25875-50-7 Usage
Chemical Properties
white or slightly yellow crystalline powder, odorless, slightly bitter taste. Very slightly soluble in ether and water, easily soluble in dilute acid or dilute alkali solution, the color gradually darkens when exposed to light.
Uses
Robenidine hydrochloride is used as a coccidiostat for use in chickens for fattening and turkeys at a minimum-maximum concentration of 30-36 mg/kg complete feed, and in rabbits for fattening at a minimummaximum concentration of 50-66 mg/kg complete feed withdrawal period of 5 days for all target animals.
Preparation
thiosemicarbazide was formed by addition and rearrangement of sodium thiocyanate with water and hydrazine. Then methylation with dimethyl sulfate and hydrazinolysis to give N.N'-diaminoguanidine sulfate. Then replaced with calcium chloride to N.N'-diaminoguanidine hydrochloride. Finally, it was condensed with p-chlorobenzaldehyde in ethanol again to produce Robenidine hydrochloride with 94% yield.
Antimicrobial activity
Robenidine hydrochloride activity against Eimeria species results from a dual action exerted upon different stages of the parasite as it develops in the intestinal mucosa (Ryley and Wilson, 1971). Initially it acts as a coccidiostat and arrests the development of the first schizont generation. Secondly, robenidine hydrochloride is coccidiocidal, killing the second generation of schizonts and possibly the merozoites. An additional effect against the sexual stage of coccidia development has been observed as well. Robenidine hydrochloride has been shown to be an inhibitor of oxidative phosphorylation (Wong et al., 1972) and is reported to affect the protein metabolism and some other metabolic process of coccidia (Lee and Millard, 1972).
Biological Activity
Robenidine Hydrochloride is an anticoccidial agent mainly for poultry which is also active against MRSA and VRE with MIC50s of 8.1 and 4.7 μM, respectively. IC50 & Target: MIC50: 8.1 μM (MRSA), 4.7 μM (VRE).In Vitro: Robenidine (compound 1) inhibits the growth of MRSA and VRE with MIC values of 8.1 and 4.7 μM, respectively. Robenidine is bactericidal against all of the S. aureus strains tested with MBC/MIC90 ratios ≤2. A profound and negative impact on the MIC values with a 4-fold decrease with Robenidine at 2% serum and no activity at 50% serum is observed.In Vivo: The time that the mean plasma concentration exceeds the concentration of 1 μg/mL is approximately 6 h in the Florfenicol (FFC) alone group; however, it is lowered to 4 h by Robenidine (ROB) pretreatment. The terminal elimination half-life (t1/2z), area under the concentration-time curve (AUC), area under the first moment curve (AUMC), and mean residence time (MRT) significantly decreased, whereas the elimination rate constant (λz) and total body clearance (CLz) obviously increased in rabbits pretreated with Robenidine.
Check Digit Verification of cas no
The CAS Registry Mumber 25875-50-7 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 2,5,8,7 and 5 respectively; the second part has 2 digits, 5 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 25875-50:
(7*2)+(6*5)+(5*8)+(4*7)+(3*5)+(2*5)+(1*0)=137
137 % 10 = 7
So 25875-50-7 is a valid CAS Registry Number.
InChI:InChI=1/C15H13Cl2N5.ClH/c16-13-5-1-11(2-6-13)9-19-21-15(18)22-20-10-12-3-7-14(17)8-4-12;/h1-10H,(H3,18,21,22);1H/b19-9+,20-10+;
25875-50-7Relevant articles and documents
Preparation method of robenidine hydrochloride
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Paragraph 0019; 0020, (2016/10/07)
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.
Robenidine Analogues as Gram-Positive Antibacterial Agents
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.
, p. 2126 - 2138 (2016/03/25)
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.
Purification of robenidine hydrochloride
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, (2008/06/13)
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.
