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Details

Stereochemistry ABSOLUTE
Molecular Formula C18H24N4O5
Molecular Weight 376.407
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RO-44-3888

SMILES

C[C@H](NC(=O)C1=CC=C(C=C1)C(N)=N)C(=O)N2CCC(CC2)OCC(O)=O

InChI

InChIKey=BHOGTSLQMNCJHA-NSHDSACASA-N
InChI=1S/C18H24N4O5/c1-11(21-17(25)13-4-2-12(3-5-13)16(19)20)18(26)22-8-6-14(7-9-22)27-10-15(23)24/h2-5,11,14H,6-10H2,1H3,(H3,19,20)(H,21,25)(H,23,24)/t11-/m0/s1

HIDE SMILES / InChI

Molecular Formula C18H24N4O5
Molecular Weight 376.407
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Sibrafiban (G-7453) is the orally administered, nonpeptide, double-prodrug of Ro 44-3888 which is a selective glycoprotein IIb/IIIa receptor antagonist. Sibrafiban is a double prodrug that undergoes bioconversion to the inactive prodrug Ro 48-3656 and to the active IIb/IIIa antagonist, Ro 44-3888, after oral administration. Sibrafiban was undergoing clinical trials for secondary prevention of cardiac events in patients stabilised after acute coronary syndromes. Sibrafiban has been shown to have comparable efficacy to aspirin in preventing recurrent ischemic events in patients suffering from acute coronary syndromes. Sibrafiban was under development by Genentech and Hoffmann-La Roche, and in phase III trials as an antithrombotic. The development of sibrafiban was discontinued in 1999 following unfavorable Phase III efficacy data.

Approval Year

PubMed

PubMed

TitleDatePubMed
Sibrafiban.
1999 Feb
Sibrafiban (Genentech).
1999 May

Sample Use Guides

In Vivo Use Guide
Curator's Comment: The Thrombolysis in Myocardial Infarction (TIMI) 12 trial was a phase II, double-blind, dose-ranging trial designed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of sibrafiban in 329 patients after acute coronary syndromes. 106 patients were randomized to receive one of seven dosing regimens of sibrafiban, ranging from 5 mg daily to 10 mg twice daily for 28 days. In the safety cohort, 223 patients were randomized to one of four dose regimens of sibrafiban (ranging from 5 mg twice daily to 15 mg once daily) or aspirin for 28 days. https://www.ncbi.nlm.nih.gov/pubmed/9468207
Patients who had stabilised after an acute coronary syndrome event were randomly assigned aspirin (80 mg orally twice daily) or low-dose or high-dose sibrafiban. Sibrafiban doses (3.0 mg, 4.5 mg, or 6.0 mg) were based on a model accounting for weight and serum creatinine and designed to achieve at least 25% steady-state inhibition of platelet aggregation (low dose) or at least 50% inhibition (high dose). The primary endpoint was the composite of death, non-fatal infarction or reinfarction, or severe recurrent ischaemia at 90 days.
Route of Administration: Oral
Sibrafiban inhibited shear-induced platelet activation and adhesion with IC50 value of 43 nM.
Substance Class Chemical
Created
by admin
on Fri Jul 07 00:53:48 UTC 2023
Edited
by admin
on Fri Jul 07 00:53:48 UTC 2023
Record UNII
F23PXB8U2L
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RO-44-3888
Code English
2-[[1-[(2S)-2-[[4-(Aminoiminomethyl)benzoyl]amino]-1-oxopropyl]-4-piperidinyl]oxy]acetic acid
Systematic Name English
RO443888
Code English
Acetic acid, 2-[[1-[(2S)-2-[[4-(aminoiminomethyl)benzoyl]amino]-1-oxopropyl]-4-piperidinyl]oxy]-
Systematic Name English
Code System Code Type Description
FDA UNII
F23PXB8U2L
Created by admin on Fri Jul 07 00:53:48 UTC 2023 , Edited by admin on Fri Jul 07 00:53:48 UTC 2023
PRIMARY
CAS
144412-18-0
Created by admin on Fri Jul 07 00:53:48 UTC 2023 , Edited by admin on Fri Jul 07 00:53:48 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Related Record Type Details
PRODRUG -> METABOLITE ACTIVE
Related Record Type Details
ACTIVE MOIETY