- Carbonic anhydrase inhibitors: Design, synthesis, kinetic, docking and molecular dynamics analysis of novel glycine and phenylalanine sulfonamide derivatives
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The inhibition of two human cytosolic carbonic anhydrase isozymes I and II, with some novel glycine and phenylalanine sulfonamide derivatives were investigated. Newly synthesized compounds G1-4 and P1-4 showed effective inhibition profiles with KI values in the range of 14.66-315 μM for hCA I and of 18.31-143.8 μM against hCA II, respectively. In order to investigate the binding mechanisms of these inhibitors, in silico docking studies were applied. Atomistic molecular dynamic simulations were performed for docking poses which utilize to illustrate the inhibition mechanism of used inhibitors into active site of CAII. These sulfonamide containing compounds generally were competitive inhibitors with 4-nitrophenylacetate as substrate. Some investigated compounds here showed effective hCA II inhibitory effects, in the same range as the clinically used sulfonamide, sulfanilamide or mafenide and might be used as leads for generating enzyme inhibitors possibly targeting other CA isoforms which have not been yet assayed for their interactions with such agents.
- Fidan, Ismail,Salmas, Ramin Ekhteiari,Arslan, Mehmet,?entürk, Murat,Durdagi, Serdar,Ekinci, Deniz,?entürk, Esra,Co?gun, Sedat,Supuran, Claudiu T.
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p. 7353 - 7358
(2015/11/27)
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- 154. Asymmetric synthesis of 3-hydroxyprolines by photocyclization of C(1′)-substituted N-(2-benzoylethyl)glycine esters
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The chiral N-(2-benzoylethyl)-N-tosylglycine esters 5a-h and the α -amino-γ-keto ester 6 were prepared from γ-(tosylamino) alcohols 7a-h. Irradiation of compounds 5a-c, e gave cis-3-hydroxyproline esters 20-23 (Scheme 6), partly with complete asymmetric induction by the C(1′)-substituent, whereas 6 gave enantiomerically pure 4-hydroxy-4-phenyl-L-proline esters 24 in good yield but low de (Scheme 6). The de of the photocyclization depended on the nature and/or size of the C(1′)-substituents. Irradiation of ketones 5d and 5f, bearing H-atoms at C(γ) with respect to the keto function, gave cyclobutanols (Scheme 9) in low yields besides the preferred Norrish-type-II cleavage product. Cyclopentanol 25 was a by-product of the photocyclization of 5c as a result of H-C(δ) abstraction from the t-Bu group The structure of products 20, 22, and 24a, b was established by NMR or X-ray analyses.
- Steiner, Andre,Wessig, Pablo,Polborn, Kurt
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p. 1843 - 1862
(2007/10/03)
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- An Improved Synthesis of Pyrroles from N-p-Toluenesulfonylglycine Esters and α,β-Unsaturated Aldehydes and Ketones
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N-p-Toluenesulfonylglycine esters 2 condensed with α,β-unsaturated carbonyl compounds 1 in the presence of the non-nucleophilic base DBU to give hydroxypyrrolidines 3.Dehydration with phosphorous oxychloride-pyridine, followed by DBU mediated elimination
- Lash, Timothy D.,Hoehner, Michael C.
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p. 1671 - 1676
(2007/10/02)
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- SYNTHESE DE DERIVES DIAMIDIQUES N-PHOSPHORYLES D'AMINOACIDES
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Twenty seven phosphordiamides incorporating one (3,3') or two (5) α aminoester residues and seven aminoamide phosphodiesters (6) were synthetised starting generally from the corresponding tetrahedral phosphorus chlorides 1 and 7, respectively.
- Mulliez, M.
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p. 209 - 220
(2007/10/02)
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