LEFRADAFIBAN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H25N3O6
Molecular Weight	439.4611
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC(=O)C[C@@H]1C[C@@H](COC2=CC=C(C=C2)C3=CC=C(C=C3)C(=N)NC(=O)OC)NC1=O

InChI

InChIKey=PGCFXITVMNNKON-ROUUACIJSA-N

InChI=1S/C23H25N3O6/c1-30-20(27)12-17-11-18(25-22(17)28)13-32-19-9-7-15(8-10-19)14-3-5-16(6-4-14)21(24)26-23(29)31-2/h3-10,17-18H,11-13H2,1-2H3,(H,25,28)(H2,24,26,29)/t17-,18-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C23H25N3O6
Molecular Weight	439.4611
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://adisinsight.springer.com/drugs/800005284 | https://www.ncbi.nlm.nih.gov/pubmed/11250974https://www.ncbi.nlm.nih.gov/pubmed/9825033
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB04863 | https://clinicaltrials.gov/ct2/show/NCT02264119 | https://www.ncbi.nlm.nih.gov/pubmed/11154975 | https://www.ncbi.nlm.nih.gov/pubmed/11250974

Lefradafiban, an orally active prodrug of fradafiban, is a novel glycoprotein (IIb/IIIa) inhibitor for the treatment of unstable angina. The pharmacokinetic and pharmacodynamic properties of lefradafiban were assessed in 130 healthy male volunteers who received a single dose of 10, 50, 75, 100, or 150 mg or multiple doses of 25, 50, 60, 75, 90, or 100 mg three times daily for one week. After both single and multiple doses, receptor occupancy and plasma lefradafiban levels correlated with platelet aggregation. Lefradafiban had been in phase II clinical trials by Boehringer Ingelheim for the treatment of thrombosis. However, it has been terminated.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Integrin alpha-IIb/beta-3 14 Target ID: CHEMBL2093869 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10544919	Antagonist 2778
Integrin alpha-IIb/beta-3 14 Target ID: CHEMBL2093869 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9286940	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unstable angina 6 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11102255	Primary		Phase II 1132	Unknown Approved Use Unknown
Myocardial infarction 121 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11102255	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
158 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11250974	30 mg 3 times / day steady-state, oral dose: 30 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FRADAFIBAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
314 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11250974	45 mg 3 times / day steady-state, oral dose: 45 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FRADAFIBAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
394 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11250974	60 mg 3 times / day steady-state, oral dose: 60 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FRADAFIBAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	Esterases 3 CYPs 33

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYPs 33	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9286940/	no
Esterases 3	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9286940/	yes

Sourcing

Vendor/Aggregator	ID	URL
MuseChem	M100481	https://www.musechem.com/product/M100481.html

PubMed

Title	Date	PubMed
Profound and sustained inhibition of platelet aggregation by Fradafiban, a nonpeptide platelet glycoprotein IIb/IIIa antagonist, and its orally active prodrug, Lefradafiban, in men.	1997 Aug 19	9286940
Fradafiban. BIBU 52, BIBU 52 ZW.	1999 May	10566068
Pharmacodynamics and safety of lefradafiban, an oral platelet glycoprotein IIb/IIIa receptor antagonist, in patients with stable coronary artery disease undergoing elective angioplasty.	2001 Apr	11250974
Clinical trials with glycoprotein IIb/IIIa antagonists - No benefit without bleeding?	2001 Aug	12743636

Patents

Sample Use Guides

In Vivo Use Guide

20, 30 and 45 mg t.i.d. of lefradafiban were used in phase II dose-escalation trial

Route of Administration: Oral

In Vitro Use Guide

One to 15 mg Fradafiban continuously infused over 30 minutes reversibly inhibited platelet aggregation in platelet-rich plasma ex vivo in response to 20 μmol/L ADP (5 mg, 100% inhibition at 27 minutes after administration) and to both 1.0 (5 mg, 100%) and 10 μg/mL (15 mg, 97±3%) collagen.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:20:47 GMT 2023` Edited by `admin` on `Sat Dec 16 17:20:47 GMT 2023`
Record UNII	0R4888YXR5
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LEFRADAFIBAN

Official Name

English

lefradafiban [INN]

Common Name

English

(3S,5S)-5-(((4'-(CARBOXYAMIDINO)-4-BIPHENYLYL)OXY)METHYL)-2-OXO-3-PYRROLIDINEACETIC ACID, DIMETHYL ESTER

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1327