CN107235959A - A kind of novel method for synthesizing for preparing cancer therapy drug Niraparib - Google Patents
A kind of novel method for synthesizing for preparing cancer therapy drug Niraparib Download PDFInfo
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- CN107235959A CN107235959A CN201710598888.7A CN201710598888A CN107235959A CN 107235959 A CN107235959 A CN 107235959A CN 201710598888 A CN201710598888 A CN 201710598888A CN 107235959 A CN107235959 A CN 107235959A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Abstract
A kind of novel method for synthesizing for preparing cancer therapy drug Niraparib; this method is reduced including the nitrobenzene methyl of 3 formoxyl of initiation material 2 through 2 nitros; diazotising; reduction; cyclisation; substitution, separation, amidatioon, de- BOC obtain the optical voidness Niraparib that purity reaches more than 97.51%.The inventive method is easy, and yield is high, and loss is few, it is easy to operates, equipment requirement is few, is a method which be suitable for industrial production.
Description
Technical field
The present invention relates to cancer therapy drug Niraparib synthetic method, belong to technical field of medicine synthesis.
Background technology
Niraparib chemical names are 2- [4- ((3S) -3- piperidyls) phenyl] -2H- indazole -7- formamides, are a kind of
Oral Poly ADP-ribose polymerase (PARP) inhibitor, suppresses reparation of the cell to DNA damage, for prominent with BRCA genes
For the cancer cell of change, if PARP activity is further suppressed, a large amount of DNA damages will be produced during these cell divisions,
Cause cancer cell death.Niraparib is applied to the cancer of BRCA1/2 gene mutations, such as oophoroma and breast cancer, by the U.S.
Biotech company Tesaro is researched and developed.The III clinical trial phases that a key name is NOVA are completed, Niraparib presents pole
For good curative effect.In experiment, researcher recruited more than 500 after platinum-based chemotherapy oophoroma there is the patient recurred, and
Whether BRCA gene mutations are carried according to reproduction cell, patient has been divided into two groups.The group that BRCA is mutated is carried in reproduction cell
In, the median by the Niraparib patient's progression free survival phases treated is up to 21 months, and 5.5 months than control group are obtained
Notable extension is arrived.
At present, the relevant patent document of synthetic method in the prior art for Niraparib includes Preparation
of pharmaceutically acceptable salts of(3S)-3-[4-[7-(aminocarbonyl)-2H-
indazol-2-yl]phenyl]piperidines as inhibitors of poly(ADP-ribose)polymerase
(PARP), Preparation of piperidinylphenylindazolylcarboxamide for use as poly
(ADP-ribose) polymerase inhibitors etc., disclose a pharmaceutical chemistry synthetic route and to Niraparib's
Discovery procedure has carried out detailed discussion.
The synthetic route using 3- methyl -2- nitrobenzoic acids as initiation material, by with methanol under conditions of acyl chlorides ester
Change obtains compound A, A and is heated to reflux in benzoyl peroxide and NBS CCl4 solution 12 hours, and bromination obtains compound B.B with
Acetonitrile and the oxidation of N-methylmorpholine-N- oxide water solutions obtain compound C.The compound C and tert-butyl group -3- (4- aminophenyls)
Piperidines -1- carboxylic acid tert-butyl esters are stirred at reflux in ethanol solution obtains compound D.Compound D and sodium azide and DMF mixtures
Reaction, cyclization formed intermediate E .. compounds E be passed through in methanol solution 60 DEG C of NH3 heating it is acylated intermediate F. compounds
F adds hydrochloric acid in ethyl acetate Yu dioxane solutions, sloughs BOC groups and obtains intermediate G, through Chiralpak AS-H positives
Chiral chromatographic column splits and obtains target compound S type rotamers Niraparib.The synthetic route is longer, uses
Chiralpak AS-H positive chiral chromatographic columns split Niraparib is difficult to realize in large-scale industrial production, and reaction
Used sodium azide etc. unstable and difficult post processing raw material, limit industrialization safety in production.
The content of the invention
In order to overcome the above-mentioned deficiencies of the prior art, cancer therapy drug is prepared it is an object of the invention to provide one kind
Niraparib novel method for synthesizing, route is novel, obtains multiple brand-new intermediates in building-up process, and intermediate
Property is stable, easy to operate, it is easy to accomplish industrialized production.
A kind of novel method for synthesizing for preparing cancer therapy drug Niraparib, synthetic route is as follows：
1) synthetic method of intermediate 1 is prepared, its structure is as follows：
Synthesis step includes:Initiation materialDone with acetic acid and ethanol
Solvent, by 2 nitros of iron powder selective reduction on aldehyde radical without influence, generates intermediate 2, it is characterised in that iron powder density is big,
Easily precipitation, easily separated to remove, and environmental pollution is small.
2) structure of intermediate 2 is as follows：
Synthesis step includes：With concentrated hydrochloric acid into salt and natrium nitrosum diazotising occurs for intermediate 1
Reaction generation intermediate 2.
3) structure of intermediate 3 is as follows：
Synthesis step includes：Intermediate 2 by sodium sulfite reduce after can obtain intermediate 3, instead
It is -10 DEG C -10 DEG C to answer temperature.
4) structure of intermediate 4 is as follows：Synthesis step includes：Intermediate 3 makees solvent with methanol, plus
Heat backflow can be cyclized as indazole ring intermediate 4 for 3 hours.
5) structure of intermediate 5 is as follows：
Synthesis step includes：The S type tert-butyl groups -3- (4- bromos phenyl) piperidines -1- carboxylic acid tert-butyl esters,
Substitution reaction occurs in the basic conditions with intermediate 4, then by being recrystallized to give intermediate 5.
6) structure of intermediate 6 is as follows：
Synthesis step includes：Intermediate 5 is in the presence of sodium methoxide, formamide, methyl esters ammonolysis
The amide structure of Niraparib intermediates 6 is formed afterwards.
7) structure of Niraparib compounds (I) is as follows：Synthesis step includes：Intermediate 6 exists
In DCM (dichloromethane), Niraparib compounds (I) are obtained with the de- BOC protection groups of trifluoroacetic acid reaction at room temperature.
Further detailed step is as follows：
1) preparation of intermediate 1 is prepared：3- formoxyl -2- nitrobenzene methyls are dissolved in absolute ethyl alcohol, Ran Houjia
Enter and be heated to reflux under conditions of iron powder and acetic acid, 40 DEG C, 2 nitros are reduced to amino, and 3 aldehyde radicals are unaffected, in addition
Fe powder is cheap, and density is big, easily precipitation, easily separated to remove, and environmental pollution is small；
2) nitrous such as potassium nitrite, calcium nitrite, silver nitrite, natrium nitrosum, barium nitrite can be used in diazo-reaction
Hydrochlorate；Nitrosylsulfuric acid or the tertiary fourth of nitrous ether (ethyl nitrite), isoamyl nitrite, isobutyl nitrite, Isopropyl Nitrite, nitrous acid
Nitrous acid ester such as ester, nitrous acid straight butyl, n-propyl nitrite etc. and carry out.It is preferred that natrium nitrosum, intermediate 1 and concentrated hydrochloric acid into
Occurs diazo-reaction generation intermediate 2 after salt with natrium nitrosum；
3) diazol that previous step is generated is added drop-wise in sodium sulfite solution and is reduced to intermediate 3；
4) intermediate 3 be heated to reflux 3h in methyl alcohol can be using cyclization as intermediate 4；
5) the S type tert-butyl groups -3- (4- bromos phenyl) piperidines -1- carboxylic acid tert-butyl esters are dissolved in 10% NaOH solution so
Reacted afterwards with intermediate 4, doing solvent recrystallization with methanol obtains Niraparib intermediates 5；
6) amide structure that intermediate 5 is formed in intermediate 6 after ammonolysis in the presence of sodium methoxide, formamide；
7) intermediate 6 takes off BOC protection groups and obtains Niraparib compounds (I)；Solvent is made with DCM, the mol ratio of material is
Intermediate：DCM：Trifluoracetic acid=1:5:1, reaction in about 3 hours is stirred at room temperature completely, is evaporated and obtains as Niraparib chemical combination
Thing (I).
The beneficial effects of the invention are as follows：
1) nitrobenzoic acid of initiation material 3- methyl -2 that the present invention is used synthesizes what field was generally used for organic drug
Raw material, it is cheap and be readily obtained；
2) synthesis step of the present invention is simple, and operating condition is easy to control.
3) present invention in each intermediate link only with such as：The operations such as extraction, dry, filtering, crystallization and recrystallization
Method, post processing is simple and convenient, is easier to realize large-scale production.
4) route of the present invention is novel, and the property of solvent and catalyst used in building-up process is stable, it is easy to production
Thing is separated, easy to operate, efficiency high, it is easy to accomplish industrialized production.
5) present invention avoids carrying out chiral resolution in final step, can reduce loss of product.
Brief description of the drawings
Fig. 1 is Niraparib HPLC chromatograms.
Embodiment
The present invention is further discussed below with reference to embodiments, but the present invention is not limited to following examples.
Embodiment
Intermediate 1Synthesis
Addition 11.2g (0.05mol) 3- formoxyl -2- nitrobenzene methyls in round-bottomed flask, absolute ethyl alcohol 17ml,
Stirring is allowed to after dissolving add iron powder 2g (35.7mmol), and acetic acid 17mL, distilled water 8.5mL is eventually adding a drop concentrated hydrochloric acid, 40
DEG C it is heated to reflux 15min (TLC monitoring reactions are complete) and stops reaction, suction filtration wash filter residue with water 10mL, collects filtrate use
CHCl3 extracts (3x15mL) and merges organic phase in three times, is washed with NaHCO3 (3x15mL) and distilled water (2x10mL), stands and divides
From organic phase, anhydrous magnesium sulfate is dried, and is concentrated to give yellow oil.Column chromatography for separation [V (ethyl acetate)：V (petroleum ether)=1:
9], the yellow oil after concentration is that Niraparib intermediates 1 are that 7.7g (0.043mol) yield is 86%.
1HNMR(300MHz,DMSO-d6)δ(ppm):10.33 (1H, s), 7.98 (1H, d, J=7.5Hz), 7.83 (1H,
D, J=7.5Hz), 7.05 (1H, t), 6.29 (2H, s), 3.90 (3H, s)；13CNMR(75MHz,DMSO-d6)δ(ppm):
193.0,168.6,149.3,139.1,136.5,130.3,119.2,110.4,51.7；MS(ESI)for(M+H)+:180.1.
Intermediate 2Synthesis
7.17g (0.04mol) Niraparib intermediates 1 are mixed with 16.5mL concentrated hydrochloric acids, when being cooled to 10 DEG C, to anti-
Answer and 4.2mL30% sodium nitrite solutions (0.04mol) are slowly added dropwise in bottle.Excessive nitrous is examined with starch potassium iodide paper
Acid, determines reaction end.Stir 3h and carry out diazo-reaction, be incubated stratification, lower floor is diazonium salt solution, obtained after drying
7.55gNiraparib intermediates 2, yield is 83.56%.
1HNMR(300MHz,DMSO-d6)δ(ppm):10.33 (1H, s), 8.35 (1H, d, J=7.2Hz), 8.12 (1H,
D, J=7.2Hz), 7.66 (1H, t), 3.90 (3H, s)；13CNMR(75MHz,DMSO-d6)δ(ppm):188.4,164.6,
136.3,134.4,132.2,130.5,129.2,123.5,51.7；MS(ESI)for(M+H)+:227.0.
Intermediate 3Synthesis
8.4mL30% sodium sulfite solutions (0.08mol) are prepared, above-mentioned diazol are added dropwise into sodium sulfite aqueous solution molten
Liquid, while need to control to react 50min below 30 DEG C with 10%NaOH solution regulation pH6-8. temperature, then exists temperature control
Less than 100 DEG C progress vacuum rotary steam dehydrations, obtain sulfonamide sodium salts A wet-milling, sulfonamide sodium salts A wet-milling are dried at less than 100 DEG C
It is dry, sulfonamide sodium salts A dry powder is obtained, dry powder is dissolved in 15mL ethyl acetate, 10-15 DEG C is cooled to, few drops of dense sulphur are added dropwise thereto
Acid, absorbs the sour gas of effusion, 35 DEG C or so insulated and stirred 1h is warming up to after adding, and is cooled to 5-10 DEG C, is added dropwise 10%
NaOH solution reaches 10 to pH, and reaction stands a point liquid after terminating, and by upper strata ester, mutually less than 50 DEG C rotary evaporations remove ethyl acetate, under
The ethyl acetate that layer aqueous phase is reclaimed through upper strata enters purification tank for liquid waste after repeatedly extracting, the ester of extraction is mutually harmonious with upper strata ester again
And；Ester is mutually removed into the agitation grinding that added water after ethyl acetate, suction filtration, washing, gained wet-milling drying Niraparib intermediates
3 finished product 5.36g, yield 80%.
1HNMR(300MHz,DMSO-d6)δ(ppm):10.33 (1H, s), 8.17 (1H, d, J=7.3Hz), 8.03 (1H,
D, J=7.3Hz), 7.10 (1H, t), 5.0 (1H, s), 3.90 (3H, s), 3.12 (2H, s)；13CNMR(75MHz,DMSO-d6)δ
(ppm):193.0,168.7,144.8,138.9,136.3,127.2,119.3,107.8,51.7；MS(ESI)for(M+H)+:
195.1.
Intermediate 4Synthesis
Fully dissolved after 4.27g (22mmol) Niraparib intermediates 3 are mixed with 30mL methanol, under conditions of 60 DEG C
3.17gNiraparib intermediates 4 can be obtained by being heated to reflux 3h, and yield is 82%.
1HNMR(300MHz,DMSO-d6)δ(ppm):13.7(1H,s),7.84-7.78(2H,m),7.56-7.55(2H,
m),3.90(3H,s)；13CNMR(75MHz,DMSO-d6)δ(ppm):167.3,133.5,132.3,128.5,125.4,51.7；
MS(ESI)for(M+H)+:177.1.
Intermediate 5Synthesis
The 10.2g S type tert-butyl groups -3- (4- bromos phenyl) piperidines -1- carboxylic acid tert-butyl esters are taken to be dissolved in 60mL10% hydroxides
Sodium solution, is stirred continuously in lower instillation 3.17gNiraparib intermediates 4, stirs 30min, stands still for crystals suction filtration, 40 DEG C of vacuum
Dry 4h,
By dried compound recrystallizing methanol, obtaining the molar yield of 7.56gNiraparib intermediates 5. is
79%.
1H-NMR(300MHz,DMSO-d6)δ(ppm):8.51 (1H, s), 8.13 (1H, d, J=7.1Hz), 7.95 (1H,
D, J=8.3Hz), 7.91 (2H, d, J=8.4Hz), 7.39 (2H, d, J=8.4Hz), 7.18 (1H, t, J=7.2Hz), 4.30-
4.10(2H,m),4.00(3H,s),2.85-2.70(3H,m),2.11-2.03(1H,m),1.83-1.75(1H,m),1.73-
1.53(2H,m),1.48(9H,s).13CNMR(75MHz,DMSO-d6)δ(ppm):167.3,153.4,145.3,136.8,
128.4,126.7,125.1,124.1,120.8,112.0,80.0,57.0,51.3,49.0,40.3,30.5,28.1,22.8；
MS(ESI)for(M+H)+:436.2.
Intermediate 6Synthesis
7.4g (17mmol) Niraparib intermediates 5 are dissolved in 40mL dry DMFs at 0 DEG C, added into this solution
10mL (252mmol) formamide, 3.0g (56mmol) sodium methoxide is warming up to 40 DEG C of reaction 3.5h.Reaction solution is cooled to room temperature,
It is poured into 200mL water, stirs 1h, suction filtration is dried, obtains the crude product 6.22g of Niraparib intermediates 6 (theoretical yield is 4.97g),
Yield is 87%.The crude product 5.0g of Niraparib intermediates 6 is added to 40mL dioxane-water (volume ratio 8: 1) at room temperature
In the mixed solvent, is warming up to 101 DEG C, complete molten rear addition 0.1g (mass fraction 2%) activated carbon of solid continues the 0.5h that flows back, taken advantage of
Hot suction filtration, filtrate is cooled to 0 DEG C, stands 2h (precipitation white needle-like crystals), suction filtration, dry Niraparib intermediates 6.1H-
NMR(300MHz,DMSO-d6)δ(ppm):9.04 (1H, br.s), 8.51 (1H, s), 8.31 (1H, d, J=6.8Hz), 7.91
(1H, d, J=8.3Hz), 7.84 (2H, d, J=8.2Hz), 7.42 (2H, d, J=8.2Hz), 7.31-7.22 (1H, m), 5.95
(1H,br,s),4.40-4.05(2H,m),2.90-2.70(3H,m),2.15-2.00(1H,m),1.85-1.75(1H,m),
1.75-1.50(2H,m),1.48(9H,s)；13CNMR(75MHz,DMSO-d6)δ(ppm):168.2,153.4,143.6,
136.8,128.9,126.5,125.1,124.3,120.8,115.1,80.0,57.0,49.3,40.5,30.7,28.4,22.5；
MS(ESI)for(M+H)+:421.2
Niraparib compounds (I)Synthesis
4.0gNiraparib intermediates 6 (9.3mmol) are added in 40ml dichloromethane after fully dissolving, are added dropwise
After 10mL trifluoroacetic acid solutions, stirring 24h, 20mL sodium hydrate aqueous solutions are added, stratification collects organic phase, uses anhydrous sulphur
Sour sodium is dried, and is concentrated to give 2.46gNiraparib, and step reaction molar yield is 82.56%, and overall yield of reaction is 26.75%.
It is 97.51% (chromatogram is illustrated in fig. 1 shown below) to determine Niraparib purity through HPLC1H-NMR(300MHz,DMSO-d6)δ
(ppm):9.28 (1H, s), 8.57 (1H, br, s), 8.06 (2H, d, J=7.2Hz), 8.04 (2H, d, J=8.4Hz), 7.88
(2H, br.s), 7.49 (2H, d, J=8.4Hz), 7.27 (1H, dd, J=8.4,7.2Hz), 3.08-2.94 (2H, m), 2.77-
2.67(1H,m),2.76-2.73(2H,m),1.75-1.47(4H,m).
13C-NMR(75MHz,DMSO-d6)δ(ppm):168.2,143.4,136.7,128.8,126.4,125.1,
123.9,120.9,115.2,52.2,48.8,43.5,30.8,25.1,MS(ESI)for(M+H)+:321.2。
Claims (9)
1. a kind of novel method for synthesizing for preparing cancer therapy drug Niraparib, it is characterised in that synthetic route is as follows：
2. a kind of novel method for synthesizing for preparing cancer therapy drug Niraparib according to claim 1, it is characterised in that
The synthetic method of intermediate 1 is prepared, its structure is as follows：
Synthesis step includes:Initiation materialSolvent is done with acetic acid and ethanol,
By 2 nitros of iron powder selective reduction on aldehyde radical without influence, intermediate 2 is generated, it is characterised in that iron powder density is big, Yi Chen
Form sediment, easily separated to remove, environmental pollution is small.
3. a kind of novel method for synthesizing for preparing cancer therapy drug Niraparib according to claim 1, it is characterised in that
The structure of intermediate 2 is as follows：
Synthesis step includes：With concentrated hydrochloric acid into salt and natrium nitrosum diazo-reaction occurs for intermediate 1
Generate intermediate 2.
4. a kind of novel method for synthesizing for preparing cancer therapy drug Niraparib according to claim 1, it is characterised in that
The structure of intermediate 3 is as follows：
Synthesis step includes：Intermediate 2 by sodium sulfite reduce after can obtain intermediate 3, reaction temperature
Spend for -10 DEG C -10 DEG C.
5. a kind of novel method for synthesizing for preparing cancer therapy drug Niraparib according to claim 1, it is characterised in that
The structure of intermediate 4 is as follows：Synthesis step includes：Intermediate 3 makees solvent with methanol, is heated to reflux 3 small
When can be cyclized as indazole ring intermediate 4.
6. a kind of novel method for synthesizing for preparing cancer therapy drug Niraparib according to claim 1, it is characterised in that
The structure of intermediate 5 is as follows：
Synthesis step includes：The S type tert-butyl groups -3- (4- bromos phenyl) piperidines -1- carboxylic acid tert-butyl esters, with centre
Substitution reaction occurs in the basic conditions for body 4, then by being recrystallized to give intermediate 5.
7. a kind of novel method for synthesizing for preparing cancer therapy drug Niraparib according to claim 1, it is characterised in that
The structure of intermediate 6 is as follows：
Synthesis step includes：Intermediate 5 is formed in the presence of sodium methoxide, formamide after methyl esters ammonolysis
The amide structure of Niraparib intermediates 6.
8. a kind of novel method for synthesizing for preparing cancer therapy drug Niraparib according to claim 1, it is characterised in that
The structure of Niraparib compounds (I) is as follows：Synthesis step includes：Intermediate 6 is in DCM (dichloromethanes
Alkane) in, obtain Niraparib compounds (I) with the de- BOC protection groups of trifluoroacetic acid reaction at room temperature.
9. a kind of novel method for synthesizing for preparing cancer therapy drug Niraparib according to claim 1, it is characterised in that
Detailed step is as follows：
1) preparation of intermediate 1 is prepared：3- formoxyl -2- nitrobenzene methyls are dissolved in absolute ethyl alcohol, iron is then added
Powder and acetic acid, are heated to reflux under conditions of 40 DEG C, 2 nitros are reduced into amino, and 3 aldehyde radicals are unaffected, in addition Fe powder
Cheap, density is big, easily precipitation, easily separated to remove, and environmental pollution is small；
2) nitrite such as potassium nitrite, calcium nitrite, silver nitrite, natrium nitrosum, barium nitrite can be used in diazo-reaction；
Nitrosylsulfuric acid or nitrous ether (ethyl nitrite), isoamyl nitrite, isobutyl nitrite, Isopropyl Nitrite, nitrite tert-butyl, Asia
Nitrous acid ester such as nitric acid N-butyl, n-propyl nitrite etc. and carry out.It is preferred that natrium nitrosum, intermediate 1 and concentrated hydrochloric acid are into after salt
Occurs diazo-reaction generation intermediate 2 with natrium nitrosum；
3) diazol that previous step is generated is added drop-wise in sodium sulfite solution and is reduced to intermediate 3；
4) intermediate 3 be heated to reflux 3h in methyl alcohol can be using cyclization as intermediate 4；
5) by the S type tert-butyl groups -3- (4- bromos phenyl) piperidines -1- carboxylic acid tert-butyl esters be dissolved in 10% NaOH solution then with
Intermediate 4 reacts, and doing solvent recrystallization with methanol obtains Niraparib intermediates 5；
6) amide structure that intermediate 5 is formed in intermediate 6 after ammonolysis in the presence of sodium methoxide, formamide；
7) intermediate 6 takes off BOC protection groups and obtains Niraparib compounds (I)；Solvent is made with DCM, the mol ratio of material is centre
Body：DCM：Trifluoracetic acid=1:5:1, reaction in about 3 hours is stirred at room temperature completely, is evaporated and obtains as Niraparib compounds
(I)。
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| CN108084157A (en) * | 2018-02-12 | 2018-05-29 | 安庆奇创药业有限公司 | A kind of synthetic method of Ni Lapani |
| CN110156751B (en) * | 2019-05-28 | 2022-01-18 | 江苏食品药品职业技术学院 | Novel method for preparing nilapanib and intermediate thereof |
| CN115611860A (en) * | 2021-07-13 | 2023-01-17 | 上海博璞诺科技发展有限公司 | Method for synthesizing nilapanib |
| CN113637002B (en) * | 2021-08-02 | 2022-09-30 | 天津太平洋化学制药有限公司 | Preparation method of Nilaparib |
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| CN107235957A (en) * | 2016-09-30 | 2017-10-10 | 陕西科技大学 | A kind of synthetic method for preparing Niraparib |
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| CN101578279A (en) * | 2007-01-10 | 2009-11-11 | P.安杰莱蒂分子生物学研究所 | Amide substituted indazoles as poly(ADP-ribose)polymerase (PARP) inhibitors |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107235957A (en) * | 2016-09-30 | 2017-10-10 | 陕西科技大学 | A kind of synthetic method for preparing Niraparib |
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| CN106632244A (en) | 2017-05-10 |
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