936563-87-0

Basic information

• Product Name: PCI-32765 (RaceMate)
• Synonyms: PCI-32765 (RaceMate);1-[3-[4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one;1-(3-(4-Amino-3-(4-phenyloxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one
• CAS NO: 936563-87-0
• Molecular Formula: C25H24N6O2
• Molecular Weight: 440.49706
• Mol File: 936563-87-0.mol
• Article Data: 55

Chemical Properties

• Appearance: /
• Storage Temp.: -20C
• Solubility: Soluble in DMSO
• CAS DataBase Reference: PCI-32765 (RaceMate)(CAS DataBase Reference)
• NIST Chemistry Reference: PCI-32765 (RaceMate)(936563-87-0)
• EPA Substance Registry System: PCI-32765 (RaceMate)(936563-87-0)

Safety Data

• Hazardous Substances Data: 936563-87-0(Hazardous Substances Data)

Usage

Biological Activity

pci-32765 is an inhibitor of bruton tyrosine kinase (btk) with ic50 value of 0.5nm [1].pci-32765 is a covalent and irreversible inhibitor of btk through bonding to cys-481 in the atp binding domain. pci-32765 inhibits phosphorylation of btk in a b cells (ic50 of 11nm) as well as the downstream substrates phosphoinositide phospholipase cγ (plc γ) and erk in cell assays. pci-32765 has in vivo efficacy in b cell lymphoma. in cll cells, pci-32765 induces cells apoptosis through inhibiting the expression of bcr-dependent udp-glucose ceramide glucosyltransferase [1].pci-32765 is oral effective in vivo. it induces lymphocytosis during the first weeks of therapy in patients with cll. it is also efficacious in autoimmune disease. in the mrl-fas lupus model, pci-32765 inhibits collagen-induced arthritis as well as autoantibody production and development of kidney disease. it also diminished fcγriii-induced production of pro-inflammatory cytokines [1].

references

[1] burger ja, buggy jj. bruton tyrosine kinase inhibitor ibrutinib (pci-32765). leuk lymphoma. 2013 nov;54(11):2385-91.

Upstream product

• 814-68-6 acryloyl chloride 
• 936563-86-9 tert-butyl 3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate 
• 330792-69-3 2-[(4-phenoxy-phenyl)-methoxy-methylene]-malononitrile 
• 330792-68-2 2-[hydroxy-(4-phenoxy-phenyl)-methylene]-malononitrile 
• 330786-24-8 3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine 
• 2215-77-2 4-Phenoxybenzoic acid 
• 1623-95-6 4-phenoxybenzoyl chloride 
• 1609467-43-7 benzyl 3-[5-amino-4-cyano-3-(4-phenoxy-phenyl)-pyrazol-1-yl]-piperidine-1-carboxylate 
• 1412418-47-3 3-(4-phenoxyphenyl)-1-(piperidine-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-4-amine 
• 19300-54-0 toluene-4-sulfonic acid pent-4-enyl ester 
• 2380-63-4 4-Aminopyrazolo<3,4-d>pyrimidin 
• 151266-23-8 4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidine 
• 1022150-12-4 (R)-3-(4-phenoxyphenyl)-1-(piperidine-3-yl)-1H-pyrazolo[3,4-d]pyrimidine-4-amine 
• 1022150-11-3 (3R)‐4‐amino‐3‐(4-phenoxyphenyl)‐1‐(1‐tert-butoxycarbonylpiperidine-3-yl)-1H-pyrazolo[3,4-d]pyrimidine 

Relevant articles and documents

A synthetic method of ibutinib

The present invention provides a preparation method of ibutinib and its application, by optimizing the feeding ratio and reaction conditions, increasing the purification step of the intermediate, and the use of inorganic alkali instead of organic base as an acid binding agent, significantly reducing the impurity content of ibutinib synthetic intermediates and final products, especially the content of isomer impurities, to ensure the quality of drugs and clinical drug safety provides a strong guarantee.

Tunable Methacrylamides for Covalent Ligand Directed Release Chemistry

Targeted covalent inhibitors are an important class of drugs and chemical probes. However, relatively few electrophiles meet the criteria for successful covalent inhibitor design. Here we describe α-substituted methacrylamides as a new class of electrophiles suitable for targeted covalent inhibitors. While typically α-substitutions inactivate acrylamides, we show that hetero α-substituted methacrylamides have higher thiol reactivity and undergo a conjugated addition-elimination reaction ultimately releasing the substituent. Their reactivity toward thiols is tunable and correlates with the pKa/pKb of the leaving group. In the context of the BTK inhibitor ibrutinib, these electrophiles showed lower intrinsic thiol reactivity than the unsubstituted ibrutinib acrylamide. This translated to comparable potency in protein labeling, in vitro kinase assays, and functional cellular assays, with improved selectivity. The conjugate addition-elimination reaction upon covalent binding to their target cysteine allows functionalizing α-substituted methacrylamides as turn-on probes. To demonstrate this, we prepared covalent ligand directed release (CoLDR) turn-on fluorescent probes for BTK, EGFR, and K-RasG12C. We further demonstrate a BTK CoLDR chemiluminescent probe that enabled a high-throughput screen for BTK inhibitors. Altogether we show that α-substituted methacrylamides represent a new and versatile addition to the toolbox of targeted covalent inhibitor design.

Preparation method of ibrutinib

The invention relates to a preparation method of ibrutinib and an intermediate thereof, belonging to the field of medicinal chemistry. According to the preparation method, the ibrutinib can be obtained through condensation, condensation, substitution, substitution and Suzuki reaction by taking a low-cost material flow as a starting material; and the method is low in cost, free of light delay reaction, high in yield, good in selectivity, short in route, few in generated three wastes and suitable for industrial large-scale production.