- Autoxidation of the Indolic Neurotoxin 5,6-Dihydroxytryptamine
-
The autoxidation of the indolic neurotoxin 5,6-dihydroxytryptamine has been studied in pH 7,2 phosphate buffer.The major initial product of the autoxidation has been isolated and by using spectral methods ist structure is shown to be 2,7'-bi(5,6-dihydroxytryptamine).Liquid chromatography-mass spectrometry has been used to identify two trihydroxytryptamines and a second dimer of 5,6-DHT as minor autoxidation products.
- Singh, Satendra,Jen, Jen-Fon,Dryhurst, Glenn
-
-
Read Online
- Gc-ms studies on derivatization of creatinine and creatine by bstfa and their measurement in human urine
-
In consideration of its relatively constant urinary excretion rate, creatinine (2-amino-1methyl-5H-imidazol-4-one, MW 113.1) in urine is a useful endogenous biochemical parameter to correct the urinary excretion rate of numerous endogenous and exogenous substances. Reliable measurement of creatinine by gas chromatography (GC)-based methods requires derivatization of its amine and keto groups. Creatinine exists in equilibrium with its open form creatine (methylguanidoacetic acid, MW 131.1), which has a guanidine and a carboxylic group. Trimethylsilylation and trifluoroacetylation of creatinine and creatine are the oldest reported derivatization methods for their GC-mass spectrometry (MS) analysis in human serum using flame-or electron-ionization. We performed GC-MS studies on the derivatization of creatinine (d0-creatinine), [methylo-2H3 ]creatinine (d3 creatinine, internal standard) and creatine (d0-creatine) with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) using standard derivatization conditions (60 min, 60?C), yet in the absence of any base. Reaction products were characterized both in the negative-ion chemical ionization (NICI) and in the positive-ion chemical ionization (PICI) mode. Creatinine and creatine reacted with BSTFA to form several derivatives. Their early eluting N,N,O-tris(trimethylsilyl) derivatives (8.9 min) were found to be useful for the precise and accurate measurement of the sum of creatinine and creatine in human urine (10 μL, up to 20 mM) by selected-ion monitoring (SIM) of m/z 271 (d0-creatinine/d0-creatine) and m/z 274 (d3-creatinine) in the NICI mode. In the PICI mode, SIM of m/z 256, m/z 259, m/z 272 and m/z 275 was performed. BSTFA derivatization of d0-creatine from a freshly prepared solution in distilled water resulted in formation of two lMate-eluting derivatives (14.08 min, 14.72 min), presumably creatinyl-creatinine, with the creatininyl residue existing in its enol form (14.08 min) and keto form (14.72 min). Our results suggest that BSTFA derivatization does not allow specific analysis of creatine and creatinine by GC-MS. Preliminary analyses suggest that pentafluoropropionic anhydride (PFPA) is also not useful for the measurement of creatinine in the presence of creatine. Both BSTFA and PFPA facilitate the conversion of creatine to creatinine. Specific measurement of creatinine in urine is possible by using pentafluorobenzyl bromide in aqueous acetone.
- Beckmann, Bibiana,Begou, Olga,Tsikas, Dimitrios,Weber, Kathrin
-
-
Read Online
- A preparation method of creatinine
-
The invention belongs to the technical field of chemical synthesis, in particular relates to a preparation method of creatinine, the method to creatine as the starting material, and containing 2 - 5 carbon of the lower saturated fatty acid reaction. The method of environmental protection, without by-product to produce, almost zero-emission, without refining can be directly used for cardiac muscle protective drug creatine phosphate sodium synthetic.
- -
-
Paragraph 0014; 0028-0042; 0055; 0056
(2019/03/31)
-
- Novel prodrugs with a spontaneous cleavable guanidine moiety
-
Water-soluble prodrug strategy is a practical alternative for improving the drug bioavailability of sparingly-soluble drugs with reduced drug efficacy. Many water-soluble prodrugs of sparingly-soluble drugs, such as the phosphate ester of a drug, have been reported. Recently, we described a novel water-soluble prodrug based on O–N intramolecular acyl migration. However, these prodrug approaches require a hydroxy group in the structure of their drugs, and other prodrug approaches are often restricted by the structure of the parent drugs. To develop prodrugs with no restriction in the structure, we focused on a decomposition reaction of arginine methyl ester. This reaction proceeds at room temperature under neutral conditions, and we applied this reaction to the prodrug strategy for drugs with an amino group. We designed and synthesized novel prodrugs of representative sparingly soluble drugs phenytoin and sulfathiazole. Phenytoin and sulfathiazole were obtained as stable salt that were converted to parent drugs under physiological conditions. Phenytoin prodrug 3 showed a short half-life (t1/2) of 13?min, whereas sulfathiazole prodrug 7 had a moderate t1/2of 40?min. Prodrugs 3 and 7 appear to be suitable for use as an injectable formulation and orally administered drug, respectively.
- Hamada, Yoshio
-
supporting information
p. 1685 - 1689
(2016/07/29)
-
- METHOD FOR PREPARING CREATINE FATTY ESTERS, CREATINE FATTY ESTERS THUS PREPARED AND USES THEREOF
-
The present invention concerns a method for preparing a creatine fatty ester or derivative thereof comprising at least one step consisting in reacting a diprotected creatinine with a molecule bearing at least one alcohol functional group and of formula R'-OH in which R' represents a hydrocarbon radical containing at least 4 carbon atoms. The present invention also concerns particular creatine fatty esters or derivative thereof and medical uses thereof.
- -
-
Page/Page column 26
(2014/02/16)
-
- 2-GUANIDINO-4-OXO-IMIDAZOLINE DERIVATIVES AS ANTIMALARIAL AGENTS, SYNTHESIS AND METHODS OF USE THEREOF
-
The present invention relates to new 2-guanidino-4-oxo-imidazoline derivatives (deoxo-IZ), methods of making these compounds, compositions containing the same, and methods of using the same to prevent, treat, or inhibit malaria in a subject.
- -
-
Page/Page column 68; 74
(2012/11/13)
-
- Novel and green protocol for the synthesis of 2-iminohydantoins
-
A novel and green protocol for the synthesis of N-1 and C-5 substituted 2-iminohydantoins has been developed. Methyl N-cyano-N-alkyl/aryl-aminoacetate reacts with aqueous ammonia at room temperature in 10-30 min. The developed protocol does not require any work-up for the isolation or purification of the products; simple filtration can lead to the pure products in good to excellent yields.
- Kumar, Vinod,Rana, Hemlata,Kaushik, M. P.
-
p. 6423 - 6425,3
(2012/12/12)
-
- Synthesis and antimalarial activity of 2-guanidino-4-oxoimidazoline derivatives
-
A series of 2-guanidino-4-oxoimidazoline (deoxo-IZ) derivatives was prepared and showed potent antimalarial activities in rodent and Rhesus models. Compound 8e, the most potent analogues of this series, is the first non-8-aminoqinoline antimalarial that demonstrated radical curative activity in non-human primate by oral route and showed causal prophylactic activity comparable to that of the commonly used clinical drugs in Rhesus monkeys infected with sporozoites of Plasmodium cynomolgi. The metabolic stability and metabolites profile indicated that the new deoxo-IZ derivatives (8) may act as prodrugs of the corresponding IZ (1 and 2) derivatives.
- Liu, Xianjun,Wang, Xihong,Li, Qigui,Kozar, Michael P.,Melendez, Victor,O Neil, Michael T.,Lin, Ai J.
-
experimental part
p. 4523 - 4535
(2011/09/15)
-
- Stable aqueous compositions comprising amide-protected bioactive creatine species and uses thereof
-
The present invention provides amide-protected creatine molecules and compositions, containing one or more bioactive forms of creatine in aqueous compositions, wherein bioactive forms of creatine do not appreciably degrade into creatinine. Also provided are various beneficial effects of administering aqueous compositions having at least one amide-protected creatine molecule.
- -
-
-
- Stable Aqueous Compositions Comprising Amide-Protected Bioactive Creatine Species and Uses Thereof
-
The present invention provides amide-protected creatine molecules and compositions, containing one or more bioactive forms of creatine in aqueous compositions, wherein bioactive forms of creatine do not appreciably degrade into creatinine. Also provided are various beneficial effects of administering aqueous compositions having at least one amide-protected creatine molecule.
- -
-
-
- Syntheses and NMR Studies of Specifically Labeled Phosphocreatine, Creatinine, and Related 15N-Labeled Compounds
-
Creatine, creatinine, creatinine, phosphocreatinine, phosphocreatinine, phosphocreatine, and phosphocreatine have been synthesized. 1H and 15N NMR analyses of the labeled creatinines have established that creatinine is protonated at low pH exclusively at the unmethylated ring nitrogen (N-3) and indicate that in the predominant resonance from at low pH, conjugation to the carbonyl is present. 31P and 15N NMR analyses of the labeled phosphocreatinines establish that the site of phosphorylation of phosphocreatinine is on the exocyclic nitrogen.The 31P-15N one-bond coupling constant in phosphocreatine is 18 Hz, not 3 Hz as reported for doubly 15N-labeled phosphocreatine by Brindle et al..Finally, 31P and 15N NMR analyses indicated that no spontaneous 15N/14N-positional isotope exchange occurs in specifically labeled phosphocreatine.The relatively large J31p-15N value and the lack of chemical scrambling are prerequisites for the use of phosphocreatine in positional isotope exchange studies in enzymatic reactions.
- Reddick, Rebeca E.,Kenyon, George L.
-
p. 4380 - 4387
(2007/10/02)
-
- THE MECHANISM OF HYDROLYSIS OF PHOSPHOROCREATINE TO CREATININE
-
The mechanism of hydrolysis of phosphorocreatine in acidic medium, leading to creatinine and inorganic phosphate, has been investigated.Rate coefficients have been measured in 2 N HCl at 30 deg C for the following processes: (i) hydrolysis of phosphorocreatine; (ii) hydrolysis of phosphorocreatinine; (iii) conversion of creatine to creatinine.The results obtained make a concerted mechanism, in which the breaking of the P-N bond and the ring closure occur in the same step, highly probable.Determination of the 18O-content in the inorganic phosphate released during the process when the reaction is carried out in 18O-enriched water showed that a molecule of solvent is involved in the cyclisation step.
- Lillocci, Claudio,Vernon, Charles A.
-
-
