CAS 280118-23-2|BMS-740808|1-(3-amino-1,2-benzoxazol-5-yl)-6-[4-(2-{[(3R)-3-hydroxypyrrolidin-1-yl]methyl}phenyl)phenyl]-3-(trifluoromethyl)-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridin-7-one|1-(3-amino-1,...

General Information

Structure

Molecular Formula

C₃₁H₂₇F₃N₆O₃

Molecular Mass

588.5796896

Exact Mass

588.20967341

Charge

InChI

InChI=1S/C31H27F3N6O3/c32-31(33,34)28-24-12-14-39(30(42)27(24)40(36-28)21-9-10-26-25(15-21)29(35)37-43-26)20-7-5-18(6-8-20)23-4-2-1-3-19(23)16-38-13-11-22(41)17-38/h1-10,15,22,41H,11-14,16-17H2,(H2,35,37)/t22-/m1/s1

InChIKey

DFRIQJHMGZBFOM-JOCHJYFZSA-N

Canonic Smiles

O[C@@H]1CCN(C1)Cc1ccccc1c1ccc(cc1)N1CCc2c(C1=O)n(nc2C(F)(F)F)c1ccc2c(c1)c(N)no2

Isomeric Smiles

c12c(C(=O)N(CC1)c1ccc(cc1)c1ccccc1CN1CC[C@H](C1)O)n(nc2C(F)(F)F)c1ccc2c(c1)c(no2)N

Calculated Properties

JChem

Acid pKa

14.840031

H Acceptors

H Donor

LogD (pH = 5.5)

0.93648887

LogD (pH = 7.4)

2.4124835

Log P

4.2342806

Molar Refractivity

157.1793

Polarizability

60.094597

Polar Surface Area

113.65

Rotatable Bonds

Lipinski's Rule of Five

false

Data Source

Commercial Catalog

Academic Data

Data Source

Names and Identifiers

Synonyms

BMS-740808

IUPAC name

1-(3-amino-1,2-benzoxazol-5-yl)-6-[4-(2-{[(3R)-3-hydroxypyrrolidin-1-yl]methyl}phenyl)phenyl]-3-(trifluoromethyl)-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridin-7-one

IUPAC Traditional name

1-(3-amino-1,2-benzoxazol-5-yl)-6-[4-(2-{[(3R)-3-hydroxypyrrolidin-1-yl]methyl}phenyl)phenyl]-3-(trifluoromethyl)-4H,5H-pyrazolo[3,4-c]pyridin-7-one

Names and Identifiers

Registration numbers

PubChem CID

6914623

PubChem SID

162037671

CAS Number

280118-23-2

Registration numbers

Properties

Pharmacology Properties

Target

Factor Xa

Product Information

Salt Data

Free Base

Safety Information

Storage Condition

-20°C

Properties

Related Proteins

No Data Available

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Molecular Spectra

No Data Available

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Molecule Details

Selleck Chemicals

S1571

Research Area

Description

Cardiovascular Disease

Biological Activity

Description

BMS-740808 is a highly potent, selective inhibitor of blood coagulation factor Xa (fXa) with K_i with 0.03 nM.

Targets

fXa

IC₅₀

0.03 nM (K_i)

In Vitro

BMS-740808 is highly potent with a rapid onset of inhibition (2.7 × 10⁷ M^-1 s^-1), selective (>1000-fold over other proteases), efficacious in the AVShunt thrombosis model. BMS-740808 is synthesized by modification of employing bicyclic pyrazolo-pyridinone scaffold to Razaxaban, a pyrazole based fXa inhibitor. Especially for BMS-740808, the introduction of a 3(R)-hydroxyl moiety on the pyrrolidine ring results in a significant enhancement in potency. BMS-740808 also shows the high affinity for thrombin. ^[1]

In Vivo

The pharmacokinetic profile for BMS-740808 is comparable to that of Razaxaban with moderate half life, whereas BMS-740808 shows low clearance, low V_dss, moderate half life and high oral bio-availability, which is quite possibly due to the hydroxyl substituent on the cyclic amino moiety. ^[1]

Clinical Trials

Features

Protocol

Kinase Assay ^[1]

Ki Determination

FXa (1 nM) is added to a 96-well plate containing BMS-740808 (5 pM to 3 μM) in buffer A (20 mM HEPES, 0.15 M NaCl, 0.1% PEG-8000, 5 mM CaCl₂, pH 7.4). S-2765 (N-α-Z-d-Arg-Gly-Arg-p Nitroanilide) at 200 μM is added, and substrate hydrolysis is monitored at 405 nm. Data are analyzed by Batch K_i software.