Bosutinib CAS 380843-75-4

Chemical name:

4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile

M.F: C26H29Cl2N5O3

Chemical properties : Pale Yellow Solid

Bosutinib is a Bcr-Abl kinase inhibitor for the treatment of Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML). Compared to other tyrosine kinase inhibitors, it has a more favourable hematologic toxicity profile. FDA approved on September 4, 2012.

Innovator: Wyeth Pharmaceuticals (Pfizer)  (US)

Applications:

Effects on cell morphology were observed at a concentration of 1 µM SKI-606 for all cell lines examined, and morphological changes were apparent at concentrations as low as 0.25 µM. SKI-606 caused the cells to adhere to each other, forming dense clusters as compared to vehicle control (DMSO) treated cells, which showed spreading over larger areas.

Dosage form: Oral administration, 100 mg/Kg/d, for 28 days

Intermediates:

CAS No. 2031-23-4  1-(3-Chloropropyl)-4-methylpiperazine dihydrochloride

CAS No. 214470-66-3 7-(3-chloropropoxy)-4-hydroxy-6-methoxyquinoline-3-carbonitrile

CAS No. 214470-68-5  4-CHLORO-7-(3-CHLORO-PROPOXY)-6-METHOXY-QUINOLINE-3-CARBONITRILE

CAS No. 263149-10-6  4-CHLORO-7-HYDROXY-6-METHOXY-QUINOLINE-3-CARBONITRILE

CAS No. 380844-49-5  7-(3-CHLORO-PROPOXY)-4-(2,4-DICHLORO-5-METHOXY-PHENYLAMINO)-6-METHOXY-QUINOLINE-3-CARBONITRILE

The targeted drug Bsutinib (Bosulif) has been approved by the FOOD and Drug Administration (FDA) for the treatment of chronic myelogenous leukemia. Besutinib is a kinase inhibitor that inhibits the Abl and Src signaling pathways. The drug is intended to treat chronic, accelerated, or acute Philadelphia chromosome-positive (Ph+) CML adult patients with prior drug resistance or intolerance, according to a Pfizer Oncology announcement. About a third of CML patients don't respond well to treatment with the standard first-line drug Gleevec, Pfizer said. About half of patients who develop resistance or intolerance to imatinib also respond poorly to other second-line tyrosine kinase inhibitors (TKI), the company said.

The approval of the oral drug was based primarily on phase I and phase II clinical trials involving 500 PH-positive CML patients who were not responsive to or intolerant to imatinib, including different groups in the chronic, accelerated, and acute stages. According to Data from Pfizer's clinical trial, a third of patients previously treated with imatinib alone achieved major cytogenetic remission after 24 weeks of taking Bosutinib (500 mg once a day). In patients who received imatinib and another tyrosine kinase inhibitor (dasatinib, Sprycel), 27% achieved major cytogenetic remission. Response rates continued to rise in both groups after 24 weeks or more of the drug, Pfizer said. Pfizer notes that only 4 percent of patients with chronic disease progress to the advanced or acute stage after taking Besutinib. Grade 3-4 side effects include thrombocytopenia (26%), neutropenia (11%), diarrhea (9%), anemia (9%), and skin rash (8%).

Bosutris (Bosutinib) bossutinib was originally developed by Pfizer and was first approved in the United States in September 2012 for use in adults with Ph+CML who have had a prior history of resistance or intolerance to the treatment in chronic, accelerated, or acute stages. BOSULIF is the first Pfizer drug to treat hematologic tumors and is an important treatment option for Ph+CML patients with previous drug resistance or intolerance. This expanded indication has the potential to have an even greater impact on the lives of patients with chronic myelogenous leukemia.

On July 13, 2020, India's Mylan Pharmaceutical opened Bosutinib (Bosutinib/Bosutinib/Bosutinib) generic generic Bosutris commercial launch. A generic version of Mylan's Bosutris costs about 25% less than Pfizer's original Bosulif. (Also: Upjohn, the generics arm of Pfizer, will merge with Mylan this year to create Viatris, the world's largest generics company, which will be completed in the fourth quarter of 2020.)