896125-11-4

Basic information

• Product Name: 2-methylpropane-1-sulfonic acid {4-[4-(3-nitrophenyl)piperazin-1-yl]butyl}amide
• Synonyms: 2-methylpropane-1-sulfonic acid {4-[4-(3-nitrophenyl)piperazin-1-yl]butyl}amide
• CAS NO: 896125-11-4
• Molecular Weight: 398.527
• Mol File: 896125-11-4.mol

Chemical Properties

• CAS DataBase Reference: 2-methylpropane-1-sulfonic acid {4-[4-(3-nitrophenyl)piperazin-1-yl]butyl}amide(CAS DataBase Reference)
• NIST Chemistry Reference: 2-methylpropane-1-sulfonic acid {4-[4-(3-nitrophenyl)piperazin-1-yl]butyl}amide(896125-11-4)
• EPA Substance Registry System: 2-methylpropane-1-sulfonic acid {4-[4-(3-nitrophenyl)piperazin-1-yl]butyl}amide(896125-11-4)

Safety Data

• Hazardous Substances Data: 896125-11-4(Hazardous Substances Data)

Upstream product

• 35432-36-1 2-methylpropane-1-sulfonyl chloride 
• 740873-02-3 4-(4-(3-nitrophenyl)piperazin-1-yl)butan-1-amine 
• 99-09-2 3-nitro-aniline 
• 54054-85-2 1-(3-nitrophenyl)piperazine 
• 740873-01-2 {4-[4-(3-nitrophenyl)piperazin-1-yl]butyl}carbamic acid tert-butyl ester 

Downstream Products

• 740873-14-7 2-methylpropane-1-sulfonic acid {4-[4-(3-aminophenyl)piperazin-1-yl]butyl}amide 
• 740873-15-8 N-(3-{4-[4-(2-methylpropane-1-sulfonylamino)butyl]piperazin-1-yl}phenyl)acetamide 

Relevant articles and documents

An integrated in silico 3D model-driven discovery of a novel, potent, and selective amidosulfonamide 5-HT1A agonist (PRX-00023) for the treatment of anxiety and depression

We report the discovery of a novel, potent, and selective amidosulfonamide nonazapirone 5-HT1A agonist for the treatment of anxiety and depression, which is now in Phase III clinical trials for generalized anxiety disorder (GAD). The discovery of 20m (PRX-00023), N-{3-[4-(4- cyclohexylmethanesulfonylaminobutyl)-piperazin-1-yl]phenyl}acetamide, and its backup compounds, followed a new paradigm, driving the entire discovery process with in silico methods and seamlessly integrating computational chemistry with medicinal chemistry, which led to a very rapid discovery timeline. The program reached clinical trials within less than 2 years from initiation, spending less than 6 months in lead optimization with only 31 compounds synthesized. In this paper we detail the entire discovery process, which started with modeling the 3D structure of 5-HT1A using the PREDICT methodology, and then performing in silico screening on that structure leading to the discovery of a 1 nM lead compound (8). The lead compound was optimized following a strategy devised based on in silico 3D models and realized through an in silico-driven optimization process, rapidly overcoming selectivity issues (affinity to 5-HT1A vs α1-adrenergic receptor) and potential cardiovascular issues (hERG binding), leading to a clinical compound. Finally we report key in vivo preclinical and Phase I clinical data for 20m tolerability, pharmacokinetics, and pharmacodynamics and show that these favorable results are a direct outcome of the properties that were ascribed to the compound during the rational structure-based discovery process. We believe that this is one of the first examples for a Phase III drug candidate that was discovered and optimized, from start to finish, using in silico model-based methods as the primary tool.

NEW ARYLPIPERAZINYL COMPOUNDS

The invention relates to 5-HT receptor agonists or antagonists. Novel arylpiperazinyl sulfonamide compounds represented by formula (I), and synthesis and uses thereof for treating diseases including those mediated directly or indirectly by 5-HT receptors, are disclosed. Such conditions include central nervous system disorders such as generalized anxiety disorder, ADD/ADHD, neural injury, stroke, and migraine. Methods of preparation and novel intermediates and pharmaceutical salts thereof are also included.