- 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
-
-
Read Online
- 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
-
-
Read Online
- 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.
-
-
Read Online
- Kinetics and mechanism of the reactions of S-4-nitrophenyl 4-methylthiobenzoate with secondary alicyclic amines and pyridines
-
The reactions of the title substrate with a series of six secondary alicyclic amines and a series of eight pyridines are subjected to a kinetic investigation in 44 wt% ethanol-water, at 25.0°C, and an ionic strength of 0.2 mol · dm-3. Under amine excess pseudo first-order rate coefficients (kobs) are obtained. Plots of kobs against free amine concentration at constant pH are linear, with the slope (k N) independent of pH. The Bronsted-type plots (log k N against pKa of the conjugate acids of the amines) are non-linear, with the curvature center located at pKa (pX a0) 9.7 and 9.4, for the reactions of secondary alicyclic amines and pyridines, respectively. The plots are consistent with a zwitterionic tetrahedral intermediate (T±) on the reaction path and a change in rate-determining step. The greater pKa0 value for secondary alicyclic amines than pyridines is explained by the greater nucleofugality from T± of secondary alicyclic amines compared to isobasic pyridines. These pKa0 values are lower than those found for the reactions of S-4-nitrophenyl 4-Y-substituted thiolbenzoates (Y = H, Cl, NO2) with the corresponding amine series. These results indicate that electron donation from the non-leaving group in T ± favors leaving group expulsion from T± relative to amine expulsion. Copyright
- Castro, Enrique A.,Aguayo, Raul,Bessolo, Jorge,Santos, Jose G.
-
-
Read Online
- Discovery of novel Bcr-AblT315I inhibitors with flexible linker. Part 1: Confirmation optimization of phenyl-1H-indazol-3-amine as hinge binding moiety
-
As a continuation to our research, a series of novel Bcr-Abl inhibitors incorporated with 6-phenyl-1H-indazol-3-amine as hinge binding moiety (HBM) were developed based on confirmation analysis. Biological results indicated that these compounds exhibited an enhanced inhibition against Bcr-AblWT and Bcr-AblT315I in kinases assays, along with improved anti-proliferative activities in K562 cell assays. In particular, compound Y9 displayed comparable potency with that of imatinib. It potently inhibited Bcr-AblWT and Bcr-AblT315I kinases with IC50 of 0.043 μM and 0.17 μM, respectively. Furthermore, compound Y9 inhibited the proliferation of K562 and K562R cells with IC50 of 1.65 μM and 5.42 μM, respectively. Therefore, 6-phenyl-1H-indazol-3amine as HBM, combined with flexible linker, is a successful strategy contribute to research on T315I mutant resistance, and compound Y9 could be served as a starting point for further optimization.
- Pan, Xiaoyan,Liang, Liyuan,Sun, Ying,Si, Ru,Zhang, Qingqing,Wang, Jin,Fu, Jia,Zhang, Junjie,Zhang, Jie
-
p. 232 - 242
(2019/06/14)
-
- Carbon bridged bis-amide-based rare-earth amine compound and its preparation and with [...][...] synthesis reaction in the application of the
-
The invention discloses a carbon-bridged diacylamino rare earth amide with a general formula of {LLn[N(SiMe3)2]}2, wherein Ln is a rare earth metal selected from lanthanum, neodymium, samarium and yttrium, L represents a carbon-bridged diacylamino ligand, and n may be 1, 2 or 3 and can represent different ligands. The chemical structural formula of the carbon-bridged diacylamino rare earth amide differs with changes of the rare earth metal and the ligand. The invention targetedly discloses four chemical structural formulas of the rare earth amide as shown in the general formula. The carbon-bridged diacylamino rare earth amide provided by the invention is simple to synthesize, has definite structure and high yield and is easy to separate and purify. The invention also provides a preparation method for the rare earth amide and a method for applying the rare earth amide as a catalyst for catalysis of amidation of aldehyde and amine. The application method has the advantages of mild conditions, high activity, good selectivity, a wide substrate adaptation scope, a small catalyst amount and high product yield.
- -
-
Paragraph 0120; 0121
(2019/04/02)
-
- 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)
-
- 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 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)
-
- Aminolysis of S-4-nitrophenyl X-substituted thiobenzoates: Effect of nonleaving-group substituents on reactivity and mechanism
-
A kinetic study is reported for aminolysis of S-4-nitrophenyl X-substituted thiobenzoates 3a-g in 80 mol % H2O/20 mol % DMSO at 25.0 ± 0.1 °C. Thiol esters 3a-g are 7.8-47.6 fold more reactive than the corresponding oxygen esters (i.e., 4-nitrophenyl X-substituted benzoates 1a-g). Such reactivity order appears to be in accordance with the expectation that 4-nitrothiophenoxide in 3a-g is a better nucleofuge than 4-nitrophenoxide in 1a-g since the former is 2.64 pKa units less basic than the latter. Hammett plot for the reactions of 3a-g exhibit poor correlation coefficients (R2 = 0.977-0.986) with negative deviation by substrates possessing an electrondonating group (EDG), while the Yukawa-Tsuno plots result in excellent linear correlation (R2 = 0.995-0.997) with ? = 0.93-1.23 and r = 0.57-0.67, indicating that the negative deviation shown by substrates possessing an EDG is caused by ground-state stabilization through resonance interactions but not due to a change in ratedetermining step upon changing the nonleaving-group substituent X. The p value increases as the incoming amine becomes more basic and more reactive, indicating that the RSP is not operative in the current reactions.
- Im, Li-Ra,Jeon, Sang-Eun,Um, Ik-Hwan
-
experimental part
p. 1153 - 1157
(2011/11/12)
-
- 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)
-
- 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)
-
- 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)
-