635702-64-6 Usage
Description
Unii-33Y9anm545, also known as Pazopanib, is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit, and c-Fms. It is used as an oral angiogenesis inhibitor targeting VEGFR and PDGFR.
Uses
Used in Oncology:
Unii-33Y9anm545 is used as an angiogenesis inhibitor for the treatment of advanced renal cell carcinoma (RCC). It works by inhibiting the biological functions of the VEGF family, which are mediated by the activation of three structurally homologous tyrosine kinase receptors, VEGFR-1, VEGFR-2, and VEGFR3. In vitro, Pazopanib inhibits VEGFR-1, VEGFR-2, and VEGFR-3 with IC50 values of 10, 30, and 47 nM, respectively.
Used in Angiogenesis Research:
Unii-33Y9anm545 is used as a research tool to study the role of VEGFR and PDGFR in angiogenesis. It has been shown to inhibit VEGF-induced proliferation more potently than basic fibroblast growth factor (bFGF)-stimulated proliferation in human umbilical vein endothelial cells (HUVEC), with an IC50 of 21 nM vs. 721 nM.
Used in Drug Development:
Unii-33Y9anm545 is used in the development of new drugs targeting angiogenesis and related pathways. Its multi-target inhibitory profile makes it a valuable compound for studying the effects of inhibiting multiple receptors involved in angiogenesis and tumor growth.
Common adverse events associated with Pazopanib (Unii-33Y9anm545) include diarrhea, hypertension, hair depigmentation, nausea, anorexia, and vomiting.
Clinical Use
Pazopanib is a potent and selective multi-targeted receptor
tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3,
PDGFR-a/b, and c-kit that blocks tumor growth and inhibits angiogenesis.
It was approved for renal cell carcinoma by the U.S. Food
and Drug Administration in 2009 and is marketed under the trade
name Votrient by the drug’s manufacturer, GlaxoSmithKline.
Side effects
Pazopanib is synthesized in five chemical steps
starting from 3-methyl-6-nitroindazole, which is converted to the corresponding
2,3-dimethylindazole analog via N-methylation with trimethyloxonium
tetrafluoroborate. Subsequent reduction of the nitro group to
the amino group using tin chloride followed by condensation with 2,4dichloropyrimidine
yields a chloropyrimidinylaminoindazole intermediate.
The final two steps leading up to pazopanib consist of an N-methylation
reaction using iodomethane and cesium carbonate followed by
condensation with 5-amino-2-methylbenzenesulfonamide.
Synthesis
The
synthesis of pazopanib begins with methylation of 3-methyl-6-
nitroindazole (82) with trimethyl orthoformate in the presence of BF3·OEt to give indazole 83 in 65% yield. Reduction
of the nitro group was achieved via transfer hydrogenation to give
84 in 97% yield, and this was followed by coupling the aniline with
2,4-dichloropyrimidine in a THF-ethanol mixture at elevated
temperature to provide diarylamine 85 in 90% yield. The aniline
nitrogen was then methylated using methyl iodide to give 86 in
83% yield prior to coupling with 5-amino-2-methylbenzenesulfonamide
(87) and salt formation using an alcoholic solution of
HCl to furnish pazopanib hydrochloride (XIV) in 81% yield.
Check Digit Verification of cas no
The CAS Registry Mumber 635702-64-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 6,3,5,7,0 and 2 respectively; the second part has 2 digits, 6 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 635702-64:
(8*6)+(7*3)+(6*5)+(5*7)+(4*0)+(3*2)+(2*6)+(1*4)=156
156 % 10 = 6
So 635702-64-6 is a valid CAS Registry Number.
InChI:InChI=1/C21H23N7O2S.ClH/c1-13-5-6-15(11-19(13)31(22,29)30)24-21-23-10-9-20(25-21)27(3)16-7-8-17-14(2)28(4)26-18(17)12-16;/h5-12H,1-4H3,(H2,22,29,30)(H,23,24,25);1H
635702-64-6Relevant articles and documents
A novel practical synthesis of pazopanib: An anticancer drug
Mei, Yi Cheng,Yang, Bao Wei,Chen, Wei,Huang, Dan Dan,Li, Ying,Deng, Xin,Liu, Bao Ming,Wang, Jing Jie,Qian, Hai,Huang, Wen Long
, p. 276 - 279 (2012)
Abstract: This paper reports a novel approach to synthesize pazopanib. In our synthetic route, the potently mutagenic alkylating agents such as dimethyl sulfate and methyl iodide are avoided. A novel regioselective methylation of the 2- position of 3-methyl-6-nitro-1H-indazole was reported. This novel route is one step shorter than the previously reported route.
Green preparation method of palatinib hydrochloride (by machine translation)
-
Paragraph 0095-0098, (2019/08/01)
The invention belongs to the technical field of chemical synthesis of medicines, and belongs to the technical field of pharmaceutical chemistry. The invention particularly relates to a green preparation method. The o-methyl aniline and N - chlorosuccinimide are chlorinated to obtain 2 - methyl -5 - chloro- aniline; the 6 - chlorine - 222H-indole hydrochloride is obtained by reacting with the nitrous acid compound; N-methyl -6 -chloro - 222H-indole; under the participation of dimethyl sulfoxide, 3 - 2-dimethyl 3 - chlorine -6 - 222H-indazole; and the like. A reaction with 2 - chloro -4 - amino - pyrimidine and iodomethane gave N - (2 -chloropyrimidine -4 -yl) - N N-methyl -2, 3 -dimethyl - 222H-indazole -6 - amine; and finally, a pimatinib hydrochloride salt was obtained by reaction with 3 - sulfanilide -4 - methyl - aniline. The method is low in raw material price, simple to operate, low in operation risk, capable of avoiding waste acid generation, high in reaction yield, and high in purity. (by machine translation)
PROCESS FOR THE PREPARATION OF PAZOPANIB OR SALTS THEREOF
-
, (2016/01/08)
The present invention provides a process for the preparation of pazopanib of Formula Ia or salts, and intermediates thereof.
