1211441-98-3

Basic information

• Product Name: LEE011
• Synonyms: 7-Cyclopentyl-N,N-dimethyl-2-[[5-(1-piperazinyl)-2-pyridinyl]amino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide;7-cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide;7-Cyclopentyl-N,N-dimethyl-2-[[5-(1-piperazinyl)-2-pyridinyl]amino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide LEE 011;LEE 011 7-Cyclopentyl-N,N-dimethyl-2-[[5-(1-piperazinyl)-2-pyridinyl]amino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide;LEE011, >=98%;LEE-011, Ribociclib;7H-Pyrrolo[2,3-d]pyrimidine-6-carboxamide, 7-cyclopentyl-N,N-dimethyl-2-[[5-(1-piperazinyl)-2-pyridinyl]amino]-;Ribociclib 7-cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide
• CAS NO: 1211441-98-3
• Molecular Formula: C₂₃H₃₀N₈O
• Molecular Weight: 434.5373
• EINECS: 1592732-453-0
• Product Categories: Inhibitors
• Mol File: 1211441-98-3.mol

Chemical Properties

• Boiling Point: 730.8±70.0 °C(Predicted)
• Appearance: /
• Density: 1.39±0.1 g/cm3(Predicted)
• Vapor Pressure: 0-0Pa at 20-25℃
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (up to 10 mg/ml)
• PKA: 8.67±0.10(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 months.
• CAS DataBase Reference: LEE011(CAS DataBase Reference)
• NIST Chemistry Reference: LEE011(1211441-98-3)
• EPA Substance Registry System: LEE011(1211441-98-3)

Safety Data

• Hazardous Substances Data: 1211441-98-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
LEE011 is used as an anticancer agent for targeting and inhibiting the growth of cancer cells, particularly in neuroblastoma-derived cell lines. Its ability to arrest the cell cycle and suppress DNA synthesis makes it a promising candidate for cancer treatment.
Used in Biological Research:
In the field of biological research, LEE011 is used in kinome-wide RNA interference screens to study its role in acquired resistance to CDK4/6 inhibition in ER-positive breast cancer. This application helps researchers understand the underlying mechanisms of cancer resistance and develop more effective treatment strategies.

Mechanism of action

Ribociclib is a dual cdk4/cdk6 inhibitor. Induces G1 phase cell cycle arrest and senescence in neuroblastoma cell lines (IC50 = 306 nM). Delays tumor growth in vivo.

Clinical Use

Protein kinase inhibitor: Treatment of breast cancer

Drug interactions

Potentially hazardous interactions with other drugs The concomitant use of strong CYP3A4 inhibitors including, but not limited to, the following must be avoided: clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir, ritonavir, nefazodone, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, verapamil and voriconazole. The concomitant use of strong CYP3A4 inducers may therefore lead to decreased exposure and consequently a risk for lack of efficacy. The concomitant use of strong CYP3A4 inducers should be avoided, including, but not limited to, phenytoin, rifampicin, carbamazepine and St John's wort. Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of drug transporters P-gp, BCRP, OATP1B1/1B3, OCT1, OCT2, MATE1 and BSEP which exhibit a narrow therapeutic index, including but not limited to digoxin, pravastatin, rosuvastatin and metformin. Co-administration of Kisqali with medicinal products with a known potential to prolong the QT interval such as anti-arrhythmic medicinal products (including, but not limited to, amiodarone, disopyramide, procainamide, quinidine and sotalol), and other medicinal products that are known to prolong the QT interval (including, but not limited to, chloroquine, halofantrine, clarithromycin, haloperidol, methadone, moxifloxacin, pimozide and intravenous ondansetron) should be avoided.

Metabolism

Ribociclib is hepatically metabolised via CYP3A4 by oxidation. Ribociclib was the main circulating drug in plasma (44%). The major circulating metabolites included metabolite M13 (CCI284, N-hydroxylation), M4 (LEQ803, N-demethylation), and M1 (secondary glucuronide). Clinical activity of ribociclib was due mainly to parent drug, with negligible contribution from circulating metabolites. Unchanged drug accounted for 17.3% and 12.1% of the dose in faeces and urine, respectively. Metabolite LEQ803 represented approximately 13.9% and 3.74% of the administered dose in faeces and urine, respectively. Numerous other metabolites were detected in both faeces and urine in minor amounts (≤2.78%). Ribociclib and its metabolites are eliminated mainly via faeces (69.1%), with a small contribution from the renal route (22.6%).

References

1) Rader?et al.?(2013),?Dual CDK4/6 inhibition induces cell-cycle arrest and senescence in neuroblastoma; Clin. Cancer Res.?19?6173 2) Kim?et al. (2013),?LEE011: an orally bioavailable, selective small-molecule inhibitor of CDK4/6 – reactivating Rb in cancer; Mol. Cancer Ther.?12?PR02 3) Tripathy?et al.?(2017),?Ribociclib(LEE011): mechanism of action and clinical impact of this selective cyclin-dependent kinase 4/6 inhibitor in various solid tumors; Clin. Cancer Res. March 28, 201

Upstream product

• 571189-16-7 4-(6-nitropyridin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester 

Downstream Products

• 1374639-75-4 7-cyclopentyl-N,N-dimethyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide succinate 
• 1211443-80-9 7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide hydrochloride 
• 110-15-6 succinic acid 
• 1374639-75-4 7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide succinate salt 
• 1374639-75-4 7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide hemi succinate 

Relevant articles and documents

AN IMPROVED PROCESS FOR THE PREPARATION OF RIBOCICLIB AND ITS SALTS

The invention relates to a process for the preparation of ribociclib of formula V or its salts. The invention provides novel crystalline forms of ribociclib succinate and ribociclib trifluoroacetate. The present invention also relates to pharmaceutical compositions comprising a crystalline form of ribociclib succinate and at least a pharmaceutically acceptable carrier. It further relates to the use of such compositions in the treatment of cancer.

Synthetic method of cyclopentyl pyrimido pyrroles compound

The invention discloses a synthetic method of a cyclopentyl pyrimido pyrroles compound, which belongs to the field of organic chemical synthesis. Through steps of reduction, oxidation, aldol condensation, aminolysis and nucleophilic substitution, the cyclopentyl pyrimido pyrroles compound is synthesized. The raw materials have the advantages of low cost and easy acquisition, a related intermediate is easily separated and purified, operation is simple, the method is friendly to environment, the purity of the product is high, and the product has good industrial prospect. The prepared cyclopentyl pyrimido pyrroles compound, especially 7-cyclopentyl-N,N-dimethyl-2-((5-(piperazine-1-yl)pyridine-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-methanamide has inhibition effect on cyclin-dependent kinase CDK4/6, and has good clinical treatment effect on melanoma and breast cancer.

SALT(S) OF 7-CYCLOPENTYL-2-(5-PIPERAZIN-1-YL-PYRIDIN-2-YLAMINO)-7H-PYRROLO[2,3-D]PYRIMIDINE-6-CARBOXYLIC ACID DIMETHYLAMIDE AND PROCESSES OF MAKING THEREOF

This invention relates to (1) process of making 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide and salts thereof; (2) novel salt(s) of 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide; (3) pharmaceutical compositions comprising the same; and (4) methods of treatment using the same.