649735-46-6

Basic information

• Product Name: 1-[[4-[(4-Fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxy]-2-propanol
• Synonyms: 1-[[4-[(4-Fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxy]-2-propanol;Brivanib;Tyrosine Kinase Inhibitor;(R)-1-(4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo(2,1-F)(1,2,4)triazin-6-yloxy)propan-2-ol;2-Propanol, 1-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-5-methylpyrrolo(2,1-F)(1,2,4)triazin-6-yl)oxy)-, (2R)-;Bms 540215;Bms540215;Unii-ddu33B674i
• CAS NO: 649735-46-6
• Molecular Formula: C₁₉H₁₉FN₄O₃
• Molecular Weight: 370.382
• Product Categories: Inhibitors
• Mol File: 649735-46-6.mol
• Article Data: 4

Chemical Properties

• Appearance: /
• Density: 1.42
• Refractive Index: 1.66
• Solubility: insoluble in H2O; ≥18.5 mg/mL in DMSO; ≥3.39 mg/mL in EtOH with ultrasonic
• PKA: 14.18±0.20(Predicted)
• CAS DataBase Reference: 1-[[4-[(4-Fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxy]-2-propanol(CAS DataBase Reference)
• NIST Chemistry Reference: 1-[[4-[(4-Fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxy]-2-propanol(649735-46-6)
• EPA Substance Registry System: 1-[[4-[(4-Fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxy]-2-propanol(649735-46-6)

Safety Data

• Hazardous Substances Data: 649735-46-6(Hazardous Substances Data)

Usage

Uses

Brivanib is an ATP-competitive inhibitor against human VEGFR2 and FGFR with IC50 of 25 nM and 148 nM, respectively.

Biological Activity

brivanib is an atp competitive inhibitor of human vegfr-2 with ic50 value of 25nm [1].brivanib is a selective rtk inhibitor that targets signaling via vegfr2 and 3, and fgfr1, 2 and 3. targeting both vegf and fgf signaling pathways inhibits tumor growth in rt2 mice, with vegf signaling predominating in initiation of tumor angiogenesis, currently, brivanib therapy is being evaluated in phase iii

references

[1] rajeev s. bhide, zhen-wei cai, yong-zheng zhang, ligang qian, donna wei, stephanie barbosa, louis j. lombardo, robert m. borzilleri, xiaoping zheng, laurence i. wu, joel c. barrish, soong-hoon kim, kenneth leavitt, arvind mathur, leslie leith, sam chao, barri wautlet, steven mortillo, robert jeyaseelan sr., daniel kukral, john t. hunt, amrita kamath, aberra fura, viral vyas, punit marathe, celia d’arienzo, george derbin, and joseph fargnoli. discovery and preclinical studies of (r)-1-(4-(4-fluoro-2-methyl-1h-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-ol (bms-540215), an in vivo active potent vegfr-2 inhibitor. journal of medicinal chemistry. 2006, 49 (7): 2143-2146.[2] elizabeth allen, ian b. walters, and douglas hanahan. brivanib, a dual fgf/vegf inhibitor, is active both first and second line against mouse pancreatic neuroendocrine tumors developing adaptive/evasive resistance to vegf inhibition. clinical cancer research. 2011 (17): 5299-5310.

InChI:InChI=1/C19H19FN4O3/c1-10-6-13-14(23-10)4-5-15(17(13)20)27-19-18-12(3)16(26-8-11(2)25)7-24(18)22-9-21-19/h4-7,9,11,23,25H,8H2,1-3H3/t11-/m1/s1

Upstream product

• 649735-41-1 4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-ol 
• 15448-47-2 (R)-propylene oxide 
• 288385-88-6 4-fluoro-2-methyl-1H-indol-5-ol 
• 310444-84-9 4-Phenoxy-5-methyl-6-hydroxypyrrolo[2,1-f][1,2,4]triazine 
• 649736-27-6 6-(benzyloxy)-4-chloro-5-methylpyrrolo[2,1-f][1,2,4]triazine 
• 649736-26-5 6-(benzyloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-4-ol 
• 886585-68-8 6-(benzyloxy)-5-methyl-4-phenoxypyrrolo[2,1-f][1,2,4]triazine 
• 649736-28-7 6-(benzyloxy)-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazine 

Downstream Products

• 649736-41-4 (S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-yl) 2-(benzyloxycarbonylamino)propanoate 
• 1016195-15-5 C₃₁H₃₂FN₅O₅ 
• 1016195-11-1 C₂₉H₃₀FN₅O₄ 
• 649736-40-3 C₃₃H₃₆FN₅O₆ 
• 1073108-78-7 C₃₀H₃₀FN₅O₆ 
• 1073110-74-3 C₃₂H₃₄FN₅O₆ 
• 1073110-65-2 C₃₂H₃₄FN₅O₆ 
• 1073110-51-6 C₃₁H₃₂FN₅O₆ 
• 1073116-90-1 C₃₆H₃₄FN₅O₆ 
• 1073113-06-0 C₃₃H₃₆FN₅O₆ 
• 1016195-19-9 C₃₁H₃₂FN₅O₅ 
• 1073100-65-8 C₂₉H₂₈FN₅O₆ 

Relevant articles and documents

Control Strategy for the Manufacture of Brivanib Alaninate, a Novel Pyrrolotriazine VEGFR/FGFR Inhibitor

This manuscript describes the control strategy for the commercial process to manufacture brivanib alaninate. The active pharmaceutical ingredient is a prodrug which is susceptible to hydrolysis. In addition to controlling hydrolysis, a robust strategy was

PROCESS FOR THE PREPARATION OF [(1R), 2S]-2-AMINOPROPIONIC ACID 2-[4-(4-FLUORO-2-METHYL-1H-INDOL-5-YLOXY)-5-METHYLPYRROLO[2,1-f][1,2,4]TRIAZIN-6-YLOXY]-1-METHYLETHYL ESTER

The invention relates to an improved process for preparing [(1R),2S]-2-aminopropionic acid 2-[4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy]-1-methylethyl ester of the formula: Compound I has been shown to be useful f