- Synthesis, surface properties and bioactivity of novel 4-Substituted 1,2,3-Triazole quaternary ammonium surfactants
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Series of novel 1,2,3-triazole based quaternary ammonium surfactants with different hydrophobic chain length and head group substituents were synthetized and characterized. Their surface properties and aggregation behavior were discussed on the basis of tensiometry and conductimetry measurements by using several parameters, including critical micelle concentration (CMC), surface tension at the cmc (γcmc), adsorption efficiency (pC20), effectiveness of surface tension reduction (Πcmc), minimum surface area occupied by a molecule (Amin) at the air ? water interface and standard Gibbs free energy of micellization ΔGMic0. These heterocyclic surfactants exhibit much lower CMC values as compared with those reported for conventional alkyltriethyl ammoniums and alkylbenzyldiethyl ammonium salts. Their micelles formation and surface adsorption in aqueous media can be tuned out through a suitable choice of the substituent attached to the polar head. Triethyl ammonium (CnTzTEA] and diethylbenzyl ammonium surfactants (CnTzBz) showed improved micellization behavior than tetradecyl diethyl ammonium (CnTzC14) homologous. The in vitro antimicrobial activity of the surfactants against B. subtilis, P. aerugenosa and A.niger strains was also investigated. CnTzBz series possessing benzyl chain showed better activity against all the tested microorganisms with minimum inhibitory concentration ranging from 6 to 57 μmol/L.
- Mechken, Karima Amel,Menouar, Mohammed,Belkhodja, Moulay,Saidi-Besbes, Salima
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- Pleuromutilin derivative with triazole side chain, and preparation method and application thereof
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The invention relates to the technical field of medicinal chemistry, in particular to a pleuromutilin derivative with a triazole side chain, and a preparation method and application thereof. The pleuromutilin derivative disclosed by the invention has the triazole side chain and a pleuromutilin parent nucleus structure; and in-vitro experiment results and animal experiment results show that the pleuromutilin derivative disclosed by the invention has good antibacterial activity on Staphylococcus aureus, and is particularly applicable as a novel antibacterial drug for systemic infections of animals or human beings.
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Paragraph 0137-0139
(2020/03/02)
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- Design, synthesis and biological activities of novel pleuromutilin derivatives with a substituted triazole moiety as potent antibacterial agents
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A series of novel pleuromutilin derivatives possessing 1,2,3-triazole moieties were synthesized via click reactions under mild conditions. The in vitro antibacterial activities of these derivatives against 4 strains of S. aureus (MRSA ATCC 43300, ATCC 29213, AD 3, and 144) and 1 strain of E. coli (ATCC 25922) were tested by the broth dilution method. The majority of the synthesized derivatives displayed potent antibacterial activities against MRSA (MIC = 0.125–2 μg/mL). It was also found that most compounds had no significant inhibitory effect on the proliferation of RAW264.7 cells at the concentration of 8 μg/mL. Among these derivatives, compound 32 (～1.71 log10 CFU/g) containing dimethylamine group side chain displayed more effective than tiamulin (～0.77 log10 CFU/g) at the dose of 20 mg/kg in reducing MRSA load in thigh infected mice. Additionally, compound 32 (the survival rate was 50%) also displayed superior in vivo efficacy to that of tiamulin (the survival rate was 20%) in the mouse systemic model. Structure-activity relationship (SAR) studies resulted in compound 32 with the most potent in vitro and in vivo antibacterial activity among the series. Moreover, compound 32 was evaluated in CYP450 inhibition assay and showed moderate in vitro inhibition of CYP3A4 (IC50 = 6.148 μM).
- Zhang, Zhe,Li, Kang,Zhang, Guang-Yu,Tang, You-Zhi,Jin, Zhen
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- Design, synthesis and biological evaluation of novel pleuromutilin derivatives containing piperazine and 1,2,3-triazole linker
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A series of novel pleuromutilin derivatives containing piperazine ring, 1, 2, 3-triazoles and secondary amines on the side chain of C14 were synthesized under mild conditions via click reaction. The in vitro antibacterial activities of the synthesized derivatives against four strains of Staphylococcus aureus (MRSA ATCC 43300, ATCC 29213, 144 and AD3) and one strain of Escherichia coli (ATCC 25922) were evaluated by the broth dilution method. Among these derivatives, 22–[2-(4-((4-nitrophenyl piperazine)methyl)-1,2,3-triazol-1-yl)-1-(piperazine-1-yl) ethyl-1-one] deoxy pleuromutilin (compound 59) showed the most prominent in vitro antibacterial effect against MRSA (MIC = 1 μg/mL). Furthermore, compound 59 displayed more rapid bactericidal kinetic than tiamulin time-kill studies and possessed a longer PAE than tiamulin against MRSA in vitro. In addition, in vivo antibacterial activities of compound 59 against MRSA were further evaluated employing thigh infection model. And compound 59 (-8.89 log10 CFU/mL) displayed superior activities than tiamulin. Compound 59 was further evaluated in CYP450 inhibition assay and the results showed that it exhibited low to moderate inhibitory effects on CYP1A2, CYP2E1, CYP2D6 and CYP3A4 enzymes. The PK properties of compound 59 were then measured. The half-life (t1/2), clearance rate (Cl) and the area under the plasma concentration time curve (AUC0→∞) of compound 59 were 0.74 h, 0.29 L/h/kg and 46.28 μg·h/mL, respectively.
- Zhang, Guang-Yu,Zhang, Zhe,Li, Kang,Liu, Jie,Li, Bo,Jin, Zhen,Liu, Ya-Hong,Tang, You-Zhi
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- Assembly of Functionalized 4-Alkynylisoxazoles by Palladium-Catalyzed Three-Component Cascade Cyclization/Alkynylation
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A novel N-heterocyclic carbene (NHC)-palladium-catalyzed three-component cascade cyclization/alkynylation for the synthesis of structurally diverse 4-alkynylisoxazoles was efficiently developed in ionic liquids. The operational simplicity, without additives, no additional ligands, and 0.5 mol % catalyst loading under air are some of the attractive features of this present protocol.
- Li, Jianxiao,Huang, Ruikang,Li, Can,Lin, Shao,Wu, Wanqing,Jiang, Huanfeng
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p. 2309 - 2315
(2019/06/24)
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- Design, synthesis,: In silico docking studies and biological evaluation of novel quinoxaline-hydrazide hydrazone-1,2,3-triazole hybrids as α-glucosidase inhibitors and antioxidants
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A new series of quinoxaline-hydrazidehydrazone-1,2,3-triazole hybrids, 14a-j, 15a-j and 16a-e, was designed, synthesized and screened for in vitro α-glucosidase and antioxidant activities. For the synthesis of the target compounds, quinoxaline hydrazides were condensed with benzaldehyde triazoles in the presence of AcOH (cat) in ethanol. The key step in the preparation of compounds 8a-j was the Cu(i)-catalyzed [3+2] cycloaddition reaction (CuAAC) with appropriate alkynes (6, 7) and azides, and 13a-j were prepared from simple aldehydes utilizing the same click reaction as the final step. Quinoxaline hydrazides (3, 3a) were synthesized from o-phenylenediamine and pyruvic acid via three-step reactions comprising cyclization, alkylation and hydrazidation. Among these hybrids, 14a (IC50 = 21.92 μg mL-1), 14b (IC50 = 22.32 μg mL-1), 14c (IC50 = 23.58 μg mL-1) and 15a (IC50 = 24.50 μg mL-1) showed good α-glucosidase inhibition compared with the standard acarbose (IC50 = 22.32 μg mL-1). Further, the scavenging abilities of the synthesized compounds as antioxidants were studied using the DPPH, H2O2, and NO methods; as per the obtained results, compounds 14a, 14b, 14c and 15a displayed good antioxidant activity. Docking studies of the active compounds and acarbose as a standard with α-glucosidase (PDB ID: 2ZEO) were performed to determine the molecular interactions between the inhibitors and the active site of the enzyme. Better binding energies of the active compounds than of the standard acarbose were observed. Therefore, our new hybrid molecules may be useful for further optimization in developing new lead molecules with both α-glucosidase inhibition and antioxidant activities.
- Settypalli, Triloknadh,Chunduri, Venkata Rao,Maddineni, Aruna Kumari,Begari, Nagaraju,Allagadda, Rajasekhar,Kotha, Peddanna,Chippada, Appa Rao
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p. 15435 - 15452
(2019/10/08)
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- Pleuromutilin derivative with 2-aminothiophenol and 1,2,3-triazole side chain, preparation and application
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The invention belongs to the field of medicinal chemistry, and particularly relates to a pleuromutilin derivative with 2-aminothiophenol and a 1,2,3-triazole side chain, preparation and application. The pleuromutilin derivative with 2-aminothiophenol and the 1,2,3-triazole side chain is a compound of a formula 2 or a pharmaceutically acceptable salt of the compound, and a solvent compound, an enantiomer, a diastereomer and a tautomer of the compound of the formula 2 or the pharmaceutically acceptable salt of the compound or a mixture of the compound of the formula 2 or the pharmaceutically acceptable salt of the compound in any ratio, and includes a racemic mixture, and the compound has good inhibition to methicillin-resistant staphylococcus aureus activity, and is especially suitable forbeing used as a novel antibacterial drug for prevention and treatment of infectious diseases caused by human or animals or methicillin-resistant staphylococcus aureus or multi-drug resistant bacteria.(Please see the specification for the formula).
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Paragraph 0096-0099
(2019/11/12)
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- Pleuromutilin derivative containing piperazine and 1, 2, 3-triazole secondary amine side chains, and preparation and applications thereof
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The invention belongs to the field of pharmaceutical chemistry, and especially relates to a pleuromutilin derivative containing piperazine and 1, 2, 3-triazole secondary amine side chains, and preparation and applications thereof. The pleuromutilin derivative containing piperazine and 1, 2, 3-triazole secondary amine side chains is a compound represented by formula 2 or a pharmaceutically acceptable salt of the compound, or a solvate, an enantiomer, a diastereomer, a tautomer of the compound represented by formula 2 or the pharmaceutically acceptable salt of the compound, or a mixture of the above substances at a random ratio comprising a racemic mixture. The compound possesses excellent in vitro antibacterial activity, the cost is lower than that of valnemulin and retapamulin, so that thecompound is especially suitable to be taken as a novel antibacterial drug in prevention and treatment of human or animal bacterial infectious diseases, especially infectious diseases caused by medicine resistant Staphylococcus aureus.
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Paragraph 0100-0102
(2019/11/29)
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- TETRAHYDROPYRIDINE DERIVATIVES AND THEIR USE AS ANTIBACTERIAL AGENTS
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The present disclosure relates to a novel tetrahydropyridine derivative compound, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, methods for preparing the compounds, methods for inhibiting UDP-3-O—(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC), methods for treating Gram-negative bacterial infections, the use of the compounds for the preparation of therapeutic medicaments for treating Gram-negative bacterial infections, and pharmaceutical compositions for prevention or treatment of Gram-negative bacterial infections, which contain the compounds. The compounds represented by formula I, stereoisomers thereof or pharmaceutically acceptable salts thereof according to the present disclosure can exhibit excellent effects on the treatment bacterial infections.
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Paragraph 0205-0207
(2018/04/20)
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- Supported copper (I) catalyst from fish bone waste: An efficient, green and reusable catalyst for the click reaction toward N-substituted 1,2,3-TRIAZOLES
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An eco-efficient, green, and multi-gram procedure is presented for one-pot multicomponent synthesis of N-substituted 1,2,3-triazoles by using waste fishbone powders supported CuBr (FBPs-CuBr) as catalyst. FBPs-CuBr is found to be an efficient heterogeneous catalyst and a series of 1,2,3-triazoles are obtained in moderate to excellent yields in water under MW irradiation (70–98%). It can be separated conveniently by a simple filtration and reused at least seven consecutive runs with a slight drop in the product yields. Furthermore, the desired product still could be obtained in 80% yield when the scale of the reaction was increased to 40.0 mmol.
- Xiong, Xingquan,Tang, Zhongke,Sun, Zhaohong,Meng, Xiaoqing,Song, Sida,Quan, Zhilong
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- Discovery of highly potent renin inhibitors potentially interacting with the S3' subsite of renin
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To exploit the S3′ subsite of renin active site for renin inhibitor design, 42 aliskiren derivatives with modified P2' portion were designed, synthesized and biologically evaluated. Some highly potent renin inhibitors (IC50 50 Combining double low line 0.9 nM) and 39 (IC50 Combining double low line 0.7 nM) were over 2.5-fold more potent than aliskiren (IC50 Combining double low line 2.3 nM). SAR analysis indicated that incorporation of polar hydrophilic moieties into the P2' portion of renin inhibitors generally enhanced the potency. Consistently with this, molecular modeling study revealed that the triazole part of 39 could provide additional interactions to the S3' subsite of renin active site. Moreover, in vivo evaluation in the double transgenic mouse hypertension model demonstrated that 39 produced greater reduction of the mean arterial blood pressure than ariskiren at the doses of 17.0 and 34.0 1/4mol/kg, respectively. Taken together, the S3' subsite of renin active site merits further consideration for renin inhibitor design.
- Sun, Xiaowei,Wen, Xiaoan,Chen, Yan-Yan,Shi, Chen,Gao, Chengzhe,Wu, Yong,Wang, Li-Jun,Yang, Xiu-Hong,Sun, Hongbin
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supporting information
p. 269 - 288
(2015/09/21)
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- 7-Chloroquinolinotriazoles: Synthesis by the azide-alkyne cycloaddition click chemistry, antimalarial activity, cytotoxicity and SAR studies
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Twenty-seven 7-chloroquinolinotriazole derivatives with different substituents in the triazole moiety were synthesized via copper-catalyzed cycloaddition (CuAAC) click chemistry between 4-azido-7-chloroquinoline and several alkynes. All the synthetic compounds were evaluated for their in vitro activity against Plasmodium falciparum (W2) and cytotoxicity to Hep G2A16 cells. All the products disclosed low cytotoxicity (CC50 > 100 μM) and five of them have shown moderate antimalarial activity (IC50 from 9.6 to 40.9 μM). As chloroquine analogs it was expected that these compounds might inhibit the heme polymerization and SAR studies were performed aiming to explain their antimalarial profile. New structural variations can be designed on the basis of the results obtained.
- Pereira, Guilherme R.,Brand?o, Geraldo Célio,Arantes, Lucas M.,De Oliveira Jr., Háliton A.,De Paula, Renata Cristina,Do Nascimento, Maria Fernanda A.,Dos Santos, Fábio M.,Da Rocha, Ramon K.,Lopes, Júlio César D.,De Oliveira, Alaíde Braga
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p. 295 - 309
(2014/02/14)
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- Design, synthesis and antimicrobial activities of some new quinoline derivatives carrying 1,2,3-triazole moiety
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A new series of [1-(6-methoxy-2-methylquinolin-4-yl)-1H-1,2,3-triazol-4-yl] methanamine derivatives were synthesized starting from 4-methoxyaniline through multi-step reactions. The title compounds 5a-y were prepared by treating the azide intermediate 4 with propargyl bromide and different alkyl/heterocyclic amines in a sequential three component synthesis. All the new compounds were characterized by spectral and elemental analyses. The newly synthesized final compounds were evaluated for their in vitro antibacterial and antifungal activities against pathogenic strains. The preliminary screening results indicated that most of the compounds demonstrated moderate to very good antibacterial and antifungal activities, comparable to the first-line drugs. Twenty five new derivatives of [1-(6-methoxy-2-methylquinolin-4-yl)-1H-1,2,3- triazol-4-yl] methanamine have been synthesized and the most effective compounds have MIC of 6.25 μg/mL, which are in comparable with present antibiotics.
- Thomas,Adhikari, Airody Vasudeva,Shetty, N. Suchetha
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experimental part
p. 3803 - 3810
(2010/09/15)
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- 6-Substituted-4-(3-bromophenylamino)quinazolines as putative irreversible inhibitors of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER-2) tyrosine kinases with enhanced antitumor activity
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A series of new 6-substituted-4-(3-bromophenylamino)quinazoline derivatives that may function as irreversible inhibitors of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER-2) tyrosine kinases have been prepared. These inhibitors have, at the C-6 position, butynamide, crotonamide, and methacrylamide Michael acceptors bearing water-solublilizing substituents. These compounds were prepared by acylation of 6-amino-4-(3-bromophenylamino)quinazoline with unsaturated acid chlorides or mixed anhydrides. We show that attaching a basic functional group onto the Michael acceptor results in greater reactivity, due to intramolecular catalysis of the Michael addition and/or an inductive effect of the protonated basic group. This, along with improved water solubility, results in compounds with enhanced biological properties. We present molecular modeling and experimental evidence that these inhibitors interact covalently with the target enzymes. One compound, 16a, was shown to have excellent oral activity in a human epidermoid carcinoma (A431) xenograft model in nude mice.
- Tsou,Mamuya,Johnson,Reich,Gruber,Ye,Nilakantan,Shen,Discafani,DeBlanc,Davis,Koehn,Greenberger,Wang,Wissner
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p. 2719 - 2734
(2007/10/03)
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- Xanthine compounds having terminally animated alkynol side chains
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Compounds of the formula I, STR1 in which one of the radicals R1 and R3 is an alkynol residue of the formula Ia or Ib STR2 are suitable for producing pharmaceuticals having a neuroprotective effect.
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- Amines and Ammonium Compounds: CCXXXI. Synthesis of Tertiary Allenic 1,5-Diamines
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Dialkylammonium salts containing both 4-penten-2-ynyl and 2-propynyl groups react with aqueous secondary amines to give 1,5-bis(dialkylamino)penta-2,3-dienes. Optimal reaction conditions are found and a mechanism of elimination of the 2-propynyl group from the initial salts is proposed.
- Kocharyan,Osyan,Grigoryan,Grigoryan,Lulukyan,Babayan
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p. 446 - 450
(2007/10/03)
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- Gas Phase Thermolysis of Allyl Cyanomethyl Amine, Diallyl Cyanomethyl Amine, Diethyl Cyanomethyl Amine, and Diethyl Propargyl Amine
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The title amines were pyrolyzed in a stirred-flow reactor at 380 - 510 deg C, pressures of 8 - 15 torr and residence times of 0.3 - 2.4 s, using toluene as carrier gas.The substrates with an allyl group yielded propene and iminonitriles as reaction products.HCN is formed by decomposition of the iminonitriles.The first-order rate coefficients for propene formation fit the Arrhenius equations.Allyl cyanomethyl amine: k(s-1) = 1013.29 +/- 0.35exp(-189 +/- 5 kJ/mol RT) Diallyl cyanomethyl amine: k(s-1) = 1013.00 +/- 0.20exp(-183 +/- 3 kJ/mol RT) Diethyl cyanomethyl amine gave a 20:1 gas mixture of ethylene and ethane, plus HCN.The liquid product fraction contained mainly N-ethyl methanaldimine.The first-order rate coefficients for ethylene formation followed the Arrhenius equation k(s-1) = 1015.30 +/- 0.24exp(-226 +/- 3 kJ/mol RT) Diethyl propargyl amine decomposed cleanly into allene and N-ethyl ethanaldimine.The first-order rate coefficients for allene formation fit the Arrhenius equation k(s-1) = 1012.84 +/- 0.30exp(-168 +/- 4 kJ/mol RT).The results suggest that the above allyl and propargyl amines decompose unimolecularly by mechanisms involving six-center cyclic transition states.For diethyl cyanomethyl amine, a nonchain free radical mechanism is proposed.
- Martin, Gonzalo,Ascanio, Julian,Rodriguez, Jesus
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- Acetylenes as Potential Antarafacial Components in Concerted Reactions. Formation of Pyrroles from Thermolyses of Propargylamines, of a Dihydrofuran from a Propargylic Ether, and of an Ethylidenepyrrolidine from a β-Amino Acetylene
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A thermal cyclization of acetylenic compounds provides evidence for the ability of acetylenic links to act as antarafacial components in processes.The cyclization competes with the normally favored acetylenic retro-ene reaction.Propargylic amines, without substituents whose presence would hinder a tight cyclic transition state, yield intermediate pyrrolines whose subsequent hydrogen elimination affords pyrroles in small amounts.The same process in 2-ethynyltetrahydropyran affords 8-oxabicyclooctane in 35percent yield.A related thermal reaction of N-methyl-3-hexyn-1-amine provides a quantitative transformation to N-methyl-2-ethylidenepyrrolidine in a nominal s + 2a + 2s + 2s> Moebius process, wherein the acetylenic unit is the antarafacial component.Evidence for concertedness in these reactions is discussed.
- Viola, Alfred,Collins, John J.,Filipp, Nicholas,Locke, John S.
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p. 5067 - 5075
(2007/10/02)
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- Studies of Tertiary Amine Oxides Part 10. Silylated Acetylenic Amines and the Corresponding N-Oxides
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Ten silylated acetylenic amines were synthesized and converted into the corresponding tertiary N-oxides by oxidation with m-chloroperbenzoic acid.All compounds were fully characterised by elemental and spectral analyses.The carbon-13 spectra of the silylated acetylenic amines and the N-oxides were analysed and the N-oxidation effect was calculated.
- Khuthier, Abdul-Hussain,Sheat, Mohammed A.,Al-Rawi, Jasim M. A.,Salih, Zuhair S.
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p. 1501 - 1518
(2007/10/02)
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- Conjugated ketone compounds in preventing platelet thrombosis
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Conjugated ketone compounds of the formula: STR1 wherein Ar is naphthyl, furyl, thienyl, or phenyl optionally bearing one or more substituents selected from the group consisting of chlorine, bromine, C1 -C4 alkyl, C1 -C4 alkoxy, C1 -C4 alkylthio, trifluoromethyl and methylenedioxy, R1 is C1 -C6 alkyl, C3 -C5 alkenyl, C3 -C6 cycloalkyl, C7 -C8 aralkyl or adamantyl, R2 is C1 -C6 alkyl, C3 -C5 alkenyl or C3 -C6 cycloalkyl, or when R1 and R2 are taken together with the nitrogen atom to which they are attached, they form a heterocyclic amino group containing up to 8 carbon atoms, A is straight or branched C1 -C3 alkylene, N-[4-(p-chlorophenyl)-4-oxo-2-trans-butenyl]morpholine and N-[4-(p-methoxyphenyl)-4-oxo-2-trans-butenyl]piperidine being excluded, and their non-toxic salts, which are useful as blood platelet anti-aggregative agents.
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- HYDROBORATION D'AMINES INSATUREES-II REGIO ET STEREOSELECTIVITE DE L'HYDROBORATION-ALKYLATION D'AMINES ACETYLENIQUES
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The hydroboration reaction of acetylenic amines R1R2N-CH(R3)-CC-R4 was studied.We report the first results of a study of the reactivity of dialkylborane R2BH towards these amines which allow us to propose a new method for the synthesis of differently substituted β-ethylenic amines.The regioselectivity and the stereoselectivity of this reaction are examined and allow us to set out the possibility of a trans hydroboration.
- Torregrosa, J. L.,Baboulene, M.,Speziale, V.,Lattes, A.
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p. 2355 - 2363
(2007/10/02)
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- Base-catalysed isomerization of 2-propynylamines. Synthesis of (dialkylamino)allenes
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A number of (dialkylamino)allenes 2 have been obtained in excellent yields and in a reasonable state of purity by isomerization of dialkyl-2-propynylamines 1 with potassium tert-butoxide in tetrahydrofuran or with the complex t-BuOK*t-BuOH in hexamethylphosphoric triamide.Treatment of the 2-propynylamines with t-BuOK in dimethyl sulfoxide leads to equilibrium mixtures of the allenic amines 2 and dialkyl-1-alkynylamines 3.
- Verkruijsse, H. D.,Bos, H. J. T.,Noten, L. J. de,Brandsma, L.
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p. 244 - 246
(2007/10/02)
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