Synthesis and stability of two indomethacin prodrugs

Shyamala Chandrasekaran; Abeer M. Al-Ghananeem; Robert M. Riggs; Peter A. Crooks

doi:10.1016/j.bmcl.2006.01.003

Synthesis and stability of two indomethacin prodrugs

Shyamala Chandrasekaran
, Abeer M. Al-Ghananeem
, Robert M. Riggs
, Peter A. Crooks

University of Kentucky

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

16 Scopus citations

Abstract

The purpose of this study was to synthesize and study the in vitro enzymatic and non-enzymatic hydrolysis of indomethacin-TEG ester and amide prodrugs. It was found that the ester conjugate 10 was comparatively stable between pH 3 and 6 (half-life >90 h), with a half-life equal to 5.2 h in 80% buffered plasma. In contrast, the amide conjugate 12 appeared to be stable over the entire pH range studied with the only observed degradation being cleavage of the indolic N-4-chlorobenzoyl moiety.

Original language	English
Pages (from-to)	1874-1879
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	7
DOIs	https://doi.org/10.1016/j.bmcl.2006.01.003
State	Published - 1 Apr 2006
Externally published	Yes

Keywords

Indomethacin
Prodrug
Stability

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10.1016/j.bmcl.2006.01.003

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title = "Synthesis and stability of two indomethacin prodrugs",

abstract = "The purpose of this study was to synthesize and study the in vitro enzymatic and non-enzymatic hydrolysis of indomethacin-TEG ester and amide prodrugs. It was found that the ester conjugate 10 was comparatively stable between pH 3 and 6 (half-life >90 h), with a half-life equal to 5.2 h in 80\% buffered plasma. In contrast, the amide conjugate 12 appeared to be stable over the entire pH range studied with the only observed degradation being cleavage of the indolic N-4-chlorobenzoyl moiety.",

keywords = "Indomethacin, Prodrug, Stability",

author = "Shyamala Chandrasekaran and Al-Ghananeem, \{Abeer M.\} and Riggs, \{Robert M.\} and Crooks, \{Peter A.\}",

year = "2006",

month = apr,

day = "1",

doi = "10.1016/j.bmcl.2006.01.003",

language = "English",

volume = "16",

pages = "1874--1879",

journal = "Bioorganic and Medicinal Chemistry Letters",

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TY - JOUR

T1 - Synthesis and stability of two indomethacin prodrugs

AU - Chandrasekaran, Shyamala

AU - Al-Ghananeem, Abeer M.

AU - Riggs, Robert M.

AU - Crooks, Peter A.

PY - 2006/4/1

Y1 - 2006/4/1

N2 - The purpose of this study was to synthesize and study the in vitro enzymatic and non-enzymatic hydrolysis of indomethacin-TEG ester and amide prodrugs. It was found that the ester conjugate 10 was comparatively stable between pH 3 and 6 (half-life >90 h), with a half-life equal to 5.2 h in 80% buffered plasma. In contrast, the amide conjugate 12 appeared to be stable over the entire pH range studied with the only observed degradation being cleavage of the indolic N-4-chlorobenzoyl moiety.

AB - The purpose of this study was to synthesize and study the in vitro enzymatic and non-enzymatic hydrolysis of indomethacin-TEG ester and amide prodrugs. It was found that the ester conjugate 10 was comparatively stable between pH 3 and 6 (half-life >90 h), with a half-life equal to 5.2 h in 80% buffered plasma. In contrast, the amide conjugate 12 appeared to be stable over the entire pH range studied with the only observed degradation being cleavage of the indolic N-4-chlorobenzoyl moiety.

KW - Indomethacin

KW - Prodrug

KW - Stability

UR - https://www.scopus.com/pages/publications/33144489030

U2 - 10.1016/j.bmcl.2006.01.003

DO - 10.1016/j.bmcl.2006.01.003

M3 - Article

C2 - 16439128

AN - SCOPUS:33144489030

SN - 0960-894X

VL - 16

SP - 1874

EP - 1879

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 7

ER -

Synthesis and stability of two indomethacin prodrugs

Abstract

Keywords

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