BMS 740808

• CAT Number: I004643
• CAS Number: 280118-23-2
• Molecular Formula: C31H27F3N6O3
• Molecular Weight: 588.59
• Purity: ≥95%
• Synonyms: BMS 740808; BMS-740808; BMS740808; UNII-LDD74E663F;;7H-Pyrazolo(3,4-c)pyridin-7-one, 1-(3-amino-1,2-benzisoxazol-5-yl)-1,4,5,6-tetrahydro-6-(2/’-(((3R)-3-hydroxy-1-pyrrolidinyl)methyl)(1,1/’-biphenyl)-4-yl)-3-(trifluoromethyl)-
• Target: Inhibitor of Factor X
• Solubility: Soluble in DMSO, not in water
• Storage: 0 - 4 °C for short term or -20 °C for long term
• IUPAC Name: 1-(3-amino-1,2-benzoxazol-5-yl)-6-[4-[2-[[(3R)-3-hydroxypyrrolidin-1-yl]methyl]phenyl]phenyl]-3-(trifluoromethyl)-4,5-dihydropyrazolo[3,4-c]pyridin-7-one
• 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
• SMILES: C1CN(CC1O)CC2=CC=CC=C2C3=CC=C(C=C3)N4CCC5=C(C4=O)N(N=C5C(F)(F)F)C6=CC7=C(C=C6)ON=C7N

BMS-740808 (Cat No.: I004643) is a potent, selective, and orally bioavailable inhibitor of blood coagulation factor Xa, exhibiting a Ki of 0.03 nM. It demonstrates rapid inhibition kinetics (2.7 × 10⁷ M⁻¹ s⁻¹) and over 1,000-fold selectivity against other proteases. Structural modifications, including the addition of a 3(R)-hydroxyl group on the pyrrolidine ring, have significantly enhanced its potency. In preclinical models, BMS-740808 effectively prevents thrombosis without compromising hemostasis, highlighting its potential as an anticoagulant therapy. ​

Reference

1:Bioorg Med Chem Lett. 2006 Aug 1;16(15):4141-7. Epub 2006 May 30. 1-[3-Aminobenzisoxazol-5/’-yl]-3-trifluoromethyl-6-[2/’-(3-(R)-hydroxy-N-pyrrolidinyl)methyl-[1,1/’]-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[3,4-c]-pyridin-7-one (BMS-740808) a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa.Pinto DJ,Orwat MJ,Quan ML,Han Q,Galemmo RA Jr,Amparo E,Wells B,Ellis C,He MY,Alexander RS,Rossi KA,Smallwood A,Wong PC,Luettgen JM,Rendina AR,Knabb RM,Mersinger L,Kettner C,Bai S,He K,Wexler RR,Lam PY, PMID: 16730984 DOI: 10.1016/j.bmcl.2006.02.069 Abstract: Attempts to further optimize the pyrazole factor Xa inhibitors centered on masking the aryl aniline P4 moiety. Scaffold optimization resulted in the identification of a novel bicyclic pyrazolo-pyridinone scaffold which retained fXa potency. The novel bicyclic scaffold preserved all binding interactions observed with the monocyclic counterpart and importantly the carboxamido moiety was integrated within the scaffold making it less susceptible to hydrolysis. These efforts led to the identification of 1-[3-aminobenzisoxazol-5/’-yl]-3-trifluoromethyl-6-[2/’-(3-(R)-hydroxy-N-pyrrolidinyl)methyl-[1,1/’]-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[3,4-c]-pyridin-7-one 6f (BMS-740808), a highly potent (fXa Ki=30 pM) with a rapid onset of inhibition (2.7×10(7) M-1 s-1) in vitro, selective (>1000-fold over other proteases), efficacious in the AVShunt thrombosis model, and orally bioavailable inhibitor of blood coagulation factor Xa.