1422509-98-5

Basic information

• Product Name: 1-(3-chloro-2,6-difluorophenyl)prop-2-en-1-one
• Synonyms: 1-(3-chloro-2,6-difluorophenyl)prop-2-en-1-one
• CAS NO: 1422509-98-5
• Molecular Weight: 202.588
• Mol File: 1422509-98-5.mol
• Article Data: 7

Chemical Properties

• CAS DataBase Reference: 1-(3-chloro-2,6-difluorophenyl)prop-2-en-1-one(CAS DataBase Reference)
• NIST Chemistry Reference: 1-(3-chloro-2,6-difluorophenyl)prop-2-en-1-one(1422509-98-5)
• EPA Substance Registry System: 1-(3-chloro-2,6-difluorophenyl)prop-2-en-1-one(1422509-98-5)

Safety Data

• Hazardous Substances Data: 1422509-98-5(Hazardous Substances Data)

Upstream product

• 1422509-97-4 1-(3-chloro-2,6-difluorophenyl)prop-2-en-1-ol 
• 190011-87-1 1-(3-chloro-2,6-difluoro-phenyl)-carboxaldehyde 

Downstream Products

• 1422510-61-9 1-(3-chloro-2,6-difluorophenyl)-3-iodo(1-²H)propan-1-(²H)ol 
• 1422509-99-6 1-(3-chloro-2,6-difluorophenyl)-3-iodopropan-1-one 
• 1422511-22-5 (1R)-1-(3-chloro-2,6-difluorophenyl)-3-iodopropan-1-ol 
• 1422511-23-6 (1S)-1-(3-chloro-2,6-difluorophenyl)-3-iodopropan-1-ol 
• 1422510-91-5 methyl N-[(10R,14S)-14-{[3-(3-chloro-2,6-difluorophenyl)-3-hydroxypropyl]amino}-10-methyl-9-oxo-16-{[2-(trimethylsilyl)ethoxy]methyl}-8,16,18-triazatricyclo[13.2.1.0^2,7]octadeca-1⁽¹⁷⁾,2,4,6,15⁽¹⁸⁾-pentaen-5-yl]carbamate 
• 1422510-92-6 methyl N-[(10R,14S)-14-[6-(3-chloro-2,6-difluorophenyl)-2-oxo-1,3-oxazinan-3-yl]-10-methyl-9-oxo-16-{[2-(trimethylsilyl)ethoxy]methyl}-8,16,18-triazatricyclo[13.2.1.0^2,7]octadeca-1⁽¹⁷⁾,2,4,6,15⁽¹⁸⁾-pentaen-5-yl]carbamate 
• 1422508-12-0 methyl N-[(10R,14S)-14-[(6R)-6-(3-chloro-2,6-difluorophenyl)-2-oxo-1,3-oxazinan-3-yl]-10-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.0^2,7]octadeca-1⁽¹⁷⁾,2,4,6,15⁽¹⁸⁾-pentaen-5-yl]carbamate 
• 1422511-13-4 methyl N-[(12E,15S)-18-chloro-15-{[3-(3-chloro-2,6-difluorophenyl)-3-oxopropyl]amino}-9-oxo-17-{[2-(trimethylsilyl)ethoxy]methyl}-8,17,19-triazatricyclo[14.2.1.0^2,7]nonadeca-1⁽¹⁸⁾,2,4,6,12,16⁽¹⁹⁾-hexaen-5-yl]carbamate 
• 1422511-14-5 methyl N-[(12E,15S)-18-chloro-15-{[3-(3-chloro-2,6-difluorophenyl)-3-hydroxybutyl]amino}-9-oxo-17-{[2-(trimethylsilyl)ethoxy]methyl}-8,17,19-triazatricyclo[14.2.1.0^2,7]nonadeca-1⁽¹⁸⁾,2,4,6,12,16⁽¹⁹⁾-hexaen-5-yl]carbamate 

Relevant articles and documents

Discovery of Milvexian, a High-Affinity, Orally Bioavailable Inhibitor of Factor XIa in Clinical Studies for Antithrombotic Therapy

Factor XIa (FXIa) is an enzyme in the coagulation cascade thought to amplify thrombin generation but has a limited role in hemostasis. From preclinical models and human genetics, an inhibitor of FXIa has the potential to be an antithrombotic agent with superior efficacy and safety. Reversible and irreversible inhibitors of FXIa have demonstrated excellent antithrombotic efficacy without increased bleeding time in animal models (Weitz, J. I., Chan, N. C. Arterioscler. Thromb. Vasc. Biol. 2019, 39 (1), 7-12). Herein, we report the discovery of a novel series of macrocyclic FXIa inhibitors containing a pyrazole P2′ moiety. Optimization of the series for (pharmacokinetic) PK properties, free fraction, and solubility resulted in the identification of milvexian (BMS-986177/JNJ-70033093, 17, FXIa Ki = 0.11 nM) as a clinical candidate for the prevention and treatment of thromboembolic disorders, suitable for oral administration.

NOVEL SUBSTITUTED GLYCINE DERIVED FXIA INHIBITORS

The present invention provides compounds of Formula (I): [INSERT CHEMICAL STRUCTURE HERE] (I) or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

MACROCYCLIC FACTOR XIA INHIBITORS CONDENSED WITH HETEROCYCLES

The present invention provides compounds of Formula (Ia): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.