- Functionalization of α-C(sp3)?H Bonds in Amides Using Radical Translocating Arylating Groups
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α-C?H arylation of N-alkylamides using 2-iodoarylsulfonyl radical translocating arylating (RTA) groups is reported. The method allows the construction of α-quaternary carbon centers in amides. Various mono- and disubstituted RTA-groups are applied to the arylation of primary, secondary, and tertiary α-C(sp3)?H-bonds. These radical transformations proceed in good to excellent yields and the cascades comprise a 1,6-hydrogen atom transfer, followed by a 1,4-aryl migration with subsequent SO2 extrusion.
- Radhoff, Niklas,Studer, Armido
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supporting information
p. 3561 - 3565
(2021/01/04)
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- Remote Regioselective Radical C-H Functionalization of Unactivated C-H Bonds in Amides: The Synthesis of gem-Difluoroalkenes
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The site-selective functionalization of unactivated aliphatic amines is an attractive and challenging synthetic approach. We herein report a general strategy for the remote site-selective functionalization of unactivated C(sp3)-H bonds in amides by photogenerated amidyl radicals to form gem-difluoroalkenes with trifluoromethyl-substituted alkenes. The site selectivity is controlled by a 1,5-hydrogen atom transfer (HAT) process of the amide. This photocatalyzed transformation shows both chemo- and site-selectivity, facilitating the formation of a secondary, tertiary, or quaternary carbon center.
- Hu, Qu-Ping,Cheng, Jing,Wang, Ying,Shi, Jie,Wang, Bi-Qin,Hu, Ping,Zhao, Ke-Qing,Pan, Fei
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supporting information
p. 4457 - 4462
(2021/05/26)
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- Photoredox-Catalyzed Difunctionalization of Unactivated Olefins for Synthesizing Lactam-Substituted gem-Difluoroalkenes
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Herein, the synthesis of lactam-substituted gem-difluoroalkenes has been developed through a photoredox-catalyzed radical cascade reaction. This developed photoredox-catalyzed, Br?nsted base-assisted intramolecular 5-exo-trig cyclization/intermolecular radical addition/β-fluoride elimination reaction offers a simple method for producing lactam, carbamate, or urea-substituted gem-difluoroalkenes with good functional group tolerance and high yields.
- Shi, Jie,Guo, Li-Yun,Hu, Qu-Ping,Liu, Yu-Tao,Li, Qing,Pan, Fei
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supporting information
p. 8822 - 8827
(2021/11/20)
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- Improvement of the anticancer activity of chlorambucil and ibuprofen via calix[4]arene conjugates
-
Background: One of the possible ways of improving the activity and selectivity profile of anticancer agents is to design drug carrier systems employing nanomolecules. Calix[4]arene derivatives and chlorambucil and ibuprofen are important compounds that ex
- Organista-Mateos, Ulises,Allende-Alarcón, Luis Isaac,Martínez-García, Marcos,Martínez-Klimova, Elena,Pedro-Hernández, Luis D.,Ramírez-ápan, Teresa
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p. 984 - 990
(2020/08/19)
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- Ethyl benzoate bearing pyrrolizine/indolizine moieties: Design, synthesis and biological evaluation of anti-inflammatory and cytotoxic activities
-
Two new series of ethyl benzoate bearing pyrrolizine and indolizine moieties 8–11 were synthesized and evaluated for their anti-inflammatory and anticancer activities. Among these derivatives, compounds 9a, 10b and 11b displayed in vivo anti-inflammatory
- Attalah, Khalid M.,Abdalla, Ashraf N.,Aslam, Akhmed,Ahmed, Muhammad,Abourehab, Mohammed A.S.,ElSawy, Naser A.,Gouda, Ahmed M.
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-
- Palladium-Catalyzed 2-(Neopentylsulfinyl)aniline Directed C–H Acetoxylation and Alkenylation of Arylacetamides
-
The 2-(neopentylsulfinyl)aniline directing group that promotes rapid palladium-catalyzed C–H acetoxylation and alkenylation of arylacetamides has been developed. The acetoxylation reaches completion within only 40 min at 100 °C and leads to the bis-functionalized products. Alternatively, the reaction can be carried out at room temperature, which is beneficial for sensitive substrates. For the alkenylation, we have developed a protocol in which easily available 1-substituted cyclopropanols were employed as equivalents of vinyl ketones.
- Barysevich, Maryia V.,Laktsevich-Iskryk, Marharyta V.,Krech, Anastasiya V.,Zhabinskii, Vladimir N.,Khripach, Vladimir A.,Hurski, Alaksiej L.
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supporting information
p. 937 - 943
(2020/02/25)
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- Antiproliferative Activity of Gold(I) N-Heterocyclic Carbene and Triphenylphosphine Complexes with Ibuprofen Derivatives as Effective Enzyme Inhibitors
-
A series of gold(I) complexes of ligand ibuprofen-alkynyl (but-3-yn-1-yl 2-(4-isobutylphenyl)propanoate, LE) with N-heterocyclic carbene (LC: 1,3-dimethylimidazol-2-ylidene) and triphenylphosphine (PPh3) ligands with formula (LE)Au (LC) (comple
- Tabrizi, Leila,Romanova, Julia
-
-
- Visible-Light-Assisted Gold-Catalyzed Fluoroarylation of Allenoates
-
A strategically novel synthetic method for the fluoroarylation of allenic ester was developed that enables the expedient construction of a host of β-fluoroalkyl-containing cinnamate derivatives. The reaction proceeds through visible-light-promoted gold redox catalysis, occurs smoothly under very mild reaction conditions, accommodates a large variety of functional groups, and more importantly allows the incorporation of fluorine and aryl groups with excellent regio- and stereoselectivity. The concomitant activation mode for both the allene motif and the hydrogen fluoride is key for the success of the reaction.
- Feng, Chao,Tang, Hai-Jun,Zhang, Xinggui,Zhang, Yu-Feng
-
supporting information
p. 5242 - 5247
(2020/02/28)
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- Photoredox Catalyst Free, Visible Light-Promoted C3?H Acylation of Quinoxalin-2(1H)-ones in Water
-
A method for the synthesis of 3-acyl quinoxalin-2(1H)-ones through visible-light promoted decarboxylative acylation of α-oxo-carboxylic acids with quinoxalin-2(1H)-ones was developed. The reaction was performed in aqueous phase and photoredox catalyst was not required to run the process. (Figure presented.).
- Lu, Juan,He, Xiang-Kui,Cheng, Xiao,Zhang, Ai-Jun,Xu, Guo-Yong,Xuan, Jun
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supporting information
p. 2178 - 2182
(2020/03/19)
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- NOVEL HIGH PENETRATION DRUGS AND COMPOSITIONS THEREOF FOR TREATMENT OF PARKINSON'S DISEASE
-
PROBLEM TO BE SOLVED: To provide novel high penetration compositions (HPCs) or high penetration prodrugs (HPPs) for treatment of Parkinson's disease. SOLUTION: The HPCs/HPPs are capable of being converted to parent active drugs or drug metabolites after c
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-
Paragraph 0140-0142
(2020/04/24)
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- One-pot method for the synthesis of 1-aryl-2-aminoalkanol derivatives from the corresponding amides or nitriles
-
We have identified a novel one-pot method for the synthesis of β-amino alcohols, which is based on C-H bond hydroxylation at the benzylic α-carbon atom with a subsequent nitrile or amide functional group reduction. This cascade process uses molecular oxygen as an oxidant and sodium bis(2-methoxyethoxy)aluminum hydride as a reductant. The substrate scope was examined on 30 entries and, although the respective products were provided in moderate yields only, the above simple protocol may serve as a direct and powerful entry to the sterically congested 1,2-amino alcohols that are difficult to prepare by other routes. The plausible mechanistic rationale for the observed results is given and the reaction was applied to a synthesis of a potentially bioactive target. This journal is
- Bobal, Pavel,Otevrel, Jan,Svestka, David
-
p. 25029 - 25045
(2020/07/14)
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- Synthesis method of ibuprofen ferulate and application of ibuprofen ferulate in preparation of immunosuppressive drugs
-
The invention discloses a synthesis method of ibuprofen ferulate and application of ibuprofen ferulate in preparation of immunosuppressive drugs. The preparation method comprises the following steps:slowly and dropwise adding a CH2Cl2 solution of SOCl2 in
- -
-
Paragraph 0025-0028
(2020/05/29)
-
- Synthesis method of ibuprofen caffeic acid ester and application of ibuprofen caffeic acid ester in preparation of immunosuppression drugs (by machine translation)
-
The invention discloses a synthesis method of ibuprofen caffeic acid ester and an application, of ibuprofen, in preparation of an immunosuppression drug slowly dropwise SOCl, with anhydrous dichloromethane and pyridine under stirring at room temperature.
- -
-
Paragraph 0026-0029
(2020/05/29)
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- L-Type Amino Acid Transporter 1 Enables the Efficient Brain Delivery of Small-Sized Prodrug across the Blood-Brain Barrier and into Human and Mouse Brain Parenchymal Cells
-
Membrane transporters have long been utilized to improve the oral, hepatic, and renal (re)absorption. In the brain, however, the transporter-mediated drug delivery has not yet been fully achieved due to the complexity of the blood-brain barrier (BBB). Because L-type amino acid transporter 1 (LAT1) is a good candidate to improve the brain delivery, we developed here four novel LAT1-utilizing prodrugs of four nonsteroidal anti-inflammatory drugs. As a result, all the prodrugs were able to cross the BBB and localize into the brain cells. The brain uptake of salicylic acid (SA) was improved five times, not only across the mouse BBB but also into the cultured mouse and human brain cells. The naproxen prodrug was also transported efficiently into the mouse brain achieving less peripheral exposure, but the brain release of naproxen from the prodrug was not improved. Contrarily, the high plasma protein binding of the flurbiprofen prodrug and the premature bioconversion of the ibuprofen prodrug in the mouse blood hindered the efficient brain delivery. Thus, the structure of the parent drug affects the successful brain delivery of the LAT1-utilizing prodrugs, and the small-sized LAT1-utilizing prodrug of SA constituted a successful model to specifically deliver its parent drug across the mouse BBB and into the cultured mouse and human brain cells.
- Montaser, Ahmed B.,J?rvinen, Juulia,L?ffler, Susanne,Huttunen, Johanna,Auriola, Seppo,Lehtonen, Marko,Jalkanen, Aaro,Huttunen, Kristiina M.
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p. 4301 - 4315
(2020/12/21)
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- Bisphosphonic acid compound for treating osteoporosis and preparation method thereof
-
The invention discloses a novel structure bisphosphonic acid compound, which has an ibuprofen structural unit and a phenylalanine structural unit. The pharmacological test shows that the bisphosphonicacid compound can be used for treating osteoporosis, an
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-
Paragraph 0022; 0023
(2019/04/26)
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- Synthesis, spectroscopic characterization, molecular docking and theoretical studies (DFT) of N-(4-aminophenylsulfonyl)-2-(4-isobutylphenyl) propanamide having potential enzyme inhibition applications
-
A mutual prodrug (1) of ibuprofen and sulphanilamide has been synthesized with dual activity and improved toxicity profile. The synthesized compound has been characterized by elemental analysis, FT-IR, 1HNMR, 13CNMR and ESI-MS. The m
- Asghar, Amina,Yousuf, Muhammad,Mubeen, Hifsa,Nazir, Rabia,Haruna, Kabiru,Onawole, Abdulmujeeb T.,Rasheed, Lubna
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supporting information
p. 2397 - 2404
(2019/01/25)
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- Direct meta-C?H Perfluoroalkenylation of Arenes Enabled by a Cleavable Pyrimidine-Based Template
-
The development of efficient and mild methods for the synthesis of organofluorine compounds is of foremost interest in various fields of chemistry. A direct pyrimidine-based selective meta-C?H perfluoroalkenylation of arenes involving several commercially
- Brochetta, Massimo,Borsari, Tania,Bag, Sukdev,Jana, Sadhan,Maiti, Siddhartha,Porta, Alessio,Werz, Daniel B.,Zanoni, Giuseppe,Maiti, Debabrata
-
supporting information
p. 10323 - 10327
(2019/07/18)
-
- Chemospecific Cyclizations of α-Carbonyl Sulfoxonium Ylides on Aryls and Heteroaryls
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The functionalization of aryl and heteroaryls using α-carbonyl sulfoxonium ylides without the help of a directing group has remained so far a neglected area, despite the advantageous safety profile of sulfoxonium ylides. Described herein are the cyclizations of α-carbonyl sulfoxonium ylides onto benzenes, benzofurans and N-p-toluenesulfonyl indoles in the presence of a base in HFIP, whereas pyrroles and N-methyl indoles undergo cyclization in the presence of an iridium catalyst. Significantly, these two sets of conditions are chemospecific for each groups of substrates.
- Clare, Daniel,Dobson, Benjamin C.,Inglesby, Phillip A.,A?ssa, Christophe
-
supporting information
p. 16198 - 16202
(2019/11/03)
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- Synthesis, enzyme inhibitory kinetics, and computational studies of novel 1-(2-(4-isobutylphenyl) propanoyl)-3-arylthioureas as Jack bean urease inhibitors
-
In this article, synthesis of a novel 1-(2-(4-isobutylphenyl)propanoyl)-3-arylthioureas (4a–j) as jack bean urease inhibitors has been described. Freshly prepared 2-(4-isobutylphenyl) propanoyl isothiocyanate was treated with substituted aromatic anilines
- Abdul Fattah, Tanzeela,Saeed, Aamer,Channar, Pervaiz Ali,Ashraf, Zaman,Abbas, Qamar,Hassan, Mubashir,Larik, Fayaz Ali
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p. 434 - 447
(2018/01/26)
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- Synthesis, characterization, and in vitro cytotoxicity of a Kiteplatin-Ibuprofen Pt(IV) prodrug
-
The Pt(IV) prodrug of kiteplatin, cis-trans-cis-[PtCl2(RS-Ibuprofen-H)2(cis-1,4-DACH)], having in the axial positions two molecules of Ibuprofen, has been synthesised, characterized and tested in vitro. The aim was to potentiate the
- Curci, Alessandra,Denora, Nunzio,Iacobazzi, Rosa Maria,Ditaranto, Nicoletta,Hoeschele, James D.,Margiotta, Nicola,Natile, Giovanni
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p. 221 - 228
(2017/10/06)
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- Synthesis and antinociceptive evaluation of bioisosteres and hybrids of naproxen, ibuprofen and paracetamol
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The aim of this work was to design, synthesize and characterize the potential anti-nociceptive and anti-inflammatory activities of a new series of bioisosteres and hybrids from known non-steroidal anti-inflammatory drugs (NSAIDs). The compounds 4-(acetylamino)phenyl (2S)-2-(6-methoxy-2-naphthyl)propanoate (GUF-1) and 4-(acetylamino)phenyl 2-(R,S)-(4-isobutylphenyl)propanoate (GUF-2) were synthesized as hybrids (also known as heterodimers); whereas those named 2-(R,S)-(4-isobutylphenyl)-N-1H-tetrazol-5-ylpropanamide (GUF-3), (2S)-2-(6-methoxy-2-naphthyl)-N-1H-tetrazol-5-ylpropanamide (GUF-4), [2-(R,S)-N-hydroxy-2-[4-(2-methylpropyl)phenyl]propanamide] (GUF-5), and (2S)-N-hydroxy-2-(6-methoxy-2-naphthyl)propanamide (GUF-6) were synthesized as bioisosteres of the NSAIDs paracetamol, ibuprofen, and naproxen, respectively. All these compounds were characterized by spectroscopic and spectrometric analysis. Antinociceptive activity of GUF-1 to GUF-6 was evaluated using the formalin test in rats. Pharmacological responses of GUF-1, GUF-2 (hybrids), and GUF-5 (bioisostere) demonstrated significant antinociceptive effects; thus these compounds were assayed in an inflammation test like carrageenan-induced paw oedema in rats. Complete molecular docking of cyclooxygenase and the GUF-1 and GUF-2 hybrids showed high docking scores, compared to the reference drugs. Our data demonstrate that compounds GUF-1, GUF-2, and GUF-5 possesses antinociceptive and antiinflammatory activities resembling and improving those known for the traditional NSAIDs, paracetamol, naproxen and ibuprofen.
- González-Trujano, María Eva,Uribe-Figueroa, Gerardo,Hidalgo-Figueroa, Sergio,Martínez, Ana Laura,Déciga-Campos, Myrna,Navarrete-Vazquez, Gabriel
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p. 553 - 562
(2018/03/08)
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- Self-assembly of a ibuprofen-peptide conjugate to suppress ocular inflammation
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In the present study, we designed and synthesized a hydrogelator comprised of ibuprofen (IPF) and GFFY peptide linked through a cleavable ester bond. We found that the synthesized hydrogelator could spontaneously self-assemble into a hydrogel under a heat
- Yu, Xinxin,Zhang, Zhaoliang,Yu, Jing,Chen, Hao,Li, Xingyi
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p. 185 - 193
(2017/11/16)
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- Synthesis, characterization and urease inhibition studies of transition metal complexes of thioureas bearing ibuprofen moiety
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Starting from ibuprofen, a non-steroidal anti-inflammatory drug, N,N'-disubstituted thiourea derivatives were synthesized by refluxing the acid chloride of ibuprofen with potassium thiocyanate followed by substituted anilines to get N-2-(4-(2-methylpropyl
- Mumtaz, Amara,Arshad, Jahanzaib,Saeed, Aamer,Nawaz, Muhammad Azhar Hyat,Iqbal, Jamshed
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p. 3934 - 3940
(2018/09/29)
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- Novel polyfunctional esters of ibuprofen and ketoprofen with hypolipidemic, lipoxygenase inhibitory and enhanced anti-inflammatory activity
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Abstract: A series of ibuprofen and ketoprofen esters were designed and synthesised, incorporating an antioxidant moiety, such as quercetin and salicylic alcohol, as well as anti-inflammatory or neuroprotective components. They showed greatly increased ac
- Theodosis-Nobelos, Panagiotis,Tziona, Paraskevi,Poptsis, Anastasios,Athanasekou, Chrysoula,Kourounakis, Panos N.,Rekka, Eleni A.
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p. 461 - 472
(2017/01/28)
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- Synthesis and anti-inflammatory effects of a series of novel 9-O-substituted berberine derivatives
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Berberine owns multiple pharmacological activities, especially anti-inflammatory activity. To enhance the anti-inflammatory therapeutic efficiency of berberine, a series of novel 9-O-substituted berberine derivatives (5a–5d) were synthesized and their anti-inflammatory activities were evaluated. 13C-NMR, 1H-NMR, IR and high resolution mass spectrum (HRMS) results indicated that these derivatives were successfully synthesized. The xylene-induced inflammatory mice model demonstrated that these derivatives showed dose-dependent inhibition of ear inflammatory swelling. Comparing to berberine, ibuprofen and naproxen-modified berberine derivatives enhanced anti-inflammatory activities, while aspirin and nicotinic acid-modified berberine derivatives showed lower anti-inflammatory effects at the same dosages. This could be attributed to the enhanced inhibition of secretion of cytokines, including interleukin-6 and tumor necrosis factor-α, by ibuprofen and naproxen berberine derivatives, while aspirin and nicotinic acid berberine derivatives showed lower inhibition of tumor necrosis factor-α than berberine. These results suggest that ibuprofen and naproxen-modified berberine derivatives are promising new anti-inflammatory drug candidates.
- Liu, Zhenbao,Wang, Xiaohong,Zhang, Hang,Zhang, Shanshan,Li, Yiqian,Liu, Yanfei,Peng, Dongming
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p. 672 - 679
(2017/02/15)
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- A general strategy to add diversity to ruthenium arene complexes with bioactive organic compounds: Via a coordinated (4-hydroxyphenyl)diphenylphosphine ligand
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Esterification of (4-hydroxyphenyl)diphenylphosphine, coordinated to the [Ru(η6-p-cymene)Cl2] fragment, allows a series of bioactive carboxylic acids to be introduced directly into the organometallic molecule. Evaluation of the compounds on human ovarian cancer cells reveals synergistic enhancements in their antiproliferative activity relative to their bioactive organic and organometallic precursors.
- Biancalana, Lorenzo,Batchelor, Lucinda K.,De Palo, Alice,Zacchini, Stefano,Pampaloni, Guido,Dyson, Paul J.,Marchetti, Fabio
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supporting information
p. 12001 - 12004
(2017/09/25)
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- Synthesis, spectroscopic and electrochemical characterization of secnidazole esters
-
We report a low-cost, less toxic to environment and simple method for the esterification of secnidazole. This is first comprehensive structural characterization of novel secnidazole esters by the spectroscopic and electrochemical methods. The important EI
- Shahid, Hafiz Abdullah,Jahangir, Sajid,Hanif, Muddasir,Xiong, Tianrou,Muhammad, Haji,Wahid, Sana,Yousuf, Sammer,Qureshi, Naseem
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p. 792 - 802
(2017/08/26)
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- Enantioselective Decarboxylative Cyanation Employing Cooperative Photoredox Catalysis and Copper Catalysis
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The merger of photoredox catalysis with asymmetric copper catalysis have been realized to convert achiral carboxylic acids into enantiomerically enriched alkyl nitriles. Under mild reaction conditions, the reaction exhibits broad substrate scope, high yields and high enantioselectivities. Furthermore, the reaction can be scaled up to synthesize key chiral intermediates to bioactive compounds.
- Wang, Dinghai,Zhu, Na,Chen, Pinhong,Lin, Zhenyang,Liu, Guosheng
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supporting information
p. 15632 - 15635
(2017/11/14)
-
- Design, Synthesis, and Biological Evaluation of Novel Selenium (Se-NSAID) Molecules as Anticancer Agents
-
The synthesis and anticancer evaluation of novel selenium-nonsteroidal anti-inflammatory drug (Se-NSAID) hybrid molecules are reported. The Se-aspirin analogue 8 was identified as the most effective agent in reducing the viability of different cancer cell
- Plano, Daniel,Karelia, Deepkamal N.,Pandey, Manoj K.,Spallholz, Julian E.,Amin, Shantu,Sharma, Arun K.
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p. 1946 - 1959
(2016/03/22)
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- Synthesis, characterization, and biological evaluation of furoxan coupled ibuprofen derivatives as anti-inflammatory agents
-
A series of furoxan-based nitric oxide releasing ibuprofen derivatives were synthesized and tested for their anti-inflammatory, analgesic, ulcerogenic, lipid peroxidation, and hepatotoxic properties. The compounds exhibited more protection than ibuprofen with regard to gastric toxicity. Among the tested compounds 4-[2-[2-(4-isobutylphenyl)propanamido]ethoxycarbonyl]-3-methylfuroxan and 4-[2-[2-(4-isobutylphenyl)propanoyl]hydrazinecarbonyl]-3-phenylfuroxan emerged as most active anti-inflammatory agents with reduced gastrotoxicity. The results showed that incorporation of NO donating group caused a moderate increase in anti-inflammatory activity with a marked decrease in gastric ulcerations compared to their parent drug ibuprofen. A molecular docking study of all the compounds was also performed to provide the binding modes of COX-1 enzyme. Among all the titled compounds, 4-[2-[2-(4-isobutylphenyl)propanamido]ethoxycarbonyl]-3-methylfuroxan was found to be most potent and have high docking score showing favorable orientation within the COX-1 binding site.
- Amir, Mohd,Akhter, Mohd Wasim,Alam, Ozair
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p. 493 - 508
(2016/03/19)
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- Design, synthesis, and biological evaluation of some novel pyrrolizine derivatives as COX inhibitors with anti-inflammatory/analgesic activities and low ulcerogenic liability
-
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed anti-inflammatory and pain relief medications. However, their use is associated with many drawbacks, including mainly serious gastric and renal complications. In an attempt to
- Gouda, Ahmed M.,Ali, Hamed I.,Almalki, Waleed H.,Azim, Mohamed A.,Abourehab, Mohammed A.S.,Abdelazeem, Ahmed H.
-
-
- Synthesis and biological evaluation of C(5)-substituted derivatives of leukotriene biosynthesis inhibitor BRP-7
-
Pharmacological intervention with 5-lipoxygenase (5-LO) pathway leading to suppression of leukotriene (LT) biosynthesis is a clinically validated strategy for treatment of respiratory and cardiovascular diseases such as asthma and atherosclerosis. Here we describe the synthesis of a series of C(5)-substituted analogues of the previously described 5-LO-activating protein (FLAP) inhibitor BRP-7 (IC50?=?0.31?μM) to explore the effects of substitution at the C(5)-benzimidazole (BI) ring as a strategy to increase the potency against FLAP-mediated 5-LO product formation. Incorporation of polar substituents on the C(5) position of the BI core, exemplified by compound 11 with a C(5)-nitrile substituent, significantly enhances the potency for suppression of 5-LO product synthesis in human neutrophils (IC50?=?0.07?μM) and monocytes (IC50?=?0.026?μM).
- Levent, Serkan,Gerstmeier, Jana,Olga?, Abdurrahman,Nikels, Felix,Garscha, Ulrike,Carotti, Andrea,Macchiarulo, Antonio,Werz, Oliver,Banoglu, Erden,?al??kan, Burcu
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supporting information
p. 510 - 519
(2016/07/19)
-
- SUBSTITUTED CYCLIC ETHER POLYMERS, AND CONJUGATES AND USES THEREOF
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Disclosed herein are substituted cyclic ether monomers, polymers, and drug conjugates thereof, which are useful for the treatment of diseases and conditions of the oral cavity. In particular, disclosed herein are monomers of Formula (I), polymers of Formu
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-
Paragraph 0099
(2016/09/22)
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- NSAIDs do not require the presence of a carboxylic acid to exert their anti-inflammatory effect – why do we keep using it?
-
The carboxylic acid group (–COOH) present in classical NSAIDs is partly responsible for the gastric toxicity associated with the administration of these drugs. This concept has been extensively proven using NSAID prodrugs. However, the screening of NSAIDs
- Ullah, Nasir,Huang, Zhangjian,Sanaee, Forough,Rodriguez-Dimitrescu, Alexandra,Aldawsari, Fahad,Jamali, Fakhreddin,Bhardwaj, Atul,Islam, Nazar Ul,Velázquez-Martínez, Carlos A.
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p. 1018 - 1028
(2016/10/09)
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- Phillygenin ibuprofen ester, preparation and applications thereof
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The present invention provides a phillygenin ibuprofen ester pharmaceutical compound represented by a formula (I), and a preparation method thereof, and applications of the phillygenin ibuprofen ester pharmaceutical compound in antivirus, fever relieving,
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-
Paragraph 0058-0059
(2017/03/08)
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- Semisynthetic hybrids of boswellic acids: A novel class of potential anti-inflammatory and anti-arthritic agents
-
A series of hybrid molecules 7-13 of boswellic acid (BA)/11-keto-β-boswellic acid (KBA) 1/2 with well-known anti-inflammatory drugs (i.e. aspirin, naproxen, ibuprofen and cinnamic acid) have been synthesized and evaluated for their anti-inflammatory and a
- Chaturvedi, Devdutt,Dwivedi, Parmesh Kumar,Chaturvedi, Amit K.,Mishra, Nisha,Siddiqui,Mishra, Vorenda
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p. 2799 - 2812
(2015/02/19)
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- Synthesis of oxazolines from amides via palladium-catalyzed functionalization of unactivated C(sp3)-H bond
-
A complementary method that enables the expeditious synthesis of oxazolines from amides via Pd-catalyzed C(sp3)-H functionalization has been described. Preliminary studies indicate that the reaction might go through a chlorination/nucleophilic cyclization sequence, and the high efficiency of this sequence is enhanced by the in situ cyclative capture of the chlorinated intermediate. The resulting oxazolines can be further converted into the corresponding β-amino alcohols without chromatography.
- Li, Bo,Wang, Si-Qing,Liu, Bin,Shi, Bing-Feng
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supporting information
p. 1200 - 1203
(2015/03/14)
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- Palladium(II)-catalyzed directed trifluoromethylthiolation of unactivated C(sp3)-H bonds
-
The synthesis of trifluoromethylthiolated aliphatic acid derivatives by Pd-catalyzed C(sp3)-H bond functionalization was developed. Using a bidentate directing group, the direct and selective introduction of a SCF3 moiety was possible on a range of amides with remarkable selectivity for C(sp3)-centers with an electrophilic SCF3 source and pivalic acid as an additive. This work constitutes an example of the unactivated C(sp3)-SCF3 bond formation by C-H activation offering a new access to relevant molecules.
- Xiong, Heng-Ying,Besset, Tatiana,Cahard, Dominique,Pannecoucke, Xavier
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p. 4204 - 4212
(2015/05/05)
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- Novel penicillin analogues as potential antimicrobial agents; Design, synthesis and docking studies
-
A number of penicillin derivatives (4a-h) were synthesized by the condensation of 6-amino penicillinic acid (6-APA) with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF) using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 ?. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents.
- Ashraf, Zaman,Bais, Abdul,Manir, Md. Maniruzzaman,Niazi, Umar
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- Synthesis and Evaluation of Novel Erlotinib-NSAID Conjugates as More Comprehensive Anticancer Agents
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A series of novel anticancer agents were designed and synthesized based on coupling of different nonsteroidal anti-inflammatory drugs (NSAIDs) with the epidermal growth-factor receptor (EGFR) tyrosine kinase inhibitor, erlotinib. Both the antiproliferative and pharmacokinetic activity of the target compounds were evaluated using HCC827 and A431 tumor cell lines. Among the derivatives made, compounds 10a, 10c, and 21g showed superb potency, comparable to that of erlotinib. Furthermore, preliminary SAR analysis showed that when the NSAIDs were conjugated via linkage to C-6 OH versus linkage to C-7 OH of the quinazoline nucleus, superior anticancer activity was achieved. Finally, the in vitro pharmacokinetic profile of several conjugates demonstrated the desired dissociation kinetics as the coupled molecules were effectively hydrolyzed, releasing both erlotinib and the specific NSAID in a time-dependent manner. The conjugation strategy represents a unique and simplified approach toward combination therapy, particularly for the treatment of cancers where both EGFR overexpression and inflammation play a direct role in disease progression.
- Zhang, Yanmei,Tortorella, Micky D,Liao, Jinxi,Qin, Xiaochu,Chen, Tingting,Luo, Jinfeng,Guan, Jiantong,Talley, John J,Tu, Zhengchao
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p. 1086 - 1090
(2015/10/20)
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- Synthesis of coenzyme A thioesters using methyl acyl phosphates in an aqueous medium
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Regioselective S-acylation of coenzyme A (CoA) is achieved under aqueous conditions using various aliphatic and aromatic carboxylic acids activated as their methyl acyl phosphate monoesters. Unlike many hydrophobic activating groups, the anionic methyl acyl phosphate mixed anhydride is more compatible with aqueous solvents, making it useful for conducting acylation reactions in an aqueous medium.
- Pal, Mohan,Bearne, Stephen L.
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supporting information
p. 9760 - 9763
(2015/01/08)
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- Synthesis of new ibuprofen derivatives with their in silico and in vitro cyclooxygenase-2 inhibitions
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Cyclooxygenase-2 (COX-2) is one of the important targets for treatment of inflammation related diseases. In the literature, most of drug candidates are first synthesized and then their COX-2 inhibitory activities are tested by in vitro and in vivo experim
- Gundogdu-Hizliates, Cevher,Alyuruk, Hakan,Gocmenturk, Mustafa,Ergun, Yavuz,Cavas, Levent
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- Synthesis and evaluation of 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides as COX-2 and serotonin reuptake inhibitors
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Based on the positive effects of COX-2 inhibitors on depressive symptoms and the desirable physicochemical and biological properties of the morpholine group, a series of novel 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides were designed, synthesized, and tested for their COX-2 inhibitory and serotonin reuptake inhibitory activities in vitro. The structure-activity relationships of the 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides as dual COX-2 and serotonin reuptake inhibitors were determined and discussed in detail. The biological assays indicated that five of the compounds possess good COX-2 selectivity (selectivity index COX-1/COX-2 42.8-158.1). The compound 2-[2-(4-benzyloxyphenyl)morpholino]ethyl 2-(4-iso-butylphenyl)-propanoate hydrochloride (1k) shows better COX-2 inhibitory activity (IC50 = 0.78 μM) than ibuprofen (IC 50 = 7.6 μM), and it simultaneously possesses favorable serotonin reuptake inhibitory activity. A series of novel 2-(2-arylmorpholino)ethyl esters of ibuprofen were tested for their COX-2 inhibitory and serotonin reuptake inhibitory activities in vitro. Most of the compounds possess good COX-2 selectivity. Compound 1k shows better COX-2 inhibitory activity than ibuprofen and possesses favorable serotonin reuptake inhibitory activity. According to the results of the biological assays, 2-arylmorpholine-substituted ibuprofen could be used as a core structure to design novel dual COX-2 and serotonin reuptake inhibitors.
- Dou, Jie,Shi, Lei,Hu, Aixi,Dong, Minyu,Xu, Jiangping,Liu, Ailin,Jiang, Yiping
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- NOVEL HIGH PENETRATION DRUGS AND THEIR COMPOSITIONS THEREOF FOR TREATMENT OF PARKINSON DISEASES
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One aspect of the invention provides a composition of novel high penetration compositions (HPC) or a high penetration prodrug (HPP) for treatment of Parkinson's disease. The HPCs/HPPs are capable of being converted to parent active drugs or drug metabolit
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Paragraph 00191; 00192
(2014/09/29)
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- Palladium-catalyzed aryl C-H olefination with unactivated, aliphatic alkenes
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Palladium-catalyzed coupling between aryl halides and alkenes (Mizoroki-Heck reaction) is one of the most popular reactions for synthesizing complex organic molecules. The limited availability, problematic synthesis, and higher cost of aryl halide precursors (or their equivalents) have encouraged exploration of direct olefination of aryl carbon-hydrogen (C-H) bonds (Fujiwara-Moritani reaction). Despite significant progress, the restricted substrate scope, in particular noncompliance of unactivated aliphatic olefins, has discouraged the use of this greener alternative. Overcoming this serious limitation, we report here a palladium-catalyzed chelation-assisted ortho C-H bond olefination of phenylacetic acid derivatives with unactivated, aliphatic alkenes in good to excellent yields with high regio- and stereoselectivities. The versatility of this operationally simple method has been demonstrated through drug diversification and sequential C-H olefination for synthesizing divinylbenzene derivatives.
- Deb, Arghya,Bag, Sukdev,Kancherla, Rajesh,Maiti, Debabrata
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supporting information
p. 13602 - 13605
(2015/02/05)
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- Design, synthesis and docking studies of some novel isocoumarin analogues as antimicrobial agents
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A number of novel isocoumarin analogues have been synthesized by the condensation of homophthalic acid anhydride with different non-steroidal anti-inflammatory drugs (NSAIDs). To investigate the antimicrobial data on a structural basis, in silico docking studies of the synthesized compounds (4a-4g) into the crystal structure of UDP-N-acetylmuramate-l-alanine ligase using an Autodock PyRx virtual screening program were performed in order to predict the affinity and orientation of the synthesized compounds at the activities. UDP-N-acetylmuramate-l-alanine ligase is essential for d-glutamate metabolism and peptidoglycan biosynthesis in bacteria. R2 values showed good agreement with predicted binding affinities obtained by molecular docking studies. The results indicate that the basic nucleic portion of the (4c), (4g), (4f) and (4a) binds into the specificity pocket. In this pocket, the isocoumarin nucleus of these compounds interacts with the amino acid residue of the target. Moreover, it is verified by in vitro antimicrobial screening, in which all of the compounds were active against tested bacterial strains. Among these compounds (4c), (4g), (4f) and (4a) showed good bacterial zone inhibition. This journal is
- Ashraf, Zaman,Saeed, Aamer,Nadeem, Humaira
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p. 53842 - 53853
(2015/02/19)
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- Synthesis and biological evaluation of new 1,3-Thiazolidine-4-one Derivatives of 2-(4-Isobutylphenyl)propionic Acid
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New thiazolidine-4-one derivatives of 2-(4-isobutylphenyl)propionic acid (ibuprofen) have been synthesized as potential anti-inflammatory drugs. The structure of the new compounds was proved using spectral methods (FR-IR, 1H-NMR, 13C-NMR, MS). The in vitro antioxidant potential of the synthesized compounds was evaluated according to the total antioxidant activity, the DPPH and ABTS radical scavenging assays. Reactive oxygen species (ROS) and free radicals are considered to be involved in many pathological events like diabetes mellitus, neurodegenerative diseases, cancer, infections and more recently, in inflammation. It is known that overproduction of free radicals may initiate and amplify the inflammatory process via upregulation of genes involved in the production of proinflammatory cytokines and adhesion molecules. The chemical modulation of acyl hydrazones of ibuprofen 3a-l through cyclization to the corresponding thiazolidine-4-ones 4a-n led to increased antioxidant potential, as all thiazolidine-4-ones were more active than their parent acyl hydrazones and also ibuprofen. The most active compounds are the thiazolidine-4-ones 4e, m, which showed the highest DPPH radical scavenging ability, their activity being comparable with vitamin E.
- Vasincu, Ioana Mirela,Apotrosoaei, Maria,Panzariu, Andreea-Teodora,Buron, Frdric,Routier, Sylvain,Profire, Lenuta
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p. 15005 - 15025
(2015/02/19)
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- The discovery of a facile access to the synthesis of NSAID dendritic prodrugs
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An efficient and straightforward method for the preparation of dendritic prodrugs is reported. Based on this new approach, a class of biodegradable dendrimers has been synthesised from L-tartaric acid and one of the nonsteroidal anti-inflammatory drugs, namely, aspirin or ibuprofen Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin Universit ,Tianjin 300072, P. R. China.
- Du, Zuyin,Lu, Yanhui,Dai, Xuedong,Negrerie, Daisy Zhang,Gao, Qingzhi
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p. 177 - 180
(2013/07/05)
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- High analgesic and anti-inflammatory in vivo activities of six new hybrids NSAIAs tetrahydropyran derivatives
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We present in this article syntheses of six new hybrids compounds (4-9) that were efficiently prepared in one or two steps (70-84.6%) from our previous prototype (±)-cis-4-chloro-6-(naphthalen-1-yl)-tetrahydro-2H-pyran-2-yl) methanol (3) and the NSAIAs: acetyl salicylic acid, indomethacin, ibuprofen, ketoprofen, naproxen and diclofenac. The acetic acid-induced writhing method is able to determine that all investigated new hybrids showed stronger antinociceptive properties (2- to 10-fold less ED50 values) than their precursors. The highest antinociceptive effect was observed for compound 9 showing more than 10-fold less ED50 values than diclofenac and ninefold less ED50 value than compound 2. All compounds presented greater activity than the control group in the tail-flick test confirming the central antinociceptive effect. New hybrids did not alter the motor performance of mice by rota-rod performance and open-field tests. Investigated compounds 4-9 were not toxic after oral administration (LD50 >2000 mg/kg).
- Capim, Saulo L.,Goncalves, Gabriela M.,Dos Santos, Gabriela C.M.,Marinho, Bruno G.,Vasconcellos, Mario L.A.A.
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p. 6003 - 6010
(2013/09/23)
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- Hybrid fluorescent conjugates of COX-2 inhibitors: Search for a COX-2 isozyme imaging cancer biomarker
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The observation that the cyclooxygenase-2 (COX-2) isozyme is over-expressed in multiple types of cancer, relative to that in adjacent non-cancerous tissue, prompted this investigation to prepare a group of hybrid fluorescent conjugates wherein the COX inhibitors ibuprofen, (S)-naproxen, acetyl salicylic acid, a chlororofecoxib analog and celecoxib were coupled via a linker group to an acridone, dansyl or rhodamine B fluorophore. Within this group of compounds, the ibuprofen-acridone conjugate (10) showed potent and selective COX-2 inhibition (COX-2 IC50 = 0.67 μM; SI = 110.6), but its fluorescence emission (λem = 417, 440 nm) was not suitable for fluorescent imaging of cancer cells that over-express the COX-2 isozyme. In comparison, the celecoxib-dansyl conjugate (25) showed a slightly lower COX-2 potency and selectivity (COX-2 IC50 = 1.1 μM; SI > 90) than the conjugate 10, and it possesses a better fluorescence emission (λem = 500 nm). Ultimately, a celecoxib-rhodamine B conjugate (28) that exhibited moderate COX-2 potency and selectivity (COX-2 IC50 = 3.9 μM; SI > 25) having the best fluorescence emission (λem= 580 nm) emerged as the most promising biomarker for fluorescence imaging using a colon cancer cell line that over-expresses the COX-2 isozyme.
- Bhardwaj, Atul,Kaur, Jatinder,Sharma, Sai Kiran,Huang, Zhangjian,Wuest, Frank,Knaus, Edward E.
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p. 163 - 168
(2013/02/23)
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