Lacidipine

Base Information

• Chemical Name: Lacidipine
• CAS No.: 103890-78-4
• Molecular Formula: C26H33NO6
• Molecular Weight: 455.551
• Hs Code.: 2933399090
• European Community (EC) Number: 638-759-0
• UNII: 260080034N
• DSSTox Substance ID: DTXSID1046429
• Nikkaji Number: J325.878E
• Wikipedia: Lacidipine
• Wikidata: Q1163827
• NCI Thesaurus Code: C80881
• Pharos Ligand ID: ULST396RWY2M
• Metabolomics Workbench ID: 152268
• ChEMBL ID: CHEMBL460291,CHEMBL1728809
• Mol file: 103890-78-4.mol

Synonyms:3,5-Pyridinedicarboxylicacid,4-[2-[(1E)-3-(1,1-dimethylethoxy)-3-oxo-1-propen-1-yl]phenyl]-1,4-dihydro-2,6-dimethyl-,3,5-diethyl ester;3,5-Pyridinedicarboxylicacid,4-[2-[(1E)-3-(1,1-dimethylethoxy)-3-oxo-1-propenyl]phenyl]-1,4-dihydro-2,6-dimethyl-,diethyl ester (9CI);3,5-Pyridinedicarboxylic acid,4-[2-[3-(1,1-dimethylethoxy)-3-oxo-1-propenyl]phenyl]-1,4-dihydro-2,6-dimethyl-,diethyl ester, (E)-;Lacimen;Lacipil;Lacirex;Midotens;Motens;

Chemical Property of Lacidipine

Chemical Property:

• Appearance/Colour: White-to-off-white crystalline solid
• Vapor Pressure: 1.67E-12mmHg at 25°C
• Melting Point: 174-175 °C
• Refractive Index: 1.54
• Boiling Point: 558.4 °C at 760 mmHg
• PKA: 3.00±0.70(Predicted)
• Flash Point: 291.5 °C
• PSA: 90.93000
• Density: 1.127 g/cm³
• LogP: 4.73130
• Storage Temp.: -20?C Freezer
• Solubility.: DMSO: soluble20mg/mL, clear
• XLogP3: 4.5
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 11
• Exact Mass: 455.23078777
• Heavy Atom Count: 33
• Complexity: 805

Purity/Quality:

99% ^*data from raw suppliers

Lacidipine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 22

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCOC(=O)C1=C(NC(=C(C1C2=CC=CC=C2C=CC(=O)OC(C)(C)C)C(=O)OCC)C)C
• Isomeric SMILES: CCOC(=O)C1=C(NC(=C(C1C2=CC=CC=C2/C=C/C(=O)OC(C)(C)C)C(=O)OCC)C)C
• Recent ClinicalTrials: Influence of Telmisartan and Lacidipine, Combined or Alone, on QT Interval in Healthy Volunteers
• Description: Lacidipine is a new second-generation dihydropyridine calcium antagonist introduced as a once a day treatment for mild to moderate hypertension. It is reported to have high selectivity for vascular smooth muscle and also a long duration of action. The use of lacidipine as an antiatherosclerotic agent is currently under investigation. Lacidipine is a dihydropyridine L-type calcium channel blocker. It induces relaxation of isolated rat aorta and inhibits calcium-induced contraction of rabbit ear artery (pA2 = 9.4). It also induces relaxation of calcium-induced contractions in isolated rat colon and bladder and guinea pig trachea (IC50s = 6.7, 6, and 7.8 nM, respectively). Lacidipine induces negative inotropy in isolated guinea pig ventricular strips (IC50 = 110 nM). It reduces mean blood pressure in spontaneously hypertensive rats (ED25 = 0.35 mg/kg) and in renal hypertensive dogs (ED25 = 0.22 mg/kg) with a transient increase in heart rate. Lacidipine inhibits copper-induced oxidation of isolated human LDL when used at concentrations of 1 and 5 μM. It reduces the extension of aortic atheromatous lesions and decreases renal injury in ApoE-/- mice in a model of Western diet-induced atherosclerosis.
• Uses: A dihydropyridine calcium channel blocker. Antihypertensive. A dihydropyridine calcium channel blocker. Antihypertensive antihypertensive;dihydropyridinr calcium channel blocker
• 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. Antidepressants: enhanced hypotensive effect with MAOIs. Antiepileptics: effect possibly reduced by carbamazepine, barbiturates, phenytoin and primidone. Antifungals: metabolism possibly inhibited by itraconazole and ketoconazole; negative inotropic effect possibly increased with itraconazole. Antihypertensives: enhanced hypotensive effect, increased risk of first dose hypotensive effect of postsynaptic alpha-blockers. Antivirals: concentration possibly increased by ritonavir. Ciclosporin: 10 kidney transplant patients on ciclosporin, prednisone and azathioprine were given 4 mg lacidipine daily. A very small increase in the trough serum levels (+6%) and AUC (+14%) of the ciclosporin occurred. Grapefruit juice: concentration increased - avoid concomitant use

Technology Process of Lacidipine

There total 4 articles about Lacidipine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 90.0%

→ Lacidipine (103890-78-4)

Guidance literature:

Purification / work up;

Reference yield: 82.45%

tert-butyl 2-(triphenyl-15-phosphanylidene)acetate + ethyl aminocrotonate (626-34-6,7318-00-5,41867-20-3) + o-phthalic dicarboxaldehyde (643-79-8) → Lacidipine (103890-78-4)

Guidance literature:

tert-butyl 2-(triphenyl-15-phosphanylidene)acetate; o-phthalic dicarboxaldehyde; In dichloromethane; for 0.666667h; Cooling with ice;

ethyl aminocrotonate; With ammonium sulfate; In ethanol; dichloromethane; for 1.5h; Cooling with ice;

Reference yield: 40.9%

(tert-butoxycarbonylmethyl)triphenylphosphonium bromide (59159-39-6) + ethyl 3-aminobut-2-enoate (626-34-6) + o-phthalic dicarboxaldehyde (643-79-8) → Lacidipine (103890-78-4)

Guidance literature:

(tert-butoxycarbonylmethyl)triphenylphosphonium bromide; o-phthalic dicarboxaldehyde; With sodium hydroxide; In dichloromethane; water; at -5 - -3 ℃; for 2.75h; Industry scale;

ethyl 3-aminobut-2-enoate; With trifluoroacetic acid; In isopropyl alcohol; at -7 ℃; for 2.75h;

With sodium hydrogencarbonate; In water; ethyl acetate; isopropyl alcohol; at 0 - 25 ℃; for 0.333333h;

upstream raw materials:

(E)-3-(2-formylphenyl)-2-propenoic acid 1,1-dimethylethylester

sodium hydrogencarbonate

ethyl 3-aminobut-2-enoate

(tert-butoxycarbonylmethyl)triphenylphosphonium bromide

Downstream raw materials:

(E)-3-(2-(3,5-bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridin-4-yl)phenyl)acrylic acid

diethyl (E)-4-<2-<3-(1,1-dimethylethoxy)-3-oxoprop-1-enyl>phenyl>-2,6-dimethylpyridine-3,5-dicarboxylate

Refernces

• 1、 -. "Lacidipine compound and preparation method thereof". Paragraph 0016. . Retrieved 2017/07/20.
• 2、 -. "ANTIHYPERTENSIVE THERAPY". . . Retrieved 2009/09/08.