02682nas a2200253   4500008004100000022001400041245007200055210006900127260007300196300001200269490000900281520182000290653002302110653001802133653002202151653001802173653000802191653002002199100002902219700002702248700002602275700002102301856010602322       2012                        eng d  a0022-286000aSynthesis and stereochemistry of highly crowded N-benzylpiperidones0 aSynthesis and stereochemistry of highly crowded Nbenzylpiperidon  aPO BOX 211, 1000 AE AMSTERDAM, NETHERLANDSbELSEVIER SCIENCE BVcJAN  a158-1670 v10073 a<p>A series of N-benzylated 3,5-diakyl-2,6-diarylpiperidin-4-ones 4-8 were conveniently synthesized in significant yields of 68-88% by N-benzylation of the corresponding 2,6-diaryl-3,5-dimethylpiperidin-4-ones 1-3 using different benzyl bromides. Initially, the new piperidone 2,6-bis(4-ethoxypheny1)-3,5-dimethylpiperidin-4-one 3 was synthesized by the condensation of 1:1:2 M ratio of 3-pentanone, ammonium acetate and para-ethoxybenzaldehyde in ethanolic medium. All the synthesized new compounds 3-8 were characterized by their analytical and spectral (IR, H-1 and C-13 NMR) interpretations. The stereochemistry of the new piperidone 3 was elucidated as chair conformation with an equatorial orientation of all substituents, suggested by its vicinal couplings from H-1 NMR spectrum. To investigate the impact on piperidone stereochemistry as well as NMR chemical shifts, all the N-benzylated products 4-8 were compared with their corresponding precursors, and as a result, it is clearly established that all the synthesized N-benzyl piperidones exist in the chair conformation with an equatorial orientation of all the substituents at C-2, C-3, C-5, C-6 and N. Contrary to the probability all N-benzylated compounds retain the same conformation and configuration as their precursors, however, a remarkable change on the chemical shifts are observed. For the further unambiguous confirmation of stereochemistry, the 1-benzyl-3,5-dimethyl-2,6-diphenylpiperidin-4-one 4 was examined by single-crystal X-ray diffraction. The compound 4, C26H27NO, crystallized in a P-1 space group under triclinic system with unit cell dimensions a, b, c (angstrom) and alpha, beta, gamma (degrees) of 10.156(2), 11.002(2), 11.348(4) and 116.74(4), 100.81(3), 100.17(3), respectively. (C) 2011 Elsevier B.V. All rights reserved.</p>10aChair conformation10aConfiguration10acrystal structure10aN-benzylation10aNMR10aPiperidin-4-one1 aDindulkar, Someshwar, D.1 aParthiban, Paramasivam1 aPuranik, Vedavati, G.1 aJeong, Yeon, Tae  uhttps://library.ncl.res.in/content/synthesis-and-stereochemistry-highly-crowded-n-benzylpiperidones-003604nas a2200385   4500008004100000022001400041245019700055210006900252260006700321300001200388490000700400520219800407653001002605653001202615653002402627653000902651653002102660653000802681653004902689653002602738653004602764653000902810653002702819653002202846100002302868700002302891700003402914700002502948700002002973700002202993700002403015700002603039700002403065856012903089       2013                        eng d  a1747-027700aDesign, synthesis, structural characterization by IR, 1H, 13C, 15N, 2D-NMR, X-ray diffraction and evaluation of a new class of phenylaminoacetic acid benzylidene hydrazines as pfENR inhibitors0 aDesign synthesis structural characterization by IR 1H 13C 15N 2D  a111 RIVER ST, HOBOKEN 07030-5774, NJ USAbWILEY-BLACKWELLcJUN  a715-7290 v813 a<p>Recent studies have revealed that plasmodial enoyl-ACP reductase (pfENR, FabI), one of the crucial enzymes in the plasmodial type II fatty acid synthesis II (FAS II) pathway, is a promising target for liver stage malaria infections. Hence, pfENR inhibitors have the potential to be used as causal malarial prophylactic agents. In this study, we report the design, synthesis, structural characterization and evaluation of a new class of pfENR inhibitors. The search for inhibitors began with a virtual screen of the iResearch database by molecular docking. Hits obtained from the virtual screen were ranked according to their Glide score. One hit was selected as a lead and modified to improve its binding to pfENR; from this, a series of phenylamino acetic acid benzylidene hydrazides were designed and synthesized. These molecules were thoroughly characterized by IR, 1H, 13C, 15N, 2D-NMR (COSY, NOESY, 1H-13C, 1H-15N HSQC and HMBC), and X-ray diffraction. NMR studies revealed the existence of conformational/configurational isomers around the amide and imine functionalities. The major species in DMSO solution is the E, E form, which is in dynamic equilibrium with the Z, E isomer. In the solid state, the molecule has a completely extended conformation and forms helical structures that are stabilized by strong hydrogen bond interactions, forming a helical structure stabilized by N-H...O interactions, a feature unique to this class of compounds. Furthermore, detailed investigation of the NMR spectra indicated the presence of a minor impurity in most compounds. The structure of this impurity was deduced as an imidazoline-4-one derivative based on 1H-13C and 1H-15H HMBC spectra and was confirmed from the NOESY spectra. The molecules were screened for in vitro activity against recombinant pfENR enzyme by a spectrophotometric assay. Four molecules, viz. 17, 7, 10, and 12 were found to be active at 7, 8, 10, and 12m concentration, respectively, showing promising pfENR inhibitory potential. A classification model was derived based on a binary QSAR approach termed recursive partitioning (RP) to highlight structural characteristics that could be tuned to improve activity.</p>10aADMET10adocking10aenoyl-ACP reductase10aFabI10ahydrogen bonding10aNMR10aphenylaminoacetic acid benzylidene hydrazine10aPlasmodium falciparum10aPlasmodium falciparum enoyl-ACP reductase10aQSAR10arecursive partitioning10aX-ray diffraction1 aSamal, Ramanuj, P.1 aKhedkar, Vijay, M.1 aPissurlenkar, Raghuvir, R. S.1 aBwalya, Angela, Gono1 aTasdemir, Deniz1 aJoshi, Ramesh, A.1 aRajamohanan, P., R.1 aPuranik, Vedavati, G.1 aCoutinho, Evans, C.  uhttps://library.ncl.res.in/content/design-synthesis-structural-characterization-ir-1h-13c-15n-2d-nmr-x-ray-diffraction-and-0