903555-98-6

Upstream product

• 903555-95-3 (±)-tert-butyl (5-bromo-2,3-dihydro-1H-inden-1-yl)carbamate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 1443238-61-6 (R)-5-bromo-2,3-dihydro-1H-inden-1-amine hydrochloride 
• 1270284-15-5 (1S)-5-bromo-2,3-dihydro-1H-inden-1-ol 
• 1334784-73-4 (1R)-1-azido-5-bromo-2,3-dihydro-1H-indene 
• 1228561-27-0 (1R)-5-bromo-2,3-dihydro-1H-inden-1-amine 
• 34598-49-7 5-Bromo-1-indanone 

Relevant academic research and scientific papers

Discovery of Aficamten (CK-274), a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic Cardiomyopathy

Hypercontractility of the cardiac sarcomere may be essential for the underlying pathological hypertrophy and fibrosis in genetic hypertrophic cardiomyopathies. Aficamten (CK-274) is a novel cardiac myosin inhibitor that was discovered from the optimization of indoline compound 1. The important advancement of the optimization was discovery of an Indane analogue (12) with a less restrictive structure-activity relationship that allowed for the rapid improvement of drug-like properties. Aficamten was designed to provide a predicted human half-life (t1/2) appropriate for once a day (qd) dosing, to reach steady state within two weeks, to have no substantial cytochrome P450 induction or inhibition, and to have a wide therapeutic window in vivo with a clear pharmacokinetic/pharmacodynamic relationship. In a phase I clinical trial, aficamten demonstrated a human t1/2 similar to predictions and was able to reach steady state concentration within the desired two-week window.

DIHYDROBENZOFURAN AND INDEN ANALOGS AS CARDIAC SARCOMERE INHIBITORS

Provided are compounds of Formula (I), or a pharmaceutically acceptable salt thereof, wherein A, Z, B, R1, R2, R3, G1, G2, and G3 are as defined herein. Also provided is a pharmaceutically acceptable composition comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof Also provided are methods of using a compound of Formula (I), or a pharmaceutically acceptable salt, thereof for use in methods of treatment heart diseases through cardiac sarcomere inhibtion.

ISOQUINOLINE COMPOUNDS, A PROCESS FOR THEIR PREPARATION, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

A compound of formula (I): wherein the substituents are as defined in the description. Medicinal products containing the same which are useful in treating or preventing pathologies which are the result of activation of the RhoA/ROCK pathway and phosphorylation of the myosin light chain.