Synthesis of brominated 2-phenitidine derivatives as valuable inhibitors of cholinesterases for the treatment of alzheimer's disease

The present study reports the synthesis of a series N-substituted derivatives of brominated 2-phenitidine. First, the reaction of 2-phenitidine [1] with benzenesulfonyl chloride [2] in aqueous media yielded N-[2-ethoxyphenyl] benzenesulfonamide [3], which was then subjected to bromination with bromine in the presence of glacial acetic acid to give N-[4,5-dibromo-2-ethoxyphenyl]benzenesulfonamide [4]. Secondly, the product [4] on further treatment with alkyl/aryl halides [5a-l] in the presence of lithium hydride [LiH] produced twelve new derivatives of N-substituted sulfonamides [6a-l]. These were characterized by 1H-NMR spectrum and screened against acetylcholinesterase [AChE], butyrylcholinesterase [BChE] and lipoxygenase [LOX] and were found to be valuable inhibitors of butyrylcholinesterase [BChE] and acetylcholinesterase [AChE]. Few of these synthesized derivatives were also active against lipoxygenase [LOX]. It was concluded from this investigation that these derivatives were moderate inhibitors of cholinesterases and are also ideally suited for further structural modification to obtain more potent and less cytotoxic therapeutic agents for the treatment of Alzheimer's disease

Synthesis, spectral characterization and enzyme inhibition studies of different chlorinated sulfonamides

Sulfonamides are adherent to a biologically dynamic category of compounds and are under consideration of many organic synthetic researches to synthesize pharmacologically important compounds. In this demonstrated research work, a benignant series of chlorinated sulfonamides were synthesized and screened against different enzymes. These various chlorinated sulfonamides [3a-i] were set up by pairing of different substituted anilines [2a-i] with 4-chlorobenzenesulfonyl chloride [1] under basic pH in an aqueous media. The structures of the synthesized chlorinated sulfonamides were furnished by [1] H-NMR, IR and EI-MS. The different enzymes used for the evaluation of bioactivity of all the synthesized compounds were urease, butyrylcholinesterase [BChE] and lipoxygenase [LOX]. All the compounds exhibited good inhibitory activities against these enzymes but the strong activity was shown against BChE and hence can be employed for discovery of 'lead' compounds against Alzheimer's disease [AD]

Synthesis of some new biologically active N-substituted-2''- [[phenylsulfonyl][piperidin-1-yl]amino]acetamide derivatives

A new series of N-aryl/aralkyl substitued-2"-[[phenylsulfonyl][piperidin-1-yl]amino]acetamide [7a-k] was synthesized. These derivatives were geared up by the pairing of benzenesulfonyl chloride [4] with 1-aminopiperidine [5] under dynamic pH control in aqueous media to afford parent compound N-[Piperidin-1-yl] benzenesulfonamide [6], followed by the substitution at nitrogen atom with different electrophiles N-aryl/aralkyl-substituted-2-bromoacetamides [3a-k] in the presence of sodium hydride [NaH] and N,N-Dimethylformamide [DMF] to give a new series of Nsubstituted derivatives of acetamide [7a-k] bearing piperidine moiety. All the synthesized compounds were confirmed on the basis of IR, EIMS and 1H-NMR spectral data. The synthesized compounds were evaluated against acetylcholinesterase and butyrylcholinesterase [AChE and BChE] respectively and lipoxygenase [LOX] enzymes. Almost all the synthesized compounds displayed promising activity but few of them remained inactive against lipoxygenase enzymes.

Synthesis, characterization and biological screening of N-substituted derivatives of 5-benzyl-1,3,4-oxadiazole-2yl-2''-sulfanyl acetamide

A series of new N-substituted derivatives of 5-benzyl-1, 3, 4-oxadiazole-2yl-2''-sulfanyl acetamide [6a-n] were synthesized in three phases. The first phase involved the sequentially converting phenyl acetic acid into ester, hydrazide and finally cyclized in the presence of CS[2] to afford 5-benzyl-1, 3, 4-oxadiazole-2-thiol. In the second phase N-substituted-2-bromoacetamides were prepared by reacting substituted amines with bromoacetyl bromide in basic media. In the third phase, 5-benzyl-1,3,4-oxadiazole-2-thiol was stirred with N-substituted-2-bromoacetamides in the presence of N,N-dimethyl formamide [DMF] and sodium hydride [NaH] to get the target compounds. Spectral techniques were used to confirm the structures of synthesized compounds. Synthesized compounds were screened against butyrylcho linesterase [BChE], acetylcholinesterase [AChE], and lipoxygenase enzymes [LOX] and were found to be relatively more active against acetylcholinesterase

Synthesis of biologically active O-substituted derivatives of 1-[[3, 5-dichloro-2-hydroxyphenyl]sulfonyl]piperidine

In the present work, a series of 2-O-substituted derivatives of 1-[[3,5-dichloro-2-hydroxy phenyl] sulfonyl]piperidine [5a-j] were synthesized. These derivatives were geared up by the coupling of 3,5-dichloro-2-hydroxy benzenesulfonyl chloride [1] with piperidine [2] under dynamic pH control in aqueous media to form parent compound 1-[[3,5-dichloro-2-hydroxyphenyl]sulfonyl]piperidine [3], followed by the substitution at oxygen atom with different electrophiles [4a-j] in the presence of sodium hydride [NaH] and dimethyl formamide [DMF] to give a series of Osubstituted derivatives of sulfonamides bearing piperidine nucleus 5a-j. The synthesized O-substituted sulfonamides were spectrally characterized. The bioactivity of all the synthesized compounds were evaluated against lipoxygenase [LOX], acetylcholinesterae [AChE] and butyrylcholinesterase [BChE] enzymes and found to be having talented activity against butyrylcholinesterase enzyme