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Chemistry

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Also known as: 103890-78-4, Lacipil, Motens, Gr-43659x, Trans lacidipine, Gr 43659x
Molecular Formula
C26H33NO6
Molecular Weight
455.5  g/mol
InChI Key
GKQPCPXONLDCMU-CCEZHUSRSA-N
FDA UNII
260080034N

Lacidipine
Lacidipine is a lipophilic dihydropyridine calcium antagonist with an intrinsically slow onset of activity. Due to its long duration of action, lacidipine does not lead to reflex tachycardia. It displays specificity in the vascular smooth muscle, where it acts as an antihypertensive agent to dilate peripheral arterioles and reduce blood pressure. Compared to other dihydropyridine calcium antagonists, lacidipine exhibits a greater antioxidant activity which may confer potentially beneficial antiatherosclerotic effects. Lacidipine is a highly lipophilic molecule that interacts with the biological membranes. Through radiotracer analysis, it was determined that lacidipine displays a high membrane partition coefficient leading to accumulation of the drug in the membrane and slow rate of membrane washout. When visualized by small-angle X-ray diffraction with angstrom resolution to examine its location within the membranes, lacidipine was found deep within the membrane's hydrocarbon core. These results may explain the long clinical half-life of lacidipine. In randomised, well-controlled trials, administration of daily single-dose lacidipine ranging from 2-6 mg demonstrated comparable antihypertensive efficacy similar to that of other long-acting dihydropyridine calcium antagonists, thiazide diuretics, atenolol (a beta-blocker) and enalapril (an ACE inhibitor). It is available as once-daily oral tablets containing 2 or 4 mg of the active compound commonly marketed as Lacipil or Motens. It is not currently FDA-approved.
1 2D Structure

Lacidipine

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
diethyl 2,6-dimethyl-4-[2-[(E)-3-[(2-methylpropan-2-yl)oxy]-3-oxoprop-1-enyl]phenyl]-1,4-dihydropyridine-3,5-dicarboxylate
2.1.2 InChI
InChI=1S/C26H33NO6/c1-8-31-24(29)21-16(3)27-17(4)22(25(30)32-9-2)23(21)19-13-11-10-12-18(19)14-15-20(28)33-26(5,6)7/h10-15,23,27H,8-9H2,1-7H3/b15-14+
2.1.3 InChI Key
GKQPCPXONLDCMU-CCEZHUSRSA-N
2.1.4 Canonical SMILES
CCOC(=O)C1=C(NC(=C(C1C2=CC=CC=C2C=CC(=O)OC(C)(C)C)C(=O)OCC)C)C
2.1.5 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
2.2 Other Identifiers
2.2.1 UNII
260080034N
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Caldine

2. Gr 43659x

3. Gr-43659x

4. Lacimen

5. Lacipil

6. Motens

2.3.2 Depositor-Supplied Synonyms

1. 103890-78-4

2. Lacipil

3. Motens

4. Gr-43659x

5. Trans Lacidipine

6. Gr 43659x

7. Lacidipine (lacipil, Motens)

8. Diethyl 2,6-dimethyl-4-[2-[(e)-3-[(2-methylpropan-2-yl)oxy]-3-oxoprop-1-enyl]phenyl]-1,4-dihydropyridine-3,5-dicarboxylate

9. Gx-1048

10. Sn-305

11. 4-(o-((e)-2-carboxyvinyl)phenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic Acid, 4-tert-butyl Diethyl Ester

12. Lacimen

13. Dsstox_cid_26429

14. Dsstox_rid_81607

15. Dsstox_gsid_46429

16. 3,5-pyridinedicarboxylic Acid, 4-(2-(3-(1,1-dimethylethoxy)-3-oxo-1-propenyl)phenyl)-1,4-dihydro-2,6-dimethyl-, Diethyl Ester, (e)-

17. Diethyl (e)-4-(2-(3-(tert-butoxy)-3-oxoprop-1-en-1-yl)phenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate

18. 260080034n

19. Lacidipinum [latin]

20. Lacidipino [spanish]

21. Lacidipino

22. Lacidipinum

23. Lacirex

24. (e)-diethyl 4-(2-(3-(tert-butoxy)-3-oxoprop-1-en-1-yl)phenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate

25. Smr000466342

26. Cas-103890-78-4

27. Sr-05000001445

28. Gr 43659 X

29. Viapres

30. Molap

31. Lacidipine [usan:inn:ban]

32. Lacidipine,(s)

33. Ncgc00164545-01

34. (e)-diethyl 4-(2-(3-tert-butoxy-3-oxoprop-1-enyl)phenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate

35. Lacidipine- Bio-x

36. Motens (tn)

37. Unii-260080034n

38. Lacidipine [mi]

39. Lacidipine [inn]

40. Lacidipine [jan]

41. Lacidipine (usan/inn)

42. Lacidipine [usan]

43. Lacidipine [vandf]

44. Lacidipine [mart.]

45. Lacidipine [who-dd]

46. Lacipil, Motens, Lacidipine

47. Schembl49277

48. Schembl49278

49. Mls000759454

50. Mls001424282

51. Chembl460291

52. Chembl1728809

53. Dtxsid1046429

54. Schembl13287288

55. Chebi:94480

56. Gtpl11740

57. Chebi:135737

58. Hms2052f03

59. Hms2089k22

60. Hms3713d20

61. Hms3884i18

62. (non-isotopelabelled)lacidipine-d9

63. Bcp02933

64. Gr43659x

65. Hy-b0347

66. Tox21_112174

67. Gx1048

68. S1994

69. Stl454986

70. Akos005066844

71. Tox21_112174_1

72. Zinc100015470

73. Bcp9000831

74. Ccg-101153

75. Ccg-220579

76. Db09236

77. Gx 1048

78. Hs-0086

79. Nc00403

80. Ncgc00263529-01

81. 3,5-pyridinedicarboxylic Acid, 1,4-dihydro-2,6-dimethyl-4-(2-(3-(1,1-dimethylethoxy)-3-oxo-1-propenyl)phenyl)-, Diethyl Ester, (e)-

82. Ac-11008

83. Ac-33195

84. Bl164603

85. Cpd000466342

86. Bcp0726000285

87. L0276

88. Sw219840-1

89. C71162

90. D04657

91. Ab00698350-05

92. Ab01275445-01

93. Ab01275445_02

94. Gx-1048,gr-43659x,sn-305

95. 890l784

96. A800840

97. J-001058

98. Q1163827

99. Sr-05000001445-1

100. Sr-05000001445-2

101. Brd-k05851096-001-01-9

102. 2,6-dimethyl-4-[2-[(e)-3-[(2-methylpropan-2-yl)oxy]-3-oxoprop-1-enyl]phenyl]-1,4-dihydropyridine-3,5-dicarboxylic Acid Diethyl Ester

103. Diethyl 2,6-dimethyl-4-[2-[(e)-3-[(2-methylpropan-2-yl)oxy]-3-oxidanylidene-prop-1-enyl]phenyl]-1,4-dihydropyridine-3,5-dicarboxylate

104. Diethyl 4-{2-[(1e)-3-tert-butoxy-3-oxoprop-1-en-1-yl]phenyl}-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate

2.4 Create Date
2005-09-13
3 Chemical and Physical Properties
Molecular Weight 455.5 g/mol
Molecular Formula C26H33NO6
XLogP34.5
Hydrogen Bond Donor Count1
Hydrogen Bond Acceptor Count7
Rotatable Bond Count11
Exact Mass455.23078777 g/mol
Monoisotopic Mass455.23078777 g/mol
Topological Polar Surface Area90.9 Ų
Heavy Atom Count33
Formal Charge0
Complexity805
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count1
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Indication

Indicated for the treatment of hypertension either alone or in combination with other antihypertensive agents, including -adrenoceptor antagonists, diuretics, and ACE-inhibitors.


5 Pharmacology and Biochemistry
5.1 Pharmacology

acidipine is a specific and potent calcium antagonist with a predominant selectivity for calcium channels in the vascular smooth muscle. Its main action is to dilate predominantly peripheral and coronary arteries, reducing peripheral vascular resistance and lowering blood pressure. Following the oral administration of 4 mg lacidipine to volunteer subjects, a minimal prolongation of QTc interval has been observed (mean QTcF increase between 3.44 and 9.60 ms in young and elderly volunteers).


5.2 MeSH Pharmacological Classification

Antihypertensive Agents

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)


Calcium Channel Blockers

A class of drugs that act by selective inhibition of calcium influx through cellular membranes. (See all compounds classified as Calcium Channel Blockers.)


5.3 ATC Code

C - Cardiovascular system

C08 - Calcium channel blockers

C08C - Selective calcium channel blockers with mainly vascular effects

C08CA - Dihydropyridine derivatives

C08CA09 - Lacidipine


5.4 Absorption, Distribution and Excretion

Absorption

Since it is a highly lipophilic compound, lacidpine is rapidly absorbed from the gastrointestinal tract following oral administration with the peak plasma concentrations reached between 30 and 150 minutes of dosing. The peak plasma concentrations display large interindividual variability, with the values ranging from 1.6 to 5.7 g/L following single-dose oral administration of lacidipine 4mg in healthy young volunteers. Absolute bioavailability is less than 10% due to extensive first-pass metabolism in the liver.


Route of Elimination

Approximately 70% of the administered dose is eliminated as metabolites in the faeces and the remainder as metabolites in the urine.


5.5 Metabolism/Metabolites

Lacidipine undergoes complete CYP3A4-mediated hepatic metabolism, with no parent drug detected in the urine or faeces. The 2 main metabolites have no pharmacological activity.


5.6 Biological Half-Life

The average terminal half-life of lacidipine ranges from between 13 and 19 hours at steady state.


5.7 Mechanism of Action

By blocking the voltage-dependent L-type calcium channels, it prevents the transmembrane calcium influx. Normally, calcium ions serve as intracellular messengers or activators in exictable cells including vascular smooth muscles. The influx of calcium ultimately causes the excitation and depolarization of the tissues. Lacidipine inhibits the contractile function in the vascular smooth muscle and reduce blood pressure. Due to its high membrane partition coefficient, some studies suggest that lacidipine may reach the receptor via a two-step process; it first binds and accumulates in the membrane lipid bilayer and then diffuses within the membrane to the calcium channel receptor. It is proposed that lacidipine preferentially blocks the inactivated state of the calcium channel. Through its antioxidant properties shared amongst other dihydropyridine calcium channel blockers, lacidipine demonstrates an additional clinical benefit. Its antiatherosclerotic effects are mediated by suppressing the formation of reactive oxygen species (ROS) and subsequent inflammatory actions by chemokines, cytokines and adhesion molecules, thus reducing atherosclerotic lesion formation. Lacidipine may also suppress cell proliferation and migration in smooth muscle cells and suppress the expression of matrix metalloproteinases, which affects the stability of atheromatous plaques.


API Reference Price

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ABOUT THIS PAGE

Lacidipine Manufacturers

A Lacidipine manufacturer is defined as any person or entity involved in the manufacture, preparation, processing, compounding or propagation of Lacidipine, including repackagers and relabelers. The FDA regulates Lacidipine manufacturers to ensure that their products comply with relevant laws and regulations and are safe and effective to use. Lacidipine API Manufacturers are required to adhere to Good Manufacturing Practices (GMP) to ensure that their products are consistently manufactured to meet established quality criteria.

click here to find a list of Lacidipine manufacturers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PhamaCompass.

Lacidipine Suppliers

A Lacidipine supplier is an individual or a company that provides Lacidipine active pharmaceutical ingredient (API) or Lacidipine finished formulations upon request. The Lacidipine suppliers may include Lacidipine API manufacturers, exporters, distributors and traders.

click here to find a list of Lacidipine suppliers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PharmaCompass.

Lacidipine USDMF

A Lacidipine DMF (Drug Master File) is a document detailing the whole manufacturing process of Lacidipine active pharmaceutical ingredient (API) in detail. Different forms of Lacidipine DMFs exist exist since differing nations have different regulations, such as Lacidipine USDMF, ASMF (EDMF), JDMF, CDMF, etc.

A Lacidipine DMF submitted to regulatory agencies in the US is known as a USDMF. Lacidipine USDMF includes data on Lacidipine's chemical properties, information on the facilities and procedures used, and details about packaging and storage. The Lacidipine USDMF is kept confidential to protect the manufacturer’s intellectual property.

click here to find a list of Lacidipine suppliers with USDMF on PharmaCompass.

Lacidipine KDMF

In Korea, the Ministry of Food and Drug Safety (MFDS) is in charge of regulating pharmaceutical products and services.

Pharmaceutical companies submit a Lacidipine Drug Master File in Korea (Lacidipine KDMF) to the MFDS, which includes comprehensive information about the production, processing, facilities, materials, packaging, and testing of Lacidipine. The MFDS reviews the Lacidipine KDMF as part of the drug registration process and uses the information provided in the Lacidipine KDMF to evaluate the safety and efficacy of the drug.

After submitting a Lacidipine KDMF to the MFDS, the registered manufacturer can provide importers or distributors with the registration number without revealing confidential information to Korean business partners. Applicants seeking to register their Lacidipine API can apply through the Korea Drug Master File (KDMF).

click here to find a list of Lacidipine suppliers with KDMF on PharmaCompass.

Lacidipine WC

A Lacidipine written confirmation (Lacidipine WC) is an official document issued by a regulatory agency to a Lacidipine manufacturer, verifying that the manufacturing facility of a Lacidipine active pharmaceutical ingredient (API) adheres to the Good Manufacturing Practices (GMP) regulations of the importing country. When exporting Lacidipine APIs or Lacidipine finished pharmaceutical products to another nation, regulatory agencies frequently require a Lacidipine WC (written confirmation) as part of the regulatory process.

click here to find a list of Lacidipine suppliers with Written Confirmation (WC) on PharmaCompass.

Lacidipine NDC

National Drug Code is a comprehensive database maintained by the FDA that contains information on all drugs marketed in the US. This directory includes information about finished drug products, unfinished drug products, and compounded drug products, including those containing Lacidipine as an active pharmaceutical ingredient (API).

Finished drug products

The FDA updates the NDC directory daily. The NDC numbers for Lacidipine API and other APIs are published in this directory by the FDA.

Unfinished drugs

The NDC unfinished drugs database includes product listing information submitted for all unfinished drugs, such as active pharmaceutical ingredients (APIs), drugs intended for further processing and bulk drug substances for compounding.

Pharmaceutical companies that manufacture Lacidipine as an active pharmaceutical ingredient (API) must furnish the FDA with an updated record of all drugs that they produce, prepare, propagate, compound, or process for commercial distribution in the US at their facilities.

Compounded drug products

The NDC directory also contains data on finished compounded human drug products that contain Lacidipine and are produced by outsourcing facilities. While these outsourcing facilities are not mandated to assign a Lacidipine NDC to their finished compounded human drug products, they may choose to do so.

click here to find a list of Lacidipine suppliers with NDC on PharmaCompass.

Lacidipine GMP

Lacidipine Active pharmaceutical ingredient (API) is produced in GMP-certified manufacturing facility.

GMP stands for Good Manufacturing Practices, which is a system used in the pharmaceutical industry to make sure that goods are regularly produced and monitored in accordance with quality standards. The FDA’s current Good Manufacturing Practices requirements are referred to as cGMP or current GMP which indicates that the company follows the most recent GMP specifications. The World Health Organization (WHO) has its own set of GMP guidelines, called the WHO GMP. Different countries can also set their own guidelines for GMP like China (Chinese GMP) or the EU (EU GMP).

PharmaCompass offers a list of Lacidipine GMP manufacturers, exporters & distributors, which can be sorted by USDMF, JDMF, KDMF, CEP (COS), WC, API price, and more, enabling you to easily find the right Lacidipine GMP manufacturer or Lacidipine GMP API supplier for your needs.

Lacidipine CoA

A Lacidipine CoA (Certificate of Analysis) is a formal document that attests to Lacidipine's compliance with Lacidipine specifications and serves as a tool for batch-level quality control.

Lacidipine CoA mostly includes findings from lab analyses of a specific batch. For each Lacidipine CoA document that a company creates, the USFDA specifies specific requirements, such as supplier information, material identification, transportation data, evidence of conformity and signature data.

Lacidipine may be tested according to a variety of international standards, such as European Pharmacopoeia (Lacidipine EP), Lacidipine JP (Japanese Pharmacopeia) and the US Pharmacopoeia (Lacidipine USP).

Inform the supplier about your product requirements, specifying if you need a product with particular monograph like EP (Ph. Eur.), USP, JP, BP, or any other quality. In addition, clarify whether you need hydrochloride (HCl), anhydricum, base, micronisatum or a specific level of purity. To find reputable suppliers, utilize the filters and select those certified by GMP, FDA, or any other certification as per your requirement.
For your convenience, we have listed synonyms and CAS numbers to help you find the best supplier. The use of synonyms and CAS numbers can be helpful in identifying potential suppliers, but it is crucial to note that they might not always indicate the exact same product. It is important to confirm the product details with the supplier before making a purchase to ensure that it meets your requirements.
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