- Commercially Available CuO Catalyzed Hydrogenation of Nitroarenes Using Ammonia Borane as a Hydrogen Source
-
Tandem ammonia borane dehydrogenation and nitroarenes hydrogenation has been reported as a novel strategy for the preparation of aromatic amines. However, the practical application of this strategy is subjected to the high-cost and tedious preparation of supported noble metal nanocatalysts. The commercially available CuO powder is herein demonstrated to be a robust catalyst for hydrogenation of nitroarenes using ammonia borane as a hydrogen source under mild conditions. Numerous amines (even sterically hindered, halogenated, and diamines) could be obtained through this method. This monometallic catalyst is characteristic of support-free, excellent chemoselectivity, low-cost, and high recyclability, which will favor its future utilization in preparative reduction chemistry. Mechanistic studies are also carried out to clarify that diazene and azoxybenzene are key intermediates of this heterogeneous reduction.
- Du, Jialei,Chen, Jie,Xia, Hehuan,Zhao, Yiwei,Wang, Fang,Liu, Hong,Zhou, Weijia,Wang, Bin
-
p. 2426 - 2430
(2020/03/30)
-
- High catalytic activity of a new Ag phosphorus ylide complex supported on montmorillonite: synthesis, characterization, and application for room temperature nitro reduction
-
In this work, the phosphorus ylide, [PPh3CHC(O)CH2Cl], was reacted with AgNO3 to give the [Ag{C(H)PPh3C(O)CH2Cl}2]+NO3? as the product. Then, it was supported on the modified montmorillonite nanoclay to prepare a new catalyst for the reduction reaction. The structure and morphology of the nanoclay catalyst were characterized by FT-IR, X-ray powder diffraction, scanning electron microscopy, energy-dispersive X-ray analysis and transmission electron microscopy techniques; also, the content of silver was obtained by inductively coupled plasma analyzer. This composition was exploited to study its catalytic activity in the reduction in aromatic nitro compounds; it displayed the high catalytic activity. Factors such as catalyst amount, solvent, temperature and reaction time were all systematically investigated to elucidate their effects on the yield of catalytic reduction in nitroarenes. This catalytic system exhibited high activity toward aromatic nitro compounds under mild conditions. The catalyst was reused five times without any significant loss in its catalytic activity.
- Karami, Kazem,Rahimi, Mahzad,Dinari, Mohammad
-
p. 281 - 291
(2018/03/29)
-
- AMINATION AND HYDROXYLATION OF ARYLMETAL COMPOUNDS
-
In one aspect, the present disclosure provides methods of preparing a primary or secondary amine and hydroxylated aromatic compounds. In some embodiments, the aromatic compound may be unsubstituted, substituted, or contain one or more heteroatoms within the rings of the aromatic compound. The methods described herein may be carried out without the need for transition metal catalysts or harsh reaction conditions.
- -
-
Paragraph 0098; 0134; 0135; 0184
(2018/03/25)
-
- FE NANOPARTICLES WITH PPM CONTENTS OF PD, CU AND/OR NI, REACTIONS IN WATER CATALYZED BY THEM
-
The present application discloses a nanoparticle composition prepared from a mixture comprising: a) a transition metal salt; b) an iron salt; and c) a reducing agent; and methods for the use of such compositions, including the reduction of an organic compound comprising a nitro group to form an organic compound comprising an amine group, the Cu-catalyzed cyclization of an azide and an alkyne (click chemistry) and cross coupling reactions, notably Suzuki-Miyaura reactions. The transition metal salts are in particular Pd, Cu and Ni salts, the content of these metals being typically in the ppm range based on the major constituent Fe in the final products.
- -
-
Paragraph 0079; 0080; 0081
(2017/07/14)
-
- N-Aryl-N’-ethyleneaminothioureas effectively inhibit acetylcholinesterase 1 from disease-transmitting mosquitoes
-
Vector control of disease-transmitting mosquitoes by insecticides has a central role in reducing the number of parasitic- and viral infection cases. The currently used insecticides are efficient, but safety concerns and the development of insecticide-resistant mosquito strains warrant the search for alternative compound classes for vector control. Here, we have designed and synthesized thiourea-based compounds as non-covalent inhibitors of acetylcholinesterase 1 (AChE1) from the mosquitoes Anopheles gambiae (An. gambiae) and Aedes aegypti (Ae. aegypti), as well as a naturally occurring resistant-conferring mutant. The N-aryl-N’-ethyleneaminothioureas proved to be inhibitors of AChE1; the most efficient one showed submicromolar potency. Importantly, the inhibitors exhibited selectivity over the human AChE (hAChE), which is desirable for new insecticides. The structure-activity relationship (SAR) analysis of the thioureas revealed that small changes in the chemical structure had a large effect on inhibition capacity. The thioureas showed to have different SAR when inhibiting AChE1 and hAChE, respectively, enabling an investigation of structure-selectivity relationships. Furthermore, insecticidal activity was demonstrated using adult and larvae An. gambiae and Ae. aegypti mosquitoes.
- Knutsson, Sofie,Kindahl, Tomas,Engdahl, Cecilia,Nikjoo, Dariush,Forsgren, Nina,Kitur, Stanley,Ekstr?m, Fredrik,Kamau, Luna,Linusson, Anna
-
p. 415 - 427
(2017/04/24)
-
- Rapid heteroatom transfer to arylmetals utilizing multifunctional reagent scaffolds
-
Arylmetals are highly valuable carbon nucleophiles that are readily and inexpensively prepared from aryl halides or arenes and widely used on both laboratory and industrial scales to react directly with a wide range of electrophiles. Although C-C bond formation has been a staple of organic synthesis, the direct transfer of primary amino (-NH2) and hydroxyl (-OH) groups to arylmetals in a scalable and environmentally friendly fashion remains a formidable synthetic challenge because of the absence of suitable heteroatom-transfer reagents. Here, we demonstrate the use of bench-stable N-H and N-alkyl oxaziridines derived from readily available terpenoid scaffolds as efficient multifunctional reagents for the direct primary amination and hydroxylation of structurally diverse aryl- and heteroarylmetals. This practical and scalable method provides one-step synthetic access to primary anilines and phenols at low temperature and avoids the use of transition-metal catalysts, ligands and additives, nitrogen-protecting groups, excess reagents and harsh workup conditions.
- Gao, Hongyin,Zhou, Zhe,Kwon, Doo-Hyun,Coombs, James,Jones, Steven,Behnke, Nicole Erin,Ess, Daniel H.,Kürti, László
-
p. 681 - 688
(2017/06/30)
-
- Safe and Selective Nitro Group Reductions Catalyzed by Sustainable and Recyclable Fe/ppm Pd Nanoparticles in Water at Room Temperature
-
As a result of a unique synergy between ligand-free Fe/ppm Pd nanoparticles and PEG-containing designer surfactants, a facile and selective reduction of nitro-containing aromatics and heteroaromatics can be effected in water at room temperature in the presence of NaBH4. This new nanotechnology involves low catalyst loadings, is highly chemoselective, and tolerates a wide variety of functional groups. The process, which includes recycling of the entire aqueous medium, offers a general, environmentally responsible, and notably safe approach to highly valued reductions of nitro-containing compounds.
- Feng, Jie,Handa, Sachin,Gallou, Fabrice,Lipshutz, Bruce H.
-
supporting information
p. 8979 - 8983
(2016/07/26)
-
- Novel Series of Dihydropyridinone P2X7 Receptor Antagonists
-
Identification of singleton P2X7 inhibitor 1 from HTS gave a pharmacophore that eventually turned into potential clinical candidates 17 and 19. During development, a number of issues were successfully addressed, such as metabolic stability, plasma stability, GSH adduct formation, and aniline mutagenicity. Thus, careful modification of the molecule, such as conversion of the 1,4-dihydropyridinone to the 1,2-dihydropyridinone system, proper substitution at C-5″, and in some cases addition of fluorine atoms to the aniline ring allowed for the identification of a novel class of potent P2X7 inhibitors suitable for evaluating the role of P2X7 in inflammatory, immune, neurologic, or musculoskeletal disorders.
- Lopez-Tapia, Francisco,Walker, Keith A. M.,Brotherton-Pleiss, Christine,Caroon, Joanie,Nitzan, Dov,Lowrie, Lee,Gleason, Shelley,Zhao, Shu-Hai,Berger, Jacob,Cockayne, Debra,Phippard, Deborah,Suttmann, Rebecca,Fitch, William L.,Bourdet, David,Rege, Pankaj,Huang, Xiaojun,Broadbent, Scott,Dvorak, Charles,Zhu, Jiang,Wagner, Paul,Padilla, Fernando,Loe, Brad,Jahangir, Alam,Alker, André
-
supporting information
p. 8413 - 8426
(2015/11/24)
-
- 2,4-Pyrimidinediamine Compounds and Their Uses
-
The present invention provides 2,4-pyrimidinediamine compounds that inhibit the IgE and/or IgG receptor signaling cascades that lead to the release of chemical mediators, intermediates and methods of synthesizing the compounds and methods of using the compounds in a variety of contexts, including in the treatment and prevention of diseases characterized by, caused by or associated with the release of chemical mediators via degranulation and other processes effected by activation of the IgE and/or IgG receptor signaling cascades.
- -
-
Paragraph 0454; 0455
(2015/11/10)
-
- 4(1H)-Quinolones Having Antimalarial Activity With Reduced Chemical Resistance
-
Provided are 4(1H)-quinolone derivatives effective in inhibiting or eliminating the viability of at least one of the stages in the life-cycle of the malarial parasite, and to show a reduced propensity to induce resistance to the compound by the target parasite. In particular, the compounds can be derivatives of phenoxyethoxy-quinolones, and including, but not only, 7-(2-phenoxyethoxy)quinolin derivatives. These compounds may be administered by themselves, with at least one other derivative compound, or with other antimalarial compounds, to an animal or human subject. The therapeutic compositions can be and formulated to reduce the extent of a Plasmodium infection in the recipient subject, or to reduce the likelihood of the onset or establishment of a Plasmodium infection if administered prior to the parasite contacting the subject. The therapeutic compositions can be formulated to provide an effective single dose amount of an antimalarial compound or multiple doses for administering over a period of time.
- -
-
Paragraph 0152; 0153; 0154
(2013/05/22)
-
- Synthesis, antimalarial activity, and structure-activity relationship of 7-(2-Phenoxyethoxy)-4(1H)-quinolones
-
ICI 56,780 (5) displayed causal prophylactic and blood schizonticidal activity (ED50 = 0.05 mg/kg) in rodent malaria models but produced rapid acquisition of parasitological resistance in P. berghei infected mice. Herein we describe the synthesis of analogues of 5 with EC50 as low as 0.15 nM against multidrug resistant P. falciparum. Optimal activity with low cross-resistance indexes (RI) to atovaquone was achieved by introducing ortho-substituted aryl moieties at the 3-position of the 7-(2-phenoxyethoxy)- 4(1H)-quinolone core. (Figure presented
- Cross, R. Matthew,Namelikonda, Niranjan K.,Mutka, Tina S.,Luong, Lisa,Kyle, Dennis E.,Manetsch, Roman
-
supporting information; experimental part
p. 8321 - 8327
(2012/02/04)
-
- Optimization of 1,2,3,4-tetrahydroacridin-9(10 H)-ones as antimalarials utilizing structure-activity and structure-property relationships
-
Antimalarial activity of 1,2,3,4-tetrahydroacridin-9(10H)-ones (THAs) has been known since the 1940s and has garnered more attention with the development of the acridinedione floxacrine (1) in the 1970s and analogues thereof such as WR 243251 (2a) in the 1990s. These compounds failed just prior to clinical development because of suboptimal activity, poor solubility, and rapid induction of parasite resistance. Moreover, detailed structure-activity relationship (SAR) studies of the THA core scaffold were lacking and SPR studies were nonexistent. To improve upon initial findings, several series of 1,2,3,4-tetrahydroacridin-9(10H)-ones were synthesized and tested in a systematic fashion, examining each compound for antimalarial activity, solubility, and permeability. Furthermore, a select set of compounds was chosen for microsomal stability testing to identify physicochemical liabilities of the THA scaffold. Several potent compounds (EC50 100 nM) were identified to be active against the clinically relevant isolates W2 and TM90-C2B while possessing good physicochemical properties and little to no cross-resistance.
- Cross, R. Matthew,Maignan, Jordany R.,Mutka, Tina S.,Luong, Lisa,Sargent, Justin,Kyle, Dennis E.,Manetsch, Roman
-
experimental part
p. 4399 - 4426
(2011/09/15)
-
- Endochin optimization: Structure-activity and structure-property relationship studies of 3-substituted 2-Methyl-4(1 H)-quinolones with antimalarial activity
-
Since the 1940s endochin and analogues thereof were known to be causal prophylactic and potent erythrocytic stage agents in avian models. Preliminary screening in a current in vitro assay identified several 4(1H)-quinolones with nanomolar EC50 against erythrocytic stages of multidrug resistant W2 and TM90-C2B isolates of Plasmodium falciparum. Follow-up structure-activity relationship (SAR) studies on 4(1H)-quinolone analogues identified several key features for biological activity. Nevertheless, structure-property relationship (SPR) studies conducted in parallel revealed that 4(1H)-quinolone analogues are limited by poor solubilities and rapid microsomal degradations. To improve the overall efficacy, multiple 4(1H)-quinolone series with varying substituents on the benzenoid quinolone ring and/or the 3-position were synthesized and tested for in vitro antimalarial activity. Several structurally diverse 6-chloro-2-methyl-7-methoxy-4(1H)-quinolones with EC50 in the low nanomolar range against the clinically relevant isolates W2 and TM90-C2B were identified with improved physicochemical properties while maintaining little to no cross-resistance with atovaquone.
- Cross, R. Matthew,Monastyrskyi, Andrii,Mutka, Tina S.,Burrows, Jeremy N.,Kyle, Dennis E.,Manetsch, Roman
-
experimental part
p. 7076 - 7094
(2010/12/25)
-
- Synthesis of 5-hydroxyquinolines
-
A series of 5-hydroxyquinolines has been prepared via the Skraup reaction. Several regioisomers were made either by selective displacement of a leaving group or by using a bromo substituent as a blocking group. The bromo group was found to be an excellent blocking group due to its stability during the Skraup reaction and easy removal thereafter. Halides at the 5-position of quinoline were found to be much more reactive than those at the 7- and 8-positions. Finally, we have also found a unique method to reduce the pyridyl ring on quinolines, leaving a halogen substituent untouched.
- Li, Jianke,Kung, Daniel W.,Griffith, David A.
-
scheme or table
p. 3876 - 3878
(2010/08/19)
-
- N-ARYL-N-PIPERIDIN-4-YL-PROPIONAMIDE DERIVATIVES AND THEIR USE AS OPIOID RECEPTOR LIGANDS
-
This invention relates to novel N-aryl -N-piperidin-4 -yl -propionamide derivatives (I) useful as opioid receptor ligands. In other aspects the invention relates to the use of these compounds in a method for therapy, such as for the treatment of pain, and to pharmaceutical compositions comprising the compounds of the invention.
- -
-
Page/Page column 14
(2009/07/18)
-
- N-ARYL-N-PIPERIDIN-4-YL-PROPIONAMIDE DERIVATIVES AND THEIR USE AS MONOAMINE NEUROTRANSMITTER RE-UPTAKE INHIBITORS
-
This invention relates to /\/-aryl-/\/-piperidin-4-yl-propionannide derivatives for use as monoamine neurotransmitter re-uptake inhibitors. In other aspects the invention relates to the use of these compounds in a method for therapy, such as for the treatment of pain, and to pharmaceutical compositions comprising the compounds, and to novel compounds.
- -
-
Page/Page column 14
(2009/07/18)
-
- ARYL SULFONAMIDES
-
Compounds are provided that act as potent antagonists of the CCR9 receptor, and which have been further confirmed in animal testing for inflammation, one of the hallmark disease states for CCR9. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR9-mediated diseases, and as controls in assays for the identification of CCR9 antagonists.
- -
-
-
- Phenylsulfonyl-1,3-dihydro-2h-indole-2-one derivatives, their preparation and their therapeutic use
-
The invention relates to compounds of formula: and also to the salts thereof with mineral or organic acids, and the solvates and/or hydrates thereof, with affinity for and selectivity towards the arginine-vasopressin V1b receptors and/or for the ocytocin receptors and, furthermore, for certain compounds, affinity for the V1a receptors. The invention also relates to the process for preparing them, to the intermediate compounds of formula (IV) that are useful for preparing them, to pharmaceutical compositions containing them and to their use for preparing medicinal products.
- -
-
Page/Page column 26
(2010/02/08)
-
- 3,3a-dihydropyrano[4,3,2-de]quinazolin-2(1H)-ones are potent non-nucleoside reverse transcriptase inhibitors
-
A series of unique 3,3a-dihydropyrano[4,3,2-de]quinazolin-2(1H)-ones and a 2a,5-dihydro-2H-thieno[4,3,2-de]quinazoline-4(3H)-thione were found to be HIV-1 non-nucleoside reverse transcriptase inhibitors. One of these compounds, as the racemate, possessed
- Corbett, Jeffrey W.,Pan, Senliang,Markwalder, Jay A.,Cordova, Beverly C.,Klabe, Ronald M.,Garber, Sena,Rodgers, James D.,Erickson-Viitanen, Susan K.
-
p. 211 - 214
(2007/10/03)
-
- Degradation products of a phenylurea herbicide, diuron: Synthesis, ecotoxicity, and biotransformation
-
The degradation products of diuron (photoproducts and metabolites), already described in the literature, were synthesized in order to carry out further investigations. Their ecotoxicity was determined using the standardized Microtox test, and most of the derivatives presented a nontarget toxicity higher than that of diuron. Therefore, the biotransformation of these compounds was tested with four fungal strains and a bacterial strain, which were known to be efficient for diuron transformation. With the exception of the 3,4-dichlorophenylurea, all the degradation products underwent other transformations with most of the strains tested, but no mineralization was observed. For many of them, the biodegradation compound for which the toxicity was important was 3,4-dichlorophenylurea. This study underlines the importance of knowing the nature of the degradation products, which has to be kept in mind while analyzing natural water samples or soil samples.
- Tixier,Sancelme,Bonnemoy,Cuer,Veschambre
-
p. 1381 - 1389
(2007/10/03)
-
- Hydroxyacetic acid derivatives for the treatment of diabetic complications
-
Racemic and chiral (2R,4R)-4-c-hydroxy-2-4-(substituted)chroman(and thiochroman)-4-acetic acids and their pharmaceutically acceptable salts, their use in the treatment of diabetic complications and intermediates therefor.
- -
-
-