Find Prucalopride (USAN/INN) manufacturers, exporters & distributors on PharmaCompass

DSSTox_CID_31459

DSSTox_CID_31459

Synopsis, Chemistry

DOSSIERs // Finished Dosage Formulations

4 Dossiers, 2 Europe, 2 Listed Dossiers

GLOBAL SALES INFORMATION

1 US Medicaid Prescriptions

1 US Medicaid Prescriptions

Product Search

API SUPPLIERS

API Suppliers

US DMFs Filed

CEP/COS Certifications

JDMFs Filed

Other Certificates

Other Suppliers

API REF. PRICE (USD / KG)

API Market Place

INTERMEDIATES

DOSSIERS // FDF

USA (Orange Book)

Europe

Canada

Australia

South Africa

Uploaded Dossiers

GLOBAL SALES (USD Million)

U.S. Medicaid

33.00

Annual Reports

FDF Market Place

EXCIPIENTS

PATENTS & EXCLUSIVITIES

USFDA Orange Book Patents

USFDA Exclusivities

DIGITAL CONTENT

Blog #PharmaFlow

News

REF STANDARD

EDQM

USP

Other Listed Suppliers

SERVICES

Also known as: 179474-81-8, Motegrity, R093877, 4-amino-5-chloro-2,3-dihydro-n-[1-(3-methoxypropyl)-4-piperidinyl]-7-benzofurancarboxamide, 4-amino-5-chloro-n-[1-(3-methoxypropyl)piperidin-4-yl]-2,3-dihydro-1-benzofuran-7-carboxamide, 4-amino-5-chloro-n-(1-(3-methoxypropyl)piperidin-4-yl)-2,3-dihydrobenzofuran-7-carboxamide

Molecular Formula

C₁₈H₂₆ClN₃O₃

Molecular Weight

367.9 g/mol

InChI Key

ZPMNHBXQOOVQJL-UHFFFAOYSA-N

FDA UNII

0A09IUW5TP

Prucalopride is a dihydrobenzofurancarboxamide derivative from the benzofurane family that selectively stimulates 5-HT4 receptors and thus, it presents enterokinetic properties. The high selectivity of prucalopride allowed further development as it prevented the cardiac adverse reactions observed due to non-target effects of precedent therapies. Prucalopride was developed by Shire Development LLC and approved for use in Europe in 2009, in Canada on December 7, 2011 and by the FDA on December 17, 2018.

Prucalopride is a Serotonin-4 Receptor Agonist. The mechanism of action of prucalopride is as a Serotonin 4 Receptor Agonist.

2 Identification

2.1 Computed Descriptors

2.1.1 IUPAC Name

4-amino-5-chloro-N-[1-(3-methoxypropyl)piperidin-4-yl]-2,3-dihydro-1-benzofuran-7-carboxamide

2.1.2 InChI

InChI=1S/C18H26ClN3O3/c1-24-9-2-6-22-7-3-12(4-8-22)21-18(23)14-11-15(19)16(20)13-5-10-25-17(13)14/h11-12H,2-10,20H2,1H3,(H,21,23)

2.1.3 InChI Key

ZPMNHBXQOOVQJL-UHFFFAOYSA-N

2.1.4 Canonical SMILES

COCCCN1CCC(CC1)NC(=O)C2=CC(=C(C3=C2OCC3)N)Cl

2.2 Other Identifiers

2.2.1 UNII

0A09IUW5TP

2.3 Synonyms

2.3.1 MeSH Synonyms

1. 4-amino-5-chloro-n-(1-(3-methoxypropyl)-4-piperidinyl)-2,3-dihydro-1-benzofuran-7-carboxamide

2. Motegrity

3. R 093877

4. R093877

5. Resolor

6. Resotran

7. Resotrans

2.3.2 Depositor-Supplied Synonyms

1. 179474-81-8

2. Motegrity

3. R093877

4. 4-amino-5-chloro-2,3-dihydro-n-[1-(3-methoxypropyl)-4-piperidinyl]-7-benzofurancarboxamide

5. 4-amino-5-chloro-n-[1-(3-methoxypropyl)piperidin-4-yl]-2,3-dihydro-1-benzofuran-7-carboxamide

6. 4-amino-5-chloro-n-(1-(3-methoxypropyl)piperidin-4-yl)-2,3-dihydrobenzofuran-7-carboxamide

7. R-093877

8. 0a09iuw5tp

9. Chembl117287

10. 179474-81-8 (free Base)

11. Resotrans

12. Unii-0a09iuw5tp

13. R-93877

14. Prucalopride [usan:inn:ban]

15. Prucalopride [mi]

16. Prucalopride (usan/inn)

17. Prucalopride [inn]

18. Prucalopride [usan]

19. Dsstox_cid_31459

20. Dsstox_rid_97345

21. Dsstox_gsid_57670

22. Schembl16952

23. Gtpl243

24. Prucalopride [mart.]

25. Prucalopride [who-dd]

26. Prucalopride [ema Epar]

27. Dtxsid5057670

28. Chebi:135552

29. Bcpp000099

30. Hms3651f04

31. Hms3748m09

32. Hms3884p20

33. Bcp02177

34. Ex-a1333

35. Zinc1891034

36. Tox21_113885

37. Bdbm50122872

38. Mfcd09837787

39. S2875

40. Akos015951096

41. Am84628

42. Ccg-268257

43. Db06480

44. Pb31402

45. 4-amino-5-chloro-2,3-dihydro-n-(1-(3-methoxypropyl)-4-piperidyl)-7-benzofurancarboxamide

46. Ncgc00253867-01

47. Ncgc00253867-02

48. 4-amino-5-chloro-n-(1-(3-methoxypropyl)-4-piperidinyl)-2,3-dihydro-1-benzofuran-7-carboxamide

49. Ac-23945

50. As-19549

51. Hy-14151

52. Cas-179474-81-8

53. Ft-0674128

54. P2467

55. Sw219198-2

56. A25458

57. D09205

58. Q68484

59. 474p818

60. L000891

61. Sr-01000945275

62. Sr-01000945275-1

63. 4-amino-5+k445-chloro-2,3-dihydro-benzofuran-7-carboxylic Acid [1-(3-methoxy-propyl)-piperidin-4-yl]-amide

64. 4-amino-5-chloro-2,3-dihydro-benzofuran-7-carboxylic Acid [1-(3-methoxy-propyl)-piperidin-4-yl]-amide

65. 7-benzofurancarboxamide, 4-amino-5-chloro-2,3-dihydro-n-[1-(3-methoxypropyl)-4-piperidinyl]-

2.4 Create Date

2005-08-09

3 Chemical and Physical Properties

Molecular Formula	C₁₈H₂₆ClN₃O₃
Molecular Weight	367.9 g/mol
XLogP3	2
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	6
Exact Mass	367.1662694 g/mol
Monoisotopic Mass	367.1662694 g/mol
Topological Polar Surface Area	76.8 Å²
Heavy Atom Count	25
Formal Charge	0
Complexity	445
Isotope Atom Count	0
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Covalently Bonded Unit Count	1

4 Drug and Medication Information

4.1 Drug Indication

Prucalopride is indicated for the treatment of chronic idiopathic constipation (CIC) in adults. CIC is one of the most common chronic functional gastrointestinal disorders worldwide. The diagnosis of this agent is very hard and it can be confirmed if the patient experience at least two of the following: -Straining during more than 25% of the bowel movements. -Lumpy or hard stools in 25% of the bowel movements. -Sensation of incomplete evacuation in more than 25% of all bowel movements. -Sensation of anorectal blockage or obstruction in more than 25% of the bowel movements. -Manual maneuvers required in more than 25% of the bowel movements. -Fewer than 3 bowel movements per week.

FDA Label

Resolor is indicated for symptomatic treatment of chronic constipation in adults in whom laxatives fail to provide adequate relief.

5 Pharmacology and Biochemistry

5.1 Pharmacology

In animal studies, prucalopride induced a dose-dependent stimulation of contractile activity in the proximal colon and inhibition of the contractility in the distal colon. As well it has been shown that prucalopride stimulates and amplifies giant migratory contraction which is the high-amplitude type of contraction that initiates the urge to defecate. Thus, prucalopride not only accelerates the colonic transit but also accelerates gastric emptying and small bowel transit. In supratherapeutic concentrations, prucalopride can be observed to interact with hERG potassium channels and L-type calcium channels. In clinical trials, prucalopride showed to significantly increase the spontaneous bowel movements with a standardized mean difference of about 0.5 after the use of 1 mg when compared with the placebo group. In this studies as well, it was observed a numerical improvement in mean colonic transit time and a significant increase in spontaneous complete bowel movement without marked changes in the anorectal function. In phase III clinical trials, 86% of the tested individuals opted to continue with the open-label study and based on Patients Assessments, 67% of the patients increase more than one point improvement in their satisfaction. In the final set of clinical trials for approval, there was a significant increase in the number of patients that reached over 3 complete spontaneous bowel movements per week when compared with the placebo.

5.2 MeSH Pharmacological Classification

Laxatives

Agents that produce a soft formed stool, and relax and loosen the bowels, typically used over a protracted period, to relieve CONSTIPATION. (See all compounds classified as Laxatives.)

Serotonin 5-HT4 Receptor Agonists

Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT4 RECEPTORS. (See all compounds classified as Serotonin 5-HT4 Receptor Agonists.)

5.3 FDA Pharmacological Classification

5.3.1 Active Moiety

PRUCALOPRIDE

5.3.2 FDA UNII

0A09IUW5TP

5.3.3 Pharmacological Classes

Serotonin-4 Receptor Agonist [EPC]; Serotonin 4 Receptor Agonists [MoA]

5.4 ATC Code

A06AX05

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355

A - Alimentary tract and metabolism

A06 - Drugs for constipation

A06A - Drugs for constipation

A06AX - Other drugs for constipation

A06AX05 - Prucalopride

5.5 Absorption, Distribution and Excretion

Absorption

Prucalopride is well absorbed and it reaches maximum plasma concentration of 3.79ng/ml with a tmax of 2.77 hours after initial administration. It presents an AUC of 96.5 mn.h/ml. The bioavailability of prucalopride is of over 90% and this bioavailability does not get influenced by the ingestion of food.

Route of Elimination

After maximum plasma concentration, prucalopride concentration decline in a biphasic manner. Prucalopride is mainly excreted by the urine, representing 84% of the administered dose while only 13% of the dose is recovered in feces.

Volume of Distribution

The mean volume of distribution of prucalopride is registered to be 623 L.

Clearance

Prucalopride renal clearance is reported to be of 17 L/h which actually exceeds the glomerular filtration rate of the kidney.

5.6 Metabolism/Metabolites

Prucalopride is not extensively metabolized in the body and does not interact with the enzymes of the family of the cytochrome P450 enzymes nor the P glycoprotein. The metabolism of prucalopride only represents 6% of the administered dose and the remaining 94% is found as the unchanged drug. From studies, it was reported the recovery of 8 metabolites being the major metabolite R107504 which is formed after the O-demethylation and oxidation of the resulting alcohol to a carboxylic acid.

5.7 Biological Half-Life

The reported half-life of prucalopride is of around 18-20 hours.

5.8 Mechanism of Action

Prucalopride acts as a selective stimulator of the 5-HT4 receptors while having no interaction with hERG channel or 5-HT1 receptors which reduces significantly the cardiovascular risk found in other similar drugs. 5-HT4 receptors can be found throughout the gastrointestinal tract primarily in smooth muscle cells, enterochromaffin cells, and myenteric plexus. Its activation produces the release of acetylcholine which is the major excitatory neurotransmitter in the GI tract. Hence, prucalopride stimulates motility by interacting specifically with 5-HT4 receptors in the GI tract which causes a release of acetylcholine and further contraction of the muscle layer of the colon and relaxation of the circular muscle layer leading to the propulsion of luminal content.