2208-07-3Relevant articles and documents
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
Von Rauch, Moriz,Schlenk, Miriam,Gust, Ronald
, p. 915 - 927 (2004)
(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).
The role of the side chain in determining relative δ- and κ-affinity in C5′-substituted analogues of naltrindole
Black, Shannon L.,Jales, Andrew R.,Brandt, Wolfgang,Lewis, John W.,Husbands, Stephen M.
, p. 314 - 317 (2003)
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.
Structure-fluorescence activation relationships of a large Stokes shift fluorogenic RNA aptamer
Bessi, Irene,H?bartner, Claudia,Lenz, Ann-Kathrin,Steinmetzger, Christian
, p. 11538 - 11550 (2019)
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.
HETEROCYCLIC SPIRO-COMPOUNDS AS AM2 RECEPTOR INHIBITORS
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Page/Page column 148; 212; 213, (2020/06/05)
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.
Synthesis, electronic structure, linear and nonlinear photophysical properties of novel asymmetric branched compounds
Cai, Zhi-Bin,Chen, Li-Jun,Li, Sheng-Li,Ye, Qing,Tian, Yu-Peng
, (2020/01/08)
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.
Method for synthesizing ethyl acetimidate hydrochloride
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Paragraph 0026-0035, (2019/10/17)
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.
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
?zil, Musa,Balayd?n, Halis Türker,?entürk, Murat
, p. 705 - 713 (2019/03/06)
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.
Ethyl N-cyanoethylimidoate preparation method
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Paragraph 0010-0011, (2019/05/16)
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.
PYRAZOLO[3,4-b]PYRIDINES AND IMIDAZO[1,5-b]PYRIDAZINES AS PDE1 INHIBITORS
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Paragraph 0346; 0347, (2018/07/15)
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.
Continuous detection of HCl and NH3 gases with a high-performance fluorescent polymer sensor
Xu, Ning,Wang, Rui-Lei,Li, Dong-Peng,Zhou, Zi-Yan,Zhang, Tian,Xie, Yu-Zhong,Su, Zhong-Min
, p. 13367 - 13374 (2018/08/21)
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.
