Synthesis and SAR of analogues of the M1 allosteric agonist TBPB. Part I: Exploration of alternative benzyl and privileged structure moieties

Thomas M Bridges; Ashley E Brady; J Phillip Kennedy; R Nathan Daniels; Nicole R Miller; Kwango Kim; Micah L Breininger; Patrick R Gentry; John T Brogan; Carrie K Jones; P Jeffrey Conn; Craig W Lindsley

doi:10.1016/j.bmcl.2008.09.023

Synthesis and SAR of analogues of the M1 allosteric agonist TBPB. Part I: Exploration of alternative benzyl and privileged structure moieties

Thomas M Bridges, Ashley E Brady, J Phillip Kennedy, R Nathan Daniels, Nicole R Miller, Kwango Kim, Micah L Breininger, Patrick R Gentry, John T Brogan, Carrie K Jones, P Jeffrey Conn, Craig W Lindsley

36 Citations (Scopus)

Abstract

This Letter describes the first account of the synthesis and SAR, developed through an iterative analogue library approach, of analogues of the highly selective M1 allosteric agonist TBPB. With slight structural changes, mAChR selectivity was maintained, but the degree of partial M1 agonism varied considerably.

Original language	English
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	18
Issue number	20
Pages (from-to)	5439-42
Number of pages	4
ISSN	0960-894X
DOIs	https://doi.org/10.1016/j.bmcl.2008.09.023
Publication status	Published - 15 Oct 2008
Externally published	Yes

Keywords

Acetylcholine/chemistry
Allosteric Regulation
Allosteric Site
Benzimidazoles/chemical synthesis
Binding Sites
Chemistry, Pharmaceutical/methods
Dose-Response Relationship, Drug
Drug Design
Humans
Inhibitory Concentration 50
Ligands
Models, Chemical
Piperidines/chemical synthesis
Receptor, Muscarinic M1/chemistry
Structure-Activity Relationship
Time Factors

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10.1016/j.bmcl.2008.09.023

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Bridges, T. M., Brady, A. E., Kennedy, J. P., Daniels, R. N., Miller, N. R., Kim, K., Breininger, M. L., Gentry, P. R., Brogan, J. T., Jones, C. K., Conn, P. J., & Lindsley, C. W. (2008). Synthesis and SAR of analogues of the M1 allosteric agonist TBPB. Part I: Exploration of alternative benzyl and privileged structure moieties. Bioorganic & Medicinal Chemistry Letters, 18(20), 5439-42. https://doi.org/10.1016/j.bmcl.2008.09.023

Synthesis and SAR of analogues of the M1 allosteric agonist TBPB. Part I : Exploration of alternative benzyl and privileged structure moieties. / Bridges, Thomas M; Brady, Ashley E; Kennedy, J Phillip et al.

In: Bioorganic & Medicinal Chemistry Letters, Vol. 18, No. 20, 15.10.2008, p. 5439-42.

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

Bridges, TM, Brady, AE, Kennedy, JP, Daniels, RN, Miller, NR, Kim, K, Breininger, ML, Gentry, PR, Brogan, JT, Jones, CK, Conn, PJ & Lindsley, CW 2008, 'Synthesis and SAR of analogues of the M1 allosteric agonist TBPB. Part I: Exploration of alternative benzyl and privileged structure moieties', Bioorganic & Medicinal Chemistry Letters, vol. 18, no. 20, pp. 5439-42. https://doi.org/10.1016/j.bmcl.2008.09.023

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AU - Kennedy, J Phillip

AU - Daniels, R Nathan

AU - Miller, Nicole R

AU - Kim, Kwango

AU - Breininger, Micah L

AU - Gentry, Patrick R

AU - Brogan, John T

AU - Jones, Carrie K

AU - Conn, P Jeffrey

AU - Lindsley, Craig W

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KW - Allosteric Regulation

KW - Allosteric Site

KW - Benzimidazoles/chemical synthesis

KW - Binding Sites

KW - Chemistry, Pharmaceutical/methods

KW - Dose-Response Relationship, Drug

KW - Drug Design

KW - Humans

KW - Inhibitory Concentration 50

KW - Ligands

KW - Models, Chemical

KW - Piperidines/chemical synthesis

KW - Receptor, Muscarinic M1/chemistry

KW - Structure-Activity Relationship

KW - Time Factors

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DO - 10.1016/j.bmcl.2008.09.023

M3 - Journal article

C2 - 18805692

SN - 0960-894X

VL - 18

SP - 5439

EP - 5442

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 20

ER -

Synthesis and SAR of analogues of the M1 allosteric agonist TBPB. Part I: Exploration of alternative benzyl and privileged structure moieties

Abstract

Keywords

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