- Effects of C2-Alkylation, N-Alkylation, and N,N′-Dialkylation on the Stability and Estrogen Receptor Interaction of (4R,5S)/(4S,5R)-4,5-Bis(4-hydroxyphenyl)-2-imidazolines
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(4R,5S)/(4S,5R)-4,5-Bis(4-hydroxyphenyl)-2-imidazolines bearing 2,2′-H (3a), 2,2′-Cl (3b), 2,2′,6-Cl (3c), and 2,2′-F (3d) substituents in the aromatic rings were C2-alkylated (5a-i), N-alkylated (7, 7a-c), and N,N′-dialkylated (9a-c). The synthesis started from the diastereomerically pure (1R,2S)/(1S,2R)-1,2-diamino-1,2-bis(4-methoxyphenyl)ethanes 1a-d, which were cyclized to the imidazolines 2a-d and 4a-i with triethylorthoesters or iminoethers. Ether cleavage with BBr3 yielded the (4R,5S)/(4S,5R)-4,5-bis(4-hydroxyphenyl)-2-imidazolines 3a-d and 5a-i. The N-alkylation and N,N′-dialkylation of 2b, employed for obtaining 7a-c and 9a-c, were performed prior to the ether cleavage with alkyl iodine in dry THF. By use of HPLC, the influence of the substitution patterns in the aromatic rings and alkyl chains at the C2- or N-atoms on the hydrolysis rate of the imidazolines was studied under in vitro conditions. It appeared that only imidazolines with C2- or N-alkyl substituents show sufficient stability to interact as heterocycles with the estrogen receptor (ER). The resulting gene activation was monitored in a luciferase assay using ERα-positive MCF-7-2a breast cancer cells stably transfected with the plasmid ERE wtcluc. It is interesting to note that C2-alkylation led to a strong reduction or even a complete loss of activity whereas N-alkylation improved the estrogenic profile. The (4R,5S)/(4S,5R)-N-ethyl-4,5-bis(2-chloro-4-hydroxyphenyl)-2-imidazoline 7b has proven to be the most active compound in this structure-activity relationship study (EC50 = 0.015 μM).
- Von Rauch, Moriz,Schlenk, Miriam,Gust, Ronald
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Read Online
- The role of the side chain in determining relative δ- and κ-affinity in C5′-substituted analogues of naltrindole
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The role of the side chain in 5′-substituted analogues of naltrindole has been further explored with the synthesis of series of amides, amidines, and ureas. Amidines (8, 13) had greatest selectivity for the K receptor, as predicted from consideration of the message-address concept. It was also found that an appropriately located carbonyl group, in ureas (10) and amides (7), led to retention of affinity and antagonist potency at the δ receptor.
- Black, Shannon L.,Jales, Andrew R.,Brandt, Wolfgang,Lewis, John W.,Husbands, Stephen M.
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Read Online
- Structure-fluorescence activation relationships of a large Stokes shift fluorogenic RNA aptamer
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The Chili RNA aptamer is a 52 nt long fluorogen-activating RNA aptamer (FLAP) that confers fluorescence to structurally diverse derivatives of fluorescent protein chromophores. A key feature of Chili is the formation of highly stable complexes with different ligands, which exhibit bright, highly Stokes-shifted fluorescence emission. In this work, we have analyzed the interactions between the Chili RNA and a family of conditionally fluorescent ligands using a variety of spectroscopic, calorimetric and biochemical techniques to reveal key structure-fluorescence activation relationships (SFARs). The ligands under investigation form two categories with emission maxima of ~540 or ~590 nm, respectively, and bind with affinities in the nanomolar to low-micromolar range. Isothermal titration calorimetry was used to elucidate the enthalpic and entropic contributions to binding affinity for a cationic ligand that is unique to the Chili aptamer. In addition to fluorescence activation, ligand binding was also observed by NMR spectroscopy, revealing characteristic signals for the formation of a G-quadruplex only upon ligand binding. These data shed light on the molecular features required and responsible for the large Stokes shift and the strong fluorescence enhancement of red and green emitting RNA-chromophore complexes.
- Bessi, Irene,H?bartner, Claudia,Lenz, Ann-Kathrin,Steinmetzger, Christian
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Read Online
- HETEROCYCLIC SPIRO-COMPOUNDS AS AM2 RECEPTOR INHIBITORS
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Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: wherein R1, R2, R4, R5, R6, R7, R8, R9, R10,Z, X1, X2, X3, L2, HET, n and q are as defined herein. The compounds are inhibitors of adrenomedullin receptor subtype 2 (AM2). Also disclosed are the compounds for use in the treatment of diseases modulated AM2, including proliferative diseases such as cancer; pharmaceutical compositions comprising the compounds; methods for preparing the compounds; and intermediates useful in the preparation of the compounds.
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Page/Page column 148; 212; 213
(2020/06/05)
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- Synthesis, electronic structure, linear and nonlinear photophysical properties of novel asymmetric branched compounds
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A series of novel asymmetric branched compounds that utilize a 1,3,5-triazine core and feature D-π-A-(π-D′-π-A′)0-2 configurations (D = donor, A = acceptor, π = conjugated bridge) were designed, successfully synthesized, and fully characterized by 1H NMR, 13C NMR, FT-IR, and HRMS. Their photophysical properties including linear absorption, one-photon excited fluorescence, two-photon absorption, and frequency up-converted fluorescence, were systematically investigated in different solvents. With a rise in the polarity of solvents, the peak positions of the one-photon excited fluorescence are red-shifted and the Stokes shifts increase, while the linear absorption wavelengths change slightly. In addition, the target compounds except CZ show the positive solvatokinetic effect. With a rise in the number of branches, the red shifts of the absorption and emission maxima, the hyperchromicity of the molar absorption coefficients, and the decrease of the Stokes shifts are observed. The peripheral electron donors (carbazole, phenothiazine) and acceptors (pyridine, benzimidazole) also exert an important influence on the photophysical properties. Under excitation of 690–930 nm fs laser pulses, all the target compounds emit frequency up-converted fluorescence with the maximal peaks at 471–575 nm, and the two-photon absorption cross-sections in THF are 132 (PTZ), 182 (CZ), 453 (CZ-Py1), 844 (CZ-Py2), 1244 (CZ-BI1), and 2072 (CZ-BI2) GM, respectively. Their two-photon response is found to be nearly additive with respect to the number of branches. The time-dependent density functional theory calculations were conducted to gain an insight into their electronic structures and to better understand the structure-photophysical property relationships. The results clearly indicate the importance of appropriate structural units on the enhancement of two-photon absorption properties.
- Cai, Zhi-Bin,Chen, Li-Jun,Li, Sheng-Li,Ye, Qing,Tian, Yu-Peng
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- Method for synthesizing ethyl acetimidate hydrochloride
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The invention discloses a new method for efficiently synthesizing ethyl acetimidate hydrochloride. The method comprises the following steps: adding ethanol and acetonitrile to a three-necked flask formixing, and cooling the system to below 5 DEG C by introducing a circulating frozen brine; introducing dried hydrogen chloride gas into the three-necked flask; and after the gas introducing is completed, heating the system to carry out a reaction under heat preservation until the reaction is completely finished to form ethyl acetimidate hydrochloride. According to the method, ethyl acetimidate hydrochloride is prepared under low temperature conditions, an obtained finished-product has good appearance and good quality, the product yield is high, and the method has great significance in the aspects such as low energy consumption and green chemical production.
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Paragraph 0026-0035
(2019/10/17)
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- Synthesis of 5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-one's aryl Schiff base derivatives and investigation of carbonic anhydrase and cholinesterase (AChE, BuChE) inhibitory properties
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Carbonic anhydrase enzymes (EC 4.2.1.1, CAs) are metalloenzyme families that catalyze the rapid conversion of H2O and CO2 to HCO3 – and H+. CAs are found in different tissues where they participate in various significant biochemical processes such as ion transport, carbon dioxide respiration, ureagenesis, lipogenesis, bone resorption, electrolyte secretion, acid-base balance, and gluconeogenesis. In such processes, many CAs are significant therapeutic targets because of their inhibitory potentials especially in the treatment of some diseases such as edema, glaucoma, obesity, cancer, epilepsy, and osteoporosis. Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) inhibitors are also valuable compounds for different therapeutic applications including Alzheimer's disease. In this work, we report a fast and effective synthesis of 5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-one's aryl Schiff base derivatives and also their CA and cholinesterases inhibitory properties. Our findings showed that these Schiff base derivatives, with triazole ring, found as strong CA and cholinesterases inhibitors.
- ?zil, Musa,Balayd?n, Halis Türker,?entürk, Murat
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p. 705 - 713
(2019/03/06)
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- Ethyl N-cyanoethylimidoate preparation method
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The invention belongs to the field of organic matter synthesis, and particularly relates to an ethyl N-cyanoethylimidoate preparation method, wherein the ethyl N-cyanoethylimidoate is prepared by using acetonitrile as a solvent, using a 50% cyanamide aqueous solution to replace cyanamide, and using ethyl acetimidate hydrochloride as an intermediate. According to the present invention, the new synthesis method is used so as to achieve advantages of cost reducing, environment protection, simple operation, convenient post-treatment, high yield and simple synthesis, and is suitable for industrialproduction.
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Paragraph 0010-0011
(2019/05/16)
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- PYRAZOLO[3,4-b]PYRIDINES AND IMIDAZO[1,5-b]PYRIDAZINES AS PDE1 INHIBITORS
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The present invention provides compounds of formula (I) that are PDE1 enzyme inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders. The present invention also provides pharmaceutical compositions comprising compounds of the invention and methods of treating disorders using the compounds of the invention.
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Paragraph 0346; 0347
(2018/07/15)
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- Continuous detection of HCl and NH3 gases with a high-performance fluorescent polymer sensor
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A novel fluorescent triazine-based covalent organic polymer (COP-1) sensor for HCl and NH3 gases has been designed and synthesized. Both the COP-1 powders that were dispersed in solvents and the COP-1 film that was formed on the surface of quartz sheets exhibited stable fluorescence and a sensitive HCl/NH3 response. Immersion in HCl-bubbled solvents weakens and red-shifts the fluorescence emission of the COP-1 powders, owing to a protonation-induced charge transfer (CT). Subsequent injection of NH3 into the solvents recovers the fluorescence via deprotonation. Interestingly, the microporous COP-1 film also shows a similar fluorescence response to HCl/NH3 gas, with high sensitivity and good reversibility, which suggests that it could serve as a solid-state optical probe for continuous and quantitative detection of HCl and NH3 gases. The formation of the red-shifting hydrogen bonds is found to be the origin of the response.
- Xu, Ning,Wang, Rui-Lei,Li, Dong-Peng,Zhou, Zi-Yan,Zhang, Tian,Xie, Yu-Zhong,Su, Zhong-Min
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p. 13367 - 13374
(2018/08/21)
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- Colchicine derivatives, and preparation method and medical application thereof
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The invention specifically relates to colchicine derivatives (I) as described in the specification and a preparation method thereof, and pharmaceutical compositions containing the colchicine derivatives, belonging to the field of medicinal chemistry. The results of pharmacodynamic experiments prove that the colchicine derivatives of the invention have treatment effect on lumbar disc herniation andliver fibrosis.
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Paragraph 0082; 0092; 0093
(2018/09/14)
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- Synthesis and glutathione reductase inhibitory properties of 5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one's aryl Schiff base derivatives
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Glutathione reductase (GR) is responsible for the existence of the reduced glutathione (GSH) molecule, a crucial antioxidant against oxidative stress reagents. The antimalarial activities of some redox active compounds are attributed to their inhibition of antioxidant flavoenzyme GR, and inhibitors are therefore expected to be useful for the treatment of malaria. In this work, a fast and effective synthesis and the GR inhibitory properties of 5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one's aryl Schiff base derivatives are reported. For this aim, the triazol nucleus was obtained, which was substituted with identical groups: ester, hydrazide, and Schiff base system at the N-2 and N-4 nitrogen atoms. The majority of the reactions were carried out by utilizing both microwave and conventional methods in order to compare their yields and reaction times. Beside this, the occuring E/Z geometrical isomers from the C?N double bond and the cis/trans amide conformers at the CO?NH single bond were studied. In the biological activity section of this work, it was found that all synthesized compounds have better inhibitory activity than N,N-bis(2-chloroethyl)-N-nitrosourea against GR; especially, two molecules, 6e and 6f, are the best among them. The evidence indicates that these Schiff base derivatives, with triazole ring, are strong GR inhibitors and novel antimalaria candidates.
- Balayd?n, Halis Türker,?zil, Musa,?entürk, Murat
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- Synthesis of Some Novel 2-Substitutedbenzyl-(4)7-phenyl-1H-benzo[d]imidazoles in Mild Conditions as Potent Anti-Tyrosinase and Antioxidant Agents
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Novel 2-substitutedbenzyl-4(7)-phenyl-1H-benzo[d]imidazole compounds were synthesized and characterized. Although 2a and 2b were reported previously in the literature, 11 compounds were synthesized (nine of them were newly synthesized) and the tyrosinase inhibitory effects and antioxidant activities of these compounds were studied for the first time. All of the synthesized compounds displayed certain inhibitory effects on tyrosinase, with IC50 values ranging from 37.86 ± 0.24 to 75.81 ± 2.49 μM. Among the compounds, 2j exhibited similar tyrosinase inhibitory effect (IC50 = 37.86 ± 0.24 μM) to the positive control, kojic acid (IC50 = 21.93 ± 0.11 μM). Kinetic studies revealed it to act as non-competitive tyrosinase inhibitor with a Ki value of 50.2 μM. The antioxidant activities of the compounds were investigated by using in vitro antioxidant assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP). All of these results indicated that the compounds might have potential application as tyrosinase inhibitors.
- Do?an, ?nci S.,?zel, Arzu,Birinci, Zeynep,Barut, Burak,Sellitepe, Hasan E.,Kahveci, Bahittin
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p. 881 - 888
(2016/11/09)
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- METHOD FOR PREPARATION OF BENZIMIDAZOLE DERIVATIVES
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The present invention provides a method for preparing a compound with a benzimidazole structure with an excellent yield using a low-cost starting material, not requiring an additional separation process, or not using a dangerous reagent during the manufacturing process. Furthermore, the present invention also provides an intermediate and a final product produced by the preparing method.
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Paragraph 142; 143; 144
(2015/02/02)
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- Phenylalanine and Phenylglycine Analogues as Arginine Mimetics in Dengue Protease Inhibitors
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Dengue virus is an increasingly global pathogen. One of the promising targets for antiviral drug discovery against dengue and related flaviviruses such as West Nile virus is the viral serine protease NS2B-NS3. We here report the synthesis and in vitro characterization of potent peptidic inhibitors of dengue virus protease that incorporate phenylalanine and phenylglycine derivatives as arginine-mimicking groups with modulated basicity. The most promising compounds were (4-amidino)-l-phenylalanine-containing inhibitors, which reached nanomolar affinities against dengue virus protease. The type and position of the substituents on the phenylglycine and phenylalanine side chains has a significant effect on the inhibitory activity against dengue virus protease and selectivity against other proteases. In addition, the non-natural, basic amino acids described here may have relevance for the development of other peptidic and peptidomimetic drugs such as inhibitors of the blood clotting cascade.
- Weigel, Lena F.,Nitsche, Christoph,Graf, Dominik,Bartenschlager, Ralf,Klein, Christian D.
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supporting information
p. 7719 - 7733
(2015/10/20)
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- Microwave-assisted synthesis of some new coumarin derivatives including 1,2,4-triazol-3-one and investigation of their biological activities
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By using the microwave technology, a new protocol has been developed for the synthesis of new coumarin derivatives including 1,2,4-triazol-3-one skeleton. This protocol proves to be efficient and environmentally friendly in terms of easy work-up and good yields. All newly synthesized compounds were screened for their antimicrobial activity and lipase inhibition. Most of the compounds were found to be effective on Escherichia coli. N'-{[4-Amino-3-(2-bromobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetyl}-6-bromo-2-oxo-2H-chromene-3-carbohydrazide and N'-{[4-amino-3-(3,4-dichlorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetyl}-6-bromo-2-oxo-2H-chromene-3-carbohydrazide had a good effect on lipase inhibition.
- Kahveci, Bahittin,Yilmaz, Fatih,Mente?e, Emre,ülker, Serdar
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p. 447 - 456
(2015/10/28)
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- One-flask synthesis of 1,3,5-trisubstituted 1,2,4-triazoles from nitriles and hydrazonoyl chlorides via 1,3-dipolar cycloaddition
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A one-flask strategy for the synthesis of 1,3,5-trisubstituted 1,2,4-triazoles 4a-s and 8a and b from nitriles 5a-i with N-arylhydrazonoyl hydrochlorides 3a-h and 7a and b under basic conditions was developed. The reaction provided the desired 1,2,4-triazoles in moderate to excellent yields (56-98%), and was applicable to aliphatic and aromatic nitriles as well as N-phenylhydrazonoyl hydrochlorides bearing ester and acetyl functionalities. A 1,3-dipolar cycloaddition between imidate and nitrilimine generated from the respective nitrile and N-arylhydrazonoyl chloride in one flask was proposed for the new transformation.
- Wang, Li-Ya,Tsai, Henry J.,Lin, Hui-Yi,Kaneko, Kimiyoshi,Cheng, Fen-Ying,Shih, Hsin-Siao,Wong, Fung Fuh,Huang, Jiann-Jyh
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p. 14215 - 14220
(2014/04/17)
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- Investigation of photophysical properties of new branched compounds with triazine and benzimidazole units
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Three new acceptor-donor-acceptor branched compounds with triazine and benzimidazole units (M1, M2, and M3) were synthesized and characterized by infrared, hydrogen-1 nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, mass spectrometry, and elemental analysis. Their photophysical properties were investigated including linear absorption, single-photon excited fluorescence, fluorescence quantum yield, two-photon absorption, and frequency up-converted fluorescence. When the number of branches increases, the spectral positions of the linear absorption and the single-photon excited fluorescence show red shifts, while the fluorescence quantum yields decrease. When the polarity of solvents increases, the spectral positions of the single-photon excited fluorescence and the Stokes shifts also show red shifts, while the fluorescence quantum yields of the two-branched compound (M2) and three-branched compound (M3) decrease. Under the excitation of an 800 nm laser with a pulse width of 80 fs, all these compounds emit intense green frequency up-converted fluorescence, and the two-photon absorption cross-sections are 210, 968, and 1613 GM for M1, M2, and M3, respectively. This result shows that significant enhancement of the two-photon absorption cross-section can be achieved by sufficient electronic coupling between the strong charge transfer acceptor-donor-acceptor quadrupolar branches through the s-triazine core. the Partner Organisations 2014.
- Cai, Zhibin,Zhou, Mao,Li, Bo,Chen, Ye,Jin, Fan,Huang, Jiuqiang
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p. 3042 - 3049
(2014/07/07)
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- New bifunctional organocatalysts based on (R,R)-cyclohexane-1,2-diamine for the asymmetric addition of nucleophiles to aldehydes
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The amide and sulfamide derivatives of (1R,2R)-N,N-diethylcyclohexane-1,2- diamine can serve as organocatalysts for addition of Me3SiCN and Et2Zn to aldehydes.
- Maleev,Gugkaeva,Tsaloev,Moskalenko,Khrustalev
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- Combinatorial synthesis of 3,5-Dimethylene substituted 1,2,4-Triazoles
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Combinatorial cyclizations of imidates and hydrazides with methylene linked R groups, generated from the corresponding nitriles and carboxylic acids, respectively, provided a large library of 3,5-dimethylene substituted 1,2,4- trizoles. 2011 Bentham Science Publishers Ltd.
- Woodard, Scott S.,Jerome, Kevin D.
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experimental part
p. 132 - 137
(2012/04/18)
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- SUBSTITUTED IMIDAZOLONE DERIVATIVES, PREPARATIONS AND USES
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The present invention relates to polysubstituted imidazolone derivatives, to the pharmaceutical compositions comprising them and to the therapeutic uses thereof in the human and animal health fields. The present invention also relates to a process for preparing these derivatives.
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Page/Page column 35
(2010/02/16)
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- New analogues of agmatine with higher affinity to imidazoline receptors
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Compilation of agmatine structure and imidazoline ring leads to a new family of imidazoline/α2-adrenoceptor ligands, 4(5)-(2-aminoethyl)imidazoline derivatives. Constraining of the guanidine moiety into heterocyclic ring improved the affinities of the resultant fusion compounds in comparison to agmatine itself. In this work, the synthetic approach and results for I1, I2, and α2-adrenoceptors affinities are reported.
- Treder, Adam P.,Andruszkiewicz, Ryszard,Zgoda, W?odzimierz,Ford, Celeste,Hudson, Alan L.
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supporting information; experimental part
p. 1009 - 1011
(2009/09/25)
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- Catalytic Mannich-type reactions of Sulfonylimidates
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A novel nucleophile, sulfonylimidate, has been successfully employed in Mannich-type reactions. Due to electronwithdrawing property of sulfonyl group of sulfonylimidate, the acidity of α-proton is enhanced so that sulfonylimidate bearing no activating functional group at α-position is deprotonated by relatively weak base. DBU-catalyzed reactions of sulfonylimidates with protected imines in DMF provided the adducts in high yields with high anti selectivity. This reaction represents a wide substrate scope and a high catalytic turnover. A thorough kinetic study revealed that ratedetermining step is most likely deprotonation step in case of Ts-imidate. Alkali earth metal alkoxide and its HMDS salt also catalyze Mannich-type reactions of sulfonylimidates. The reactions catalyzed by Mg(O tBu)2 in DMF provided the adducts with high anti selectivity, while those catalyzed by [Sr(HMDS)2]2 gave syn selectivity. The asymmetric variant of Mannich-type reaction of sulfonylimidate was also achieved. Several transformations of sulfonylimidates to other functional groups were also demonstrated. Finally, direct-type catalytic formation of cβ-amino acid ester from aldehyde and sulfonylimidate was achieved via in situ formation of sulfonylimine and DBU-assisted hydrolysis of sulfonylimidate.
- Matsubara, Ryosuke,Berthiol, Florian,Nguyen, Huy V.,Kobayashi, Shu
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experimental part
p. 1083 - 1102
(2009/12/25)
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- Sulfonylimidates as nucleophiles in catalytic addition reactions
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The first catalytic addition reactions of sulfonylimidates have been accomplished. In the presence of a catalytic amount of DBU (normally 5-10 mol %), sulfonylimidates reacted with several N-protected imines, methyl acrylate, and azodicarboxylate to afford the corresponding addition adducts, sulfonylimidates, in excellent yields. In the addition reactions to imines, high anti-selectivity was observed. A novel direct formation of β-amino acid derivatives from aldehyde and sulfonylimidate is also described. Copyright
- Matsubara, Rvosuke,Berthiol, Florian,Kobayashi, Shu
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p. 1804 - 1805
(2008/09/18)
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- DBU-catalyzed addition reactions of sulfonylimidates
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Sulfonylimidates react with various types of N-protected imines in the presence of a catalytic amount of DBU to afford β-aminosulfonylimidates in high yields and high anti-selectivities. The experimental procedure is described in detail. Georg Thieme Verlag Stuttgart.
- Matsubara, Ryosuke,Kobayashi, Shu
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experimental part
p. 3009 - 3011
(2009/04/10)
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- NOVEL DUAL ACTION RECEPTORS ANTAGONISTS (DARA) AT THE AT1 AND ETA RECEPTORS
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The present invention relates to new compounds of the formula [Chemical formula should be inserted here. Please see paper copy] wherein R1, R2, R3, and R31 are as specified herein. The invention also relates to a method for preparation thereof, as well as combinations of the new compounds with previously known agents. The invention also relates to the use of the above-mentioned compounds and combinations for the preparation of a medicament for treating hypertension of different kinds, alleviating organ damage of different kinds, treating or preventing diabetic nephropathy, treating endothelin and angiotensin mediated disorders, and treating prostate cancer.
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Page/Page column 280-281
(2010/11/28)
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- FUNGICIDAL HETEROCYCLIC COMPOUNDS
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A compound which can specifically or selectively expresses an antifungal activity with a broad spectrum, based on the functional mechanism of 1,6-β-glucan synthesis inhibition, is provided, and an antifungal agent which comprises such a compound, a salt thereof or a solvate thereof is provided. A compound represented by the following formula (I), a salt thereof or a solvate thereof.
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Page/Page column 57
(2010/11/24)
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- An enantioselective ketene-imine cycloaddition method for synthesis of substituted ring-fused 2-pyridinones
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Previously, a method for the stereoselective synthesis of β-lactams, starting from 2H-δ2-thiazolines and Meldrum's acid derivatives, has been reported from our laboratory. We now report a new method for the synthesis of optically active, highly substituted ring-fused 2-pyridinones. This was discovered when 2-alkyl-δ2-thiazolines and Meldrum's acid derivatives were treated with HCl(g) in benzene at 5 → 78 °C. Further refinement of the synthetic protocol revealed that use of 1,2-dichloroethane as solvent at 0 → 64 °C led to the desired 2-pyridinones in good yields and with excellent enantioselectivity. Use of these conditions allowed preparation of 2-pyridinones from several different δ2-thiazolines and Meldrum's acid derivatives and may be a general route to 2-pyridinones.
- Emtenaes,Alderin,Almqvist
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p. 6756 - 6761
(2007/10/03)
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- An efficient method for the preparation of N,N-disubstituted 1,2-diamines
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C2-Symmetric 1,2-diamines are useful precursors to numerous reagents used in asymmetric synthesis and catalysis. We report here an efficient protocol for converting the two most commonly used trans-1,2-diamines to N,N-disubstituted derivatives, a transformation that simplifies the preparation of non-C2-symmetric diamines. Central to the method is the high-yielding conversion of the diamines to the corresponding monoacetylated derivatives via imidazoline intermediates. (C) 2000 Published by Elsevier Science Ltd.
- Mitchell,Finney
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p. 8431 - 8434
(2007/10/03)
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- 4-[4-[4-(4-HYDROXYPHENYL)-l-PIPERAZINYL]-PHENYL]-5-METHYL-3H-1,2,4-TRIAZOL-3-ONE DERIVATIVES
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2-[2-(4-chlorophenyl)-2-(hydroxy or oxo)ethyl]-2,4-dihydro-4-[4-[4-(4-hydroxyphenyl)-1 -piperazinyl]-phenyl]-5-methyl-3H-l,2,4-triazol-3-one having the formula wherein X represents C= 0 or CHOH, for use as 5-lipoxygenase inhibitors. Pharmaceutical compositions, processes for preparing said compounds and compositions; and a method of treating leukotriene mediated diseases
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- Process for the preparation of organo N-hydroxyimidates
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Organo N-hydroxyimidates are prepared by reacting an organonitrile with an organic alcohol and with a hydrogen halide, in the presence of an organic solvent (which may include an excess of the organonitrile reactant), under anhydrous conditions, to form the corresponding organoimidate hydrohalide, and then reacting said organoimidate hydrohalide with a hydroxylamine salt and ammonia gas in the presence of an organic solvent (which can be the excess organonitrile from the first step), under anhydrous conditions, to produce the corresponding organo N-hydroxyimidate.
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- Purines, Pyrimidines, and Imidazoles. Part 64. Alkylation and Acylation of Some Aminoimidazoles Related to Intermediates in Purine Nucleotide de novo and Thiamine Biosynthesis
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Treatment of ethyl-5-amino-1-benzylimidazole-4-carboxylate with butyl-lithium and methyl iodide gave the 5-N-methylamino derivative (4b) and the 3-methiodide (5) whereas ethyl-5-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)imidazole-4-carboxylate gave both the 5-N-methylamino (6b) and 2-methyl (6d) derivatives.Ethyl 5-amino-1-benzylimidazole-4-carboxylate with acetic anhydride or acetyl chloride gave various products, according to the conditions, including the 5-N-mono- and -N,N-di-acetylamino derivatives (4d) and (4c), respectively, and N,N'-dibenzyloxamide (9).The oxamide also arose from treatment of the imidazole (4a) with formaldehyde. 3-Cyanopropanimidate with ethyl α-amino-α-cyano acetate followed by benzylamine or 2,3-O-isopropylidene-D-ribosylamine afforded ethyl 5-amino-1-benzyl-2-(2-cyanoethyl)imidazole-4-carboxylate and ethyl 5-amino-1-(2,3-O-isopropylidene-α- and β-D-ribofuranosyl)imidazole-4-carboxylates, respectively.Ethyl 5-amino-(2,3-O-isopropylidene-β-D-ribofuranosyl)-2-ethoxycarbonylethylimidazole-4-carboxylate and the corresponding 2-ethoxyethyl nucleoside (6i) were similarly prepared.Oxidation of ethyl 5-amino-2-methylimidazole-4-carboxylate with N-chlorosuccinimide and potassium hydroxide led to ethyl 5-amino-1-benzyl-2-formylimidazole-4-carboxylate and oxidation of the protected 2-ethoxycarbonylethyl nucleoside (6j) with selenium dioxide produced the urea derivative (6l).
- Mackenzie, Grahame,Wilson, Hilary A.,Shaw, Gordon,Ewing, David
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p. 2541 - 2546
(2007/10/02)
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- Synthesis and Structure of Alkyl N-Acylimidates
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Alkyl N-acylimidates 1 are prepared more easily and in higher yields than before by reaction of alkyl imidate hydrochlorides 5 with acyl halides 7 in the presence of 2.2 mol of base (14 examples).The X-ray analysis of a crystalline derivative (1dbd) shows, that the C=N- and C=O parts are twisted significantly (torsional angle 77.6 deg).The stereochemical, dynamic and electronic properties of the compounds 1 are interpreted by means of ab initio 3-21 G calculations on conformers of the parent system HO-CH=N-CH=O (8).Low rotational (ca. 6 kcal/mol) and inversional (max. 8 kcal/mol) barriers indicate the many favourable electronic interactions between the C=N- and the C=O groups in such N-functionalised imine derivatives.The compound 1 are significantly higher in energy than bisacylamines and are therefore suggested to be superior, more reactive synthetic C-N-C building blocks.The spectroscopic properties (IR, 13C- and 1H NMR, MS) are given and discussed.
- Kupfer, Rainer,Nagel, Michael,Wuerthwein, Ernst-Ulrich,Allmann, Rudolf
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p. 3089 - 3104
(2007/10/02)
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