Manidipine hydrochloride
Manidipine hydrochloride Basic information
- Product Name:
- Manidipine hydrochloride
- Synonyms:
-
- 4-(diphenylmethyl)-1-piperazinyl)ethylmethylester,dihydrochloride
- cv-4093dihydrochlorde
- franidipinehydrochloride
- MANIDIPINE DIHYDROCHLORIDE
- MANIDIPINE HYDROCHLORIDE
- 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-[4-(diphenylmethyl)-1-piperazinyl]ethyl methyl ester hydrochloride
- 3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-, 2-[4-(diphenylmethyl)-1-piperazinyl]ethyl methyl ester, dihydrochloride (9CI)
- Calslot
- CAS:
- 89226-75-5
- MF:
- C35H40Cl2N4O6
- MW:
- 683.62
- EINECS:
- 680-304-3
- Product Categories:
-
- Antihypertensive
- API
- Mol File:
- 89226-75-5.mol
Manidipine hydrochloride Chemical Properties
- Melting point:
- 157-163°; mp 174-180°; mp 167-170°
- storage temp.
- under inert gas (nitrogen or Argon) at 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)
Manidipine hydrochloride Usage And Synthesis
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
Manidipine Dihydrochloride is a metabolite of Manidipine (M16400), a dihydropyridine calcium channel blocker that exhibits antihypertensive properties.
Uses
aldosterone antagonist
Definition
ChEBI: Manidipine dihydrochloride is a diarylmethane.
Synthesis
89226-50-6
89226-75-5
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
[1] MITSURU KAKIHANA Akinobu N Masahiro SUNO. Antihypertensive Effect of CV-4093-2HCI, a New Calcium Antagonist, in Three Rat Models of Hypertension[J]. Japanese journal of pharmacology, 1988, 48 2: Pages 223-228. DOI:10.1254/jjp.48.223
[2] KATE MCKEAGE Lesley J S. Manidipine: a review of its use in the management of hypertension.[J]. Drugs, 2004, 64 17: 1923-1940. DOI:10.2165/00003495-200464170-00011
[3] MOHAMMAD M. GHAHREMANPOUR. Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2[J]. ACS Medicinal Chemistry Letters, 2020, 11 12: 2526-2533. DOI:10.1021/acsmedchemlett.0c00521
[4] BEATRICE MERCORELLI . Repurposing the clinically approved calcium antagonist manidipine dihydrochloride as a new early inhibitor of human cytomegalovirus targeting the Immediate-Early 2 (IE2) protein[J]. Antiviral research, 2018, 150: Pages 130-136. DOI:10.1016/j.antiviral.2017.12.014
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