- Preparation method of robenidine hydrochloride
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The invention discloses a preparation method of robenidine hydrochloride. 1, 3-diaminoguanidine hydrochloride as a raw material, methanol as a solvent and p-chlorobenzaldehyde undergoes a condensation reaction to produce the robenidine hydrochloride. The preparation method comprises adding 1, 3-diaminoguanidine hydrochloride and methanol into a reactor, heating the raw materials to a temperature of 45-55 DEG C until the reactants are completely dissolved, adjusting pH of the solution to 1.5-2 by hydrochloric acid methanol, dropwisely adding a p-chlorobenzaldehyde-methanol solution into the reaction solution at a temperature of 45-55 DEG C at a stirring speed of 80r/min, after dropwise addition, carrying out a reflux reaction process for 1-2h, carrying out distillation to recover methanol, adding water into the reaction product, carrying out beating, and carrying out filtration, water washing and drying to obtain robenidine hydrochloride. The condensation reaction under waterless conditions is conducive to smooth reaction and greatly improves a reaction yield. The solvent can be recovered and recycled, product content is high, further purification is avoided and high economical efficiency and environmental friendliness are obtained.
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Paragraph 0019; 0020
(2016/10/07)
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- Robenidine Analogues as Gram-Positive Antibacterial Agents
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Robenidine, 1 (2,2′-bis[(4-chlorophenyl)methylene]carbonimidic dihydrazide), was active against MRSA and VRE with MIC's of 8.1 and 4.7 μM, respectively. SAR revealed tolerance for 4-Cl isosteres with 4-F (8), 3-F (9), 3-CH3 (22), and 4-C(CH3)3 (27) (23.7-71 μM) and with 3-Cl (3), 4-CH3 (21), and 4-CH(CH3)2 (26) (8.1-13.0 μM). Imine carbon alkylation identified a methyl/ethyl binding pocket that also accommodated a CH2OH moiety (75; 2,2′-bis[1-(4-chlorophenyl)-2-hydroxyethylidene]carbonimidic dihydrazide). Analogues 1, 27 (2,2′-bis{[4-(1,1-dimethylethyl)phenyl]methylene}carbonimidic dihydrazide), and 69 (2,2′-bis[1-(4-chlorophenyl)ethylidene]carbonimidic dihydrazide hydrochloride) were active against 24 clinical MRSA and MSSA isolates. No dose-limiting cytotoxicity at ≥2× MIC or hemolysis at ≥8× MIC was observed. Polymyxin B addition engendered Escherichia coli and Pseudomonas aeruginosa Gram-negative activity MIC's of 4.2-21.6 μM. 1 and 75 displayed excellent microsomal stability, intrinsic clearance, and hepatic extraction ratios with T1/2 > 247 min, CLint H 0.22 in both human and mouse liposomes for 1 and in human liposomes for 75.
- Abraham, Rebecca J.,Stevens, Andrew J.,Young, Kelly A.,Russell, Cecilia,Qvist, Anastasia,Khazandi, Manouchehr,Wong, Hui San,Abraham, Sam,Ogunniyi, Abiodun D.,Page, Stephen W.,O'Handley, Ryan,McCluskey, Adam,Trott, Darren J.
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p. 2126 - 2138
(2016/03/25)
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- Purification of robenidine hydrochloride
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A superior grade of 1,3-bis(4-chlorobenzylideneamino)-guanidine hydrochloride is obtained by dispersing crude material in a suitable solvent, slowly adding to the dispersion an amount of base at least equivalent to the number of moles of 1,2,3-tris(4-chlorobenzylideneamino)guanidine hydrochloride present in said crude 1,3-bis(4-chlorobenzylideneamino)guanidine hydrochloride, separating the purified 1,3-bis(4-chlorobenzylideneamino)guandidine hydrochloride therefrom, and washing and drying the same.
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