Bosutinib monohydrateProduct ingredient for Bosutinib

Name
Bosutinib monohydrate
Drug Entry
Bosutinib

Bosutinib is a 7-alkoxy-3-quinolinecarbonitrile that functions as a potent, dual SRC and ABL tyrosine kinase inhibitor indicated for chronic myelogenous leukemia (CML), specifically Philadelphia chromosome-positive (Ph+) CML. Philadelphia chromosome is a hallmark of CML due to the reciprocal translocation t(9;22)(q34;q11), resulting in a BCR-ABL fusion protein.2,3,5 The first BCR-ABL inhibitor, imatinib, was introduced over a decade ago as a breakthrough in CML management; however, emerging resistance to imatinib poses challenges in achieving remission.4 Second-generation BCR-ABL inhibitors like bosutinib inhibit most resistance-conferring BCR-ABL mutations except V299L and T315, thus providing more therapeutic options for patients.1,4

Bosutinib was first approved by the FDA in 2012 for the treatment of adult chronic, accelerated, or blast-phase Ph+ CML with resistance or intolerance to prior therapy.10 On September 26, 2023, bosutinib was also approved by the FDA for the treatment of pediatric CML that is newly diagnosed or resistant/intolerant to prior therapy. This approval was based on favorable results obtained from the open-label, randomized, multicenter trial BFORE that showed a significant improvement in major molecular response, defined as a ≤0.1% BCR ABL ratio on an international scale, with bosutinib treatment.11

Accession Number
DBSALT002837
Structure
Synonyms
Bosutinib hydrate
UNII
844ZJE6I55
CAS Number
918639-08-4
Weight
Average: 548.47
Monoisotopic: 547.1753099
Chemical Formula
C26H31Cl2N5O4
InChI Key
BXPOSPOKHGNMEP-UHFFFAOYSA-N
InChI
InChI=1S/C26H29Cl2N5O3.H2O/c1-32-6-8-33(9-7-32)5-4-10-36-25-13-21-18(11-24(25)35-3)26(17(15-29)16-30-21)31-22-14-23(34-2)20(28)12-19(22)27;/h11-14,16H,4-10H2,1-3H3,(H,30,31);1H2
IUPAC Name
4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile hydrate
SMILES
O.COC1=CC(NC2=C(C=NC3=CC(OCCCN4CCN(C)CC4)=C(OC)C=C23)C#N)=C(Cl)C=C1Cl
ChemSpider
10163295
ChEBI
68533
Predicted Properties
PropertyValueSource
Water Solubility0.0095 mg/mLALOGPS
logP4.87ALOGPS
logP4.09Chemaxon
logS-4.8ALOGPS
pKa (Strongest Acidic)15.48Chemaxon
pKa (Strongest Basic)8.03Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count8Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area82.88 Å2Chemaxon
Rotatable Bond Count9Chemaxon
Refractivity142.12 m3·mol-1Chemaxon
Polarizability56.14 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon