A new synthetic method and GABA transporter inhibitory activities of Tiagabine and its analogues are described. The key intermediates 4-tosyl-1,1-diaryl/heteroaryl-l-butene 10a-10e were synthesized by Wittig reaction,...A new synthetic method and GABA transporter inhibitory activities of Tiagabine and its analogues are described. The key intermediates 4-tosyl-1,1-diaryl/heteroaryl-l-butene 10a-10e were synthesized by Wittig reaction, and followed by N-alkylation with （R）-3-piperidinecarboxylate. The resulting N-diheterocyclylalkenylpiperidine-3-carboxylic acid ester 11a-11e were saponified and then acidified to.get the target compounds 1a-1e. The preliminary bioassays show that compound 1a-1e exhibited excellent inhibition of [ 3H ]-GABA uptake in vitro of culture ceils.展开更多
This research work deals with formulation and evaluation of nanosized Tiagabine loaded bio-flexy films consisting of Cocos nucifera biopolymer(isolated from coconut kernels).Prepared formulations were administered thr...This research work deals with formulation and evaluation of nanosized Tiagabine loaded bio-flexy films consisting of Cocos nucifera biopolymer(isolated from coconut kernels).Prepared formulations were administered through soft palatal route for brain targeting for epilepsy treatment.Soft palate,part of oral mucosa serves as novel drug delivery platform and mucoadhesive site for systemic drug delivery.It provides sustained and controlled drug delivery system,does not interfere with patient’s regular activities like talking,eating,drinking,etc.It bypasses first-pass metabolism in the liver,reduces dose frequency and minimizes drug’s side effects.Tiagabine,anticonvulsant drug possesses t1/2:7-9 h(low);Protein binding:96%;Water solubility:22 mg/L,acts as selective gamma amino butyric acid(GABA)reuptake inhibitor.Cocos nucifera biopolymer used as bio-excipient to prepare bio-flexy films due to its biodegradability,biocompatibility,non-toxicity,non-irritantancy on soft palatal surface along with inbuilt filmability,mucoadhesive properties.Nanosized drug loaded bio-flexy films were formulated using standard solvent casting method.Bio-flexy films were prepared using varying ratios of nanosized Tiagabine:isolated Cocos nucifera biopolymer(FCT1-FCT6).These prepared formulations were compared with same ratios of nanosized Tiagabine:sodium carboxyl methyl cellulose standard polymer flexy films(FET1-FET6).The%yield of Cocos nucifera biopolymer was found to be 10.2±0.04%.Thickness of nanosized Tiagabine loaded bio-flexy films containing Cocos nucifera biopolymer(FCT1-FCT6)was ranging from 0.026±0.04 mm to 0.040±0.02 mm;Folding endurance:84-107;Surface pH:7.01±0.04 to 7.01±0.02;Weight uniformity:0.012±0.04 to 0.020±0.02;Drug content uniformity:69.5±0.35%to 72.9±0.26%;Swelling percentage:65±0.5%to 73±0.2%;Percentage moisture uptake(PTU):2.0±0.14%to 2.8±0.12%;Mucoadhesivity:20-90 min;Mucoretentivity:60-180 min.The drug release pattern for formulations FCT1-FCT6 containing Cocos nucifera biopolymer based on the T50%and T80%was found to be FCT1(1:0.5)>FCT5(1:6)>FCT3(1:3)>FCT2(1:1)>FCT4(1:5)>FCT6(1:10).Based on all above-mentioned evaluation parameters,FCT1(containing Tiagabine:Cocos nucifera biopolymer(1:0.5))bio-flexy film having R2=0.9221,Higuchi matrix as best fit model,follows anomalous transport release mechanism,T50%:38.45 h.,T80%:41.20 h.using BITS Software 1.12.Stability study revealed stable formulations.Prepared formulations were suitable for soft palatal delivery.展开更多
A new method for the synthesis of 4, 4-diaryl/diheteroaryl-3-butenyl derivatives of nipecotic acid as GABA transporter inhibitors is described. The key intermediates 4-tosyl-1, 1-diaryl/diheteroaryl-1-butene 10a-d wer...A new method for the synthesis of 4, 4-diaryl/diheteroaryl-3-butenyl derivatives of nipecotic acid as GABA transporter inhibitors is described. The key intermediates 4-tosyl-1, 1-diaryl/diheteroaryl-1-butene 10a-d were synthesized by Wittig reaction, and followed by alkylation with （R）-3-piperidinecarboxylate. The resulting N-cycloalkylated amino acid esters 11a-d were saponified and then acidified to get the target compounds 1a-d. The preliminary bioassays showed that la-d exhibited excellent inhibition of [3H]-GABA uptake in vitro of culture cells.展开更多
文摘A new synthetic method and GABA transporter inhibitory activities of Tiagabine and its analogues are described. The key intermediates 4-tosyl-1,1-diaryl/heteroaryl-l-butene 10a-10e were synthesized by Wittig reaction, and followed by N-alkylation with （R）-3-piperidinecarboxylate. The resulting N-diheterocyclylalkenylpiperidine-3-carboxylic acid ester 11a-11e were saponified and then acidified to.get the target compounds 1a-1e. The preliminary bioassays show that compound 1a-1e exhibited excellent inhibition of [ 3H ]-GABA uptake in vitro of culture ceils.
文摘This research work deals with formulation and evaluation of nanosized Tiagabine loaded bio-flexy films consisting of Cocos nucifera biopolymer(isolated from coconut kernels).Prepared formulations were administered through soft palatal route for brain targeting for epilepsy treatment.Soft palate,part of oral mucosa serves as novel drug delivery platform and mucoadhesive site for systemic drug delivery.It provides sustained and controlled drug delivery system,does not interfere with patient’s regular activities like talking,eating,drinking,etc.It bypasses first-pass metabolism in the liver,reduces dose frequency and minimizes drug’s side effects.Tiagabine,anticonvulsant drug possesses t1/2:7-9 h(low);Protein binding:96%;Water solubility:22 mg/L,acts as selective gamma amino butyric acid(GABA)reuptake inhibitor.Cocos nucifera biopolymer used as bio-excipient to prepare bio-flexy films due to its biodegradability,biocompatibility,non-toxicity,non-irritantancy on soft palatal surface along with inbuilt filmability,mucoadhesive properties.Nanosized drug loaded bio-flexy films were formulated using standard solvent casting method.Bio-flexy films were prepared using varying ratios of nanosized Tiagabine:isolated Cocos nucifera biopolymer(FCT1-FCT6).These prepared formulations were compared with same ratios of nanosized Tiagabine:sodium carboxyl methyl cellulose standard polymer flexy films(FET1-FET6).The%yield of Cocos nucifera biopolymer was found to be 10.2±0.04%.Thickness of nanosized Tiagabine loaded bio-flexy films containing Cocos nucifera biopolymer(FCT1-FCT6)was ranging from 0.026±0.04 mm to 0.040±0.02 mm;Folding endurance:84-107;Surface pH:7.01±0.04 to 7.01±0.02;Weight uniformity:0.012±0.04 to 0.020±0.02;Drug content uniformity:69.5±0.35%to 72.9±0.26%;Swelling percentage:65±0.5%to 73±0.2%;Percentage moisture uptake(PTU):2.0±0.14%to 2.8±0.12%;Mucoadhesivity:20-90 min;Mucoretentivity:60-180 min.The drug release pattern for formulations FCT1-FCT6 containing Cocos nucifera biopolymer based on the T50%and T80%was found to be FCT1(1:0.5)>FCT5(1:6)>FCT3(1:3)>FCT2(1:1)>FCT4(1:5)>FCT6(1:10).Based on all above-mentioned evaluation parameters,FCT1(containing Tiagabine:Cocos nucifera biopolymer(1:0.5))bio-flexy film having R2=0.9221,Higuchi matrix as best fit model,follows anomalous transport release mechanism,T50%:38.45 h.,T80%:41.20 h.using BITS Software 1.12.Stability study revealed stable formulations.Prepared formulations were suitable for soft palatal delivery.
文摘A new method for the synthesis of 4, 4-diaryl/diheteroaryl-3-butenyl derivatives of nipecotic acid as GABA transporter inhibitors is described. The key intermediates 4-tosyl-1, 1-diaryl/diheteroaryl-1-butene 10a-d were synthesized by Wittig reaction, and followed by alkylation with （R）-3-piperidinecarboxylate. The resulting N-cycloalkylated amino acid esters 11a-d were saponified and then acidified to get the target compounds 1a-d. The preliminary bioassays showed that la-d exhibited excellent inhibition of [3H]-GABA uptake in vitro of culture cells.
