Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ACCESS DATA

Json Xml

Publications

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

Similar Datasets

1'-Methyl-2-oxo-5'-phenyl-spiro-[indoline-3,3'-pyrrolidine]-4',4'-dicarbo-nitrile.

Project description:The title spiro-compound, C(20)H(16)N(4)O, crystallizes with four independent mol-ecules in the asymmetric unit. In all of them, the oxindole unit is planar, the r.m.s. deviations ranging from 0.07 to 0.08?Å, while the pyrrolinyl ring adopts an envelope conformation (with the N atom representing the flap). In the crystal, adjacent mol-ecules are linked by N-H?N and N-H?O hydrogen bonds.

| S-EPMC2980256 | biostudies-literature

Ethyl 4'-ethenyl-2'-oxo-4-phenyl-2-(3,4,5-trimethoxy-phen-yl)spiro-[pyrrolidine-3,3'-indoline]-5-carboxyl-ate monohydrate.

Project description:In the title compound, C(31)H(32)N(2)O(6)·H(2)O, the pyrrolidine ring adopts an envelope conformation. The ethyl C atoms of the ethoxy-cabonyl group are disordered over two positions with occupancies of ca 0.80 and 0.20. Intra-molecular N-H⋯O hydrogen bonds form S(5) and S(6) ring motifs. Mol-ecules are linked into a three-dimensional framework by O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds, and by C-H⋯π inter-actions.

| S-EPMC2959656 | biostudies-literature

1-Benzyl-4',5'-diphenyl-piperidine-3-spiro-3'-pyrrolidine-2'-spiro-3''-indoline-4,2''-dione.

Project description:The asymmetric unit of the title compound, C(34)H(31)N(3)O(2), consists of two independent mol-ecules which differ slightly in the orientations of the phenyl rings with respect to the pyrrolidine ring. In both mol-ecules, the piperidin-4-one ring adopts a chair conformation, whereas the pyrrolidine ring adopts an envelope conformation in one of the mol-ecules and a twisted conformation in the other. An intra-molecular C-H?O hydrogen bond is observed. The crystal packing is stabilized by inter-molecular N-H?O hydrogen bonds and C-H?? inter-actions.

| S-EPMC2968062 | biostudies-literature

1'-Methyl-2,2''-dioxoindoline-3-spiro-2'-pyrrolidine-3'-spiro-3''-indoline-4',4'-di-carbonitrile.

Project description:In the title compound, C(21)H(15)N(5)O(2), the pyrrolidine ring adopts a twist conformation. Both the oxindole rings are planar [maximum deviations of 0.076 (1) and 0.029 (1) Å in the two rings] and are oriented at a dihedral angle of 72.7 (1)°. The crystal structure is stabilized by C-H⋯O, N-H⋯O, N-H⋯N and C-H⋯π inter-actions.

| S-EPMC2977508 | biostudies-literature

5,6-Dimeth-oxy-4',5'-diphenyl-indane-2-spiro-3'-pyrrolidine-2'-spiro-3''-indoline-1,2''-dione.

Project description:In the title compound, C(33)H(28)N(2)O(4), the central pyrrolidine ring adopts a half-chair conformation. Both the indolinone and indanone groups are twisted, with their five-membered rings adopting a half-chair and an envelope conformation, respectively. The two benzene rings and the mean plane of the indolinone and indanone groups make dihedral angles of 71.98 (10), 84.32 (10), 86.26 (9) and 78.50 (9)°, respectively, with the central pyrrolidine ring. Intra-molecular C-H⋯O hydrogen bonds stabilize the mol-ecular conformation. In the crystal, pairs of inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into centrosymmetric dimers. The dimers are inter-connected into ribbons propagating along [110] via weak inter-molecular C-H⋯O hydrogen bonds. Weak inter-molecular C-H⋯π and π-π [centroid-centroid distance = 3.6509 (11) Å] inter-actions are also observed.

| S-EPMC2983396 | biostudies-literature

Organocatalysed one-pot three component synthesis of 3,3'-disubstituted oxindoles featuring an all-carbon quaternary center and spiro[2<i>H</i>-pyran-3,4'-indoline].

Project description:A simple and efficient methodology for the one-pot synthesis of 3,3'-disubstituted oxindoles featuring an all-carbon quaternary center has been demonstrated through l-proline catalysed three-component reaction based on sequential Knoevenagel condensation/Michael addition and also one-pot synthesis of spiro[2H-pyran-3,4'-indoline] through consecutive Knoevenagel condensation/Michael addition/reduction/cyclization reactions from readily available isatin derivatives, malononitrile, and ketones. The present methodology presents several advantages, including simple reaction set-up, short reaction times, and easy to work-up. Also, this strategy offers broad substrate scope with excellent yields and high atom economy, under mild reaction conditions.

| S-EPMC10140734 | biostudies-literature

Methyl 5''-chloro-1',1''-dimethyl-2,2''-dioxodi-spiro-[indoline-3,2'-pyrrolidine-3',3''-indoline]-4'-carboxyl-ate.

Project description:In the title compound, C22H20ClN3O4, the central pyrrolidine ring adopts an envelope conformation on the N atom. The indolinone systems are individually roughly planar, with maximum deviations from their mean planes of 0.130 Å for the spiro C atom of the indolinone unit and 0.172 Å for the carbonyl C atom of the 5-chloro-1-methyl-indolinone unit. They make dihedral angles of 77.7 (8) and 86.1 (8)° with the mean plane through the central pyrrolidine ring. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds supported by C-H⋯O contacts into chains along the ab diagonal. The structure also features C-H⋯O hydrogen bonds, forming R 2 (2)(8) and R 2 (2)(16) rings and generating a three-dimensional array.

| S-EPMC3684914 | biostudies-literature

1'-Methyl-4'-phenyl-dispiro-[chromane-3,3'-pyrrolidine-2',3''-indoline]-2,2''-dione.

Project description:In the title compound, C(26)H(22)N(2)O(3), the pyrrolidine ring adopts an envelope conformation with the N atom as the flap. In the crystal, pairs of centrosymmetrically related mol-ecules are linked into dimers by N-H⋯O hydrogen bonds. In addition, there are C-H⋯O hydrogen bonds.

| S-EPMC3297956 | biostudies-literature

4'-(2,4-Dichloro-phen-yl)-1,1'-dimethyl-piperidine-3-spiro-3'-pyrrolidine-2'-spiro-3''-indoline-4,2''-dione.

Project description:In the title compound, C(23)H(23)Cl(2)N(3)O(2), the pyrroline ring adopts an envelope conformation and the piperidinone ring assumes a slightly twisted chair form. In the crystal, inversion dimers linked by pairs of N-H?O hydrogen bonds generate an R(2) (8) graph-set motif and a short Cl?Cl contact of 3.478?(1)?Å occurs.

| S-EPMC2983500 | biostudies-literature

1''-Benzyl-1'-methyl-4'-(naphthalen-1-yl)naphthalene-2-spiro-3'-pyrrolidine-2'-spiro-3''-indoline-1,2''-dione.

Project description:In the title compound, C(38)H(32)N(2)O(2), the pyrrolidine ring adopts an envelope conformation, whereas the cyclo-hexa-none ring in the tetra-hydro-naphthalene fused-ring system adopts a half-chair conformation. The benzyl ring is oriented at an angle of 67.1?(1)° with respect to the naphthyl ring system. Four intra-molecular C-H?O close contacts and C-H?? inter-action are observed. In the crystal, mol-ecules associate via C-H?O hydrogen bonds, forming a C(12) chain motif along the ac plane.

| S-EPMC3151757 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data