- Synthesis of guanidinopropyl triethoxysilane and its homopolymer as a new class of organosilicon antibacterial agents
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In current work guanidinopropyl triethoxysilane was synthesized for the first time. It was shown that this compound is stable as a salt of hydroiodic acid, however, it easily undergoes condensation when heated in water, forming a water-soluble branched homopolymer. Aqueous solutions of guanidinopropyl triethoxysilane and its branched homopolymer showed moderate antibacterial activity against Staphylococcus aureus and Escherichia coli.
- Cherkaev, G. V.,Drozdov, F. V.,Muzafarov, A. M.,Parshina, M. S.,Strukova, E. N.,Tarasenkov, A. N.
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Read Online
- Novel potent organoselenium compounds as cytotoxic agents in prostate cancer cells
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A series of 17 symmetrical substituted imidothiocarbamate and imidoselenocarbamate derivatives has been synthesized by reacting appropriately substituted acyl chlorides with alkyl imidothiocarbamates and alkyl imidoselenocarbamates. The antitumoral activities of the compounds were evaluated in vitro by examining their cytotoxic effects against human prostate cancer cells (PC-3). Five compounds showed interesting activity levels and 3p (IC50 = 1.85 μM) was 7.3 times more active than the standard etoposide used in the treatment of prostate cancer and emerges as the most interesting compound.
- Plano, Daniel,Sanmartin, Carmen,Moreno, Esther,Prior, Celia,Calvo, Alfonso,Palop, Juan Antonio
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Read Online
- Efficient Catalysts of Acyclic Guanidinium Iodide for the Synthesis of Cyclic Carbonates from Carbon Dioxide and Epoxides under Mild Conditions
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We have studied the synthesis of five-membered cyclic carbonates through the cycloaddition of CO 2 to epoxides by using acyclic guanidinium salts. We have found that the cycloaddition reactions proceed smoothly at ordinary temperatures and pressures and result in good yields when acyclic guanidinium iodides are employed as catalysts. Both cation moiety and anion moiety of the guanidinium salts play important roles in their catalytic activity. It is essential to have active hydrogens on the cation moiety as well as an iodide ion as the anion moiety so as to achieve good catalytic activity. Guanidinium iodides with three or more active hydrogens give cyclic carbonates in high yields in polar solvents such as 1-methylpyrrolidin-2-one, whereas the guanidinium iodides with one or two active hydrogens show good catalytic activity in less polar solvents such as 2-methyltetrahydrofuran.
- Aoyagi, Naoto,Endo, Takeshi,Furusho, Yoshio
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p. 150 - 158
(2019/12/26)
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- Regioselective microwave synthesis and derivatization of 1,5-diaryl-3-amino-1,2,4-triazoles and a study of their cholinesterase inhibition properties
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Herein we describe the development of an efficient one-pot regioselective synthesis protocol to obtain N-protected or N-deprotected 1,5-diaryl-3-amino-1,2,4-triazoles from N-acyl-N-Boc-carbamidothioates. This improved protocol using microwave irradiation and low reaction times (up to 1 h) furnished desired compounds in yields ranging from 50 to 84%. This chemistry is useful for a variety of aromatic groups with electronically diverse substituents. The design and correct derivation of the amino group led to compounds able to inhibit cholinesterases with good IC50 of up to 1 μM. Also, the mode of action (mixed-type) and SAR analysis for this series of compounds was described by means of kinetic and molecular modelling evaluations, showing potential for this class of compounds as new scaffolds for this biological activity.
- Santos, Sabrina Neves,Alves De Souza, Gabriela,Pereira, Thiago Moreira,Franco, Daiana Portella,De Nigris Del Cistia, Catarina,Sant'anna, Carlos Mauricio R.,Lacerda, Renata Barbosa,Kümmerle, Arthur Eugen
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p. 20356 - 20369
(2019/07/09)
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- Rapid access to novel 2-alkylthiopyrimidine derivatives and attempt of their Tacrine analogs synthesis
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A variety of novel 2-alkylthiopyrimidines were synthesized through simple condensation of arylidenemalononitriles with different 2-alkylthiouronium halide derivatives catalyzed by anhydrous potassium carbonate (K2CO3). The reactions have been carried out under mild conditions in i-PrOH, and the products were obtained in moderate to good yields with a simple work-up method. Subsequently, some examples of these compounds have been converted into Tacrine analogs by applying the Friedl?nder reaction.
- Derabli, Chamseddine,Boulcina, Raouf,Kirsch, Gilbert,Debache, Abdelmadjid
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supporting information
p. 395 - 403
(2019/01/21)
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- GUANIDINE DERIVATIVE AND MEDICAL USE THEREOF
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A compound has a guanidine skeleton that inhibits the protease activity of MALT1 and exerts a therapeutic or prophylactic effect on autoimmune disease such as psoriasis or allergic disease such as atopic dermatitis. The guanidine derivative is typified by the following formula or a pharmacologically acceptable salt thereof.
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Paragraph 0500-0502
(2019/08/22)
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- Norbornane-based cationic antimicrobial peptidomimetics targeting the bacterial membrane
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The design, synthesis and evaluation of a small series of potent amphiphilic norbornane antibacterial agents has been performed (compound 10 MIC = 0.25 μg/mL against MRSA). Molecular modelling indicates rapid aggregation of this class of antibacterial agent prior to membrane association and insertion. Two fluorescent analogues (compound 29 with 4-amino-naphthalimide and 34 with 4-nitrobenz-2-oxa-1,3-diazole fluorophores) with good activity (MIC = 0.5 μg/mL against MRSA) were also constructed and confocal microscopy studies indicate that the primary site of interaction for this family of compounds is the bacterial membrane.
- Hickey, Shane M.,Ashton, Trent D.,Boer, Gareth,Bader, Christie A.,Thomas, Michael,Elliott, Alysha G.,Schmuck, Carsten,Yu, Heidi Y.,Li, Jian,Nation, Roger L.,Cooper, Matthew A.,Plush, Sally E.,Brooks, Douglas A.,Pfeffer, Frederick M.
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supporting information
p. 9 - 22
(2018/10/20)
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- DIPHENYL PYRAZOLE DERIVATIVE AND PHARMACEUTICAL USE THEREOF
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PROBLEM TO BE SOLVED: To provide a compound that functions to inhibit MALT1 protease activity and is useful as an agent for treating or for preventing autoimmune disease such as multiple sclerosis and psoriasis. SOLUTION: The present invention provides a diphenyl pyrazole derivative represented by the following formula or a pharmacologically acceptable salt thereof. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPO&INPIT
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Paragraph 0131; 0132
(2018/02/28)
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- Synthesis and evaluation of cationic norbornanes as peptidomimetic antibacterial agents
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A series of structurally amphiphilic biscationic norbornanes have been synthesised as rigidified, low molecular weight peptidomimetics of cationic antimicrobial peptides. A variety of charged hydrophilic functionalities were attached to the norbornane scaffold including aminium, guanidinium, imidazolium and pyridinium moieties. Additionally, a range of hydrophobic groups of differing sizes were incorporated through an acetal linkage. The compounds were evaluated for antibacterial activity against both Gram-negative and Gram-positive bacteria. Activity was observed across the series; the most potent of which exhibited an MIC's ≤ 1 μg mL-1 against Streptococcus pneumoniae, Enterococcus faecalis and several strains of Staphylococcus aureus, including multi-resistant methicillin resistant (mMRSA), glycopeptide-intermediate (GISA) and vancomycin-intermediate (VISA) S. aureus.
- Hickey, Shane M.,Ashton, Trent D.,Khosa, Simren K.,Robson, Ryan N.,White, Jonathan M.,Li, Jian,Nation, Roger L.,Yu, Heidi Y.,Elliott, Alysha G.,Butler, Mark S.,Huang, Johnny X.,Cooper, Matthew A.,Pfeffer, Frederick M.
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supporting information
p. 6225 - 6241
(2015/06/08)
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- Convenient synthesis of acyclic guanidines from isothiouronium iodides and amines without protection of the amino groups
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Acyclic guanidines were obtained in one step by reaction of isothiouronium iodides with an equimolar amount of various amines in tetrahydrofuran. The reactions proceeded under ambient conditions without N-protection/deprotection to afford the corresponding substituted guanidines in quantitative yields. Georg Thieme Verlag Stuttgart New York.
- Aoyagi, Naoto,Furusho, Yoshio,Endo, Takeshi
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supporting information
p. 983 - 986
(2014/05/06)
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- An optimised synthesis of 2-[2,3-Bis(tert -butoxycarbonyl)guanidino] ethylamine
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This short report describes an improved, reliable, and high-yielding (>90%) synthesis of 2-[2,3-bis(tert-butoxycarbonyl)guanidino]ethylamine. The method is scalable (>5 g), and the product obtained directly from the reaction mixture requires no further purification. In addition, this methodology can be successfully applied to other diamine substrates (1,3-propyl and 1,4-butyl; 70% and 61% yield, respectively).
- Hickey, Shane M.,Ashton, Trent D.,Khosa, Simren K.,Pfeffer, Frederick M.
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supporting information; experimental part
p. 1779 - 1782
(2012/08/29)
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- Synthesis and antiproliferative activity of novel symmetrical alkylthio- and alkylseleno-imidocarbamates
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The study described here concerns the synthesis of a series of thirty new symmetrically substituted imidothiocarbamate and imidoselenocarbamate derivatives and their evaluation for antitumoral activity in vitro against a panel of five human tumor cell lines: breast adenocarcinoma (MCF-7), colon carcinoma (HT-29), lymphocytic leukemia (K-562), hepatocarcinoma (Hep-G2), prostate cancer (PC-3) and one non-malignant mammary gland-derived cell line (MCF-10A). The GI50 values for eighteen of the compounds were below 10 μM in at least one cell line. Two cancer cells (MCF-7 and HT-29) proved to be the most sensitive to five compounds (1b, 2b, 3b, 4b and 5b), with growth inhibition in the nanomolar range, and compounds 1b, 3b, 7b, 8b and 9b gave values of less than 1 μM. In addition, all of the aforementioned compounds exhibited lower GI50 values than some of the standard chemotherapeutic drugs used as references. The results also reveal that the nature of the aliphatic chain (methyl is better than benzyl) at the selenium position and the nature of the heteroatom (Se better than S) have a marked influence on the antiproliferative activity of the compounds. These findings reinforce our earlier hypothesis concerning the determinant role of the selenomethyl group as a scaffold for the biological activity of this type of compound. Considering both the cytotoxic parameters and the selectivity index (which was compared in MCF-7 and MCF-10A cells), compounds 2b and 8b (with a selenomethyl moiety) displayed the best profiles, with GI50 values ranging from 0.34 nM to 6.07 μM in the five cell lines tested. Therefore, compounds 2b and 8b were evaluated by flow cytometric analysis for their effects on cell cycle distribution and apoptosis in MCF-7 cells. 2b was the most active, with an apoptogenic effect similar to camptothecin, which was used as a positive control. Both of them provoked cell cycle arrest leading to the accumulation of cells in either G2/M and S phase. These two compounds can therefore be considered as the most promising candidates for the development of novel generations of antitumor agents.
- Ibá?ez, Elena,Plano, Daniel,Font, María,Calvo, Alfonso,Prior, Celia,Palop, Juan Antonio,Sanmartín, Carmen
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experimental part
p. 265 - 274
(2011/02/27)
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- The synthesis of 5,7-dimethyl-1,2,4-triazolo[1,5a(14C)] pyrimidine-2-carbaldehyde from [14C]aminoguanidine: A key intermediate for the radiochemical GMP synthesis of a drug candidate
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Hydrazination of barium [14C]cyanamide and hydrazinolysis of S-methylisothio[14C]urea were compared for their ability to efficiently prepare [14C]aminoguanidine bicarbonate. [ 14C]Aminoguanidine bicarbonate was converted in three steps to 5, 7-dimethyl-1,2,4-triazolo[1,5a(14C)]pyrimidine-2-carbaldehyde, a key radiochemical GMP starting material. Copyright
- Rane, Anil M.,Klaas, Schildknegt
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scheme or table
p. 257 - 260
(2011/05/06)
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- SELECTIVE INHIBITORS AGAINST Cdk4 AND Cdk6 HAVING AMINOTHIAZOLE SKELETON
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The present invention relates to a compound represented by Formula [I]: wherein X is O, S, NH or CH 2 ; Y 1 , Y 2 , Y 3 , Y 4 and Y 5 , which may be identical or different, are each CH or N; however, at least one of Y 1 , Y 2 , Y 3 , Y 4 and Y 5 is N; Z 1 and Z 2 , which may be identical or different, are each CH or N; n is an integer from 1 to 3; R 1 is a C 3 -C 8 cycloalkyl group, a C 6 -C 10 aryl group, an aliphatic heterocyclic ring or an aromatic heterocyclic ring, or a bicyclic aliphatic saturated hydrocarbon group; R 2 and R 3 , which may be identical or different, are each a hydrogen atom, a lower alkyl group, a lower alkenyl group, a C 3 -C 8 cycloalkyl group, a C 6 -C 10 aryl group, an aromatic heterocyclic ring, or the like; and R 4 is a hydrogen atom, a lower alkyl group, a C 3 -C 6 cycloalkyl group or the like, or a pharmaceutically acceptable salt or ester thereof, and a selective inhibitor against Cdk4 and/or Cdk6 or an anticancer agent containing the compound or a pharmaceutically acceptable salt or ester thereof.
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Page/Page column 93-94
(2010/11/25)
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- PYRIMIDINE DERIVATIVES FOR THE TREATMENT OP GABA B MEDIATED NERVOUS SYSTEM DISORDERS
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The invention relates to novel heterocyclic compounds of the formula (I) in free base form or in acid addition salt form, in which R1, R2, R3, R4 and A are as defined in the specification, to their preparation, to their use as medicaments for the treatment of certain nervous system disorders and to medicaments comprising them.
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Page/Page column 18-20
(2010/11/25)
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- Synthesis of sulfides by reactions of 1,1-dichloro-2-chloro- methylcyclopropane with S-nucleophiles
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1,1-Dichloro-2-chloromethylcyclopropane reacts with thiolates to give 2,2-dichlorocyclopropylmethyl sulfides via replacement of the side-chain chlorine atom. The resulting sulfides are readily oxidized to the corresponding sulfones.
- Mikhed'kina,Nedel'ko,Prezhdo
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p. 370 - 375
(2007/10/03)
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- Accelerated degradation of methyl iodide by agrochemicals
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The fumigant methyl iodide (Mel, iodomethane) is considered a promising alternative to methyl bromide (MeBr) for soil-borne pest control in high-cash-value crops. However, the high vapor pressure of Mel results in emissions of a significant proportion of the applied mass into the ambient air, and this may lead to pollution of the environment. Integrating the application of certain agrochemicals with soil fumigation provides a novel approach to reduce excessive fumigant. emissions. This study investigated the potential for several agrochemicals that are commonly used in farming operations, including fertilizers and nitrification inhibitors, to transform Mel in aqueous solution. The pseudo-first-order hydrolysis half-life (t1/2) of Mel was ~ 108 d, while the transformation of Mel in aqueous solutions containing selected agrochemicals was more rapid, with t1/2 1/2 1/2 of Mel was 1/2 > 300 h).
- Zheng, Wei,Papiernik, Sharon K.,Guo, Mingxin,Yates, Scott R.
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p. 673 - 679
(2007/10/03)
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- Piperazine and homopiperazine derivatives, pharmaceutical compositions containing them and process for preparing same
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This invention relates to novel compounds of the general formula (I) and the pharmaceutically acceptable acid addition salts thereof. In the general formula (I) STR1 wherein Lip, A1, A2, Het and n are defined as in the specification. The compounds of the general formula (I) inhibit the lipid peroxidation and therefore, they are useful for the treatment or prevention of diseases and conditions wherein the inhibition of lipid peroxidation is desirable.
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- Piperazine and homopiperazine derivatives, pharmaceutical compositions containing them and process for preparing the same
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The lipid peroxidation inhibiting piperazine and homopiperazine derivatives of the general formula (I) and the pharmaceutically acceptable acid addition salts thereof, Lip stands for hydrogen; C15 20 alkyl; C10 20 alkanoyl or C10 20 alkenoyl; trityl optionally substituted by halogen; adamantyl; 1- or 2-naphthyloxy or oxo-substituted tetrahydronaphthyloxy; or an amine protective group commonly used e.g. in the peptide chemistry;, A1 and A2 are selected independently from the group consisting of a single bond and C2 3 alkylene optionally substituted by hydroxy or oxo;, n is 1 or 2; and, Het represents, a group of the general formula (a), wherein, R1 is amino or 1-pyrrolidinyl;, or a 4-chloro-3-oxo-2,3-dihydro-5-pyridazinyl group of the formula (b); or a 4-amino-6,7-dimethoxy-2-quinazolinyl group of the formula (c); or a 4,7-diamino-6-phenyl-2-pteridinyl group of the formula (d); or a 2,7-diamino-6-phenyl-4-pteridinyl group of the formula (e); or a 2,4,7-triamino-6-pteridinylcarbonyl group of the formula (f); or a group of the general formula (g); wherein, X means oxygen, sulfur or nitrogen optionally substituted by lower alkyl,with the frist proviso that, when Het stands for a group of the general fromula (a) and both A1 and A2 mean single bonds then Lip may not be hydrogen;, with the second priviso that, when Lip is different from naphthyloxy or oxo-substituted tetrahydronaphthyloxy then A1 means a single bond;, with the third proviso that, when Lip represents naphthyloxy or oxo-substituted tetrahydronaphthyloxy then A1 may not be a single bond, as well as with the fourth proviso that, A1 and A2 cannot simultaneously stand for C2 3 alkylene optionally substituted by hydroxy or oxo.
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- PYRIDYL ALKYLGUANIDINE COMPOUNDS, COMPOSITION THEREWITH, AND METHODS OF INHIBITING H-2 HISTAMINE RECEPTORS
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The compounds are pyridyl alkylguanidines, for example N-benzenesulphonyl-N'-methyl-N"-2-((3-hydroxy-2-pyridyl)methylthio) ethyl!guanidine, which are inhibitors of histamine activity. "
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