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172732-68-2 molecular structure
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2-{[1-benzyl-3-(carbamoylcarbonyl)-2-ethyl-1H-indol-4-yl]oxy}acetic acid

ChemBase ID: 72518
Molecular Formular: C21H20N2O5
Molecular Mass: 380.3939
Monoisotopic Mass: 380.13722175
SMILES and InChIs

SMILES:
c1(n(c2c(c1C(=O)C(=O)N)c(ccc2)OCC(=O)O)Cc1ccccc1)CC
Canonical SMILES:
CCc1c(C(=O)C(=O)N)c2c(n1Cc1ccccc1)cccc2OCC(=O)O
InChI:
InChI=1S/C21H20N2O5/c1-2-14-19(20(26)21(22)27)18-15(9-6-10-16(18)28-12-17(24)25)23(14)11-13-7-4-3-5-8-13/h3-10H,2,11-12H2,1H3,(H2,22,27)(H,24,25)
InChIKey:
BHLXTPHDSZUFHR-UHFFFAOYSA-N

Cite this record

CBID:72518 http://www.chembase.cn/molecule-72518.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
2-{[1-benzyl-3-(carbamoylcarbonyl)-2-ethyl-1H-indol-4-yl]oxy}acetic acid
IUPAC Traditional name
varespladib
Synonyms
LY-333013
LY315920
CAS Number
172732-68-2
PubChem SID
162037443
PubChem CID
155815

DATA SOURCES

DATA SOURCES

All Sources Commercial Sources Non-commercial Sources
Data Source Data ID Price
Selleck Chemicals
S1110 external link Add to cart Please log in.
Data Source Data ID
PubChem 155815 external link

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem
Acid pKa 3.6349342  H Acceptors
H Donor LogD (pH = 5.5) 0.9112057 
LogD (pH = 7.4) -0.5576755  Log P 2.7728517 
Molar Refractivity 102.8952 cm3 Polarizability 40.314198 Å3
Polar Surface Area 111.62 Å2 Rotatable Bonds
Lipinski's Rule of Five true 

PROPERTIES

PROPERTIES

Physical Property Safety Information Pharmacology Properties Product Information Bioassay(PubChem)
Solubility
DMSO expand Show data source
Storage Condition
-20°C expand Show data source
Target
sPLA2 expand Show data source
Salt Data
Free Base expand Show data source

DETAILS

DETAILS

Selleck Chemicals Selleck Chemicals
Selleck Chemicals - S1110 external link
Research Area
Description Inflammation
Biological Activity
Description LY315920 (Varespladib) is a potent and selective secretory phospholipase A2 (sPLA) inhibitor with IC50 of 7 nM.
Targets sPLA2
IC50 7 nM [1]
In Vitro LY315920 exhibits the significant inhibitory effect on sPLA2 activity in serum from various species including rat, rabbit, guinea pig and human with IC50 of 8.1 nM, 5.0 nM, 3.2 nM and 6.2 nM, respectively. [2] In BAL cells challenged with human sPLA2, LY315920 at doses ranging from 0.1 μM–3 μM reduces the formation of thromboxane mediated by human sPLA2 in a concentration-dependent manner with an IC50 of approximately 0.8 μM. [2] In human conjunctival epithelial cell line (HCjE), LY315920 (10 μM) significantly inhibits all-trans-retinoic acid (RA) -induced membrane-associated mucin MUC16 expression by 100% at 24 hours and 99% at 48 hours. [3]
In Vivo Ex vivo, LY315920 at doses ranging from 3 mg/kg to 30 mg/kg via i.v. inhibits human sPLA2-induced release of thromboxane from guinea pig BAL cells with ED50 of 16.1 mg/kg. [2] In Transgenic Mice Expressing Human sPLA2, both oral and i.v. administration of LY315920 (0.3 mg/kg–3 mg/kg) abolishes serum sPLA2 activity in a dose and time dependent manner. [2]
Clinical Trials Study on Varespladib Methyl has been completed in Phase II clinical trials in patients with Acute Coronary Syndrome.
Features LY315920 (Varespladib) is a potent and selective secretory phospholipase A2 inhibitor.
Protocol
Kinase Assay [1]
DOC/PC Phospholipase A2 Inhibition Assay Aliquots of 10 μL of LY315920 solutions in DMSO are added to 20 μL (10 ng) of enzyme in 25 mM Tris.HCl (pH 8) with 0.25 mg/mL BSA and 150 μL of assay buffer containing 50mM Tris (pH 8), 0.2 M NaCl, 2 mM CaCl2, and 1 mg/mL fatty acid free BSA. To each tube is added 20 μL of a freshly prepared, iced stock solution of the PC and bile salt, which have been sonicated and concocted such that the final 200 μL reaction volume would contain 3 mM DOC/1 mM total PC and approximately 1 × 105 cpm of [14C]PC. To prepare the lipid substrate, aliquots of labeled PC (1-palmitoyl-2[14C]-oleoylphosphatidyl choline) and 100 mM stock cold PC in chloroform, and 100 mM DOC (sodium salt of deoxycholic acid) in ethanol are mixed, dried under a N2 stream, and then reconstituted in 10 mM Tris with 0.2 mM NaCl, before sonicating for 10 minutes. The assay tubes are incubated for 1 hour in a 40 °C water bath. The reaction is stopped with 1.5 mL of Doles 2-propanol/heptane/0.5 M H2SO4 at 40:10:1 (v/v) with 1 mg/mL palmitic acid. The mixtures are then heated for 1 minute at 60 °C before 1 mL of H2O and 1.25 mL of heptane are added and mixed thoroughly. After the two phases are allowed to separate, the upper phase is transferred to 1 mL of heptane containing 150 mg of dried silica and mixed again before centrifugation for 5 minutes at 1500 g. The supernatant is removed for scintillation counting of the liberated [14C]oleic acid. The degree of inhibition is compared to diluent controls, and the inhibitory concentrations are calculated.
Animal Study [2]
Animal Models Transgenic Mice Expressing Human sPLA2 Protein.
Formulation LY315920 is dissolved in 5% DMSO, 5% ethanol, and 30% polyethylene glycol 300.
Doses ≤3 mg/kg
Administration Administered via i.v. and p.o.
References
[1] Draheim SE, et al. J Med Chem. 1996, 39(26), 5159-5175.
[2] Snyder DW, et al. J Pharmacol Exp Ther. 1999, 288(3), 1117-1124.
[3] Hori Y, et al. Invest Ophthalmol Vis Sci. 2005, 46(11), 4050-4061.

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