5773-80-8Relevant articles and documents
Ruthenium-catalyzed ester reductions applied to pharmaceutical intermediates
Shaalan, Youssef,Boulton, Lee,Jamieson, Craig
supporting information, p. 2745 - 2751 (2020/11/30)
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.
Carboxylation of Aryl Triflates with CO2 Merging Palladium and Visible-Light-Photoredox Catalysts
Bhunia, Samir Kumar,Das, Pritha,Nandi, Shantanu,Jana, Ranjan
supporting information, p. 4632 - 4637 (2019/06/27)
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.
BIARYL DERIVATIVE AS GPR120 AGONIST
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Paragraph 0306, (2017/11/17)
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.
Design, synthesis and biological evaluation of GPR55 agonists
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.
, p. 4355 - 4367 (2017/07/22)
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.
Process for synthesizing 6-bromo-2-naphthol
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Paragraph 0035, (2017/05/23)
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.
Evaluation of the antibacterial and antibiofilm activities of novel CRAMP-vancomycin conjugates with diverse linkers
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.
supporting information, p. 7477 - 7486 (2015/07/15)
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.
Evaluation of the antibacterial and antibiofilm activities of novel CRAMP-vancomycin conjugates with diverse linkers
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.
supporting information, p. 7477 - 7486 (2015/11/27)
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.
PRODUCTION METHOD FOR REFINED 6-BROMO-2-NAPHTHALENECARBOXYLIC ACID PRODUCT
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Paragraph 0042; 0043, (2013/09/12)
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.
Synthesis and evaluation of non-basic inhibitors of urokinase-type plasminogen activator (uPA)
Venkatraj, Muthusamy,Messagie, Jonas,Joossens, Jurgen,Lambeir, Anne-Marie,Haemers, Achiel,Van Der Veken, Pieter,Augustyns, Koen
supporting information; experimental part, p. 1557 - 1568 (2012/04/17)
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.
AMIDE DERIVATIVES AS ION-CHANNEL LIGANDS AND PHARMACEUTICAL COMPOSITIONS AND METHODS OF USING THE SAME
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Page/Page column 47-48, (2012/04/18)
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.
