6587-25-3Relevant academic research and scientific papers
Phosphate-based self-immolative linkers for the delivery of amine-containing drugs
Dud, Mateja,Baszczyňski, Ond?ej,Procházková, Eli?ka,Tichotová, Markéta
, (2021/09/03)
Amine-containing drugs often show poor pharmacological properties, but these disadvan-tages can be overcome by using a prodrug approach involving self-immolative linkers. Accordingly, we designed L-lactate linkers as ideal candidates for amine delivery. Furthermore, we designed linkers bearing two different cargos (aniline and phenol) for preferential amine cargo release within 15 min. Since the linkers carrying secondary amine cargo showed high stability at physiological pH, we used our strategy to prepare phosphate-based prodrugs of the antibiotic Ciprofloxacin. Therefore, our study will facilitate the rational design of new and more effective drug delivery systems for amine-containing drugs.
Kinetics and mechanism of the anilinolysis of (2R,4R,5S)-(+)-2-chloro-3,4- dimethyl-5-phenyl-1,3,2-oxazaphospholidine 2-sulfide in acetonitrile
Barai, Hasi Rani,Lee, Hai Whang
experimental part, p. 1037 - 1041 (2012/05/20)
The nucleophilic substitution reactions of (2R,4R,5S)-(+)-2-chloro-3,4- dimethyl-5-phenyl-1,3,2-oxazapho-spholidine 2-sulfide (3) with substituted anilines (XC6H4NH2) and deuterated anilines (XC6H4ND2) are investigated kinetically in acetonitrile at 5.0 °C. The anilinolysis rate of 3 involving a cyclic five-membered ring is considerably fast because of small negative value of the entropy of activation (ΔS≠ = -2 cal mol-1 K -1) over considerably unfavorable enthalpy of activation (ΔH≠ = 18.0 kcal mol-1). Great enthalpy and small negative entropy of activation are ascribed to sterically congested transition state (TS) and bulk solvent structure breaking in the TS. A concerted S N2 mechanism with a backside nucleophilic attack is proposed on the basis of the secondary inverse deuterium kinetic isotope effects, k H/kD 1.
Kinetics and mechanism of the pyridinolysis of (2R,4R,5S)-(+)-2-chloro-3,4- dimethyl-5-phenyl-1,3,2-oxazaphospholidine 2-sulfide in acetonitrile
Barai, Hasi Rani,Lee, Hai Whang
scheme or table, p. 1047 - 1051 (2012/05/20)
The nucleophilic substitution reactions of (2R,4R,5S)-(+)-2-chloro-3,4- dimethyl-5-phenyl-1,3,2-oxa-zaphospholidine 2-sulfide with X-pyridines are investigated kinetically in acetonitrile at 5.0 °C. The free energy relationships for substituent X variations in the nucleophiles exhibit biphasic concave upwards with a break point at X = 3-Ac. Unusual positive ρX (= +4.73) and negative βX (= -0.75) values are obtained with the weakly basic pyridines, and rationalized by the isokinetic relationship with isokinetic temperature at tISOKINETIC = 39.3 °C. A concerted mechanism involving a change of nucleophilic attacking direction from a frontside attack with the strongly basic pyridines to a backside attack with the weakly basic pyridines is proposed on the basis of greater magnitudes of selectivity parameters (ρX = -6.15 and βX = 1.11) with the strongly basic pyridines compared to those (ρX = 4.73 and βX = -0.75) with the weakly basic pyridines.
Kinetics and mechanism of the anilinolysis of ethylene phosphorochloridate in acetonitrile
Barai, Hasi Rani,Lee, Hai Whang
experimental part, p. 4185 - 4190 (2012/03/26)
The nucleophilic substitution reactions of ethylene phosphorochloridate (1c) with substituted anilines (XC6H4NH2) and deuterated anilines (XC6H4ND2) are investigated kinetically in acetonit
ACID-CATALYZED HYDROLYSIS OF N-PHENYL PHOSPHORIC AMIDES. KINETIC IMPLICATION OF THE REACTION VIA THE O-PROTONATED INTERMEDIATE
Moerat, A.,Modro, T. A.
, p. 179 - 184 (2007/10/02)
Rates of the acid-catalyzed hydrolysis of N-phenyl dimethylphosphoramidate, 2-(phenylamino)-2-oxo-1,3,2-dioxaphospholan and 2-ethoxy-2-oxo-3-phenyl-1,3,2-oxazaphospholan, as well as of the corresponding non-cyclic monoester amidates were determined.In cyc
