Palbociclib

Base Information

• Chemical Name: Palbociclib
• CAS No.: 571190-30-2
• Molecular Formula: C24H29N7O2
• Molecular Weight: 447.54
• European Community (EC) Number: 810-186-2
• UNII: G9ZF61LE7G
• DSSTox Substance ID: DTXSID40972590
• Nikkaji Number: J3.007.984A
• Wikipedia: Palbociclib
• Wikidata: Q15269707
• NCI Thesaurus Code: C49176
• RXCUI: 1601374
• Pharos Ligand ID: KWDWHUTKXUR4
• Metabolomics Workbench ID: 152128
• ChEMBL ID: CHEMBL189963
• Mol file: 571190-30-2.mol

Synonyms:6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-ylpyridin-2-ylamino)-8H-pyrido(2,3-d)pyrimidin-7-one;Ibrance;palbociclib;PD 0332991;PD-0332991;PD0332991

Chemical Property of Palbociclib

Chemical Property:

• Vapor Pressure: 4.32E-20mmHg at 25°C
• Melting Point: 200 °C
• Refractive Index: 1.647
• Boiling Point: 711.5 °C at 760 mmHg
• PKA: 8.66±0.10(Predicted)
• Flash Point: 384.1°C
• PSA: 105.04000
• Density: 1.313 g/cm³
• LogP: 3.43260
• Storage Temp.: room temp
• Solubility.: Soluble in DMSO (up to 2 mg/ml with warming)
• XLogP3: 1.8
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 5
• Exact Mass: 447.23827319
• Heavy Atom Count: 33
• Complexity: 775

Purity/Quality:

99%min ^*data from raw suppliers

Palbociclib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CC1=C(C(=O)N(C2=NC(=NC=C12)NC3=NC=C(C=C3)N4CCNCC4)C5CCCC5)C(=O)C
• Recent ClinicalTrials: Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial
• Recent EU Clinical Trials: PHASE 1/2A DOSE ESCALATION, FINDING AND EXPANSION STUDY EVALUATING SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS AND ANTI TUMOR ACTIVITY OF PF-07104091 AS A SINGLE AGENT AND IN COMBINATION THERAPY
• Recent NIPH Clinical Trials: A Randomised, Double-Blind, Phase III Study of AZD9833 plusPalbociclib versus Anastrozole plus Palbociclib in Patients with ER-Positive HER2-Negative Breast Cancer Who Have Not Received Any Systemic Treatment for Advanced Disease
• Description: Palbociclib is a cyclin-dependent kinase (CDK) 4 and CDK6 inhibitor approved by the FDA to treat hormone receptor-positive (HR+) human epidural growth factor 2-negative (HER2-) metastatic breast cancer. It is used in combination with letrazole as the first-line hormonal-based therapy in postmenopausal women, or with fulvestrant in women with disease progression following hormonal therapy. Palbociclib was discovered at Warner- Lambert and developed by Pfizer after their merger. Pfizer is also studying the effectiveness of palbociclib in a variety of other cancers at various stages in the clinic.
• Uses: Palbociclib (also known as compound number PD-0332991) is an experimental drug for the treatment of breast cancer being developed by Pfizer. It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6.
• Indications: Palbociclib (Ibrane(R), Pfizer), a selective CDK4 and CDK6 inhibitor, received accelerated approval from FDA in 2015 for women with estrogen receptor-positive and HER2-negative breast cancer in combination with letrozole.
• Clinical Use: Protein kinase inhibitor: Treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)- negative locally advanced or metastatic breast cancer
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: concentration possibly increased by clarithromycin - avoid or reduce palbociclib dose; concentration reduced by rifampicin - avoid. Antidepressants: concentration possibly reduced by St John’s wort - avoid. Antiepileptics: concentration possibly reduced by carbamazepine, fosphenytoin and phenytoin - avoid. Antifungals: concentration possibly increased by itraconazole, ketoconazole, posaconazole and voriconazole - avoid or reduce palbociclib dose. Antipsychotics: increased risk of agranulocytosis with clozapine - avoid. Antivirals: concentration possibly increased by indinavir, lopinavir, ritonavir, saquinavir and telaprevir - avoid or reduce palbociclib dose. Cytotoxics: concentration possibly reduced by enzalutamide - avoid. Grapefruit juice: concentration possibly increased - avoid

Technology Process of Palbociclib

There total 71 articles about Palbociclib which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 98.6%

C24H28ClN7O2 → PD 0332991 (571190-30-2)

Guidance literature:

With hydrogen; sodium hydroxide; In ethanol; at 40 - 50 ℃; for 4h; Reagent/catalyst; Solvent;

Reference yield: 98.5%

4-[6-(6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)pyridine-3-yl]piperazine-1-carboxylic acid tert-butyl ester (1651214-74-2) → PD 0332991 (571190-30-2)

Guidance literature:

With hydrogenchloride; In tetrahydrofuran; water; at 25 - 30 ℃; for 5h;

Reference yield: 98.0%

tert?butyl 4?(6?((6?(1?butoxyvinyl)?8?cyclopentyl?5?methyl?7?oxo?7,8?dihydropyrido[2,3?d]pyrimidin?2?yl)amino)pyridin?3?yl)piperazine?1?carboxylate (866084-31-3) → PD 0332991 (571190-30-2)

Guidance literature:

With methanesulfonic acid; In water; acetone; at 45 - 55 ℃; Solvent; Reagent/catalyst; Large scale;

upstream raw materials:

6-acetyl-8-cyclopentyl-5-methyl-2-{[5-(piperazin-1-yl)pyridin-2yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one hydrochloride

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate

Cyclopentamine

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine

Downstream raw materials:

PD 0332991 isethionate

N-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)butyl)-2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamide

Refernces

• 1、 -. "Preparation method of palbociclib". . . Retrieved 2021/06/09.
• 2、 -. "Preparation method and product of palbociclib". . . Retrieved 2019/02/27.