Development of selective agents targeting serotonin 5HT 1A receptors with subnanomolar activities based on a coumarin core

A series of 18 new 5-[3-(4-aryl-1-piperazinyl)propoxy]coumarin derivatives from the corresponding bromoalkyl derivatives have been designed and synthesized by us using a microwave-assisted protocol. Radioligand binding assays of this series of compounds as well as a previously synthesized series of...

Full description

Saved in:
Bibliographic Details
Published inMedChemComm Vol. 8; no. 8; pp. 1690 - 1696
Main Authors Ostrowska, K, Grzeszczuk, D, Głuch-Lutwin, M, Gryboś, A, Siwek, A, Dobrzycki, Ł, Trzaskowski, B
Format Journal Article
LanguageEnglish
Published England 01.08.2017
Online AccessGet full text

Cover

Abstract A series of 18 new 5-[3-(4-aryl-1-piperazinyl)propoxy]coumarin derivatives from the corresponding bromoalkyl derivatives have been designed and synthesized by us using a microwave-assisted protocol. Radioligand binding assays of this series of compounds as well as a previously synthesized series of 17 structurally-similar compounds showed that six systems have very high affinities to the 5-HT receptor (0.3-1.0 nM) and good selectivity against the 5-HT receptor. Molecular docking, structural studies and structure-activity relationship studies were used to gain more insight into the atomistic details of ligand binding and rationalize the obtained results.
AbstractList A series of 18 new 5-[3-(4-aryl-1-piperazinyl)propoxy]coumarin derivatives from the corresponding bromoalkyl derivatives have been designed and synthesized by us using a microwave-assisted protocol. Radioligand binding assays of this series of compounds as well as a previously synthesized series of 17 structurally-similar compounds showed that six systems have very high affinities to the 5-HT receptor (0.3-1.0 nM) and good selectivity against the 5-HT receptor. Molecular docking, structural studies and structure-activity relationship studies were used to gain more insight into the atomistic details of ligand binding and rationalize the obtained results.
A series of 18 new 5-[3-(4-aryl-1-piperazinyl)propoxy]coumarin derivatives from the corresponding bromoalkyl derivatives have been designed and synthesized by us using a microwave-assisted protocol. Radioligand binding assays of this series of compounds as well as a previously synthesized series of 17 structurally-similar compounds showed that six systems have very high affinities to the 5-HT 1A receptor (0.3–1.0 nM) and good selectivity against the 5-HT 2A receptor. Molecular docking, structural studies and structure–activity relationship studies were used to gain more insight into the atomistic details of ligand binding and rationalize the obtained results.
Author Dobrzycki, Ł
Trzaskowski, B
Gryboś, A
Grzeszczuk, D
Siwek, A
Głuch-Lutwin, M
Ostrowska, K
Author_xml – sequence: 1
  givenname: K
  orcidid: 0000-0002-5990-646X
  surname: Ostrowska
  fullname: Ostrowska, K
  email: kostrowska@wum.edu.pl
  organization: Department of Organic Chemistry , Faculty of Pharmacy , Medical University of Warsaw , 1 Banacha Str. , 02 097 Warsaw , Poland . Email: kostrowska@wum.edu.pl
– sequence: 2
  givenname: D
  surname: Grzeszczuk
  fullname: Grzeszczuk, D
  email: kostrowska@wum.edu.pl
  organization: Department of Organic Chemistry , Faculty of Pharmacy , Medical University of Warsaw , 1 Banacha Str. , 02 097 Warsaw , Poland . Email: kostrowska@wum.edu.pl
– sequence: 3
  givenname: M
  surname: Głuch-Lutwin
  fullname: Głuch-Lutwin, M
  organization: Department of Pharmacobiology , Faculty of Pharmacy , Jagiellonian University Collegium Medicum , Kraków , Poland
– sequence: 4
  givenname: A
  surname: Gryboś
  fullname: Gryboś, A
  organization: Department of Pharmacobiology , Faculty of Pharmacy , Jagiellonian University Collegium Medicum , Kraków , Poland
– sequence: 5
  givenname: A
  surname: Siwek
  fullname: Siwek, A
  organization: Department of Pharmacobiology , Faculty of Pharmacy , Jagiellonian University Collegium Medicum , Kraków , Poland
– sequence: 6
  givenname: Ł
  surname: Dobrzycki
  fullname: Dobrzycki, Ł
  organization: Crystallochemistry Laboratory, Faculty of Chemistry , University of Warsaw , 1 Pasteura Str. , 02 093 Warsaw , Poland
– sequence: 7
  givenname: B
  orcidid: 0000-0003-2385-1476
  surname: Trzaskowski
  fullname: Trzaskowski, B
  organization: Centre of New Technologies , University of Warsaw , 2C Banacha Str. , 02-097 , Poland
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30108880$$D View this record in MEDLINE/PubMed
BookMark eNpFkE9PwzAMxSM0xMbYhQ-AckYqOEn_pMdpGwxpiMvuVZq6o6hNqiQbgk9Pp8HwxZb909PzuyYjYw0ScsvggYHIHxfZ6xKAS7a6IBMOMUQ8YWx0nkGMycz7DxhKcCnz-IqMBTCQUsKEfC_xgK3tOzSB2pp6bFGH5oBU7YaVp0G5HYbG7IaTs8GaxtBkvaVsTh1q7IN1nn424Z36fWmUsZ1tlaPqKNKEBj0tlceKWkMV1XbfKTcoaOvwhlzWqvU4--1Tsn1abRfraPP2_LKYbyKd5xCxBFIpYyg1q2SqyjpJeI6iUhlAmVQxhxo4F8N3qlSCcSZQp0mmMEurOo8zMSX3J1ntrPcO66J3zeDiq2BQHCMs_iMc4LsT3O_LDqsz-heY-AE98G4r
CitedBy_id crossref_primary_10_1002_med_22049
crossref_primary_10_3390_ph14030179
crossref_primary_10_1080_07391102_2022_2104376
crossref_primary_10_1016_j_jsps_2019_11_025
crossref_primary_10_1016_j_bmc_2017_12_016
crossref_primary_10_3390_ijms24032779
crossref_primary_10_1016_j_ejphar_2020_173635
crossref_primary_10_1016_j_bioorg_2020_103912
crossref_primary_10_1016_j_ejps_2018_01_011
Cites_doi 10.1016/S0960-894X(98)00646-5
10.2174/092986710790936284
10.1016/j.ejmech.2014.01.012
10.1007/s00706-016-1725-7
10.1016/j.ejmech.2016.09.050
10.1021/jm00071a006
10.1016/j.ejmech.2017.05.047
10.1021/jm00125a020
10.1007/s00044-013-0543-2
10.1007/s10822-010-9349-1
10.1021/ml4004843
10.1016/S0960-894X(02)00933-2
10.1021/jm049504o
10.1111/j.1471-4159.1986.tb12926.x
10.1021/cr078224o
10.1016/j.ejmech.2014.09.070
10.1016/S0223-5234(02)01357-0
10.1002/prot.10613
10.1021/jm200421e
10.1021/jm400408r
10.1021/jm980420n
10.1021/jm050826h
10.1002/jcc.21256
10.1016/j.phrs.2015.11.023
ContentType Journal Article
DBID NPM
AAYXX
CITATION
DOI 10.1039/C7MD00281E
DatabaseName PubMed
CrossRef
DatabaseTitle PubMed
CrossRef
DatabaseTitleList PubMed
CrossRef
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Pharmacy, Therapeutics, & Pharmacology
EISSN 2040-2511
EndPage 1696
ExternalDocumentID 10_1039_C7MD00281E
30108880
Genre Journal Article
GroupedDBID ---
-JG
0-7
0R~
4.4
705
7~J
AAEMU
AAIWI
AAJAE
AANOJ
AARTK
AAWGC
AAXHV
ABASK
ABDVN
ABEMK
ABJNI
ABPDG
ABRYZ
ABXOH
ACGFO
ACGFS
ACIWK
ACLDK
ACPRK
ADBBV
ADMRA
ADSRN
AEFDR
AENEX
AENGV
AESAV
AETIL
AFLYV
AFOGI
AFRAH
AFVBQ
AGEGJ
AGRSR
AGSTE
AHGCF
AKBGW
ALMA_UNASSIGNED_HOLDINGS
ANBJS
ANUXI
AOIJS
APEMP
ASKNT
AUDPV
AUNWK
AZFZN
BLAPV
BSQNT
C6K
EBS
ECGLT
EE0
EF-
EJD
H13
HYE
HZ~
H~N
J3I
NPM
O-G
O9-
P2P
RAOCF
RCNCU
RNS
RPM
RPMJG
RRC
RSCEA
RVUXY
SKF
SKH
SKJ
SKM
SKR
SKZ
SLC
SLF
AAYXX
AHGXI
ANLMG
ASPBG
AVWKF
CAG
CITATION
COF
FEDTE
HVGLF
J3G
J3H
L-8
OK1
ROYLF
SMJ
ID FETCH-LOGICAL-c990-15068840bc1d86abf5529e3da700b5d420f0223000aba31213ec657ae76df9473
ISSN 2040-2503
IngestDate Fri Aug 23 03:06:20 EDT 2024
Sat Nov 02 12:20:24 EDT 2024
IsPeerReviewed true
IsScholarly true
Issue 8
Language English
LinkModel OpenURL
MergedId FETCHMERGED-LOGICAL-c990-15068840bc1d86abf5529e3da700b5d420f0223000aba31213ec657ae76df9473
ORCID 0000-0003-2385-1476
0000-0002-5990-646X
PMID 30108880
PageCount 7
ParticipantIDs crossref_primary_10_1039_C7MD00281E
pubmed_primary_30108880
PublicationCentury 2000
PublicationDate 2017-Aug-01
PublicationDateYYYYMMDD 2017-08-01
PublicationDate_xml – month: 08
  year: 2017
  text: 2017-Aug-01
  day: 01
PublicationDecade 2010
PublicationPlace England
PublicationPlace_xml – name: England
PublicationTitle MedChemComm
PublicationTitleAlternate Medchemcomm
PublicationYear 2017
References Ransom (C7MD00281E-(cit3)/*[position()=1]) 1986; 46
Perrone (C7MD00281E-(cit4)/*[position()=1]) 1999; 42
Li (C7MD00281E-(cit21)/*[position()=1]) 2004; 47
Nowak (C7MD00281E-(cit18)/*[position()=1]) 2006; 49
Gonzalez-Gomez (C7MD00281E-(cit13)/*[position()=1]) 2003; 13
Morris (C7MD00281E-(cit20)/*[position()=1]) 2009; 16
Jacobson (C7MD00281E-(cit16)/*[position()=1]) 2004; 55
Liegeois (C7MD00281E-(cit17)/*[position()=1]) 2014; 5
Prandi (C7MD00281E-(cit22)/*[position()=1]) 2012; 55
Franchini (C7MD00281E-(cit23)/*[position()=1]) 2014; 87
Ostrowska (C7MD00281E-(cit15)/*[position()=1]) 2016; 147
Ostrowska (C7MD00281E-(cit14)/*[position()=1]) 2017; 137
Teran (C7MD00281E-(cit10)/*[position()=1]) 1998; 8
Greenwood (C7MD00281E-(cit19)/*[position()=1]) 2010; 24
van Steen (C7MD00281E-(cit5)/*[position()=1]) 1993; 36
Santana (C7MD00281E-(cit9)/*[position()=1]) 2002; 37
Mandala (C7MD00281E-(cit7)/*[position()=1]) 2013; 22
Nichols (C7MD00281E-(cit1)/*[position()=1]) 2008; 108
Chen (C7MD00281E-(cit11)/*[position()=1]) 2013; 56
Franchini (C7MD00281E-(cit24)/*[position()=1]) 2017; 125
Chen (C7MD00281E-(cit12)/*[position()=1]) 2014; 74
Skalicka-Woźniak (C7MD00281E-(cit8)/*[position()=1]) 2016; 103
Riveiro (C7MD00281E-(cit6)/*[position()=1]) 2010; 17
Martin (C7MD00281E-(cit2)/*[position()=1]) 1989; 32
References_xml – volume: 8
  start-page: 3567
  year: 1998
  ident: C7MD00281E-(cit10)/*[position()=1]
  publication-title: Bioorg. Med. Chem. Lett.
  doi: 10.1016/S0960-894X(98)00646-5
  contributor:
    fullname: Teran
– volume: 17
  start-page: 1325
  year: 2010
  ident: C7MD00281E-(cit6)/*[position()=1]
  publication-title: Curr. Med. Chem.
  doi: 10.2174/092986710790936284
  contributor:
    fullname: Riveiro
– volume: 74
  start-page: 427
  year: 2014
  ident: C7MD00281E-(cit12)/*[position()=1]
  publication-title: Eur. J. Med. Chem.
  doi: 10.1016/j.ejmech.2014.01.012
  contributor:
    fullname: Chen
– volume: 147
  start-page: 1615
  year: 2016
  ident: C7MD00281E-(cit15)/*[position()=1]
  publication-title: Monatsh. Chem.
  doi: 10.1007/s00706-016-1725-7
  contributor:
    fullname: Ostrowska
– volume: 125
  start-page: 435
  year: 2017
  ident: C7MD00281E-(cit24)/*[position()=1]
  publication-title: Eur. J. Med. Chem.
  doi: 10.1016/j.ejmech.2016.09.050
  contributor:
    fullname: Franchini
– volume: 36
  start-page: 2751
  year: 1993
  ident: C7MD00281E-(cit5)/*[position()=1]
  publication-title: J. Med. Chem.
  doi: 10.1021/jm00071a006
  contributor:
    fullname: van Steen
– volume: 137
  start-page: 108
  year: 2017
  ident: C7MD00281E-(cit14)/*[position()=1]
  publication-title: Eur. J. Med. Chem.
  doi: 10.1016/j.ejmech.2017.05.047
  contributor:
    fullname: Ostrowska
– volume: 32
  start-page: 1052
  year: 1989
  ident: C7MD00281E-(cit2)/*[position()=1]
  publication-title: J. Med. Chem.
  doi: 10.1021/jm00125a020
  contributor:
    fullname: Martin
– volume: 22
  start-page: 5481
  year: 2013
  ident: C7MD00281E-(cit7)/*[position()=1]
  publication-title: Med. Chem. Res.
  doi: 10.1007/s00044-013-0543-2
  contributor:
    fullname: Mandala
– volume: 24
  start-page: 591
  year: 2010
  ident: C7MD00281E-(cit19)/*[position()=1]
  publication-title: J. Comput.-Aided Mol. Des.
  doi: 10.1007/s10822-010-9349-1
  contributor:
    fullname: Greenwood
– volume: 5
  start-page: 358
  year: 2014
  ident: C7MD00281E-(cit17)/*[position()=1]
  publication-title: ACS Med. Chem. Lett.
  doi: 10.1021/ml4004843
  contributor:
    fullname: Liegeois
– volume: 13
  start-page: 175
  year: 2003
  ident: C7MD00281E-(cit13)/*[position()=1]
  publication-title: Bioorg. Med. Chem. Lett.
  doi: 10.1016/S0960-894X(02)00933-2
  contributor:
    fullname: Gonzalez-Gomez
– volume: 47
  start-page: 6681
  year: 2004
  ident: C7MD00281E-(cit21)/*[position()=1]
  publication-title: J. Med. Chem.
  doi: 10.1021/jm049504o
  contributor:
    fullname: Li
– volume: 46
  start-page: 68
  year: 1986
  ident: C7MD00281E-(cit3)/*[position()=1]
  publication-title: J. Neurochem.
  doi: 10.1111/j.1471-4159.1986.tb12926.x
  contributor:
    fullname: Ransom
– volume: 108
  start-page: 1614
  year: 2008
  ident: C7MD00281E-(cit1)/*[position()=1]
  publication-title: Chem. Rev.
  doi: 10.1021/cr078224o
  contributor:
    fullname: Nichols
– volume: 87
  start-page: 248
  year: 2014
  ident: C7MD00281E-(cit23)/*[position()=1]
  publication-title: Eur. J. Med. Chem.
  doi: 10.1016/j.ejmech.2014.09.070
  contributor:
    fullname: Franchini
– volume: 37
  start-page: 503
  year: 2002
  ident: C7MD00281E-(cit9)/*[position()=1]
  publication-title: Eur. J. Med. Chem.
  doi: 10.1016/S0223-5234(02)01357-0
  contributor:
    fullname: Santana
– volume: 55
  start-page: 351
  year: 2004
  ident: C7MD00281E-(cit16)/*[position()=1]
  publication-title: Proteins: Struct., Funct., Bioinf.
  doi: 10.1002/prot.10613
  contributor:
    fullname: Jacobson
– volume: 55
  start-page: 23
  year: 2012
  ident: C7MD00281E-(cit22)/*[position()=1]
  publication-title: J. Med. Chem.
  doi: 10.1021/jm200421e
  contributor:
    fullname: Prandi
– volume: 56
  start-page: 4671
  year: 2013
  ident: C7MD00281E-(cit11)/*[position()=1]
  publication-title: J. Med. Chem.
  doi: 10.1021/jm400408r
  contributor:
    fullname: Chen
– volume: 42
  start-page: 490
  year: 1999
  ident: C7MD00281E-(cit4)/*[position()=1]
  publication-title: J. Med. Chem.
  doi: 10.1021/jm980420n
  contributor:
    fullname: Perrone
– volume: 49
  start-page: 205
  year: 2006
  ident: C7MD00281E-(cit18)/*[position()=1]
  publication-title: J. Med. Chem.
  doi: 10.1021/jm050826h
  contributor:
    fullname: Nowak
– volume: 16
  start-page: 2785
  year: 2009
  ident: C7MD00281E-(cit20)/*[position()=1]
  publication-title: J. Comput. Chem.
  doi: 10.1002/jcc.21256
  contributor:
    fullname: Morris
– volume: 103
  start-page: 188
  year: 2016
  ident: C7MD00281E-(cit8)/*[position()=1]
  publication-title: Pharmacol. Res.
  doi: 10.1016/j.phrs.2015.11.023
  contributor:
    fullname: Skalicka-Woźniak
SSID ssj0000328894
Score 2.1325758
Snippet A series of 18 new 5-[3-(4-aryl-1-piperazinyl)propoxy]coumarin derivatives from the corresponding bromoalkyl derivatives have been designed and synthesized by...
SourceID crossref
pubmed
SourceType Aggregation Database
Index Database
StartPage 1690
Title Development of selective agents targeting serotonin 5HT 1A receptors with subnanomolar activities based on a coumarin core
URI https://www.ncbi.nlm.nih.gov/pubmed/30108880
Volume 8
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lj9MwELbKcuGCeLMsoJFg99JNSfN0jqW7qEIU7SFIe6vs2AEJkayadFH7U_i1zDgvF_awcIlaK65Uz6eZ8fibz4y9DeNEK-4G1KKsnCBU2uFCxQ7GpszTnohjTXXI5edo8SX4eBlejka_LNbSppaTbHdjX8n_WBXH0K7UJfsPlu1_FAfwM9oXn2hhfN7Kxhbjh5K-ytxpQ1Qg8dU0rjU0b1Mx0OuypsrrOFyk4-lsjI5OX5mbdlqSuixEUf6gja7R17g2SqtjCnKKDhTEOCuJjW1o6-s9_tBSK5IdoFaTvmRb1bi9r743_WaTgeSz09Uu222MCz4bxo_n4TH3Ntk359Om_tnIGiytaVtZ0ivJe-PKJnapAsNfR5RrPZpH9EXMuRqPpu2x1uO2LplbyOOWe6UzPStU49foxjDg-qSiOo-XZ7SnnJ4Pwa474P8jBvbMRHMm7yerYe4ddtdDJ8atSpCJ8r7Hublns_9Xnfqtn7wbpu_lO3s7F5PBpA_Y_XbrAbMGRw_ZSBeP2MlFo12-PYV0aMWrTuEELgZV8-1jtrPABmUOPdigARv0YIMebIBgg-kMerABgQ1ssMEANjBgg7IAAR3YgMD2hKUfztP5wmkv7nAyTG4cEq3kPHBlNlU8EjIPQy_RvhKx68pQBZ6bY-bo4xoKKXzSFNRZFMZCx5HKkyD2n7KDoiz0cwa50IGMZcQlps5Rzjkl-CpL3EwkInTlIXvTre7qqpFnWf1twkP2rFn4_h0MaxheufviVvOP2L0Bzi_ZQb3e6FeYi9bytQHFbx-fiSI
link.rule.ids 315,783,787,27938,27939
linkProvider National Library of Medicine
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Development+of+selective+agents+targeting+serotonin+5HT+1A+receptors+with+subnanomolar+activities+based+on+a+coumarin+core&rft.jtitle=MedChemComm&rft.au=Ostrowska%2C+K.&rft.au=Grzeszczuk%2C+D.&rft.au=G%C5%82uch-Lutwin%2C+M.&rft.au=Grybo%C5%9B%2C+A.&rft.date=2017-08-01&rft.issn=2040-2503&rft.eissn=2040-2511&rft.volume=8&rft.issue=8&rft.spage=1690&rft.epage=1696&rft_id=info:doi/10.1039%2FC7MD00281E&rft.externalDBID=n%2Fa&rft.externalDocID=10_1039_C7MD00281E
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2040-2503&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2040-2503&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2040-2503&client=summon