4-Alkylpiperidines related to SR-48968: Potent antagonists of the neurokinin-2 (NK2) receptor

The Combinatorial Synthesis of Bicyclic Privileged Structures or Privileged Substructures

“…Neurokinin antagonists are implicated in a variety of disease states, including migraine, emesis, pain, arthritis, asthma, depression, and anxiety. − Many neurokinin-1 receptor antagonists have been reported in the literature based on the arylpiperidine scaffold. ,, Less effort has been applied to the discovery of non-peptide antagonists of the neurokinin-2 and -3 receptors . Possible applications of drugs specific for these receptors include the treatment of asthma, as well as psychosis and anxiety. , It should be noted that the endogenous ligands of the neurokinin-1, -2, and -3 receptors (substance P, neurokinin A, and neurokinin B, respectively) have the highest affinity for their native receptor subtypes, but all three peptides have a relatively high affinity for, and are able to act as full agonists for all three receptor subtypes 3 The cis -(2 S ,3 S )-piperidine framework is a basic framework for high-affinity neurokinin-1 receptor (NK 1 ) antagonists …”

“…186 Possible applications of drugs specific for these receptors include the treatment of asthma, as well as psychosis and anxiety. 186,190 It should be noted that the endogenous ligands of the neurokinin-1, -2, and -3 receptors (substance P, neurokinin A, and neurokinin B, respectively) have the highest affinity for their native receptor subtypes, but all three peptides have a relatively high affinity for, and are able to act as full agonists for all three receptor subtypes. 186 The arylpiperidine moiety is also found in antagonists for other neuroreceptors.…”

Synthesis of (R)-Modafinil via Organocatalyzed and Non-Heme Iron-Catalyzed Sulfoxidation Using H2O2 as an Environmentally Benign Oxidant

“…There are several examples that playing an important role in medicinal and pharmaceutical chemistry [2], including Esomeprazole [7,8], which acts as proton-pump inhibitor; the selective NK 2 antagonist ZD7944 [9]; and the anti-cancer agent Sulindac ® (Figure 1) [10].…”

“…There are several examples that playing an important role in medicinal and pharmaceutical chemistry [2], including Esomeprazole [7,8], which acts as proton-pump inhibitor; the selective NK2 antagonist ZD7944 [9]; and the anti-cancer agent Sulindac ® (Figure 1) [10]. Modafinil (also known as Provigil ® [11], Figure 2), another important sulfoxide, is administered as a drug against narcolepsy [12] with significant advantages compared to dexamphetamine [13] and several other stimulants [14] because of a lower abuse potential [15,16].…”

The First de Novo-Designed Antagonists of the Human NK2 Receptor

“…To date, in addition to a number of peptidic antagonists, , there are currently two main classes of nonpeptidic NK 2 receptor antagonists (Figure ); the benzamide piperidine antagonists, e.g., 1 , − and those derived from indolium piperidines, e.g., 2 (Figure ). Although much elegant work has been done to refine the structure−activity relationships within these classes, essentially all of the known antagonists have resulted from compound library screening methods.…”