TY - JOUR
T1 - Negative allosteric modulators of group II metabotropic glutamate receptors
T2 - A patent review (2015–present)
AU - Qunies, Alshaima’a M.
AU - Emmitte, Kyle A.
N1 - Funding Information:
KA Emmitte is an employee of the University of North Texas Health Science Center and receives funding from the National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health. KA Emmitte is an inventor on multiple issued patents concerning small molecule allosteric modulators of metabotropic glutamate receptors. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Publisher Copyright:
© 2021 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021
Y1 - 2021
N2 - Introduction: Group II metabotropic glutamate (mGlu) receptors have emerged as an attractive potential target for the development of novel CNS therapeutics in areas such as Alzheimer’s disease (AD), anxiety, cognitive disorders, depression, and others. Several small molecules that act as negative allosteric modulators (NAMs) on these receptors have demonstrated efficacy and/or target engagement in animal models, and one molecule (decoglurant) has been advanced into clinical trials. Areas covered: This review summarizes patent applications published between January 2015 and November 2020. It is divided into three sections: (1) small molecule nonselective mGlu2/3 NAMs, (2) small molecule selective mGlu2 NAMs, and (3) small molecule selective mGlu3 NAMs. Expert Opinion: Much progress has been made in the discovery of novel small molecule mGlu2 NAMs. Still, chemical diversity remains somewhat limited and room for expansion remains. Progress with mGlu3 NAMs has been more limited; however, some promising molecules have been disclosed. The process of elucidating the precise role of each receptor in the diseases associated with group II receptors has begun. Continued studies in animals with selective NAMs for both receptors will be critical in the coming years to inform researchers on the right compound profile and patient population for clinical development.
AB - Introduction: Group II metabotropic glutamate (mGlu) receptors have emerged as an attractive potential target for the development of novel CNS therapeutics in areas such as Alzheimer’s disease (AD), anxiety, cognitive disorders, depression, and others. Several small molecules that act as negative allosteric modulators (NAMs) on these receptors have demonstrated efficacy and/or target engagement in animal models, and one molecule (decoglurant) has been advanced into clinical trials. Areas covered: This review summarizes patent applications published between January 2015 and November 2020. It is divided into three sections: (1) small molecule nonselective mGlu2/3 NAMs, (2) small molecule selective mGlu2 NAMs, and (3) small molecule selective mGlu3 NAMs. Expert Opinion: Much progress has been made in the discovery of novel small molecule mGlu2 NAMs. Still, chemical diversity remains somewhat limited and room for expansion remains. Progress with mGlu3 NAMs has been more limited; however, some promising molecules have been disclosed. The process of elucidating the precise role of each receptor in the diseases associated with group II receptors has begun. Continued studies in animals with selective NAMs for both receptors will be critical in the coming years to inform researchers on the right compound profile and patient population for clinical development.
KW - Alzheimer’s disease
KW - Decoglurant
KW - anxiety
KW - cognition
KW - depression
KW - metabotropic glutamate receptor subtype 2
KW - metabotropic glutamate receptor subtype 3
KW - negative allosteric modulator
UR - http://www.scopus.com/inward/record.url?scp=85103591337&partnerID=8YFLogxK
U2 - 10.1080/13543776.2021.1903431
DO - 10.1080/13543776.2021.1903431
M3 - Article
C2 - 33719801
AN - SCOPUS:85103591337
VL - 31
SP - 687
EP - 708
JO - Expert Opinion on Therapeutic Patents
JF - Expert Opinion on Therapeutic Patents
SN - 1354-3776
IS - 8
ER -