AMELUBANT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C33H34N2O5
Molecular Weight	538.6335
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC(=O)NC(=N)C1=CC=C(OCC2=CC=CC(COC3=CC=C(C=C3)C(C)(C)C4=CC=C(O)C=C4)=C2)C=C1

InChI

InChIKey=SBVYURPQULDJTI-UHFFFAOYSA-N

InChI=1S/C33H34N2O5/c1-4-38-32(37)35-31(34)25-8-16-29(17-9-25)39-21-23-6-5-7-24(20-23)22-40-30-18-12-27(13-19-30)33(2,3)26-10-14-28(36)15-11-26/h5-20,36H,4,21-22H2,1-3H3,(H2,34,35,37)

HIDE SMILES / InChI

Molecular Formula	C33H34N2O5
Molecular Weight	538.6335
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11259574
Curator's Comment: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/24440167 | https://www.ncbi.nlm.nih.gov/pubmed/17170051 | http://adisinsight.springer.com/drugs/800015866 | http://www.ema.europa.eu/docs/en_GB/document_library/Orphan_designation/2009/10/WC500005934.pdf

Amelubant, its metabolite BIIL 260 (formed by removal of the ethoxycarbonyl protecting group), and its major metabolite BIIL 315 (formed by removal of the protecting group and glucuronidation) had potent in vitro and in vivo Leukotriene B4 receptor antagonistic properties. Amelubant has been in phase II clinical trials by Boehringer Ingelheim for the treatment of cystic fibrosis, chronic obstructive pulmonay disease, bronchial asthma and rheumatoid arthritis. However, this research has been discontinued. In 2002, orphan drug designation was received in E.U. for the treatment of cystic fibrosis. Serious adverse events of Amelubant were characterized by increased presentation of respiratory signs and/or symptoms associated with pulmonary exacerbation and resulted in admission to a hospital and/or administration of IV antibiotics.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Leukotriene B4 receptor 1 4 Target ID: CHEMBL3911 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11259574	Antagonist 2778		1.7 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Rheumatoid arthritis 316 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17170051 https://www.ncbi.nlm.nih.gov/pubmed/14722206	Primary	Phase II 1132	Unknown Approved Use Unknown
Cystic fibrosis 120 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24440167	Primary	Phase II 1132	Unknown Approved Use Unknown
Chronic obstructive pulmonary disease 174 Sources: https://www.pharmacodia.com/yaodu/html/v1/chemicals/f4b27d5d47e27996af75486f6045a8a6.html https://clinicaltrials.gov/ct2/show/NCT02249338	Primary	Phase II 1132	Unknown Approved Use Unknown
Asthma 241 Sources: https://www.pharmacodia.com/yaodu/html/v1/chemicals/f4b27d5d47e27996af75486f6045a8a6.html	Primary	Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	Esterases 3

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
Esterases 3	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11259574/	yes

Sourcing

Vendor/Aggregator	ID	URL
MuseChem	I001989	https://www.musechem.com/product/I001989.html

PubMed

Title	Date	PubMed
Clinical trial of a leucotriene B4 receptor antagonist, BIIL 284, in patients with rheumatoid arthritis.	2007 May	17170051
A randomized double blind, placebo controlled phase 2 trial of BIIL 284 BS (an LTB4 receptor antagonist) for the treatment of lung disease in children and adults with cystic fibrosis.	2014 Mar	24440167
BIIL 284 reduces neutrophil numbers but increases P. aeruginosa bacteremia and inflammation in mouse lungs.	2014 Mar	24183915

Patents

Sample Use Guides

In Vivo Use Guide

75, 150 mg once daily for 24 weeks

Route of Administration: Oral

In Vitro Use Guide

Ubiquitous esterases metabolize Amelubant to the active metabolites BIIL 260 and BIIL 315. BIIL 260 and its glucuronide BIIL 315 inhibited LTB4-induced intracellular Ca2+ release in human neutrophils with IC50 values of 0.82 and 0.75 nM/L, respectively.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 16:21:24 GMT 2023` Edited by `admin` on `Sat Dec 16 16:21:24 GMT 2023`
Record UNII	E0018IF0K4
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AMELUBANT

Official Name

English

BIIL-284BS

Code

English

amelubant [INN]

Common Name

English

BIIL-284

Code

English

BIIL284 BS

Code

English

ETHYL ((4-((3-((4-(1-(4-HYDROXYPHENYL)-1-METHYLETHYL)PHENOXY)METHYL)BENZYL)OXY)PHENYL)(IMINO)METHYL)CARBAMATE

Systematic Name

English

LS-49968

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

148601