- Colchicine derivatives, and preparation method and medical application thereof
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The invention specifically relates to colchicine derivatives (I) as described in the specification and a preparation method thereof, and pharmaceutical compositions containing the colchicine derivatives, belonging to the field of medicinal chemistry. The results of pharmacodynamic experiments prove that the colchicine derivatives of the invention have treatment effect on lumbar disc herniation andliver fibrosis.
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Paragraph 0092; 0093; 0240; 0242; 0243
(2018/09/14)
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- Guanidine Synthesis: Use of Amidines as Guanylating Agents
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The use of amidines for the tandem or one-pot synthesis of guanidines is reported. Guanidines are obtained by oxidative rearrangement of readily available and stable amidines into carbodiimides, followed by in situ reaction with amines. The protocol can be executed under mild reaction conditions (30°C), in a green solvent (dimethyl carbonate). The amine scope is broad, including sterically hindered, oxidation-sensitive and chiral amines. Examples for the synthesis of both acyclic and cyclic guanidines are provided. 2-Propoxyphenyl iodide (2-PrOPhI) by-product, generated from the oxidant [N-(p-toluenesulfonyl)imino](2-propoxyphenyl)iodinane (2-PrOPhINTs), can be isolated in high yields making regeneration of the hypervalent iodine reagent possible. The utility and greenness of the synthetic method versus the state-of-the-art is demonstrated by a new route towards the antihypertensive drug Pinacidil. The process mass intensity (PMI) of the new route is only 24% of the classical one.
- Baeten, Mattijs,Maes, Bert U. W.
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supporting information
p. 826 - 833
(2016/03/12)
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- Copper(II)-Mediated Aerobic Oxidation of Benzylimidates: Synthesis of Primary α-Ketoamides
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A simple and straightforward method for the synthesis of primary α-ketoamides has been discovered. The reaction represents the first example of benzylimidates directly converting to primary α-ketoamides by using sustainable molecular oxygen as an oxidant. This reaction proceeds in the presence of copper(II) salt via cleavage of benzylic C-H and C-O bonds of the benzylimidates with liberation of alcohols as the only byproduct. A wide substrate scope, operationally mild conditions, the use of single substrates, and a reaction scaled up to grams make this strategy very attractive and practical. Furthermore, mechanistic studies illustrate that the imidate group adjacent to the benzylic position plays crucial role in facilitating this chemical process.
- Kumar, Yogesh,Shaw, Mukta,Thakur, Rima,Kumar, Amit
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p. 6617 - 6625
(2016/08/16)
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- Synthesis of Some Novel 2-Substitutedbenzyl-(4)7-phenyl-1H-benzo[d]imidazoles in Mild Conditions as Potent Anti-Tyrosinase and Antioxidant Agents
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Novel 2-substitutedbenzyl-4(7)-phenyl-1H-benzo[d]imidazole compounds were synthesized and characterized. Although 2a and 2b were reported previously in the literature, 11 compounds were synthesized (nine of them were newly synthesized) and the tyrosinase inhibitory effects and antioxidant activities of these compounds were studied for the first time. All of the synthesized compounds displayed certain inhibitory effects on tyrosinase, with IC50 values ranging from 37.86 ± 0.24 to 75.81 ± 2.49 μM. Among the compounds, 2j exhibited similar tyrosinase inhibitory effect (IC50 = 37.86 ± 0.24 μM) to the positive control, kojic acid (IC50 = 21.93 ± 0.11 μM). Kinetic studies revealed it to act as non-competitive tyrosinase inhibitor with a Ki value of 50.2 μM. The antioxidant activities of the compounds were investigated by using in vitro antioxidant assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP). All of these results indicated that the compounds might have potential application as tyrosinase inhibitors.
- Do?an, ?nci S.,?zel, Arzu,Birinci, Zeynep,Barut, Burak,Sellitepe, Hasan E.,Kahveci, Bahittin
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p. 881 - 888
(2016/11/09)
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- Copper(II)-Catalyzed Benzylic C(sp3)-H Aerobic Oxidation of (Hetero)Aryl Acetimidates: Synthesis of Aryl-α-ketoesters
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A straightforward method is developed in this paper for the synthesis of α-ketoesters through copper-catalyzed aerobic oxidation of (hetero)aryl acetimidates using molecular oxygen as a sustainable oxidant. The reaction represents the first example of the direct synthesis of aryl-α-ketoesters from arylacetimidates through the aerobic oxidation of a benzylic C(sp3)-H (CO) bond in moderate to good yield. This transformation occurs under mild reaction conditions with a wide range of substrates and utilizes a readily available oxidant and catalyst. The synthetic utility of this transformation is demonstrated through scaled-up synthesis. A plausible reaction mechanism is also proposed.
- Kumar, Yogesh,Jaiswal, Yogesh,Kumar, Amit
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p. 12247 - 12257
(2016/12/23)
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- 1,2,4-TRIAZOL-5-ONES AND ANALOGS EXHIBITING ANTI-CANCER AND ANTI-PROLIFERATIVE ACTIVITIES
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Described are compounds of Formula I which find utility in the treatment of cancer, autoimmune diseases and metabolic bone disorders through inhibition of c-FMS (CSF-lR), c-KIT, and/or PDGFR kinases. These compounds also find utility in the treatment of other mammalian diseases mediated by c-FMS, c-KIT, or PDGFR kinases.
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Paragraph 0383
(2014/09/29)
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- Antiviral activity of benzimidazole derivatives. III. Novel anti-CVB-5, anti-RSV and anti-Sb-1 agents
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A library of eighty-six assorted benzimidazole derivatives was screened for antiviral activity against a panel of ten RNA and DNA viruses. Fifty-two of them displayed different levels of activity against one or more viruses, among which CVB-5, RSV, BVDV a
- Tonelli, Michele,Novelli, Federica,Tasso, Bruno,Vazzana, Iana,Sparatore, Anna,Boido, Vito,Sparatore, Fabio,La Colla, Paolo,Sanna, Giuseppina,Giliberti, Gabriele,Busonera, Bernardetta,Farci, Pamela,Ibba, Cristina,Loddo, Roberta
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p. 4893 - 4909
(2014/10/16)
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- Mapping pilicide anti-virulence effect in Escherichia coli, a comprehensive structure-activity study
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Pilicides prevent pili formation and thereby the development of bacterial biofilms in Escherichia coli. We have performed a comprehensive structure activity relationship (SAR) study of the dihydrothiazolo ring-fused 2-pyridone pilicide central fragment by varying all open positions. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) was used to distinguish active from inactive compounds in which polarity proved to be the most important factor for discrimination. A quantitative SAR (QSAR) partial least squares (PLS) model was calculated on the active compounds for prediction of biofilm inhibition activity. In this model, compounds with high inhibitory activity were generally larger, more lipophilic, more flexible and had a lower HOMO. Overall, this resulted in both highly valuable SAR information and potent inhibitors of type 1 pili dependent biofilm formation. The most potent biofilm inhibitor had an EC50 of 400 nM.
- Chorell, Erik,Pinkner, Jerome S.,Bengtsson, Christoffer,Banchelin, Thomas Sainte-Luce,Edvinsson, Sofie,Linusson, Anna,Hultgren, Scott J.,Almqvist, Fredrik
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scheme or table
p. 3128 - 3142
(2012/06/29)
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- Combinatorial synthesis of 3,5-Dimethylene substituted 1,2,4-Triazoles
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Combinatorial cyclizations of imidates and hydrazides with methylene linked R groups, generated from the corresponding nitriles and carboxylic acids, respectively, provided a large library of 3,5-dimethylene substituted 1,2,4- trizoles. 2011 Bentham Science Publishers Ltd.
- Woodard, Scott S.,Jerome, Kevin D.
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experimental part
p. 132 - 137
(2012/04/18)
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- Two new types of π-conjugation between a fullerene sphere and an addend
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Diazirine addition reactions to C60, followed by an HCl elimination step, yielded [6,6] and [5,6] sp2 carbon bridged fullerenes. The [5,6] adducts (alkylidenehomofullerenes) are the first examples of fullerene structures where the ad
- Kooistra, Floris B.,Leuning, Tessa M.,Maroto Martinez, Enrique,Hummelen, Jan C.
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supporting information; scheme or table
p. 2097 - 2099
(2010/08/22)
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- SUBSTITUTED IMIDAZOLONE DERIVATIVES, PREPARATIONS AND USES
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The present invention relates to polysubstituted imidazolone derivatives, to the pharmaceutical compositions comprising them and to the therapeutic uses thereof in the human and animal health fields. The present invention also relates to a process for preparing these derivatives.
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Page/Page column 36
(2010/02/16)
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- AMIDINE-CONTAINING COMPOUNDS USEFUL AS MUSCARINIC RECEPTOR ANTAGONISTS
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The invention relates to compounds of formula I: or a pharmaceutically acceptable salt thereof, where R1-3, R5, R7, a, b, Q, X, X′, X″, Y, Z, and Ar are as defined in the specification. These compounds are muscarinic recep
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Page/Page column 19
(2009/07/17)
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- EPOTHILONE ANALOGUES MODIFIED AT POSITIONS C12-C13 AS ANTICANCER DRUGS
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The invention relates to analogues of epothilones of formulae (A), (B), (I) and (II), uses and methods of making the same.
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Page/Page column 28-29
(2008/12/06)
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- PROTEIN KINASE INHIBITORS
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Compounds that inhibit protein kinases, compositions containing the compounds and methods of treating diseases using the compounds are disclosed.
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Page/Page column 69
(2010/11/28)
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- Heterocyclic compounds
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The inventive subject matter relates to compounds, pharmaceutical compositions, and kits containing a heterocyclic compound represented by the formula (I) wherein R is an alkyl group optionally having substituent(s) etc., X is an amino group optionally having substituent(s), Y1 and Y2 are nitrogen atoms etc., an isomer or solvate thereof or a pharmaceutically acceptable salt thereof as an active ingredient.
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Page/Page column 10
(2010/02/14)
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- Synthesis and cytotoxicity of substituted 2-benzylnaphth[2,3-d]imidazoles
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Designed as a new series of so called "bivalent ligand" containing the proposed 2-benzylnaphthimidazole-type structure, a number of 2-benzylnaphth[2,3-d]imidazoles, bearing various substituents, have been prepared by a synthetic approach involving an hete
- Grella,Cabras,Murineddu,Pau,Pinna
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p. 267 - 272
(2007/10/03)
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- Amidine compounds
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A compound of the formula [I] wherein R1, R2and R3are the same or different and each is hydrogen atom, wherein each symbol is as defined in the specification, a salt thereof or a prodrug thereof. The compound of the presen
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- An enantioselective ketene-imine cycloaddition method for synthesis of substituted ring-fused 2-pyridinones
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Previously, a method for the stereoselective synthesis of β-lactams, starting from 2H-δ2-thiazolines and Meldrum's acid derivatives, has been reported from our laboratory. We now report a new method for the synthesis of optically active, highly substituted ring-fused 2-pyridinones. This was discovered when 2-alkyl-δ2-thiazolines and Meldrum's acid derivatives were treated with HCl(g) in benzene at 5 → 78 °C. Further refinement of the synthetic protocol revealed that use of 1,2-dichloroethane as solvent at 0 → 64 °C led to the desired 2-pyridinones in good yields and with excellent enantioselectivity. Use of these conditions allowed preparation of 2-pyridinones from several different δ2-thiazolines and Meldrum's acid derivatives and may be a general route to 2-pyridinones.
- Emtenaes,Alderin,Almqvist
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p. 6756 - 6761
(2007/10/03)
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- Stereoselective synthesis of quaternary benzylic carbons using C2 symmetric imidazolines and tetrahydrofuran as electrophile
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Alkylative ring opening of tetrahydrofuran in the presence of 9-BBN triflate is studied. Dianions derived from C2 symmetric imidazolines induce excellent to modest acyclic diastereoselectivity to form quaternary benzylic centers, using the 9-BBN triflate/THF system or methyl iodide as electrophiles. The direction of the stereoinduction is consistent in both cases. Absolute configuration for the newly created stereogenic center was established by chemical correlation. Low-temperature NMR studies of the dilithiated intermediates 42 and 43 suggest the presence of N- and C- metalated compounds, where the metal-bearing benzylic carbon is sp3 hybridized.
- Dalko, Peter I.,Langlois, Yves
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p. 8107 - 8117
(2007/10/03)
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- Potent tetracyclic guanine inhibitors of PDE1 and PDE5 cyclic guanosine monophosphate phosphodiesterases with oral antihypertensive activity
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Tetracyclic guanines have been shown to be potent and selective inhibitors of the cGMP-hydrolyzing enzymes PDE1 and PDE5. In general, these compounds are inactive or only weakly active as inhibitors of PDE3, which is a major isozyme involved in cAMP hydrolysis. Structureactivity relationships are developed at N-l, C-2, N-3, and N-5 on the core nucleus. Compound 31, with an IC50 of 70 pM, is the most potent inhibitor of PDE1, while 50, with an IC50 of 4 nM, is the most potent inhibitor of PDE5. Compounds 20, 22, 30, and 50 are potent dual inhibitors with IC50 values below 30 nM for both PDE1 and PDE5. Compounds 12, 20, and 28 reduced blood pressure by more than 45 mmHg when administered orally at 10 mg/kg to the spontaneously hypertensive rat (SHR).
- Ahn, Ho-Sam,Bercovici, Ana,Boykow, George,Bronnenkant, Alan,Chackalamannil, Samuel,Chow, Jason,Cleven, Renee,Cook, John,Czarniecki, Michael,Domalski, Carol,Fawzi, Ahmad,Green, Michael,Gündes, Asli,Ho, Ginny,Laudicina, Malvina,Lindo, Neil,Ma, Ke,Manna, Mahua,McKittrick, Brian,Mirzai, Bita,Nechuta, Terry,Neustadt, Bernard,Puchalski, Chester,Pula, Kathryn,Silverman, Lisa,Smith, Elizabeth,Stamford, Andrew,Tedesco, Richard P.,Tsai, Hsingan,Tulshian, Deen,Vaccaro, Henry,Watkins, Robert W.,Weng, Xiaoyu,Witkowski, Joseph T.,Xia, Yan,Zhang, Hongtao
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p. 2196 - 2210
(2007/10/03)
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- 8-Amino-3-benzyl-1,2,4-triazolopyrazines. Synthesis and Anticonvulsant Activity
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Eleven substituted 8-amino-3-benzyl-1,2,4-triazolopyrazines were synthesized and tested for anticonvulsant activity against maximal electroshock-induced seizures (MES) in rats.The compounds were prepared in four stages from the phenylacetonitriles
- Kelley, James L.,Linn, James A.,Bankston, Donald D.,Burchall, Christopher J.,Soroko, Francis E.,Cooper, Barrett R.
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p. 3676 - 3679
(2007/10/03)
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- Synthesis and choleretic activity of 3-[2-(3-R', 4-R'', 5-R'''-benzyl)-5- R-benzimidazol-1-yl]-butanoic acids
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On the ground of the evidentiated choleretic activity of 3-[2- benzylbenzimidazol-1-yl]butanoic acid, 28 new acids were prepared in order to evaluate the influence of suitable substitutions in either C5 of heteroring or C3', C4', C5' of benzyl group in po
- Grella,Paglietti,Sparatore,Satta,Manca,Peana
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- Biologically Active Metabolites of Fungi, I.-Isolation, Synthesis, and Biological Activity of Coniothyriomycin as well as Bioassay of Analogous Open-Chain Imides
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The mixed open-chain imide N-(3-chloro-4-hydroxyphenylacetyl)fumarate (1), named coniothyriomycin, was isolated as a metabolite of the fungus Coniothyrium.The natural product 1 and the analoguos imides 13-15 and 22-24 have been synthesized by base-catalyzed condensation of the imidates 12a-f with acid chlorides 6a-c or the mixed anhydride 21.The compounds 1 and 13-15 were shown to posess remarkable fungicidal and herbicidal activities in short-termed tests. Key Words: Fungal metabolites / Imides, open-chain / Fungicidal activity / Coniothriomycin
- Krohn, Karsten,Franke, Claudia,Jones, Peter G.,Aust, Hans-Juergen,Draeger, Sigfried,Schulz, Barbara
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p. 789 - 798
(2007/10/02)
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- REACTIVE INTERMEDIATES IN THE PHOTOLYSIS AND THERMOLYSIS OF 3-CHLORO-3-BENZYLDIAZIRINE
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The photochemical and thermal decomposition of 3-chloro-3-benzyldiazirine have been studied in different reaction conditions.The decomposition gives rise to benzylchlorocarbene which can rearrange to E and Z chlorostyrene and/or react with the environment.In the presence of acetic acid the main product is 1-chloro-2-phenylethyl acetate.Experiments with acetic acid-d4 showed that some of the chlorostyrene is formed from the carbocation; other experiments conducted with tetramethylethylene as a carbene trapping agent show that the carbene is formed even in the presence of acetic acid.
- Liu, Michael T. H.,Chishti, Najmul H.,Tencer, Michael,Tomioka, Hideo,Izawa, Yasuji
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p. 887 - 892
(2007/10/02)
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- Synthesis and Antiinflammatory Activity of 2,2'-Diaminobiphenyl Derivatives
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A series of 2,2'-diaminobiphenyl derivatives was prepared and tested for antiinflammatory activity.Several compounds showed antiinflammatory activity, particularly 2-amino>-2'-amino>biphenyl (4), which als
- Calcinari, Romano,Case, Nadia,Guerrato, Alfredo,Milanino, Roberto,Passarella, Elda,et al.
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p. 632 - 634
(2007/10/02)
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- Optically Active Derivatives of Imidazolines. α-Adrenergic Blocking Properties
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The synthesis and α-adrenergic blocking activity of a series of optically active 2,4-disubstituted imidazolines are presented.The substituted analogues of naphazoline, tolazoline, and clonidine possess moderate α-adrenergic blocking activity with -logKsu
- Hsu, Fu-Lian,Hamada, Akihiko,Booher, Mark E.,Fuder, H.,Patil, P. N.,Miller, Duane D.
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p. 1232 - 1235
(2007/10/02)
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