3-(1-Indolinyl)benzylamines: a new class of analgesic agents

Abstract

An extensive series of 3-(1-indolinyl)benzylamines and related compounds was synthesized and tested for analgesic activity. After a detailed study of structure-activity relationships, 3-(1-indolinyl)benzylamine (2b) was selected for further investigation as the most interesting member of this novel class of compounds. It was active in both the phenylquinone writhing and tail-flick assays for analgesic activity. No motor deficits were observed in the rotorod test, and 2b was found to be free of any other effects on the central nervous system. The compound did not bind to opiate receptors, since it was inactive in inhibiting the stereospecific binding of [3H]naloxone in rat brain homogenates. Thus, 3-(1-indolinyl)benzylamine represents a novel analgesic with an unusual chemical structure and biological profile.

A Comprehensive Listing of Bioactivation Pathways of Organic Functional Groups

“…17). A few drug candidates containing the primary benzylamine moiety have also been considered for development including antifungal agents [135], NK-1 receptor antagonists [136], factor Xa inhibitors [137] and analgesics [138]. However the development of many compounds (e.g., factor Xa inhibitors) were suspended because of toxicities observed in various preclinical species.…”

“…The mechanism of formation of 139 has been speculated to occur via the formation of the reactive imine-methide 137. Thus initial N-oxygenation of L-745, 870 would afford the positively charged N-oxide metabolite 136, β-elimination would then lead to 137 and N-hydroxy-4-chlorophenylpiperazine (138). Nucleophilic addition of GSH across 137 followed by peptide cleavage of GSH and acetylation would generate 139.…”

One-Pot N-Arylation of Indoles Directly from N-Arylsulfonylindoles via Consecutive Deprotection and SNAr Reactions with Activated Aryl Halides

“…N-Arylindoles are known to be important subunits due to their key role in medically biological activities, such as those displaying antiestrogen, 1) analgesic, 2) antimicrobial, 3) neuroleptic, 4) antiallergy, 5) 5-HT 6 receptor antagonists, 6) FTase inhibitors (FTIs), 7) and anti-human immunodeficiency virus (HIV)-1 activities. 8) Although the development of new methodologies for the N-arylation of indoles catalyzed by palladium or copper has received much attention in recent years, [9][10][11][12][13][14] the nucleophilic aromatic substitutions (SNAr) of aryl halides, activated by electron-withdrawing substituents, with indoles represent an alternate route to N-arylindoles for certain substrate combinations.…”

Development of Brönsted–Lewis acidic solid catalytic system of 3-methyl-1-sulfonic acid imidazolium transition metal chlorides for the preparation of bis(indolyl)methanes

“…As we know, both Lewis and Brönsted acids play important roles in acid catalysed processes [19][20]. These considerations incited us to construct three new catalytic frameworks of 3-methyl-1-sulfonic acid imidazolium transition [25][26][27]. A large number of synthetic methods have been reported in the literature with various limitations for the preparation of bis(indolyl)methanes in presence of Lewis or protic acids [28][29][30].…”