14777-27-6Relevant articles and documents
Potent and selective indolomorphinan antagonists of the kappa-opioid receptor
Stevens Jr., William C.,Jones, Robert M.,Subramanian, Govindan,Metzger, Thomas G.,Ferguson, David M.,Portoghese, Philip S.
, p. 2759 - 2769 (2000)
The indole moiety in the delta-opioid antagonist, naltrindole (2, NTI), was employed as a scaffold to hold an 'address' for interaction with the kappa-opioid receptor. The attachment of the address to the 5'-position of the indole moiety was based on superposition of NTI upon the kappa antagonist, norbinaltorphimine (1, norBNI). A variety of cationic groups were employed as a kappa address in an effort to investigate its interaction with the anionic address subsite, Glu297, on the kappa receptor. Some of the groups that were employed for this purpose were amines, amidines, guanidines, and quaternary ammonium. Members of the series were found to have a varying degree of kappa antagonist potency and kappa selectivity when tested in smooth muscle preparations. The 5'-guanidine derivative 12a (GNTI) was the most potent member of the series and had the highest kappa selectivity ratio. GNTI was 2 times more potent and 6-10-fold more selective than norBNI (1). In general, the order of potency in the series was: guanidines amines. The kappa antagonist potency appeared to be a function of a combination of the pK(a) and distance constraint of the cationic substituent of the ligand. Receptor binding studies were qualitatively in agreement with the pharmacological data. Molecular modeling studies on 12a suggested that the protonated N-17 and guanidinium groups of GNTI are associated with Asp138 (TM3) and Glu297 (TM6), respectively, while the phenolic hydroxyl may be involved in donor - acceptor interactions with the imidazole ring of His291. It was concluded that the basis for the high kappa selectivity of GNTI is related both to association with the nonconserved Glu297 residue and to unfavorable interactions with an equivalent position in mu- and delta-opioid receptors.
Preparation method of cefathiamidine hydrochloride
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Paragraph 0047; 0062; 0064; 0065; 0068; 0070; 0071; ..., (2021/09/01)
The invention provides a preparation method of cefathiamidine hydrochloride. In particular, by adopting a reverse dropwise adding manner, the intermediate product vinylidene chloride is added dropwise to the ammonia methanol to generate stable cefathiamidine, and the reverse dripping mode not only effectively inhibits the decomposition of the aramidine, but also the yield of cefathiamidine hydrochloride can reach 95% or above. The method is safe to operate. The method is high in yield and low in energy consumption, and is very suitable for large-scale application.
METHOD FOR PREPARATION OF BENZIMIDAZOLE DERIVATIVES
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Paragraph 138; 139; 140, (2015/02/02)
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.
METHOD FOR PRODUCING IMIDE ETHER COMPOUND
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, (2008/06/13)
A method for producing an imide ether compound in high yield is provided. The method is characterized in that a nitrile compound, an alcohol and a hydrogen halide are continuously introduced into a flow reaction apparatus comprising a mixing vessel and a flow reactor, to react them with one another. Since the reaction proceeds with 1 : 1 by the use of a flow reactor, an improved selectivity is achieved and the formation of a by-product is reduced, which results in the efficient production of an imide ether compound.
