Pyrrolidinones as orally bioavailable antagonists of the human melanocortin-4 receptor with anti-cachectic activity

Joe A. Tran; Fabio C. Tucci; Wanlong Jiang; Dragan Marinkovic; Caroline W. Chen; Melissa Arellano; Stacy Markison; Beth A. Fleck; Jenny Wen; Nicole S. White; Joseph Pontillo; John Saunders; Daniel Marks; Sam R. Hoare; Ajay Madan; Alan C. Foster; Chen Chen

doi:10.1016/j.bmc.2007.05.026

Pyrrolidinones as orally bioavailable antagonists of the human melanocortin-4 receptor with anti-cachectic activity

Joe A. Tran, Fabio C. Tucci, Wanlong Jiang, Dragan Marinkovic, Caroline W. Chen, Melissa Arellano, Stacy Markison, Beth A. Fleck, Jenny Wen, Nicole S. White, Joseph Pontillo, John Saunders, Daniel Marks, Sam R. Hoare, Ajay Madan, Alan C. Foster, Chen Chen

Pediatrics

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

13 Scopus citations

Abstract

A series of pyrrolidinones derived from phenylalanines were synthesized as potent antagonists of the human melanocortin-4 receptor. These compounds showed high potencies and selectivities, and several of them had good oral bioavailabilities. In addition, 12e demonstrated in vivo efficacy in a murine cachexia model.

Original language	English (US)
Pages (from-to)	5166-5176
Number of pages	11
Journal	Bioorganic and Medicinal Chemistry
Volume	15
Issue number	15
DOIs	https://doi.org/10.1016/j.bmc.2007.05.026
State	Published - Aug 1 2007

Keywords

Animal model
Antagonist
Cachexia
Melanocortin-4 receptor
Pharmacokinetics
Pyrrolidinone
Synthesis

ASJC Scopus subject areas

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

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10.1016/j.bmc.2007.05.026

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Tran, J. A., Tucci, F. C., Jiang, W., Marinkovic, D., Chen, C. W., Arellano, M., Markison, S., Fleck, B. A., Wen, J., White, N. S., Pontillo, J., Saunders, J., Marks, D., Hoare, S. R., Madan, A., Foster, A. C., & Chen, C. (2007). Pyrrolidinones as orally bioavailable antagonists of the human melanocortin-4 receptor with anti-cachectic activity. Bioorganic and Medicinal Chemistry, 15(15), 5166-5176. https://doi.org/10.1016/j.bmc.2007.05.026

Tran, JA, Tucci, FC, Jiang, W, Marinkovic, D, Chen, CW, Arellano, M, Markison, S, Fleck, BA, Wen, J, White, NS, Pontillo, J, Saunders, J, Marks, D, Hoare, SR, Madan, A, Foster, AC & Chen, C 2007, 'Pyrrolidinones as orally bioavailable antagonists of the human melanocortin-4 receptor with anti-cachectic activity', Bioorganic and Medicinal Chemistry, vol. 15, no. 15, pp. 5166-5176. https://doi.org/10.1016/j.bmc.2007.05.026

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abstract = "A series of pyrrolidinones derived from phenylalanines were synthesized as potent antagonists of the human melanocortin-4 receptor. These compounds showed high potencies and selectivities, and several of them had good oral bioavailabilities. In addition, 12e demonstrated in vivo efficacy in a murine cachexia model.",

keywords = "Animal model, Antagonist, Cachexia, Melanocortin-4 receptor, Pharmacokinetics, Pyrrolidinone, Synthesis",

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AU - Tran, Joe A.

AU - Tucci, Fabio C.

AU - Jiang, Wanlong

AU - Marinkovic, Dragan

AU - Chen, Caroline W.

AU - Arellano, Melissa

AU - Markison, Stacy

AU - Fleck, Beth A.

AU - Wen, Jenny

AU - White, Nicole S.

AU - Pontillo, Joseph

AU - Saunders, John

AU - Marks, Daniel

AU - Hoare, Sam R.

AU - Madan, Ajay

AU - Foster, Alan C.

AU - Chen, Chen

PY - 2007/8/1

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AB - A series of pyrrolidinones derived from phenylalanines were synthesized as potent antagonists of the human melanocortin-4 receptor. These compounds showed high potencies and selectivities, and several of them had good oral bioavailabilities. In addition, 12e demonstrated in vivo efficacy in a murine cachexia model.

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KW - Antagonist

KW - Cachexia

KW - Melanocortin-4 receptor

KW - Pharmacokinetics

KW - Pyrrolidinone

KW - Synthesis

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ER -

Pyrrolidinones as orally bioavailable antagonists of the human melanocortin-4 receptor with anti-cachectic activity

Abstract

Keywords

ASJC Scopus subject areas

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