Design, synthesis, and structure-activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists

Takao Kiyoi; Mark York; Stuart Francis; Darren Edwards; Glenn Walker; Andrea K Houghton; Jean E Cottney; James Baker; Julia M Adam

doi:10.1016/j.bmcl.2010.06.067

Design, synthesis, and structure-activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists

Takao Kiyoi, Mark York, Stuart Francis, Darren Edwards, Glenn Walker, Andrea K Houghton, Jean E Cottney, James Baker, Julia M Adam

Strathclyde Institute Of Pharmacy And Biomedical Sciences

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

14 Citations (Scopus)

Abstract

Novel tricyclic indole-3-carboxamides were synthesized as structurally restricted analogs of bicyclic indoles, and found to be potent CB1 cannabinoid receptor agonists. The CB1 agonist activity depended on the absolute configuration of the chiral center of the tricyclic ring. The preferred enantiomer was more potent than the structurally unconstrained lead compound. Structure-activity relationships in the amide side chain of the indole C-3 position were also investigated.

Original language	English
Pages (from-to)	4918-4921
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	16
DOIs	https://doi.org/10.1016/j.bmcl.2010.06.067
Publication status	Published - 15 Aug 2010

Keywords

amides
animals
drug design
humans
indoles
mice
microsomes
receptor, Cannabinoid, CB1
structure-activity relationships

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10.1016/j.bmcl.2010.06.067

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Kiyoi, T., York, M., Francis, S., Edwards, D., Walker, G., Houghton, A. K., Cottney, J. E., Baker, J., & Adam, J. M. (2010). Design, synthesis, and structure-activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists. Bioorganic and Medicinal Chemistry Letters, 20(16), 4918-4921. https://doi.org/10.1016/j.bmcl.2010.06.067

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title = "Design, synthesis, and structure-activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists",

abstract = "Novel tricyclic indole-3-carboxamides were synthesized as structurally restricted analogs of bicyclic indoles, and found to be potent CB1 cannabinoid receptor agonists. The CB1 agonist activity depended on the absolute configuration of the chiral center of the tricyclic ring. The preferred enantiomer was more potent than the structurally unconstrained lead compound. Structure-activity relationships in the amide side chain of the indole C-3 position were also investigated.",

keywords = "amides, animals, drug design, humans, indoles, mice, microsomes, receptor, Cannabinoid, CB1, structure-activity relationships",

author = "Takao Kiyoi and Mark York and Stuart Francis and Darren Edwards and Glenn Walker and Houghton, {Andrea K} and Cottney, {Jean E} and James Baker and Adam, {Julia M}",

year = "2010",

month = aug,

day = "15",

doi = "10.1016/j.bmcl.2010.06.067",

language = "English",

volume = "20",

pages = "4918--4921",

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Kiyoi, T, York, M, Francis, S, Edwards, D, Walker, G, Houghton, AK, Cottney, JE, Baker, J & Adam, JM 2010, 'Design, synthesis, and structure-activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists', Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 16, pp. 4918-4921. https://doi.org/10.1016/j.bmcl.2010.06.067

Design, synthesis, and structure-activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists. / Kiyoi, Takao; York, Mark; Francis, Stuart et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 20, No. 16, 15.08.2010, p. 4918-4921.

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

TY - JOUR

T1 - Design, synthesis, and structure-activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists

AU - Kiyoi, Takao

AU - York, Mark

AU - Francis, Stuart

AU - Edwards, Darren

AU - Walker, Glenn

AU - Houghton, Andrea K

AU - Cottney, Jean E

AU - Baker, James

AU - Adam, Julia M

PY - 2010/8/15

Y1 - 2010/8/15

N2 - Novel tricyclic indole-3-carboxamides were synthesized as structurally restricted analogs of bicyclic indoles, and found to be potent CB1 cannabinoid receptor agonists. The CB1 agonist activity depended on the absolute configuration of the chiral center of the tricyclic ring. The preferred enantiomer was more potent than the structurally unconstrained lead compound. Structure-activity relationships in the amide side chain of the indole C-3 position were also investigated.

AB - Novel tricyclic indole-3-carboxamides were synthesized as structurally restricted analogs of bicyclic indoles, and found to be potent CB1 cannabinoid receptor agonists. The CB1 agonist activity depended on the absolute configuration of the chiral center of the tricyclic ring. The preferred enantiomer was more potent than the structurally unconstrained lead compound. Structure-activity relationships in the amide side chain of the indole C-3 position were also investigated.

KW - amides

KW - animals

KW - drug design

KW - humans

KW - indoles

KW - mice

KW - microsomes

KW - receptor, Cannabinoid, CB1

KW - structure-activity relationships

UR - http://www.journals.elsevier.com/bioorganic-and-medicinal-chemistry-letters

U2 - 10.1016/j.bmcl.2010.06.067

DO - 10.1016/j.bmcl.2010.06.067

M3 - Article

C2 - 20634067

SN - 0960-894X

VL - 20

SP - 4918

EP - 4921

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 16

ER -

Design, synthesis, and structure-activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists

Abstract

Keywords

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