X-ray structure based evaluation of analogs of citalopram

X-ray structure based evaluation of analogs of citalopram: Compounds with increased affinity and selectivity compared with R-citalopram for the allosteric site (S2) on hSERT

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

X-ray structure based evaluation of analogs of citalopram : Compounds with increased affinity and selectivity compared with R-citalopram for the allosteric site (S2) on hSERT. / Topiol, Sid; Bang-Andersen, Benny; Sanchez, Connie; Plenge, Per; Loland, Claus J; Juhl, Karsten; Larsen, Krestian; Bregnedal, Peter; Bøgesø, Klaus P.

In: Bioorganic & Medicinal Chemistry Letters, Vol. 27, No. 3, 01.02.2017, p. 470-478.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Topiol, S, Bang-Andersen, B, Sanchez, C, Plenge, P, Loland, CJ, Juhl, K, Larsen, K, Bregnedal, P & Bøgesø, KP 2017, 'X-ray structure based evaluation of analogs of citalopram: Compounds with increased affinity and selectivity compared with R-citalopram for the allosteric site (S2) on hSERT', Bioorganic & Medicinal Chemistry Letters, vol. 27, no. 3, pp. 470-478. https://doi.org/10.1016/j.bmcl.2016.12.037

APA

Topiol, S., Bang-Andersen, B., Sanchez, C., Plenge, P., Loland, C. J., Juhl, K., Larsen, K., Bregnedal, P., & Bøgesø, K. P. (2017). X-ray structure based evaluation of analogs of citalopram: Compounds with increased affinity and selectivity compared with R-citalopram for the allosteric site (S2) on hSERT. Bioorganic & Medicinal Chemistry Letters, 27(3), 470-478. https://doi.org/10.1016/j.bmcl.2016.12.037

Vancouver

Topiol S, Bang-Andersen B, Sanchez C, Plenge P, Loland CJ, Juhl K et al. X-ray structure based evaluation of analogs of citalopram: Compounds with increased affinity and selectivity compared with R-citalopram for the allosteric site (S2) on hSERT. Bioorganic & Medicinal Chemistry Letters. 2017 Feb 1;27(3):470-478. https://doi.org/10.1016/j.bmcl.2016.12.037

Author

Topiol, Sid ; Bang-Andersen, Benny ; Sanchez, Connie ; Plenge, Per ; Loland, Claus J ; Juhl, Karsten ; Larsen, Krestian ; Bregnedal, Peter ; Bøgesø, Klaus P. / X-ray structure based evaluation of analogs of citalopram : Compounds with increased affinity and selectivity compared with R-citalopram for the allosteric site (S2) on hSERT. In: Bioorganic & Medicinal Chemistry Letters. 2017 ; Vol. 27, No. 3. pp. 470-478.

Bibtex

@article{40ee26a213a0481e832f5818420eebe2,

title = "X-ray structure based evaluation of analogs of citalopram: Compounds with increased affinity and selectivity compared with R-citalopram for the allosteric site (S2) on hSERT",

abstract = "The recent publication of X-ray structures of SERT includes structures with the potent antidepressant S-Citalopram (S-Cit). Earlier predictions of ligand binding at both a primary (S1) and an allosteric modulator site (S2), were confirmed. We provide herein examples of a series of Citalopram analogs, showing distinct structure-activity relationship (SAR) at both sites that is independent of the SAR at the other site. Analogs with a higher affinity and selectivity than benchmark R-Citalopram (R-Cit) for the S2 versus the S1 site were identified. We deploy structural and computational analyses to explain this SAR and demonstrate the potential utility of the newly emerging X-ray structures within the neurotransmitter:sodium Symporter family for drug design.",

author = "Sid Topiol and Benny Bang-Andersen and Connie Sanchez and Per Plenge and Loland, {Claus J} and Karsten Juhl and Krestian Larsen and Peter Bregnedal and B{\o}ges{\o}, {Klaus P}",

year = "2017",

month = feb,

day = "1",

doi = "10.1016/j.bmcl.2016.12.037",

language = "English",

volume = "27",

pages = "470--478",

journal = "Bioorganic & Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Pergamon Press",

number = "3",

}

RIS

TY - JOUR

T1 - X-ray structure based evaluation of analogs of citalopram

T2 - Compounds with increased affinity and selectivity compared with R-citalopram for the allosteric site (S2) on hSERT

AU - Topiol, Sid

AU - Bang-Andersen, Benny

AU - Sanchez, Connie

AU - Plenge, Per

AU - Loland, Claus J

AU - Juhl, Karsten

AU - Larsen, Krestian

AU - Bregnedal, Peter

AU - Bøgesø, Klaus P

PY - 2017/2/1

Y1 - 2017/2/1

N2 - The recent publication of X-ray structures of SERT includes structures with the potent antidepressant S-Citalopram (S-Cit). Earlier predictions of ligand binding at both a primary (S1) and an allosteric modulator site (S2), were confirmed. We provide herein examples of a series of Citalopram analogs, showing distinct structure-activity relationship (SAR) at both sites that is independent of the SAR at the other site. Analogs with a higher affinity and selectivity than benchmark R-Citalopram (R-Cit) for the S2 versus the S1 site were identified. We deploy structural and computational analyses to explain this SAR and demonstrate the potential utility of the newly emerging X-ray structures within the neurotransmitter:sodium Symporter family for drug design.

AB - The recent publication of X-ray structures of SERT includes structures with the potent antidepressant S-Citalopram (S-Cit). Earlier predictions of ligand binding at both a primary (S1) and an allosteric modulator site (S2), were confirmed. We provide herein examples of a series of Citalopram analogs, showing distinct structure-activity relationship (SAR) at both sites that is independent of the SAR at the other site. Analogs with a higher affinity and selectivity than benchmark R-Citalopram (R-Cit) for the S2 versus the S1 site were identified. We deploy structural and computational analyses to explain this SAR and demonstrate the potential utility of the newly emerging X-ray structures within the neurotransmitter:sodium Symporter family for drug design.

U2 - 10.1016/j.bmcl.2016.12.037

DO - 10.1016/j.bmcl.2016.12.037

M3 - Journal article

C2 - 28041833

VL - 27

SP - 470

EP - 478

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

SN - 0960-894X

IS - 3

ER -

ID: 172849302

Department of Neuroscience