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Details

Stereochemistry ABSOLUTE
Molecular Formula C19H24N6O2
Molecular Weight 368.4336
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BMS-690514

SMILES

COc1cccc(c1)N=c2c3c(ccn3[nH]cn2)CN4CC[C@]([H])([C@@]([H])(C4)O)N

InChI

InChIKey=CSGQVNMSRKWUSH-IAGOWNOFSA-N
InChI=1S/C19H24N6O2/c1-27-15-4-2-3-14(9-15)23-19-18-13(5-8-25(18)22-12-21-19)10-24-7-6-16(20)17(26)11-24/h2-5,8-9,12,16-17,26H,6-7,10-11,20H2,1H3,(H,21,22,23)/t16-,17-/m1/s1

HIDE SMILES / InChI

Molecular Formula C19H24N6O2
Molecular Weight 368.4336
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800025400 https://www.ncbi.nlm.nih.gov/pubmed/23490650

BMS-690514 is a potent, reversible oral inhibitor of epidermal growth factor receptor (EGFR/HER-1), HER-2 and -4, and vascular endothelial growth factor receptors (VEGFRs)-1 to -3 offering targeted inhibition of tumour growth and vascularisation in a single agent. Bristol-Myers Squibb was developing BMS 690514, as an oral treatment for cancer. BMS-690514 had being in phase II for the treatment of breast cancer; non-small cell lung cancer, but later these studies were discontinued.

CNS Activity

Curator's Comment:: BMS-690514 was able to cross the blood-brain barrier with a brain-to-plasma ratio of approximately 1.

Originator

Curator's Comment:: # Bristol-Myers Squibb

Approval Year

OverviewDrug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major [Km ~1 uM]
no (pharmacogenomic study)
Comment: No clinically relevant differences between poor and extensive metabolizers
major [Km ~23 uM]
yes (co-administration study)
Comment: Ketoconazole increased dose-normalized Cmax and AUCinf by 55% and 127%.
major
no
no
no
no
no
no
no
no
no
no
no
no
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
yes
yes
yes
yes (co-administration study)
Comment: Ketoconazole increased dose-normalized Cmax and AUCinf by 55% and 127%.
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
A novel epidermal growth factor receptor inhibitor promotes apoptosis in non-small cell lung cancer cells resistant to erlotinib.
2007 Jul 1
Preclinical pharmacokinetics and in vitro metabolism of BMS-690514, a potent inhibitor of EGFR and VEGFR2.
2010 Aug
Mechanistic studies on a P450-mediated rearrangement of BMS-690514: conversion of a pyrrolotriazine to a hydroxypyridotriazine.
2011 Jan 14
Patents

Sample Use Guides

Tablets, Oral, 200 mg, once daily,
Route of Administration: Oral
Non–small cell lung tumor cells with exon 19 deletion (HCC4006, HCC827, and PC9) were highly sensitive to BMS-690514, which inhibits their proliferation with IC50 values of 2 to 35 nmol/L. Breast and gastric tumor cell lines that have HER2 gene amplification (N87, SNU-216, AU565, BT474, KPL4, and HCC202) were inhibited with IC50 values of 20 to 60 nmol/L
Substance Class Chemical
Created
by admin
on Sat Jun 26 14:46:14 UTC 2021
Edited
by admin
on Sat Jun 26 14:46:14 UTC 2021
Record UNII
VKU5X213Q7
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BMS-690514
Common Name English
3-PIPERIDINOL, 4-AMINO-1-((4-((3-METHOXYPHENYL)AMINO)PYRROLO(2,1-F)(1,2,4)TRIAZIN-5-YL)METHYL)-, (3R,4R)-
Systematic Name English
BMS 690514
Common Name English
BMS 6690514
Common Name English
(3R,4R)-4-AMINO-1-((4-((3-METHOXYPHENYL)AMINO)PYRROLO(2,1-F)(1,2,4)TRIAZIN-5-YL)METHYL)-3-PIPERIDINOL
Systematic Name English
BMS 690514 [WHO-DD]
Common Name English
Code System Code Type Description
PUBCHEM
11349170
Created by admin on Sat Jun 26 14:46:15 UTC 2021 , Edited by admin on Sat Jun 26 14:46:15 UTC 2021
PRIMARY
CAS
859853-30-8
Created by admin on Sat Jun 26 14:46:15 UTC 2021 , Edited by admin on Sat Jun 26 14:46:15 UTC 2021
PRIMARY
DRUG BANK
DB11665
Created by admin on Sat Jun 26 14:46:15 UTC 2021 , Edited by admin on Sat Jun 26 14:46:15 UTC 2021
PRIMARY
FDA UNII
VKU5X213Q7
Created by admin on Sat Jun 26 14:46:15 UTC 2021 , Edited by admin on Sat Jun 26 14:46:15 UTC 2021
PRIMARY
ChEMBL
CHEMBL3545396
Created by admin on Sat Jun 26 14:46:15 UTC 2021 , Edited by admin on Sat Jun 26 14:46:15 UTC 2021
PRIMARY
EVMPD
SUB194073
Created by admin on Sat Jun 26 14:46:15 UTC 2021 , Edited by admin on Sat Jun 26 14:46:15 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
TARGET -> INHIBITOR
TRANSPORTER -> SUBSTRATE
TARGET -> INHIBITOR
IC50
TARGET -> INHIBITOR
IC50
EXCRETED UNCHANGED
AMOUNT EXCRETED
FECAL
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC SINGLE DOSE

ORAL ADMINISTRATION

Tmax PHARMACOKINETIC SINGLE DOSE

ORAL ADMINISTRATION