Design and synthesis of 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (citalopram) analogues as novel probes for the serotonin transporter S1 and S2 binding sites

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

Standard

Design and synthesis of 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (citalopram) analogues as novel probes for the serotonin transporter S1 and S2 binding sites. / Banala, Ashwini K; Zhang, Peng; Plenge, Per; Cyriac, George; Kopajtic, Theresa; Katz, Jonathan L; Loland, Claus Juul; Newman, Amy Hauck.

In: Journal of Medicinal Chemistry, Vol. 56, No. 23, 12.12.2013, p. 9709-24.

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

Harvard

Banala, AK, Zhang, P, Plenge, P, Cyriac, G, Kopajtic, T, Katz, JL, Loland, CJ & Newman, AH 2013, 'Design and synthesis of 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (citalopram) analogues as novel probes for the serotonin transporter S1 and S2 binding sites', Journal of Medicinal Chemistry, vol. 56, no. 23, pp. 9709-24. https://doi.org/10.1021/jm4014136

APA

Banala, A. K., Zhang, P., Plenge, P., Cyriac, G., Kopajtic, T., Katz, J. L., Loland, C. J., & Newman, A. H. (2013). Design and synthesis of 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (citalopram) analogues as novel probes for the serotonin transporter S1 and S2 binding sites. Journal of Medicinal Chemistry, 56(23), 9709-24. https://doi.org/10.1021/jm4014136

Vancouver

Banala AK, Zhang P, Plenge P, Cyriac G, Kopajtic T, Katz JL et al. Design and synthesis of 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (citalopram) analogues as novel probes for the serotonin transporter S1 and S2 binding sites. Journal of Medicinal Chemistry. 2013 Dec 12;56(23):9709-24. https://doi.org/10.1021/jm4014136

Author

Banala, Ashwini K ; Zhang, Peng ; Plenge, Per ; Cyriac, George ; Kopajtic, Theresa ; Katz, Jonathan L ; Loland, Claus Juul ; Newman, Amy Hauck. / Design and synthesis of 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (citalopram) analogues as novel probes for the serotonin transporter S1 and S2 binding sites. In: Journal of Medicinal Chemistry. 2013 ; Vol. 56, No. 23. pp. 9709-24.

Bibtex

@article{ca4b3dedbdf44d9a8243fdb1c32a7d6e,
title = "Design and synthesis of 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (citalopram) analogues as novel probes for the serotonin transporter S1 and S2 binding sites",
abstract = "The serotonin transporter (SERT) is the primary target for antidepressant drugs. The existence of a high affinity primary orthosteric binding site (S1) and a low affinity secondary site (S2) has been described, and their relation to antidepressant pharmacology has been debated. Herein, structural modifications to the N, 4, 5, and 4' positions of (±)citalopram (1) are reported. All of the analogues were SERT-selective and demonstrated that steric bulk was tolerated at the SERT S1 site, including two dimeric ligands (15 and 51). In addition, eight analogues were identified with similar potencies to S-1 for decreasing the dissociation of [(3)H]S-1 from the S1 site via allosteric modulation at S2. Both dimeric compounds had similar affinities for the SERT S1 site (Ki = 19.7 and 30.2 nM, respectively), whereas only the N-substituted analogue, 51, was as effective as S-1 in allosterically modulating the binding of [(3)H]S-1 via S2.",
keywords = "Allosteric Site, Animals, Binding Sites, Brain, COS Cells, Cercopithecus aethiops, Citalopram, Humans, Serotonin Plasma Membrane Transport Proteins",
author = "Banala, {Ashwini K} and Peng Zhang and Per Plenge and George Cyriac and Theresa Kopajtic and Katz, {Jonathan L} and Loland, {Claus Juul} and Newman, {Amy Hauck}",
year = "2013",
month = dec,
day = "12",
doi = "10.1021/jm4014136",
language = "English",
volume = "56",
pages = "9709--24",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "23",

}

RIS

TY - JOUR

T1 - Design and synthesis of 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (citalopram) analogues as novel probes for the serotonin transporter S1 and S2 binding sites

AU - Banala, Ashwini K

AU - Zhang, Peng

AU - Plenge, Per

AU - Cyriac, George

AU - Kopajtic, Theresa

AU - Katz, Jonathan L

AU - Loland, Claus Juul

AU - Newman, Amy Hauck

PY - 2013/12/12

Y1 - 2013/12/12

N2 - The serotonin transporter (SERT) is the primary target for antidepressant drugs. The existence of a high affinity primary orthosteric binding site (S1) and a low affinity secondary site (S2) has been described, and their relation to antidepressant pharmacology has been debated. Herein, structural modifications to the N, 4, 5, and 4' positions of (±)citalopram (1) are reported. All of the analogues were SERT-selective and demonstrated that steric bulk was tolerated at the SERT S1 site, including two dimeric ligands (15 and 51). In addition, eight analogues were identified with similar potencies to S-1 for decreasing the dissociation of [(3)H]S-1 from the S1 site via allosteric modulation at S2. Both dimeric compounds had similar affinities for the SERT S1 site (Ki = 19.7 and 30.2 nM, respectively), whereas only the N-substituted analogue, 51, was as effective as S-1 in allosterically modulating the binding of [(3)H]S-1 via S2.

AB - The serotonin transporter (SERT) is the primary target for antidepressant drugs. The existence of a high affinity primary orthosteric binding site (S1) and a low affinity secondary site (S2) has been described, and their relation to antidepressant pharmacology has been debated. Herein, structural modifications to the N, 4, 5, and 4' positions of (±)citalopram (1) are reported. All of the analogues were SERT-selective and demonstrated that steric bulk was tolerated at the SERT S1 site, including two dimeric ligands (15 and 51). In addition, eight analogues were identified with similar potencies to S-1 for decreasing the dissociation of [(3)H]S-1 from the S1 site via allosteric modulation at S2. Both dimeric compounds had similar affinities for the SERT S1 site (Ki = 19.7 and 30.2 nM, respectively), whereas only the N-substituted analogue, 51, was as effective as S-1 in allosterically modulating the binding of [(3)H]S-1 via S2.

KW - Allosteric Site

KW - Animals

KW - Binding Sites

KW - Brain

KW - COS Cells

KW - Cercopithecus aethiops

KW - Citalopram

KW - Humans

KW - Serotonin Plasma Membrane Transport Proteins

U2 - 10.1021/jm4014136

DO - 10.1021/jm4014136

M3 - Journal article

C2 - 24237160

VL - 56

SP - 9709

EP - 9724

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 23

ER -

ID: 120074578