923288-90-8

Basic information

• Product Name: Nilotinib hcl monohydrate
• Synonyms: Nilotinib hcl monohydrate;Nilotinibhydrochloridemonohydratesalt;Nilotinib hydrochloride Monohydrate;Nilotinib (Monohydrochloride Monohydrate);4-Methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide hydrochloride hydrate (1:1:1);Nilotinib hydrochloride Monohydrate (1:1:1);Nilotinib monohydrochloride monohydrate 4-Methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide hydrochloride hydrate (1:1:1);Nilotinib Hydrochloride Hydrate
• CAS NO: 923288-90-8
• Molecular Formula: C₂₈H₂₂F₃N₇O*ClH*H₂O
• Molecular Weight: 583.9920096
• Mol File: 923288-90-8.mol

Chemical Properties

• Appearance: White solid
• Storage Temp.: -20°C Freezer
• Solubility: Aqueous Acid (Slightly), DMSO (Slightly), Ethanol (Slightly, Heated)
• CAS DataBase Reference: Nilotinib hcl monohydrate(CAS DataBase Reference)
• NIST Chemistry Reference: Nilotinib hcl monohydrate(923288-90-8)
• EPA Substance Registry System: Nilotinib hcl monohydrate(923288-90-8)

Safety Data

• Hazardous Substances Data: 923288-90-8(Hazardous Substances Data)

Usage

Clinical Use

Nilotinib hydrochloride monohydrate was approved by FDA in 2007 for the treatment of chronic and accelerated phase Ph chromosome-positive CML adult patients which have developed resistance or intolerance to prior therapy that included imatinib. In 2012, apart from these previous indications, nilotinib hydrochloride monohydrate has also been indicated for the treatment of newly diagnosed adult patients with Ph chromosome-positive CML in chronic phase.

Mechanism of action

Tasigna (nilotinib hydrochloride monohydrate) is an orally available signal transduction inhibitor of the Bcr-Abl kinase, c-kit and Platelet Derived Growth Factor (PDGF). Nilotinib binds to and stabilizes the inactive conformation of the kinase domain of Abl protein. In vitro, nilotinib inhibited Bcr-Abl mediated proliferation of murine leukemic cell lines and human cell lines derived from Ph+ CML patients. In vivo, nilotinib reduced the tumor size in a murine Bcr-Abl xenograft model.

Side effects

a headache, fatigue, gastrointestinal problems such as nausea, vomiting, diarrhea and constipation, muscle and joint pain, rash and other skin conditions, flu-like symptoms, and reduced blood cell count. Less typical side effects are those of the cardiovascular system, such as hypertension (high blood pressure), various types of arrhythmia, and prolonged QT interval. Interaction of nilotinib with OATP1B1 and OATP1B3 may alter its hepatic disposition and can lead to transporter mediated drug-drug interactions.

in vitro

In vitro, nilotinib inhibited Bcr-Abl mediated proliferation of murine leukemic cell lines and human cell lines derived from Ph+ CML patients. Under the conditions of the assays, nilotinib was able to overcome imatinib resistance resulting from Bcr-Abl kinase mutations, in 32 out of 33 mutations tested. In vivo, nilotinib reduced the tumor size in a murine Bcr-Abl xenograft model. Nilotinib inhibited the autophosphorylation of the following kinases at IC50 values as indicated: Bcr-Abl (20-60 nM), PDGFR (69 nM) and c-Kit (210 nM). Nilotinib is currently being trialed in people with Parkinson's disease, as it appears to be able to halt progression of the disease and even improve their symptoms.

Synthetic route

nilotinib (641571-10-0) → 4-methyl-N-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide monohydrochloride monohydrate (923288-90-8)

Conditions	Yield
With hydrogenchloride; water In methanol at 30 - 50℃; for 0.75h; Product distribution / selectivity;
With hydrogenchloride; water In methanol at 23 - 50℃; for 4.5h;
With hydrogenchloride; water In methanol at -10 - 64℃; for 2.5h; Product distribution / selectivity;

Upstream product

• 641571-10-0 nilotinib 

Relevant articles and documents

CRYSTALLINE FORMS OF 4-METHYL-N-[3-(4-METHYL-IMIDAZOL-1-YL)-5-TRIFLUOROMETHYL-PHENYL]-3-(4-PYRIDIN-3-YL-PYRIMIDIN-2-YLAMINO)-BENZAMIDE

Crystalline forms of 4-methyl-N-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide free base and salts thereof are prepared by various processes.

SALTS OF 4-METHYL-N-[3-(4-METHYL-IMIDAZOL-1-YL)-5-TRIFLUOROMETHYL-PHENYL]-3-(4-PYRIDIN-3-YL-PYRIMIDIN-2-YLAMINO)-BENZAMIDE

Salts of 4-methyl-N-[3-(4-methyl-imidazol-l-yl)-5-trifluoromethyl-phenyl]-3-(4- pyridin-3-yl-pyrimidin-2-ylamino)-benzamide are prepared by various processes.