- Solar and visible-light active nano Ni/g-C3N4photocatalyst for carbon monoxide (CO) and ligand-free carbonylation reactions
-
In this study, we investigate the amino and alkoxycarbonylation reaction between various substituted aryl halides, benzyl iodides, and iodocyclohexane with different types of amines and alcohols in the absence of carbon monoxide gas and ligands. Similar reactions are carried out at high temperatures, in the presence of appropriate ligands, stoichiometric amounts of bases, and gaseous carbon monoxide, which endanger the health of organic chemists. We present a novel method that does not utilize ligands, bases, gaseous CO, and special conditions. This procedure is a redox reaction carried out by new economic nano Ni/g-C3N4at room temperature and under visible light. Mo(CO)6was used toin situgenerate CO, to resolve the problems caused by the use of CO gas. This protocol has the ability to be used on a gram scale by using a continuous flow reactor.
- Hosseini-Sarvari, Mona,Akrami, Zahra
-
p. 956 - 969
(2021/02/26)
-
- Looking toward the Rim of the Active Site Cavity of Druggable Human Carbonic Anhydrase Isoforms
-
We report the synthesis and biochemical evaluation of a series of substituted 4-(4-aroylpiperazine-1-carbonyl)benzenesulfonamides (5a-s) developed as inhibitors of druggable carbonic anhydrase (CA) isoforms, as tools for the identification of new therapeu
- Mancuso, Francesca,Di Fiore, Anna,De Luca, Laura,Angeli, Andrea,Monti, Simona M.,De Simone, Giuseppina,Supuran, Claudiu T.,Gitto, Rosaria
-
supporting information
p. 1000 - 1005
(2020/03/23)
-
- NMR-based investigations of acyl-functionalized piperazines concerning their conformational behavior in solution
-
Selected N-benzoylated piperazine compounds were synthesized to study their conformational behavior using temperature-dependent 1H NMR spectroscopy. All investigated piperazines occur as conformers at room temperature resulting from the restric
- Wodtke, Robert,Steinberg, Janine,K?ckerling, Martin,L?ser, Reik,Mamat, Constantin
-
p. 40921 - 40933
(2019/01/03)
-
- Application of substituted o-hydroxybenzophenone compound or pharmaceutically acceptable salt thereof to preparation of drug for treating neurodegenerative disease
-
The invention discloses application of a substituted o-hydroxybenzophenone compound or a pharmaceutically acceptable salt thereof to preparation of a drug for treating a neurodegenerative disease. Thestructure of the compound is shown in a formula I; in t
- -
-
Paragraph 0105; 0106; 0107; 0111; 0112; 0113
(2018/10/19)
-
- Substituted O-hydroxyphenyl ketone compound as well as preparation method and application thereof
-
The invention discloses a substituted O-hydroxyphenyl ketone compound, a preparation method of the substituted O-hydroxyphenyl ketone compound, and an application of the substituted O-hydroxyphenyl ketone compound to preparation of a BRD4 protein activity
- -
-
Paragraph 0100; 0102; 0106-0108
(2018/11/22)
-
- N?-Acryloyllysine Piperazides as Irreversible Inhibitors of Transglutaminase 2: Synthesis, Structure-Activity Relationships, and Pharmacokinetic Profiling
-
Transglutaminase 2 (TGase 2)-catalyzed transamidation represents an important post-translational mechanism for protein modification with implications in physiological and pathophysiological conditions, including fibrotic and neoplastic processes. Consequently, this enzyme is considered a promising target for the diagnosis of and therapy for these diseases. In this study, we report on the synthesis and kinetic characterization of N?-acryloyllysine piperazides as irreversible inhibitors of TGase 2. Systematic structural modifications on 54 new compounds were performed with a major focus on fluorine-bearing substituents due to the potential of such compounds to serve as radiotracer candidates for positron emission tomography. The determined inhibitory activities ranged from 100 to 10?000 M-1 s-1, which resulted in comprehensive structure-activity relationships. Structure-activity correlations using various substituent parameters accompanied by covalent docking studies provide an advanced understanding of the molecular recognition for this inhibitor class within the active site of TGase 2. Selectivity profiling of selected compounds for other transglutaminases demonstrated an excellent selectivity toward transglutaminase 2. Furthermore, an initial pharmacokinetic profiling of selected inhibitors was performed, including the assessment of potential membrane permeability and liver microsomal stability.
- Wodtke, Robert,Hauser, Christoph,Ruiz-Gómez, Gloria,J?ckel, Elisabeth,Bauer, David,Lohse, Martin,Wong, Alan,Pufe, Johanna,Ludwig, Friedrich-Alexander,Fischer, Steffen,Hauser, Sandra,Greif, Dieter,Pisabarro, M. Teresa,Pietzsch, Jens,Pietsch, Markus,L?ser, Reik
-
supporting information
p. 4528 - 4560
(2018/05/07)
-
- Oxazolo[4,5-b]pyridine-Based Piperazinamides as GSK-3β Inhibitors with Potential for Attenuating Inflammation and Suppression of Pro-Inflammatory Mediators
-
Recent studies reveal that glycogen synthase kinase-3β (GSK-3β) acts as a pro-inflammatory enzyme, and by inhibiting this kinase, inflammation can be controlled. In this regard, a series of 17 piperazine-linked oxazolo[4,5-b]pyridine-based derivatives was
- Tantray, Mushtaq A.,Khan, Imran,Hamid, Hinna,Alam, Mohammad Sarwar,Dhulap, Abhijeet,Ganai, Ajaz Ahmad
-
-
- Synthesis, dynamic NMR characterization and XRD studies of novel N,N′-substituted piperazines for bioorthogonal labeling
-
Novel, functionalized piperazine derivatives were successfully synthesized and fully characterized by 1H/13C/19F NMR, MS, elemental analysis and lipophilicity. All piperazine compounds occur as conformers resulting from the partial amide double bond. Furthermore, a second conformational shape was observed for all nitro derivatives due to the limited change of the piperazine chair conformation. Therefore, two coalescence points were determined and their resulting activation energy barriers were calculated using 1H NMR. To support this result, single crystals of 1-(4-nitrobenzoyl)piperazine (3a, monoclinic, space group C2/c, a = 24.587(2), b = 7.0726(6), c = 14.171(1) ?, β = 119.257(8)°, V = 2149.9(4) ?3, Z = 4, Dobs = 1.454 g/cm3) and the alkyne derivative 4-(but-3-yn-1-yl)-1-(4-fluorobenzoyl)piperazine (4b, monoclinic, space group P21/n, a = 10.5982(2), b = 8.4705(1), c = 14.8929(3) ?, β = 97.430(1)°, V = 1325.74(4) ?3, Z = 4, Dobs = 1.304 g/cm3) were obtained from a saturated ethyl acetate solution. The rotational conformation of these compounds was also verified by XRD. As proof of concept for future labeling purposes, both nitropiperazines were reacted with [18F]F-. To test the applicability of these compounds as possible 18F-building blocks, two biomolecules were modified and chosen for conjugation either using the Huisgen-click reaction or the traceless Staudinger ligation.
- Mamat, Constantin,Pretze, Marc,Gott, Matthew,K?ckerling, Martin
-
p. 2478 - 2489
(2016/12/07)
-
- Synthesis, characterization, and anti-inflammatory activities of methyl salicylate derivatives bearing piperazine moiety
-
In this study, a new series of 16 methyl salicylate derivatives bearing a piperazine moiety were synthesized and characterized. The in vivo anti-inflammatory activities of target compounds were investigated against xylol-induced ear edema and carrageenan-induced paw edema in mice. The results showed that all synthesized compounds exhibited potent anti-inflammatory activities. Especially, the anti-inflammatory activities of compounds M15 and M16 were higher than that of aspirin and even equal to that of indomethacin at the same dose. In addition, the in vitro cytotoxicity activities and anti-inflammatory activities of four target compounds were performed in RAW264.7 macrophages, and compound M16 was found to significantly inhibit the release of lipopolysaccharide (LPS)-induced interleukin (IL)-6 and tumor necrosis factor (TNF)-α in a dose-dependent manner. In addition, compound M16 was found to attenuate LPS induced cyclooxygenase (COX)-2 up-regulation. The current preliminary study may provide information for the development of new and safe anti-inflammatory agents.
- Li, Jingfen,Yin, Yong,Wang, Lisheng,Liang, Pengyun,Li, Menghua,Liu, Xu,Wu, Lichuan,Yang, Hua
-
-
- Flavonoid derivatives as selective ABCC1 modulators: Synthesis and functional characterization
-
A series of chromones, bearing substituted amino groups or N-substituted carboxamide moieties in position 2, was synthesized and characterized in cellular assays for modulation of the ABC transporters ABCC1 (MDCKII-MRP1 cells), ABCB1 (Kb-V1 cells) and ABCG2 (MCF-7/Topo cells). The most potent ABCC1 modulators identified among these flavonoid-type compounds were comparable to the reference compound reversan regarding potency, but superior in terms of selectivity concerning ABCB1 and ABCG2 (2-[4-(Benzo[c][1,2,5]oxadiazol-5-ylmethyl)piperazin-1-yl]-5,7-dimethoxy-4H-chromen-4-one (51): ABCC1, IC50 11.3-1/4M; inactive at ABCB1 and ABCG2). Compound 51 was as effective as reversan in reverting ABCC1-mediated resistance to cytostatics in MDCKII-MRP1 cells and proved to be stable in mouse plasma and cell culture medium. Modulators, such as compound 51, are of potential value as pharmacological tools for the investigation of the (patho)physiological role of ABCC1.
- Obreque-Balboa, José Esteban,Sun, Qiu,Bernhardt, Günther,K?nig, Burkhard,Buschauer, Armin
-
supporting information
p. 124 - 133
(2016/01/20)
-
- Synthesis and biological evaluation of substituted 4-(thiophen-2-ylmethyl)- 2H-phthalazin-1-ones as potent PARP-1 inhibitors
-
We have developed a series of substituted 4-(thiophen-2-ylmethyl)-2H- phthalazin-1-ones as potent PARP-1 inhibitors. Preliminary biological evaluation indicated that most compounds possessed inhibitory potencies comparable to, or higher than AZD-2281. Among these compounds, 18q appeared to be the most notable one, which displayed an 8-fold improvement in enzymatic activity compared to AZD-2281. These efforts lay the foundation for our further investigation.
- Wang, Ling-Xiao,Zhou, Xin-Bo,Xiao, Meng-Liang,Jiang, Ning,Liu, Feng,Zhou, Wen-Xia,Wang, Xiao-Kui,Zheng, Zhi-Bing,Li, Song
-
p. 3739 - 3743
(2014/09/17)
-
- Comparison of aminolysis of 2-pyridyl and 4-pyridyl x-substituted benzoates in acetonitrile: Evidence for a concerted mechanism involving a cyclic transition state
-
A kinetic study on reactions of 2-pyridyl X-substituted benzoates (6a-i) with a series of cyclic secondary amines in MeCN is reported. The Hammett plot for the reaction of 6a-i with piperidine consists of two intersecting straight lines while the Yukawa-Tsuno plot exhibits an excellent linear correlation with ρX = 1.28 and r = 0.63, indicating that the nonlinear Hammett plot is not caused by a change in the rate-determining step but rather by resonance stabilization of substrates possessing an electron-donating group (EDG) in the benzoyl moiety. The Bronsted-type plots are linear with βnuc = 0.59 ± 0.02, which is typical of reactions reported to proceed through a concerted mechanism. A cyclic transition state (TS), which forces the reaction to proceed through a concerted mechanism, is proposed. The deuterium kinetic isotope effect of 1.3 ± 0.1 is consistent with the proposed mechanism. Analysis of activation parameters reveals that ΔH? increases linearly as the substituent X changes from an electron-withdrawing group (EWG) to an EDG, while TΔS ? remains nearly constant with a large negative value. The constant TΔS? value further supports the proposal that the reaction proceeds through a concerted mechanism with a cyclic TS.
- Um, Ik-Hwan,Bae, Ae-Ri,Um, Tae-Il
-
supporting information
p. 1206 - 1212
(2014/03/21)
-
- CDI-mediated monoacylation of symmetrical diamines and selective acylation of primary amines of unsymmetrical diamines
-
A highly efficient and green protocol for monoacylation of symmetrical diamines and chemoselective acylation of primary amines of unsymmetrical diamines has been developed.
- Verma, Sanjeev K.,Ghorpade, Ramarao,Pratap, Ajay,Kaushik
-
experimental part
p. 326 - 329
(2012/04/10)
-
- Imidazole-catalyzed monoacylation of symmetrical diamines
-
Figure Presented. An imidazole-catalyzed protocol for monoacylation of symmetrical diamines has been developed. The protocol gave selective monoacylation of aliphatic (cyclic and acyclic) primary and secondary diamines. In the reaction, imidazole acts as both catalyst and a leaving group. Different monoacylated piperazines and other diamines were synthesized at room temperature in an ethanol/water solvent system.
- Verma, Sanjeev K.,Acharya,Kaushik
-
supporting information; experimental part
p. 4232 - 4235
(2010/11/04)
-
- Synthesis and biological evaluation of benzopyran analogues bearing class III antiarrhythmic pharmacophores
-
We have synthesized a series of compounds combining the hydroxy-benzopyran ring of vitamin E with the methylsulfonylaminophenyl group of class III antiarrhythmic drugs, connected through tertiary amine moieties. Evaluation of the antiarrhythmic and antioxidant activity of the new compounds was carried out on isolated rat heart preparations using the non-recirculating Langendorff mode. The new analogues were present, at 10 μM concentration, during ischemia and reperfusion. Selected compounds were further studied by a conventional microelectrode method in order to get insight into their cellular mode of action. The most active compound, N-[4-[2-[[2-(3,4-dihydro-6-hydroxy-2,2,7,8-tetramethyl-2H-1-benzopyran-5 -yl)ethyl] methylamine]ethyl]phenyl]methanesulfonamide (19a), reduces premature beats, prolongs QT and QRS intervals during ischemia and reperfusion, and reduces MDA content, leading to a fast recovery of the heart. In addition, it exhibits moderate class III antiarrhythmic action.
- Koufaki, Maria,Kiziridi, Christina,Papazafiri, Panagiota,Vassilopoulos, Athanasios,Varro, Andras,Nagy, Zsolt,Farkas, Attila,Makriyannis, Alexandros
-
p. 6666 - 6678
(2007/10/03)
-
- Kinetics and mechanism of the reactions of S-2,4-dinitrophenyl 4-substituted thiobenzoates with secondary alicyclic amines
-
The title reactions, in 44 wt % ethanol-water at 25.0 °C, exhibit slightly curved Bronsted-type plots (log kN versus pK a of amines) with slopes β1 = 0.1-0.44 (at high pKa) and β2 ca. 0.7 (at low pKa). The magnitude of some of these slopes, together with the fact that the curvature center (pKa0 = 9.5-10.8) does not change with the electronic effects of the benzoyl substituent, suggests that these reactions are not stepwise, but concerted.
- Castro, Enrique A.,Aguayo, Raul,Bessolo, Jorge,Santos, Jose G.
-
p. 7788 - 7791
(2007/10/03)
-
- Direct synthesis of N-acylalkylenediamines from carboxylic acids under mild conditions
-
Monoacylated piperazine derivatives were prepared directly from carboxylic acids and piperazine using triphenylphosphine (TPP) and N-bromosuccinimide (NBS) in dichloromethane. Inexpensive and readily available reagents, excellent yields, short reaction times and mild reaction conditions are important features of this method.
- Bandgar,Bettigeri
-
p. 2917 - 2924
(2007/10/03)
-
- Kinetic investigation of the reactions of S-4-nitrophenyl 4-substituted thiobenzoates with secondary alicyclic amines in aqueous ethanol
-
The reactions of S-4-nitrophenyl 4-X-substituted thiobenzoates (X = H, Cl, and NO2: 1, 2, and 3, respectively) with a series of secondary alicyclic amines (SAA) were subjected to a kinetic investigation in 44 wt % ethanol-water, at 25.0 °C and an ionic strength of 0.2 M (KCl). The reactions were followed spectrophotometrically by monitoring the release of 4-nitrobenzenethiolate anion at 420-425 nm. Under excess amine, pseudo-first-order first-order rate constants (kobsd) are obtained for all reactions. The plots of kobsd vs [SAA] at constant pH are linear with the slope (kN) independent of pH. The statistically corrected Bronsted-type plots (log kN/q vs pKa + log p/q) for the reactions of 1 and 2 are nonlinear with slopes at high pK a, β1 = 0.27 and 0.10, respectively, and slopes at low pKa, β2 = 0.86 and 0.84, respectively. The Bronsted curvature is centered at pKa (pKa 0) 10.0 and 10.4, respectively. The reactions of SAA with 3 exhibit a linear Bronsted-type plot of slope 0.81. These results are consistent with a stepwise mechanism, through a zwitterionic tetrahedral intermediate (Ti±). For the reactions of 1 and 2, there is a change in rate-determining step with amine basicity, from T± breakdown to products at low pKa, to T± formation at high pKa. For the reactions of 3, breakdown to products of T ± is rate limiting for all the SAA series (pKa 0 > 11). The increasing pKa0 value as the substituent in the acyl group becomes more electron withdrawing is attributed to an increasing nucleofugality of SAA from T±. The greater pKa0 value for the reactions of SAA with 1, relative to that found in the pyridinolysis of 2,4-dinitrophenyl benzoate (pK a0 = 9.5), is explained by the greater nucleofugality from T± of the former amines, compared to isobasic pyridines, and the greater leaving ability from T± of 2,4-dinitrophenoxide relative to 4-nitrobenzenethiolate.
- Castro, Enrique A.,Bessolo, Jorge,Aguayo, Raul,Santos, Jose G.
-
p. 8157 - 8161
(2007/10/03)
-
- Highly rapid and direct synthesis of monoacylated piperazine derivatives from carboxylic acids under mild conditions
-
A series of monoacylated piperazine derivatives were obtained by the reaction of carboxylic acids with 2-chloro-4,6-dimethoxy-1,3,5-triazine in dichloromethane at room temperature. Good to excellent yields, short reaction times and mild reaction conditions are important features of this methodology.
- Bandgar,Pandit
-
p. 3855 - 3858
(2007/10/03)
-
- Reaction of piperazine with trimethylacetic arylcarboxylic anhydride; a convenient method for preparing monoacylated piperazine derivatives
-
A series of monosubstituted piperazine derivatives were obtained by the reaction of piperazine with trimethylacetic arylcarboxylic anhydrides in good yields, which were prepared in situ from arylcarboxylic acid with trimethylacetyl chloride in the presence of triethylamine.
- Lai,Wang,Luh
-
p. 361 - 363
(2007/10/03)
-
- Certain substituted 1-aryl-3-piperazin-1′-yl propanones
-
Disclosed are compounds of formula I: wherein X is a carbonyl, sulfonyl, methylene, or methylene substituted with optionally substituted phenyl; Z is nitrogen or CH; Ar1and Ar2independently represent aryl groups; and Y is hydrogen; o
- -
-
-
- Synthesis and class III type antiarrhythmic activity of 4-Aroyl (and Aryl)-1-aralkylpiperazines
-
The synthesis and in vitro Class III antiarrhythmic activity of several 4-aroyl (and aryl)-1-aralkylpiperazine and piperidine derivatives are described. Among several potent compounds identified in the series, RWJ-28810 (3), with its EC20 of 3 nM, ranks as one of the most potent (in vitro) compounds reported. (C) 2000 Elsevier Science Ltd.
- Kanojia, Ramesh M.,Salata, Joseph J.,Kauffman, Jack
-
p. 2819 - 2823
(2007/10/03)
-
- Effect of Acyl Substituents on the Reaction Mechanism for Aminolyses of 4-Nitrophenyl X-Substituted Benzoates
-
Second-order rate constants (kN) have been measured spectrophotometrically for the reaction of 4-nitrophenyl X-substituted benzoates with a series of alicyclic secondary amines in H2O containing 20 mol % dimethyl sulfoxide at 25.0°C.
- Um, Ik-Hwan,Min, Ji-Sook,Ahn, Jung-Ae,Hahn, Hyun-Joo
-
p. 5659 - 5663
(2007/10/03)
-
- Study of synthesis and cardiovascular activity of some furoxan derivatives as potential NO-donors
-
A series of hybrid molecules incorporating the furoxan and nicorandil moieties were designed as potential NO donors with cardiovascular and cerebrovascular activities. Thirty-six target molecules were successfully synthesized by conventional methods and characterized by infrared spectroscopy, 1H-NMR spectroscopy and high resolution mass spectra. The compounds were tested for their effects on KCl-induced contraction of rabbit thoracic aorta whose endothelium was denuded. Eight compounds were found to reduce KCl-induced contraction by more than 30% at 10 μM. All except one of these compounds are characterized by the presence of electron withdrawing groups in the phenyl ring attached via an amide or ester linkage to the furoxan moiety. The nature of the terminal carbonyl linkage (ester or amide) and the length or type of the alkyl chain bridging the two carbonyl functions have little effect on the activity. One of the active compounds, N-(4- methoxy-benzoyl)-N'-[3-methylfuroxanyl-4-carbonyl)piperazine (17i) was tested for hypotensive effects on anaesthetized rats at 1.5 mg/kg, and found to demonstrate a gradual and sustained hypotensive effect. The results suggest that the furoxannicorandil derivatives are a useful lead in the design of NO- donor compounds for hypertension.
- Mu, Li,Feng, Si-Shen,Go, Mei Lin
-
p. 808 - 816
(2007/10/03)
-
- Triazenes as robust and simple linkers for amines in solid-phase organic synthesis
-
A new linker strategy for the attachment of aliphatic amines has been developed. Starting from Merrifield resin, an immobilized diazonium salt was prepared in two steps. Reaction of various amines gave rise to triazenes, which in turn were cleaved off upon treament with mild acids. The triazenes have been proven to be base stable and were used in various types of transformations. The overall process is high-yielding and efficient.
- Braese, Stefan,Koebberling, Johannes,Enders, Dieter,Lazny, Ryszard,Wang, Mingfei,Brandtner, Siegfried
-
p. 2105 - 2108
(2007/10/03)
-
- Structure-reactivity correlations in the reaction of 2,4-dinitrophenyl X-substituted benzoates with alicyclic secondary amines
-
Apparent second-order rate constants (kapp) have been measured spectrophotometrically for the reaction of 2,4-dinitrophenyl X-substituted benzoates with a series of alicyclic secondary amines in H2O containing 20 mol% DMSO at 25°C. The microconstants involved in the reaction (k-1/k2, K1, and k1k2/k-1) have also been calculated. The magnitude of kapp, k1, and k1k2/k-1 values increases with increasing amine basicity and with increasing acid strengthening ability of the acyl substituent X. The k-1/k2 value decreases from ca. 6.5 to 0.3 with increasing the amine basicity, but remains almost constant upon changing the acyl substituent X for a given amine, indicating that the ratedetermining step is governed by the basicity of amine but not by the electronic nature of the acyl substituent X. The Bronsted-type plots for kapp show a break at pKa = 9.1, supporting the assumption that a change in the rate-determining step occurs from rate-limiting breakdown to formation of the addition intermediate as amine basicity increases. The corresponding Bronsted-type plots for k-1/k2, k1, and k1k2/k-1 are linear but their β values are different. σ+ constants show better correlation with log kapp, log kl and log k1k2/k-1 for the reaction with low basic amines (pKa a > 9.1). The magnitude of ρ1 is identical to that of ρapp and ρeq for a given amine.
- Um, Ik-Hwan,Min, Ji-Sook,Lee, Hye-Won
-
p. 659 - 666
(2007/10/03)
-
- Certain substituted 1-aryl-3-piperazin-1'-yl propanones to treat Alzheimer's Disease
-
Disclosed are compounds of formula I: STR1 or the pharmaceutically acceptable salts thereof wherein X is a carbonyl, sulfonyl, methylene, or methylene substituted with optionally substituted phenyl; Z is nitrogen or CH; Ar1 and Ar2 i
- -
-
-
- Substituted 1-aryl-3-piperazin-1'-yl propanones
-
Disclosed are compounds of formula I: STR1 wherein X is a carbonyl, sulfonyl, methylene, or methylene substituted with optionally substituted phenyl; Z is nitrogen or CH; Ar1 and Ar2 independently represent aryl groups; and Y is hydr
- -
-
-