907991-13-3

Upstream product

• 75336-86-6 (2R)-methylpiperazine 
• 610-40-2 3,4-dinitro-chlorobenzene 
• 700-37-8 4-chloro-2-fluoro-nitrobenzene 
• 170033-47-3 (R)-tert-butyl 2-methylpiperazine-1-carboxylate 

Downstream Products

• 907991-14-4 (R)-4-(5-Chloro-2-nitro-phenyl)-2-methyl-piperazine-1-carboxylic acid benzyl ester 
• 556113-62-3 {(R)-4-[5-Chloro-2-(4-methoxy-phenylsulfanyl)-phenyl]-2-methyl-piperazin-1-yl}-acetic acid 
• 907991-19-9 (R)-1-[5-Chloro-2-(4-methoxy-phenylsulfanyl)-phenyl]-3-methyl-piperazine 
• 907991-18-8 (R)-4-[5-Chloro-2-(4-methoxy-phenylsulfanyl)-phenyl]-2-methyl-piperazine-1-carboxylic acid benzyl ester 
• 907991-20-2 {4-[5-chloro-2-(4-methoxy-phenylsulfanyl)-phenyl]-2-methyl-piperazin-1-yl}-acetic acid tert-butyl ester 
• 907991-16-6 (R)-4-(5-Chloro-2-iodo-phenyl)-2-methyl-piperazine-1-carboxylic acid benzyl ester 
• 907991-15-5 (R)-4-(2-Amino-5-chloro-phenyl)-2-methyl-piperazine-1-carboxylic acid benzyl ester 

Relevant academic research and scientific papers

An improved synthesis of Lu AA20465

A solution phase synthesis for the preparation of the glycine transporter 1 (GlyT1) inhibitor Lu AA20465 is presented, which relies on the straightforward assembly of the target molecule through a series of innovative reaction steps. The key steps include a regioselective amination reaction, a chemoselective reduction of an aryl nitro group, a diazotization and iodination sequence under nonaqueous conditions and a copper catalyzed thioarylation reaction.

MODULATORS OF THE G PROTEIN-COUPLED MAS RECEPTOR AND THE TREATMENT OF DISORDERS RELATED THERETO

The present invention relates to compounds of Formula (Ia) and pharmaceutically acceptable salts, solvates, and hydrates thereof, that modulate the activity of the Mas receptor, and are useful in methods of treatment and alleviation of diseases and disorders of the heart, brain, kidney, immune system, and reproductive system resulting from ischemia, or reperfusion subsequent to ischemia, and any downstream complication(s) related thereto. These diseases and disorders include, for example, vascular disorders, such as: coronary heart disease, atherosclerosis, ischemia, reperfusion injury, angina pectoris, myocardial infarction, the no-reflow phenomenon, hypertension, transient ischemic attack, ischemic colitis, mesenteric ischemia, acute limb ischemia, and skin discoloration caused by reduced blood flow to the skin; and calcium-signaling disorders such as: arrhythmia, tachycardia, bradycardia, atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, Wolff-Parkinson-White syndrome, ventricular arrhythmia, ventricular tachycardia, ventricular fibrillation, reperfusion arrhythmia, and reperfusion-induced cardiomyocyte cell death.

The synthesis and SAR of 2-arylsulfanyl-phenyl piperazinyl acetic acids as glyT-1 inhibitors

Elevation of glycine levels and activation of the NMDA receptor by inhibition of the glycine transporter 1 (GlyT-1) is a potential strategy for the treatment of schizophrenia. A novel series of GlyT-1 inhibitors have been identified containing the 2-arylsulfanyl-phenylpiperazine motif. The most prominent member of this series, (R)-4-[5-chloro-2-(4-methoxy-phenylsulfanyl)- phenyl]-2-methyl-piperazin-1-yl-acetic acid (31) is a potent glycine transporter-1 inhibitor (IC50=150nM), which elevated glycine levels in rat ventral hippocampus as measured by microdialysis in vivo at doses of 1.2-4.6mg/kg s.c.