Rucaparib

Base Information

• Chemical Name: Rucaparib
• CAS No.: 283173-50-2
• Molecular Formula: C19H18FN3O
• Molecular Weight: 323.37
• Hs Code.: 2933990090
• European Community (EC) Number: 814-445-0
• UNII: 8237F3U7EH
• DSSTox Substance ID: DTXSID10182563
• Nikkaji Number: J2.564.160D
• Wikipedia: Rucaparib
• Wikidata: Q7376558
• NCI Thesaurus Code: C137800
• RXCUI: 1862579
• Pharos Ligand ID: 7AGVRT34WGZ2
• Metabolomics Workbench ID: 153340
• ChEMBL ID: CHEMBL1173055
• Mol file: 283173-50-2.mol

Synonyms:AG 014699;AG-014699;AG014699;PF-01367338;Rubraca;rucaparib

Chemical Property of Rucaparib

Chemical Property:

• Boiling Point: 625.248 °C at 760 mmHg
• PKA: 14.10±0.20(Predicted)
• Flash Point: 331.938 °C
• PSA: 56.92000
• Density: 1.281 g/cm³
• LogP: 3.69900
• Storage Temp.: 2-8°C(protect from light)
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• XLogP3: 2.5
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 3
• Exact Mass: 323.14339037
• Heavy Atom Count: 24
• Complexity: 466

Purity/Quality:

Rucaparib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CNCC1=CC=C(C=C1)C2=C3CCNC(=O)C4=C3C(=CC(=C4)F)N2
• Recent ClinicalTrials: PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors and Small Cell Cancers
• Recent EU Clinical Trials: A randomized phase II trial of Mirvetuximab soravtansine (IMGN853), in folate receptor alpha (FRα) high recurrent ovarian cancer eligible for platinum-based chemotherapy.
• Recent NIPH Clinical Trials: A Study in Ovarian Cancer Patients Evaluating Rucaparib and Nivolumab as Maintenance Treatment Following Response to Front-Line Platinum-Based Chemotherapy (ATHENA)
• Description: Rucaparib is a PARP inhibitor used as an anti-cancer agent. Rucaparib is a first-in-class pharmaceutical drug targeting the DNA repair enzyme poly-ADP ribose polymerase-1 (PARP-1). It was discovered as part of a collaboration between scientists working at the Northern Institute of Cancer Research and Medical School of Newcastle University and Agouron Pharmaceuticals in San Diego, California. It is being developed by Clovis Oncology. Rucaparib was approved in the US as an oral treatment for advanced ovarian cancer. Development of rucaparib began with collaborations between Cancer Research UK and Agouron Pharmaceuticals (later acquired by Pfizer). Global development rights for rucaparib were ultimately granted to Clovis Oncology via a licensing agreement from Pfizer. To qualify for treatment with rucaparib monotherapy, patients must demonstrate deleterious breast cancer (BRCA) mutation (germline and/or somatic)- associated advanced ovarian cancer and also must have previously been treated with two or more chemotherapy regimens. Rucaparib functions as a small molecule poly(ADPribose) polymerase (PARP) inhibitor, which plays an important role in DNA repair. This newly approved drug displays nanomolar potency against PARP-1, -2, and -3 enzymes, which translates into improved efficacy over alternative therapies such as olaparib or niraparib. Furthermore, rucaparib is also known to cause vasodilation, which is thought to induce tumor perfusion and increased accumulation of the drug in cancer cells. Although rucaparib shows higher cytotoxicity in cancer cells with mutation of BRCA1/2 genes and other DNA repair genes, reduced tumor growth was observed in mouse xenograft models of human cancers with and without BRCA mutations.Rucaparib is also being pursued as a treatment for breast cancer and has displayed promising initial results in trials for pancreatic cancer. Poly(ADP-ribose) polymerases (PARPs) are activated by DNA single- and double-strand breaks and promote repair of DNA damage through the relaxation of chromatin and recruitment of other repair proteins. Inhibition of PARP activity has been linked to synthetic lethality in cells with mutations in BRCA1 or BRCA2 and is used as a therapeutic strategy to selectively target cancers. Rucaparib is a potent, cell-permeable inhibitor of PARP1 (Ki = <5 nM) that is used in clinical therapy to sensitize cancer cells to chemotherapy. Rucaparib inactivates PARP activity in cells with homologous recombination DNA repair pathway mutations at LC50 values ranging from 1.3-5.5 μM. At 25 mg/kg, rucaparib arrests tumor growth in mice bearing epigenetically silenced BRCA1 UACC3199 xenograft tumors. It has been shown to increase efficacy of temozolomide in medulloblastoma cells and xenografts.
• Uses: Rucaparib is PARP1 inhibitor. It can be used in biological study of chemical screening to identify drugs that enhance or mitigate cellular responses to antibody-toxin fusion proteins using human B cell precursor leukemia cells and cervical adenocarcinoma cells.

Technology Process of Rucaparib

There total 54 articles about Rucaparib 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: 90.83%

C19H16FN3O → Rucaparib (283173-50-2)

Guidance literature:

C₁₉H₁₆FN₃O; With sodium tetrahydroborate; In ethanol; for 1h;

With sodium hydroxide; In water; at 10 ℃; for 2h;

Reference yield: 89.7%

[4-(8-fluoro-6-oxo-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-2-yl)-benzyl]-methyl-carbamic acid methyl ester (880160-69-0) → Rucaparib (283173-50-2)

Guidance literature:

With hydrogen bromide; acetic acid; at 20 ℃; for 12h;

Reference yield: 88.0%

C35H40FN3O4 → Rucaparib (283173-50-2)

Guidance literature:

With diphenylether; trifluoroacetic acid; at 100 ℃; for 24h;

upstream raw materials:

[4-(8-fluoro-6-oxo-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-2-yl)-benzyl]-methyl-carbamic acid methyl ester

4-(8-fluoro-6-oxo-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd] indol-2-yl)-benzaldehyde

2-phenyl-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-6-one

8-fluoro-2-((4-methylaminomethyl)phenyl)-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one hydrochloride

Refernces

• 1、 Beckers, Igor,De Vos, Dirk,O'Rourke, Galahad. "Late-Stage C-H Arylation of Azepinoindole via Pd/Cu Catalysis: A Step Efficient and Convergent Synthesis of Rucaparib". . . Retrieved 2021/10/01.
• 2、 -. "CRYSTALLINE OF CAMPHORSULFONIC ACID SALT OF RUCAPARIB AND METHOD OF PREPARING OF TRICYCLIC COMPOUNDS, RUCAPARIB AND CRYSTALLINE OF CAMPHORSULFONIC ACID SALT OF RUCAPARIB". Paragraph 0077-0082; 0085. . Retrieved 2020/06/15.