- Oxalohydrazide Ligands for Copper-Catalyzed C?O Coupling Reactions with High Turnover Numbers
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Here, we report a class of ligands based on oxalohydrazide cores and N-amino pyrrole and N-amino indole units that generates long-lived copper catalysts for couplings that form the C?O bonds in biaryl ethers. These Cu-catalyzed coupling of phenols with aryl bromides occurred with turnovers up to 8000, a value which is nearly two orders of magnitude higher than those of prior couplings to form biaryl ethers and nearly an order of magnitude higher than those of any prior copper-catalyzed coupling of aryl bromides and chlorides. This ligand also led to copper systems that catalyze the coupling of aryl chlorides with phenols and the coupling of aryl bromides and iodides with primary benzylic and aliphatic alcohols. A wide variety of functional groups including nitriles, halides, ethers, ketones, amines, esters, amides, vinylarenes, alcohols and boronic acid esters were tolerated, and reactions occurred with aryl bromides in pharmaceutically related structures.
- Ray, Ritwika,Hartwig, John F.
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supporting information
p. 8203 - 8211
(2021/03/08)
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- 1-[(Imidazolidin-2-yl)imino]-1H-indoles as new hypotensive agents: synthesis and in vitro and in vivo biological studies
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A series of 1-[(imidazolidin-2-yl)imino]-1H-indole analogues of hypotensive α2-AR agonists, 1-[(imidazolidin-2-yl)imino]-1H-indazoles, was synthesized and tested in vitro for their activities at α1- and α2-adrenoceptors as well as imidazoline I1 and I2 receptors. The most active 1-[(imidazolidin-2-yl)imino]-1H-indoles displayed high or moderate affinities for α1- and α2-adrenoceptors and substantial selectivity for α2-adrenoceptors over imidazoline-I1 binding sites. The in vivo cardiovascular properties of indole derivatives 3 revealed that substitution at C-7 position of the indole ring may result in compounds with high cardiovascular activity. Among them, 7-fluoro congener 3g showed the most pronounced hypotensive and bradycardic activities in this experiment at a dose as low as 10?μg/kg i.v. Metabolic stability of the selected compounds of type 3 was determined using both in vitro and in silico approaches. The results indicated that these compounds are not vulnerable to rapid first-phase oxidative metabolism.
- Kornicka, Anita,Wasilewska, Aleksandra,S?czewski, Jaros?aw,Hudson, Alan L.,Boblewski, Konrad,Lehmann, Artur,Gzella, Karol,Belka, Mariusz,S?czewski, Franciszek,Gdaniec, Maria,Rybczyńska, Apolonia,B?czek, Tomasz
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p. 400 - 410
(2017/04/03)
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- HETEROARYL COMPOUNDS FOR KINASE INHIBITION
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Compounds and pharmaceutical compositions that modulate kinase activity, including mutant EGFR and mutant HER2 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including mutant EGFRand mutant HER2 activity, are described herein.
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Paragraph 463
(2016/04/26)
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- N-amination of indoles on pilot-plant scale via simultaneous and proportional metering of reagents
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The N-amination of indoles on large scale, utilizing a portable Coriolis mass flow metering and pumping system that provides precise dispensing of two reagent streams simultaneously and proportionally, is described.
- Weiberth, Franz J.,Hanna, Reda G.,Lee, George E.,Polverine, Yvonne,Klein, Joseph T.
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experimental part
p. 704 - 709
(2011/12/04)
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- USE OF NEUROPROTECTIVE COMPOUNDS IN OBTAINING MEDICAMENTS INTENDED FOR THE TREATMENT OF NEURODEGENERATING DISEASES
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Use of neuroprotective compounds in obtaining medicaments intended for the curative treatment of neurodegenerative disease and/or the prevention of the appearance of disorders ensuing from those diseases.
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- 1H-Indole-Pyridinecarboxamide and 1H-Indole-Piperidinecarboxamide Compounds
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Compounds of formula (I): wherein: A represents a divalent radical: wherein: Z represents an oxygen atom or a sulphur atom,R6 represents a hydrogen atom, an alkyl, alkenyl, arylalkyl or polyhaloalkyl group or a substituted, linear or branched alkyl chain, represents a single bond or a double bond,R1, R2, R3 and R4 represent a hydrogen or halogen atom,an alkyl, alkoxy, hydroxy, cyano, nitro, polyhaloalkyl or optionally substituted amino group, or a linear or branched alkyl chain substituted by one or more groups,R5 represents a hydrogen atom or an alkyl, aminoalkyl or hydroxyalkyl group,X and Y represent a hydrogen atom or an alkyl group,Ra, Rb, Rc and Rd represent a hydrogen or halogen atom, an alkyl, hydroxy, alkoxy, cyano, nitro, polyhaloalkyl, optionally substituted amino group, or a substituted, linear or branched alkyl chain,Re represents a hydrogen atom or an alkyl, arylalkyl or alkenyl group or a substituted, linear or branched alkyl chain, their enantiomers, diastereoisomers, and N-oxides, and also addition salts thereof with a pharmaceutically acceptable acid or base.
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Page/Page column 7
(2009/10/21)
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- Naphthalocyanine dye and method for producing the same
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A compound of the following formula (I): wherein L11, L21, L31 and L41 represent a divalent group; Q11, Q21, Q31 and Q41 represent a non-metallic atomic group necessary for forming a hetero ring; R12, R22, R32 and R42 represent a substituent; n11, n12, n21, n22, n31, n32, n41 and n42 indicate an integer of from 0 to 6; provided that (n11+n21+n31+n41) is not 0; M1 represents two hydrogen atoms, two monovalent metal atoms, a divalent metal atom, or a divalent substituted metal atom including a trivalent or tetravalent metal atom.
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Page/Page column 18
(2008/06/13)
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- Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives
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This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with azaindoleoxoacetyl piperazine derivatives. These compounds possess unique antiv
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- Syntheses of novel indole lipoic acid derivatives and their antioxidant effects on lipid peroxidation
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The aim of the study was to examine antioxidant properties of conjugates based on indole and lipoic acid moieties. The design and syntheses of novel indole α-lipoic acid derivatives were performed. The antioxidant properties of target compounds were investigated using rat liver microsomal, NADPH-dependent lipid peroxidation inhibition. Some of the target compounds, especially those containing amide linker at position 5 of indole ring, proved to be highly effective in inhibiting lipid peroxidation as compared to α-lipoic acid.
- Gurkan, A. Selen,Karabay, Arzu,Buyukbingol, Zeliha,Adejare, Adeboye,Buyukbingol, Erdem
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- PROCESS FOR THE PREPARATION OF N-AMINO SUBSTITUTED HETEROCYCLIC COMPOUNDS
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An improved process for the preparation of N-amino nitrogen heterocyclic compounds is disclosed and claimed. In an ambodiment of this invention, a compound of the formula (VI) is prepared starting from the corresponding indole derivative by way of N-amination and subsequently forming an hydrazone by the reaction with a keto compound in a single step. Further reduction of the hydrazone and subsequent coupling with a pyridine compound affords the compound of formula VI or a suitable salt thereof.
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Page/Page column 22; 25; 26
(2008/06/13)
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- N-Amination of Pyrrole and Indole Heterocycles with Monochloramine (N H2Cl)
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A survey of several electrophilic ammonia reagents for the N-amination of indole- and pyrrole-containing heterocycles revealed that monochloramine (NH2Cl) is an excellent reagent for this transformation. Pyrroles and indoles containing a variety of substitution were aminated on nitrogen with isolated yields ranging from 45% to 97%.
- Hynes Jr., John,Doubleday, Wendel W.,Dyckman, Alaric J.,Godfrey Jr., Jollie D.,Grosso, John A.,Kiau, Susanne,Leftheris, Katerina
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p. 1368 - 1371
(2007/10/03)
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- Inhibitors of cytosolic phospholipase A2
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This invention provides substituted indole compounds of the general formula: and pharmaceutically acceptable salt forms thereof, and methods for using the compounds as inhibitors of the activity of various phospholipase enzymes, particularly phospholipase A2 enzymes, and for the medical treatment, prevention and inhibition of pain and inflammation.
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- Novel aromatic compounds and poly(oxyalkylene) containing aromatic compounds possessing antibacterial, antifungal or antitumor activity
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The present invention provides novel compounds possessing one or more of the following activities: antibacterial, antifungal and antitumor activity. The compounds are of Formula (I): Pharmaceutical compositions containing these compounds, methods of making and methods for using these compounds are also provided.
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- Novel compounds possessing antibacterial, antifungal or antitumor activity
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The present invention provides novel compounds possessing one or more of the following activities: antibacterial, antifungal and antitumor activity. The compounds are of Formula (I): Pharmaceutical compositions containing these compounds, methods of making and methods for using these compounds are also provided.
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- Antiviral azaindole derivatives
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The present invention is directed to a series of chemical entities that express HIV-1 inhibitory activities.
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- Antiviral azaindole derivatives
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The present invention is directed to a series of chemical entities that express HIV-1 inhibitory activities.
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- Synthesis and structure-activity relationships of N-propyl-N-(4- pyridinyl)-1H-indol-1-amine (besipirdine) and related analogs as potential therapeutic agents for Alzheimer's disease
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A series of novel N-(4-pyridinyl)-1H-indol-1-amines and other heteroaryl analogs was synthesized and evaluated in tests to determine potential utility for the treatment of Alzheimer's disease. From these compounds, N-propyl-N- (4-pyridinyl)-1H-indol-1-amine (besipirdine, 4c) was selected for clinical development based on in-depth biological evaluation. In addition to cholinomimetic properties based initially on in vitro inhibition of [3H]quinuclidinyl benzilate binding, in vivo reversal of scopolamine- induced behavioral deficits, and subsequently on other results, 4c also displayed enhancement of adrenergic mechanisms as evidenced in vitro by inhibition of [3H]clonidine binding and synaptosomal biogenic amine uptake, and in vivo by reversal of tetrabenazine-induced ptosis. The synthesis, structure-activity relationships for this series, and the biological profile of 4c are reported.
- Klein,Davis,Olsen,Wong,Huger,Smith,Petko,Cornfeldt,Wilker,Blitzer,Landau,Haroutunian,Martin,Effland
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p. 570 - 581
(2007/10/03)
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- 3-substituted cephem compounds
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The present invention relates to novel cephalosporins of the formula (I); STR1 wherein, R1 represents a C1 ?C4 alkyl group or STR2 wherein, R2 and R3, independently, represent hydrogen or a C1 ?C3 alkyl group and R4 represents hydrogen or a C1 ?C4 alkyl group; R1a represents hydrogen or an amino-protecting group; Q represents CH or N; and the formula STR3 represents a saturated or unsaturated heterocyclic group which contains 1 to 4 nitrogen atoms of which one is substituted with an amino group to form quaternary ammonium, and oxygen or sulfur, or a fused heterocyclic group thereof formed together with a substituted or unsubstituted benzene or an optional heterocyclic group, or a pharmaceutically acceptable salt thereof, to processes for preparing the same and to a pharmaceutical composition containing the same as an active ingredient. The compounds(1) according to the invention exhibit potent antibacterial activity and broad antibacterial spectrum against the Gram-positive strains including Staphylococcus as well as Gram-negative strains including Pseudomonas, and, therefore, are expected to be very useful in treatment of various diseases caused by bacterial infection in human beings and animals.
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- Indazole compounds, pharmaceutical compositions and use
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The invention provides a series of novel heterocyclic amides of the formula I in which the group A CRa can be --CRb=CRa--, --CHRb--CHRa-- or --N=CRa--, the amidic group Re.L can be Re.X.CO.NH, Re.X.CS.NH or Re.NH.CO attached at position 4, 5 or 6 of the benzenoid moiety, Z is an acid group selected from the group consisting of carboxy, an acylsulphonamide residue of the formula CO.NH.SOn Rg and a tetrazolyl residue of the formula II, and the radicals Ra, Rb, Rc, Rd, Re, Rf, Rg, Rh, n, X, G1, Q and G2 have the meanings defined in the following specification. The compounds of formula I are leukotriene antagonists. The invention also provides pharmaceutically acceptable salts of the formula I compounds; pharmaceutical compositions containing the formula I compounds, or their salts, for use in the treatment of, for example, allergic or inflammatory diseases, or endotoxic or traumatic shock conditions; and processes for the manufacture of the formula I compounds, as well as intermediates for use in such manufacture.
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- Aminations with O-Diphenylphosphinylhydroxylamine. A Critical Evaluation
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A critical evaluation is presented of the scope of amination reactions with O-diphenylphosphinylhydroxylamine (ODPH) as compared to those using hydroxylamine-O-sulfonic acid (HOSA).Aminations with ODPH of isopropyl, t-butyl and cyclohexyl carbanions derived from the corresponding Grignard reagents, gave the corresponding amines in 36, 34 and 50 percent yields, respectively.The amination with HOSA of the same carbanions under similar conditions was unsuccessful.The aminative quaternization of the tertiary nitrogen of pyridine and quinoline with ODPH proceeded with comparable yields to those obtained with HOSA.An improved one flask amination with ODPH of indole, skatole and carbazole was achieved in 52 - 62 percent yields.The amination under the same conditions using HOSA gave consistently lower yields.Several other amination reactions which have been reported for HOSA were unsuccessful using ODPH.The conclusion is reached that overall the ODPH reagent is much less versatile than HOSA.Nevertheless, in the aminations of NH groups of heterocyclic compounds ODPH appears to be superior to HOSA and is the reagent of choice, in particular, since the preparation of ODPH is much less harzardous than that of HOSA. - Keywords: Synthesis, O-Diphenylphosphinylhydroxylamine, Hydroxylamine-O-sulfonic Acid, N-Amino Derivatives, N-Amino Heterocyclic Compounds
- Sosnovsky, George,Purgstaller, Klaus
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p. 582 - 586
(2007/10/02)
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- Modified Procedure for the Preparation of 5-Nitro-2-furylmethylene Diacetate and Its Use in the Synthesis of Some Novel (5-Nitro-2-furyl)azomethines via 5-Nitro-2-furaldehyde
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A modified two-step procedure for the preparation of 5-nitro-2-furylmethylene diacetate (3) by nitration of 2-furaldehyde (1) or 2-furylmethylene diacetate (4) with acetyl nitrate via 2-acetoxy-5-nitro-2,5-dihydro-2-furylmethylene diacetate (2), or 1,1,5-triacetoxy-2-hydroxy-5-nitro-3-penten (5) and 1,1,5-triacetoxy-2-hydroxy-5-nitro-2,4-pentadiene (6), has been developed.Acid hydrolysis of 3 yields 5-nitro-2-furaldehyde (7) which is used in the carbonylamine condensation with various hydrazines (9-11, 14, 17, 19, 21, 24, 25, 28, 29, 32, 34, 36, 38, 39, 41 and 44-54) prepared by known methods, in order to obtain some novel potentially pharmaceutically active (5-nitro-2-furyl)azomethines.
- Vlaovic, Djordje,Milic, Bozidar Lj.,Mackenzie, Kenneth
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p. 1201 - 1218
(2007/10/02)
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