| Identification | More | [Name]
Manidipine hydrochloride | [CAS]
89226-75-5 | [Synonyms]
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-[4-(diphenylmethyl)-1-piperazinyl]ethyl methyl ester hydrochloride
MANIDIPINE DIHYDROCHLORIDE
MANIDIPINE HYDROCHLORIDE
4-(diphenylmethyl)-1-piperazinyl)ethylmethylester,dihydrochloride
cv-4093dihydrochlorde
franidipinehydrochloride
3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-, 2-[4-(diphenylmethyl)-1-piperazinyl]ethyl methyl ester, dihydrochloride (9CI)
Calslot
CV 4093
1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-[4-(diphenylmethyl)-1-piperazinyl]ethyl methyl ester hydrochloride
CV-4093(2HCl) | [EINECS(EC#)]
680-304-3 | [Molecular Formula]
C35H40Cl2N4O6 | [MDL Number]
MFCD00896434 | [Molecular Weight]
683.62 | [MOL File]
89226-75-5.mol |
| Chemical Properties | Back Directory | [Melting point ]
157-163°; mp 174-180°; mp 167-170° | [storage temp. ]
Inert atmosphere,2-8°C | [solubility ]
Soluble in DMSO (>25 mg/ml) | [form ]
solid | [color ]
White | [Water Solubility ]
Soluble in DMSO. Slightly soluble in water and ethanol
/n | [Merck ]
14,5743 | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. | [InChIKey]
UFIXGLLGFBWKAV-UHFFFAOYSA-N | [SMILES]
C1(C)NC(C)=C(C(OCCN2CCN(C(C3=CC=CC=C3)C3=CC=CC=C3)CC2)=O)C(C2=CC=CC([N+]([O-])=O)=C2)C=1C(OC)=O.[H]Cl | [CAS DataBase Reference]
89226-75-5(CAS DataBase Reference) |
| Safety Data | Back Directory | [RIDADR ]
UN 2811 6.1/PG III | [RTECS ]
US7975300 | [HS Code ]
2933.59.8000 | [HazardClass ]
6.1 | [PackingGroup ]
III | [Toxicity]
LD50 in male, female mice, male, female rats (mg/kg): 387, 340, 222, 199 s.c.; 62.2, 68.0, 66.5, 48.8 i.p.; 190, 171, 247, 156 orally (Chiba) |
| Hazard Information | Back Directory | [Description]
Manidipine (89226-75-5) is a clinically useful antihypertensive.1,2 It is an inhibitor of L- and T-type calcium channels with high selectivity for vasculature.? Manidipine has recently been found to be an inhibitor (IC50 = 4.8 μM) of the SARS-CoV-2 main protease, 3CLpro.3 It also acts as an early entry inhibitor of human cytomegalovirus (EC50 = 3.57 μM) via inhibition of the Immediate-Early 2 (IE2) protein.4 | [Uses]
aldosterone antagonist | [Uses]
Manidipine Dihydrochloride is a metabolite of Manidipine (M16400), a dihydropyridine calcium channel blocker that exhibits antihypertensive properties. | [Definition]
ChEBI: Manidipine dihydrochloride is a diarylmethane. | [Synthesis]
Synthesis of 3-(2-(4-phenylpiperazin-1-yl)ethyl)-5-methyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate from 3-(2-(4-phenylpiperazin-1-yl)ethyl)-5-methyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5- Dicarboxylate dihydrochloride was prepared in the following general procedure: manidipine base (2.25 kg) was dissolved in a solvent mixture of dichloromethane (6.75 L) and methanol (4.5 L) and cooled to 0-10°C. Concentrated hydrochloric acid (1.07 L) was slowly added dropwise under stirring, and after completion of the dropwise addition, the reaction was continued with stirring for 1 hour by keeping the temperature at 0-10 °C. Subsequently, methyl tert-butyl ether (13.5 L) was added to the reaction system and stirring was continued for 1 h. A large amount of solid was observed to precipitate. Filtration was carried out and the filter cake was washed with a small amount of methyl tert-butyl ether. The filter cake was mixed with dichloromethane (22 L), refluxed and pulped for 1 hour, then cooled to room temperature and filtered again. The filter cake was washed with a small amount of methyl tert-butyl ether and finally dried at 40-50 °C in a blast to give a yellow solid product (2.05 kg). The yield of this step was 81.8% and the purity of the product was 99.8869% (see Figure 2 for HPLC analysis). | [in vivo]
Manidipine dihydrochloride (10 mg/kg, i.p., b.i.d. at day 4, day 5) prolongs survival in SFTSV-infected mice[4].
Manidipine dihydrochloride (25 mg/kg, i.p., b.i.d. for 2 d, then daily for 19 d) protects mice from JEV infection[5].
Manidipine dihydrochloride (3 mg/kg, i.g., once per day, 7 d) prevents isoproterenol-induced left ventricular hypertrophy in rats[7].
| Animal Model: | IFNAR-/- mice[4] | | Dosage: | 10 mg/kg | | Administration: | Intraperitoneal injection (i.p. ), b.i.d. at day 4, day 5 | | Result: | Exhibited a modest, but statistically significant increase in the survival rate of lethal animal model with SFTSV infection, significantly reduced viral titers in the spleen and kidney. |
| Animal Model: | Adult female BALB/c mice (age, 4 weeks) [5] | | Dosage: | 25 mg/kg | | Administration: | Intraperitoneal injection (i.p. ), b.i.d. for 2 days, then daily for 19 days | | Result: | Reduced the mortality rate from 73% to 20%, significantly reduced the viral load in infected mice while remarkably alleviated brain damage phenomena. Had little effect on peripheral JEV infection, which indicated that manidipine protected the mice against JEV-induced lethality by decreasing the viral load in the brain. |
| Animal Model: | 8-week-old male Wistar rats[7] | | Dosage: | 3 mg/kg | | Administration: | Intragastric gavage (i.g.), once per day for 7 d | | Result: | Prevented isoproterenol-induced left ventricular hypertrophy (2.26±0.02 g/kg; p<0.01) as isoproterenol increased left ventricular weight (2.40±0.04 g/kg; p<0.01). Inhibited expression of mRNA of ANP (0.9-fold of the control value; p<0.01), collagen types I (1.1-fold; p<0.01) and type III (1.6-fold; p<0.01), and fibronectin (1.1-fold; p<0.01). |
| [IC 50]
T-type calcium channel | [References]
Kakihana et al. (1988), Antihypertensive effect of CV-4093·2HCl, a new calcium antagonist, in three rat models of hypertension; Jpn. J. Pharmacol., 48 223
McKeage (2004), Manidipine: a review of its use in the management of hypertension; Drugs, 64 1923
Ghahremanpour et al. (2020), Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2; ACS Med. Chem. Lett., 11 2526
Mercorelli et al. (2018), Repurposing the clinically approved calcium antagonist manidipine dihydrochloride as a new early entry inhibitor of human cytomegalovirus targeting the Immediate-Early 2 (IE2) protein; Antiviral Res., 150 130 |
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