658084-80-1

Usage

Uses

Used in Pharmaceutical Research and Development:
ETHYL 4-CHLORO-5-ISOPROPYLPYRROLO[2,1-F][1,2,4]TRIAZINE-6-CARBOXYLATE is used as a research compound for exploring its pharmacological effects. Its unique molecular structure and functional groups allow it to interact with biological systems, providing a basis for studying its potential therapeutic applications.
Used in Drug Discovery:
In the field of drug discovery, ETHYL 4-CHLORO-5-ISOPROPYLPYRROLO[2,1-F][1,2,4]TRIAZINE-6-CARBOXYLATE is utilized as a lead compound. Its chemical properties and the possibility of modifying its structure to enhance biological activity make it a promising candidate for the development of new pharmaceutical agents.
Used in Chemical Synthesis:
ETHYL 4-CHLORO-5-ISOPROPYLPYRROLO[2,1-F][1,2,4]TRIAZINE-6-CARBOXYLATE is also used as a synthetic intermediate in the preparation of other related compounds. Its versatile structure can be further modified or used as a building block in the synthesis of novel molecules with potential applications in various fields, including medicine, agrochemicals, and materials science.

Upstream product

• 651744-40-0 ethyl 5-isopropyl-4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4]triazine-6-carboxylate 
• 651744-40-0 5-(1-methylethyl)pyrrolo[2,1-f][1,2,4]triazin-4(3H)-one-6-carboxylic acid ethyl ester 
• 15790-86-0 ethyl-4-methyl-2-(E)-penteneoate 
• 104398-21-2 ethyl 4-(propan-2-yl)-1H-pyrrole-3-carboxylate 
• 651744-39-7 diethyl 1-amino-3-(propan-2-yl)-1H-pyrrole-2,4-dicarboxylate 
• 651744-38-6 diethyl 3-(propan-2-yl)-1H-pyrrole-2,4-dicarboxylate 
• 2999-46-4 Ethyl isocyanoacetate 

Downstream Products

• 658084-85-6 4-[[3-[(methoxyamino)carbonyl]-4-methylphenyl]amino]-5-(1-methylethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid ethyl ester 
• 658084-83-4 4-[[2-fluoro-5-[(methoxyamino)carbonyl]phenyl]amino]-5-(1-methylethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid ethyl ester 
• 658084-87-8 4-[[2,4-fluoro-5-[(methoxyamino)carbonyl]phenyl]amino]-5-(1-methylethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid ethyl ester 
• 658084-97-0 4-(2,4-difluoro-5-(methoxycarbamoyl)phenylamino)-5-isopropylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid 
• 658085-52-0 5-(6-(azidocarbonyl)-5-isopropylpyrrolo[2,1-f][1,2,4]triazin-4-ylamino)-2,4-difluoro-N-methoxybenzamide 

Relevant academic research and scientific papers

Synthesis and SAR of 4-(3-hydroxyphenylamino)pyrrolo[2,1-f][1,2,4]triazine based VEGFR-2 kinase inhibitors

A versatile synthesis of the suitably functionalized pyrrolo[2,1-f][1,2,4] triazine nucleus is described. SAR at the C-5 and C-6 positions of the 4-(3-hydroxy-4-methylphenylamino)pyrrolo[2,1-f][1,2,4]triazine template led to compounds with good in vitro potency against VEGFR-2 kinase. Glucuronidation of the phenol group is mitigated by incorporation of a basic amino group on the C-6 side chain of the pyrrolotriazine nucleus.

New dual inhibitors of EGFR and HER2 protein tyrosine kinases

A novel series of dual EGFR and HER2 inhibitors based on the pyrrolo[2,1-f][1,2,4]triazine nucleus is described. A general route toward their synthesis, which enables functionalization at multiple sites, has been developed. Biological evaluation in enzyma

Design, synthesis, and evaluation of orally active 4-(2,4-difluoro-5- (methoxycarbamoyl)phenylamino)pyrrolo[2,1-f][1,2,4]triazines as dual vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1 inhibitors

A series of substituted 4-(2,4-difluoro-5-(methoxycarbamoyl)phenylamino) pyrrolo[2,1-f][1,2,4]-triazines was identified as potent and selective inhibitors of the tyrosine kinase activity of the growth factor receptors VEGFR-2 (Flk-1, KDR) and FGFR-1. The enzyme kinetics associated with the VEGFR-2 inhibition of compound 50 (Ki = 52 ± 3 nM) confirmed that the pyrrolo-[2,1-f][1,2,4]triazine analogues are competitive with ATP. Several analogues demonstrated low-nanomolar inhibition of VEGF- and FGF-dependent human umbilical vein endothelial cell (HUVEC) proliferation. Replacement of the C6-ester substituent of the pyrrolo[2,1-f][1,2,4]-triazine core with heterocyclic bioisosteres, such as substituted 1,3,5-oxadiazoles, afforded compounds with excellent oral bioavailability in mice (i.e., 50 Fpo = 79%). Significant antitumor efficacy was observed with compounds 44, 49, and 50 against established L2987 human lung carcinoma xenografts implanted in athymic mice. A full account of the synthesis, structure-activity relationships, pharmacology, and pharmacokinetic properties of analogues within the series is presented.

PYRROLOTRIAZINE KINASE INHIBITORS

The present invention provides compounds of formula I, (I) and pharmaceutically acceptable salts thereof. The formula I compounds inhibit the tyrosine kinase activity of growth factor receptors such as VEGFR-2 and FGFR-1, thereby making them useful as ant