2H-Indazole-7-carboxamide, 2-[4-(3S)-3-piperidinylphenyl]-
Niraparib
CAS: 1038915-60-4
Molecular Formula: C19H20N4O
2H-Indazole-7-carboxamide, 2-[4-(3S)-3-piperidinylphenyl]- - Names and Identifiers
2H-Indazole-7-carboxamide, 2-[4-(3S)-3-piperidinylphenyl]- - Physico-chemical Properties
| Molecular Formula | C19H20N4O |
| Molar Mass | 320.39 |
| Density | 1.34 |
| Melting Point | 187-189°C |
| Boling Point | 463.6±45.0 °C(Predicted) |
| Appearance | Form Solid, color Pale Yellow to Light Yellow |
| pKa | 15.36±0.30(Predicted) |
| Storage Condition | 2-8°C(protect from light) |
| Use | MK-4827(Niraparib) is a highly active PARP1/PARP2 inhibitor with IC50 of 3.8 nM/2.1 nM respectively. It has good activity in BRCA-1 and BRCA-2 mutant tumor cells, which is more than 330 times higher than PARP3,V-PARP and Tank1. |
2H-Indazole-7-carboxamide, 2-[4-(3S)-3-piperidinylphenyl]- - Upstream Downstream Industry
2H-Indazole-7-carboxamide, 2-[4-(3S)-3-piperidinylphenyl]- - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 3.121 ml | 15.606 ml | 31.212 ml |
| 5 mM | 0.624 ml | 3.121 ml | 6.242 ml |
| 10 mM | 0.312 ml | 1.561 ml | 3.121 ml |
| 5 mM | 0.062 ml | 0.312 ml | 0.624 ml |
Last Update：2024-01-02 23:10:35
2H-Indazole-7-carboxamide, 2-[4-(3S)-3-piperidinylphenyl]- - Uses and synthesis methods
overview
Nirapani (niraparib, trade name Zejula) is a polyadenosine diphosphate ribose polymerase (polybosphateadenosineribosepolymerase,PARP) inhibitor developed by Tesaro, which can inhibit DNA repair. Its active component is free alkali, and the stable component is p-toluene sulfonate (niraparibtosylatemonohydrate) or hydrochloride containing one molecule of crystal water (niraparibhydrochloride, the effective component is niraparibtosylatemonohydrate). And on March 27, 2017, FDA approved the listing, mainly for the treatment of recurrent epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer, and maintenance treatment for adult patients with complete or partial response to platinum-based chemotherapy drugs.
mechanism of action
PARP includes a variety of subtypes, which have high homology, involving cell DNA repair, gene expression, cycle control, intracellular transport and energy metabolism and other functions. Previous studies have pointed out that PARP-1 inhibitors and BRCA1/2 defects act on tumor cells at the same time, which can cause tumor cell death (especially breast cancer and ovarian cancer), and have no effect on normal cells. Niraparib are PARP-1 and PARP-2 inhibitors with IC50 of 3.8nM and 2.1nM, respectively. Preclinical studies have shown that niraparib induced cytotoxic effects, including inhibition of PARP catalytic activity and promotion of PARP-DNA complex formation, lead to DNA damage, apoptosis and cell death. niraparib induced cytotoxicity can be observed regardless of whether the tumor cell line has BRCA1/2 defect. niraparib inhibited tumor growth in both mouse xenograft models with BRCA1/2-deficient human tumor cell lines and human tumor xenograft models with defective or wild-type BRCA1/2 homologous recombination defects.
Preparation method
Using 3-methyl-2-nitrobenzoic acid as the starting material, it is oxidized after esterification and bromination to obtain methyl 3-formyl-2-nitrobenzoate (2),2 and 3 under ethanol reflux conditions React to form Schiff's base, then cyclize under the action of sodium azide to obtain 2-{4-[1-(tert-butoxycarbonyl) piperidin-3-yl] phenyl}-2H-indazole-7-carboxylic acid methyl ester (4),4 2-{4-[1-(tert-butoxycarbonyl) piperidin-3-yl] phenyl}-2H-indazol-7-formamide (5) was obtained by ammoniation, 5 Boc protecting group was removed by acidolysis to obtain 2-[4-(3-piperidinyl) phenyl]-2H-indazol-7-formamide (6), and finally the niraparib was obtained by manual resolution.
Last Update：2024-04-10 22:29:15
2H-Indazole-7-carboxamide, 2-[4-(3S)-3-piperidinylphenyl]- - Uses and synthesis methods
precautions
1. the recommended dose of the Niraparib is 300mg(3 tablets) per day. for adverse reactions caused by the drug, it can be considered to reduce the dose to 200mg(2 tablets) per day. If necessary, the dose can be reduced again to 100mg(1 capsule) per day. After reducing the dose twice, the adverse reactions have not been alleviated, and it is necessary to consider stopping the drug.
2. for non-hematological adverse reactions of grade 3 and above that cannot be prevented or have nothing to do with treatment, the administration may be suspended until the adverse reactions are eliminated, but the longest withdrawal time shall not exceed 28 days; Or continue to administer with reduced dose, and the low dose can be reduced up to 2 times.
3. hematological adverse reactions requiring blood transfusion: when the platelet count of the patient does not exceed 1 × 1010?L-1, the patient needs to be injected with platelets. If there are anticoagulants or antiplatelet drugs in the combined dosing regimen, interrupt these drugs and give the patient a higher dose of platelets; or reduce the dose and continue administration.
Main References
[1] Hao Bojun, Du Jingnan, Bi Huanglei, Zheng Zhibing. Oral polyadenosine diphosphate ribose polymerase inhibitor-nirapanib [J]. Journal of clinical drug therapy, 2017,15(06):13-17.
[2] Han Yu, Zhao Linxiang. Nirapani (Niraparib)[J]. Chinese journal of medicinal chemistry, 2017,27(05):421.
[3] Chen Benchuan, a new drug for ovarian cancer-nirapanib (niraparib)[J]. 2017,36(10):1209-1215.
Last Update：2024-04-10 22:29:15
2H-Indazole-7-carboxamide, 2-[4-(3S)-3-piperidinylphenyl]- - Nature
| Solubility | DMSO (Slightly), Methanol (Slightly) |
Last Update：2024-04-09 20:52:54
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Product Name: Niraparib Request for quotation
CAS: 1038915-60-4
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CAS: 1038915-60-4
Tel: 17505222756
Email: pules.cn@gmail.com
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Product Name: MK-4827 (Niraparib) Visit Supplier Webpage Request for quotationCAS: 1038915-60-4
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View History
Raw Materials for 2H-Indazole-7-carboxamide, 2-[4-(3S)-3-piperidinylphenyl]-
methyl 2-(4-(1-(tert-butoxycarbonyl)piperidin-3-yl)phenyl)-2H-indazole-7-carboxylate
Niraparib intermediate 1
2-(4-(piperidin-3-yl)phenyl)-2H-indazole-7-carboxamide hydrochloride
3-Formyl-2-nitrobenzoic acid methyl ester
Niraparib intermediate 1
2-(4-(piperidin-3-yl)phenyl)-2H-indazole-7-carboxamide hydrochloride
3-Formyl-2-nitrobenzoic acid methyl ester