- Novel method for preparation of monoesters of symmetric diphenolic compounds like curcumin (1,7-bis(4-hydroxy-3-methoxy phenyl)-1,6-heptadiene-3,5- dione) via solid-phase synthesis
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Synthesis of a monoester of symmetrical diphenolic compound curcumin (1,7-bis(4-hydroxy-3-methoxy phenyl)-1,6-heptadiene-3,5-dione) with glycine has been carried out by anchoring one of its free phenolic groups to an insoluble polymeric solid-support resin controlled pore glass-long chain alkylamine (CPG-LCAA) via a 2-carbon linker by solid-phase synthesis. The other free phenolic was esterified selectively with N-protected glycinoyl chloride to give the monoester exclusively. Subsequent deprotection of the amino group and deblocking of the monoester from polymer support by treatment with hydriodic acid (HI) gave the desired product. We earlier reported synthesis of a large number of diesters of curcumin, but selective esterification of one phenolic has been accomplished by this novel method, which can be used for preparing monoesters of any symmetric diphenol in quantitative yields. Copyright Taylor & Francis Group, LLC.
- Dubey, Shiv Kumar,Dwivedi, Vishnu,Misra, Krishna
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- 5,15-diaminotetrabenzoporphyrins: Synthesis and spectral properties
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A zinc complex of 5,15-di(N-phthalimidyl)tetrabenzoporphyrin was obtained by the reaction of Ncarboxymethylphthalimide with 1-oxo-1H-3-(1-oxoisoindolin-3- ylidenemethyl)isoindole and zinc oxide. The complex demetallation affords 5,15-di(N-phthalimidyl)tetrabenzoporphyrin. The reaction of N- phthalimidylsubstituted tetrabenzoporphyrins with hydrazine hydrate leads to the formation of 5,15-diaminotetrabenzoporphyrins. Spectral properties of these compounds were studied. Pleiades Publishing, Ltd., 2012.
- Yakubov,Galanin,Shaposhnikov
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- The first example of linear peptides containing a N-trifluoroethylated backbone amide linkage and the surprising solution dynamics observed by 19F NMR
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The α-amino group of (l)phenylalanine methyl ester was trifluoroethylated using (2,2,2-trifluoroethyl)phenyliodonium N,N-bis(trifluoromethylsulfonyl)imide. A dipeptide Gly(l)Phe containing a trifluoroethylated peptide bond was synthesized by removing the α-amino proton of Nα-trifluoroethyl (l)phenylalanine methyl ester followed by coupling with Nα-phthaloyl glycine acid fluoride. The dipeptide was further coupled with (l)leucine methyl ester under conventional carboxyl activation conditions to provide two diastereomers of the tripeptide Gly(d,l)Phe(l)Leu. The solution dynamic behavior of the tripeptide was investigated as a function of solvents, by NOESY and variable temperature (VT) 19F NMR experiments.
- Lu, Changqing,DesMarteau, Darryl D.
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- Synthesis and anticonvulsant activities of functionalized 5-(isoindole-1,3-dione)-pyrimidinones
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The present work involves the synthesis of previously unknown 5-(isoindole-1,3-dione) pyrimidinones by [4?+?2] cycloaddition reactions of functionalized 1,3-diazabuta-1,3-dienes with phthalimidoketene, generated in situ from phthaloylglycine, tosyl chloride, and triethylamine. The 5-(isoindole-1,3-dione)-pyrimidinones have been screened in vivo for their anticonvulsant activities using MES and PTZ methods. A comparative study for in vivo anticonvulsant activities of these functionalized pyrimidinones with a variety of substitutions at different positions was also conducted. 2-(4-Dimethylamino-6-oxo-1,2-diphenyl-1,6-dihydro-pyrimidin-5-yl)-isoindole-1,3-dione has shown the maximum anticonvulsant activities at 100?mg/kg test dose using MES and PTZ tests.
- Sharma, Rashmi,Gawande, Dinesh Y.,Mohan, Chander,Goel, Rajesh Kumar
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- Structural, spectroscopic, nonlinear optical and electronic properties of calcium N-phthaloylglycinate: A combined experimental and theoretical study
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A calcium complex of N-phthaloylglycine (CaNPG) has been synthesized, and its crystal structure has been characterized by X-ray diffraction method. The FT-IR and fluorescence spectra for CaNPG have been recorded. N-phthaloylglycine ligand coordinates to Ca ion through the carboxylate O atoms as a bidentate ligand, and Ca ion does not play an important role in florescence spectrum. In order to support experimental findings and also investigate molecular surfaces, natural bond orbital (NBO) and nonlinear optical (NLO) optical properties of CaNPG complex, density functional theory calculations have been performed by hybrid B3LYP level. The very small energy gap between α-spin frontier molecular orbitals (FMOs) is demonstrated that CaNPG is a very reactive, chemically soft and optically active complex. The high stabilization energies of hyperconjugative interactions are also demonstrate that the charge mobility in CaNPG is very high. As consistent with above findings, first static hyperpolarizability of CaNPG has been found to be 10 times higher than pNA which is a NLO material.
- Tamer, ?mer,Bhatti, Moazzam H.,Yunus, Uzma,Avc?, Davut,Atalay, Yusuf,Nadeem, Muhammad,Shah, Syed Raza,Helliwell, Madeleine
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- A trio of quinoline-isoniazid-phthalimide with promising antiplasmodial potential: Synthesis, in-vitro evaluation and heme-polymerization inhibition studies
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Quinoline-isoniazid-phthalimide triads have been synthesised to assess their antiplasmodial efficacy and cytotoxicity against chloroquine-resistant W2 strain of P. falciparum and Vero cells, respectively. Most of the synthesized compounds displayed IC50 in lower nM range and appeared to be approximately five to twelve fold more active than chloroquine. Heme-binding studies were also carried out to delineate the mode of action. The promising compounds with IC50s in range of 11–30 nM and selectivity index >2800, may act as promising template for the design of new antiplasmodials.
- Rani, Anu,Sharma, Anny,Legac, Jenny,Rosenthal, Philip J.,Singh, Parvesh,Kumar, Vipan
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- Hg2+-selective "turn-on" fluorescent chemodosimeter derived from glycine and living cell imaging
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A new nonfluorescent benzthiazole derivative of dithio-N-phthaloylglycine was prepared, and its fluorogenic chemodosimetric behaviors toward transition metal ions were investigated. The dithio-N-phthaloylglycine derivative showed highly Hg2+-selective fluorescence enhancing ("turn-on") properties in 20% aqueous acetonitrile solution (H2O/CH3CN = 80:20, v/v). The chemodosimetric behavior is based on the Hg2+ triggered desulfurization of dithio-N-phthaloylglycine derivative into its oxygen analogue. To observe the cell permeability of 3 into Pollen grains, we also employed it for the fluorescence detection of the changes of intracellular Hg2+ in cultured cells.
- Mahapatra, Ajit Kumar,Roy, Jagannath,Manna, Saikat Kumar,Kundu, Supratim,Sahoo, Prithidipa,Mukhopadhyay, Subhra Kanti,Banik, Avishek
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- Design and synthesis of 4-Aminoquinoline-isoindoline-dione-isoniazid triads as potential anti-mycobacterials
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A series of 4-aminoquinoline-isoindoline-dione-isoniazid triads were synthesized and assessed for their anti-mycobacterial activities and cytotoxicity. Most of the synthesized compounds exhibited promising activities against the mc26230 strain of M. tuberculosis with MIC in the range of 5.1–11.9 μM and were non-cytotoxic against Vero cells. The conjugates lacking either isoniazid or quinoline core in their structural framework failed to inhibit the growth of M. tuberculosis; thus, further strengthening the proposed design of triads in the present study.
- Rani, Anu,Johansen, Matt D.,Roquet-Banères, Fran?oise,Kremer, Laurent,Awolade, Paul,Ebenezer, Oluwakemi,Singh, Parvesh,Sumanjit,Kumar, Vipan
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- The switch-on luminescence sensing of histidine-rich proteins in solution: A further application of a Cu2+ ligand
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A new probe/Cu2+ complex for the detection of his-tagged protein has been developed, based on an improved probe, Dansyl-Gly-Py (1), by closely mimicing the structure of a peptide, ATCUN. In aqueous solution, 1/Cu 2+ has good selectivity to histidine and cysteine, and further can detect histidine-rich protein by releasing the quenched fluorescence of 1.
- Wang, Bin,Gao, Yang,Li, Hong-Wei,Hu, Zhi-Peng,Wu, Yuqing
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- Amino acid conjugates of aminothiazole and aminopyridine as potential anticancer agents: Synthesis, molecular docking and in vitro evaluation
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Purpose: The development of resistance to available anticancer drugs is increasingly becoming a major challenge and new chemical entities could be unveiled to compensate this therapeutic failure. The current study demonstrated the synthesis of 2-aminothiazole [S3 (a-d) and S5(a-d)] and 2-aminopyridine [S4(a-d) and S6(a-d)] derivatives that can target multiple cellular networks implicated in cancer development. Methods: Biological assays were performed to investigate the antioxidant and anticancer potential of synthesized compounds. Redox imbalance and oxidative stress are hallmarks of cancer, therefore, synthesized compounds were preliminarily screened for their antioxidant activity using DPPH assay, and further five derivatives S3b, S3c, S4c, S5b, and S6c, with significant antioxidant potential, were selected for investigation of in vitro anticancer potential. The cytotoxic activities were evaluated against the parent (A2780) and cisplatin-resistant (A2780CISR) ovarian cancer cell lines. Further, Molecular docking studies of active compounds were performed to determine binding affinities. Results: Results revealed that S3c, S5b, and S6c displayed promising inhibition in cisplatin-resistant cell lines in comparison to parent cells in terms of both resistance factor (RF) and IC50 values. Moreover, S3c proved to be most active compound in both parent and resistant cell lines with IC50 values 15.57 μM and 11.52 μM respectively. Our docking studies demonstrated that compounds S3c, S5b, and S6c exhibited significant binding affinity with multiple protein targets of the signaling cascade. Conclusion: Anticancer activities of compounds S3c, S5b, and S6c in cisplatin-resistant cell lines suggested that these ligands may contribute as lead compounds for the development of new anticancer drugs.
- Ali, Tahir,Imran, Muhammad,Li, Jing Bo,Li, Shupeng,Nadeem, Humaira,Naz, Shagufta,Sarwar, Sadia,Shah, Fawad Ali,Tan, Zhen
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p. 1459 - 1476
(2021/04/19)
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- Potent antiproliferative activity of bradykinin B2 receptor selective agonist FR-190997 and analogue structures thereof: A paradox resolved?
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Βradykinin stimulation of B2 receptor is known to activate the oncogenic ERK pathway and overexpression of bradykinin receptors B1 and B2 has been reported to occur in glioma, colorectal and cervical cancers. B1R and B2R antagonists have been shown to reverse tumor proliferation and invasion. Paradoxically, B1R and B2R agonism has also been reported to elicit antiproliferative benefits. In order to complement the data accumulated to date with the natural substrate bradykinin and peptidic B2R antagonists, we decided to examine for the first time the response elicited by B2R stimulation in breast cancer lines with a non-peptidic small molecule B2R agonist. We synthesized and assessed the highly selective and potent B2R partial agonist FR-190997 in MCF-7 and MDA-MBA-231 breast cancer lines and found it possessed significant antiproliferative activity (IC50 2.14 and 0.08 μΜ, respectively). The modular nature of FR-190997 allowed us to conduct a focused SAR study and discover compound 10 which exhibits subnanomolar antiproliferative activity (IC 50 0.06 nΜ) in the TNBC MDA-MBA-231 cell line. This performance surpasses, in most cases by several orders of magnitude, those of established anticancer agents and FDA-approved breast cancer drugs. In line with the established literature we suggest that this remarkable activity precipitates from a dual mode of action involving agonist-induced receptor internalization/degradation combined with sequestration of functional intracellular B2 receptors and inhibition of the associated endosomal signaling. The latter mode may be realized by appropriate ligands regardless of B2R agonist/antagonist designation which only relates to membrane residing GCPRs. Under this prism the controversy over the antiproliferative effects of B2 agonists and antagonists is potentially neutralized.
- Rassias, Gerasimos,Leonardi, Sofia,Rigopoulou, Dionisia,Vachlioti, Eleanna,Afratis, Konstantinos,Piperigkou, Zoi,Koutsakis, Christos,Karamanos, Nikos K.,Gavras, Haralambos,Papaioannou, Dionissios
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supporting information
(2020/11/12)
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- Synthesis of new amides based on N-Phthaloyl-α-Amino Acids
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N-phthaloyl derivatives of aliphatic α-amino acids were synthesized using phthalanhydride under standard conditions. The optimization reaction carried out by the thermal method to obtain the amides of these N-phthaloyl amino acids resulted in transimitted rather than amidation. The target amides of N-phthaloyl-α-amino acids were obtained by acylation of the amine with the corresponding acid chloroanhydrides in dichloromethane. These results were compared with the results of a similar acylation in a non-polar solvent (benzene). The dependence of the direction of the reaction on the duration of the acylation and the amount of amine used was established. The conditions for the formation of the corresponding N-phthaloyl-α-amino acid amides and asymmetric phthalic acid diamides were found. It is noteworthy that the formation of diamides is directly proportional to the equivalent amount of amine and the duration of the reaction, which makes it possible to purposefully control the synthesis in one reactor.
- Tukhtaev,Yusupov,Vinogradova
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p. 3049 - 3058
(2021/05/28)
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- HETEROCYCLIC COMPOUNDS AS MODULATORS OF STIMULATOR OF INTERFERON GENES (STING)
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The present invention relates to compounds of formula (I) and salts, stereoisomers, tautomers or N-oxides thereof that are useful as modulators of STING (Stimulator of Interferon Genes). The present invention further relates to the compounds of formula (I) for use as a medicament and to a pharmaceutical composition comprising said compounds.
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(2021/06/22)
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- FUNCTIONALIZED HETEROCYCLIC COMPOUNDS AS MODULATORS OF STIMULATOR OF INTERFERON GENES (STING)
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The present invention relates to compound-linker constructs and antibody-drug-conjugates of compounds of formula (I) that are useful as modulators of STING (Stimulator of Interferon Genes).
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(2021/06/22)
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- Synthesis method N -phthalimide-based acetic acid
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The invention discloses a synthesis method of N -phthalimide-based acetic acid. Based on N - hydroxyethyl phthalimide as a base, N -hydroxyphthalimide (NOP) was used as a catalyst, and N - phthalimide-based acetic acid was obtained by air oxidation. The mass of the catalyst NOP is N - of the mass of 1 - 10% hydroxyethyl phthalimide, the reaction employs cyclohexane as a solvent, and the mass of the solvent is N - times the mass of 20 - 50 hydroxyethyl phthalimide. The reaction temperature was between 50 and 100 °C, the air ventilation rate was 1L/seconds, and the aeration time was 5 - 48 hours. The method replaces the toxic raw materials such as toluene used in the prior literature report. The production is reduced. The method has the advantages of low management cost, mild reaction conditions and low production cost.
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Paragraph 0011; 0012-0024
(2021/09/11)
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- Synthesis, in silico Study and Antimicrobial Evaluation of New Diesters Derived from Phthaloylglycine
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New diesters derived from phthaloylglycine (7a-7i) were synthesized and their structures characterized by infrared, 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. The compounds were evaluated in an in silico study, which demonstrated positive features indicating a possible drug candidate. The diesters showed antifungal activity ranging from moderate to strong against strains of Candida. Compounds 7a, 7b, 7c, 7e and 7i had a moderate minimum inhibitory concentration (MIC) of 1024 μg mL?1 against all fungal strains, while 7h showed a very good MIC of 256 μg mL?1 against Candida albicans, Candida parapsilosis and Candida krusei and 64 μg mL?1 against Candida tropicalis. However, only 7h and 7i were able to inhibit bacterial growth of strains of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Escherichia coli with an MIC of 1024 μg mL?1
- Alves, Francinara S.,Barbosa-Filho, José M.,Cordeiro, Laísa V.,Huang, Min-Fu N.,Lima, Edeltrudes O.,Neto, Hermes Diniz,Souza, Helivaldo D. S.,Trindade, Emmely O.,de Athayde-Filho, Petr?nio F.,de Lima, Priscila S. V.,de Oliveira, Rafael F.,de Sousa, Abra?o P.
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p. 953 - 962
(2020/10/14)
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- AMINO ACID DERIVATIVES FOR THE TREATMENT OF INFLAMMATORY DISEASES
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The present disclosure provides certain amino acid derivatives that inhibit NF-kB activation and are therefore useful for the treatment of inflammatory diseases. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
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Page/Page column 36
(2020/08/13)
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- [3 + 2] Cycloaddition with photogenerated azomethine ylides in β-cyclodextrin
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Stability constants for the inclusion complexes of cyclohexylphthalimide 2 and adamantylphthalimide 3 with β-cyclodextrin (β-CD) were determined by 1H NMR titration, K = 190 ± 50 M?1, and K = 2600 ± 600 M?1, respectively. Photochemical reactivity of the inclusion complexes 2&at;β-CD and 3&at;β-CD was investigated, and we found out that β-CD does not affect the decarboxylation efficiency, while it affects the subsequent photochemical H-abstraction, resulting in different product distribution upon irradiation in the presence of β-CD. The formation of ternary complexes with acrylonitrile (AN) and 2&at;β-CD or 3&at;β-CD was also essayed by 1H NMR. Although the formation of such complexes was suggested, stability constants could not be determined. Irradiation of 2&at;β-CD in the presence of AN in aqueous solution where cycloadduct 7 was formed highly suggests that decarboxylation and [3 + 2] cycloaddition take place in the ternary complex, whereas such a reactivity from bulky adamantane 3 is less likely. This proof of principle that decarboxylation and cycloaddition can be performed in the β-CD cavity has a significant importance for the design of new supramolecular systems for the control of photoreactivity.
- Basari?, Nikola,Mandi?, Leo,Sohora, Margareta
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supporting information
p. 1296 - 1304
(2020/07/10)
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- Synthesis and anti-inflammatory intestinal activity of new glucocorticoid derivatives
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Glucocorticoids (GCs) are used worldwide in the treatment of chronic inflammatory diseases. This study describes the synthesis of new glucocorticoid derivatives and evaluates anti-inflammatory activity in rat models with ulcerative colitis (UC). Six compounds (5a–f) were synthetized using the molecular hybridization strategy with yields of 40–80%. The compounds 5e and 5f showed a total regression of ulceration in 83.3% and 75% of treated animals, respectively. Moreover, 5e improved several clinical signs, such as weight gain and survival rates. The compounds 5a and 5c showed total regression of ulceration in 33.3% of the rats. This is higher than prednisolone. Glucocorticoid derivatives showed potential anti-inflammatory intestinal activity with regression of ulceration in colitis.
- Machado, Marcella Gabrielle Mendes,Scarim, Cauê Benito,de Andrade, Cleverton Roberto,dos Santos, Jean Leandro,Chin, Chung Man
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p. 206 - 216
(2019/11/26)
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- Tetrasubstituted Furans by Nucleophile-Induced Cleavage of Carbonyl Ylide-DMAD Cycloadducts
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Compounds incorporating a 4-aza-8-oxabicyclo[3.2.1]oct-6-en-2-one moiety, which were prepared by a tandem carbenoid carbonyl ylide cyclization/[3+2]-cycloaddition reaction from ethyl 2-diazo-3-oxo-4-phthalimidobutanoates, undergo a nucleophile-induced two-bond ring cleavage when treated with protic heteronucleophiles. In this manner, tetrasubstituted furantricarboxylates, tethered with α-amino acids, esters, thioesters, and amides by a 2-carbonylphenyl moiety, are obtained.
- Dobesch, Matthias,Greiner, Julian,Maas, Gerhard
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p. 2987 - 3000
(2020/08/10)
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- Flupirtine and retigabine as templates for ligand-based drug design of KV7.2/3 activators
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Drug induced liver injury (DILI) and tissue discoloration led to the recent discontinuation of the therapeutic use of the closely related drugs flupirtine and retigabine, respectively. Experience gained with these drugs strongly suggests that heterotetramer, voltage-gated potassium channels 2 and 3 (KV7.2/3) are valid targets for effective treatment of pain and epilepsy. Because the adverse effects are not related to the mechanism of action, it appears promising to investigate chemical modifications of these clinically validated, drug-like leads. In the present retro-metabolic drug design study, a series of 43 compounds were synthesized and characterized with regard to KV7.2/3 opening activity and efficacy. The most active compound 22d displays excellent potency (EC50 = 4 nM) and efficacy (154%) as a KV7.2/3 opener. Limited aqueous solubility hampered toxicity testing at concentrations higher than 63 μM, but this concentration was nontoxic to two hepatocellular cell lines (HEP-G2 and TAMH) in culture. The slightly less active but more soluble compound 25b (EC50 = 11 nM, efficacy 111%) showed an improved toxicity/activity ratio compared to flupirtine by three orders of magnitude and represents an attractive lead structure for the development of safer analgesics and antiepileptics.
- Surur, Abdrrahman S.,Bock, Christian,Beirow, Kristin,Wurm, Konrad,Schulig, Lukas,Kindermann, Markus K.,Siegmund, Werner,Bednarski, Patrick J.,Link, Andreas
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supporting information
p. 4512 - 4522
(2019/05/17)
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- Synthesis, anti-mycobacterial and cytotoxic evaluation of substituted isoindoline-1,3-dione-4-aminoquinolines coupled: Via alkyl/amide linkers
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A series of secondary amine-substituted isoindoline-1,3-dione-4-aminoquinolines were prepared via microwave heating and assayed for their anti-mycobacterial activities. The compound with a butyl chain as a spacer between the two pharmacophores and piperidine as the secondary amine component on the isoindoline ring was the most potent and non-cytotoxic among the synthesized compounds, exhibiting a minimum inhibitory concentration (MIC99) of 6.25 μg mL-1 against Mycobacterium tuberculosis.
- Rani, Anu,Viljoen, Albertus,Johansen, Matt D.,Kremer, Laurent,Kumar, Vipan
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supporting information
p. 8515 - 8528
(2019/03/21)
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- Substituted 1,3-dioxoisoindoline-4-aminoquinolines coupled via amide linkers: Synthesis, antiplasmodial and cytotoxic evaluation
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Synthesis of C-5-substituted 1,3-dioxoisoindoline-4-aminoquinolines having amide group as a spacer was developed with an intent to evaluate their antiplasmodial activities. The synthesized dioxoisoindoline-aminoquinolines tethered with β-alanine as a spacer and secondary amine as substituent displayed good anti-plasmodial activities. Compound 7j, with an optimum combination of β-alanine and an ethyl chain length as linker along with diethylamine as the secondary amine counterpart at dioxoisoindoline proved to be most potent and non-cytotoxic with IC50 of 0.097 μM against W2 strain of P. falciparum and a selective index of >2000.
- Rani, Anu,Legac, Jenny,Rosenthal, Philip J.,Kumar, Vipan
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- Efficient Kinetic Resolution of Sulfur-Stereogenic Sulfoximines by Exploiting CpXRhIII-Catalyzed C?H Functionalization
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Chiral sulfoximines with stereogenic sulfur atoms are promising motifs in drug discovery. We report an efficient method to access chiral sulfoximines through a C?H functionalization based kinetic resolution. A rhodium(III) complex equipped with a chiral Cpx ligand selectively participates in conjunction with phthaloyl phenylalanine in the C?H activation of just one of the two sulfoximine enantiomers. The intermediate reacts with various diazo compounds, providing access to chiral 1,2-benzothiazines with synthetically valuable substitution patterns. Both sulfoximines and 1,2-benzothiazines were obtained in high yields and excellent enantioselectivity, with s-values of up to 200. The utility of the method is illustrated by the synthesis of the key intermediates of two pharmacologically relevant kinase inhibitors.
- Brauns, Marcus,Cramer, Nicolai
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supporting information
p. 8902 - 8906
(2019/06/04)
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- Rh(III)-Catalyzed C-H Amidation of Arenes with N-Methoxyamide as an Amidating Reagent
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The Rh(III)-catalyzed amidation of C(sp2)-H bonds has been reported by employing the N-methoxyamide as a novel amino source. An excellent level of functional group tolerance can be achieved when N-methoxyamide derivatives are used as the amidating reagents. Importantly, several known bioactive compounds such as Aminalon, Pregabalin, Gabapentin, and Probenecid can be transformed to effective amidating reagents, as a way to facilitate the development of new bioactive molecules.
- Ju, Guodong,Li, Guobao,Qian, Guanwen,Zhang, Jingyu,Zhao, Yingsheng
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supporting information
p. 7333 - 7336
(2019/10/08)
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- Oxidative Damage in Aliphatic Amino Acids and Di- and Tripeptides by the Environmental Free Radical Oxidant NO3?: the Role of the Amide Bond Revealed by Kinetic and Computational Studies
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Kinetic and computational data reveal a complex behavior of the important environmental free radical oxidant NO3? in its reactions with aliphatic amino acids and di- and tripeptides, suggesting that attack at the amide N-H bond in the peptide backbone is a highly viable pathway, which proceeds through a proton-coupled electron transfer (PCET) mechanism with a rate coefficient of about 1 × 106 M-1 s-1 in acetonitrile. Similar rate coefficients were determined for hydrogen abstraction from the α-carbon and from tertiary C-H bonds in the side chain. The obtained rate coefficients for the reaction of NO3? with aliphatic di- and tripeptides suggest that attack occurs at all of these sites in each individual amino acid residue, which makes aliphatic peptide sequences highly vulnerable to NO3?-induced oxidative damage. No evidence for amide neighboring group effects, which have previously been found to facilitate radical-induced side-chain damage in phenylalanine, was found for the reaction of NO3? with side chains in aliphatic peptides.
- Nathanael, Joses G.,Wille, Uta
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p. 3405 - 3418
(2019/03/11)
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- Amides of N-Deacetyllappaconitine and Amino Acids
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Amides were prepared from N-deacetyllappaconitine and the amino acids glycine, taurine, and γ-aminobutyric acid.
- Gabbasov,Tsyrlina,Spirikhin,Yunusov
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p. 951 - 955
(2018/09/27)
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- Silver-Catalyzed Efficient Synthesis of Oxindoles and Pyrroloindolines via α-Aminoalkylation of N-Arylacrylamides with Amino Acid Derivatives
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α-Aminoalkylation of N-arylacrylamides with amino acid derivatives was achieved by silver-catalysis in moderate to high yields. The reaction provides an efficient strategy for the synthesis of functionalized oxindoles, and is suitable for a wide range of N-arylacrylamides and amino acids, both of which are inexpensive and readily available. The oxindoles obtained were readily transformed into densely functionalized pyrroloindolines by deprotection and cyclization in one pot.
- Kanyiva, Kyalo Stephen,Makino, Sohei,Shibata, Takanori
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supporting information
p. 496 - 499
(2018/03/06)
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- Synthesis and study of modified polyvinyl alcohol containing amino acid moieties as anticancer agent
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A series of new phthalimides compounds[3-7]a-i were synthesized from reaction of Malic anhydride, phthalic anhydride, nitro phthalic anhydride, 2-phenyl-4H-benzo[d][1,3]oxazin-4-one, 2-(4-nitrophenyl)-4H-benzo[d][1,3]oxazin-4-one with different amino acids as glycine, alanine, valine, leucine, isoleucine, serine, threonine, tyrosine and Phenyl alanine [1]a-i under fusion conditions. Compounds [3-7]a-i react with SOCl2 in the presence of benzene to produce compounds [8-12]a-i. Chemical modification of Poly(vinyl alcohol)were obtained by reaction of PVA with compounds [8-12]a-i using the dimethyl formamide to give compounds [13-17]a-i. The structure of the synthesized compounds was characterized by their analytical and spectral data as, IR spectra, 1H, 13C-NMR, Elemental analysis (CHN), UV-Vis Spectroscopy, Scanning electron microscopy (SEM), Antibacterial activity were screened via two kinds of bacteria. Also, anticancer activity were examined for most of the modified polyvinyl alcohol.
- Samir, Ali H.,Saeed, Ruwaidah S.,Matty, Fadhel S.
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p. 286 - 294
(2018/03/21)
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- Synthesis and characterization of unique new lithium, sodium and potassium coordination polymers
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Five new alkali metal coordination compounds [Li(NPG)](1a), [Na(NPG)2]?2H2O(2a), [C8H5KO4](3a), [Li(NPA)2H2O](1b) and [Na(NPA)2](2b) wherein (NPG = N-phthaloyl glycine, NPA = N-phthaloyl-?-alanine) have been synthesized and characterized by means of X ray single crystal analysis, Infrared spectroscopy (IR), Thermogravimetric analysis (TGA) and Florescence spectroscopy. The compounds 1a, 2a, 3a and 2b showed metal directed self-assembly supramolecular network structures. The crystal structure of compounds 1a and 1b showed distorted tetrahedral geometry with coordination number 4 around lithium. The carboxylate coordination modes were η2μ3and η1μ1 in 1a and 1b respectively. The compounds 2a and 2b exhibited distorted octahedral geometry with coordination number 6 around sodium. The carboxylate coordination mode in 2a and 2b is η2μ2. The objective was to synthesize potassium complex [K(NPG)], but N-phthaloyl glycine was hydrolysed due to exothermic reaction in the presence of strong base, resulted, the formation of 3a. The multiple coordination modes of alkali metal ions to the carboxylate and ring carbonyl oxygen atoms of NPG and NPA produced unique three dimensional architectures. The compounds 1b and 2b showed two strong fluorescence emissions enhancement (blue emission maxima) with greater intensity comparative to NPA, while the compounds 1a and 2a showed two weak fluorescence emissions with less intensity comparative to ligand (NPG). The base hydrolysis of NPG with in the compound 3a resulted the change of ligand based fluorochrome, which produced different shape emission spectrum as compared to other compounds.
- Nadeem, Muhammad,Bhatti, Moazzam H.,Yunus, Uzma,Mehmood, Mazhar,Asif, Hafiz Muhammad,Mehboob, Shoaib,Fl?rke, Ulrich
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p. 179 - 188
(2018/05/09)
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- DIRECT INHIBITORS OF KEAP1-NRF2 INTERACTION AS ANTIOXIDANT INFLAMMATION MODULATORS
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A method of identifying compounds as direct inhibitors of Keap1-Nrf2 interaction through high-throughput screening and lead development. The direct inhibitors of Keap1-Nrf2 interaction are more specific and free of various undesirable effects than existing indirect inhibitors, and are potential drug candidates of chemopreventive and therapeutic agents for treatment of various diseases or conditions involving oxidative stress and/or inflammation, including but not limited to cancers, diabetes, Alzheimer's, and Parkinson's. Novel compounds are identified and methods of preventing or treating diseases or conditions related to Keap1-Nrf2 interaction activity by use of the novel compounds identified or compositions containing such compounds are also disclosed.
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Paragraph 0350
(2018/06/09)
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- Antiplasmodial activity of hydroxyethylamine analogs: Synthesis, biological activity and structure activity relationship of plasmepsin inhibitors
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Malaria, particularly in endemic countries remains a threat to the human health and is the leading the cause of mortality in the tropical and sub-tropical areas. Herein, we explored new C2 symmetric hydroxyethylamine analogs as the potential inhibitors of Plasmodium falciparum (P. falciparum; 3D7) in in-vitro cultures. All the listed compounds were also evaluated against crucial drug targets, plasmepsin II (Plm II) and IV (Plm IV), enzymes found in the digestive vacuole of the P. falciparum. Analog 10f showed inhibitory activities against both the enzymes Plm II and Plm IV (Ki, 1.93 ± 0.29 μM for Plm II; Ki, 1.99 ± 0.05 μM for Plm IV). Among all these analogs, compounds 10g selectively inhibited the activity of Plm IV (Ki, 0.84 ± 0.08 μM). In the in vitro screening assay, the growth inhibition of P. falciparum by both the analogs (IC50, 2.27 ± 0.95 μM for 10f; IC50, 3.11 ± 0.65 μM for 10g) displayed marked killing effect. A significant growth inhibition of the P. falciparum was displayed by analog 12c with IC50 value of 1.35 ± 0.85 μM, however, it did not show inhibitory activity against either Plms. The hemolytic assay suggested that the active compounds selectively inhibit the growth of the parasite. Further, potent analogs (10f and 12c) were evaluated for their cytotoxicity towards mammalian HepG2 and vero cells. The selectivity index (SI) values were noticed greater than 10 for both the analogs that suggested their poor toxicity. The present study indicates these analogs as putative lead structures and could serve as crucial for the development of new drug molecules.
- Kumar Singh, Amit,Rajendran, Vinoth,Singh, Snigdha,Kumar, Prashant,Kumar, Yogesh,Singh, Archana,Miller, Whelton,Potemkin, Vladimir,Poonam,Grishina, Maria,Gupta, Nikesh,Kempaiah, Prakasha,Durvasula, Ravi,Singh, Brajendra K.,Dunn, Ben M.,Rathi, Brijesh
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p. 3837 - 3844
(2018/07/13)
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- Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis
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Bisphosphonates such as zoledronic, alendronic and risedronic acids are a class of drugs clinically used to prevent bone density loss and osteoporosis. Novel P-C-P bisphosphonates were synthesized for targeting human farnesyl pyrophosphate synthase (hFPPS) and human geranylgeranyl pyrophosphate synthase (hGGPPS), key enzymes of the mevalonate pathway, and capable of anti-proliferative action on a number of cell lines (PC3, MG63, MC3T3, RAW 264.7, J774A.1, bone marrow cells and their co-colture with PC3) involved in bone homeostasis, bone formation and death. Among sixteen compounds, [1-hydroxy-2-(pyrimidin-2-ylamino)ethane-1,1-diyl]bis(phosphonic acid) (10) was effective in reducing PC3 and RAW 264.7 cell number in crystal-violet and cell-dehydrogenase activity assays at 100 μM concentration. 10 reduced differentiated osteoclasts number similarly with zoledronic acid in osteoclastogenesis assay. At nanomolar concentrations, 10 was more effective than zoledronic acid in inducing mineralization in MC3T3 and murine bone marrow cells. Further, 10 significantly inhibited the activity of hFPPS showing an IC50 of 0.31 μM and a remarkable hydroxyapatite binding of 90%. Docking calculations were performed identifying putative interactions between some representative novel bisphosphonates and both hFPPS and hGGPPS. Then, 10 was found to behave similarly or even better than zoledronic acid as a anti-resorptive agent.
- Savino, Salvatore,Toscano, Annamaria,Purgatorio, Rosa,Profilo, Emanuela,Laghezza, Antonio,Tortorella, Paolo,Angelelli, Mariacristina,Cellamarea, Saverio,Scala, Rosa,Tricarico, Domenico,Thomas Marobbio, Carlo Marya,Perna, Filippo,Vitale, Paola,Agamennone, Mariangela,Dimiccoli, Vincenzo,Tolomeo, Anna,Scilimati, Antonio
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p. 184 - 200
(2018/09/18)
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- 1-Imidoalkylphosphonium salts with modulated Cα–P+ bond strength: synthesis and application as new active α-imidoalkylating agents
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An effective synthesis of the hitherto unknown 1-imidoalkylphosphonium salts has been developed in the reported study. The crucial step in the method included the decarboxylative α-methoxylation of N-phthaloyl- or N-succinylamino acids to the corresponding N-(1-methoxyalkyl)imides, followed by the displacement of the methoxy group by the triarylphosphonium group through melting of the imide derivative with triarylphosphonium tetrafluoroborate. The imidoalkylating properties of the obtained 1-imidoalkylphosphonium salts were tested using the Tscherniac–Einhorn-type reaction with aromatic hydrocarbons as a model reaction. It was found that the Cα–P+ bond strength can be considerably reduced and the imidoalkylation of arenes can be markedly facilitated using 1-imidoalkylphosphonium salts derived from triarylphosphines with electron-withdrawing substituents such as tris(m-chorophenyl)phosphine, tris(p-chlorophenyl)phosphine and tris[p-(trifluoromethyl)phenyl]phosphine. Microwave irradiation also considerably facilitates the cleavage of the highly polar Cα–P+ bond.
- Adamek, Jakub,Mazurkiewicz, Roman,W?grzyk, Anna,Erfurt, Karol
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supporting information
p. 1446 - 1455
(2017/08/02)
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- Novel thiazolidinedione-5-acetic-acid-peptide hybrid derivatives as potent antidiabetic and cardioprotective agents
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Thiazolidinediones (TZDs) are one of the important clinically established antidiabetic agents. Amino-acid and peptides have an advantage of better target selectivity and specificity. As hybrids, they also improved absorption and showed better bioavailability, which in turn makes them safer. Hence, here an effort has been made to synthesize hybrids of thiazolidinedione with amino-acids and peptides and evaluate their antidiabetic and cardioprotective effect in streptozotocin-nicotinamide (STZ-NA) induced Type 2 diabetes mellitus (T2DM) rat models. A series of 14 thiazolidinedione-5-acetic acid hybrids with of different amino-acids and peptide combinations were synthesized, characterized and further screened for antidiabetic and cardioprotective activity. Among all, six compounds T1 (SSDMA1), T4 (SSDMA4), T5 (SSDMA5), T7 (SDMA13), T9 (SSDMA15) and T13 (SSDMA49) showed better antioxidant activity and comparable % glucose uptake by yeast cells. Hence, the in vivo antidiabetic screening was done for these six compounds. Among all six T1, T7, T13 showed significant blood glucose level decrease compared to standard pioglitazone HCl. Also T1, T7 and T13 showed better antioxidant activity with lower IC50 value than standard ascorbic acid, and hence in vivo cardioprotective studies were done for these. The ECG studies showed that T1 (SSDMA1) and T7 (SSDMA13) were better effective than SDMA49 (T13) in restoring the normal functioning of the heart, thus may help in preventing the development of diabetic cardiomyopathy (DCM) and controlling T2DM.
- Maji,Samanta
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p. 1163 - 1172
(2017/02/23)
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- Reagent-free continuous thermal tert-butyl ester deprotection
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Continuous processing enables the use of non-standard reaction conditions such as high temperatures and pressures while in the liquid phase. This expands the chemist's toolbox and can enable previously unthinkable chemistry to proceed with ease. For a series of amphoteric amino acid derivatives, we have demonstrated the ability to hydrolyze the tert-butyl ester functionality in protic solvent systems. Using a continuous plug flow reactor at 120–240 °C and 15–40 min reaction times, no pH modification or additional reagents are needed to achieve the desired transformation. The method was then expanded to encompass a variety of more challenging substrates to test selectivity and racemization potential. The acid products were generally isolated as crystalline solids by simple solvent exchange after the deprotection reaction in good to high yield and purity.
- Cole, Kevin P.,Ryan, Sarah J.,Groh, Jennifer McClary,Miller, Richard D.
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p. 6209 - 6217
(2017/09/30)
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- Phthiobuzonum derivative and its preparation and use
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The invention relates to a ftibamzone derivative and a preparation method and an application thereof, and belongs to the technical field of ftibamzone medicament synthesis. Pharmacological experiments prove that the ftibamzone derivative of the invention has obvious cytotoxic activity and antiviral activity, and can be used for treating viral diseases such as tumor, herpes, trachoma, and the like.
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-
Paragraph 0088; 0090
(2016/11/09)
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- Direct, visible light-sensitized benzylic C[sbnd]H fluorination of peptides using dibenzosuberenone: selectivity for phenylalanine-like residues
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A visible light-sensitized benzylic sp3C[sbnd]H fluorination protocol using dibenzosuberenone (5?mol?%) and Selectfluoris optimized for the direct functionalization of phenylalanine-like residues in short chain peptides. Amino acids, dipeptides, and tripeptides undergo benzylic fluorination with remarkable regioselectivity in the presence of protected basic, acidic, and nonpolar side chains (including those with tertiary sites). Additionally, protecting group compatibility, a gram scale application, and competition experiments were explored.
- Bume, Desta Doro,Pitts, Cody Ross,Jokhai, Rayyan Trebonias,Lectka, Thomas
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supporting information
p. 6031 - 6036
(2016/09/16)
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- [3H]UR-DE257: Development of a tritium-labeled squaramide-type selective histamine H2 receptor antagonist
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A series of new piperidinomethylphenoxypropylamine-type histamine H2 receptor (H2R) antagonists with different substituted "urea equivalents" was synthesized and characterized in functional in vitro assays. Based on these data as selection criteria, radiosynthesis of N-[6-(3,4-dioxo-2-{3-[3-(piperidin-1-ylmethyl)phenoxy]propylamino}cyclobut-1-enylamino)hexyl]-(2,3-3H2)propionic amide ([3H]UR-DE257) was performed. The radioligand (specific activity: 63Cimmol-1) had high affinity for human, rat, and guinea pig H2R (hH2R, Sf9 cells: Kd, saturation binding: 31 nM, kinetic studies: 20 nM). UR-DE257 revealed high H2R selectivity on membranes of Sf9 cells, expressing the respective hHxR subtype (Ki values: hH1R: > 10000 nM, hH2R: 28 nM, hH3R: 3800 nM, hH4R: > 10000 nM). In spite of insurmountable antagonism, probably due to rebinding of [3H]URDE257 to the H2R (extended residence time), the title compound proved to be a valuable pharmacological tool for the determination of H2R affinities in competition binding assays.
- Baumeister, Paul,Erdmann, Daniela,Biselli, Sabrina,Kagermeier, Nicole,Elz, Sigurd,Bernhardt, Günther,Buschauer, Armin
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supporting information
p. 83 - 93
(2015/06/01)
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- A multigram-scale lower E-factor procedure for MIBA-catalyzed direct amidation and its application to the coupling of alpha and beta aminoacids
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The development of direct and atom-economical amidation methods is of high priority because of the importance of amides and peptides as components of pharmaceuticals and commodity chemicals. This article describes the identification of more economical and more practical conditions for direct amidation of carboxylic acids and amines using the MIBA catalyst (5-methoxy-2-iodophenylboronic acid, 6) and its application to the coupling of α- and β-amino acid derivatives. It is now possible to use half of the quantity of molecular sieves prescribed in the original procedure, at a higher concentration leading to a reduction of waste and a substantially improved E-factor. This procedure was validated in the multigram scale preparation of prototypical amides, including aminoacids, using toluene as the solvent. Because of substrate inhibition of the catalyst with monoprotected α-aminoacids, the use of doubly-protected N-phthaloyl α-aminoacids or α-azidoacids is required in order to produce dipeptide products in moderate yields. β-Aminoacids do not suffer from this problem, and Boc-β-aminoacids can be coupled successfully. Unlike other boronic acid catalysts, 6 is active under ambient and low-heat conditions, which helps prevent any epimerization of chiral α-aminoacid derivatives.
- Fatemi, Solmaz,Gernigon, Nicolas,Hall, Dennis G.
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p. 4016 - 4028
(2015/07/15)
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- Silicon-containing poly(esters) with halogenated bulky side groups. Synthesis, characterization and thermal studies
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Poly(esters) (PEs) derived from diacids containing bulky side groups, which have an halogenated (Cl, Br) imide ring, an aminoacidic residue (glycine, l-alanine, l-valine) and an amide group were obtained with a silicon-containing diphenol. Also PEs without the aminoacidic residue were obtained. PEs were characterized by IR and NMR spectroscopy, and the results were in agreement with the proposed structures. PEs were obtained with good yields and moderate or high ηinh values. PEs were soluble in aprotic polar solvents and were swollen in other solvents like m-cresol and THF. The Tg values were determined and it was possible to see a tendency in the sense that when the size of the atom (Cl, Br) bonded to the imidic ring is increased, the Tg values decreased, also for those PEs obtained without the aminoacidic residue. The thermal decomposition temperatures showed that only two PEs can be considered as thermostable, considering TDT values above 400°C at 10% of weight lost. The other PEs showed good thermal stability, showing in general a decrease of the TDT values when the volume of the side group, is increased. PEs showed UV-vis transparency at 400 nm lower than 20%, but between 500 and 600 nm, showed 80% transparency. PEs containing halogen atoms showed flame retardancy in a simple essay, with respect to PEs without halogen atoms in which the combustion was complete.
- Tagle,Terraza,Tundidor-Camba,Coll
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p. 49132 - 49142
(2015/06/16)
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- Phthaloyl amino acids as anti-inflammatory and immunomodulatory prototypes
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A series of phthalimide analogs were synthesized by derivatization of phthalic anhydride, a highly toxic substance, using a "one pot" condensation reaction to α-amino acids. All phthaloyl amino acid derivatives presented anti-oral inflammatory activity, but compounds 2e and 2g were found to possess the best activities comparable to thalidomide.Most of the compounds effectively suppressed nitric oxide production inmurine cells stimulatedwith lipopolysaccharide. N-phthaloyl amino acids did not exhibit any significant cytotoxicity in vitro when tested against tumor cells as well as a spleen cell culture of BALB/c mice. Compounds 2a, 2g, and 2h were able to inhibit TNF-α and IL-1β production by macrophages. At the same concentration, thalidomide did not exhibit significant inhibitory activity. Springer Science+Business Media 2013.
- Leite, Ana Cristina Lima,Barbosa, Fabio Fernandes,Cardoso, Marcos Verissimo De Oliveira,Moreira, Diogo R. M.,Coelho, Lucas Cunha D.,Da Silva, Elany Barbosa,Filho, Gevanio Bezerra De Oliveira,De Souza, Valdenia Maria Oliveira,Pereira, Valeria Rego A.,Reis, Luiza De C.,Ferreira, Paulo Michel Pinheiro,Pessoa, Claudia,Wanderley, Almir Goncalves,Mota, Fernanda Virginia B.,Da Silva, Teresinha G.
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p. 1701 - 1708
(2014/05/06)
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- Synthesis, characterization, andcomputational studies on phthalic anhydride-based benzylidene-hydrazide derivatives as novel,potential anti-inflammatory agents
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A series of phthalic anhydride-based substituted benzylidene-hydrazide derivatives (3a-i) was synthesized. The synthesized derivatives were authenticated by TLC, UV-visible, FTIR, NMR, and mass spectroscopic techniques and further screened for in vivo anti-inflammatory and analgesic activities by carrageenan-induced rat paw oedema and tail immersion methods, respectively, using diclofenac sodium as standard drug. The derivatives 3d, 3e, and 3h were found to be most active anti-inflammatory and analgesic agents among all the synthesized derivatives. The physico-chemical similarity of the derivatives with standard drugs was assessed by calculating various physicochemical properties using software programs. The percent similarity of synthesized derivatives was found to be good except 3i. The derivatives were subjected to QSAR by multilinear regression using Analyze it version 3.0 software and two statistically sound models were developed with R2 (0.933-0.960), Radj2 (0.595-0.762) and Q2 (0.999) with good F (2.76-4.84) values. Molecular docking studies were performed by MVD software (version 2012.5.0.0). The derivative 3h has emerged out as most potent anti-inflammatory agent with highest dock score, i.e., -93.64. Springer Science+Business Media 2013.
- Kajal, Anu,Bala, Suman,Kamboj, Sunil,Saini, Vipin
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p. 2676 - 2689
(2014/05/06)
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- Silver-catalyzed radical phosphonofluorination of unactivated alkenes
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We report herein a mild and catalytic phosphonofluorination of unactivated alkenes. With catalysis by AgNO3, the condensation of various unactivated alkenes with diethyl phosphite and Selectfluor reagent in CH 2Cl2/H2O/HOAc at 40 C led to the efficient synthesis of β-fluorinated alkylphosphonates with good stereoselectivity and wide functional group compatibility. A mechanism involving silver-catalyzed oxidative generation of phosphonyl radicals and silver-assisted fluorine atom transfer is proposed.
- Zhang, Chengwei,Li, Zhaodong,Zhu, Lin,Yu, Limei,Wang, Zhentao,Li, Chaozhong
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supporting information
p. 14082 - 14085
(2013/10/21)
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- Synthesis of a novel water soluble phthalimide derivative of acetaminophen as potential analgesic and antipyretic agent
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A short process for the preparation of water soluble, potential analgesic compound, N-[(4-hydroxy-phenylcarbamoyl)-methyl]- phthalamic acid 4 has been developed. Two synthetic routes (A and B) have been established for the preparation of 2-(1,3-dioxo- 1,3-dihydro-isoindol-2-yl)-N-(4-hydroxyphenyl) acetamide 3. In route A, 4-aminophenol 5 is reacted with chloroacetyl chloride 6 in solution of potassium acetate and acetic acid at 0-5°C to yield N-(4-hydroxyphenyl)-2-chloroacetamide 7. The latter is reacted with potassium phthalimide 8 and KI in DMF at 130°C to give 3. Alternatively, in route B, reaction of phthalic anhydride 8 with glycine 9 at 150°C yields the acid intermediate (1,3-dioxo-1,3- dihydro-isoindol-2-yl)-acetic acid 11, which on reaction with 4- aminophenol 6 in DMF and in the presence of dicyclohexylcarbodimide gives 3. The latter is hydrolysed in ethanolic KOH to afford 4.
- Dathu Reddy,Bharathi Kumari,Dubey
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p. 691 - 693
(2013/07/05)
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- A facile and green synthesis of novel imide and amidic acid derivatives of phenacetin as potential analgesic and anti-pyretic agents
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Facile and green syntheses of potential analgesic and antipyretic compounds, N-(4-ethoxy-phenyl)-2-(1,3- dioxo-1,3-dihydroisoindol-2-yl)acetamide derivatives 6a-g and N-[(4-ethoxy-phenylcarbamoyl)methyl]phthalamic acid derivatives 10a-g have been developed. Two synthetic routes (A and B) have been established for the preparation of 6a-g. In the route-A, 4-ethoxyaniline 2 was reacted with chloroacetyl chloride 3 in a solution of potassium acetate and acetic acid to yield N-(4-ethoxyphenyl)-2-chloroacetamide 4. The latter was reacted with imide compounds 5a-g either in triethanolamine as a green solvent or in solid phase in the presence of TEBAC and KI to yield 6a-g. Alternatively, in the route-B, reaction of anhydrides 7a-g with glycine 8 yielded the (1, 3-dioxo-1, 3-dihydroisoindol-2-yl)acetic acid derivatives 9a-g which on reaction with 2 either in triethnolamine and DCC as a dehydrating agent or in solid phase in the presence of DCC gave 6a-g. The latter were hydrolyzed in 0.5N ethanolic KOH to afford 10a-g.
- Reddy, Yervala D.,Kumar, Padam P.,Devi, Bhoomireddy R.,Dubey, Pramod K.,Kumari, Yalamanchili B.
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-
- Asymmetric hydrogenation of α- Or β-acyloxy α,β- unsaturated phosphonates catalyzed by a Rh(i) complex of monodentate phosphoramidite
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The Rh(i) complex of a monodentate phosphoramidite bearing a primary amine moiety (DpenPhos) has been disclosed to be highly efficient for the asymmetric hydrogenation of a variety of α- or β-acyloxy α,β- unsaturated phosphonates, providing the corresponding biologically important chiral α- or β-hydroxy phosphonic acid derivatives with excellent enantioselectivities (90->99% ee).
- Zhang, Jinzhu,Dong, Kaiwu,Wang, Zheng,Ding, Kuiling
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supporting information; experimental part
p. 1598 - 1601
(2012/03/22)
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- Nitroxyl radical/PhI(OAc)2: One-pot oxidative cleavage of vicinal diols to (di)carboxylic acids
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A mild and user-friendly one-pot oxidative cleavage of vicinal diols to their corresponding (di)carboxylic acids using AZADOs and PhI(OAc)2 is described. 1,2-Diols and 2,3-diols as well as 1,2,3-triol gave one- or two-carbon-unit-shorter carboxylic acids. Internal vicinal diols also smoothly underwent one-pot oxidative cleavage to afford the corresponding dicarboxylic acids. Cyclic vicinal diols are converted to their corresponding open-form dicarboxylic acids.
- Shibuya, Masatoshi,Shibuta, Takuro,Fukuda, Hayato,Iwabuchi, Yoshiharu
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supporting information
p. 5010 - 5013
(2013/01/15)
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- BORONIC ACID CATALYSTS AND METHODS OF USE THEREOF FOR ACTIVATION AND TRANSFORMATION OF CARBOXYLIC ACIDS
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The present application provides methods and catalysts for activation of carboxylic acids for organic reactions. In particular, methods are disclosed for direct nucleophilic addition reactions, such as, amidation reactions with amines, cycloadditions, and conjugate additions, using boronic acid catalysts of formula I, II or III: Also included are novel boronic acid catalysts of formula IV, V and III:
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Page/Page column 45-46
(2012/09/10)
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- Synthesis and anticonvulsant properties of new acetamide derivatives of phthalimide, and its saturated cyclohexane and norbornene analogs
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The synthesis and anticonvulsant properties of new piperazine or morpholine acetamides derived from 2-(1,3-dioxoisoindolin-2-yl)-, 2-(1,3-dioxo-3a,4,5,6,7, 7a-hexahydroisoindol-2-yl-) and (3,5-dioxo-4-azatricyclo[5.2.1.0 2,6]dec-8-en-4-yl)-acetic acid were described. Initial anticonvulsant screening was performed using maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizures tests. The neurotoxicity was determined applying the minimal motor impairment rotarod test. The in vivo results revealed that numerous compounds were effective in the MES screen. The most active was 2-{2-[4-(4-fluorophenyl)piperazin-1-yl]-2-oxoethyl}isoindoline-1,3-dione (12) that revealed protection in the electrically induced seizures at a dose of 30 mg/kg and 100 mg/kg 0.5 h and 4 h after i.p. administration in mice respectively. This molecule given orally in rats at a dose of 30 mg/kg was more potent than reference anticonvulsant - phenytoin.
- Kamiński, Krzysztof,Obniska, Jolanta,Wiklik, Beata,Atamanyuk, Dmytro
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experimental part
p. 4634 - 4641
(2011/11/04)
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- Synthesis of phthalyl substituted imidazolones and schiff bases as antimicrobial agents
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A new series of phthalyl substituted imidazolones (4a-g) and Schiff bases (5a-d) were synthesized from 2-methyl-(m-nitro-1,3- dioxo-1,3-dihydro- (2H)-isoindole-2-yl)-5-amino-1,3,4-thiadiazole (3 a-b). Compounds (3a-b) were prepared by cyclisation of 2-(m-nitro-1,3-dioxo-1,3-dihydro-(2H)-isoindole-2- yl)methyl ethanoate (2) with thiosemicarbazide. 2-(m-nitro-1,3-dioxo-1,3- dihydro-(2H)-isoindole-2-yl) ethanoic acid (1) in presence of thionyl chloride and methanol gave the ester (2) while compound (1) was synthesized by aminolysis of phthalic anhydride with glycine. The compounds were characterized by spectral techniques of IR, 1H NMR, Mass and elemental analysis. All the synthesized compounds (4a-g) and (5a-d) were screened for their antibacterial activity against the pathogenic strains E. coli, P. aureus, C. freundii while antifungal activity was evaluated against A. niger, A. flavus, Penicillium sp. and C. albicans.
- Sah, Pramilla,Saraswat, Neha,Seth, Manu
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experimental part
p. 427 - 434
(2012/02/02)
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- Synthesis and antiviral activity of novel 1,3,4-thiadiazine derivatives
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A series of novel 1,3,4-thiadiazine derivatives were synthesized via chemical optimization on phthiobuzone. Their anti-herpes simplex virus (HSV) activities in vitro were also tested. Several compounds exhibited more highly potent anti-HSV activity and much higher selectivity index (SI) values than those of phthiobuzone. The most potent anti-HSV compound was 4f, which showed marked inhibition against HSV-1 (IC50=77.04μg/ml) and HSV-2 (IC50=30.00μg/ml). Meanwhile it had low cytotoxicity (CC 50=1000.00μg/ml), resulting in high (SIHSV-1= 12.98, SIHSV-2=33.33, respectively). Furthermore, a computational study for prediction of absorption, distribution, metabolism, excretion (ADME) properties of compound 4f was performed by determination of topological polar surface area, absorption and Lipinski parameters.
- Yang, Yajun,Feng, Ziming,Jiang, Jianshuang,Yang, Yanan,Pan, Xiandao,Zhang, Peicheng
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scheme or table
p. 1016 - 1019
(2011/10/08)
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