6938-07-4Relevant articles and documents
Synthesis and evaluation of novel bone-targeting ibuprofen prodrug based on dendritic aspartic acid
Zhao, Yi,Zhao, Ze,Cui, Yamin,Chen, Changqing,Xie, Changwei,Yang, Yang
, p. 329 - 337 (2021/09/14)
Bone diseases, such as osteoarthritis, osteomyelitis, are notoriously difficult diseases to treat due to the comparatively low blood flows in bone tissue. Ibuprofen is a well-known potent non-steroid anti-inflammatory drug (NSAID), which plays an important role in the treatment of osteoarthritis. However, its poor bone-targeting ability hinders its further application. Herein, several novel dendritic aspartic acid-modified ibuprofen prodrugs were designed and further synthesized. The stability of these prodrugs was investigated in buffer solutions and plasma, respectively. In addition, the solubility, hydroxyapatite (HAP) binding, cytotoxicity, acute toxicity, and bone targeting ability in vivo were all evaluated. All the novel prodrugs showed the superior physicochemical property in vitro. The bone-targeting study in vivo provided the evidence that these prodrugs could increase ibuprofen levels in bone tissue, among which the Ibu-Asp8 showed the best affinity due to the increased aspartic acid residues conjugated to the drug. The dendritic Asp carriers were efficient as bone-targeting moieties, and the conjugation with ibuprofen ensured the increased accumulation of drugs in the bone region. In general, our findings provided a novel and effective drug for the treatment of bone diseases.
Synthesis and structural characterization of 20-membered macrocyclic rings bearing: Trans -chelating bis(N-heterocyclic carbene) ligands and the catalytic activity of their palladium(ii) complexes
Thapa, Rajesh,Kilyanek, Stefan M.
, p. 12577 - 12590 (2019/08/26)
Macrocycles consisting of a 20-membered ring containing two imidazolium salt functionalities and of the formula [PhCH2N(CH2CH2CH2)Im(CH2CH2CH2)2][Br]2 (Im = imidazole = 3a, benzimidazole = 3b) were synthesized in 70-75% yields. These salts serve as precursors to macrocycles containing two N-heterocyclic carbene (NHC) moieties. Reaction of the macrocyclic salts 3a and 3b with silver oxide afforded macrocyclic-bis(NHC)silver(i) complexes 4a and 4b. Single-crystal X-ray diffraction studies of macrocyclic-bis(NHC)silver(i) complex 4a revealed a tetranuclear silver core with a short Ag-Ag distance (2.9328 ?). Complexes 4a and 4b serve as carbene transfer reagents to Pd. The treatment of macrocyclic-bis(NHC)silver(i) complexes 4a and 4b with one equivalent of PdCl2(MeCN)2 in methylene chloride afforded square-planar trans-macrocyclic-bis(NHC)Pd(ii)X2 complexes 5a and 5b. Preliminary screening of these palladium complexes showed they are competent precatalysts for Heck and Suzuki coupling reactions.
Aza-Michael mono-addition using acidic alumina under solventless conditions
Bosica, Giovanna,Abdilla, Roderick
, (2016/07/07)
Aza-Michael reactions between primary aliphatic and aromatic amines and various Michael acceptors have been performed under environmentally-friendly solventless conditions using acidic alumina as a heterogeneous catalyst to selectively obtain the corresponding mono-adducts in high yields. Ethyl acrylate was the main acceptor used, although others such as acrylonitrile, methyl acrylate and acrylamide were also utilized successfully. Bi-functional amines also gave the mono-adducts in good to excellent yields. Such compounds can serve as intermediates for the synthesis of anti-cancer and antibiotic drugs.
