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.
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.
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.
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.
