Nε-Boc-L-lysine allyl ester hydrochloride

This work describes ultrasound-assisted phenol-yne addition of p-hydroxybenzaldehyde and propargylic ester of betaine hydrochloride giving only 2-((3-(4-formylphenoxy)allyl)oxy)-N,N,N-trimethyl-2-oxoethan-1-aminium chloride as a product at 100kHz 300W in water. The ultrasonic assisted phenol-yne addition was enhanced to chitosan chemistry. Phenolic chitosan derivatives were obtained by treatment of chitosan with o-, m- or p-hydroxybenzaldehyde followed by reduction of the formed CN bound by NaBH4. The phenolic chitosan derivatives (phenolic component) were involved in ultrasound-mediated reaction with propargylic ester of betaine hydrochloride (yne component). The reaction led to betaine chitosan derivatives in different degree of substitution as o-, m- and p-isomers. The phenolic and betaine derivatives were tested as antibacterial agents against E. coli in comparison with reference antibiotic Tetracycline. Betaine derivatives showed high antibacterial activity. The most effective polymer was p-isomer of high substituted betaine derivative and its activity was more than 2 times higher than the activity of Tetracycline. The nanoparticles based on this polymer were obtained by ionic gelation method. They had 2Rh 126nm, ξ-potential 20mV and were more effective than the corresponding chitosan derivative.

A series of dopamine agonists were studied on contraversive circling behavior in seven 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced hemiparkinsonian monkeys. The compounds selected included [1R,3S]3-(1' adamantyl)-1-aminomethyl-3,4-dihydro-5-6- dihydroxy-1H-2-benzopyran hydrochloride (A-77636), L-3,4-dihydroxyphenylalanine methyl ester hydrochloride ester (L-dopa-methyl ester), (-)-2-[N-propyl-N-(2-thienyl) ethyl-amino-5-hydroxy-tetralin]hydrochloride (N-0923), pergolide, (+)-(4aR)-trans-3,4,4a,5,6,10b-hexahydro-4-propyl-2H-n aphth[1,2-b]-1,2-oxazin-9-ol, naxagolide (PHNO), (+/-)6-chloro-7, 8-dihydroxy-2,3,4,5-tetrahydro-1-phenyl-1H-3-benzazepine hydrobromide, (+-) chloro-PB hydrobromide (SKF-81297) and (+-) 6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benza zep ine hydrobromide, (+-) chloro-APB hydrobromide (SKF-82958). The dose-effect relationship of each of these compounds was determined by measuring contraversive turns/120 min after an i.m. injection. There were marked differences in the potency and efficacy of the various compounds studied. The most potent compounds were the selective D2 agonists PHNO and N-0923. L-dopa methyl ester was equally effective, but much less potent. The D1 agonist A-77636 was equally effective. The D1 agonist SKF-82958 was also effective, but less potent. In the doses studied, the D1 agonist SKF-81297 was ineffective. With the exception of L-dopa methyl ester, the greater the D1/D2 affinity ratio, the greater the 50% of maximal dose to induce contraversive circling (r = 0.974, P < .05).

Spurred by significant progress in materials chemistry and drug delivery, charge-reversal nanocarriers are being developed to deliver anticancer formulations in spatial-, temporal- and dosage-controlled approaches. Charge-reversal nanoparticles can release their drug payload in response to specific stimuli that alter the charge on their surface. They can elude clearance from the circulation and be activated by protonation, enzymatic cleavage, or a molecular conformational change. In this review, we discuss the physiological basis for, and recent advances in the design of charge-reversal nanoparticles that are able to control drug biodistribution in response to specific stimuli, endogenous factors (changes in pH, redox gradients, or enzyme concentration) or exogenous factors (light or thermos-stimulation).