763111-47-3

Basic information

• Product Name: 4-(4-fluoro-3-(piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one
• Synonyms: 4-(4-fluoro-3-(piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one;1-[5-[(3,4-Dihydro-4-oxo-1-phthalazinyl)methyl]-2-fluorobenzoyl]piperazine;4-[[4-fluoro-3-(piperazine-1-carbonyl)phenyl]Methyl]-2H-phthalazin-1-one;4-[4'-fluoro-3'-(piperazine-1''-carbonyl)benzyl]-2H-phthalazin-1-one
• CAS NO: 763111-47-3
• Molecular Formula: C₂₀H₁₉FN₄O₂
• Molecular Weight: 366.3888632
• EINECS: 1592732-453-0
• Mol File: 763111-47-3.mol

Chemical Properties

• Appearance: /
• Density: 1.39±0.1 g/cm3(Predicted)
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• PKA: 12.07±0.40(Predicted)
• CAS DataBase Reference: 4-(4-fluoro-3-(piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(4-fluoro-3-(piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one(763111-47-3)
• EPA Substance Registry System: 4-(4-fluoro-3-(piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one(763111-47-3)

Safety Data

• Hazardous Substances Data: 763111-47-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4-(4-fluoro-3-(piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one is used as a chemical intermediate for the development of PARP inhibitors. These inhibitors are designed to target and inhibit the activity of PARP-1 and PARP-2 enzymes, which are involved in DNA repair mechanisms. By inhibiting these enzymes, the compound can potentially enhance the effectiveness of DNA-damaging anticancer agents, leading to the prevention of cancer cell growth and the promotion of apoptosis (cell death).
The application of 4-(4-fluoro-3-(piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one in the pharmaceutical industry is primarily due to its role in the development of novel therapeutic agents for cancer treatment. Its ability to inhibit PARP enzymes makes it a valuable component in the creation of drugs that can effectively combat various types of cancer by exploiting the DNA repair deficiencies in cancer cells.

Upstream product

• 70-18-8 GLUTATHIONE 
• 1431328-64-1 2,4-dinitrophenyl 4-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]-benzoyl]piperazine-1-yl-1-ium-1,2-diolate 
• 763114-26-7 2-fluoro-5-[(4’-oxo-3’H-phthalazin-1’-yl)methyl]benzoic acid 
• 61260-15-9 dimethyl (3-oxo-1,3-dihydroisobenzofuran-1-yl)phosphonate 
• 16859-59-9 3-hydroxy-1(3H)-isobenzofuranone 
• 110-85-0 piperazine 
• 1062292-60-7 4-(3-bromo-4-fluorobenzyl)phthalazin-1(2H)-one 
• 1021298-68-9 2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzonitrile 
• 142-64-3 piperazine dihydrochloride 
• 218301-22-5 2-fluoro-5-formylbenzonitrile 
• 763114-25-6 2-fluoro-5-(3-oxo-1,3-dihydroisobenzofuranylidene methyl)benzonitrile 
• 119-67-5 o-carboxybenzaldehyde 
• 763114-04-1 tert-butyl 4-[2’-fluoro-5’-[(4’’-oxo-3’’H-phthalazin-1’’-yl)methyl]benzoyl]piperazine-1-carboxylate 

Downstream Products

• 763113-22-0 olaparib 

Relevant articles and documents

Novel synthesis method of olaparib bulk drug

The invention introduces a novel synthesis method of an antitumor drug, namely olaparib. According to the invention, a dimer impurity is effectively removed by an acid-base pouring method in virtue of the different chemical properties that the dimer impurity cannot form salt and a previous intermediate of olaparib can form salt, and the HPLC purity of the obtained finished product can reach 99.9%. According to a route in the invention, the yield of the olaparib finished product is effectively improved, the total yield of six steps reaches 42.4%, and the route has important significance on industrial production of olaparib.

Chemical Proteomics Approach for Profiling the NAD Interactome

Nicotinamide adenine dinucleotide (NAD+) is a multifunctional molecule. Beyond redox metabolism, NAD+ has an equally important function as a substrate for post-translational modification enzymes, the largest family being the poly-ADP-ribose polymerases (PARPs, 17 family members in humans). The recent surprising discoveries of noncanonical NAD (NAD+/NADH)-binding proteins suggests that the NAD interactome is likely larger than previously thought; yet, broadly useful chemical tools for profiling and discovering NAD-binding proteins do not exist. Here, we describe the design, synthesis, and validation of clickable, photoaffinity labeling (PAL) probes, 2- and 6-ad-BAD, for interrogating the NAD interactome. We found that 2-ad-BAD efficiently labels PARPs in a UV-dependent manner. Chemical proteomics experiments with 2- and 6-ad-BAD identified known and unknown NAD+/NADH-binding proteins. Together, our study shows the utility of 2- and 6-ad-BAD as clickable PAL NAD probes.

PARP Inhibitor - alkylated bifunctional molecule and preparation method and application thereof

The invention discloses a potent polyadenine diphosphate ribose polymerase inhibitor (Poly ADP-Ribose Polymerase). PARP) The inhibitors - are alkylated bifunctional molecules and the present invention relates to compounds having the structure of Formula I, and also to pharmaceutically acceptable salts and solvates thereof. The preparation method comprises the following steps: condensation of 5 - [(3,4 -dihydro -4 - oxo -1 - phthalazinyl) methyl] -2 -fluorobenzoic acid and N-Boc - piperazine condensation and after-deprotection Boc groups and finally performing condensation connection with a mustard group to obtain the compound shown I. The invention further relates to a pharmaceutical composition containing the compound of the formula I and a pharmaceutical use thereof, and can be used for treating tumors and other targets PARP or DNA. .

A Nickel(II)-Mediated Thiocarbonylation Strategy for Carbon Isotope Labeling of Aliphatic Carboxamides

A series of pharmaceutically relevant small molecules and biopharmaceuticals bearing aliphatic carboxamides have been successfully labeled with carbon-13. Key to the success of this novel carbon isotope labeling technique is the observation that 13C-labeled NiII-acyl complexes, formed from a 13CO insertion step with NiII-alkyl intermediates, rapidly react in less than one minute with 2,2’-dipyridyl disulfide to quantitatively form the corresponding 2-pyridyl thioesters. Either the use of 13C-SilaCOgen or 13C-COgen allows for the stoichiometric addition of isotopically labeled carbon monoxide. Subsequent one-pot acylation of a series of structurally diverse amines provides the desired 13C-labeled carboxamides in good yields. A single electron transfer pathway is proposed between the NiII-acyl complexes and the disulfide providing a reactive NiIII-acyl sulfide intermediate, which rapidly undergoes reductive elimination to the desired thioester. By further optimization of the reaction parameters, reaction times down to only 11 min were identified, opening up the possibility of exploring this chemistry for carbon-11 isotope labeling. Finally, this isotope labeling strategy could be adapted to the synthesis of 13C-labeled liraglutide and insulin degludec, representing two antidiabetic drugs.

Design, synthesis and biological evaluation of novel phthalazinone acridine derivatives as dual PARP and Topo inhibitors for potential anticancer agents

In this study, we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo inhibitors. MTT assays indicated that most of the compounds significantly inhibited multiple cancer cells proliferation. In addition, all the compounds displayed Topo II inhibition activity at 10 mol/L, and also possessed good PARP-1 inhibitory activities. Subsequent mechanistic studies showed that compound 9a induced remarkable apoptosis and caused prominent S cell cycle arrest in HCT116 cells. Our study suggested that 9a inhibiting Topo and PARP concurrently can be a potential lead compound for cancer therapy.

Discovery of SK-575 as a Highly Potent and Efficacious Proteolysis-Targeting Chimera Degrader of PARP1 for Treating Cancers

The nuclear protein poly(ADP-ribose) polymerase-1 (PARP1) has a well-established role in the signaling and repair of DNA and is a validated therapeutic target for cancers and other human diseases. Here, we have designed, synthesized, and evaluated a series of small-molecule PARP1 degraders based on the proteolysis-targeting chimera (PROTAC) concept. Our efforts have led to the discovery of highly potent PARP1 degraders, as exemplified by compound 18 (SK-575). SK-575 potently inhibits the growth of cancer cells bearing BRCA1/2 mutations and induces potent and specific degradation of PARP1 in various human cancer cells even at low picomolar concentrations. SK-575 achieves durable tumor growth inhibition in mice when used as a single agent or in combination with cytotoxic agents, such as temozolomide and cisplatin. These data demonstrate that SK-575 is a highly potent and efficacious PARP1 degrader.

Synthesis, Cytotoxicity, and Mechanistic Investigation of Platinum(IV) Anticancer Complexes Conjugated with Poly(ADP-ribose) Polymerase Inhibitors

Many clinical trials using combinations of platinum drugs and PARP-1 inhibitors (PARPi) have been carried out, with the hope that such combinations will lead to enhanced therapeutic outcomes against tumors. Herein, we obtained seven potential PARPi with structural diversity and then conjugated them with cisplatin-based platinum(IV) complexes. Both the synthesized PARPi ligands and PARPi-Pt conjugates [PARPi-Pt(IV)] show inhibitory effects against PARP-1's catalytic activity. The PARPi-Pt(IV) conjugates are cytotoxic in a panel of human cancer cell lines, and the leading ones display the ability to overcome cisplatin resistance. A mechanistic investigation reveals that the representative PARPi-Pt(IV) conjugates efficiently enter cells, bind to genomic DNA, disturb cell cycle distribution, and induce apoptotic cell death in both cisplatin-sensitive and-resistant cells. Our study provides a strategy to improve the cytotoxicity of platinum(IV)-based anticancer complexes and overcome cisplatin resistance by using a small-molecule anticancer complex that simultaneously damages DNA and inhibits PARP.

Induction of apoptosis in MDA-MB-231 breast cancer cells by a PARP1-targeting PROTAC small molecule

Poly (ADP-ribose) polymerase-1 (PARP1) is a major member of the PARP superfamily that is involved in DNA damage signalling and other important cellular processes. Here we report the development of a small molecule targeting PARP1 based on the PROTAC strategy. In the MDA-MB-231 cell line, the representative compound 3 can induce significant PARP1 cleavage and programmed cell death.

PROCESS FOR THE PREPARATION OF OLAPARIB AND POLYMORPHS THEREOF

The present invention is directed to process for preparation of Olaparib of formula (I). The present invention further relates to novel polymorphic forms of Olaparib, pharmaceutical compositions containing them, and method of treatment using the same.

Phthalazone hydroxamic acid derivative as well as preparation method and application thereof

The invention discloses a phthalazone hydroxamic acid compound with poly(ADP-ribose) polymerase (PARP) and/or histone deacetylase (HDAC) inhibitory activity as well as a preparation method and application thereof. A structural formula of the phthalazone hydroxamic acid compound is shown in a formula I described in the specification, wherein R1 is a hydrogen atom or halogen, R2 is a hydrogen atom or halogen, Y is an oxygen atom, methylene or difluorine-substituted methylene, Z is described in the specification, and G is a chemical bond, methylene, fluoromethylene or a double bond. In vitro cell proliferation experiments show that the compound shown in the formula I can well inhibit proliferation of multiple tumor cells. A PARP and HDAC inhibitory experiment shows that the compound shown in the formula I is a compound with good inhibitory activity on PARP and/or HDAC.