1508256-20-9

Usage

Uses

Used in Pharmaceutical Applications:
(R,E)-N-(7-chloro-1-(1-(4-(dimethylamino)but-2-enoyl)azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide is used as a potential candidate in the development of new pharmaceuticals for various medical conditions. Its unique structure and functional groups may allow it to interact with biological targets in ways that could be beneficial for treating specific diseases or disorders.
Used in Medicinal Chemistry Research:
In the field of medicinal chemistry, (R,E)-N-(7-chloro-1-(1-(4-(dimethylamino)but-2-enoyl)azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide can be used as a research tool to study the interactions between complex organic compounds and biological systems. This may lead to a better understanding of the molecular mechanisms underlying certain diseases and the development of more effective therapeutic strategies.
Used in Drug Design and Development:
(R,E)-N-(7-chloro-1-(1-(4-(dimethylamino)but-2-enoyl)azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide may also be utilized in the process of drug design and development, where its unique structural features could be exploited to create new drugs with improved efficacy, selectivity, and safety profiles. Its potential applications in this area would depend on the results of further research and development efforts.
Used in Chemical Synthesis:
(R,E)-N-(7-chloro-1-(1-(4-(dimethylamino)but-2-enoyl)azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide could be employed as a starting material or intermediate in the synthesis of other complex organic compounds, potentially leading to the discovery of new molecules with valuable properties and applications.

Upstream product

• 1130155-48-4 (E)-4-(dimethylamino)-2-butenoic acid hydrochloride 
• 2106-49-2 1-chloro-2-fluoro-3-nitrobenzene 
• 4021-11-8 2-methylisonicotinic acid 

Relevant academic research and scientific papers

Discovery of (R,E)-N-(7-chloro-1-(1-[4-(dimethylamino)but-2-enoyl]azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide (EGF816), a novel, potent, and WT sparing covalent inhibitor of oncogenic (L858R, ex19del) and resistant (T790M) EGFR mutants for the treatment of EGFR mutant non-small-cell lung cancers

Over the past decade, first and second generation EGFR inhibitors have significantly improved outcomes for lung cancer patients with activating mutations in EGFR. However, both resistance through a secondary T790M mutation at the gatekeeper residue and dose-limiting toxicities from wild-type (WT) EGFR inhibition ultimately limit the full potential of these therapies to control mutant EGFR-driven tumors and new therapies are urgently needed. Herein, we describe our approach toward the discovery of 47 (EGF816, nazartinib), a novel, covalent mutant-selective EGFR inhibitor with equipotent activity on both oncogenic and T790M-resistant EGFR mutations. Through molecular docking studies we converted a mutant-selective high-throughput screening hit (7) into a number of targeted covalent EGFR inhibitors with equipotent activity across mutants EGFR and good WT-EGFR selectivity. We used an abbreviated in vivo efficacy study for prioritizing compounds with good tolerability and efficacy that ultimately led to the selection of 47 as the clinical candidate.

PHARMACEUTICAL COMPOSITIONS

The present invention relates to pharmaceutical compositions comprising the drug substance (R,E)-N-(7-chloro-1-(1-(4-(dimethylamino)but-2-enoyl)azepan-3-yl)-1H-benzo[d]imidazol-2- yl)-2-methylisonicotinamide, and processes to prepare said pharmaceutical compositions.

EGFR INHIBITOR FORMS

The present disclosure generally discloses polymorphic forms of (R,E)-N-(7-chloro-1-(1-(4-(dimethylamino)but-2-enoyl)azepan-3- yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide (Compound EGFRi). A pharmaceutical composition comprising the form(s), as well of methods of using the form(s) in the treatment of cancer indication, and methods for obtaining such forms are also disclosed.

EGFR INHIBITOR FORMS

The present disclosure generally relates to polymorphic form(s) of 184 (R,E)-N-(7-chloro-1-(1-(4-(dimethylamino)but-2-enoyl)azepan-3-yl)-1H-benzo[d]imidazol-2 -yl)-2-methylisonicotinamide (Compound EGFRi). The present disclosure also generally relates to a pharmaceutical composition comprising the form(s), as well of methods of using the form(s) in the treatment of cancer indications, and methods for obtaining such forms.

FORMS OF THE EGFR INHIBITOR

The present disclosure generally relates to polymorphic form(s) of (R,E)-N-(7-chloro-1-(1-(4-(dimethylamino)but-2-enoyl)azepan-3-yl)-1H-benzo[d]imidazol-2 -yl)-2-methylisonicotinamide (Compound EGFRi). The present disclosure also generally relates to a pharmaceutical composition comprising the form(s), as well of methods of using the form(s) in the treatment of cancer indications, and methods for obtaining such forms.

COMPOUNDS AND COMPOSITIONS FOR MODULATING EGFR ACTIVITY

The invention provides compounds and pharmaceutical compositions thereof, which are useful for modulating EGFR activity, as well as methods for using such compounds to treat, ameliorate or prevent a condition associated with abnormal or deregulated EGFR activity.