- Leonurine derivative and application thereof in preparing medicine for preventing or treating ischemic cerebrovascular diseases
-
The invention provides a leonurine derivative and application of the leonurine derivative in preparation of a medicine for preventing or treating ischemic cerebrovascular diseases. The leonurine derivative has a structure as shown in a general formula (I), wherein X is selected from O or NH; Y is selected from any one of natural amino acid, substituted amino acid or amino alcohol; Z is selected from H, proline and any substituted proline. Pharmacological experiments prove that the leonurine derivative provided by the invention has the effects of neuroprotection, cerebral infarction area reduction and animal neurobehavioral scoring, and is good in safety, so that the leonurine derivative has important significance for developing novel medicines for preventing or treating ischemic cerebrovascular diseases.
- -
-
Paragraph 0050-0052
(2021/03/30)
-
- Design, synthesis, and biological evaluation of novel stachydrine derivatives as potent neuroprotective agents for cerebral ischemic stroke
-
Stachydrine is a natural product with multiple protective biological activities, including those involved in preventing cancer, ischemia, and cardiovascular disease. However, its use has been limited by low bioavailability and unsatisfactory efficacy. To address this problem, a series of stachydrine derivatives (A1/A2/A3/A4/B1/B2/B3/B4) were designed and synthesized, and biological studies were carried out in vitro and in vivo. When compared with stachydrine, Compound B1 exhibited better neuroprotective effects in vitro, and significantly reduced infarction size in the model of the middle cerebral artery occlusion rat model. Therefore, Compound B1 was selected for further research on ischemic stroke. [Figure not available: see fulltext.].
- Zhang, Liang,Li, Feng,Hou, Chenhui,Zhu, Sifeng,Zhong, Lili,Zhao, Jianchun,Song, Cai,Li, Wenbao
-
p. 2529 - 2542
(2020/05/25)
-
- A Copper-Catalyzed Sonogashira Coupling Reaction of Diverse Activated Alkyl Halides with Terminal Alkynes Under Ambient Conditions
-
We describe a copper-catalyzed Sonogashira coupling reaction of alkyl halides with terminal alkynes under ambient conditions, efficiently providing a versatile tool for the construction of substituted alkynes. A new proline-based N,N,P-ligand is utilized to promote the transformation under a mild reaction condition. Diverse alkyl halides, such as primary and secondary (hetero)benzyl chlorides and bromides, secondary and tertiary α-bromo amides and propargylic bromide, are applicable to provide a wide array of alkynes. (Figure presented.).
- Cao, Yu-Xi,Dong, Xiao-Yang,Yang, Jun,Jiang, Sheng-Peng,Zhou, Shuangliu,Li, Zhong-Liang,Chen, Guo-Qiang,Liu, Xin-Yuan
-
supporting information
p. 2280 - 2284
(2020/05/08)
-
- MORPHINAN DERIVATIVE
-
A compound represented by the following general formula (I), wherein R1 represents hydrogen, C1-10 alkyl, cycloalkylalkyl where the cycloalkyl moiety has 3 to 6 carbon atoms and the alkylene moiety has 1 to 5 carbon atoms, or the like, R2 represents a 4- to 7-membered saturated heterocycle containing one or two heteroatoms which may be the same or different and are selected from N, O, and S, and two or more carbon atoms as ring-constituting atoms, the heterocycle may be substituted with a substituent such as an oxo group, R2 binds to Y via a carbon atom as a ring-constituting atom of R2, R3, R4, and R5, which are the same or different, represent hydrogen; hydroxy; or the like, R6a and R6b, which are the same or different, represent hydrogen or the like, R7 and R8, which are the same or different, represent hydrogen or the like, R9 and R10, which are the same or different, represent hydrogen or the like, X represents O or CH2, and Y represents C(= O) or the like), a tautomer of the compound, a stereoisomer of the compound, a pharmaceutically acceptable salt thereof, or a solvate thereof is used as an anxiolytic, an antidepressant, or the like.
- -
-
Paragraph 0127-0128
(2019/06/27)
-
- A CONJUGATE OF A TUBULYSIN ANALOG WITH BRANCHED LINKERS
-
The present invention relates to the conjugation of a tubulysin analog compound to a cell-binding molecule with branched/side-chain linkers for having better delivery of the conjugate compound and targeted treatment of abnormal cells. It also relates to a branched-linkage method of conjugation of a tubulysin analog molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and autoimmune disease.
- -
-
Page/Page column 10
(2019/07/17)
-
- Stachydrine derivative, preparation method thereof, and application thereof in preparation of cardiovascular and cerebrovascular disease treatment medicines
-
The invention provides a stachydrine derivative, a preparation method thereof, and an application thereof in the preparation of cardiovascular and cerebrovascular disease treatment medicines. The stachydrine derivative has a structure represented by general formula (I). The synthesis method comprises the following steps: carrying out a hydrogenation reaction on L-proline a and formaldehyde under the catalysis of a catalyst to prepare N-methyl-L-proline b; and carrying out a condensation reaction on the N-methyl-L-proline b and anthranilic acid, gamma-aminobutyramide, glutamine or glycine underthe action of dicyclohexylcarbodiimide (DCC) to prepare the stachydrine derivative B-1, B-2, B-3 or B-4. Pharmacologic experiments prove that the stachydrine derivative has a nerve protection effectand a cardiovascular and cerebrovascular disease treatment effect. The invention also provides the application of the stachydrine derivative in the preparation of the cardiovascular and cerebrovascular disease treatment medicines.
- -
-
Paragraph 0046-0048
(2018/05/07)
-
- Photolysis of Tertiary Amines in the Presence of CO2: The Paths to Formic Acid, α-Amino Acids, and 1,2-Diamines
-
The photolysis of triethylamine (1a) in the presence of carbon dioxide leads to the hydrogenation of CO2, the α-C-C coupling of 1a, and the CO2 insertion into the α-C-H σ-bond of amine 1a. This reaction is proposed to proceed through the radical ion pair [R3N?+·CO2?-] generated by the photoionization of amine 1a and the electron capture by CO2. The presence of lithium tetrafluoroborate in the reaction medium promotes the efficient and stereoselective α-C-C coupling of 1a by enhancing the production of α-dialkylamino radicals and the isomerization of N,N,N′,N′-tetraethylbutane-2,3-diamine (4a).
- Berton, Mateo,Mello, Rossella,Acerete, Rafael,González Núnez, María Elena
-
-
- HEPATITIS C VIRUS INHIBITORS
-
The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
- -
-
Paragraph 0356-0357
(2017/07/05)
-
- Synthesis of a series of amino acid derived ionic liquids and tertiary amines: Green chemistry metrics including microbial toxicity and preliminary biodegradation data analysis
-
A series of l-phenylalanine ionic liquids (ILs), l-tyrosine ILs, tertiary amino analogues and proposed transformation products (PTPs) have been synthesised. Antimicrobial toxicity data, as part of the green chemistry metrics evaluation and to supplement preliminary biodegradation studies, was determined for ILs, tertiary amino analogues and PTPs. Good to very good overall yields (76 to 87%) for the synthesis of 6 ILs from l-phenylalanine were achieved. A C2-symmetric IL was prepared from TMS-imidazole in a one-pot two-step method in excellent yield (91%). Synthesis of the l-tyrosine IL derivatives utilised a simple protection group strategy by using an extra equivalent of the bromoacetyl bromide reagent. Improvements in the synthesis of the α-bromoamide alkylating reagent from l-phenylalanine were achieved, directed by green chemistry metric analysis. A solvent switch from dichloromethane to THF is described, however the yield was 15% lower. Antimicrobial activity testing of l-phenylalanine ILs, l-tyrosine ILs, tertiary amino analogues and PTPs, against 8 bacteria and 12 fungi strains, showed that no compound had a high antimicrobial activity, apart from an l-proline analogue. In this exceptional case, the highest toxicity (IC95 = 125 and 250 μM) was observed towards the two Gram positive strains Staphylococcus aureus and Staphylococcus epidermidis respectively. High antimicrobial activity was not found for the other bacteria or fungi strains screened. The limitations of the antimicrobial activity study is discussed in relation to SAR studies. Preliminary analysis of biodegradation data (Closed Bottle Test, OECD 301D) is presented. The pyridinium IL derivative is the preferred green IL of the series based on synthesis, toxicity and biodegradation considerations. This work is a joint study with Kümmerer and co-workers and the PTPs were selected as target compounds based on concurrent biodegradation studies by the Kümmerer group. For the comprehensive biodegradation and transformation product analysis see the accompanying paper.
- Jordan, Andrew,Hai?, Annette,Spulak, Marcel,Karpichev, Yevgen,Kümmerer, Klaus,Gathergood, Nicholas
-
supporting information
p. 4374 - 4392
(2016/08/19)
-
- Design, synthesis, and in vitro antiplasmodial activity of 4-aminoquinolines containing modified amino acid conjugates
-
Abstract: A new series of side chain-modified 4-aminoquinolines were synthesized and screened for in vitro antiplasmodial activity against both chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum. Among the series, compounds 30 and 31 showed significant inhibition of parasite growth against K1 strain of P. falciparum with IC50 values 0.28 and 0.31?μM, respectively, whereas compounds 34, 35, and 38 exhibited superior activity against K1 strain with IC50 values 0.18, 0.22, and 0.17?μM, respectively, as compared to 0.255?μM for chloroquine (CQ). All the compounds displayed good resistance factor between 1.54 and >34.48 as against 51.0 for CQ. All these analogues were found to form strong complex with hematin and inhibited the β-hematin formation in vitro, suggesting that this class of compounds act on a heme polymerization target. Overall results suggest that present series of compounds appear to be promising for further lead optimization to obtain compounds active against drug-resistant parasites. Graphical Abstract: [Figure not available: see fulltext.]
- Srinivasarao, Kondaparla,Agarwal, Pooja,Srivastava, Kumkum,Haq,Puri, Sunil K.,Katti
-
p. 1148 - 1162
(2016/07/06)
-
- N-Methylation of Amines with Methanol at Room Temperature
-
N-Methylation of amines with methanol proceeds at room temperature in the presence of a silver-loaded titanium dioxide (Ag/TiO2) photocatalyst under UV-vis light irradiation. This method allows facile synthesis/isolation of N-methylamines bearing various functional groups including N-benzyl, N-allyl, N-Boc, hydroxyl, ether, acetal, carboxamide, formamide, and olefin groups. (Chemical Presented)
- Tsarev, Vasily N.,Morioka, Yuna,Caner, Joaquim,Wang, Qing,Ushimaru, Richiro,Kudo, Akihiko,Naka, Hiroshi,Saito, Susumu
-
supporting information
p. 2530 - 2533
(2015/05/27)
-
- Catalytic conversion of glycerol to allyl alcohol; Effect of a sacrificial reductant on the product yield
-
A continuous process for the conversion of glycerol to allyl alcohol, where ammonia or organic acids are added to the feed as sacrificial reductants, was investigated. Significant enhancement on the rate of formation and yield of the allyl alcohol is observed with some of the reducing agents examined over an alumina-supported iron catalyst. Optimising the molar ratio of the reductant relative to feed glycerol results in an increase in the yield of allyl alcohol from 9% (in the absence of additives) to 11.3% with ammonia, 15.1% with ammonium hydroxide, 17.8% with oxalic acid and 19.5% with formic acid. Moreover, the addition of other organic acids, which are produced in a typical glycerol conversion experiment, was studied. However, acetic and propanoic acids had little effect on the rate of formation of allyl alcohol. Analysis of the product distribution in the liquid and gas phases when oxalic and formic acids were added suggests a two-step process for the formation of allyl alcohol under the operating conditions of the reaction; the initial step involves the dehydration of glycerol while the second comprises the reduction of the species produced in step one. the Partner Organisations 2014.
- Sanchez, Gizelle,Friggieri, Jarrod,Adesina, Adesoji A.,Dlugogorski, Bogdan Z.,Kennedy, Eric M.,Stockenhuber, Michael
-
p. 3090 - 3098
(2014/08/18)
-
- Synthesis of chiral triazine coupling reagents based on esters of n-alkylproline and their application in the enantioselective incorporation of d or l amino acid residue directly from racemic substrate
-
Esters of N-methylproline and N-allylproline were prepared and used as component for synthesis of chiral triazine based coupling reagents. N-Triazinylammonium tetrafluoroborate obtained from methylester of L-N-methylproline, 2-chloro-4,6-dimethozxy-1,3,5-
- Kasperowicz-Frankowska, Katarzyna,Gzik, Anna,Dziemidkiewicz, Michal,Kolesi-Ska, Beata,Kamiski, Zbigniew J.
-
p. 994 - 1003
(2015/02/02)
-
- Zinc catalyzed and mediated asymmetric propargylation of trifluoromethyl ketones with a propargyl boronate
-
The development of zinc-mediated and -catalyzed asymmetric propargylations of trifluoromethyl ketones with a propargyl borolane and the N-isopropyl-l-proline ligand is presented. The methodology provided moderate to high stereoselectivity and was successfully applied on a multikilogram scale for the synthesis of the Glucocorticoid agonist BI 653048. A mechanism for the boron-zinc exchange with a propargyl borolane is proposed and supported by modeling at the density functional level of theory. A water acceleration effect on the zinc-catalyzed propargylation was discovered, which enabled a catalytic process to be achieved. Reaction progress analysis supports a predominately rate limiting exchange for the zinc-catalyzed propargylation. A catalytic amount of water is proposed to generate an intermediate that catalyzes the exchange, thereby facilitating the reaction with trifluoromethyl ketones.
- Fandrick, Daniel R.,Reeves, Jonathan T.,Bakonyi, Johanna M.,Nyalapatla, Prasanth R.,Tan, Zhulin,Niemeier, Oliver,Akalay, Deniz,Fandrick, Keith R.,Wohlleben, Wolfgang,Ollenberger, Swetlana,Song, Jinhua J.,Sun, Xiufeng,Qu, Bo,Haddad, Nizar,Sanyal, Sanjit,Shen, Sherry,Ma, Shengli,Byrne, Denis,Chitroda, Ashish,Fuchs, Victor,Narayanan, Bikshandarkoil A.,Grinberg, Nelu,Lee, Heewon,Yee, Nathan,Brenner, Michael,Senanayake, Chris H.
-
p. 3592 - 3615
(2013/05/23)
-
- Quaternary ammonium oxidative demethylation: X-ray crystallographic, resonance raman, and uv-visible spectroscopic analysis of a Rieske-type demethylase
-
Herein, the structure resulting from in situ turnover in a chemically challenging quaternary ammonium oxidative demethylation reaction was captured via crystallographic analysis and analyzed via single-crystal spectroscopy. Crystal structures were determined for the Rieske-type monooxygenase, stachydrine demethylase, in the unliganded state (at 1.6 A resolution) and in the product complex (at 2.2 A resolution). The ligand complex was obtained from enzyme aerobically cocrystallized with the substrate stachydrine (N,N-dimethylproline). The ligand electron density in the complex was interpreted as proline, generated within the active site at 100 K by the absorption of X-ray photon energy and two consecutive demethylation cycles. The oxidation state of the Rieske iron-sulfur cluster was characterized by UV-visible spectroscopy throughout X-ray data collection in conjunction with resonance Raman spectra collected before and after diffraction data. Shifts in the absorption band wavelength and intensity as a function of absorbed X-ray dose demonstrated that the Rieske center was reduced by solvated electrons generated by X-ray photons; the kinetics of the reduction process differed dramatically for the liganded complex compared to unliganded demethylase, which may correspond to the observed turnover in the crystal.
- Daughtry, Kelly D.,Xiao, Youli,Stoner-Ma, Deborah,Cho, Eunsun,Orville, Allen M.,Liu, Pinghua,Allen, Karen N.
-
supporting information; experimental part
p. 2823 - 2834
(2012/03/22)
-
- HEPATITIS C VIRUS INHIBITORS
-
The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
- -
-
Page/Page column 42
(2012/02/15)
-
- 7-(Piperazine-1-Ymethyl)-1H-Indole-2-Carboxylic Acid (Phenyl)-Amide Derivatives and Allied Compounds as P38 Map Kinase Inhibitors for the Treatment of Respiratory Diseases
-
The present invention provides compounds according to general formula (I) which are proposed for the treatment of respiratory complaints, particularly asthma and COPD.
- -
-
Page/Page column 44
(2011/11/12)
-
- Catalyst-free one-pot reductive alkylation of primary and secondary amines and N,N-dimethylation of amino acids using sodium borohydride in 2,2,2-trifluoroethanol
-
A simple and convenient procedure for the reductive alkylation of primary and secondary amines and N,N-dimethylation of amino acids is described using sodium borohydride as a reducing agent in 2,2,2- trifluoroethanol without use of a catalyst or any other additive. The solvent can be readily recovered from reaction products in excellent purity for direct reuse. Georg Thieme Verlag Stuttgart - New York.
- Tajbakhsh, Mahmood,Hosseinzadeh, Rahman,Alinezhad, Heshmatollah,Ghahari, Somayeh,Heydari, Akbar,Khaksar, Samad
-
experimental part
p. 490 - 496
(2011/03/20)
-
- AZAINDOLE DERIVATIVES
-
The present invention provides compounds of formula (I): compositions comprising such compounds; the use of such compounds in therapy (such as asthma or COPD); and methods of treating patients with such compounds; wherein R1 to R20 and A1 are as defined herein.
- -
-
Page/Page column 67
(2011/05/11)
-
- AMINOTHIAZOLE DERIVATIVES USEFUL AS KLK1 INHIBITORS
-
The present invention provides compounds of formula (I): compositions comprising such compounds; the use of such compounds in therapy (such as asthma or COPD); and methods of treating patients which such compounds; wherein R1 to R17 and A1 are as defined herein.
- -
-
Page/Page column 66
(2011/05/11)
-
- HEPATITIS C VIRUS INHIBITORS
-
This disclosure concerns novel compounds of Formula (I) or as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds.
- -
-
Page/Page column 129-130
(2011/06/16)
-
- HEPATITIS C VIRUS INHIBITORS
-
The present disclosure relates to methods for making compounds useful in the treatment of Hepatitis C virus (HCV) infection.
- -
-
Page/Page column 44
(2011/06/16)
-
- HEPATITIS C VIRUS INHIBITORS
-
The present disclosure relates to compounds, compositions and methods for the treatment of Hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
- -
-
Page/Page column 39-40
(2011/07/07)
-
- BI-1H-BENZIMIDAZOLES AS HEPATITIS C VIRUS INHIBITORS
-
The present disclosure relates to compounds, compositions and methods for the treatment of Hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
- -
-
Page/Page column 193
(2010/04/03)
-
- HEPATITIS C VIRUS INHIBITORS
-
This disclosure concerns novel compounds of Formula (I) or Formula (II) as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds.
- -
-
Page/Page column 91; 92
(2010/11/04)
-
- HEPATITIS C VIRUS INHIBITORS
-
This disclosure concerns novel compounds of Formula (I) as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds.
- -
-
Page/Page column 85
(2010/12/26)
-
- HEPATITIS C VIRUS INHIBITORS
-
The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
- -
-
Page/Page column 44
(2010/12/26)
-
- Hepatitis C Virus Inhibitors
-
This disclosure concerns novel compounds of Formula (I) as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds.
- -
-
Page/Page column 30
(2010/10/19)
-
- HEPATITIS C VIRUS INHIBITORS
-
This disclosure concerns novel compounds of Formula (I) as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds.
- -
-
Page/Page column 163
(2010/11/03)
-
- Asymmetric addition of terminal alkynes to n-(Diphenylphosphinoyl)imines promoted by stoichiometric amounts of a proline-derlved ss-amino alcohol
-
A new synthetic methodology for the preparation of optically active propargylamines is described. The alkynylation of aromatic, heteroaromatic, aliphatic and α,β-unsaturated N-(di-phenylphosphinoyl)imines was investigated by using dieth-ylzinc and a proline-derived β-amino alcohol, N-(Diphenylphosphinoyl)-protected propargylic amines can be synthesized in high yields and with good to excellent: enantio-selectivities.
- Yan, Wenjin,Mao, Bin,Zhn, Shaoqun,Jiang, Xianxing,Liu, Zhongli,Wang, Rui
-
supporting information; experimental part
p. 3790 - 3794
(2009/12/07)
-
- AMINOPYRIDINE DERIVATIVES
-
The present invention provides compounds of formula (I): compositions comprising such compounds; the use of such compounds in therapy (such as asthma or COPD); and methods of treating patients with such compounds; wherein R1 - R11 ar
- -
-
Page/Page column 82
(2009/12/05)
-
- Hepatitis C Virus Inhibitors
-
The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
- -
-
Page/Page column 22
(2009/09/28)
-
- HEPATITIS C VIRUS INHIBITORS
-
The present disclosure relates to (4-4' -diimidazolyl) biphenyls compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
- -
-
Page/Page column 49
(2009/10/09)
-
- Hepatitis C Virus Inhibitors
-
The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
- -
-
Page/Page column 36
(2008/06/13)
-
- Hepatitis C Virus Inhibitors
-
The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
- -
-
Page/Page column 37
(2008/06/13)
-
- HEPATITIS C VIRUS INHIBITORS
-
The present disclosure relates to compounds of the following formula (I) or a pharmaceutically acceptable salt thereof, wherein A and B are each phenyl; D and E are each five-membered aromatic rings containing one, two, or three i hcteroatoms independently selected from nitrogen, oxygen, and sulfur; provided that ', at least one of D and E is other than imidazole; compositions and methods for the treatment of Hepatitis C virus (HCV) inf ection. Also disclosed are pharmaceutical compositions containing such compounds and methods f or using these compounds in the treatment of HCV inf ection.
- -
-
Page/Page column 53-54
(2009/01/20)
-
- Reductive methylation of primary and secondary amines and amino acids by aqueous formaldehyde and zinc
-
Amines can be methylated when treated with formaldehyde and zinc in aqueous medium. Selective mono- or dimethylation can be achieved by proper choice of pH, stoichiometry and reaction time. This method can also be applied for amino acids.
- da Silva, Renato A.,Estevam, Idália H.S.,Bieber, Lothar W.
-
p. 7680 - 7682
(2008/03/30)
-
- Stable-isotope dimethylation labeling combined with LC-ESI MS for quantification of amine-containing metabolites in biological samples
-
One of the challenges associated with metabolome profiling in complex biological samples is to generate quantitative information on the metabolites of interest. In this work, a targeted metabolome analysis strategy is presented for the quantification of amine-containing metabolites. A dimethylation reaction is used to introduce a stable isotopic tag onto amine-containing metabolites followed by LC-ESI MS analysis. This labeling reaction employs a common reagent, formaldehyde, to label globally the amine groups through reductive animation. The performance of this strategy was investigated in the analysis of 20 amino acids and 15 amines by LC-ESI MS. It is shown that the labeling chemistry is simple, fast (13C-dimethylation does not show any isotope effect on either RPLC or HILIC LC, indicating that 13C-labeling is a preferred approach for relative quantification of amine-containing metabolites in different samples. The isotopically labeled 35 amine-containing analogues were found to be stable and proved to be effective in overcoming matrix effects in both relative and absolute quantification of these analytes present in a complicated sample, human urine. Finally, the characteristic mass difference provides additional structural information that reveals the existence of primary or secondary amine functional groups in amine-containing metabolites. As an example, for a human urine sample, a total of 438 pairs of different amine-containing metabolites were detected, at signal-to-noise ratios of greater than 10, by using the labeling strategy in conjunction with RP LC-ESI Fourier-transform ion cyclotron resonance MS.
- Guo, Kevin,Ji, Chengjie,Li, Liang
-
p. 8631 - 8638
(2008/03/15)
-
- Simple derivatives of natural amino acids as chiral ligands in the catalytic asymmetric addition of phenylacetylene to aldehydes
-
Optically active propargylic alcohols are important chiral building blocks in asymmetric synthesis, and asymmetric addition of terminal alkynes to aldehydes is one of the most important and interesting procedures by which to prepare these chiral building
- Han, Zhi-Jian,Wang, Rui,Zhou, Yi-Feng,Liu, Lei
-
p. 934 - 938
(2007/10/03)
-
- N-METHYL AMINO ACIDS
-
The present invention relates to a compound of formula (I) or (II), processes for preparing them, peptides including them and kits involving them.
- -
-
-
- An efficient synthesis of N-methyl amino acids by way of intermediate 5-oxazolidinones
-
N-Methyl amino acids occur in many natural products. Experimental strategies are presented for a unified approach to the synthesis of N-methyl derivatives through 5-oxazolidinones of the 20 common L-amino acids. The amino acids with reactive side chains that required protecting groups or devoted syntheses for side chain construction for N-methylation to proceed included serine, threonine, tyrosine, cysteine, methionine, tryptophan, asparagine, histidine, and arginine. The studies have provided improved methods for the preparation of N-methyl serine, threonine, and tyrosine. All 20 of the common L-amino acids are now available in suitable forms for solid or solution-phase peptide synthesis.
- Aurelio, Luigi,Box, John S.,Brownlee, Robert T. C.,Hughes, Andrew B.,Sleebs, Marianne M.
-
p. 2652 - 2667
(2007/10/03)
-
- Amino acid derivatives with anticonvulsant activity
-
A series of benzylamides of N-alkylated, N-acylated or free nine cyclic and one linear amino acids as potential anticonvulsants have been synthesized. The structures of the obtained compounds were designed on the basis of the previously determined structure and physicochemical properties/anticvonvulsant activity relationship of the formerly synthesized compounds of this type. The obtained compounds were evaluated in mice after intraperitoneal (ip) administration, by maximal electroshock seizure test (MES test), subcutaneous (sc) pentylenetetrazol test (sc PTZ test) and by the rotarod neurotoxicity test (Tox test). The results were the basis for their classification into one of three classes of the Anticonvulsant Screening Project (ASP) of the Antiepileptic Drug Development Program (ADDP) of the NIH. Three selected compounds were tested quantitatively in rats after oral administration. The MES ED50, sc PTZ ED50, Tox TD50 were determined and their protective index (PI) values were calculated. Anticonvulsant activity of the most promising compound (15) was examined in different seizure models. The respective ED50 and PI values of this compound were as follows: against bicuculline, 73 and 1.4; against PTZ, 47 and 2.2; against strychnine, 73 and 1.4; against pilocarpine 156, and 0.7; against kainic acid (2-carboxy-4-isopropenyl-3-pyrrolidineacetic acid), 39 and 2.6; against AMPA (α-amino-3-hydroxy-5methyl-4-isoxazolepropionic acid), 10 and 10.3 and against NMDA (N-methyl-D-Aspartic acid), 114 and 0.9.
- Paruszewski,Strupinska,Stables,Swiader,Czuczwar,Kleinrok,Turski
-
p. 629 - 631
(2007/10/03)
-
- Intermediates for the preparation of enantiomerically-pure-3-methyl-5-(1-C1-C3-alkyl)-2-pyrrolidinyl)isoxazole
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Novel compounds useful in the preparation of enantiomerically-pure 3-methyl-5-(1-(C1 -C3 -alkyl)-2-pyrrolidinyl)isoxazole in high yield, namely 5(S)-(3-methyl-5-isoxazolyl)-2-pyrrolidinone, 3-methyl-5-(1-methyl-2-pyrrolidinyl)-5-hydroxy-4,5-dihydro-isoxazole, and 1-(1-methyl-2(S)-pyrrolidinyl)-1,3-butanedione-3-oxime.
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- Method of preparing enantiomerically-pure 3-methyl-5-(1-alkyl-2(s)-pyrrolidinyl)isoxazoles
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A novel process for preparing enantiomerically-pure 3-methyl-5-(1-(C1 -C3 -alkyl)-2-pyrrolidinyl)isoxazole in high yield, wherein a protected 2-oxo-pyrrolidine starting material is reacted with a suitable organic anion and a resulting beta-keto oxime intermediate is cyclized and dehydrated.
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- Synthese optisch aktiver neungliedriger Lactame durch zwitterionische Aza-Claisen-Reaktion
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Stichworte: Aza-Claisen-Reaktion * Azoninone * Chiralitaetstransfer * Lactame
- Diederich, Michel,Nubbemeyer, Udo
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p. 1095 - 1098
(2007/10/02)
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- Method of preparing enantiomerically-pure 3-methyl-5-(1-alkyl-2(S)-pyrrolidinyl) isoxazoles
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A novel process for preparing enantiomerically-pure 3-methyl-5-(1-(C1 -C3 -alkyl)-2-pyrrolidinyl)isoxazole in high yield, wherein a protected pyrrolidine or 2-oxo-pyrrolidine starting material is reacted with a suitable organic anion and a resulting beta-keto oxime intermediate is cyclized and dehydrated, as well as intermediates useful in the preparation thereof.
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- Search for Configurationally Stable, Aracemic α-Amino Organolithiums
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The search for configurationally stable α-amino carbanions has led to an interesting observation of differing reactivity of diastereomeric organolithiums and to the characterization of aracemic 2-lithio-N-methylpiperidine and 2-lithio-N-methylpyrrolidine as configurationally stable α-aminoorganolithiums.Details for the preparation of these and related α-lithioheterocycles, evaluation of their and configurational stability, and a preliminary evaluation of the stereoselevtivity of their reactions with electrophiles is presented. - Keywords: α-Amino organolithiums; α-amino carbaions; 2-lithiopiperidine; 2-lithiopyrrrolidine; configurationally stable carbanions.
- Gawley, Robert E.,Zhang, Qianhui
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p. 6077 - 6088
(2007/10/02)
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- (Amidomethyl)nitrogen heterocyclic analgesics
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This invention relates to (amidomethyl)nitrogen heterocyclic and pyrrolidine compounds, pharmaceutical compositions containing them, methods of using such compounds and processes for making such compounds.
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