- Synthesis of Size-Tunable Hollow Polypyrrole Nanostructures and Their Assembly into Folate-Targeting and pH-Responsive Anticancer Drug-Delivery Agents
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Chemotherapeutic drugs currently used in clinical settings have high toxicity, low specificity, and short half-lives. Herein, polypyrrole-based anticancer drug nanocapsules were prepared by tailoring the size of the nanoparticles with a template method, controlling drug release by means of an aromatic imine, increasing nanoparticle stability through PEGylation, and improving tumor-cell selectivity by folate mediation. The nanoparticles were characterized by TEM and dynamic light scattering. α-Folate receptor expression levelsof tumor cells and normal cells were investigated by western blot and quantitative polymerase chain reaction analyses. Flow cytometry and fluorescence imaging were used to verify the cell uptake of the different-sized nanoparticles. From the different-sized polypyrrole nanoparticles, the optimally functionalized nanoparticles of 180 nm hydrodynamic diameter were chosen and further usedfor in vitroandin vivotests. The nanoparticles showed excellent biocompatibility and the drug-loaded nanoparticles exhibited effective inhibition of tumor cell growth in vitro. Moreover, the drug-loaded nanoparticles showed substantially enhanced accumulation in tumor regions and effectively inhibitedin vivotumor growth. Furthermore, the nanoparticles showed reduced doxorubicin-induced toxicity andno significant side effects in normal organs of tumor-bearing mice, as measured by body-weight shifts and evaluationof drug distribution. Overall, the functionalized nanoparticles are promising nanocarriers for tumor-targeting drug delivery.
- Chen, Jian,Li, Xiufang,Sun, Yanhua,Hu, Yuwei,Peng, Yulong,Li, Yimin,Yin, Gang,Liu, Hui,Xu, Jiangfeng,Zhong, Shian
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Read Online
- Construction of pyrrole- and indole-fused CF3-piperazine derivatives
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A series of pyrrole- and indole-fused trifluoromethyl-functionalized piperazine derivatives were constructed in moderate to good yields with excellent chemoselectivities via a Pictet-Spengler reaction under mild and operationally simple conditions. The synthetic utility of this protocol was further extended by the facile preparation of indole-fused CF3-1,4-diazocane and enantioenriched CF3-piperazines via a vinylogous Pictet-Spengler reaction and an asymmetric Pictet-Spengler reaction, respectively.
- Tian, Yu-Ting,Zong, Yu-Wei,Nie, Jing,Zhang, Fa-Guang,Ma, Jun-An
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- EIS INHIBITORS
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Compounds and compositions are disclosed, which are useful as inhibitors of acetyltransferase Eis, a mediator of kanamycin resistance in Mycobacterium tuberculosis.
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Paragraph 0025; 0131; 0132
(2018/06/30)
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- Compound as potassium channel modulator
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The invention relates to a compound as a potassium channel modulator, which is a compound of a formula (I) or a pharmaceutically acceptable salt thereof. The compound or the pharmaceutically acceptable salt thereof is effective for curing and preventing diseases and symptoms influenced by the activity of potassium ion channels.
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Paragraph 0787; 0789; 0790; 0791
(2018/07/30)
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- Design, synthesis and evaluation of novel N-phenylbutanamide derivatives as KCNQ openers for the treatment of epilepsy
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KCNQ (Kv7) has emerged as a validated target for the development of novel anti-epileptic drugs. In this paper, a series of novel N-phenylbutanamide derivatives were designed, synthesized and evaluated as KCNQ openers for the treatment of epilepsy. These compounds were evaluated for their KCNQ opening activity in vitro and in vivo. Several compounds were found to be potent KCNQ openers. Compound 1 with favorable in vitro activity was submitted to evaluation in vivo. Results showed that compound 1 owned significant anti-convulsant activity with no adverse effects. It was also found to posses favorable pharmacokinetic profiles in rat. This research may provide novel potent compounds for the discovery of KCNQ openers in treating epilepsy.
- Yang, Shaoning,Lu, Dingqiang,Ouyang, Pingkai
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supporting information
p. 3004 - 3008
(2018/07/31)
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- Combating Enhanced Intracellular Survival (Eis)-Mediated Kanamycin Resistance of Mycobacterium tuberculosis by Novel Pyrrolo[1,5-a]pyrazine-Based Eis Inhibitors
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Tuberculosis (TB) remains one of the leading causes of mortality worldwide. Hence, the identification of highly effective antitubercular drugs with novel modes of action is crucial. In this paper, we report the discovery and development of pyrrolo[1,5-a]p
- Garzan, Atefeh,Willby, Melisa J.,Ngo, Huy X.,Gajadeera, Chathurada S.,Green, Keith D.,Holbrook, Selina Y. L.,Hou, Caixia,Posey, James E.,Tsodikov, Oleg V.,Garneau-Tsodikova, Sylvie
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p. 302 - 309
(2017/04/21)
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- Organocatalytic enantioselective multicomponent synthesis of pyrrolopiperazines
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The first organocatalytic multicomponent synthesis of enantioenriched pyrrolopiperazines is reported. These biologically relevant fused tricyclic products were obtained under catalytic iminium activation through a reaction sequence involving an enantioselective Michael addition followed by an iminium ion trapping via Pictet-Spengler cyclization (MAPS sequence). Substantial possibilities for variation on the three reaction partners [β-keto ester, enal and N-(2-aminoethyl)pyrrole] along with excellent enantioselectivities are the highlights of the present transformation.
- Du, Haiying,Rodriguez, Jean,Bugaut, Xavier,Constantieux, Thierry
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supporting information
p. 851 - 856
(2014/04/03)
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- PHTHALAZINONE KETONE DERIVATIVE, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL USE THEREOF
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A phthalazinone ketone derivative as represented by formula (I), a preparation method thereof, a pharmaceutical composition containing the derivative, a use thereof as a poly (ADP-ribose) polymerase (PARP) inhibitor, and a cancer treatment method thereof.
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Paragraph 0082: 0083
(2013/06/28)
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- PHTHALAZINONE KETONE DERIVATIVE, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL USE THEREOF
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A phthalazinone ketone derivative as represented by formula (I), a preparation method thereof, a pharmaceutical composition containing the derivative, a use thereof as a poly (ADP-ribose) polymerase (PARP) inhibitor, and a cancer treatment method thereof are described.
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Paragraph 0104
(2013/06/04)
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- Substituted Tetrahydropyrrolopyrazine Compounds
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Tetrahydropyrrolopyrazine compounds, methods for their preparation, pharmaceutical compositions containing such compounds, and a method of using such compounds for the treatment of pain and other conditions mediated at least partially by Bradykinin 1 rece
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Page/Page column 28-29
(2012/03/26)
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- SUBSTITUTED TETRAHYDROPYRROLOPYRAZINE DERIVATIVES
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The present invention relates to tetrahydropyrrolopyrazines, methods for the preparation thereof, medicaments containing these compounds and compounds for the use of treating, amongst other things, pain.
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Page/Page column 59
(2012/03/26)
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- Direct synthesis of chiral 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazines via a catalytic asymmetric intramolecular aza-Friedel-Crafts reaction
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The direct asymmetric intramolecular aza-Friedel-Crafts reaction of N-aminoethylpyrroles with aldehydes catalyzed by a chiral phosphoric acid represents the first efficient method for the preparation of medicinally interesting chiral 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazines with high yields and high enantioselectivities. This strategy has been shown to be quite general toward various aldehydes and pyrrole derivatives.
- He, Yuwei,Lin, Maohui,Li, Zhongmin,Liang, Xinting,Li, Guilong,Antilla, Jon C.
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supporting information; experimental part
p. 4490 - 4493
(2011/10/09)
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- SULFONYLATED TETRAHYDROAZOLOPYRAZINES AND THEIR USE AS MEDICINAL PRODUCTS
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The present invention relates to sulfonylated tetrahydroazolopyrazines, methods for the preparation thereof, medicinal products containing these compounds and the use of substituted indole compounds for the preparation of medicinal products (Formula I).
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Page/Page column 75-76
(2010/09/18)
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- Substituted Sulfonamide Compounds
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Substituted sulfonamide compounds corresponding to the formula I wherein m, n, p, Q, R1, R2, R3, R4, X, Y and Z have the respective meanings defined herein, pharmaceutical compositions containing such compounds, a process for their preparation, and the use of such compounds for the treatment and/or inhibition of pain and other conditions mediated by bradykinin receptor 1 (B1R) and/or bradykinin receptor 2 (B2R).
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Page/Page column 35; 41
(2009/07/25)
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- SUBSTITUTED SULFONAMIDE DERIVATIVES
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The invention relates to substituted sulfonamide derivatives of the general formula (I'); processes for their preparation, medicaments containing these compounds, and the use of substituted sulfonamide derivatives for the preparation of medicaments
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Page/Page column 103; 104
(2009/08/16)
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- SUBSTITUTED SULFONAMIDE COMPOUNDS
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Substituted sulfonamide derivatives, a process for their preparation, pharmaceutical compositions containing these compounds, and to the use of substituted sulfonamide derivatives in the treatment or inhibition of pain and/or various disorders or disease states.
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Page/Page column 75
(2008/12/06)
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- Substituted Tetrahydropyrrolopyrazine Compounds and the Use Thereof in the Treatment and/or Inhibition of Pain
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Substituted tetrahydropyrrolopyrazine compounds corresponding to the formula I: processes for their preparation, pharmaceutical compositions comprising these compounds and the use of these compounds for the treatment and/or inhibition of pain and other disorders or disease states at least partly mediated by KCNQ2/3 K+ channels.
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Page/Page column 13
(2008/12/06)
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- Pyrrolodiazines. 6. Palladium-catalyzed arylation, heteroarylation, and amination of 3,4-dihydropyrrolo[1,2-α]pyrazines
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The palladium-catalyzed Suzuki cross-coupling reaction of arylboronic acids and 6-bromo- and 6,8-dibromo-3,4-dihydropyrrolo[1,2-α]pyrazines afforded 6-substituted and 6,8-disubstituted 3,4-dihydropyrrolo[1,2-α]pyrazines in good yields. Stille and Negishi coupling reactions have been used to prepare 6-heteroaryl-substituted derivatives in moderate yields by employing heteroaryl halides and 6-metalated 3,4-dihydropyrrolo[1,2-α]pyrazines as reaction partners. A variety of cyclic secondary amines have also been incorporated at position C-6 of 6-bromo-1-phenyl-3,4-dihydropyrrolo[1,2-α]pyrazine in the presence of the palladium catalyst Pd2(dba)3 in conjunction with BINAP as ligand. This amination reaction is one of the few reported examples of such a palladium-catalyzed transformation on a pyrrole ring, although the reaction could not be extended to less nucleophilic amines.
- Castellote, Isabel,Vaquero, Juan J.,Fernandez-Gadea, Javier,Alvarez-Builla, Julio
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p. 8668 - 8675
(2007/10/03)
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- Design of chiral poly(pyrroles)
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The synthesis of three 3-substituted and one N-substituted chiral pyrrole derivatives as well as their electropolymerization conditions are described. The new materials thus obtained possess recognition properties as enantioselective electrodes.
- Pleus, Susanne,Schwientek, Marion
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p. 2917 - 2930
(2007/10/03)
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- A convenient method for the preparation of 1-substituted and 1,3-disubstituted pyrroles from acetals of 3-alkenals
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1-substituted and 1,3-disubstituted pyrroles were obtained in 3 steps starting from readily accessible acetals of 3-alkenals in good yields.
- Kulinkovitsch,Sorokin,Azzuz,Sviridov,Masalov
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p. 1059 - 1060
(2007/10/02)
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- Bridged 2,2'-biazole derivatives by 1,3-dipolar cycloaddition
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Azomethine ylides derived from 3,4-dihydropyrrolo[1,2-a]pyrazinium salts undergo 1,3-dipolar cycloaddition reactions to yield 5,6-dihydrodipyrrolo[1,2-a:2',1'-c]-pyrazine and 5,6-dihydroimidazo[1,2-a]pyrrolo[2,1-c]pyrazin-4-inium-2-olate and 2-thiolate de
- De Pablo,Gandasegui,Vaquero,Garcia Navio,Alvarez-Builla
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p. 8793 - 8800
(2007/10/02)
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- Tetracyclic pyrrole lactam derivatives
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Disclosed are the compounds of formula I STR1 wherein R and R1 -R3 independently represent hydrogen or lower alkyl, and m represents the integer 2 or 3; their methods of preparation; pharmaceutical compositions thereof, and their use
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- Heterotertracyclic lactam derivatives, pharmaceutical compositions, and method of treating impaired memory and learning
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Disclosed are the compounds of formula I: STR1 wherein R1 -R3 represent hydrogen or lower alkyl; m represents the integer 2 or 3; n represents the integer 1 or 2; Het represents a pyrrole or imidazole ring bonded at any two adjacent positions and optionally substituted by one or two or lower alkyl; and pharmaceutically acceptable salts of compounds of formula I wherein Het represents optionally substituted imidazole; their methods of preparation; pharmaceutical compositions thereof, and their use for treating cognitive disorders in mammals.
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- 1,2,3,4-Tetrahydropyrrolo(1,2-A)pyrazines
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1,2,3,4-tetrahydropyrrolo(1,2-a)pyrazine derivatives characterized by having a lower alkyl, cyclo(lower)alkyl, phenyl or substituted phenyl at position 1 of the nucleus and optionally further substituted at position 2 of the nucleus with a lower alkyl, cy
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