41513-78-4Relevant academic research and scientific papers
Synthesis of phthalimides, isoindolin-1-ones and isoindolines bearing aminobenzoic acids as a new fluorescent compounds
Solis-Santos, Melchor,Ordó?ez, Mario,Ochoa-Terán, Adrián,Morales-Cueto, Rodrigo,Labastida-Galván, Victoria
, (2021/03/30)
Both experimental and theoretical methods were used in order to study the fluorescent properties of nine new compounds based on phthalimides, isoindolin-1-ones and isoindolines bearing aminobenzoic acids (2-aminobenzoic acid, 3-aminobenzoic acid and 4-aminobenzoic acid), which were obtained under mild reaction conditions. The photophysical properties of all the compounds were studied by electronic absorption and fluorescence spectroscopy in methanol solutions. All compounds exhibited fluorescence emission and high quantum yields. Additionally, it was found that the intramolecular charge in these donor-acceptor systems is significantly depending on electron-withdrawing substituents at the carboxylic acid position.
Coordination among Bond Formation/Cleavage in a Bifunctional-Catalyzed Fast Amide Hydrolysis: Evidence for an Optimized Intramolecular N-Protonation Event
Affeldt, Ricardo F.,Caramori, Giovanni F.,De Souza, Fábio P. S.,Ferraz, Matheus S.,Menger, Fredric M.,Nome, Faruk,Oliveira, Bruno S.,Scorsin, Leandro,Silveira, Eduardo V.,Souza, Bruno S.
, p. 4663 - 4671 (2020/05/01)
A density functional theory (DFT) computational analysis, using the ωB97X-D functional, of a rapid amide cleavage in 2-carboxyphthalanilic acid (2CPA), where the amide group is flanked by two catalytic carboxyls, reveals key mechanistic information: (a) General base catalysis by a carboxylate coupled to general acid catalysis by a carboxyl is not operative. (b) Nucleophilic attack by a carboxylate on the amide carbonyl coupled to general acid catalysis at the amide oxygen can also be ruled out. (c) A mechanistic pathway that remains viable involves general acid proton delivery to the amide nitrogen by a carboxyl, while the other carboxylate engages in nucleophilic attack upon the amide carbonyl; a substantially unchanged amide carbonyl in the transition state; two concurrent bond-forming events; and a spatiotemporal-base rate acceleration. This mechanism is supported by molecular dynamic simulations which confirm a persistent key intramolecular hydrogen bonding. These theoretical conclusions, although not easily verified by experiment, are consistent with a bell-shaped pH/rate profile but are at odds with hydrolysis mechanisms in the classic literature.
Inhibitory and Cooperative Effects Regulated by pH in Host-Guest Complexation between Cationic Pillar[5]arene and Reactive 2-Carboxyphthalanilic Acid
Affeldt, Ricardo F.,Garcia-Rio, Luis,Micke, Gustavo A.,Nascimento, Vanessa,Nome, Faruk,Silveira, Eduardo V.,Wanderlind, Eduardo H.
supporting information, p. 9684 - 9692 (2019/08/26)
The study of host-guest complexation between reactive 2-carboxyphthalanilic acid (CPA) and two cationic pillararenes has been carried out. Host-guest complexation with significant kinetic effects was observed only with the smaller cavity size pillararene (P5A). Kinetics in the pH range 1.50-6.40, ESI-MS, 1H NMR titration, and ROESY experiments were performed to characterize the complexes. High binding stoichiometry (H:G2) was observed for all CPA protonation states. The system is pH-dependent, and inversion of cooperativity (negative to positive) occurs by increasing the dianionic CPA2- concentration (allosteric behavior). Toward physiological pH, association constant K1:1 does not change (104 M-1), and K1:2 increased from 102 to 104 M-1, as well as the inhibitory effect increased up to 222-fold. NMR results elucidated the structure of the complex and allowed us to create a map of H-H interactions that describes well the diversity and number of interactions in the complex. ?
Synthetic strategy and antiviral evaluation of diamide containing heterocycles targeting dengue and yellow fever virus
Saudi, Milind,Zmurko, Joanna,Kaptein, Suzanne,Rozenski, Jef,Gadakh, Bharat,Chaltin, Patrick,Marchand, Arnaud,Neyts, Johan,Van Aerschot, Arthur
, p. 158 - 168 (2016/06/09)
High-Throughput screening of a subset of the CD3 chemical library (Centre for Drug Design and Discovery; KU Leuven) provided us with a lead compound 1, displaying low micromolar potency against dengue virus and yellow fever virus. Within a project aimed at discovering new inhibitors of flaviviruses, substitution of its central imidazole ring led to synthesis of variably substituted pyrazine dicarboxylamides and phthalic diamides, which were evaluated in cell-based assays for cytotoxicity and antiviral activity against the dengue virus (DENV) and yellow fever virus (YFV). Fourteen compounds inhibited DENV replication (EC50 ranging between 0.5 and 3.4 1/4M), with compounds 6b and 6d being the most potent inhibitors (EC50 0.5 1/4M) with selectivity indices (SI) > 235. Compound 7a likewise exhibited anti-DENV activity with an EC50 of 0.5 1/4M and an SI of >235. In addition, good antiviral activity of seven compounds in the series was also noted against the YFV with EC50 values ranging between 0.4 and 3.3 1/4M, with compound 6n being the most potent for this series with an EC50 0.4 1/4M and a selectivity index of >34. Finally, reversal of one of the central amide bonds as in series 13 proved deleterious to the inhibitory activity.
Docking, synthesis, and pharmacological evaluation of isoindoline derivatives as anticonvulsant agents
Davood, Asghar,Amini, Mohsen,Azimidoost, Leila,Rahmatpour, Somaieh,Nikbakht, Ali,Iman, Maryam,Shafaroodi, Hamed,Ansari, Abdollah
, p. 3177 - 3184 (2013/07/19)
Eleven analogs of N-arylisoindoline pharmacophore were synthesized and evaluated for their anticonvulsant activities. The in vivo screening data acquired indicate that all the analogs have the ability to protect against pentylenetetrazole-induced seizure. Compounds 2, 6, and 11 elevated clonic seizure thresholds at 30 min which were more active than reference drug phenytoin, and compounds 2, 7, and 11 showed marked anticonvulsant activity on tonic seizure. The most potent compounds were 2 and 11 which had comparative activity to the phenytoin. Using a model of the open pore of the Na channel, we have docked all compounds. Docking studies have revealed that these compounds interacted mainly with residues II-S6 of NaV1.2 by making hydrogen bonds and have additional hydrophobic interactions with other domains in the channel's inner pore.
A novel approach to isoindolo[2,1-a]indol-6-ones
Duncanson, Philip,Cheong, Yuen-Ki,Motevalli, Majid,Griffiths, D. Vaughan
supporting information; experimental part, p. 4266 - 4279 (2012/07/13)
A convenient route to isoindolo[2,1-a]indol-6-ones has been developed starting from the appropriate 2-(N-phthaloyl)benzoic acids. Formation of the acid chlorides with thionyl chloride followed by heating with triethyl phosphite in a suitable solvent resulted in a multistep reaction giving tetracyclic β-ketophosphonates that on reduction with sodium borohydride gave the required indolones in good overall yields. Analogous β-ketophosphonates were also prepared starting with N,N-(1,8-naphthaloyl)-2-aminobenzoic acid and 2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoic acids although of these only the naphthaloyl product could be reduced with sodium borohydride without cleaving the amide bond in the ring system.
Structural studies on solvates of cyclic imide tethered carboxylic acids with pyridine and quinoline
Singh, Devendra,Bhattacharyya, Pradip K.,Baruah, Jubaraj B.
experimental part, p. 348 - 356 (2011/10/31)
Structures of eight solvates of cyclic imide tethered carboxylic acids and aromatic tetra carboxylic acids with pyridine (solvate I-VI) and quinoline (VII-VIII) are determined. Different types of hydrogen bond motifs (discrete or cyclic) in these solvates are identified. Solvates I and II possess discrete O-H...N interactions, solvates III and VIII possess combinations of cyclic interactions arising from O-H-... -N and C-H- ? -O interactions, solvates IV, V, and VII have both the above namely discrete and cyclic types of interactions, whereas, solvate VI is an exception which possesses discrete O-H...N as well as fl22(8) types of interactions and provides a model system for incomplete cleavage of dimeric assembly of carboxylic acid moiety. On the basis of the results of various hydrogen bond motifs, density functional theory calculations (DFT) on similar motifs generated from formic acid and its interaction with pyridine and quinoline are carried out. In the case of a pyridine formic acid system, DFT calculations show that the energy difference between the cyclic R22(7) motif and the discrete motif is ～0.6 kcal/mol. Such a small difference accounts for the formation of both types of structural patterns in solvates I-V depending on the steric requirements. The observed motif of VI is established by comparison of theoretical energies between a dimeric carboxylic acid moiety generated from two formic acids interactions and a trimeric moiety that exhibits two formic acids and pyridine interactions. The energy of different types of hydrogen bond motifs formed by the interactions between quinoline and formic acid is also calculated. Calculations based on DFT show that the salt formation between formic acid and pyridine is not a favorable process, but it may occur in the case of quinoline.
Solvation controlling reaction paths and gel-formation in imide derivatives
Singh, Devendra,Baruah, Jubaraj B.
, p. 4374 - 4377 (2008/09/21)
1,8-Naphthalic anhydride condenses with 4-nitro-1,2-diaminobenzene in acetic acid to give 11-nitrobenzo[d,e]benzo[2,1-a]isoquinoline-1,3-dione (1), whereas the same reaction carried out in DMF gives 2-(2-amino-4-nitrophenyl)-benzo[d,e]isoquinoline-1,3-dione (2). The condensation reaction of 1,8-naphthalic anhydride with 1-amino 3,5-benzene dicarboxylic acid leads to corresponding imide, which forms a gel in a mixed solvent such as water in DMSO. A similar compound 5-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-isophthalic acid derived from phthalic anhydride forms gel in a mixed solvent of DMSO and water, whereas a crystalline solvate of DMSO with 2 could be obtained upon crystallization from DMSO. The crystal structure of this solvate is determined and its structure is compared with 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-benzoic acid. The latter does not form a gel in the mixed solvent and adopts an intermolecular hydrogen bonded structure.
Design, synthesis and antiinflammatory activity of novel phthalimide derivatives, structurally related to thalidomide
Machado, Alexandre Legora,Lima, Lidia Moreira,Araujo-Jr, Joao Xavier,Fraga, Carlos Alberto M.,Goncalves Koatz, Vera Lucia,Barreiro, Eliezer J.
, p. 1169 - 1172 (2007/10/03)
As part of an ongoing effort to develop new thalidomide analogues as antiinflammatory lead-candidates, this paper describes the synthesis and antiinflammatory activity of novel N-phenyl-phthalimide functionalized derivatives (4a-d, 5a,b, 6a,b). The target compounds were assayed in an acute lung inflammatory model and all compounds were able to inhibit TNF-α production and subsequent neutrophil recruitment in the LPS-acute lung inflammatory model.
Nonsteroidal anti-inflammatory drugs and their analogues as inhibitors of aldo-keto reductase AKR1C3: New lead compounds for the development of anticancer agents
Gobec, Stanislav,Brozic, Petra,Rizner, Tea Lanisnik
, p. 5170 - 5175 (2007/10/03)
Nonsteroidal anti-inflammatory drugs (NSAIDs) like indomethacin, flufenamic acid, and related compounds have been recently identified as potent inhibitors of AKR1C3. We report that some other NSAIDs (diclofenac and naproxen) also inhibit AKR1C3, with the IC50 values in the low micromolar range. In order to obtain more information about the structure-activity relationship and to identify new leads, a series of compounds designed on the basis of NSAIDs were synthesized and screened on AKR1C3. The most active compounds were 2-[(2,2-diphenylacetyl)amino]benzoic acid 4 (IC50 = 11 μM) and 3-phenoxybenzoic acid 10 (IC50 = 0.68 μM). These compounds represent promising starting points for the development of new anticancer agents.
