyl group affords the anthranilate esters. Subsequent fusion with methylsuccinic anhydride affords the N-substituted anthranilate derivatives containing the key pharmacophore present in a range of commonly occurring Delphinium and Aconitum alkaloids.
The design and synthesis of novel orally active inhibitors of AP-1 and NF-κB mediated transcriptional activation. SAR of in vitro and in vivo studies
Palanki, Moorthy S. S.,Erdman, Paul E.,Ren, Minghuan,Suto, Mark,Bennett, Brydon L.,Manning, Anthony,Ransone, Lynn,Spooner, Cheryl,Desai, Sonal,Ow, Arnie,Totsuka, Ryuichi,Tsao, Peter,Toriumi, Wataru
, p. 4077 - 4080 (2007/10/03)
We have developed novel orally active quinazoline analogues as inhibitors of AP-1 and NF-κB mediated transcriptional activation. Among the derivatives prepared, 1-[2-(2-thienyl)quinazolin-4-ylamino]-3-methyl-3- pyrroline-2,5-dione (10) showed significant activity in an adjuvant-induced arthritis rat model by reducing the swelling by 65% in the non-injected foot. The synthesis, structure-activity relationship, and in vivo activity are described.
FUSED-RING PYRIMIDIN-4(3H)-ONE DERIVATIVES, PROCESSES FOR THE PREPARATION AND USES THEREOF
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Page 320; 321, (2010/02/06)
AbstractNovel compounds of the following formula (I) and pharmacologically acceptable salt and esters thereof can modulate LXR function and as a result show excellent anti-arteriosclerotic and anti-inflammatory activity:wherein:A represents aryl or heteroaryl;R1, R2 and R3 are the same or different and each represents hydrogen, hydroxyl, nitro, cyano, amino, halogen, carboxy, carbamoyl, mercapto, alkyl, haloalkyl, alkylcarbonyloxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, alkylcarbonylamino, N-(alkylcarbonyl)-N-(alkyl)amino, alkoxycarbonylamino, N-(alkoxycarbonyl)-N-(alkyl)amino, alkylsulfonylamino, N-(alkylsulfonyl)-N-(alkyl)amino, haloalkylsulfonylamino, N-(haloalkylsulfonyl)-N-(alkyl)amino, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl group, or R1 and R2 together are alkylenedioxy;R4 and R5 are the same or different and each represents hydrogen, hydroxyl, amino, halogen, mercapto, alkyl, haloalkyl, alkoxy, alkoxycarbonyl or alkylthio;X represents hydrogen, hydroxyl, halogen, alkoxy or haloalkoxy; andY represents an optionally substituted alkyl, cycloalkyl, heterocyclyl, aryl, cycloalkylalkyl, heterocyclylalkyl or aralkyl group.
Hydrolysis of an Amide in a Carboxypeptidase Model Using Co(III) and Bifunctional Catalysts
Schepartz, Alanna,Breslow, Ronald
, p. 1814 - 1826 (2007/10/02)
The ability of a metal ion to cooperate with various inter- and intramolecular acids and bases and promote amide hydrolysis has been investigated.Phenolic and carboxylic functional groups were placed within reach of Co(III)-chelated amides in complexes th
Intramolecular Catalysis of Organic Reactions. III. Hydrolysis of 5-nitro-2-(trifluoroacetylamino)benzoic Acid
Broxton, Trevor J.
, p. 1885 - 1893 (2007/10/02)
The hydrolysis of 5-nitro-2-(trifluoroacetylamino)benzoic acid (2) has been studied over the pH range 0-12.In acidic solution (pH 0-3.5), the hydrolysis occurs with intramolecular general acid catalysis by the adjacent CO2H group.Between pH 3.5 and 8, a plateau is observed in the pH-rate profile, and this is interpreted as acid catalysis by a water molecule of the breakdown of the tetrahedral intermediate formed between (2) and another water molecule.In alkaline solution (pH above 8), hydrolysis occurs with general acid-catalysed C-N bond breaking.Catalysis by phosphate and borate buffers was observed in the pH range 6-10.Phthalate buffers did not catalyse the reaction.For phosphate and borate buffers, plots of buffer concentration against rate showed a saturation phenomenon which was interpreted as indicating a change from rate-limiting decomposition of the tetrahedral intermediate to rate-limiting formation of the tetrahedral intermediate as the buffer concentration was increased.The pKa of the acid group was found to be about 2.5 as expected, but the pKa of the NH group is 10.4, higher than expected.The reduced acidity of the NH group is attributed to electrostatic effects of the adjacent ionized carboxy group.Unlike for aspirin, intramolecular catalysis by the ionized carboxy group was not observed, a result, perhaps, of intramolecular hydrogen bonding between the carboxylate ion and the adjacent NH group.Such an interaction would be geometrically unfavourable for either intramolecular general base or nucleophilic participation by the carboxylate ion.
