827022-32-2

Basic information

• Product Name: PD 0332991 HCl
• Synonyms: PD 0332991 HCl;PD-0332991 (Palbociclib);PD 0332991 hydrochloride;Palbociclib HCl;Palbociclib (hydrochloride);Palbociclib (PD-0332991) HCl;6-acetyl-8-cyclopentyl-5-Methyl-2-(5-(piperazin-1-yl)pyridin-2-ylaMino)pyrido[2,3-d]pyriMidin-7(8H)-one hydrochloride;6-Acetyl-8-cyclopentyl-5-methyl-2-[[5-(1-piperazinyl)-2-pyridinyl]amino]pyrido[2,3-d]pyrimidin-7(8H)-one hydrochloride Palbociclib (PD-0332991) HCl
• CAS NO: 827022-32-2
• Molecular Formula: C₂₄H₂₉N₇O₂*ClH
• Molecular Weight: 483.9937
• EINECS: 1592732-453-0
• Product Categories: Inhibitors
• Mol File: 827022-32-2.mol

Chemical Properties

• Boiling Point: 727 °C at 760 mmHg
• Flash Point: 393.5 °C
• Appearance: /
• Storage Temp.: = -70C
• Solubility: ≥14.48 mg/mL in H2O; ≥2.42 mg/mL in DMSO; ≥2.79 mg/mL in EtOH with gentle warming and ultrasonic
• CAS DataBase Reference: PD 0332991 HCl(CAS DataBase Reference)
• NIST Chemistry Reference: PD 0332991 HCl(827022-32-2)
• EPA Substance Registry System: PD 0332991 HCl(827022-32-2)

Safety Data

• Hazardous Substances Data: 827022-32-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
PD 0332991 HCl is used as an antiproliferative agent for targeting retinoblastoma-positive tumor cells, blocking retinoblastoma phosphorylation, and inducing G1 arrest at nanomolar concentrations.
Used in Cancer Treatment:
PD 0332991 HCl is used as a treatment for certain ER-positive or HER2-amplified breast cancer cells, with IC50s as low as 4 nM. It demonstrates synergy with tamoxifen and trastuzumab, enhancing their therapeutic effects.
Used in Diabetes Research:
PD 0332991 HCl is used as a research tool to study the role of insulin-activated cyclinD1-Cdk4 signaling in the control of glucose metabolism, independent of cell cycle progression.
Used in Stem Cell Research:
PD 0332991 HCl is used to improve endoderm differentiation of late G1-human embryonic stem cells expressing Smad2 or Smad3, and further enhances endoderm differentiation into hepatic and pancreatic progenitor cells.
Used in Preclinical Cancer Models:
PD 0332991 HCl is used to regress the growth of human breast tumor xenografts in murine models, with an effective dosage of approximately 150 mg/kg, administered orally and daily.

Biochem/physiol Actions

Cell permeable: yes

references

[1] ivan diaz-padilla, lillian l. siu and ignacio duran. cyclin-dependent kinase inhibitors as potential targeted anticancer agents. invest new drugs. 2009, 27: 586–594.[2] richard s finn, judy dering, dylan conklin, ondrej kalous, david j cohen, amrita j desai, charles ginther, mohammad atefi, isan chen, camilla fowst, gerret los and dennis j slamon. pd 0332991, a selective cyclin d kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. breast cancer research. 2009, 11: r77.

Upstream product

• 1651214-74-2 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 
• 1016636-76-2 2-chloro-5-methyl-6-bromo-8-cyclopentylpyridine[2,3-d]pyrimidin-8-hydro-7-one 
• 571188-59-5 tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate 
• 1244949-62-9 C₁₁H₁₄ClN₃O 
• 571190-30-2 PD 0332991 
• 866084-31-3 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 
• 571188-82-4 tert?butyl 4?(6?((6?bromo?8?cyclopentyl?5?methyl?7?oxo?7,8?dihydropyrido[2,3?d]pyrimidin?2?yl)amino)pyridin?3?yl)piperazine?1?carboxylate 
• 571189-10-1 4-{6-[8-cyclopentyl-6-(1-ethoxyvinyl)-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino]pyridin-3-yl}piperazine-1-carboxylic acid tert-butyl ester 

Downstream Products

• 571190-30-2 PD 0332991 

Relevant articles and documents

Preparation method and process of palbociclib

The invention relates to a preparation method of palbociclib. The preparation method comprises the steps of 1 reacting a compound I with a compound II to obtain an intermediate I; 2 carrying out a coupling reaction on the intermediate I and vinyl n-butyl ether to obtain an intermediate II; 3 removing a protecting group from the intermediate II under the action of an acid reagent to obtain palbociclib silicate; and 4 carrying out alkali replacement on the palbociclib silicate to obtain palbociclib.

Palbociclib preparation method

The invention discloses a palbociclib preparation method, and relates to the field of organic synthesis. The method includes taking a compound I as a starting material; and preforming a five-step reaction to obtain palbociclib. The method has the advantages of simple operation, low requirement on equipment, easily-available raw materials, mild reaction conditions and high yield, so that the methodis suitable for industrial production.

PALBOCICLIB SALTS

The subject of the invention relates to various new salts of palbociclib, furthermore to their hydrate and solvate forms, such as the palbociclib hydrogen bromide (1:1) salt, the palbociclib hydrogen bromide (1:2) dihydrate salt, the palbociclib hydrogen chloride (1:1) salt Form E, the palbociclib sulphate (2:1) dihydrate salt, the palbociclib camsylate (1:1) salt, the palbociclib napsylate (1:1) salt, the palbociclib napsylate (1:2) dihydrate salt, the palbociclib tosylate (1:1) salt, the palbociclib citrate (1:1) monohydrate salt, the palbociclib maleate (1:1) salt Form I, the palbociclib maleate (1:1) salt Form II and the palbociclib oxalate (1:1) salt. The subject of the invention also relates to the production of the above palbociclib salts, medicinal preparations containing these and the medical use of the above forms.

Now crystal form of antitumor drug, preparation method and uses thereof

The present invention discloses the crystal form C of a compound represented by a formula I, a preparation method and uses thereof, wherein the X-ray powder diffraction (XRPD) of the crystal form C has the following 2[theta] angle characteristic peaks: 5.56+/-0.2 DEG, 7.68+/-0.2 DEG and 8.67+/-0.2 DEG. The formula I is defined in the specification.

Preparation method for Palbociclib

The invention relates to a preparation method for Palbociclib. The method comprises the following steps: taking 4-[6-(6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyridino[2,3-d]pyridine-2-yl-amino)-pyridine-3-yl]-piperazine-1-carboxylic acid tert-butyl ester as a starting raw material; performing Heck reaction, rearrangement, deprotection and neutral reaction to obtain the Palbociclib, wherein the total yield is 70 to 80 percent. According to the preparation method disclosed by the invention, non-Pd-catalyzed heck reaction is investigated, such that a phosphorus-containing ligand which is high in cost and needs harsh reaction conditions is avoided, and the production cost and the technological operation risk are reduced; acetylchloride is used for rearrangement and deprotection reaction to obtain Palbociclib hydrochloride, and the Palbociclib hydrochloride is alkalized to obtain the high-purity Palbociclib.

SYNTHESIS OF 2-(PYRIDIN-2-YLAMINO)-PYRIDO[2,3-D]PYRIMIDIN-7-ONES

The present invention provides methods of preparing substituted 2-(pyridin-2-ylamino)-pirido[2,3- d]pyrimidin-7-ones (formula 1 ), useful in treating cell proliferative disorders, or a pharmaceutically acceptable salt thereof.

ISETHIONATE SALT OF A SELECTIVE CDK4 INHIBITOR

Disclosed are polymorphs of the isethionate salt of 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one, which is a selective cyclin-dependent kinase 4 (CDK4) inhibitor useful for treating inflammation and cell proliferative diseases such as cancer and restenosis.