1126-09-6Relevant articles and documents
Synthesis and SAR studies of 1-substituted-n-(4-alkoxycarbonylpiperidin-1-yl)alkanes as potent antiarrhythmic agents
Tripathi, Ravish C.,Pandey, Suresh K.,Kar,Dikshit,Saxena, Anil K.
, p. 2693 - 2698 (1999)
Synthesis and SAR studies of the title compounds have resulted in the identification of structural and physicochemical parameter (Vw) contributing for antiarrhythmic activity. Among the two most promising compounds 3a and 3b, the 3a has shown antiarrhythmic activity comparable to quinidine.
Design, synthesis and biological evaluation of novel diazaspiro[4.5]decan-1-one derivatives as potential chitin synthase inhibitors and antifungal agents
Li, Bing,Wang, Kaiyuan,Zhang, Rui,Li, Baihui,Shen, Yangli,Ji, Qinggang
, (2019)
A series of 2,8-diazaspiro[4.5]decan-1-one derivatives were designed, synthesized and screened for their inhibition activities against chitin synthase (CHS) and antimicrobial activities in vitro. The biological assays revealed that compounds 4a, 4e, 4h, 4j, 4o, 4q and 4r exhibited moderated to excellent potency against CHS with IC50 values ranging from 0.12 to 0.29 mM. Compounds 4e, 4j with IC50 value of 0.13 mM, 0.12 mM respectively, showed excellent inhibition potency among these compounds, which were similar to that of polyoxin B whose IC50 value was 0.08 mM. Meanwhile, the screening of the antifungal activity showed that compounds 4j and 4r had the same potency of inhibiting the growth of A. fumigatus with MIC value of 0.08 mmol/L. Compound 4d displayed excellent activity against C. albicans (ATCC 90023) with MIC value of 0.04 mmol/L, which was superior to fluconazole (0.104 mmol/L) and polyoxin B (0.129 mmol/L). The result of antibacterial assay showed that these compounds had little potency against those selected bacteria strains including three Gram-positive bacteria and three Gram-negative bacteria. Furthermore, the combination use of 4c-fluconazole, 4i-fluconazole, 4j-fluconazole, and 4o-fluconazole against C. albicans,A. fumigatus and A. flavus showed additive or synergistic effects. These results indicated that the designed compounds serve as potential chitin synthase inhibitors and have selectively antifungal activities.
A novel approach for the synthesis of hydrogel nanoparticles and a removal study of reactive dyes from industrial effluent
Mahida, Viran P.,Patel, Manish P.
, p. 21577 - 21589 (2016)
A novel amphoteric monomer, N,N-diallyl carboxypiperidinium bromide (DACPB), has been synthesized by the stepwise condensation of isonipecotic acid to an ester and then with allyl chloride and allyl bromide. The present research study highlights the UV-irradiation synthesis of poly(NIPAAm/DACPB/APTAC) superabsorbent nanohydrogels by free radical polymerization. Nanohydrogel (VUV-05) shows faster swelling and a greater swelling percentage (～43000%), which was responsible for the high adsorption of dyes, than that in our previous research study. The synthesized nanohydrogel (VUV-05) was applied for a removal study of Reactive Red 152 dye from industrial effluent. Also, a removal study for a mixture of three reactive dyes, namely Reactive Red 195, Reactive Blue 222 and Reactive Black 5, was carried out from a sole industrial effluent. The nanohydrogels with and without dye adsorption were characterized by FT-IR, TGA, SEM and zeta potential analysis. The effect of parameters such as the initial dye concentration, treatment time, pH, and adsorbent dose were investigated to determine the maximum adsorption. From the removal study it was observed that ～87% of RR-152 dye can be removed from industrial effluent. Also, the nanohydrogel was able to remove the mixture of reactive dyes, and its removal efficiency was 53.14%, 51.90% and 51.06% for RR-195, RB-222 and RB-5 from a lone industrial effluent (30%), respectively. After the removal study, it was concluded that the pseudo-second order and Langmuir models may well describe the Reactive Red 152 dye adsorption process.
Late-Stage Intermolecular Allylic C-H Amination
Clark, Joseph R.,Dixon, Charlie F.,Feng, Kaibo,Han, Wei,Ide, Takafumi,Koch, Vanessa,Teng, Dawei,Wendell, Chloe I.,White, M. Christina
supporting information, p. 14969 - 14975 (2021/10/01)
Allylic amination enables late-stage functionalization of natural products where allylic C-H bonds are abundant and introduction of nitrogen may alter biological profiles. Despite advances, intermolecular allylic amination remains a challenging problem due to reactivity and selectivity issues that often mandate excess substrate, furnish product mixtures, and render important classes of olefins (for example, functionalized cyclic) not viable substrates. Here we report that a sustainable manganese perchlorophthalocyanine catalyst, [MnIII(ClPc)], achieves selective, preparative intermolecular allylic C-H amination of 32 cyclic and linear compounds, including ones housing basic amines and competing sites for allylic, ethereal, and benzylic amination. Mechanistic studies support that the high selectivity of [MnIII(ClPc)] may be attributed to its electrophilic, bulky nature and stepwise amination mechanism. Late-stage amination is demonstrated on five distinct classes of natural products, generally with >20:1 site-, regio-, and diastereoselectivity.
Optimization of a Benzoylpiperidine Class Identifies a Highly Potent and Selective Reversible Monoacylglycerol Lipase (MAGL) Inhibitor
Granchi, Carlotta,Lapillo, Margherita,Glasmacher, Sandra,Bononi, Giulia,Licari, Cristina,Poli, Giulio,El Boustani, Maguie,Caligiuri, Isabella,Rizzolio, Flavio,Gertsch, Jürg,Macchia, Marco,Minutolo, Filippo,Tuccinardi, Tiziano,Chicca, Andrea
, p. 1932 - 1958 (2019/02/26)
Monoacylglycerol lipase (MAGL) is the enzyme degrading the endocannabinoid 2-arachidonoylglycerol, and it is involved in several physiological and pathological processes. The therapeutic potential of MAGL is linked to several diseases, including cancer. The development of MAGL inhibitors has been greatly limited by the side effects associated with the prolonged MAGL inactivation. Importantly, it could be preferable to use reversible MAGL inhibitors in vivo, but nowadays only few reversible compounds have been developed. In the present study, structural optimization of a previously developed class of MAGL inhibitors led to the identification of compound 23, which proved to be a very potent reversible MAGL inhibitor (IC50 = 80 nM), selective for MAGL over the other main components of the endocannabinoid system, endowed of a promising antiproliferative activity in a series of cancer cell lines and able to block MAGL both in cell-based as well as in vivo assays.
Light-Mediated Formal Radical Deoxyfluorination of Tertiary Alcohols through Selective Single-Electron Oxidation with TEDA2+.
Aguilar Troyano, Francisco José,Ballaschk, Frederic,Jaschinski, Marcel,?zkaya, Yasemin,Gómez-Suárez, Adrián
supporting information, p. 14054 - 14058 (2019/11/11)
The synthesis of tertiary alkyl fluorides through a formal radical deoxyfluorination process is described herein. This light-mediated, catalyst-free methodology is fast and broadly applicable allowing for the preparation of C?F bonds from (hetero)benzylic, propargylic, and non-activated tertiary alcohol derivatives. Preliminary mechanistic studies support that the key step of the reaction is the single-electron oxidation of cesium oxalates—which are readily available from the corresponding tertiary alcohols—with in situ generated TEDA2+. (TEDA: N-(chloromethyl)triethylenediamine), a radical cation derived from Selectfluor.
Polysilane-Immobilized Rh-Pt Bimetallic Nanoparticles as Powerful Arene Hydrogenation Catalysts: Synthesis, Reactions under Batch and Flow Conditions and Reaction Mechanism
Miyamura, Hiroyuki,Suzuki, Aya,Yasukawa, Tomohiro,Kobayashi, Shu
supporting information, p. 11325 - 11334 (2018/09/06)
Hydrogenation of arenes is an important reaction not only for hydrogen storage and transport but also for the synthesis of functional molecules such as pharmaceuticals and biologically active compounds. Here, we describe the development of heterogeneous Rh-Pt bimetallic nanoparticle catalysts for the hydrogenation of arenes with inexpensive polysilane as support. The catalysts could be used in both batch and continuous-flow systems with high performance under mild conditions and showed wide substrate generality. In the continuous-flow system, the product could be obtained by simply passing the substrate and 1 atm H2 through a column packed with the catalyst. Remarkably, much higher catalytic performance was observed in the flow system than in the batch system, and extremely strong durability under continuous-flow conditions was demonstrated (>50 days continuous run; turnover number >3.4 × 105). Furthermore, details of the reaction mechanisms and the origin of different kinetics in batch and flow were studied, and the obtained knowledge was applied to develop completely selective arene hydrogenation of compounds containing two aromatic rings toward the synthesis of an active pharmaceutical ingredient.
A general method for the direct transformation of common tertiary amides into ketones and amines by addition of Grignard reagents
Huang, Pei-Qiang,Wang, Yu,Xiao, Kai-Jiong,Huang, Ying-Hong
, p. 4248 - 4254 (2015/06/02)
The direct transformation of amides into ketones by addition of organometallic reagents has attracted the attention of organic chemists for a long time. However limited methods are reliable for common amides and have found synthetic applications. Here we report a method featuring in situ activation of tertiary amides with triflic anhydride (Tf2O) followed by addition of Grignard reagents. The method displays a good generality in scope for both amides and Grignard reagents, and it can be viewed as the acylation of Grignard reagents using amides as stable and selective acylating agents. Moreover, this deaminative alkylation reaction provides a mild method for the N-Deacylation of amides to give free amines.
An improved and simple route for the synthesis of 3-quinuclidinone hydrochloride
Soni, Jigar Y.,Premasagar,Thakore, Sonal
, p. 277 - 279 (2015/06/22)
An improved method for the synthesis of 3-quinuclidinone hydrochloride 4 from piperidine-4-carboxylic acid 1 has been described. Reaction of piperidine-4-carboxylic acid 1 with thionyl chloride and ethanol gave ethyl piperidine 4-carboxylate 2. It was further condensed with methyl chloroacetate in presence of sodium carbonate to give ethyl 1-(2-methoxy-2-oxoethyl)piperidine-4-carboxylate 3. One pot Dieckmann reaction of 3 in presence of potassium tertbutoxide followed by hydrolysis and decarboxylation gave title compound azabicyclo[2.2.2]oct-3-one hydrochloride 4.
Structure-activity relationship exploration of Kv1.3 blockers based on diphenoxylate
Nguyen, William,Howard, Brittany L.,Jenkins, David P.,Wulff, Heike,Thompson, Philip E.,Manallack, David T.
supporting information, p. 7106 - 7109 (2013/01/15)
Diphenoxylate, a well-known opioid agonist and anti-diarrhoeal agent, was recently found to block Kv1.3 potassium channels, which have been proposed as potential therapeutic targets for a range of autoimmune diseases. The molecular basis for this Kv1.3 blockade was assessed by the selective removal of functional groups from the structure of diphenoxylate as well as a number of other structural variations. Removal of the nitrile functional group and replacement of the C-4 piperidinyl substituents resulted in several compounds with submicromolar IC50 values.
