486-56-6Relevant articles and documents
Synthesis and preliminary binding studies of 4,4-ditritio(-)nicotine of high specific activity
Vincek,Martin,Aceto,Bowman
, p. 960 - 962 (1980)
4,4-Ditritio-(-)nicotine (5) of high specific activity (4.7 Ci/mmol) has been synthesized from (-) nicotine via the readily prepared 4,4-dibromocotinine. Scatchard analysis of the binding of 5 to the crude mitochondrial fraction of whole rat brain revealed a K(a) of 4.7 x 106 M-1 and 13 fmol of binding sites/mg of protein.
Nicotine metabolism and urinary elimination in mouse: In vitro and in vivo
Raunio,Pokela,Puhakainen,Rahnasto,Mauriala,Auriola,Juvonen
, p. 34 - 47 (2008)
This study aimed at elucidating the in vivo metabolism of nicotine both with and without inhibitors of nicotine metabolism. Second, the role of mouse CYP2A5 in nicotine oxidation in vitro was studied as such information is needed to assess whether the mouse is a suitable model for studying chemical inhibitors of the human CYP2A6. The oxidation of nicotine to cotinine was measured and the ability of various inhibitors to modify this reaction was determined. Nicotine and various inhibitors were co-administered to CD2F1 mice, and nicotine and urinary levels of nicotine and four metabolites were determined. In mouse liver microsomes anti-CYP2A5 antibody and known chemical inhibitors of the CYP2A5 enzyme blocked cotinine formation by 85-100%, depending on the pre-treatment of the mice. The amount of trans-3-hydroxycotine was five times higher than cotinine N-oxide, and ten times higher than nicotine N-1-oxide and cotinine. Methoxsalen, an irreversible inhibitor of CYP2A5, significantly reduced the metabolic elimination of nicotine in vivo, but the reversible inhibitors had no effect. It is concluded that the metabolism of nicotine in mouse is very similar to that in man and, therefore, that the mouse is a suitable model for testing novel chemical inhibitors of human CYP2A6.
Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes
Yamazaki, Hiroshi,Inoue, Kiyoshi,Hashimoto, Masafumi,Shimada, Tsutomu
, p. 65 - 70 (1999)
Nicotine C-oxidation by recombinant human cytochrome P450 (P450 or CYP) enzymes and by human liver microsomes was investigated using a convenient high-performance liquid chromatographic method. Experiments with recombinant human P450 enzymes in baculovirus systems, which co-express human nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH)-P450 reductase, revealed that CYP2A6 had the highest nicotine C-oxidation activities followed by CYP2B6 and CYP2D6; the K(m) values by these three P450 enzymes were determined to be 11.0, 105, and 132 μM, respectively, and the V(max) values to be 11.0, 8.2, and 8.6 nmol/min per nmol P450, respectively. CYP2E1, 2C19, 1A2, 2C8, 3A4, 2C9, and 1A1 catalysed nicotine C-oxidation only at high (500 μM) substrate concentration. CyP1B1, 2C18, 3A5, and 4A11 had no measurable activities even at 500 μM nicotine. In liver microsomes of 16 human samples, nicotine C-oxidation activities were correlated with CYP2A6 contents at 10 μM substrate concentration, whereas such correlation coefficients were decreased when the substrate concentration was increased to 500 μM. Contribution of CYP2B6 (as well as CYP2A6) was demonstrated by experiments with the effects of orphenadrine (and also coumarin and anti- CYP2A6) on the nicotine C-oxidation activities by human liver microsomes at 500 μM nicotine. CYP2D6 was found to have minor roles since quinidine did not inhibit microsomal nicotine C-oxidation at both 10 and 500 μM substrate concentrations. These results support the view that CYP2A6 has major roles for nicotine C-oxidation at lower substrate concentration and both CYP2A6 and 2B6 play roles at higher substrate concentrations in human liver microsomes.
Method for preparing bioactive (S)-(-)-nicotine
-
, (2021/07/17)
The invention relates to the field of organic synthesis, and discloses a method for preparing bioactive (S)-(-)-nicotine. The method comprises the steps of carrying out first reaction on methyl nicotinate and tert-butyl succinic acid diester, and then carrying out second reaction; and carrying out contact reaction on the system after the second reaction and an acidic material to obtain 4-oxo-4-(3-pyridyl) butyric acid; carrying out asymmetric reduction reaction on 4-oxo-4-(3-pyridyl) butyric acid and (R)-(+)-2-methyl-CBS-oxazoborane to obtain 5-(3-pyridyl) dihydrofuran-2 (3H)-ketone; carrying out third reaction on the 5-(3-pyridyl) dihydrofuran-2 (3H)-ketone and methylamine hydrobromide to obtain 1-methyl-5-(3-pyridyl)-2-pyrrolidone; and carrying out fourth reaction on the 1-methyl-5-(3-pyridyl)-2-pyrrolidone and a reducing agent to obtain the bioactive (S)-(-)-nicotine. According to the method, the bioactive body (S)-(-)-nicotine can be obtained with high yield and high purity.
Evaluation of the Edman degradation product of vancomycin bonded to core-shell particles as a new HPLC chiral stationary phase
Hellinghausen, Garrett,Lopez, Diego A.,Lee, Jauh T.,Wang, Yadi,Weatherly, Choyce A.,Portillo, Abiud E.,Berthod, Alain,Armstrong, Daniel W.
, p. 1067 - 1078 (2018/08/01)
A modified macrocyclic glycopeptide-based chiral stationary phase (CSP), prepared via Edman degradation of vancomycin, was evaluated as a chiral selector for the first time. Its applicability was compared with other macrocyclic glycopeptide-based CSPs: TeicoShell and VancoShell. In addition, another modified macrocyclic glycopeptide-based CSP, NicoShell, was further examined. Initial evaluation was focused on the complementary behavior with these glycopeptides. A screening procedure was used based on previous work for the enantiomeric separation of 50 chiral compounds including amino acids, pesticides, stimulants, and a variety of pharmaceuticals. Fast and efficient chiral separations resulted by using superficially porous (core-shell) particle supports. Overall, the vancomycin Edman degradation product (EDP) resembled TeicoShell with high enantioselectivity for acidic compounds in the polar ionic mode. The simultaneous enantiomeric separation of 5 racemic profens using liquid chromatography-mass spectrometry with EDP was performed in approximately 3?minutes. Other highlights include simultaneous liquid chromatography separations of rac-amphetamine and rac-methamphetamine with VancoShell, rac-pseudoephedrine and rac-ephedrine with NicoShell, and rac-dichlorprop and rac-haloxyfop with TeicoShell.