- A new kind of acetylcholine esterase inhibitors and its preparation method and application (by machine translation)
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The present invention provides a novel acetyl choline esterase inhibitor and its preparation method and application, in particular, the invention discloses a formula A shown with double AChE binding site of substituted acridine compound, and its preparation method and as acetylcholinesterase inhibitors. The preparation of the novel compounds of this invention demonstrate good inhibit acetylcholine esterase role, can be used as a preparation for treating and preventing HAMER (AD) application value. (by machine translation)
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Paragraph 0104; 0105; 0108; 0109
(2018/04/03)
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- 13C kinetic isotope effects on the reaction of a flavin amine oxidase determined from whole molecule isotope effects
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A large number of flavoproteins catalyze the oxidation of amines. Because of the importance of these enzymes in metabolism, their mechanisms have previously been studied using deuterium, nitrogen, and solvent isotope effects. While these results have been valuable for computational studies to distinguish among proposed mechanisms, a measure of the change at the reacting carbon has been lacking. We describe here the measurement of a 13C kinetic isotope effect for a representative amine oxidase, polyamine oxidase. The isotope effect was determined by analysis of the isotopic composition of the unlabeled substrate, N, N’-dibenzyl-1,4-diaminopropane, to obtain a pH-independent value of 1.025. The availability of a 13C isotope effect for flavoprotein-catalyzed amine oxidation provides the first measure of the change in bond order at the carbon involved in this carbon-hydrogen bond cleavage and will be of value to understanding the transition state structure for this class of enzymes.
- Tormos, José R.,Suarez, Marina B.,Fitzpatrick, Paul F.
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p. 115 - 119
(2016/11/11)
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- Characterization of unstable products of flavin- and pterin-dependent enzymes by continuous-flow mass spectrometry
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Continuous-flow mass spectrometry (CFMS) was used to monitor the products formed during the initial 0.25-20 s of the reactions catalyzed by the flavoprotein N-acetylpolyamine oxidase (PAO) and the pterin-dependent enzymes phenylalanine hydroxylase (PheH) and tyrosine hydroxylase (TyrH). N,N′-Dibenzyl-1,4-diaminobutane (DBDB) is a substrate for PAO for which amine oxidation is rate-limiting. CFMS of the reaction showed formation of an initial imine due to oxidation of an exo-carbon-nitrogen bond. Nonenzymatic hydrolysis of the imine formed benzaldehyde and N-benzyl-1,4-diaminobutane; the subsequent oxidation by PAO of the latter to an additional imine could also be followed. Measurement of the deuterium kinetic isotope effect on DBDB oxidation by CFMS yielded a value of 7.6 ± 0.3, in good agreement with a value of 6.7 ± 0.6 from steady-state kinetic analyses. In the PheH reaction, the transient formation of the 4a-hydroxypterin product was readily detected; tandem mass spectrometry confirmed attachment of the oxygen to C(4a). With wild-type TyrH, the 4a-hydroxypterin was also the product. In contrast, no product other than a dihydropterin could be detected in the reaction of the mutant protein E332A TyrH.
- Roberts, Kenneth M.,Tormos, José R.,Fitzpatrick, Paul F.
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p. 2672 - 2679
(2014/05/20)
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- Synthesis and selected properties of N-substituted pyrrolo[2,1-c]-1,3- diazacycloalkano[1,2-a]pyrazinones
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The reactions of methyl α-(2-formyl-1H-pyrrol-1-yl)carboxylates with N-substituted aliphatic 1,2-, 1,3-, and 1,4-diamines afford new pyrrole-containing heterocyclic systems: 1,2,3,10b-tetrahydroimidazo[1,2-a] pyrrolo[2,1-c]pyrazin-5(6H)-ones, 1,3,4,11b-tetrahydro-2H-pyrrolo[2′, 1′:3,4]pyrazino[1,2-a]pyrimidin-6(7H)-ones, and 1,2,3,4,5,12b-hexahydro- pyrrolo[2′,1′:3,4]pyrazino[1,2-a][1,3]diazepin-7(8H)-ones. The reduction of these compounds with different reagents was studied.
- Mokrov,Likhosherstov,Lezina,Gudasheva,Bushmarinov,Antipin, M. Yu.
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experimental part
p. 1254 - 1266
(2011/02/23)
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- Modular fluorescence sensors for saccharides
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Modular photoinduced electron transfer (PET) sensors bearing two phenylboronic acid groups, a pyrene group and alkylene linkers, from trimethylene to octamethylene, have been prepared and evaluated. The diboronic acid systems with tetramethylene 34 pentamethylene 35 and hexamethylene 36 linkers display the greatest enhancement in binding relative to monoboronic acid 4 with D-glucose. The diboronic acid system with the hexamethylene 36 linker is particularly D-glucose selective and sensitive. Whilst the diboronic acid systems with the longer heptamethylene 37 and octamethylene 38 linkers display the greatest enhancement in binding relative to monoboronic acid 4 with D-galactose. All saccharide titrations were performed in methanolic aqueous solution.
- Arimori, Susumu,Bell, Michael L.,Oh, Chan S.,Frimat, Karine A.,James, Tony D.
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p. 803 - 808
(2007/10/03)
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- CsOH-promoted chemoselective mono-N-alkylation of diamines and polyamines
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Selective N-alkylation of diamines and polyamines was carried out using cesium hydroxide, 4 ? molecular sieves, and DMF. This protocol was highly chemoselective, favoring mono-N-alkylation over overalkylations. (C) 2000 Published by Elsevier Science Ltd.
- Salvatore,Schmidt,Shin,Nagle,Worrell,Jung
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p. 9705 - 9708
(2007/10/03)
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- Solid phase organic synthesis of polyamine derivatives and initial biological evaluation of their antitumoral activity
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A series of N1-monosubstituted putrescine and spermine derivatives was synthesised using a solid phase methodology. We evaluated their cytotoxicity, calmodulin antagonism and polyamine uptake inhibition, pharmacological properties shared by som
- Tomasi, Sophie,Le Roch, Myriam,Renault, Jacques,Corbel, Jean-Charles,Uriac, Philippe,Carboni, Bertrand,Moncoq, Damien,Martin, Benedicte,Delcros, Jean-Guy
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p. 635 - 640
(2007/10/03)
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- Solid phase synthesis of polyamine conjugates for the study of trypanothione reductase
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A number of polyamine scaffolds were synthesised, enabling the facile preparation of a variety of polyamine conjugates using both Boc and Fmoc protecting group strategies. Products were released from the solid support by treatment with either triflic acid/trifluoroacetic acid or trifluoroacetic acid. The trypanosomal metabolite N1, N6-bis(glurathionyl)spermidine [trypanothione], and a range of related analogues were prepared for biological evaluation as previously communicated.
- Marsh, Ian R.,Bradley, Mark
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p. 17317 - 17334
(2007/10/03)
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- Synthesis of Amido-ureas and the Nature of Caracasanamide, the Hypotensive Principle of Verbesina caracasana
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Syntheses of the (E)-1 and (Z)-2 forms of 1-(3-methylbut-2-enyl)-3-(4-butyl)urea, proposed structures for the natural hypotensive caracasanamide, have been carried out.The compounds were found not to be identical wit
- Crombie, Leslie,Jarrett, Sandra R. M.
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p. 3179 - 3184
(2007/10/02)
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- Alkylene diamines
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A cholinesterase inhibiting agent which contains an alkylene diamine of the formula STR1 wherein R 1 and R 2 each independently is a hydrogen atom or a hydrocarbon residue which may optionally be substituted, or R 1 and R 2 combinedly form, together with the adjacent nitrogen atom, a condensed heterocyclic group, R 3 is a hydrogen atom or a hydrocarbon residue or an acyl group which may optionally be substituted and R 4 is a hydrogen atom, or R 3 and R 4 combinedly form a group of the formula STR2 or --(CH 2) m+1 -- (m being 0, 1 or 2), A is --(CH 2) l -- (l being 0, 1 or 2) or --CH CH--, X is a substituent or substituents and n is an integer of 4 to 7, or a salt thereof, which are useful as cerebral function improving agents for the prevention or treatment of senile dementia, Alzheimer''s disease, Huntington''s chorea, hyperkinesia, mania and so forth.
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- Reagents for the Stepwise Functionalization of Spermidine, Homospermidine, and Bis(3-aminopropyl)amine
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A high-yield synthesis of reagents for the selective mono-, di-, or tri-N-functionalization of the polyamines spermidine, homospermidine, and norspermidine is described.The polyamine protecting groups utilized in these reagents are each easily removable u
- Bergeron, Raymond J.,Garlich, Joseph R.,Stolowich, Neal J.
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p. 2997 - 3001
(2007/10/02)
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- CATALYTIC ALKYL GROUP EXCHANGE REACTION OF PRIMARY AND SECONDARY AMINES.
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It has been shown that primary and secondary amines undergo alkyl group exchange reactions upon treatment with palladium catalyst as depicted in an operationally simple and efficient reaction which provides a convenient method for synthesis of unsymmetrical amines. The application of the reaction for the preparation of various substituted amines and heterocyclic compounds such as hexahydropyrimidine tetrahydropyrimidine, imidazolidine, and imidazoles is described. The preparation of polyamines such as H//2N(CH//2)//mNH(CH//2)//nNH//2 (10) and H//2N(CH//2)//lNH(CH//2)//mNH(CH//2)//nNH//2 (l-n, equals 2,3; 11) is readily performed by the appadium-catalyzed reactions of azetidine (6) and aziridine (7) via azetine (9) and azirine intermediates. The mechanism the palladium-catalyzed reaction has been extensively studied on the carbonylation, racemization, and deuteurium-exchange reaction of (S)-( minus )- alpha -phenylethylamine (17).
- Murahashi,Yoshimura,Tsumiyama,Kojima
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p. 5002 - 5011
(2007/10/02)
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- Fibrin stabilizing factor inhibitors. 12. 5 dibenzylaminopentylamine and related compounds, a new type of FSF inhibitors
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A series of omega dibenzylaminoalkylamines and related compounds have been prepared and tested as inhibitors of fibrin cross linking. This structural type was chosen in an attempt to develop noncompetitive inhibitors of fibrinoligase. By the combination o
- Hoffmann,Stenberg,Ljunggren,Svensson,Nilsson
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p. 278 - 284
(2007/10/04)
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