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Spiro[pyrrolidine-3,3'-oxindoles] and Their Indoline Analogues as New 5-HT6 Receptor Chemotypes.

ABSTRACT: Synthetic derivatives of spiro[pyrrolidinyl-3,3'-oxindole] alkaloids (coerulescine analogues) were investigated as new ligands for aminergic G-protein coupled receptors (GPCRs). The chemical starting point 2'-phenylspiro[indoline-3,3'-pyrrolidin]-2-one scaffold was identified by virtual fragment screening utilizing ligand- and structure based methods. As a part of the hit-to-lead optimization a structure-activity relationship analysis was performed to explore the differently substituted 2'-phenyl-derivatives, introducing the phenylsulphonyl pharmacophore and examining the corresponding reduced spiro[pyrrolidine-3,3'-indoline] scaffold. The optimization process led to ligands with submicromolar affinities towards the 5-HT? receptor that might serve as viable leads for further optimization.

SUBMITTER: Kelemen AA

PROVIDER: S-EPMC6149751 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Spiro[pyrrolidine-3,3'-oxindoles] and Their Indoline Analogues as New 5-HT6 Receptor Chemotypes.

Kelemen Ádám A ÁA Satala Grzegorz G Bojarski Andrzej J AJ Keserű György M GM

Molecules (Basel, Switzerland) 20171214 12

Synthetic derivatives of spiro[pyrrolidinyl-3,3'-oxindole] alkaloids (coerulescine analogues) were investigated as new ligands for aminergic G-protein coupled receptors (GPCRs). The chemical starting point 2'-phenylspiro[indoline-3,3'-pyrrolidin]-2-one scaffold was identified by virtual fragment screening utilizing ligand- and structure based methods. As a part of the hit-to-lead optimization a structure-activity relationship analysis was performed to explore the differently substituted 2'-pheny ...[more]

PMID: 29240714

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