- A fragment merging approach towards the development of small molecule inhibitors of Mycobacterium tuberculosis EthR for use as ethionamide boosters
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With the ever-increasing instances of resistance to frontline TB drugs there is the need to develop novel strategies to fight the worldwide TB epidemic. Boosting the effect of the existing second-line antibiotic ethionamide by inhibiting the mycobacterial
- Nikiforov, Petar O.,Surade, Sachin,Blaszczyk, Michal,Delorme, Vincent,Brodin, Priscille,Baulard, Alain R.,Blundell, Tom L.,Abell, Chris
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Read Online
- Two-directional photoinduced electron transfer in a trichromophoric system
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Competition bewtween electron transfer via a through σ-bond and a through π-bond mechanism has been studied in 1-(4-cyanophenyl)-4-(cyanomethylene)piperidine. In this trichromophoric system designed in a configuration acceptor-donor-acceptor, where the do
- Depaemelaere, Sigrid,De Schryver, Frans C.,Verhoeven, Jan W.
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Read Online
- Phospha-adamantanes as ligands for organopalladium chemistry: Aminations of aryl halides
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The use of Pd2dba3·CHCl3 and 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phenyl-6-phospha-adamantane has been shown to facilitate the effective amination of aryl halides with aromatic or aliphatic amines in high yields.
- Gerristma, David,Brenstrum, Timothy,McNulty, James,Capretta, Alfredo
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Read Online
- Modified (NHC)Pd(allyl)Cl (NHC = N-heterocyclic carbene) complexes for room-temperature Suzuki-Miyaura and Buchwald-Hartwig reactions
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A series of (NHC)Pd(R-allyl)Cl complexes [NHC: IPr = N,N′-bis(2,6- diisopropylphenyl)imidazol-2-ylidene, SIPr = N,N′-bis(2,6- diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene; R = H, Me, gem-Me2, Ph] have been synthesized and fully characterized. When compared to (NHC)Pd(allyl)Cl, substitution at the terminal position of the allyl scaffold favors a more facile activation step. This translates into higher catalytic activity in the Suzuki-Miyaura and Buchwald-Hartwig reactions, allowing for the coupling of unactivated aryl chlorides at room temperature in minutes. In the Suzuki-Miyaura reaction, aryl triflates, bromides, and chlorides react with boronic acids using very low catalyst loading. In the N-aryl amination reaction, a wide range of substrates has been coupled efficiently; primary-, secondary-, alkyl-, or aryl-amines react in high yields with unactivated, neutral, and activated aryl chlorides and bromides. In both reactions, extremely hindered substrates such as tri-ortho-substituted biaryls and tetra-ortho-substituted diarylamines can be produced without loss of activity. Finally, the present catalytic system has proven to be efficient with as low as 10 parts-per-million (ppm) of precatalyst in the Buchwald-Hartwig reaction and 50 ppm in the Suzuki-Miyaura reaction.
- Marion, Nicolas,Navarro, Oscar,Mei, Jianguo,Stevens, Edwin D.,Scott, Natalie M.,Nolan, Steven P.
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Read Online
- Studies on Pd/imidazolium salt protocols for aminations of aryl bromides and iodides using lithium hexamethyldisilazide (LHMDS)
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The reactions of a range of secondary amines with aryl bromides and iodides have been performed using an in situ protocol involving palladium and imidazolium salts. Many of these reactions proceed at room temperature, providing a mild protocol for aminations of aryl iodides and bromides. Key to the success of this procedure is the use of lithium hexamethyldisilazide (LHMDS) as base.
- Conesa Lerma, Israel,Cawley, Mark J.,Cloke, F. Geoffrey N.,Arentsen, Katherine,Scott, James S.,Pearson, Stuart E.,Hayler, John,Caddick, Stephen
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Read Online
- (IPr)Pd(acac)Cl: An easily synthesized, efficient, and versatile precatalyst for C-N and C-C bond formation
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A very straightforward synthesis of (IPr)Pd(acac)Cl from two commercially available starting materials, Pd(acac)2 and IPr·HCl [acac = acetylacetonate; IPr = N,N′-bis(2,6-diisopropylphenyl)imidazol-2-ylidene], has been developed. The resulting complex, (IPr)Pd(acac)Cl (1), has proven to be a highly active PdII precatalyst in the Buchwald-Hartwig and the α-ketone arylation reactions. A wide range of substrates has been screened, including unactivated, sterically hindered, and heterocyclic aryl chlorides.
- Marion, Nicolas,Ecarnot, Elise C.,Navarro, Oscar,Amoroso, Dino,Bell, Andrew,Nolan, Steven P.
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Read Online
- Electrochemical Cross-Dehydrogenative Aromatization Protocol for the Synthesis of Aromatic Amines
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The introduction of amines onto aromatics without metal catalysts and chemical oxidants is synthetically challenging. Herein, we report the first example of an electrochemical cross-dehydrogenative aromatization (ECDA) reaction of saturated cyclohexanones and amines to construct anilines without additional metal catalysts and chemical oxidants. This reaction exhibits a broad scope of cyclohexanones including heterocyclic ketones, affording a variety of aromatic amines with various functionalities, and shows great potential in the synthesis of biologically active compounds.
- Tao, Shao-Kun,Chen, Shan-Yong,Feng, Mei-Lin,Xu, Jia-Qi,Yuan, Mao-Lin,Fu, Hai-Yan,Li, Rui-Xiang,Chen, Hua,Zheng, Xue-Li,Yu, Xiao-Qi
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supporting information
p. 1011 - 1016
(2022/02/05)
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- Palladium-Catalyzed Cyanation of Aryl Halides Using Formamide and Cyanuric Chloride as a New “CN” Source
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A new source of “CN” employing formamide and cyanuric chloride is introduced for the cyanation reactions. The treatment of formamide and 2,4,6-trichloro-1,3,5-triazine (TCT; cyanuric chloride) afforded an efficient cyanating agent which it can be used as a nontoxic, readily available, and non-expensive reagent in the cyanation transformations. In this study, palladium-catalyzed cyanation of aryl halides was successfully accomplished using this new “CN” source in high yields.
- Niknam, Esmaeil,Panahi, Farhad,Khalafi-Nezhad, Ali
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p. 2699 - 2707
(2020/04/08)
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- Integrating CuO?Fe2O3 Nanocomposites and Supramolecular Assemblies of Phenazine for Visible-Light Photoredox Catalysis
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A photoredox catalytic ensemble consisting of CuO-Fe2O3 nanocomposites and oligomeric derivative of phenazine has been developed. The prepared system acts as an efficient photoredox catalyst for C?N bond formation reaction via SET mechanism under ‘green’ conditions (aerial environment, mixed aqueous media, recyclable), requiring less equivalents of base and amine substrate. The present study demonstrates the significant role of supramolecular assemblies as photooxidants and reductants upon irradiation and their important contribution towards the activation of the metallic centre through energy transfer and electron transfer pathways. The potential of oligomer 4: CuO-Fe2O3 has also been explored for C?C bond formation reactions via the Sonogashira protocol.
- Kaur, Lovjot,Deol, Harnimarta,Kumar, Manoj,Bhalla, Vandana
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supporting information
p. 892 - 898
(2020/03/04)
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- General Paradigm in Photoredox Nickel-Catalyzed Cross-Coupling Allows for Light-Free Access to Reactivity
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Self-sustained NiI/III cycles are established as a potentially general paradigm in photoredox Ni-catalyzed carbon–heteroatom cross-coupling reactions through a strategy that allows us to recapitulate photoredox-like reactivity in the absence of light across a wide range of substrates in the amination, etherification, and esterification of aryl bromides, the latter of which has remained, hitherto, elusive under thermal Ni catalysis. Moreover, the accessibility of esterification in the absence of light is especially notable because previous mechanistic studies on this transformation under photoredox conditions have unanimously invoked energy-transfer-mediated pathways.
- Nocera, Daniel G.,Qin, Yangzhong,Sun, Rui
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supporting information
p. 9527 - 9533
(2020/04/08)
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- Phenazine-Based Donor Acceptor Systems as Organic Photocatalysts for "metal-free" C-N/C-C Cross-Coupling
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With an aim to achieve a balance between ground-state and excited-state reduction potential of donor acceptor systems for efficient C-N/C-C cross-coupling, a series of donor acceptor systems DA1-DA4 have been synthesized by varying the donor strength and connecting positions. With an increase in donor strength, systematic elevation in the ground-state reduction potential and decrease in the HOMO-LUMO gap was observed. Interestingly, all the derivatives DA1-DA4 could catalyze the C-N bond formation reaction between activated aryl halides and amines at low catalytic loading under metal-free conditions without the need of any external base upon irradiation with white LED. A balance was realized in the case of derivative DA2, which exhibits high efficiency in C-N couplings. Different control experiments support the validity of the energy as well as electron transfer pathways in the visible light-mediated C-N bond formation. This study further reveals the potential of derivative DA1 in "metal-free"Sonogashira coupling involving activated aryl halides which is attributed to its high excited-state reduction potential.
- Deol, Harnimarta,Singh, Gurpreet,Kumar, Manoj,Bhalla, Vandana
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p. 11080 - 11093
(2020/10/12)
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- Nickel-catalyzed cyanation of aryl halides and triflates using acetonitrile: Via C-CN bond cleavage assisted by 1,4-bis(trimethylsilyl)-2,3,5,6-tetramethyl-1,4-dihydropyrazine
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We developed a non-toxic cyanation reaction of various aryl halides and triflates in acetonitrile using a catalyst system of [Ni(MeCN)6](BF4)2, 1,10-phenanthroline, and 1,4-bis(trimethylsilyl)-2,3,5,6-tetramethyl-1,4-dihydropyrazine (Si-Me4-DHP). Si-Me4-DHP was found to function as a reductant for generating nickel(0) species and a silylation reagent to achieve the catalytic cyanation via C-CN bond cleavage.
- Ueda, Yohei,Tsujimoto, Nagataka,Yurino, Taiga,Tsurugi, Hayato,Mashima, Kazushi
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p. 994 - 999
(2019/02/03)
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- A group of diphosphine-thiosemicarbazone complexes of palladium: Efficient precursors for catalytic C–C and C–N coupling reactions
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Reaction of 4-R-benzaldehyde thiosemicarbazone (denoted in general as HL-R; where H stands for the dissociable acidic proton and R (R = OCH3, CH3, H, Cl and NO2) for the substituent) with [Pd(dppe)(EtOH)2]2+, generated in situ via interaction of [Pd(dppe)Cl2] (dppe = 1,2-bis(diphenylphosphino)ethane) with AgNO3 in hot ethanol, in the presence of triethylamine affords a group of orange complexes of the type [Pd(dppe)(L-R)]NO3. Structures of [Pd(dppe)Cl2] and [Pd(dppe)(L-OCH3)]NO3 have been determined by X-ray crystallography. In the [Pd(dppe)(L-R)]NO3 complexes, the thiosemicarbazone ligands are coordinated to the metal center as monoanionic bidentate N,S-donors forming five-membered chelate rings. The [Pd(dppe)(L-R)]NO3 complexes show intense absorptions in the visible and ultraviolet regions, which have been analyzed by TDDFT calculations. All the [Pd(dppe)(L-R)]NO3 complexes are found to efficiently catalyze Suzuki-type C–C and Buchwald-type C–N coupling reactions.
- Thapa, Kiran,Paul, Piyali,Bhattacharya, Samaresh
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p. 232 - 239
(2018/11/06)
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- Practical heterogeneous photoredox/nickel dual catalysis for C-N and C-O coupling reactions
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Efficient C-N and C-O coupling reactions of aryl halides with amines and alcohols have been developed by using the strategy of heterogeneous visible light photoredox and nickel dual catalysis. Obviously, the joint use of inexpensive and bench-stable CdS and nickel salts, together with mild reaction conditions, makes these two transformations attractive for the synthetic community. This heterogeneous dual catalysis system also proved to be successful in the ligand-free catalytic hydroxylation of aryl bromide with water as a nucleophile. The practicality of this protocol is further emphasized by the scaled-up reaction and the reusability of heterogeneous photocatalysts.
- Liu, Yi-Yin,Liang, Dong,Lu, Liang-Qiu,Xiao, Wen-Jing
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supporting information
p. 4853 - 4856
(2019/05/02)
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- Identification of N-Benzyl 3,5-Dinitrobenzamides Derived from PBTZ169 as Antitubercular Agents
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A series of benzamide scaffolds were designed and synthesized by the thiazinone ring opening of PBTZ169, and N-benzyl 3,5-dinitrobenzamides were finally identified as anti-TB agents in this work. 3,5-Dinitrobenzamides D5, 6, 7, and 12 exhibit excellent in vitro activity against the drug susceptive Mycobacterium tuberculosis H37Rv strain (MIC: 0.0625 μg/mL) and two clinically isolated multidrug-resistant strains (MIC 0.016-0.125 μg/mL). Compound D6 displays acceptable safety and better pharmacokinetic profiles than PBTZ169, suggesting its promising potential to be a lead compound for future antitubercular drug discovery.
- Li, Linhu,Lv, Kai,Yang, Yupeng,Sun, Jingquan,Tao, Zeyu,Wang, Apeng,Wang, Bin,Wang, Hongjian,Geng, Yunhe,Liu, Mingliang,Guo, Huiyuan,Lu, Yu
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supporting information
p. 741 - 745
(2018/07/05)
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- Nickel-Catalyzed Cyanation of Aryl Chlorides and Triflates Using Butyronitrile: Merging Retro-hydrocyanation with Cross-Coupling
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We describe a nickel-catalyzed cyanation reaction of aryl (pseudo)halides that employs butyronitrile as a cyanating reagent instead of highly toxic cyanide salts. A dual catalytic cycle merging retro-hydrocyanation and cross-coupling enables the conversion of a broad array of aryl chlorides and aryl/vinyl triflates into their corresponding nitriles. This new reaction provides a strategically distinct approach to the safe preparation of aryl cyanides, which are essential compounds in agrochemistry and medicinal chemistry.
- Yu, Peng,Morandi, Bill
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p. 15693 - 15697
(2017/12/02)
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- An efficient heterogeneous ligand free C-N coupling reaction catalyzed by palladium supported on magnetic nanoparticles
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The catalytic activity of palladium supported on magnetic nanoparticles in the amination coupling reaction of different nitrogen containing substrates with aryl halides was investigated. C-N bond formation was achieved in moderate to excellent yields and the catalyst could be separated by magnetic decantation.
- Rafiee, Ezzat,Ataei, Ali,Joshaghani, Mohammad
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p. 219 - 222
(2015/12/31)
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- Structural diversity of phenoxy functionalized triazol-5-ylidene palladium(II) complexes and their application in C-N bond formation
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The preparation and isolation of a variety of mono-, bis-, and heteroleptic mesoionic triazol-5-ylidene palladium(II) complexes is reported. Treatment of phenoxy functionalized triazolium salts [Bn-MIC(H)]+I- (1) and [Mes-MIC(H)]+I- (2) with half equivalent of palladium acetate, produced complexes 3 and 4 with a general structure of [(MIC)2Pd(I)2] as isomeric cis/trans mixtures. When the reaction of palladium acetate and the cationic precursors was carried out with equimolar amounts in presence of sodium iodide, the μ2-I2 bridged complexes 5 and 6 of the type [(MIC)PdI2]2 were obtained as unique products. Additionally, the preparation of the heteroleptic PEPPSI-type complexes ([Py(PdI2)MIC]) 7 and 8 was readily achieved by the thermal treatment of the triazolium precursors with PdCl2, K2CO3, and sodium iodide in pyridine. All complexes have been fully characterized by 1H and 13C NMR, FT-IR, elemental analysis, and in the case of 2, 3trans, 6, and 7 single crystal X-ray diffraction. Preliminary catalytic results with the palladium series established the enhanced performance of PEPPSI complexes 7 and 8 in the Buchwald-Hartwing catalyzed formation of C-N bonds between aryl halides and primary/secondary amines under mild reaction conditions.
- Mendoza-Espinosa, Daniel,González-Olvera, Rodrigo,Osornio, Cecilia,Negrón-Silva, Guillermo E.,álvarez-Hernández, Alejandro,Bautista-Hernández, Claudia I.,Suárez-Castillo, Oscar R.
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supporting information
p. 142 - 149
(2016/01/12)
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- Buchwald-Hartwig amination reaction using supported palladium on phosphine-functionalized magnetic nanoparticles
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The supported palladium on phosphine-functionalized magnetic nanoparticles (Pd-PFMN) was found to be an efficient magnetically separable catalyst for the Buchwald-Hartwig amination reaction (BHAR) under solvent-free conditions. All of the reactions in the presence of Pd-PFMN catalyst afforded the corresponding products in good to excellent yields. The catalyst can be easily separated from the reaction mixture using an external magnetic field, and it can be reused at least five cycles without significant loss in its initial catalytic activity.
- Zarnaghash, Narges,Panahi, Farhad,Khalafi-Nezhad, Ali
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p. 2057 - 2064
(2015/10/06)
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- First Application of Heterogeneous Cobalt Catalysis in Csp2-N Cross-Coupling of Activated Chloroarenes under Ligand-Free Conditions
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A heterogeneous CoII/Al2O3 catalyst efficiently catalyses the N-arylation of N-heterocycles and open-chain secondary amines by activated chloroarenes and chloroheteroarenes under ligand-free conditions in water to give a series of functionalized tertiary amines. The catalyst was prepared by immobilizing CoBr2 onto the surface of Al2O3, and was characterized by X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, and energy-dispersive X-ray analysis. This catalyst could be recycled up to six times without any appreciable loss of catalytic activity. A heterogeneous CoII/Al2O3 catalyst efficiently catalyses the N-arylation of N-heterocycles and open- or closed-chain secondary amines by activated chloroarenes and chloroheteroarenes under ligand-free conditions in water to give a series of functionalized tertiary amines.
- Mukherjee, Nirmalya,Chatterjee, Tanmay,Ranu, Brindaban C.
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p. 4018 - 4023
(2015/06/30)
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- A tuned bicyclic proazaphosphatrane for catalytically enhanced n-arylation reactions with aryl chlorides
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The N-arylation of various amines with aryl chlorides proceeded in good-to-excellent yields in the presence of P[N{(p-NMe2)C6H4CH2}CH2CH2]3N (1e, a new electron-rich proazaphosphatrane ligand) and small amounts of Pd2(dba)3 (dba = dibenzylideneacetone). This catalytic system was also very effective for the synthesis of carbazoles. An efficient palladium-catalyzed N-arylation reaction of amines under mild conditions with a tuned bicyclic proazaphosphatrane has been developed.
- Kim, So Han,Kim, Min,Verkade, John G.,Kim, Youngjo
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p. 1954 - 1960
(2015/03/18)
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- N-(1-Oxy-2-picolyl)oxalamic Acid as an Efficient Ligand for Copper-Catalyzed Amination of Aryl Iodides at Room Temperature
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N-(1-Oxy-pyridin-2-ylmethyl)oxalamic acid was identified as efficient ligand for CuI-catalyzed amination of aryl halides at room temperature. In our catalytic system, N-arylation of cyclic secondary amines, primary amines, amino acids, and ammonia proceeded with moderate to excellent yields and high functional group tolerance.
- Wang, Yongbin,Ling, Jing,Zhang, Yu,Zhang, Ao,Yao, Qizheng
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p. 4153 - 4161
(2015/07/01)
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- Anti-Inflammation Compounds
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The present invention refers to: a compound having the general formula (I), wherein n is 0, 1, 2 or; m is 0, 1, 2 or 3; o is 0, 1, 2 or 3; W, X, Y and Z are independently selected from CH, N or N-oxide; A is NR4, C═O, C═S, OP(O)(O), P═O, CH2, or a heteroarly selected from the group consisting of (a), (b), (c), (d), (e), (f), (g); V is C═O, O, S, CH2, or NR5; as well as its use in treating inflammatory diseases such as asthma, COPD, inflammation post infection, arthritis, atherosclerosis, pain and dermatitis.
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Paragraph 0117; 0119
(2014/06/23)
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- Lead optimization of a novel series of imidazo[1,2-a]pyridine amides leading to a clinical candidate (Q203) as a multi- and extensively-drug- resistant anti-tuberculosis agent
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A critical unmet clinical need to combat the global tuberculosis epidemic is the development of potent agents capable of reducing the time of multi-drug-resistant (MDR) and extensively-drug-resistant (XDR) tuberculosis therapy. In this paper, we report on the optimization of imidazo[1,2-a]pyridine amide (IPA) lead compound 1, which led to the design and synthesis of Q203 (50). We found that the amide linker with IPA core is very important for activity against Mycobacterium tuberculosis H37Rv. Linearity and lipophilicity of the amine part in the IPA series play a critical role in improving in vitro and in vivo efficacy and pharmacokinetic profile. The optimized IPAs 49 and 50 showed not only excellent oral bioavailability (80.2% and 90.7%, respectively) with high exposure of the area under curve (AUC) but also displayed significant colony-forming unit (CFU) reduction (1.52 and 3.13 log10 reduction at 10 mg/kg dosing level, respectively) in mouse lung.
- Kang, Sunhee,Kim, Ryang Yeo,Seo, Min Jung,Lee, Saeyeon,Kim, Young Mi,Seo, Mooyoung,Seo, Jeong Jea,Ko, Yoonae,Choi, Inhee,Jang, Jichan,Nam, Jiyoun,Park, Seijin,Kang, Hwankyu,Kim, Hyung Jun,Kim, Jungjun,Ahn, Sujin,Pethe, Kevin,Nam, Kiyean,No, Zaesung,Kim, Jaeseung
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p. 5293 - 5305
(2014/07/08)
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- Cobalt-catalyzed electrophilic amination of arylzincs with N-chloroamines
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Roles reversed: An efficient cobalt-catalyzed electrophilic amination of arylzinc reagents has been achieved. A variety of functionalized arylzincs and N-chloroamines were coupled under mild conditions (see scheme). Both secondary and tertiary arylamines were obtained in moderate to excellent yields. Copyright
- Qian, Xin,Yu, Zailu,Auffrant, Audrey,Gosmini, Corinne
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p. 6225 - 6229
(2013/07/05)
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- "TRPV1 VANILLOID RECEPTOR ANTAGONISTS WITH A BICYCLIC PORTION"
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The invention discloses compounds of formula I wherein Y is a group of formula A, B, C, D, or E: and W, Q, n, R1, R2, R3, U1-U5, J and K have the meanings given in the description. The compounds of formula I are TRPV1 antagonists and are useful as active
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Page/Page column 46; 134
(2011/10/13)
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- TRPV1 vanilloid receptor antagonists with a bicyclic portion
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The invention discloses compounds of formula I wherein Y s selected from a group of formula and W, Q, n, R1, R2, R3, U1-U5 have the meanings given in the description. The compounds of formula I are TRPV1 antagonists and are useful as active ingredients of pharmaceutical compositions for the treatment of pain and other conditions ameliorated by the inhibition of the vanilloid receptor TRPV1. 1.
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Page/Page column 17
(2011/11/01)
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- ANTI-INFECTIVE COMPOUNDS
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The present invention relates to small molecule compounds and their use in the treatment of bacterial infections, in particular Tuberculosis.
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Page/Page column 19-20
(2011/10/10)
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- Transition-metal-free electrophilic amination between aryl grignard reagents and N-chloroamines
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In the presence of N,N,N′,N′-tetramethylethylenediamine (TMEDA) as an additive, easily prepared and handled N-chloroamines react with aryl Grignard reagents to give a variety of arylamines in good to excellent yields. Functional groups such as ester and nitrile are compatible under the reaction conditions (Figure Presented).
- Hatakeyama, Takuji,Yoshimoto, Yuya,Ghorai, Sujit K.,Nakamura, Masaharu
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supporting information; experimental part
p. 1516 - 1519
(2010/06/20)
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- Synthesis and evaluation of some novel dibenzo[b,d]furan carboxylic acids as potential anti-diabetic agents
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A series of novel dibenzo[b,d]furan mono-carboxylic acid derivatives were synthesized, characterized and evaluated for their ability to inhibit Protein Tyrosine Phosphatase 1B (PTP1B) in vitro in order to use them as potential anti-diabetic agents. Structure-activity relationship study led to the identification of potent compound 5E which inhibited PTP1B with IC50 value of 82 ± 0.43 nM. Compound 5E was screened in vivo as drug candidate for anti-diabetic activity using rosiglitazone maleate as the standard. Compound 5E showed significant reduction in body weight, fed-state whole blood glucose (WBG), fasting WBG, plasma glucose and plasma cholesterol levels and non-significant reduction in fasting plasma triglyceride levels in ob/ob mice. A series of dibenzo[b,d]furan carboxylic acids were synthesized and evaluated for anti-diabetic activity. Compound 5E inhibited PTP1B with IC50 of 82 nM and reduced WBG and plasma glucose in ob/ob mice.
- Lakshminarayana,Prasad, Y. Rajendra,Gharat, Laxmikant,Thomas, Abraham,Narayanan, Shridhar,Raghuram,Srinivasan,Gopalan, Balasubramanian
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experimental part
p. 3709 - 3718
(2010/11/04)
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- Novel, soluble diphenyl-diketo-pyrrolopyrroles: Experimental and theoretical study
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Derivatives of diphenyl-diketo-pyrrolopyrrole, possessing electron-donating or withdrawing groups in the p-position of the phenyl, were synthesized and studied using optical characterization (absorption, fluorescence, time-resolved fluorescence) and quant
- Vala,Vyňuchal,Toman,Weiter,Luňák Jr.
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experimental part
p. 176 - 182
(2010/11/02)
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- SUBSTITUTED SULFONAMIDE COMPOUNDS
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Substituted sulfonamide derivatives, a process for their preparation, pharmaceutical compositions containing these compounds, and to the use of substituted sulfonamide derivatives in the treatment or inhibition of pain and/or various disorders or disease states.
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Page/Page column 46
(2008/12/06)
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- In vitro structure-activity relationship and in vivo characterization of 1-(aryl)-3-(4-(amino)benzyl)urea transient receptor potential vanilloid 1 antagonists
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The synthesis and structure-activity relationship of 1-(aryl)-3-(4-(amino) benzyl)urea transient receptor potential vanilloid 1 (TRPV1) antagonists are described. A variety of cyclic amine substituents are well tolerated at the 4-position of the benzyl group on compounds containing either an isoquinoline or indazole heterocyclic core. These compounds are potent antagonists of capsaicin activation of the TRPV1 receptor in vitro. Analogues, such as compound 45, have been identified that have good in vivo activity in animal models of pain. Further optimization of 45 resulted in compound 58 with substantially improved microsome stability and oral bioavailability, as well as in vivo activity.
- Perner, Richard J.,DiDomenico, Stanley,Koenig, John R.,Gomtsyan, Arthur,Bayburt, Erol K.,Schmidt, Robert G.,Drizin, Irene,Guo, Zhu Zheng,Turner, Sean C.,Jinkerson, Tammie,Brown, Brian S.,Keddy, Ryan G.,Lukin, Kurill,McDonald, Heath A.,Honore, Prisca,Mikusa, Joe,Marsh, Kennan C.,Wetter, Jill M.,St. George, Karen,Jarvis, Michael F.,Faltynek, Connie R.,Lee, Chih-Hung
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p. 3651 - 3660
(2008/02/12)
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- Substituted compounds derived from N-(benzyl)phenylacetamide, preparation and uses
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This invention relates to poly-substituted derivatives of the N-(benzyl)phenylacetamide type, pharmaceutical compositions comprising same, therapeutic uses thereof, more particularly in the fields of human and animal health. This invention also relates to a process for the preparation of such derivatives.
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Page/Page column 34
(2010/10/20)
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- Pyrrolobenzodiazepine pyridine carboxamides and derivatives as follicle-stimulating hormone receptor antagonists
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This invention provides pyrrolobenzodiazepine pyridine carboxamides selected from those of Formula (1), which act as follicle stimulating hormone receptor antagonists. The invention also provides pharmaceutical compositions and methods of treatment utilizing the compounds of Formulae (1) and (2).
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Page/Page column 53-54
(2010/11/25)
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- NUCLEOPHILIC HETEROCYCLIC CARBENE DERIVATIVES OF PD(ACAC)2 FOR CROSS-COUPLING REACTIONS
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Embodiments in accordance with the present invention provide for a palladium complex characterized by the general Formula (I): where A is a bidentate monoanionic ligand, NHC is a nucleophilic heterocyclic carbene, and Z is an anionic ligand. Such palladium complexes are useful in initiating cross-coupling reactions.
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Page/Page column 17, 32-33
(2010/11/25)
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- Amino acid promoted CuI-catalyzed C-N bond formation between aryl halides and amines or N-containing heterocycles
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CuI-catalyzed coupling reaction of electron-deficient aryl iodides with aliphatic primary amines occurs at 40 °C under the promotion of N-methylglycine. Using L-proline as the promoter, coupling reaction of aryl iodides or aryl bromides with aliphatic primary amines, aliphatic cyclic secondary amines, or electron-rich primary arylamines proceeds at 60-90 °C; an intramolecular coupling reaction between aryl chloride and primary amine moieties gives indoline at 70 °C; coupling reaction of aryl iodides with indole, pyrrole, carbazole, imidazole, or pyrazole can be carried out at 75-90 °C; and coupling reaction of electron-deficient aryl bromides with imidazole or pyrazole occurs at 60-90 °C to provide the corresponding N-aryl products in good to excellent yields. In addition, N,N-dimethylglycine promotes the coupling reaction of electron-rich aryl bromides with imidazole or pyrazole to afford the corresponding N-aryl imidazoles or pyrazoles at 110 °C. The possible action of amino acids in these coupling reactions is discussed.
- Zhang, Hui,Cai, Qian,Ma, Dawei
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p. 5164 - 5173
(2007/10/03)
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- Scope and utility of CsOH·H2O in animation reactions via direct coupling of aryl halides and sec-alcyclic amines
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Direct coupling of aryl halides with sec-alicyclic amines promoted by CsOH·H2O in DMSO to the corresponding aryl substituted amines, with good to excellent yields, is reported herein. A variety of aryl halides and sec-alicyclic amines with a broad range of electronic diversity and functional groups was studied in this transformation, thus offering general applicability in organic synthesis.
- Varala, Ravi,Ramu,Alam, M. Mujahid,Adapa, Srinivas R.
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p. 1747 - 1750
(2007/10/03)
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- P[N(i-Bu)CH2CH2]3N: A versatile ligand for the Pd-catalyzed amination of aryl chlorides
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(Matrix presented) Palladium-catalyzed amination reactions of aryl chlorides with amines proceeded in the presence of the bicyclic triaminophosphine P[N(i-Bu)CH2CH2]3N to afford the corresponding arylamines in good to excellent yields. Electron-poor, electron-neutral, and electron-rich aryl chlorides all participated with equal ease.
- Urgaonkar, Sameer,Nagarajan,Verkade, John G.
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p. 815 - 818
(2007/10/03)
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- Study of ultrasound promoted aromatic nucleophilic substitution of halobenzenes with amines
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The sonochemical nucleophilic aromatic substitution of substituted haloarenes with different amines were studied. The reaction course was found to be strongly depended on basicity, bulkiness, and boiling point of amines as well as on the electron-withdrawing property of the substituents.
- Meciarova, Maria,Toma, Stefan,Podlesna, Jana,Kiripolsky, Michal,Cisarova, Ivana
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- FUROISOQUINOLINE DERIVATIVES, PROCESS FOR PRODUCING THE SAME AND USE THEREOF
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A compound having a partial structure represented by Formula: or a salt thereof has an excellent phosphodiesterase (PDE) IV-inhibiting effect, and is useful as a prophylactic or therapeutic agent against inflammatory diseases, for example, bronchial asthma, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, autoimmune disease, diabetes and the like.
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- Method of inhibiting neoplastic cells with imidazoquinazoline derivatives
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A method for inhibiting neoplasia, particularly cancerous and precancerous lesions by exposing the affected cells to imidazoquinazoline derivatives.
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- Imidazoquinazoline derivatives
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PCT No. PCT/JP97/03023 Sec. 371 Date Apr. 27, 1998 Sec. 102(e) Date Apr. 27, 1998 PCT Filed Aug. 29, 1997 PCT Pub. No. WO98/08848 PCT Pub. Date Mar. 5, 1998Imidazoquinoline derivatives of the formula (wherein X may be O or S) provide selective cyclic guanosine 3',5' monophosphate (cGMP)-specific phosphodiesterase (PDE) inhibitory activity. The compounds are useful for treating or ameliorating cardiovascular disease such as thrombosis, angina pectoris, hypertension, heart failure and arterial sclerosis, as well as asthma, impotence and the like.
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- Scope and Limitations of the Pd/BINAP-Catalyzed Amination of Aryl Bromides
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Mixtures of Pd2(dba)3 or Pd(OAc)2 and BINAP catalyze the cross-coupling of amines with a variety of aryl bromides. Primary amines are arylated in high yield, and certain classes of secondary amines are also effectively transformed. The process tolerates the presence of several functional groups including methyl and ethyl esters, enolizable ketones, and nitro groups provided that cesium carbonate is employed as the base. Most reactions proceed to completion with 0.5-1.0 mol % of the palladium catalyst; in some cases, catalyst levels as low as 0.05 mol % Pd may be employed. Reactions are considerably faster if Pd(OAc)2 is employed as the precatalyst, and the order in which reagents are added to the reaction has a substantial effect on reaction rate. It is likely that the catalytic process proceeds via bis(phosphine)palladium complexes as intermediates. These complexes are less prone to undergo undesirable side reactions which lead to diminished yields or catalyst deactivation than complexes of the corresponding monodentate triarylphosphines.
- Wolfe, John P.,Buchwald, Stephen L.
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p. 1144 - 1157
(2007/10/03)
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- A facile route to aryl amines: Nucleophilic substitution of aryl triflates
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The aromatic nucleophilic substitution (S(N)Ar) between aryl triflates and secondary amines has been studied. In the absence of solvent, the reaction proceeds at room temperature for nitro and cyano activated aryl triflates and requires higher temperatures in the case of carboxy activation. Variable triflate reactivity could be explained in terms of frontier molecular orbital theory. This methodology has been applied for the synthesis of substituted piperidyl pyridines.
- Schio, Laurent,Lemoine, Guy,Klich, Michel
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p. 1559 - 1562
(2007/10/03)
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- Palladium-catalyzed amination of aryl chlorides
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Pd(PCy3)Cl2 (Cy = cyclohexyl) catalyzed the reaction of aryl chlorides and secondary amines in the presence of NaO(t)Bu to give the corresponding aryl amines in good to excellent yields. In some of the reactions, an excess amount of aryl chloride (aryl chloride/amine = 2) improved the yields.
- Reddy, Nagavelli Prabhakar,Tanaka, Masato
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p. 4807 - 4810
(2007/10/03)
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- Improved functional group C compatibility in the palladium-catalyzed amination of aryl bromides
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Aryl bromides are coupled with amines in the presence of a palladium catalyst and a stoichiometric amount of cesium carbonate. Using these conditions base-sensitive functional groups, which were incompatible with our previously reported catalytic-amination reaction conditions, are well tolerated.
- Wolfe, John P.,Buchwald, Stephen L.
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p. 6359 - 6362
(2007/10/03)
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- Reductive one batch synthesis of N-arylpiperidines from primary amines and glutaraldehyde
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The construction of the piperidine ring about an aromatic nitrogen atom, by a 5C + N reductiye condensation reaction, using glutaraldehyde (pentanedial) and sodium borohydride in acidic water/methanol medium is described. The reaction is fast, affords good to excellent yields and appears insensitive to electronic effects and severe steric hindrance; it is found to be compatible with a large variety of aryl substituents, including nitro and oxo groups.
- Verardo,Giumanini,Favret,Strazzolini
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p. 447 - 450
(2007/10/02)
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- Studies of Tetriary Amine Oxides. 9. Thermal Rearrangement of 1-(4-Substituted-phenyl)piperidine N-Oxides to the Corresponding N-Hydroxylamines
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(4-Substituted - phenyl)piperidine N-oxides undergo a thermal rearrangement to O-arylhydroxylamines.Electron withdrawing substituents are essential for the rearrangement and must be ortho or para relative to the N-O function.The reaction has been found to be first order in substrate when rates were measured in dioxane, and the activation parameters were calculated.The order of reactivity in this rearrangement is NO2 >> CN > COPh > COMe > COOEt > CONH2.The rates correlate very well with ?- constants and the ρ value was positive and large (+3.6) pointing to a highly po lar activated complex with an electron-rich reaction center.All results strongly support an intramolecular cyclic mechanism.
- Khuthier, Abdul-Hussain,Al-Mallah, Khawla Y.,Hanna, Salim Y.,Abdulla, Noor-Aldeen I.
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p. 1710 - 1713
(2007/10/02)
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- Mesogenic Esters of the 4-(Alkylpiperidino) Benzoic Acids
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A number of alkyl and 4-substituted phenyl 4-(4-alkylpiperidino) benzoates have been prepared and their proprties examined.
- Adomenas, P.,Sirutkaitis, R.
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p. 269 - 276
(2007/10/02)
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