132866-11-6

Basic information

• Product Name: Lercanidipine hydrochloride
• Synonyms: 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-[(3,3-diphenylpropyl)methylamino]-1,1-dimethylethyl methyl ester hydrochloride;LERCANIDIPINE HCL;LERCANIDIPINE HYDROCHLORIDE;1,4-Dihydro-2,6-dimethyl-4-(3-nittrophenyl)-3,5-pyridinedicarboxylicAcid2-[(3,3-Diphenylpropyl)methylamino]-1,1-dimeth;1,4-Dihydro-2,6-dimethyl-4-(3-nittrophenyl)-3,5-pyridinedicarboxylic Acid 2-[(3,3-Diphenylpropyl)methylamino]-1,1-dimethylethyl Methyl Ester Hydrochloride;LERCANIDIPINEHYDROCHLORIDE(FORR&DONLY);Lercanidipine hemihydrate hydrochloride;2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid O3-[2-[3,3-diphenylpropyl(methyl)amino]-1,1-dimethyl-ethyl] ester O5-methyl ester hydrochloride
• CAS NO: 132866-11-6
• Molecular Formula: C₃₆H₄₁N₃O₆*ClH
• Molecular Weight: 648.19
• EINECS: 1308068-626-2
• Product Categories: Miscellaneous Natural Products;Dihydropyridine Class Chemicals;Intermediates & Fine Chemicals;Pharmaceuticals;Calcium Channel Modulators;Inhibitors and Activators;Voltage-gated Ion Channels;Aromatics;Dihydropyridine;Heterocycles;API;Cardiovascular APIs
• Mol File: 132866-11-6.mol
• Article Data: 8

Chemical Properties

• Melting Point: 175-177°C
• Boiling Point: 712.5 °C at 760 mmHg
• Flash Point: 384.7 °C
• Appearance: yellow/
• Vapor Pressure: 3.77E-20mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: soluble in Methanol
• Merck: 14,5446
• CAS DataBase Reference: Lercanidipine hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Lercanidipine hydrochloride(132866-11-6)
• EPA Substance Registry System: Lercanidipine hydrochloride(132866-11-6)

Safety Data

• Hazard Codes: T
• Statements: 25
• Safety Statements: 36/37-45
• RIDADR: UN 2811
• WGK Germany: 3
• Hazardous Substances Data: 132866-11-6(Hazardous Substances Data)

Usage

Chemical Properties

Pale-Yellow Powder

Uses

Different sources of media describe the Uses of 132866-11-6 differently. You can refer to the following data:
1. A dihydropyridine calcium channel blocker. Antihypertensive.
2. long-acting dihydropyridine calcium channel blocker, antihypertensive

Biological Activity

L-type Ca 2+ channel blocker that displays higher vascular selectivity than Felodipine (4-(2,3-Dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid ethyl methyl ester ). Causes peripheral vasodilation with only weak negative inotropic activity. Antihypertensive.

Biochem/physiol Actions

Lercanidipine hydrochloride is a L-type (Cav1.2b) vascular channel antagonist; L-type (Cav1.2a) cardiac channel agonist voltage-dependent and highly lipophylic compound, which exhibits a slower onset and longer duration of action than other calcium channel antagonists; an antihypertensive agent in patients with mild-to-moderate hypertension; more vasoselective than lacidipine and amlodipine.

Clinical Use

#N/A

Drug interactions

Potentially hazardous interactions with other drugs Aminophylline and theophylline: possibly increased aminophylline and theophylline concentration. Anaesthetics: enhanced hypotensive effect. Antibacterials: metabolism possibly inhibited by clarithromycin, erythromycin and telithromycin - avoid with erythromycin. Antidepressants: enhanced hypotensive effect with MAOIs. Antiepileptics: effect reduced by carbamazepine, barbiturates, phenytoin and primidone. Antifungals: metabolism possibly inhibited by itraconazole and ketoconazole - avoid; negative inotropic effect possibly increased with itraconazole. Antihypertensives: enhanced hypotensive effect, increased risk of first dose hypotensive effect of postsynaptic alpha-blockers. Antivirals: concentration increased by ritonavir - avoid. Cardiac glycosides: digoxin concentration increased. Ciclosporin: concentration of both drugs may be increased - avoid. Grapefruit juice: concentration increased - avoid

InChI:InChI=1/C36H41N3O6.ClH/c1-24-31(34(40)44-6)33(28-18-13-19-29(22-28)39(42)43)32(25(2)37-24)35(41)45-36(3,4)23-38(5)21-20-30(26-14-9-7-10-15-26)27-16-11-8-12-17-27;/h7-19,22,30,33,37H,20-21,23H2,1-6H3;1H

Synthetic route

(R,S) 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-[(3,3-diphenylpropyl)methylamino]-1,1-dimethylethyl methyl ester oxalate (957215-03-1) → lercanidipine hydrochloride (132866-11-6)

Conditions	Yield
Stage #1: (R,S) 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-[(3,3-diphenylpropyl)methylamino]-1,1-dimethylethyl methyl ester oxalate With potassium carbonate In dichloromethane; water Stage #2: With hydrogenchloride In dichloromethane; water	95%

lercanidipine (100427-26-7) → lercanidipine hydrochloride (132866-11-6)

Conditions	Yield
With hydrogenchloride In diethyl ether; tert-butyl methyl ether Product distribution / selectivity;	90%
With hydrogenchloride In ethanol; tert-butyl methyl ether Product distribution / selectivity;	90%
With hydrogenchloride In water; acetone for 0.0833333 - 24h; Product distribution / selectivity;	85%
With hydrogenchloride In ethanol; water for 0.0833333h; Product distribution / selectivity;	85%

methyl 3-aminocrotonate (21731-17-9) → lercanidipine hydrochloride (132866-11-6)

Conditions	Yield
Stage #1: 2-[(3-nitrophenyl)methylene]-3-oxobutanoic acid 2-[(3,3-diphenylpropyl)methylamino]-1,1-dimethyl ethyl ester hydrochloride With triethylamine In propan-1-ol; dichloromethane at 25 - 30℃; pH=~ 8 - ~ 9; Stage #2: methyl 3-aminocrotonate In propan-1-ol; dichloromethane at 75 - 80℃; for 10h; Stage #3: With hydrogenchloride In propan-1-ol at 20 - 30℃; for 0.5h; pH=~ 3 - ~ 4;	42%

1-chloro-2-methyl-2-propyl methyl 1 ,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-1-pyridine-3 ,5-dicarboxylate (890045-70-2) + N-methyl-3,3-diphenylpropylamine (28075-29-8) → lercanidipine hydrochloride (132866-11-6)

Conditions	Yield
Stage #1: 1-chloro-2-methyl-2-propyl methyl 1 ,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-1-pyridine-3 ,5-dicarboxylate; N-methyl-3,3-diphenylpropylamine In xylene for 10h; Heating / reflux; Basic conditions; Stage #2: With hydrogenchloride In diethyl ether; xylene for 24h;

C20H25N2O8PS + 2,N-dimethyl-N-(3,3-diphenylpropyl)-1-amino-2-propanol (100442-33-9) → lercanidipine hydrochloride (132866-11-6)

Conditions	Yield
Stage #1: C20H25N2O8PS; 2,N-dimethyl-N-(3,3-diphenylpropyl)-1-amino-2-propanol In toluene for 4h; Heating / reflux; Stage #2: With hydrogenchloride In water; ethyl acetate Product distribution / selectivity;

C20H25N2O9P + 2,N-dimethyl-N-(3,3-diphenylpropyl)-1-amino-2-propanol (100442-33-9) → lercanidipine hydrochloride (132866-11-6)

Conditions	Yield
Stage #1: C20H25N2O9P; 2,N-dimethyl-N-(3,3-diphenylpropyl)-1-amino-2-propanol In toluene for 4h; Heating / reflux; Stage #2: With hydrogenchloride In water; ethyl acetate Product distribution / selectivity;

2-[(3-nitrophenyl)methylene]-3-oxobutanoic acid 2-[(3,3-diphenylpropyl)methylamino]-1,1-dimethyl ethyl ester hydrochloride (929212-20-4) + methyl 3-aminocrotonate (14205-39-1) → lercanidipine hydrochloride (132866-11-6)

Conditions	Yield
Stage #1: 2-[(3-nitrophenyl)methylene]-3-oxobutanoic acid 2-[(3,3-diphenylpropyl)methylamino]-1,1-dimethyl ethyl ester hydrochloride With triethylamine In propan-1-ol at 25 - 40℃; for 0.166667h; Stage #2: methyl 3-aminocrotonate In propan-1-ol at 75 - 80℃; for 10h; Stage #3: With hydrogenchloride In propan-1-ol at 25 - 30℃; for 0.5h; pH=2;

2,N-dimethyl-2-(trimethylsilyloxy)-N-(3,3-diphenylpropyl)-1-propanamine + 1,4-dihydro-2,6-dimethyl-3-methoxycarbonyl-4-(3-nitrophenyl)-pyridine-5-carboxylic acid chloride (88712-56-5, 125185-92-4) → lercanidipine hydrochloride (132866-11-6)

Conditions	Yield
In dichloromethane at -10 - 30℃;

3-nitro-benzaldehyde (99-61-6) + 1,1,N-trimethyl-N-(3,3-diphenylpropy)-2-aminoethyl acetoacetate (100427-51-8) → lercanidipine hydrochloride (132866-11-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydrogenchloride / toluene / 9 h / 0 °C 2.1: triethylamine / propan-1-ol / 0.17 h / 25 - 40 °C 2.2: 10 h / 75 - 80 °C 2.3: 0.5 h / 25 - 30 °C / pH 2 View Scheme

2,N-dimethyl-N-(3,3-diphenylpropyl)-1-amino-2-propanol (100442-33-9) → lercanidipine hydrochloride (132866-11-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: zinc / xylene / 7 h / 25 - 145 °C 2.1: hydrogenchloride / toluene / 9 h / 0 °C 3.1: triethylamine / propan-1-ol / 0.17 h / 25 - 40 °C 3.2: 10 h / 75 - 80 °C 3.3: 0.5 h / 25 - 30 °C / pH 2 View Scheme

lercanidipine hydrochloride (132866-11-6) → lercanidipine (100427-26-7)

Conditions	Yield
With sodium methylate In methanol at 20 - 25℃; for 4.5h; Product distribution / selectivity;	77.1%
With borax In methanol; water at 20℃; pH=9.2; Product distribution / selectivity;
With potassium carbonate In water; ethyl acetate at 20℃; for 1.91667h; Product distribution / selectivity;
With sodium hydroxide In methanol; water at 20℃; Product distribution / selectivity;

lercanidipine hydrochloride (132866-11-6) + benzenesulfonic acid (98-11-3) → methyl 1,1,N-trimethyl-N-(3,3-diphenylpropyl)-2-aminoethyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate besylate (877372-46-8)

Conditions	Yield
Stage #1: lercanidipine hydrochloride With sodium hydroxide In methanol; water Stage #2: benzenesulfonic acid In tetrahydrofuran

Upstream product

• 21731-17-9 methyl 3-aminocrotonate 
• 100442-33-9 2,N-dimethyl-N-(3,3-diphenylpropyl)-1-amino-2-propanol 
• 99-61-6 3-nitro-benzaldehyde 
• 100427-51-8 1,1,N-trimethyl-N-(3,3-diphenylpropy)-2-aminoethyl acetoacetate 
• 88712-56-5 1,4-dihydro-2,6-dimethyl-3-methoxycarbonyl-4-(3-nitrophenyl)-pyridine-5-carboxylic acid chloride 
• 929212-20-4 2-[(3-nitrophenyl)methylene]-3-oxobutanoic acid 2-[(3,3-diphenylpropyl)methylamino]-1,1-dimethyl ethyl ester hydrochloride 
• 14205-39-1 methyl 3-aminocrotonate 
• 890045-70-2 1-chloro-2-methyl-2-propyl methyl 1 ,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-1-pyridine-3 ,5-dicarboxylate 
• 28075-29-8 N-methyl-3,3-diphenylpropylamine 
• 100427-26-7 lercanidipine 
• 957215-03-1 (R,S) 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-[(3,3-diphenylpropyl)methylamino]-1,1-dimethylethyl methyl ester oxalate 

Downstream Products

• 877372-46-8 methyl 1,1,N-trimethyl-N-(3,3-diphenylpropyl)-2-aminoethyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate besylate 
• 100427-26-7 lercanidipine 

Related news

Original ArticleApplication of planar chromatography for estimation of Lercanidipine hydrochloride (cas 132866-11-6) in dosage form08/25/2019

A new simple, precise, accurate, and selective high performance thin-layer chromatographic (HPTLC) method has been developed for analysis of lercanidipine hydrochloride (LER) in a tablet, using chloroform:toluene:methanol:acetic acid (8:1:1:1; v/v/v/v) as mobile phase. Chromatographic separation...detailed

Relevant articles and documents

METHODS FOR TREATING CHRONIC FATIGUE SYNDROME AND MYALGIC ENCEPHALOMYELITIS

In one aspect the invention relates to a method of treatment selected from the group consisting of: (a) treating a symptom such as pain in a subject identified or diagnosed as having Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS); (b) treating a symptom such as pain in a subject having dysfunctional TRPM3 ion channel activity; (c) restoring NK cell function in a subject having dysfunctional TRPM3 ion channel activity; and (d) restoring calcium homeostasis in a subject having dysfunctional TRPM3 ion channel activity. The method comprises the step of administering to the subject a therapeutically effective amount of at least one therapeutic compound selected from the group consisting of: (i) an opioid receptor antagonist; (ii) an opioid antagonist; and (iii) a therapeutic compound that restores TRPM3 ion channel activity. In some embodiments the therapeutic compound is naltrexone hydrochloride.

LERCANIDIPINE HYDROCHLORIDE POLYMORPHS AND AN IMPROVED PROCESS FOR PREPARATION OF 1,1,N-TRIMETHYL-N-(3,3-DIPHENYLPROPYL)-2-AMINOETHYL ACETOACETATE

Disclosed herein is an improved, commercially viable and industrially advantageous process for the preparation of substantially pure Lercanidipine intermediate, 1,1,N- trimethyl-N-(3,3-diphenylpropyl)-2-aminoethyl acetoacetate. The intermediate is useful for preparing Lercanidipine, or a pharmaceutically acceptable salt thereof, in high yield and purity. The present invention further provides a novel crystalline form of Lercanidipine hydrochloride and a process for its preparation. The present invention also provides a process for the preparation of amorphous form of Lercanidipine hydrochloride.

PROCESS FOR PREPARING AMORPHOUS LERCANIDIPINE HYDROCHLORIDE

The invention provides a process for preparing substantially pure amorphous lercanidipine hydrochloride. The amorphous lercanidipine hydrochloride prepared as disclosed herein is substantially pure and has a greater aqueous solubility and faster onset of