- THE MECHANISM OF N-ALKYLATION OF WEAK N-H-ACIDS BY PHASE TRANSFER CATALYSIS
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The alkylation of aromatic amines in the presence of inorganic bases is accelerated by a PT catalyst even if KHCO3 is the base.ArNR(1-) ions seem not to be involved.A novel type of mechanism for a PTC process is proposed.
- Dehmlow, Eckehard V.,Thieser, Rainer,Zahalka, Hayder Ali,Sasson, Yoel
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- Unusual reactivity of zinc borohydride - Reduction of amides to amines
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Zinc borohydride reduces secondary amides to the corresponding N-ethyl amines in excellent yields. The reduction requires only stoichiometric quantities of hydride and does not require the addition of any Lewis acid. The amides are isolated by simple hydrolysis of the reaction mixture.
- Narasimhan,Madhavan,Balakumar,Swarnalakshmi
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- Synthesis of new 1,2,3-triazole linked benzimidazole molecules as anti-proliferative agents
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One pot click chemistry is used to link triazole and benzimidazole pharmacophore to get N-((1-((1H-benzo[d]imidazol-2-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)aniline and its derivatives. Flexible linkages in the form of –CH2–R or –O–R/–N–R were designed during synthesis. All the newly synthesized compounds were characterized by FT-IR and NMR spectroscopy as well as high-resolution mass spectrometry. Selected compounds were screened for in vitro anti-proliferative activity using National Cancer Institute (NCI)-60 human tumor cell line screening program. The most potent structure N-((1-((1H-benzo[d]imidazol-2-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)-4-chloroaniline 7e showed 40% growth inhibition in renal cancer cell line (UO-31) at 10 μM concentration.
- Sahay, Ishani I.,Ghalsasi, Prasanna S.
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- Synthesis and evaluation of some new (1,2,4) triazolo(4,3-a)quinoxalin- 4(5h)-one derivatives as AMPA receptor antagonists
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This study involves the synthesis and anticonvulsant evaluation of 1-ethyl-3-hydrazinylquinoxaline-2-(1H)-one (8), its chemical confirmations 9 and 10 and certain (1,2,4) triazolo(4,3-a)quinoxalin-4(5H)-one compounds 11, 12, 13, 13a, 13b, 13c, 13d, 13e, 13f, 14, 15, 16. The structure of the synthesized compounds was confirmed chemically by elemental analyses and spectral data (IR, 1H NMR, 13C NMR, and Mass). Docking studies were preformed to all of the synthesized compounds to predict, in a qualitative way, the anticonvulsant activity of the proposed compounds. There is a promising correlation between the results of molecular modeling and the anticonvulsant activity of the synthesized compounds. The highest fitting value was noticed for compounds 9 and 10, which showed the highest anticonvulsant activity.
- Abul-Khair, Hamada,Elmeligie, Salwa,Bayoumi, Ashraf,Ghiaty, Adel,El-Morsy, Ahmed,Hassan, Memy H.
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- Synthesis and in vitro antifungal evaluation of benzoimidazolyl-piperazinyl-phenylmethanone derivatives
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Benzimidazole and piperazines are the important pharmacophores in the structures of many antifungal compounds. Further, the phenylmethanone are also a unique class of compounds whose antifungal profile is not much exploited. So to exploit their antifungal potential we have selected these three combinations and framed the novel parent structure for our research work. In this study a novel series of benzimidazoles derivatives was synthesized by microwave irradiation and characterized by 1H NMR, 13C NMR, Infra Red (IR), and Mass Spectroscopy (MS), and by elemental analysis. The screening of compound for in vitro (turbidimetric method) antifungal activity against C.albicans revealed activity in many of the compounds as comparable to that of ketoconazole.
- Kankate, Rani S.,Gide, Parag S.,Belsare, Deepak P.
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- In vivo- and in silico-driven identification of novel synthetic quinoxalines as anticonvulsants and AMPA inhibitors
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The lack of effective therapies for epileptic patients and the potentially harmful consequences of untreated seizure incidents have made epileptic disorders in humans a major health concern. Therefore, new and more potent anticonvulsant drugs are continually sought after,?to combat epilepsy. On the basis of the pharmacophoric structural specifications of effective α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonists with an efficient anticonvulsant activity, the present work reports the design and synthesis of two novel sets of quinoxaline derivatives. The anticonvulsant activity of the synthesized compounds was evaluated in vivo according to the pentylenetetrazol-induced seizure protocol, and the results were compared with those of perampanel as a reference drug. Among the synthesized compounds, 24, 28, 32, and 33 showed promising activities with ED50 values of 37.50, 23.02, 29.16, and 23.86 mg/kg, respectively. Docking studies of these compounds suggested that AMPA binding could be the mechanism of action of these derivatives. Overall, the pharmacophore-based structural optimization, in vivo?and in silico docking, and druglikeness studies indicated that the designed compounds could serve as promising candidates for the development of effective anticonvulsant agents with good pharmacokinetic profiles.
- Abulkhair, Hamada S.,Elmeligie, Salwa,Ghiaty, Adel,El-Morsy, Ahmed,Bayoumi, Ashraf H.,Ahmed, Hany E. A.,El-Adl, Khaled,Zayed, Mohamed F.,Hassan, Memy H.,Akl, Eman N.,El-Zoghbi, Mona S.
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- Tetraphenylethylene-based blue light material containing benzimidazole unit as well as preparation method and application
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The invention discloses a tetraphenylethylene-based blue light material containing a benzimidazole unit. The tetraphenylethylene-based blue light material is shown as a structural formula I or II, wherein R1 is H, tert-butyl, n-butyl or hydroxyl, and R2 is alkyl. A 2-nitro-N-tert-butylphenyl amine or 2-nitro-N-n-butylphenyl amine precursor and a 4-formyl tetraphenylethylene precursor is firstly prepared, and then cyclization reaction is carried out to prepare a compound shown as the formula I or II. A preparation method of the compound is easy to operate, the reaction is moderate and the yield is high; the compound has relatively high decomposition temperature and glass-transition temperature, and shows blue fluorescence; the compound has a relatively good single-color property, so that an OLED (Organic Light Emitting Diode) device prepared by taking the compound as a luminescent material emits blue light; the starting voltage is 3.3V and the maximum brightness efficiency is 1.48cd/A. (The formula I and the formula II are shown in the description).
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Paragraph 0027; 0028; 0029; 0090; 0091; 0092
(2017/10/10)
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- The thermal instability of 2,4 and 2,6-N-alkylamino-disubstituted and 2-N-alkylamino-substituted nitrobenzenes in weakly alkaline solution: Sec-amino effect
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We report herein the preparation of two families of secondary amines by the reactions of two equivalents of monoamines with either 2,4 or 2,6-difluoronitrobenzenes in N,N-dimethylacetamide in the presence of anhydrous potassium carbonate, as precursors of biologically important nitric oxide donating N-nitrosamines. In both instances, these compounds could be prepared in quantitative yield when the reaction temperature was held below 130°C. Above this reaction temperature, an unexpected cyclization reaction between the nitro and newly formed adjacent secondary amine group leads to the formation of benzimidazole or quinoxaline rings in low yields. Reasonable reaction mechanisms for the cyclization reaction are proposed.
- Walczak, Christopher,Payne, Thomas J.,Wade, Colin B.,Yonkey, Matthew,Scheid, Melissa,Badour, Alec,Mohanty, Dilip K.
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p. 681 - 687
(2015/05/13)
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- Imidoyl dichlorides as new reagents for the rapid formation of 2-aminobenzimidazoles and related azoles
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The development of a reagent for the efficient synthesis of five- and six-membered azoles at room temperature is proposed. A variety of substituted 2-aminobenzimidazoles are synthesized in good to excellent yields. The ability to incorporate various protecting groups makes the imidoyl dichloride reagent amenable to a large number of syntheses. The reagent is applied to the total synthesis of the 2-aminobenzimidazole containing carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), from 2-chloro-3-nitropyridine in >60% yield in 6 steps.
- Pollock, Julie A.,Kim, Sung Hoon,Katzenellenbogen, John A.
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p. 6097 - 6099
(2015/10/28)
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- Indole RSK inhibitors. Part 2: Optimization of cell potency and kinase selectivity
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A series of inhibitors for the 90 kDa ribosomal S6 kinase (RSK) based on an 1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide scaffold were optimized for cellular potency and kinase selectivity. This led to the identification of compound 24, BIX 02565, an attractive candidate for use in vitro and in vivo to explore the role of RSK as a target for the treatment heart failure.
- Kirrane, Thomas M.,Boyer, Stephen J.,Burke, Jennifer,Guo, Xin,Snow, Roger J.,Soleymanzadeh, Lida,Swinamer, Alan,Zhang, Yunlong,Madwed, Jeffery B.,Kashem, Mohammed,Kugler, Stanley,O'Neill, Margaret M.
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scheme or table
p. 738 - 742
(2012/03/11)
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- Optimizing sensitization processes in dinuclear luminescent lanthanide oligomers: Selection of rigid aromatic spacers
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This work illustrates a simple approach for optimizing the lanthanide luminescence in molecular dinuclear lanthanide complexes and identifies a particular multidentate europium complex as the best candidate for further incorporation into polymeric materials. The central phenyl ring in the bis-tridentate model ligands L3-L5, which are substituted with neutral (X = H, L3), electron-withdrawing (X = F, L4), or electron-donating (X = OCH 3, L5) groups, separates the 2,6-bis(benzimidazol-2-yl)pyridine binding units of linear oligomeric multi-tridentate ligand strands that are designed for the complexation of luminescent trivalent lanthanides, Ln(III). Reactions of L3-L5 with [Ln(hfac)3(diglyme)] (hfac- is the hexafluoroacetylacetonate anion) produce saturated single-stranded dumbbell-shaped complexes [Ln2(Lk)(hfac)6] (k = 3-5), in which the lanthanide ions of the two nine-coordinate neutral [N 3Ln(hfac)3] units are separated by 12-14 A. The thermodynamic affinities of [Ln(hfac)3] for the tridentate binding sites in L3-L5 are average (6.6 ≥ log(β2,1Y,Lk) ≥ 8.4) but still result in 15-30% dissociation at millimolar concentrations in acetonitrile. In addition to the empirical solubility trend found in organic solvents (L4 > L3 ? L5), which suggests that the 1,4-difluorophenyl spacer in L4 is preferable, we have developed a novel tool for deciphering the photophysical sensitization processes operating in [Eu2(Lk)(hfac) 6]. A simple interpretation of the complete set of rate constants characterizing the energy migration mechanisms provides straightforward objective criteria for the selection of [Eu2(L4)(hfac)6] as the most promising building block.
- Lemonnier, Jean-Francois,Guenee, Laure,Beuchat, Cesar,Wesolowski, Tomasz A.,Mukherjee, Prasun,Waldeck, David H.,Gogick, Kristy A.,Petoud, Stephane,Piguet, Claude
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supporting information; experimental part
p. 16219 - 16234
(2011/12/01)
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- Bicyclic Benzimidazole Compounds and Their Use as Metabotropic Glutamate Receptor Potentiators
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Compounds of Formula I: wherein A, B, D, L, R1, R2, R3, R4, m, and n are as defined for Formula I in the description. The invention also relates to processes for the preparation of the compounds and to new intermediates employed in the preparation, pharmaceutical compositions containing the compounds, and to the use of the compounds in therapy.
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(2009/08/14)
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- 1- Or 3-(3-amino-2-hydroxy-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2- ones: Potent, selective, and orally efficacious norepinephrine reuptake inhibitors
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Sequential structural modifications of the aryloxypropanamine template (e.g., atomoxetine, 2) led to a novel series of 1-(3-amino-2-hydroxy-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors (NRIs). In general, this series of compounds potently blocked the human norepinephrine transporter (hNET) while exhibiting selectivity at hNET against both the human serotonin (hSERT) and dopamine transporters (hDAT). Numerous compounds (e.g., 19-22) had low nonamolar hNET potency with IC 50 values of 7-10 nM and excellent selectivity (>500 fold) at hNET over hSERT and hDAT. Several compounds, such as 20 and 22, were tested in a telemetric rat model of ovariectomized-induced thermoregulatory dysfunction and were efficacious at oral doses of 3 mg/kg in reducing the tail skin temperature. In addition, compound 20 was also studied in the rat hot plate and spinal nerve ligation (SNL) models of acute and neuropathic pain, respectively, and was orally efficacious at doses of 3-10 mg/kg.
- Zhang, Puwen,Terefenko, Eugene A.,Bray, Jenifer,Deecher, Darlene,Fensome, Andrew,Harrison, Jim,Kim, Callain,Koury, Elizabeth,Mark, Lilly,McComas, Casey C.,Mugford, Cheryl A.,Trybulski, Eugene J.,Vu, An T.,Whiteside, Garth T.,Mahaney, Paige E.
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experimental part
p. 5703 - 5711
(2010/02/28)
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- 4-(Benzimidazol-2-yl)-1,2,5-oxadiazol-3-ylamine derivatives: Potent and selective p70S6 kinase inhibitors
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We report herein the design and synthesis of 4-(benzimidazol-2-yl)-1,2,5-oxadiazol-3-amine derivatives as inhibitors of p70S6 kinase. Screening hits containing the 4-(benzimidazol-2-yl)-1,2,5-oxadiazol-3-ylamine scaffold were optimized for p70S6K potency and selectivity against related kinases. Structure-based design employing an active site homology model derived from PKA led to the preparation of benzimidazole 5-substituted compounds 26 and 27 as highly potent inhibitors (Ki 100-fold selectivity against PKA, ROCK and GSK3.
- Bandarage, Upul,Hare, Brian,Parsons, Jonathan,Pham, Ly,Marhefka, Craig,Bemis, Guy,Tang, Qing,Moody, Cameron Stuver,Rodems, Steve,Shah, Sundeep,Adams, Chris,Bravo, Jose,Charonnet, Emmanuelle,Savic, Vladimir,Come, Jon H.,Green, Jeremy
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scheme or table
p. 5191 - 5194
(2010/03/24)
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- A simple chemical tuning of the effective concentration: Selection of single-, double-, and triple-stranded binuclear lanthanide helicates
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The replacement of terminal 2-benzimidazol-6-carboxypyridine (two internal rotational degrees of freedom) with 2-benzimidazol-8-hydroxyquinoline (one internal rotational degree of freedom) into segmental bis-tridentate ligands in going from L2 and [L32H]2- to [L12D-2H]2- does not significantly affect the structures of the resulting binuclear lanthanide triplestranded helical complexes [Ln2(L2)3]6+, [Ln2(L3-2H)3], and [Ln2(L12b-2H)3] (palindromic helices, intermetallic contact distance 9 A, helical pitch 1.4 nm per turn). However, their thermodynamic assemblies are completely different in solution, as evidenced by the spectacular decrease of the effective concentrations by two orders of magnitude for [L12b-2H] 2-. This key parameter in the [Ln2(L12b-2H)n] (n = 2, 3) complexes is further abruptly modulated along the lanthanide series (Ln = La to Lu), which provides an unprecedented tool for 1) tuning the number of ligand strands in the final helicates, 2) selectively coordinating lanthanides in the various complexes, and 3) controlling the ratio of lanthanide-containing polymers over discrete assemblies.
- Terazzi, Emmanuel,Guenee, Laure,Bocquet, Bernard,Lemonnier, Jean-Francois,Favera, Natalia Dalla,Piguet, Claude
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scheme or table
p. 12719 - 12732
(2010/06/14)
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- QUINOXALINONE DERIVATIVES AS INSULIN SECRETION STIMULATORS, METHODS FOR OBTAINING THEM AND USE THEREOF FOR THE TREATMENT OF DIABETES
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The present invention relates to quinoxalinone derivatives of formula (I), wherein R1, R2, R3, R4, R5 and R6 are as defined in claim 1, as insulin secretion stimulators. The invention also relates to the preparation and use of these quinoxalinone derivatives for the prophylaxis and/or treatment of diabetes and pathologies associated. Other preferred compounds are compounds of general formula (I), wherein R1, R2, R3, R4, R5 and R6 can be optionally substituted by one or more groups selected from Z.
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(2009/10/22)
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- Synthesis and activity of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors
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A series of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors was discovered. Several compounds such as 15 and 20 showed good hNET potency. Compounds 15 and 20 also displayed excellent selectivity at hNET that appeared superior to those of reboxetine and atomoxetine (4 and 5).
- Zhang, Puwen,Terefenko, Eugene A.,McComas, Casey C.,Mahaney, Paige E.,Vu, An,Trybulski, Eugene,Koury, Elizabeth,Johnston, Grace,Bray, Jenifer,Deecher, Darlene
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scheme or table
p. 6067 - 6070
(2009/08/07)
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- Reactions of arenediazonium o-benzenedisulfonimides with aliphatic triorganoindium compounds
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The reaction of various arenediazonium o-benzenedisulfonimides with aliphatic triorganoindium compounds is described. Surprisingly, with triethyl- or tributylindium we obtained N-ethyl- or N-butylanilines, respectively. This is the first case in which, at least formally, the reactive site of a diazonium salt is the nitrogen atom directly bonded to the aromatic ring. In contrast, with trimethylindium we obtained only formaldehyde (aryl)hydrazones. In order to explain the difference between trimethyl- and triethylindium we have proposed some reaction mechanisms, supported by detailed density functional (DFT) calculations. The possible role of diazene/hydrazone tautomerism initially assumed was discarded and therefore three mechanisms for the key step (nucleophilic addition of the trialkylindium to the N=N double bond of diazene) were studied. For the favoured mechanism there is a difference in the energy barriers of 2 kcalmol-1 between the reactions with trimethyl- and triethylindium. This difference is explained on the basis of the different C-In bond energies in the two organometallics and it is assumed to be enough to explain their different behaviour under the experimental conditions. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Barbero, Margherita,Cadamuro, Silvano,Dughera, Stefano,Ghigo, Giovanni
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scheme or table
p. 862 - 868
(2009/04/11)
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- Lead identification of 2-iminobenzimidazole antagonists of the chemokine receptor CXCR3
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Modification of a 2-iminobenzimidazole series derived from an HTS hit resulted in compounds with improved in-vitro species selectivity. Incorporation of an 8-quinoline amide and conformational rigidification of an aliphatic tether furnished potent compounds suitable for further lead optimization.
- Hayes, Martin E.,Breinlinger, Eric C.,Wallace, Grier A.,Grongsaard, Pintipa,Miao, Wenyan,McPherson, Michael J.,Stoffel, Robert H.,Green, David W.,Roth, Gregory P.
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p. 2414 - 2419
(2008/09/20)
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- Substituted propylamine derivatives and methods of their use
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The present invention is directed to substituted propylamine derivatives of formula I: or a pharmaceutically acceptable salt thereof, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nervous system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, and combinations thereof.
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Page/Page column 26
(2010/11/26)
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- Highly chemoselective nitration of aromatic amines using the Ph3P/Br2/AgNO3 system
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The use of PPh3/Br2/AgNO3 provides a new reagent system for the novel and highly chemoselective nitration of aromatic amines under mild reaction conditions.
- Iranpoor, Nasser,Firouzabadi, Habib,Nowrouzi, Najmeh,Firouzabadi, Dena
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p. 6879 - 6881
(2007/10/03)
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- A versatile method for the synthesis of benzimidazoles from o-nitroanilines and aldehydes in one step via a reductive cyclization
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A highly efficient and versatile method for the synthesis of benzimidazoles was achieved in one step via the Na2S2O4 reduction of o-nitroanilines in the presence of aldehydes. Heating a solution of o-nitroaniline (Ic) and an aldehyde in EtOH or another appropriate solvent, in the presence of aqueous or solid Na2S2O4, provided facile access to a series of 2-substituted N-H benzimidazoles 5a-m containing a wide range of functional groups not always compatible with the existing synthetic methods. This methodology has also been applied to the regioselective synthesis of N-alkyl and N-aryl benzimidazoles 6a-f via the cyclization of the corresponding N-substituted nitroanilines 13a-e, respectively. In addition, the method was applied successfully to the synthesis of other imidazole containing heterocyclic ring systems such as 1H-imidazo[4,5-b]pyridines 14a,b and 1H-imidazo[4,5-f]quinoline 15.
- Yang, Donglai,Fokas, Demosthenes,Li, Jingzhou,Yu, Libing,Baldino, Carmen M.
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- Synthesis and evaluation of 3-anilino-quinoxalinones as glycogen phosphorylase inhibitors
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A series of 3-anilino-quinoxalinones has been identified as a new class of glycogen phosphorylase inhibitors. The lead compound 1 was identified through high throughput screening as well as through pharmacophore-based electronic screening. Modifications were made to the scaffold of 1 to produce novel analogues, some of which are 25 times more potent than the lead compound.
- Dudash Jr., Joseph,Zhang, Yongzheng,Moore, John B.,Look, Richard,Liang, Yin,Beavers, Mary Pat,Conway, Bruce R.,Rybczynski, Philip J.,Demarest, Keith T.
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p. 4790 - 4793
(2007/10/03)
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- Zirconium borohydride - A versatile reducing agent for the reduction of electrophilic and nucleophilic substrates
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Zirconium borohydride, a potential reducing agent, reduces acids, esters, imines to the corresponding alcohols and secondary amines in good yield at room temperature within two hours. This facile reducing property was taken advantage off in the synthesis of pheromones and some novel chiral precursors for asymmetric synthesis.
- Narasimhan,Balakumar
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p. 4387 - 4395
(2007/10/03)
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- Reductive N-monoalkylation of primary aromatic amines
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Primary aromatic amines 1 with a variety of ring substituents are easily converted to their N-monoalkyl derivatives 3 by a simple variation of the sodium borohydride/sulfuric acid/carbonyl compound procedure previously described for their N-permethylations. The procedure is suitable for the α-minodeuterium labelling of the new N-substituent.
- Verardo,Giumanini,Strazzolini,Poiana
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p. 121 - 125
(2007/10/02)
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- Reaction of 6-Ethylamino-3-methyluracil with Nitrobenzenes
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Reaction of 6-ethylamino-3-methyluracil (1) with nitrobenzenes in hexamethylphosphoric triamide gave isoalloxazines in 3.8-18 percent yield.In the presence of potassium carbonate, reaction of 1 with o-fluoronitrobenzene afforded 5-substituted uracil 3 in moderate yield.
- Harayama, Takashi,Jinno, Hideto,Tezuka, Yasuhiro,Yoneda, Fumio
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p. 1507 - 1509
(2007/10/02)
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