- Ruthenium-catalyzed ester reductions applied to pharmaceutical intermediates
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Ruthenium pincer complexes were synthesized and used for catalytic ester reductions under mild conditions (~5 bar of hydrogen). An experimental design approach was used to optimize the conditions for yield, purity, and robustness. Evidence for the catalytically active ruthenium dihydride species is presented. Observed intermediates and side products, as well as time-course data, were used to build mechanistic insight. The optimized procedure was further demonstrated through scaled-up reductions of two pharmaceutically relevant esters, both in batch and continuous flow.
- Shaalan, Youssef,Boulton, Lee,Jamieson, Craig
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supporting information
p. 2745 - 2751
(2020/11/30)
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- Carboxylation of Aryl Triflates with CO2 Merging Palladium and Visible-Light-Photoredox Catalysts
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We report herein a visible-light-promoted, highly practical carboxylation of readily accessible aryl triflates at ambient temperature and a balloon pressure of CO2 by the combined use of palladium and photoredox Ir(III) catalysts. Strikingly, the stoichiometric metallic reductant is replaced by a nonmetallic amine reductant providing an environmentally benign carboxylation process. In addition, one-pot synthesis of a carboxylic acid directly from phenol and modification of estrone and concise synthesis of pharmaceutical drugs adapalene and bexarotene have been accomplished via late-stage carboxylation reaction. Furthermore, a parallel decarboxylation-carboxylation reaction has been demonstrated in an H-type closed vessel that is an interesting concept for the strategic sector. Spectroscopic and spectroelectrochemical studies indicated electron transfer from the Ir(III)/DIPEA combination to generate aryl carboxylate and Pd(0) for catalytic turnover.
- Bhunia, Samir Kumar,Das, Pritha,Nandi, Shantanu,Jana, Ranjan
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supporting information
p. 4632 - 4637
(2019/06/27)
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- BIARYL DERIVATIVE AS GPR120 AGONIST
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The present invention relates to a biaryl derivative expressed by the chemical formula 1, a method for producing the biaryl derivative, a pharmaceutical composition comprising same, and use of same, the biaryl derivative expressed by the chemical formula 1, as a GPR120 agonist, promoting GLP-1 generation in the gastro-intestinal tract, reducing insulin resistance in the liver, muscles and the like from anti-inflammatory activity in the macrophage, pancreatic cells and the like, and allowing effective use in prevention or treatment of inflammation or metabolic diseases such as diabetes, complications from diabetes, obesity, non-alcoholic fatty liver disease, fatty liver disease, and osteoporosis.
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- Process for synthesizing 6-bromo-2-naphthol
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The invention relates to a process for synthesizing 6-bromo-2-naphthol. The process comprises the following steps: (S1) mixing 2-naphthol and a bromo salt, and adding the mixture into a reactor; (S2) adding an acetic solution into the reactor in the step (S1); (S3) dropwise adding an oxidant into the reactor while carrying out stirring, and carrying out a heat-insulating reaction after dropwise adding is completed, so as to obtain an intermediate solution; (S4) heating the temperature of the reactor to a definite value, adding nano Pd/Fe into the intermediate solution obtained in the step (S3), introducing nitrogen gas into the reactor, and carrying out a reaction while controlling the temperature and pressure to definite values; (S5) cooling the reactor, adding pure water into the reactor in the step (S4) for dilution, and carrying out standing for a period of time for crystallization; and (S6) subjecting the crystals obtained in the step (S5) to filtering and washing, adding the crystals into an acetic solution for recrystallization, and subjecting the recrystallized crystals to filtering, washing and drying, thereby obtaining a finished product. According to the process, on one hand, the utilization ratio of atoms is increased, and large-area pollution to environments caused by reactions is prevented; and on the other hand, the requirements of a reaction process on public works are relatively low, the reaction rate is relatively high, and the purity and yield of the obtained final product are relatively high, so that the process is applicable to industrial mass production.
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Paragraph 0035
(2017/05/23)
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- Design, synthesis and biological evaluation of GPR55 agonists
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GPR55, a G protein-coupled receptor, is an attractive target to alleviate inflammatory and neuropathic pain and treat osteoporosis and cancer. Identifying a potent and selective ligand will aid to further establish the specific physiological roles and pharmacology of the receptor. Towards this goal, a targeted library of 22 compounds was synthesized in a modular fashion to obtain structure-activity relationship information. The general route consisted of coupling a variety of p-aminophenyl sulfonamides to isothiocyanates to form acylthioureas. For the synthesis of a known naphthyl ethyl alcohol motif, route modification led to a shorter and more efficient process. The 22 analogues were analyzed for their ability to serve as agonists at GPR55 and valuable information for both ends of the molecule was ascertained.
- Fakhouri, Lara,Cook, Christopher D.,Al-Huniti, Mohammed H.,Console-Bram, Linda M.,Hurst, Dow P.,Spano, Michael B.S.,Nasrallah, Daniel J.,Caron, Marc G.,Barak, Larry S.,Reggio, Patricia H.,Abood, Mary E.,Croatt, Mitchell P.
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p. 4355 - 4367
(2017/07/22)
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- Evaluation of the antibacterial and antibiofilm activities of novel CRAMP-vancomycin conjugates with diverse linkers
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We report the design, synthesis and antibacterial activity analysis of conjugates of vancomycin and cathelicidin-related antimicrobial peptides (CRAMP). Vancomycin inhibits the nascent peptidoglycan synthesis and is highly active against Gram-positive bacteria, whereas Gram-negative bacteria are generally insensitive due to a protective outer membrane. CRAMP is known to translocate across the Gram-negative outer membrane by a self-promoted uptake mechanism. Vancomycin-CRAMP conjugates were synthesized using click chemistry with diverse hydrophilic and hydrophobic linkers, with CRAMP functioning as a carrier peptide for the transfer of vancomycin through the outer membrane. Small hydrophobic linkers with an aromatic group result in the most active conjugates against planktonic Gram-negative bacteria, while maintaining the high activity of vancomycin against Gram-positive bacteria. These conjugates thus show a broad-spectrum activity, which is absent in CRAMP or vancomycin alone, and which is strongly improved compared to an equimolar mixture of CRAMP and vancomycin. In addition, these conjugates also show a strong inhibitory activity against S. Typhimurium biofilm formation.
- Mishra, Nigam M.,Briers, Yves,Lamberigts, Chris,Steenackers, Hans,Robijns, Stijn,Landuyt, Bart,Vanderleyden, Jos,Schoofs, Liliane,Lavigne, Rob,Luyten, Walter,Van Der Eycken, Erik V.
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supporting information
p. 7477 - 7486
(2015/07/15)
-
- Evaluation of the antibacterial and antibiofilm activities of novel CRAMP-vancomycin conjugates with diverse linkers
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We report the design, synthesis and antibacterial activity analysis of conjugates of vancomycin and cathelicidin-related antimicrobial peptides (CRAMP). Vancomycin inhibits the nascent peptidoglycan synthesis and is highly active against Gram-positive bacteria, whereas Gram-negative bacteria are generally insensitive due to a protective outer membrane. CRAMP is known to translocate across the Gram-negative outer membrane by a self-promoted uptake mechanism. Vancomycin-CRAMP conjugates were synthesized using click chemistry with diverse hydrophilic and hydrophobic linkers, with CRAMP functioning as a carrier peptide for the transfer of vancomycin through the outer membrane. Small hydrophobic linkers with an aromatic group result in the most active conjugates against planktonic Gram-negative bacteria, while maintaining the high activity of vancomycin against Gram-positive bacteria. These conjugates thus show a broad-spectrum activity, which is absent in CRAMP or vancomycin alone, and which is strongly improved compared to an equimolar mixture of CRAMP and vancomycin. In addition, these conjugates also show a strong inhibitory activity against S. Typhimurium biofilm formation.
- Mishra, Nigam M.,Briers, Yves,Lamberigts, Chris,Steenackers, Hans,Robijns, Stijn,Landuyt, Bart,Vanderleyden, Jos,Schoofs, Liliane,Lavigne, Rob,Luyten, Walter,Van Der Eycken, Erik V.
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supporting information
p. 7477 - 7486
(2015/11/27)
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- PRODUCTION METHOD FOR REFINED 6-BROMO-2-NAPHTHALENECARBOXYLIC ACID PRODUCT
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The present invention provides a method, as a means for industrially producing a refined 6-bromo-2-naphthalenecarboxylic acid product from a crude 6-bromo-2-naphthalenecarboxylic acid product, comprising: causing the above crude product to react with sodium hydroxide in water to precipitate a sodium salt of 6-bromo-2-naphthalenecarboxylic acid; performing recrystallization treatment for the obtained precipitate; causing the obtained crystal to react with acid in water to precipitate 6-bromo-2-naphthalenecarboxylic acid; and recovering the obtained precipitate.
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Paragraph 0042; 0043
(2013/09/12)
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- Synthesis and evaluation of non-basic inhibitors of urokinase-type plasminogen activator (uPA)
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Recent drug discovery programs targeting urokinase plasminogen activator (uPA) have resulted in nonpeptidic inhibitors consisting of amidine or guanidine functional groups attached to aromatic or heteroaromatic scaffolds. There is a general problem of poor oral bioavailability of these charged inhibitors. In this paper, we report the synthesis and evaluation of a series of naphthamide and naphthalene sulfonamides as uPA inhibitors containing non-basic groups as substitute for amidine or guanidine groups.
- Venkatraj, Muthusamy,Messagie, Jonas,Joossens, Jurgen,Lambeir, Anne-Marie,Haemers, Achiel,Van Der Veken, Pieter,Augustyns, Koen
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supporting information; experimental part
p. 1557 - 1568
(2012/04/17)
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- AMIDE DERIVATIVES AS ION-CHANNEL LIGANDS AND PHARMACEUTICAL COMPOSITIONS AND METHODS OF USING THE SAME
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Compounds are disclosed that have a formula represented by the following: Formula (I). The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, pain, inflammation, traumatic injury, and others.
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Page/Page column 47-48
(2012/04/18)
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- New synthesis of 6[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid and evaluation of the influence of adamantyl group on the DNA binding of a naphthoic retinoid
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6[3-(1-Adamantyl)-4-methoxyphenyl]-2-naphthoic acid (Adapalene), a synthetic aromatic retinoid specific for RARβ and RARγ receptors, has been prepared utilizing a Pd/C-mediated Suzuki coupling between 6-bromo-2-naphthoic acid and 4-methoxyphenyl boronic acid, followed by introduction of an adamantyl group in the position 3 of the formed 6-(4-methoxyphenyl)-2-naphthoic acid. The interaction of 6-(4-methoxyphenyl)-2- naphthoic acid/ethyl ester and the 3-adamantyl analogs with DNA was studied in aqueous solution at physiological conditions by UV-vis spectroscopy. The calculated binding constants Kligand-DNA ranged between 1.1 × 104 M-1 and 1.1 × 105 M-1, the higher values corresponding to those of the adamantylated compounds. Molecular modeling studies have emphasized that the intercalative binding of adapalene and its derivatives to DNA is mainly stabilized by hydrophobic interactions related to the presence of the adamantyl group.
- Milanese, Alberto,Gorincioi, Elena,Rajabi, Mehdi,Vistoli, Giulio,Santaniello, Enzo
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experimental part
p. 151 - 158
(2011/11/07)
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- ANT1VIRAL COMPOUNDS AND USES THEREOF
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This invention relates to: (a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.
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Page/Page column 73-74
(2010/11/05)
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- URACIL OR THYMINE DERIVATIVE FOR TREATING HEPATITIS C
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Present application relates to the compounds of formula I useful to treat hepatitis C (HCV) infections. In the structure of the disclosed compounds is the uracil or thymine derivative linked via a phenylene into either fused 2-ring cyclic system (R6) or alternatively via additional two-atom linker (L) to a 5-6 membered monocycle (R6). Application further discloses polymorphs and pseudopolymorphs of two specific compounds: N-(6(3-t-butyl-5-(2>4-dioxo-3,4-dihydropyrimidin-1 (2H)- y!)2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide and (E)-N-(4(3-t- butyl-5-(2,4-dioxo-3)4-dihydropyrimidin-1 (2H)-yl)2-methoxy-styryl- phenyl)methanesulfonamide.
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Page/Page column 174
(2009/04/25)
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- ANTI-INFECTIVE PYRIMIDINES AND USES THEREOF
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This invention relates to: (a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.
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Page/Page column 103
(2009/04/25)
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- Inhibitors of factor Xa
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Novel compounds, their salts and compositions related thereto having activity against mammalian factor Xa are disclosed. The compounds are useful in vitro or in vivo for preventing or treating coagulation disorders.
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- Inhibitors of factor Xa
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Novel compounds, their salts and compositions related thereto having activity against mammalian factor Xa are disclosed. The compounds are useful in vitro or in vivo for preventing or treating coagulation disorders.
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- Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities
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Aryl-substituted and aryl and (3-oxo-1-propenly)-substituted benzopyran, benzothiopyran, 1,2-dihydroquinoline, and 5,6-dihydronaphthalene derivatives have retinoid negative hormone and/or antagonist-like biological activities. The invented RAR antagonists can be administered to mammals, including humans, for the purpose of preventing or diminishing action of RAR agonists on the bound receptor sites. Specifically, the RAR agonists are administered or coadministered with retinoid drugs to prevent or ameliorate toxicity or side effects caused by retinoids or vitamin A or vitamin A precursors. The retinoid negative hormones can be used to potentiate the activities of other retinoids and nuclear receptor agonists. For example, the retinoid negative hormone called AGN 193109 effectively increased the effectiveness of other retinoids and steroid hormones in in vitro transactivation assays. Additionally, transactivation assays can be used to identify compounds having negative hormone activity. These assays are based on the ability of negative hormones to down-regulate the activity of chimeric retinoid receptors engineered to possess a constitutive transcription activator domain.
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- SYNTHESIS AND USE OF RETINOID COMPOUNDS HAVING NEGATIVE HORMONE AND/OR ANTAGONIST ACTIVITIES
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2,2-Dialkyl-4-aryl-substituted benzopyran and benzothiopyran derivatives of the formula STR1 where the symbols have the meaning described in the specification, have retinoid negative hormone and/or antagonist-like biological activities. The invented RAR antagonists can be administered to mammals, including humans, for the purpose of preventing or diminishing action of RAR agonists on the bound receptor sites. Specifically, the RAR agonists are administered or coadministered with retinoid drugs to prevent or ameliorate toxicity or side effects caused by retinoids or vitamin A or vitamin A precursors. The retinoid negative hormones can be used to potentiate the activities of other retinoids and nuclear receptor agonists.
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- N[(2-Naphthalenyl)thioxomethyl]glycine derivatives
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Herein disclosed are N-[(2-naphthalenyl)thioxomethyl]glycine derivatives of the formula STR1 wherein R1 is lower alkyl and R2 is hydrogen, lower alkyl, lower alkoxy, halo or trifluoromethyl. The derivatives have aldose reductase inhibiting activity and are useful for treating diabetic complications.
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- Naphthyl or tetrahydronaphthyl-substituted naphthoic acid and derivatives
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Compounds of the formulas: STR1 where X is methyl, methoxy, chlorine, or hydrogen, Y and Y1 are fluorine or hydrogen, R is hydroxy, alkoxy with 0 or 1 hydroxy substituent, aroxy, or NR1 R2 where R1 is hydrogen, alkyl with 0 or 1 hydroxy substituent or aryl and R2 is alkyl with 0 or 1 hydroxy substituent or aryl with the proviso that when Y or Y1 is fluorine, the other Y or Y1 is hydrogen. These compounds are useful as chemopreventive agents for inhibiting tumor promotion in epithelial cells and for treating nonmalignant skin disorders.
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- Kinetics of Base-catalysed Iodination of Substituted Acetonaphthones
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Kinetics of iodination of 6-substituted 2-acetonaphthones and of 4-substituted 1-acetonaphthones in 20percent pyridine-20percent methanol-60percent water (v/v) have been followed at three temperatures.The Hammett equation applies very well to these reactions.The rate constants for various heterocyclic base-catalysed iodination of acetophenone and of 1- and 2-acetonaphthones in 60percent (v/v) methanol-water solvent have been correlated with pKa values of the conjugate acids of the heterocyclic bases via the Broensted equation giving β values of 0.88, 1.01 and 0.92 for acetophenone, 1-acetonaphthone and 2-acetonaphthone respectively.The influence of solvent on the rates of pyridine-catalysed iodination of acetophenone and of 1- and 2-acetonaphthones has also been studied.
- Ananthakrishnanadar, P.,Gnanasekaran, C.
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p. 646 - 649
(2007/10/02)
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