- Direct subphthalocyanine conjugation to bombesin: Vs. indirect conjugation to its lipidic nanocarrier
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Bombesin (BBN) was covalently bound to graftable subphthalocyanine (SubPc) or to a cholesterol derivative, a component of a liposome that encapsulates non-graftable SubPc. The latter bioconjugation approach was suitable to address the stability of SubPc and was achieved by copper-free click-chemistry on the outer-face of the liposome. Liposomes were purified (FPLC) and then analyzed in size (outer diameter about 60 nm measured by DLS). In vitro binding studies allowed to determine the IC50 13.9 nM for one component of the liposome, cholesterol, conjugated to BBN. Hence, azido- (or alkynyl-) liposomes give fluorophores with no reactive functional group available on their backbone a second chance to be (indirectly) bioconjugated (with bombesin).
- Bernhard, Yann,Gigot, Elodie,Goncalves, Victor,Moreau, Mathieu,Sok, Nicolas,Richard, Philippe,Decréau, Richard A.
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Read Online
- Insights into the mechanism and catalysis of peptide thioester synthesis by alkylselenols provide a new tool for chemical protein synthesis
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While thiol-based catalysts are widely employed for chemical protein synthesis relying on peptide thioester chemistry, this is less true for selenol-based catalysts whose development is in its infancy. In this study, we compared different selenols derived from the selenocysteamine scaffold for their capacity to promote thiol-thioester exchanges in water at mildly acidic pH and the production of peptide thioesters from bis(2-sulfanylethyl)amido (SEA) peptides. The usefulness of a selected selenol compound is illustrated by the total synthesis of a biologically active human chemotactic protein, which plays an important role in innate and adaptive immunity.
- Agouridas, Vangelis,Bogard, Gemma,Drobecq, Hervé,Kerdraon, Florent,Melnyk, Oleg,Pichavant, Muriel,Snella, Beno?t
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Read Online
- Preparation method of doxylamine succinate impurity C
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The invention discloses a preparation method of a doxylamine succinate impurity C. The preparation method comprises steps as follows: alpha-phenyl-2-pyridinemethanol and an organic solvent are added to a reactor, stirred and dissolved, after air in the reactor is subjected to N2 replacement, alkali liquor is added, a 2-dimethylaminoethyl chloride solution is dropwise added during stirring, a mixed solution is heated to produce backflow and is cooled after the reaction, water is added to a reaction product, a mixture is layered and purified, and a target product is obtained. According to the preparation method, alpha-phenyl-2-pyridinemethanol is taken as a raw material and subjected to an elimination reaction with 2-dimethylaminoethyl chloride under the alkaline condition, and the target product is obtained; the method has the advantages of adopting mild reaction conditions and short synthesis route and being simple and convenient to operate and can be applied to qualitative and quantitative analysis of impurities in doxylamine succinate production, and therefore, quality standard of doxylamine succinate can be improved; the product is high in yield and purity.
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Paragraph 0036-0037; 0043-0044; 0050-0051; 0057-0058
(2018/03/28)
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- Isoflavone amide type derivative, preparation method and medical application thereof
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The invention relates to the field of medicinal chemistry, and relates to an isoflavone amide type derivative, a preparation method and a medical application thereof, in particular to an isoflavone amide type derivative with the general formula (I), a preparation method thereof, medicine compositions including the isoflavone amide type derivative and a medical application thereof, especially an application of the isoflavone amide type derivative as a medicine for preventing or curing hyperlipemia, obesity or type II diabetes. The general formula (I) is shown in the description.
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Paragraph 0016; 0080; 0081; 0082; 0089; 0090; 0091
(2016/10/10)
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- Design, Synthesis, and Biological Evaluation of Scutellarein Derivatives Based on Scutellarin Metabolic Mechanism in Vivo
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Three series of scutellarein derivatives have been designed and synthesized based on metabolic mechanism of scutellarin (1) in vivo. Their thrombin inhibition activities were tested through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB). The antioxidant activities of these target products were assessed by 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay and the ability to protect PC12 cells against H2O2-induced cytotoxicity, and their solubilities were evaluated by ultraviolet (UV) spectrophotometer. The results showed that the two isopropyl groups substituted derivative (18c) demonstrated stronger anticoagulant activity, better water solubility, and good antioxidant activity compared with scutellarein (2), which warrants further development of 18c as a promising agent for ischemic cerebrovascular disease treatment. Three series of scutellarein derivatives have been designed and synthesized based on metabolic mechanism of scutellarin (1) in vivo. The results of the biological evaluation showed that the two isopropyl groups substituted derivative (18c) demonstrated stronger anticoagulant activity, better water solubility, and good antioxidant activity compared with scutellarein (2), which warrants further development of 18c as a promising agent for ischemic cerebrovascular disease treatment.
- Dong, Ze-Xi,Shi, Zhi-Hao,Li, Nian-Guang,Zhang, Wei,Gu, Ting,Zhang, Peng-Xuan,Wu, Wen-Yu,Tang, Yu-Ping,Fang, Fang,Xue, Xin,Li, He-Min,Cheng, Hai-Bo,Yang, Jian-Ping,Duan, Jin-Ao
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p. 946 - 957
(2016/05/24)
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- Highly Water-Soluble Cyclopentadienyl and Indenyl Molybdenum(II) Complexes - Second Generation of Molybdenum-Based Cytotoxic Agents
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A series of the cyclopentadienyl and indenyl molybdenum compounds bearing alkylammonium functions [(η5-Cp′)Mo(CO)2(N,NL)][BF4]2 were synthesized and characterized by analytical and spectroscopic methods. The structures of [{η5-C5H4CH2CH2NH(CH2)5}Mo(CO)2(4,7-Ph2-phen)][BF4]2 (4,7-Ph2-phen = 4,7-diphenyl-1,10-phenanthroline) and [(η5-C9H6CH2CH2NHMe2)Mo(CO)2(phen)][BF4]2 (phen = 1,10-phenanthroline) were determined by X-ray crystallography. All of the synthesized compounds exhibit high activity against the human leukemia cell lines MOLT-4 and HL-60. They are approximately one order of magnitude more active than cisplatin. This study has proven that the modification of the outer coordination sphere of molybdenum complexes has a strong impact on their activity and may be successfully used for the design of new highly cytotoxic active species. A series of highly cytotoxic molybdenum(II) complexes are synthesized, and their activity against MOLT-4 and HL-60 leukemia cells is established.
- Mr?zek, Ond?ej,?ebestová, Lucie,Vinklárek, Jaromír,?ezá?ová, Martina,Eisner, Ale?,R??i?ková, Zdeňka,Honzí?ek, Jan
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p. 519 - 529
(2016/02/16)
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- Synthesis of scutellarein derivatives to increase biological activity and water solubility
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In order to improve the biological activity and water solubility of scutellarin (1), some derivatives of its main metabolite (scutellarein) were designed and synthesized. All the compounds were tested for their thrombin inhibition activity through the analyzation of thrombin time (TT), activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen (FIB). Their antioxidant activities were assessed by measuring their scavenging capacities toward 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and the ability to protect PC12 cells against H2O2-induced cytotoxicity, their water solubility were also assessed by ultraviolet (UV) spectrophotometer. The results showed that compound 8b demonstrated stronger anticoagulant and antioxidant activity, better water solubility compared with scutellarein (2), which warrants it as a promising agent for the treatment of ischemic cerebrovascular disease.
- Shi, Zhi-Hao,Li, Nian-Guang,Shi, Qian-Ping,Zhang, Wei,Dong, Ze-Xi,Tang, Yu-Ping,Zhang, Peng-Xuan,Gu, Ting,Wu, Wen-Yu,Fang, Fang,Xin-Xue,Li, He-Min,Yang, Jian-Ping,Duan, Jin-Ao
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p. 6875 - 6884
(2015/11/11)
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- Photoinitiated release of an aziridinium ion precursor for the temporally controlled alkylation of nucleophiles
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A photo-activatable aziridinium precursor has been developed to investigate the possibility of a photo-initiated traditional nucleophilic reaction. The photolysis of a quaternary amine yields a tertiary amine and has allowed us to temporally control aziridinium formation and subsequent alkylation of a colorimetric nucleophilic reporter molecule. We have also used this photo-initiated reaction to alkylate a sulfhydryl group. This new photo-initiated alkylation strategy is water-soluble and expands the toolkit of photo-activated crosslinkers for protein labeling research.
- McCarron, Stephen T.,Feliciano, Mariel,Johnson, Jeffreys N.,Chambers, James J.
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p. 2395 - 2398
(2013/05/21)
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- SELECTIVE ALLOSTERIC MODULATORS OF THE SEROTONIN TRANSPORTER
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Compounds of formula (I) are provided wherein R1 represents H, CN and CF3; R2 represents 1-naphthyl, 3,5-dichlorophenyl, 4-(4-fluorophenylthio)phenyl or phenyl substituted with one or more substituent selected from halogen, methoxy, cyano, methyl and trifluorom ethyl; R3 and R4 independently represent H, C1-3-alkyl or R3 and R4 together with the carbon atom to which they are attached form a C4-6-cyclic alkyl; R5 and R6 independently represent H or C1-6-alkyl; n represents 1 or 2; and pharmaceutically acceptable acid addition salts thereof, provided that if n is 2 then R2 is not 1-naphthyl, which compounds are selective allosteric SERT ligands.
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Page/Page column 29-30
(2013/08/15)
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- NOVEL PROCESS FOR SYNTHESIS OF ITOPRIDE AND ITS NOVEL INTERMEDIATE N-(4-HYDROXYBENZYL)- 3,4-DIMETHOXYBENZAMIDE
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The present invention relates to a novel and improved process for the preparation of N-[4-[2-(dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide—known as Itopride, via a novel intermediate N-(4?hydroxybenzyl)-3,4-dimethoxybenzamide.
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Page/Page column 3
(2009/07/18)
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- AMINOALKOXY ARYL SULFONAMIDE COMPOUNDS AND THEIR USE AS 5-HT6 LIGANDS
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The present invention relates to novel aminoalkoxy arylsulfonamide compounds of the formula (I), their derivatives, their stereoisomers, their pharmaceutically acceptable salts and pharmaceutically acceptable compositions containing them. The present invention also relates to a process for the preparation of above said novel compounds, their derivatives, their stereoisomers, their pharmaceutically acceptable salts and pharmaceutically acceptable compositions containing them. These compounds are useful in the treatment of various disorders that are related to 5-HT6 receptor functions. Specifically, the compounds of this invention are also useful in the treatment of various CNS disorders, hematological disorders, eating disorders, diseases associated with pain, respiratory diseases, genito-urological disorders, cardiovascular diseases and cancer.
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Page/Page column 25
(2009/01/20)
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- A NOVEL PROCESS FOR SYNTHESIS OF ITOPRIDE AND IT’S NOVEL INTERMEDIATE-N-(4-HYDROXYBENZYL)-3,4-DIMETHOXYBENZAMIDE
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The present invention relates to a novel and improved process for the preparation of N-[4-[2-(dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide-known as Itopride, via a novel intermediate N-(4~hydroxybenzyl)-3,4-dimethoxybenzamide.
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Page/Page column 9-10
(2008/06/13)
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- QUATERNARY AMMONIUM COMPOUND, PROCESS FOR PRODUCING THE SAME, THERAPEUTIC AGENT FOR CEREBROVASCULAR DISORDER, AND THERAPEUTIC AGENT FOR HEART DISEASE
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A quaternary ammonium compound of the present invention is a quaternary ammonium compound represented by general formula (I) or (I') (wherein, A represents a linear alkyl group having 1 to 4 carbon atoms, a branched alkyl group having 2 to 4 carbon atoms, a linear alkyl group having 1 to 4 carbon atoms and a hydroxyl group, or a branched alkyl group having 2 to 4 carbon atoms and a hydroxyl group, R 1 to R 3 may be the same or different and represent a linear or branched alkyl group having 1 to 12 carbon atoms, one of R 4 to R 8 represents CO 2 - or SO 3 - , while no more than three of the remaining R 4 to R 8 represent a group selected from the group consisting of a hydroxyl group and an alkoxy group having 1 to 4 carbon atoms, and other R 4 to R 8 represent a hydrogen atom, one of R' 4 to R' 8 represents CO 2 H or SO 3 H, no more than three of the remaining R' 4 to R' 8 represent a group selected from a protected hydroxyl group and an alkoxy group having 1 to 4 carbon atoms, while other R' 4 to R' 8 represent a hydrogen atom, and X - represents an anion capable of forming a salt with a quaternary ammonium group).
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Page/Page column 13
(2010/11/25)
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- Receptor ligands
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Use of a compound selected from the group consisting of 3,5-diiodo-4-(2-N, N-diethylaminoethoxy)phenyl-(2-butylbenzofur-3-yl)methanol hydrochloride (001), 2-methyl-3-(3,5-diiodo-4-(2-N,N-diethylaminoethoxy)-benzoyl)benzofuran hydrochloride (003), 2-n-butyl-3-(3,5-diiodo-4-carboxymethoxybenzoyl)benzofuran (005), 2-methyl-3-(3,5-diiodo-4-hydroxy-benzoyl)benzofuran (011), 2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (015), 4'-hydroxy-3'-iodo-3,5-diiodo-4-(2-N,N-diethylaminoethoxy)benzophenon hydrochloride (024), 2-butyl-3-(3-iodo-4-hydroxy-benzoyl)benzofuran (029), 4'4'-dihydroxy-3'3,5-triiododiphenylmethan (032), which compound is a 3,5,3'-triiodothyronine (T-3) receptor ligand, for the preparation of a medicament for the therapeutic or prophylactic treatment of a disorder which depends on the expression of T-3 regulated genes, and pharmaceutical preparations comprising said compounds, are disclosed. Further, a method of prophylactically or therapeutically treating a patient having a disorder which depends on the expression of 3,5,3"-triiodo-thyronine (T-3) regulated genes is also disclosed. The invention additionally comprises product protection for all the above listed compounds, except the compound (011).
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- Linear dicarbonylation of difunctionalized butenes
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Difunctional butenes are linearly dicarbonylated into 3-hexene-1,6-dioic acid or alkyl diesters thereof, well suited for the ultimate production of, e.g., adipic acid, by reacting such difunctional butene with carbon monoxide and, if appropriate, an alcohol, at an elevated temperature under superatmospheric pressure, in the presence of at least one source of hydrogen chloride and a catalytically effective amount of palladium, at least a portion of which palladium being in the zero oxidation state, as well as a quaternary onium chloride of nitrogen or phosphorus, the nitrogen or phosphorus atom being tetracoordinated to carbon atoms, with the proviso that the nitrogen atom may be coordinated to two pentavalent phosphorus atoms.
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- Introduction of Pharmacorphoric Groups into Polycyclis Systems. Part 3. Amine Derivatives of Adamantane and Diaza-adamantane
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Methods for introducing various pharmacophoric amine-containing substituents into the adamantane system have been investigated.These include β- and α-aminoalkyloxyimino, β-aminoalkylidine, β-hydroxyethylamino, and β-phenylethylamino.Aminoalkoxyimines were prepared by alkylation of the anion of adamantanone oxime with the corresponding aminoalkyl chloride, and a 2-aminoethylidene derivative was prepared by Witting reaction of 2-dimethylaminoethyltriphenylphosphonium bromide with adamantanone.The reaction of 6-hydroxy-7-methyl-6-phenyladamantane-2,4-dione with aqueous sodium cyanide has been shown to be both regio- and stereo-selective, only the C-2 carbonyl group reacting from the most hindered direction.This is possibly due to stabilisation of the cyanohydrin by hydrogen bonding between the hydroxy and C-4 carbonyl groups.When trimethyl cyanide was used in place of sodium cyanide, the reaction remained regioselective but, in the absence of hydrogen bond stabilisation, the stereoselectivity was lost and two trimethylsilyloxy cyanides were isolated, epimeric at C-2.The stereochemistry of one epimer has been determined by X-ray crystallography, details of which are reported here.Hydrogenation of the trimethylsilyloxy cyanides then gave the corresponding β-hydroxyamine, isolated as the hydrochloride.Finally 5,7-diphenyl-1,3-diaza-adamantan-6-one was prepared by a literature method and converted, with difficulty, into the oxime which was reduced by RedAl to the corresponding amine.
- Hickmott, Peter W.,Wood, Simon,Murray-Rust, Peter
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p. 2033 - 2038
(2007/10/02)
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