Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II: development of a potent and highly selective M1 PAM

Thomas M Bridges; J Phillip Kennedy; Meredith J Noetzel; Micah L Breininger; Patrick R Gentry; P Jeffrey Conn; Craig W Lindsley

doi:10.1016/j.bmcl.2010.01.109

Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II: development of a potent and highly selective M1 PAM

Thomas M Bridges, J Phillip Kennedy, Meredith J Noetzel, Micah L Breininger, Patrick R Gentry, P Jeffrey Conn, Craig W Lindsley

48 Citationer (Scopus)

Abstract

This Letter describes a chemical lead optimization campaign directed at VU0119498, a pan G_q mAChR M₁, M₃, M₅ positive allosteric modulator (PAM) with the goal of developing a selective M₁ PAM. An iterative library synthesis approach delivered a potent (M₁ EC₅₀ = 830 nM) and highly selective M₁ PAM (>30 μM vs M₂-M₅).

Originalsprog	Engelsk
Tidsskrift	Bioorganic & Medicinal Chemistry Letters
Vol/bind	20
Udgave nummer	6
Sider (fra-til)	1972-5
Antal sider	4
ISSN	0960-894X
DOI	https://doi.org/10.1016/j.bmcl.2010.01.109
Status	Udgivet - 15 mar. 2010
Udgivet eksternt	Ja

Adgang til dokumentet

10.1016/j.bmcl.2010.01.109

Citationsformater

Bridges, T. M., Phillip Kennedy, J., Noetzel, M. J., Breininger, M. L., Gentry, P. R., Conn, P. J., & Lindsley, C. W. (2010). Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II: development of a potent and highly selective M1 PAM. Bioorganic & Medicinal Chemistry Letters, 20(6), 1972-5. https://doi.org/10.1016/j.bmcl.2010.01.109

Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II: development of a potent and highly selective M1 PAM. / Bridges, Thomas M; Phillip Kennedy, J; Noetzel, Meredith J et al.
I: Bioorganic & Medicinal Chemistry Letters, Bind 20, Nr. 6, 15.03.2010, s. 1972-5.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Bridges, TM, Phillip Kennedy, J, Noetzel, MJ, Breininger, ML, Gentry, PR, Conn, PJ & Lindsley, CW 2010, 'Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II: development of a potent and highly selective M1 PAM', Bioorganic & Medicinal Chemistry Letters, bind 20, nr. 6, s. 1972-5. https://doi.org/10.1016/j.bmcl.2010.01.109

@article{486e5ea4593b4e3fa1d1d454214da27a,

title = "Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II: development of a potent and highly selective M1 PAM",

abstract = "This Letter describes a chemical lead optimization campaign directed at VU0119498, a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) with the goal of developing a selective M1 PAM. An iterative library synthesis approach delivered a potent (M1 EC50 = 830 nM) and highly selective M1 PAM (>30 μM vs M2-M5).",

keywords = "Allosteric Regulation, Cholinergic Agents/chemistry, Drug Design, Receptors, Muscarinic/drug effects, Structure-Activity Relationship",

author = "Bridges, {Thomas M} and {Phillip Kennedy}, J and Noetzel, {Meredith J} and Breininger, {Micah L} and Gentry, {Patrick R} and Conn, {P Jeffrey} and Lindsley, {Craig W}",

year = "2010",

month = mar,

day = "15",

doi = "10.1016/j.bmcl.2010.01.109",

language = "English",

volume = "20",

pages = "1972--5",

journal = "Bioorganic & Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Pergamon Press",

number = "6",

}

TY - JOUR

T1 - Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II

T2 - development of a potent and highly selective M1 PAM

AU - Bridges, Thomas M

AU - Phillip Kennedy, J

AU - Noetzel, Meredith J

AU - Breininger, Micah L

AU - Gentry, Patrick R

AU - Conn, P Jeffrey

AU - Lindsley, Craig W

PY - 2010/3/15

Y1 - 2010/3/15

N2 - This Letter describes a chemical lead optimization campaign directed at VU0119498, a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) with the goal of developing a selective M1 PAM. An iterative library synthesis approach delivered a potent (M1 EC50 = 830 nM) and highly selective M1 PAM (>30 μM vs M2-M5).

AB - This Letter describes a chemical lead optimization campaign directed at VU0119498, a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) with the goal of developing a selective M1 PAM. An iterative library synthesis approach delivered a potent (M1 EC50 = 830 nM) and highly selective M1 PAM (>30 μM vs M2-M5).

KW - Allosteric Regulation

KW - Cholinergic Agents/chemistry

KW - Drug Design

KW - Receptors, Muscarinic/drug effects

KW - Structure-Activity Relationship

U2 - 10.1016/j.bmcl.2010.01.109

DO - 10.1016/j.bmcl.2010.01.109

M3 - Journal article

C2 - 20156687

SN - 0960-894X

VL - 20

SP - 1972

EP - 1975

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 6

ER -

Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II: development of a potent and highly selective M1 PAM

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater