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

• ChemBase ID: 72750
• Molecular Formular: C31H27F3N6O3
• Molecular Mass: 588.5796896
• Monoisotopic Mass: 588.20967341
• SMILES: c12c(C(=O)N(CC1)c1ccc(cc1)c1ccccc1CN1CC[C@H](C1)O)n(nc2C(F)(F)F)c1ccc2c(c1)c(no2)N
• Canonical SMILES: O[C@@H]1CCN(C1)Cc1ccccc1c1ccc(cc1)N1CCc2c(C1=O)n(nc2C(F)(F)F)c1ccc2c(c1)c(N)no2
• 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

NAMES AND DATABASE IDS

Names

• 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
• Synonyms: BMS-740808

Database IDs

• CAS Number: 280118-23-2
• PubChem SID: 162037671
• PubChem CID: 6914623

CALCULATED PROPERTIES

• Acid pKa: 14.840031
• H Acceptors: 6
• H Donor: 2
• LogD (pH = 5.5): 0.93648887
• LogD (pH = 7.4): 2.4124835
• Log P: 4.2342806
• Molar Refractivity: 157.1793 cm^3
• Polarizability: 60.094597 Å^3
• Polar Surface Area: 113.65 Å^2
• Rotatable Bonds: 6
• Lipinski's Rule of Five: false

PROPERTIES

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: Factor Xa

Product Information

• Salt Data: Free Base

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; Rabbit AVshunt; Thrombin
• IC50: 0.03 nM (K_i); 135 nM; 35 nM (K_i) ^[1]
• In Vitro: BMS-740808 is highly potent with a rapid onset of inhibition (2.7 × 10^7 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]

Protocol

• 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.
• Protocol: Animal Study ^[1]
• Animal Models: Male rabbit AVShunt thrombosis model.
• Formulation: BMS-740808 is dissolved in saline.
• Doses: 2 μM
• Administration: Given as continuous i.v. infusion via the jugular vein

References

• References: [1] Pinto DJ, et al, Bioorg Med Chem Lett, 2006, 16(15), 4141-4147.

REFERENCES

• Pinto DJ, et al, Bioorg Med Chem Lett, 2006, 16(15), 4141-4147.