- Synthesis and evaluation of novel bone-targeting ibuprofen prodrug based on dendritic aspartic acid
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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.
- Zhao, Yi,Zhao, Ze,Cui, Yamin,Chen, Changqing,Xie, Changwei,Yang, Yang
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p. 329 - 337
(2021/09/14)
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- N-HETEROCYCLIC CARBENE (NHC) BASED LIGANDS AND RELATED METHODS
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Polydentate macrocyclic NHCs (NHC ligands) and related methods are disclosed. Such ligands advantageously facilitate a variety of ligand coordination modes and stabilize oxidation states of metal complexes with a number of coordination environments and shapes. The NHC ligands described herein comprise pendant groups configured to facilitate a variety of reactions including: cis-trans isomerization, proton shuttling and facilitating changes in coordination environments as a result of redox reactions.
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Paragraph 0031
(2019/03/02)
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- 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
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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.
- Thapa, Rajesh,Kilyanek, Stefan M.
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p. 12577 - 12590
(2019/08/26)
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- RECYCLABLE CATALYSTS FOR CHLORINATION OF ORGANIC ACIDS AND ALCOHOLS
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The present invention discloses recyclable polymeric catalyst of Formula I, for chlorination of organic acids and alcohols using chlorinating agents such as carbonyl chloride, oxalyl chloride or thionyl chloride, wherein, ‘m’ on the pendent groups on polystyrene backbone can have values from 1 to 5 and R is the alkyl group ranging from C1 to C5.
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Paragraph 0063-0065
(2017/10/10)
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- Aza-Michael mono-addition using acidic alumina under solventless conditions
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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.
- Bosica, Giovanna,Abdilla, Roderick
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- O-benzenedisulfonimide as a reusable brnsted acid catalyst for hetero-michael reactions
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The hetero-Michael reactions among various oxygen, sulfur, and nitrogen nucleophiles and ,-unsaturated compounds were carried out in the presence of catalytic amounts of o-benzenedisulfonimide as Brnsted acid organocatalyst. The reaction conditions were very mild, and the yields of target products were good. The catalyst was easily recovered and purified, ready to be used in further reactions. This ability grants economic and ecological advantages. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.
- Barbero, Margherita,Cadamuro, Silvano,Dughera, Stefano
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p. 758 - 767
(2013/01/15)
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- New bidentate trans-chelating N-heterocyclic carbene ligands for palladium
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A family of imidazolium salts of the type [BnN(CH2CH 2CH2RIm)2]A·2[Cl] (Bn = CH2Ph; RIm = 1-methylimidazole (1a), 1-tert-butylimidazole (1b), 1-benzylimidazole (1c), 1-methylbenzimidazole (1d)), which contain a tertiary amine linking two imidazolium groups, has been synthesized. These imidazolium salts can be deprotonated with Ag2O to generate the Ag carbene complexes [{BnN(CH2CH2CH2 RIm)2}Ag].[AgCl2] (RIm = 1-methylimidazole (2a), 1-tert-butylimidazole (2b), 1-benzylimidazole (2c), 1-methylbenzimidazole (2d)). In the solid state 2d exists as an unusual tetramer, which consists of an [Ag2Cl4]2- core bridging two Ag(NHC) cations. Subsequent reaction of the Ag complexes with PdCl2(MeCN)2 generates Pd species of the type {BnN(CH 2CH2CH2RIm)2}PdCl 2 (RIm = 1-methylimidazole (3a), 1-tert-butylimidazole (3b), 1-benzylimidazole (3c), 1-methylbenzimidazole (3d)), which is a rare example of a family of Pd complexes that contain a bidentate trans-chelating N-heterocyclic carbene ligand. Compounds 3a and 3c were crystallographically characterized by X-ray crystallography and contain unusual 12-membered metallacycles. DFT calculations suggest that the preference for trans binding of the ligand is related to conformational effects of the linker. Compound 3b reacts with excess MeI to form {BnN(CH2CH2CH 2tBuIm)2}PdI2 (5b), a reaction in which we believe a Pd(IV) intermediate is generated. Compound 5b was crystallographically characterized. Compounds 3a-d are all active catalysts for the Heck reaction, and 3a can also catalyze the Suzuki reaction.
- Blakemore, James D.,Chalkley, Matthew J.,Farnaby, Joy H.,Guard, Louise M.,Hazari, Nilay,Incarvito, Christopher D.,Luzik, Eddie D.,Suh, Hee Won
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experimental part
p. 1818 - 1829
(2011/06/24)
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- Synthesis and characterization of N-substitutional ethylenediamine derivatives
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N-Substituted and N,N-disubstituted ethylenediamine derivatives were prepared rapidly in aqueous conditions from 30 to 76 % yields, respectively, on a multi-gram scale starting from inexpensive and commercially available starting materials. The steps involved Michael addition, hydrazinolysis and Curtius rearrangements. The highlight of this method lies on its convenience and economy in accessing these intermediates.
- Yao, Ri-Sheng,Jiang, Lai-En,Wu, Sheng-Hua,Deng, Sheng-Song,Yang, Yang
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experimental part
p. 3792 - 3794
(2012/01/05)
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- Synthesis of dendritic tryptophan derivatives and investigation on dendritic effects of their fluorescence and reactivity
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Two series of dendritic tryptophan derivatives have been synthesized and characterized, their emission spectra in different solvents and the reactivity of tryptophan were investigated and compared. There was a progressive shielding effect of the tryptophan in the emissive wavelengths of dendrimers increased with the size or generation of the dendritic shell.
- He, Dongsheng,He, Gu,Guo, Li
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p. 454 - 460
(2012/04/10)
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- Bone targeting prodrugs based on peptide dendrimers, synthesis and hydroxyapatite binding in vitro
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Novel bone targeting naproxen prodrugs with poly(aspartic acid) moieties and with two and three poly(aspartic acid) sequences peptide dendrimers were synthesized using a conventional method. The modified naproxen conjugates were incubated with hydroxyapatite in PBS at physiological conditions over 16h. The study revealed the hydroxyapatite binding properties of poly(aspartic acid) and it was found that the peptide dendrimer prodrugs exhibited a faster initial binding and a greater total binding. The obtained binding data in vitro indicated that the peptide dendrimers with poly(aspartic acid) sequences were useful for the development of new bone targeting molecules for drug delivery to bone.
- Ouyanga, Liang,Huang, Wencai,Hea, Gu,Guo, Li
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experimental part
p. 272 - 277
(2010/04/23)
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- Synthesis of second-and third-generation asp oligopeptide conjugated dendrimers for bone-targeting drug delivery
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The second-and third-generation multiple dendrimers based on naproxen in core and Asp(4-6) oligopeptides in periphery were synthesized in a convergent approach and well characterized by NMR and mass spectral (MS) techniques. These conjugates showed a high affinity to hydroxyapatite in vitro and provided an effective entry for the synthesis of a peptide dendrimer used for bone targeting.
- Ouyang, Liang,Pan, Junzhu,Zhang, Yu,Guo, Li
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body text
p. 4039 - 4052
(2010/02/27)
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- Synthesis and in-vitro activity of new 1β-methylcarbapenem derivatives as antibacterial agents
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The synthesis of a new series of 1β-methylcarbapenems having pyrrolidine and piperidine moieties is described. Their in-vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of substituents on the pyrrolidine ring was investigated. A particular compound III b having an oxime-pyrrolidine moiety showed the most potent antibacterial activity.
- Jung, Myung-Ho,Joon, Hee Hong,Cho, Jung-Hyuck,Oh, Chang-Hyun
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scheme or table
p. 780 - 786
(2009/04/07)
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- Natural phosphate modified with lithium nitrate: A new efficient catalyst for the construction of carbon-carbon, carbon-sulfur, and carbon-nitrogen bonds
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The addition of small amounts of lithium nitrate to natural phosphate followed by calcination gives a new catalyst Li/NP (weight ratio LiNO3/NP = 1/15). This material showed catalytic activity in the Michael addition of amines, mercaptans, and active methylene compounds to chalcone derivatives with high yields under mild reaction conditions. Li/NP is used as the catalyst for a facile synthesis of -amino acids, -sulfur acids, and 4 H-chromenes under heterogeneous conditions. The usual, undesirable byproducts from the Michael condensation such as 1,2-addition, bis-addition, and polymerization compounds are not observed with this method. The work-up procedure is simplified by simple filtration with the use of Li/NP.
- Zahouily, Mohamed,Mounir, Bahija,Cherki, Hind,Bahlaouan, Bouchaib,Rayadh, Ahmed,Sebti, Said
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p. 1203 - 1217
(2008/02/02)
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- Cerium(IV) ammonium nitrate (CAN) catalyzed aza-Michael addition of amines to α,β-unsaturated electrophiles
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Cerium(IV) ammonium nitrate (CAN) catalyzed facile and efficient aza-Michael addition of aromatic and aliphatic amines with α,β-unsaturated electrophiles in the absence of solvent under ultrasound irradiation.
- Duan, Zheng,Xuan, Xuejie,Li, Ting,Yang, Chenfei,Wu, Yangjie
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p. 5433 - 5436
(2007/10/03)
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- Solution chemistry of 1,15-bis(N,N-dimethyl)-5,11-dioxo-8-(N-benzyl)-1,4,8, 12,15-pentaazapentadecane with metal ions of biological interest - Insights toward active metal ion containing therapeutics and diagnostic agents
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The equilibrium constants of Cu(ii), Zn(ii), Ca(ii) and Gd(iii) with 1,15-bis(N,N-dimethyl)-5,11-dioxo-8-(N-benzyl)-1,4,8,12,15-pentaazapentadecane (La) have been studied at 25 °C and an ionic strength of 0.15 mol dm-3. Copper forms more stable complexes with La than the other metal ions investigated. This is probably due to the ease with which Cu(ii) deprotonates the nitrogen donor atoms of the amide groups. UV/Vis spectrophotometric data indicate tetradentate binding of the ligand towards copper in [CuLaH-1] and pentadentate binding in [CuL aH-2]. Octanol-water partition coefficients of Cu(ii)-La complexes indicate that although these species are largely hydrophilic, approximately 5.62% of the [CuLaH-1] complex goes into the organic phase. This percentage may promote dermal absorption of copper with a calculated penetration rate of 3.75 × 10-4 mm h-1. The [CuLaH-1] species which predominates at pH 7.4 is a poor mimic of native copper-zinc superoxide dismutase. Blood-plasma simulation studies predict that La is unable to increase the low molecular mass copper fraction in vivo. This has been confirmed by biodistribution patterns, which are similar to those of 64CuCl 2. The Royal Society of Chemistry 2006.
- Nomkoko, Thembelani E.,Jackson, Graham E.,Nakani, Bandile S.,Hunter, Roger
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p. 4029 - 4038
(2007/10/03)
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- Natural phosphate and potassium fluoride doped natural phosphate: Efficient catalysts for the construction of a carbon-nitrogen bond
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The application of natural phosphates doped with potassium fluoride as heterogeneous catalysts for the Michael addition of aromatic and aliphatic amines to α,β-unsaturated carbonyl compounds is presented. The natural phosphate catalyst can be regenerated and reused without loss of activity, which makes it an attractive alternative to homogeneous basic reagents. Doping natural phosphate with potassium fluoride significantly enhances the rate and yield of the reaction.
- Zahouily, Mohamed,Bahlaouan, Bouchaib,Rayadh, Ahmed,Sebti, Sa?d
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p. 4135 - 4138
(2007/10/03)
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- A green, ionic liquid and quaternary ammonium salt-catalyzed aza-Michael reaction of α,β-ethylenic compounds with amines in water
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The first environmentally benign, highly efficient conjugate addition of aliphatic amines to α,β-unsaturated compounds catalysed by simple quaternary ammonium salts and ionic liquids in the green solvent, water, is described.
- Xu, Li-Wen,Li, Jing-Wei,Zhou, Shao-Lin,Xia, Chun-Gu
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p. 183 - 184
(2007/10/03)
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- Synthesis and Stereochemistry of Some 3-Azabicyclo[3.3.1]nonane Derivatives
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Michael reactions of methyl (ethyl) 1-benzyl-4-oxopiperidine-3- carboxylates with a number of α,β-unsaturated carbonyl compounds result in formation of 6- and 6,8-substituted methyl (ethyl) 3-benzyl-9-oxo-3-azabicyclo[3.3.1]nonane-1-carboxylates. Stereochemical aspects of these reactions were studied, and some further transformations of the products were performed.
- Vafina,Yakhina,Khakimova,Spirikhin,Galin,Yunusov
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- Clay catalyzed chemoselective Michael type addition of aliphatic amines to α,β-ethylenic compounds
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Application of acidic clays as heterogeneous catalysts for the Michael type addition reaction of aliphatic amines to α,β-ethylenic compounds is presented. Aromatic amines do not participate in this transformation.
- Shaikh, Nadim S.,Deshpande, Vishnu H.,Bedekar, Ashutosh V.
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p. 9045 - 9048
(2007/10/03)
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- Metal Chelates of Medical Interest, III. - 99mTc Complexes with Tetradentate Dicatechol Ligands
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The dicatechol ligand bisamine hydrochloride, DIPACE (6), reduces the 99m- ion to lower valent 99mTc and subsequently forms a complex with the reduced 99mTc.The structure of benzylbisamine (4) is determined by X-ray crystallography.
- Hahn, Ekkehardt F.,Rupprecht, Stefan
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p. 487 - 491
(2007/10/02)
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- Benzimidazolinone derivatives
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Novel benzimidazolinone derivatives and therapeutically acceptable acid addition salts thereof, said compounds being useful as long acting neuroleptic agents.
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