Optimization of physicochemical properties of pyrrolidine GPR40 AgoPAMs results in a differentiated profile with improved pharmacokinetics and reduced off-target activities

Elizabeth A. Jurica; Ximao Wu; Kristin N. Williams; Lauren E. Haque; Richard A. Rampulla; Arvind Mathur; Min Zhou; Gary Cao; Hong Cai; Tao Wang; Heng Liu; Carrie Xu; Lori K. Kunselman; Thomas M. Antrilli; Michael B. Hicks; Qin Sun; Elizabeth A. Dierks; Atsu Apedo; Douglas B. Moore; Kimberly A. Foster; Mary Ellen Cvijic; Reshma Panemangalore; Purnima Khandelwal; Jason J. Wilkes; Bradley A. Zinker; Donald G. Robertson; Evan B. Janovitz; Michael Galella; Yi Xin Li; Julia Li; Thangeswaran Ramar; Prasada Rao Jalagam; Ramya Jayaram; Jean M. Whaley; Joel C. Barrish; Jeffrey A. Robl; William R. Ewing; Bruce A. Ellsworth

doi:10.1016/j.bmc.2023.117273

Optimization of physicochemical properties of pyrrolidine GPR40 AgoPAMs results in a differentiated profile with improved pharmacokinetics and reduced off-target activities

Elizabeth A. Jurica
, Ximao Wu
, Kristin N. Williams
, Lauren E. Haque
, Richard A. Rampulla
, Arvind Mathur
, Min Zhou
, Gary Cao
, Hong Cai
, Tao Wang
, Heng Liu
, Carrie Xu
, Lori K. Kunselman
, Thomas M. Antrilli
, Michael B. Hicks
, Qin Sun
, Elizabeth A. Dierks
, Atsu Apedo
, Douglas B. Moore
, Kimberly A. Foster

Mary Ellen Cvijic, Reshma Panemangalore, Purnima Khandelwal, Jason J. Wilkes, Bradley A. Zinker, Donald G. Robertson, Evan B. Janovitz, Michael Galella, Yi Xin Li, Julia Li, Thangeswaran Ramar, Prasada Rao Jalagam, Ramya Jayaram, Jean M. Whaley, Joel C. Barrish, Jeffrey A. Robl, William R. Ewing, Bruce A. Ellsworth

Bristol-Myers Squibb

Research output: Contribution to journal › Article › peer-review

Original language	English
Article number	117273
Journal	Bioorganic and Medicinal Chemistry
Volume	85
DOIs	https://doi.org/10.1016/j.bmc.2023.117273
State	Published - May 1 2023
Externally published	Yes

ASJC Scopus Subject Areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Keywords

AgoPAM
Chirality
FFAR1
GLP-1
GPR40
Hyperglycemia
Polarity
Pyrrolidine
Saturation
Type 2 diabetes

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10.1016/j.bmc.2023.117273

Cite this

Jurica, E. A., Wu, X., Williams, K. N., Haque, L. E., Rampulla, R. A., Mathur, A., Zhou, M., Cao, G., Cai, H., Wang, T., Liu, H., Xu, C., Kunselman, L. K., Antrilli, T. M., Hicks, M. B., Sun, Q., Dierks, E. A., Apedo, A., Moore, D. B., ... Ellsworth, B. A. (2023). Optimization of physicochemical properties of pyrrolidine GPR40 AgoPAMs results in a differentiated profile with improved pharmacokinetics and reduced off-target activities. Bioorganic and Medicinal Chemistry, 85, Article 117273. https://doi.org/10.1016/j.bmc.2023.117273

Optimization of physicochemical properties of pyrrolidine GPR40 AgoPAMs results in a differentiated profile with improved pharmacokinetics and reduced off-target activities. / Jurica, Elizabeth A.; Wu, Ximao; Williams, Kristin N. et al.
In: Bioorganic and Medicinal Chemistry, Vol. 85, 117273, 01.05.2023.

Research output: Contribution to journal › Article › peer-review

Jurica, EA, Wu, X, Williams, KN, Haque, LE, Rampulla, RA, Mathur, A, Zhou, M, Cao, G, Cai, H, Wang, T, Liu, H, Xu, C, Kunselman, LK, Antrilli, TM, Hicks, MB, Sun, Q, Dierks, EA, Apedo, A, Moore, DB, Foster, KA, Cvijic, ME, Panemangalore, R, Khandelwal, P, Wilkes, JJ, Zinker, BA, Robertson, DG, Janovitz, EB, Galella, M, Li, YX, Li, J, Ramar, T, Jalagam, PR, Jayaram, R, Whaley, JM, Barrish, JC, Robl, JA, Ewing, WR & Ellsworth, BA 2023, 'Optimization of physicochemical properties of pyrrolidine GPR40 AgoPAMs results in a differentiated profile with improved pharmacokinetics and reduced off-target activities', Bioorganic and Medicinal Chemistry, vol. 85, 117273. https://doi.org/10.1016/j.bmc.2023.117273

@article{cec1ae7966a34adb89dcf07dbbcefb54,

title = "Optimization of physicochemical properties of pyrrolidine GPR40 AgoPAMs results in a differentiated profile with improved pharmacokinetics and reduced off-target activities",

keywords = "AgoPAM, Chirality, FFAR1, GLP-1, GPR40, Hyperglycemia, Polarity, Pyrrolidine, Saturation, Type 2 diabetes",

author = "Jurica, \{Elizabeth A.\} and Ximao Wu and Williams, \{Kristin N.\} and Haque, \{Lauren E.\} and Rampulla, \{Richard A.\} and Arvind Mathur and Min Zhou and Gary Cao and Hong Cai and Tao Wang and Heng Liu and Carrie Xu and Kunselman, \{Lori K.\} and Antrilli, \{Thomas M.\} and Hicks, \{Michael B.\} and Qin Sun and Dierks, \{Elizabeth A.\} and Atsu Apedo and Moore, \{Douglas B.\} and Foster, \{Kimberly A.\} and Cvijic, \{Mary Ellen\} and Reshma Panemangalore and Purnima Khandelwal and Wilkes, \{Jason J.\} and Zinker, \{Bradley A.\} and Robertson, \{Donald G.\} and Janovitz, \{Evan B.\} and Michael Galella and Li, \{Yi Xin\} and Julia Li and Thangeswaran Ramar and Jalagam, \{Prasada Rao\} and Ramya Jayaram and Whaley, \{Jean M.\} and Barrish, \{Joel C.\} and Robl, \{Jeffrey A.\} and Ewing, \{William R.\} and Ellsworth, \{Bruce A.\}",

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier Ltd",

year = "2023",

month = may,

day = "1",

doi = "10.1016/j.bmc.2023.117273",

language = "English",

volume = "85",

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T1 - Optimization of physicochemical properties of pyrrolidine GPR40 AgoPAMs results in a differentiated profile with improved pharmacokinetics and reduced off-target activities

AU - Jurica, Elizabeth A.

AU - Wu, Ximao

AU - Williams, Kristin N.

AU - Haque, Lauren E.

AU - Rampulla, Richard A.

AU - Mathur, Arvind

AU - Zhou, Min

AU - Cao, Gary

AU - Cai, Hong

AU - Wang, Tao

AU - Liu, Heng

AU - Xu, Carrie

AU - Kunselman, Lori K.

AU - Antrilli, Thomas M.

AU - Hicks, Michael B.

AU - Sun, Qin

AU - Dierks, Elizabeth A.

AU - Apedo, Atsu

AU - Moore, Douglas B.

AU - Foster, Kimberly A.

AU - Cvijic, Mary Ellen

AU - Panemangalore, Reshma

AU - Khandelwal, Purnima

AU - Wilkes, Jason J.

AU - Zinker, Bradley A.

AU - Robertson, Donald G.

AU - Janovitz, Evan B.

AU - Galella, Michael

AU - Li, Yi Xin

AU - Li, Julia

AU - Ramar, Thangeswaran

AU - Jalagam, Prasada Rao

AU - Jayaram, Ramya

AU - Whaley, Jean M.

AU - Barrish, Joel C.

AU - Robl, Jeffrey A.

AU - Ewing, William R.

AU - Ellsworth, Bruce A.

PY - 2023/5/1

Y1 - 2023/5/1

KW - AgoPAM

KW - Chirality

KW - FFAR1

KW - GLP-1

KW - GPR40

KW - Hyperglycemia

KW - Polarity

KW - Pyrrolidine

KW - Saturation

KW - Type 2 diabetes

UR - https://www.scopus.com/pages/publications/85151813441

UR - https://www.scopus.com/pages/publications/85151813441#tab=citedBy

U2 - 10.1016/j.bmc.2023.117273

DO - 10.1016/j.bmc.2023.117273

M3 - Article

C2 - 37030194

AN - SCOPUS:85151813441

SN - 0968-0896

VL - 85

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

M1 - 117273

ER -

Optimization of physicochemical properties of pyrrolidine GPR40 AgoPAMs results in a differentiated profile with improved pharmacokinetics and reduced off-target activities

ASJC Scopus Subject Areas

Keywords

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