ChemicalBook > CAS DataBase List > Nintedanib esylate

Nintedanib esylate

Product Name
Nintedanib esylate
CAS No.
656247-18-6
Chemical Name
Nintedanib esylate
Synonyms
Nintedanib esylate;Nintedanib ethanesulfonate;Nintedani;NSC 116056;BIBF-1120 esylate;BIBF 1120 esylate;Nintedanib (Ofev);BIBF 1120 BIBF-1120;Trinidad Neeb esylate;Intedanib ethanesulfonate
CBNumber
CB02509952
Molecular Formula
C33H39N5O7S
Formula Weight
649.76
MOL File
656247-18-6.mol
More
Less

Nintedanib esylate Property

Melting point:
>233°C (dec.)
storage temp. 
-20°C Freezer
solubility 
DMSO (Slightly), Methanol (Slightly)
form 
Yellow solid.
color 
Light Yellow to Yellow
More
Less

Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

More
Less

N-Bromosuccinimide Price

TRC
Product number
N478290
Product name
NintedanibEsylate
Packaging
5mg
Price
$65
Updated
2021/12/16
ChemScene
Product number
CS-3475
Product name
Nintedanibesylate
Purity
99.93%
Packaging
10mg
Price
$66
Updated
2021/12/16
AK Scientific
Product number
9942AL
Product name
Nintedanibesylate
Packaging
25mg
Price
$67.2
Updated
2021/12/16
ChemScene
Product number
CS-3475
Product name
Nintedanibesylate
Purity
99.93%
Packaging
50mg
Price
$96
Updated
2021/12/16
Biosynth Carbosynth
Product number
FD71497
Product name
Nintedanib ethanesulfonate
Packaging
50mg
Price
$100
Updated
2021/12/16
More
Less

Nintedanib esylate Chemical Properties,Usage,Production

Description

Nintedanib esylate is a potent, oral triple angiokinase inhibitor developed by Boehringer Ingelheim that targets proangiogenic and pro-fibrotic pathways mediated by the vascular endothelial growth factor receptor, fibroblast growth factor receptor and plateletderived growth factor receptor families, as well as Src and Flt-3 kinases. It was approved for the treatment of idiopathic pulmonary fibrosis (IPF), a condition in which the lungs become progressively scarred over time, by the US FDA in October 2014 and by the EMA in January 2015. The FDA granted nintedanib esylate fast-track, priority review, orphan product, and breakthrough designations. The drug was also approved by the EMA in November 2014 for treatment of non-small cell lung cancer in combination with docetaxel after first-line chemotherapy.

Uses

Nintedanib Esylate is the salt form of Nintedanib, which is angiokinase inhibitor and is used in the treatment of idiopathic pulmonary fibrosis. Also inhibits the process blood vessel formation which may be used to assist in cancer therapy.

Definition

ChEBI: An organosulfonate salt obtained by combining nintedanib with one molar equivalent of ethanesulfonic acid. A kinase inhibitor used for the treatment of idiopathic pulmonary fibrosis and cancer.

Synthesis

The synthesis of indolinone 197 commenced with commercial 4-chloro-3-nitro-benzoic acid (194)?aesterification of which preceded displacement of the chloride by dimethyl malonate (195) in the presence of base to generate nitrobenzene 196. Hydrogenation of 196 under acidic conditions furnished 6-methyoxycarbonyl- substituted oxindole 197 by decarboxylative cyclization in 87% yield. Acylation of indolinone 197 with chloroacetic anhydride in refluxing toluene and subsequent condensation with trimethyl orthobenzoate resulted in indolone 198, which was isolated in 86% yield over the two-step sequence. While these two steps could reportedly be combined into a one-pot protocol using acetic anhydride as the solvent, the stepwise procedure was found to be more amenable for large-scale synthesis due to fewer complications with undesired side products. Subjection of 198 to methanolic potassium hydroxide followed by condensation with aniline fragment 199 in refluxing methanol and then exposure to aqueous ethanesulfonic acid in methanol provided nintedanib esylate (XXIII) in 82% over the three-step sequence.
Aniline fragment 199 was prepared in three steps and 82% overall yield via initial acylation of N-methyl-4-nitroaniline 200 with chloro acetylchloride followed by displacement of the a-amidochloride with N-methylpiperazine and hydrogenative reduction of the nitro group gave the desired aniline.183,184

Properties and Applications

Nintedanib esylate (NE) is used in the treatment of idiopathic pulmonary fibrosis (IPF) and in diverse cancers, including nonsmall cell lung cancer (NSCLC). NE has a pH-dependent solubility profile with low aqueous solubility under neutral pH and increased solubility at acidic pH. The oral bioavailability of NE is 4.7% because it is a P-gp substrate and also undergoes first-pass metabolism in the liver by esterases. However, the administration of NE along with food increases the area under the curve (AUC) and maximum concentration (Cmax) when the drug is taken with food; hence, it has a positive food effect[1].

References

[1] Priyanshi Patel, Mitali Patel. “Enhanced oral bioavailability of nintedanib esylate with nanostructured lipid carriers by lymphatic targeting: In vitro, cell line and in vivo evaluation.” European Journal of Pharmaceutical Sciences 159 (2021): Article 105715.
[2] Veerareddy Arava, Surendrareddy Gogireddy. “An improved process for the synthesis of nintedanib esylate.” Synthetic Communications 47 10 (2017): Pages 975-981.
[3] Esylate, Nintedanib. “Nintedanib Esylate.” Definitions 10 1 (2020).
[4] Shabari Girinath Kala, Santhivardhan Chinni. “Bioavailability enhancement of vitamin E TPGS liposomes of nintedanib esylate: formulation optimization, cytotoxicity and pharmacokinetic studies.” Drug Delivery and Translational Research 12 11 (2022): 2856–2864.

Nintedanib esylate Preparation Products And Raw materials

Raw materials

Preparation Products

More
Less

Nintedanib esylate Suppliers

China 275 China Hong Kong 1 Finland 1 India 10 United Kingdom 2 United States 11 Global 300
Joyochem Co.,Ltd
Tel
531-82687558 13290333633
Email
sales@joyochem.com
Country
China
ProdList
19
Advantage
58
Jinan XuanDe Chemical Co., Ltd.
Tel
0531-88803958; 18866891188
Fax
0531-82777287
Email
zhaojiangxia@shiningpharm.com
Country
China
ProdList
264
Advantage
58
Chembest Research Laboratories Limited
Tel
021-20908456
Fax
021-58180499
Email
sales@BioChemBest.com
Country
China
ProdList
6011
Advantage
61
WuHu Linze pharmaceutical Co.,Ltd.
Tel
0553-0553-5802116 18356571950
Fax
-
Email
2592492800@qq.com
Country
China
ProdList
57
Advantage
58
Nanjing Puxin Pharmaceutical Technology Co., Ltd
Tel
17366295326
Fax
QQ360829978
Email
puxinpharma_2017@126.com
Country
China
ProdList
2436
Advantage
58
Shandong Yuhe Pharmaceutical Technology Co., LTD
Tel
15263077727
Fax
QQ：2938966534
Email
1436425847@qq.com
Country
China
ProdList
164
Advantage
58
Cangzhou Enke Pharma-tech Co., Ltd.
Tel
0317-5296180 15533709196
Fax
0317-5106596
Email
sale@enkepharma.com
Country
China
ProdList
1650
Advantage
55
Shouguang Jiasheng Chemical Co., Ltd.
Tel
0536-7971999 18232719690
Fax
0536-7971999
Email
sgjiasheng@hotmail.com
Country
China
ProdList
399
Advantage
58
Shanghai Youna Biopharmaceutical Co., Ltd
Tel
18164002430
Email
511710754@qq.com
Country
China
ProdList
223
Advantage
58
Shanghai Boyle Chemical Co., Ltd.
Tel
Fax
86-21-57758967
Email
sales@boylechem.com
Country
China
ProdList
2923
Advantage
55
BeiJing Hwrk Chemicals Limted
Tel
0757-86329057 18501085097
Fax
010-89508210
Email
sales3.gd@hwrkchemical.com
Country
China
ProdList
7583
Advantage
55
Adamas Reagent, Ltd.
Tel
400-6009262 16621234537
Fax
021-64823266
Email
zhangsn@titansci.com
Country
China
ProdList
14113
Advantage
59
WUHAN SUN-SHINE BIO-TECHNOLOGY Co., Ltd.
Tel
17702719238 17702719238
Email
sales@sun-shinechem.com
Country
China
ProdList
905
Advantage
64
Nanjing Chemlin Chemical Co., Ltd
Tel
025-83697070
Fax
+86-25-83453306
Email
info@chemlin.com.cn
Country
China
ProdList
17940
Advantage
64
Shanghai Hanhong Scientific Co.,Ltd.
Tel
021-54306202 13764082696;
Email
info@hanhongsci.com
Country
China
ProdList
42982
Advantage
64
Hunan Hui Bai Shi Biotechnology Co., Ltd.
Tel
0731-85526065 13308475853
Email
ivy@hnhbsj.com
Country
China
ProdList
4548
Advantage
62
Wuhan Fortuna Chemical Co., Ltd
Tel
027-027-59207852 13308628970
Fax
QQ3130921841
Email
buy@fortunachem.com
Country
China
ProdList
2894
Advantage
58
Changzhou Joyous Chemical Co., Ltd.
Tel
0519-85607258
Fax
0519-85607278
Email
sales@joyouschem.com
Country
China
ProdList
296
Advantage
60
SHANGHAI YINGRUI CHEMICAL TECHNOLOGY CO.,LTD.
Tel
021-34666753 13311639313
Fax
+86-21-34979012
Email
info@shyrchem.com
Country
China
ProdList
570
Advantage
55
Haoyuan Chemexpress Co., Ltd.
Tel
021-58950125
Fax
(86) 21-58955996
Email
info@chemexpress.com
Country
China
ProdList
7553
Advantage
61
Chengdu D-innovation Pharmaceutical Co.，LTD
Tel
028-85929779 18980797963
Email
lijinxi@d-innovation.com
Country
China
ProdList
61
Advantage
55
TargetMol Chemicals Inc.
Tel
021-33632979 15002134094
Fax
021-33632979
Email
marketing@targetmol.com
Country
China
ProdList
7934
Advantage
58
Ningbo Taikang Chemical Co., Ltd.
Tel
0574-87365517 18074210286
Fax
87367735
Email
sales@taikangchem.com
Country
China
ProdList
303
Advantage
58
Shanghai DiBai Chemicals Co., Ltd.
Tel
021-54359730 400-008-9730
Fax
021-54353864
Email
info@chemxyz.com
Country
China
ProdList
3993
Advantage
60
Chengdu Climb Pharmaceutical Technology Co., Ltd.
Tel
028-87608726 13540107218
Fax
028-87608725
Email
sales@cdclimb.com
Country
China
ProdList
104
Advantage
58
ChemStrong Scientific Co.,Ltd
Tel
0755-66853366 13670046396
Fax
0755-28363542
Email
sales@chem-strong.com
Country
China
ProdList
17982
Advantage
56
Nanjing First Pharmaceutical Co., Ltd.
Tel
025-83172655 13585105703
Fax
+86-25-86501191
Email
sales@njfirstpharm.com
Country
China
ProdList
110
Advantage
60
Finetech Industry Limited
Tel
027-87465837 19945049750
Fax
027-8777-2287
Email
sales@finetechnology-ind.com
Country
China
ProdList
9533
Advantage
58
Shanghai Kewel Chemical Co., Ltd.
Tel
021-64609169 18901607656
Fax
021-64609160
Email
greensnown@163.com
Country
China
ProdList
9911
Advantage
50
Shanghai QianJin Chemical Technology Co., Ltd
Tel
021-20900665 17321230821
Fax
021-20900665
Email
2986274987@qq.com
Country
China
ProdList
949
Advantage
55
AdooQ Bioscience CHINA
Tel
025-58849295 18951903616;
Fax
025-68650336
Email
info@adooq.cn
Country
China
ProdList
2989
Advantage
60
Hunan Cangood Medical Technology Ltd.
Tel
400-026-9899
Fax
+86-731-86905278
Country
China
ProdList
71
Advantage
50
Cool Pharm, Ltd
Tel
021-60455363 18019463053
Fax
50966098
Email
sales@coolpharm.com
Country
China
ProdList
12357
Advantage
58
AN PharmaTech Co Ltd
Tel
86(21)68097365
Fax
86(21)33321566
Email
sales@anpharma.net
Country
China
ProdList
4901
Advantage
55
Tianjing Geneston Bio-tech Co.,Ltd.
Tel
022-60131465 18920720807
Fax
022-58558581
Email
zishan_1986@163.com
Country
China
ProdList
742
Advantage
58
ZHEJIANG ZETIAN FINE CHEMICALS CO.,LTD
Tel
0571-0571-87322520/800182836 18305707819
Fax
QQ:3007632051
Email
sales@zetchem.com
Country
China
ProdList
483
Advantage
55
Anqing CHICO Pharmaceutical Co., Ltd.
Tel
13585175604 13585175604
Fax
+86-25-52261140
Email
sales@chicopharm.com
Country
China
ProdList
487
Advantage
65
Nanjing Chempioneer Pharmaceutical Co., Ltd.
Tel
18068075658
Fax
-
Email
sales@chempioneer.com
Country
China
ProdList
1811
Advantage
58
Changzhou Fang Nan Medical Technology Co., Ltd.
Tel
0519-85283268
Country
China
ProdList
116
Advantage
55
Shanghai Biolang biotechnology Co.,Ltd
Tel
17764003753
Fax
13669031409
Email
2326587775@qq.com
Country
China
ProdList
188
Advantage
55
Shanghai Biolang biotechnology Co.,Ltd
Tel
17764003753
Fax
13669031409
Email
2326587775@qq.com
Country
China
ProdList
188
Advantage
55
Struchem Co., Ltd.
Tel
0512-0512-63009836 15365350169
Fax
0512-63006936
Email
helen@struchem.com
Country
China
ProdList
3989
Advantage
60
DebyeTec.com Inc.
Tel
18086626237 18086626237
Fax
qq:2693528373
Email
sales@debyesci.com
Country
China
ProdList
2642
Advantage
56
Shanghai Better-In Pharmaceutical Technology Co.,Ltd.
Tel
021-38921049 13564871374
Fax
+86-21-38921049
Email
sales@better-in.com
Country
China
ProdList
44
Advantage
55
Yangzhou QinYuan Pharmaceutical Co., Ltd.
Tel
0514-80939770 13773367191
Fax
0514-82664689
Email
yzqyyykj@163.com
Country
China
ProdList
228
Advantage
55
Shanghai Send Pharmaceutical Technology Co., Ltd.
Tel
021-58088081 Q3252066219
Fax
QQ3382968513
Email
hailey@shsendpharm.com
Country
China
ProdList
3169
Advantage
55
Jinan Putubio Tech Co., Ltd.
Tel
+86 (531) 8099-2215
Fax
+86 (531) 8099-2215
Email
putubio@outlook.com
Country
China
ProdList
1261
Advantage
55
ATK CHEMICAL COMPANY LIMITED
Tel
3429815786 13301662590
Fax
+86-21-51619052
Email
sales@atkchemical.com
Country
China
ProdList
10006
Advantage
55
Shanghai BLT Biological Pharmaceutical Co., Ltd.
Tel
021-20786057 18918495077
Fax
021-20786057
Email
3116390381@qq.com
Country
China
ProdList
220
Advantage
58
Shanghai EFE Biological Technology Co., Ltd.
Tel
021-65675885 18964387627
Fax
021-65675885
Email
info@efebio.com
Country
China
ProdList
9709
Advantage
58
More
Less

View Lastest Price from Nintedanib esylate manufacturers

Nanjing Fred Technology Co., Ltd
Product
Nintedanib Esylate 656247-18-6
Price
US $0.00-0.00/kg
Min. Order
1kg
Purity
99%, Single impurity＜0.1
Supply Ability
1 ton
Release date
2023-12-19
Hebei Yanxi Chemical Co., Ltd.
Product
Nintedanib Ethanesulfonate Salt 656247-18-6
Price
US $0.00/kg
Min. Order
1kg
Purity
0.99
Supply Ability
20tons
Release date
2023-10-08
WUHAN FORTUNA CHEMICAL CO., LTD
Product
Nintedanib Ethanesulfonate Salt 656247-18-6
Price
US $0.00/g
Min. Order
1g
Purity
99%min HPLC
Supply Ability
1000G
Release date
2021-07-23

656247-18-6, Nintedanib esylateRelated Search:

Nintedanib Methyl 2-oxoindole-6-carboxylate (3E)-2,3-Dihydro-3-(methoxyphenylmethylene)-2-oxo-1H-indole-6-carboxylic acid methyl ester BIBF-1120 2-CHLORO-N-METHYL-N-(4-NITROPHENYL)ACETAMIDE 2-broMo-N-Methyl-N-(4-nitrophenyl)acetaMide N-(4-aminophenyl)-N-methyl-2-(4-methylpiperazin-1-yl)acetamide N-methyl-2-(4-methylpiperazin-1-yl)-N-(4-nitrophenyl)acetamide 1,3-DiMethyl 2-[4-(Methoxycarbonyl)-2-nitrophenyl]propanedioate Ruxolitinib phosphate Alectinib Hydrochloride PLX4032 Olaparib Crizotinib Afatinib (BIBW 2992) PLERIXAFOR Propylparaben Methylparaben Nintedanib Esylate

  • (3Z)-2,3-Dihydro-3-[[[4-[methyl[2-(4-methyl-1-piperazinyl)acetyl]amino]phenyl]amino]phenylmethylene]-2-oxo-1H-indole-6-carboxylic acid methyl ester ethanesulfonate
  • Nintedanib ethanesulfonate
  • BIBF 1120 esylate
  • BIBF-1120 esylate
  • Nintedanib esylate
  • BIBF1120/nintedanib ethanesulfonate salt
  • Trinidad Neeb esylate
  • Intedanib ethanesulfonate
  • Nintedanib ethanesulfonate salt
  • Trinidad Neeb ethanesulfonate
  • Nintedanib(ethanesulfonic acid)
  • BIBF1120 ethanesulfonate salt
  • (Z)-Methyl 3-(((4-(N-methyl-2-(4-methylpiperazin-1-yl)acetamido)phenyl)amino)(phenyl)methylene
  • 1H-Indole-6-carboxylic acid,2,3-dihydro-3-[[[4-[methyl[(4-methyl-1-piperazinyl)acetyl]amino]phenyl]amino]-phenylmethylene]-2-oxo-, methylester, (3Z)-, ethanesulfonate (1:1)
  • 1H-Indole-6-carboxylic acid, 2,3-dihydro-3-[[[4-[methyl[2-(4-methyl-1-piperazinyl)acetyl]amino]phenyl]amino]phenylmethylene]-2-oxo-, methyl ester, (3Z)-, ethanesulfonate (1:1)
  • Nintedanib (Ofev)
  • (Z)-methyl 3-(((4-(N-methyl-2-(4-methylpiperazin-1-yl)acetamido)phenyl)amino)(phenyl)methylene)-2-oxoindoline-6-carboxylate ethanesulfonate
  • BIBF 1120 BIBF-1120
  • BIBF1120; BIBF 1120 BIBF-1120; NINTEDANIB ESYLATE. NINTEDANIB ETHANESULFONATE SALT; INTEDANIB; BRAND NAME OFEV. VARGATEF.
  • Brand name OFEV. Vargatef.
  • Nintedanib esylate. Nintedanib ethanesulfonate salt
  • Nintedanib Ethanesulfonate (Intedanib Ethanesulfonate)
  • Nintedani
  • NSC 116056
  • 6-Benzofuranpropanenitrile,β-oxo-
  • methyl (Z)-3-(((4-(N-methyl-2-(4-methylpiperazin-1-yl)acetamido)phenyl)amino)(phenyl)methylene)-2-oxoindoline-6-carboxylate ethanesulfonate
  • Buprenorphine Impurity 24
  • 656247-18-6
  • 1217052-38-5
  • C31H33N5O4C2H6O3S
  • C33H39N5O7S
  • API