1448347-49-6

Basic information

• Product Name: RG120
• Synonyms: RG120;Ivosidenib;(S)-N-((S)-1-(2-chlorophenyl)-2-((3,3-difluorocyclobutyl)amino)-2-oxoethyl)-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide;(2S)-1-(4-Cyano-2-pyridinyl)-5-oxo-L-prolyl-2-(2-chlorophenyl)-N-(3,3-difluorocyclobutyl)-N2-(5-fluoro-3-pyridinyl)glycinamide;Glycinamide, 1-(4-cyano-2-pyridinyl)-5-oxo-L-prolyl-2-(2-chlorophenyl)-N-(3,3-difluorocyclobutyl)-N2-(5-fluoro-3-pyridinyl)-, (2S)-;EOS-60845;Ivosidenib(AG-120);(2S)-N-{(1S)-1-(2-chlorophenyl)-2-[(3,3-difluorocyclobutyl)amino]-2-oxoethyl}-1(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide
• CAS NO: 1448347-49-6
• Molecular Formula: C₂₈H₂₂ClF₃N₆O₃
• Molecular Weight: 582.9608896
• EINECS: -0
• Product Categories: API
• Mol File: 1448347-49-6.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 854.3±65.0 °C(Predicted)
• Appearance: /
• Density: 1.51±0.1 g/cm3(Predicted)
• Storage Temp.: -20°C Freezer, Under inert atmosphere
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 11.58±0.40(Predicted)
• CAS DataBase Reference: RG120(CAS DataBase Reference)
• NIST Chemistry Reference: RG120(1448347-49-6)
• EPA Substance Registry System: RG120(1448347-49-6)

Safety Data

• Hazardous Substances Data: 1448347-49-6(Hazardous Substances Data)

Usage

Description

RG120, also known as AG-120, is an orally available inhibitor of isocitrate dehydrogenase type 1 (IDH1) that specifically targets a mutated form of IDH1 in the cytoplasm. It prevents the formation of 2-hydroxyglutarate, a metabolite associated with cancer development. RG120 has the potential to induce cellular differentiation and inhibit proliferation in IDH1-expressing tumor cells, making it a promising therapeutic agent for IDH1 mutant cancers.

Uses

Used in Oncology:
RG120 is used as a first-in-class mutant IDH1 inhibitor for the treatment of IDH1 mutant cancers. By inhibiting the mutated IDH1 enzyme, RG120 can potentially reduce the levels of the oncometabolite 2-hydroxyglutarate, which contributes to the development and progression of cancer. This targeted approach may help to induce cellular differentiation and inhibit the proliferation of IDH1-expressing tumor cells, offering a more precise and effective treatment option for patients with IDH1 mutant cancers.

in vitro

tf-1 cells or primary human aml patient samples expressing mutant idh1 were treated with ag-120, and the results showed that in tf-1 idh1-r132h cells, ag-120 was able to decrease the intracellular 2-hg levels, inhibit growth factor independent proliferation and restore erythropoietin-induced differentiation [1].

IC 50

< 100 nm

references

[1] erica hansen et al. ag-120, an oral, selective, first-in-class, potent inhibitor of mutant idh1, reduces intracellular 2hg and induces cellular differentiation in tf-1 r132h cells and primary human idh1 mutant aml patient samples treated ex vivo. blood 2014 124:3734.[2] http://www. aacr.org/newsroom/pages/news-release-detail.aspx itemid=789#.wlauom997iu

Upstream product

• 1355328-30-1 N-(3,3-difluorocyclobutyl)formamide 
• 1355328-31-2 1,1-difluoro-3-isocyanocyclobutane 
• 33252-30-1 2-chloro-4-pyridinenitrile 
• 89-98-5 2-chloro-benzaldehyde 
• 210169-05-4 5-fluoropyridin-3-amine 
• 2070009-31-1 (2S)-N-{(1R)-1-(2-chlorophenyl)-2-[(3,3-difluorocyclobutyl)amino]-2-oxoethyl}-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide 
• 149-87-1 Pyroglutamic acid 
• 10386-27-3 2-bromoisonicotinonitrile 
• 109904-41-8 rac-α-chloro-2-chlorophenylacetic acid 
• 85259-19-4 methyl 2-bromo-2-(2-chlorophenyl)acetate 
• 7149-65-7 ethyl (S)-pyroglutamate 
• 1448348-28-4 (S)-1-(4-cyanopyridin-2-yl)-5-oxopyrrolidine-2-carboxylic acid 

Relevant articles and documents

IMPROVED PROCESS FOR THE PREPARATION OF (2S)-N-{(1S)-1-(2-CHLOROPHENYL)-2-[(3,3-DIFLUOROCYCLOBUTYL)-AMINO]-2-OXOETHYL}-1-(4-CYANOPYRIDIN-2-YL)-N-(5-FLUOROPYRIDIN-3-YL)-5-OXOPYRROLIDINE-2-CARBOXAMIDE

The present invention relates to improved process for the preparation of (2S)-N-{(1S)-1-(2-chlorophenyl)-2-[(3,3-difluorocyclobutyl)-amino]-2-oxoethyl}-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide and its pharmaceutically acceptable salts represented by the following structural formula. Formula-1 The present invention relates to novel intermediates useful in the preparation of Ivosidenib of formula-1 and novel process for the preparation of (2S)-N-{(1S)-1-(2-chlorophenyl)-2-[(3,3-difluorocyclobutyl)-amino]-2-oxoethyl}-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide. The present invention also relates to solid state forms of (2S)-N-{(1S)-1-(2-chlorophenyl)-2-[(3,3-difluorocyclobutyl)-amino]-2- oxoethyl}-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide.

AN IMPROVED PROCESS OF PREPARATION OF IVOSIDENIB

The present invention relates to an improved process of preparation of Ivosidenib a compound of Formula (I). More particularly, present invention provides process of preparation of intermediates. Also provide process of preparation of amorphous form of Ivosidenib. Further, present invention provides process of preparation of chirally pure Ivosidenib a compound of Formula (I).

Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers

Somatic point mutations at a key arginine residue (R132) within the active site of the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) confer a novel gain of function in cancer cells, resulting in the production of d-2-hydroxyglutarate (2-HG), an oncometabolite. Elevated 2-HG levels are implicated in epigenetic alterations and impaired cellular differentiation. IDH1 mutations have been described in an array of hematologic malignancies and solid tumors. Here, we report the discovery of AG-120 (ivosidenib), an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models and the ability to effect differentiation of primary patient AML samples ex vivo. Preliminary data from phase 1 clinical trials enrolling patients with cancers harboring an IDH1 mutation indicate that AG-120 has an acceptable safety profile and clinical activity.