19077-27-1

Upstream product

• 3763-80-2 3-(2-chloro-10H-phenothiazin-10-yl)propan-1-amine hydrochloride 
• 98-59-9 p-toluenesulfonyl chloride 
• 92-39-7 2-chlorophenothiazine 
• 180388-71-0 N-[3-(2-chloro-phenothiazin-10-yl)-propyl]-phthalimide 

Downstream Products

• 22724-19-2 N-[3-(2-chloro-phenothiazin-10-yl)-propyl]-N-(toluene-4-sulfonyl)-acetamide 

Relevant academic research and scientific papers

Reengineered tricyclic anti-cancer agents

The phenothiazine and dibenzazepine tricyclics are potent neurotropic drugs with a documented but underutilized anti-cancer side effect. Reengineering these agents (TFP, CPZ, CIP) by replacing the basic amine with a neutral polar functional group (e.g., RTC-1, RTC-2) abrogated their CNS effects as demonstrated by in vitro pharmacological assays and in vivo behavioral models. Further optimization generated several phenothiazines and dibenzazepines with improved anti-cancer potency, exemplified by RTC-5. This new lead demonstrated efficacy against a xenograft model of an EGFR driven cancer without the neurotropic effects exhibited by the parent molecules. Its effects were attributed to concomitant negative regulation of PI3K-AKT and RAS-ERK signaling.

TRICYCLIC COMPOUNDS AS ANTICANCER AGENTS

Tricyclic chemical modulators of FOXO transcription factor proteins are disclosed. The compounds are useful to treat cancer, age-onset proteotoxicity, stress-induced depression, inflammation, and acne. The compounds are of phenothiazine, dibenzoazepine and annulene and similar genera.