Development of matrix metalloproteinase-13 inhibitors – A structure activity/structure-property relationship study

Rita Fürst, Jun Yong Choi, Anna M. Knapinska, Lyndsay Smith, Michael D. Cameron, Claudia Ruiz, Gregg B. Fields, William R. Roush

Research output: Contribution to journalArticleResearchpeer-review

Abstract

A structure-activity/structure-property relationship study based on the physicochemical as well as in vitro pharmacokinetic properties of a first generation matrix metalloproteinase (MMP)-13 inhibitor (2) was undertaken. After systematic variation of inhibitor 2, compound 31 was identified which exhibited microsomal half-life higher than 20 min, kinetic solubility higher than 20 μM, and a permeability coefficient greater than 20 x 10-6 cm/s. Compound 31 also showed excellent in vivo PK properties after IV dosing (Cmax = 56.8 μM, T1/2 (plasma) = 3.0 h, Cl = 0.23 mL/min/kg) and thus is a suitable candidate for in vivo efficacy studies in an OA animal model.
Translated title of the contributionEntwicklung von Matrix Metalloproteinase-13 Inhibitoren – Eine Studie zur Untersuchung der Struktur-Wirkbeziehung der Inhibitoren
Original languageEnglish
Number of pages11
JournalBioorganic & Medicinal Chemistry
Volume26
Issue number18
DOIs
Publication statusPublished - 15 Aug 2018

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Development of matrix metalloproteinase-13 inhibitors – A structure activity/structure-property relationship study. / Fürst, Rita; Choi, Jun Yong; Knapinska, Anna M.; Smith, Lyndsay; Cameron, Michael D. ; Ruiz, Claudia ; Fields, Gregg B.; Roush, William R. .

In: Bioorganic & Medicinal Chemistry, Vol. 26, No. 18, 15.08.2018.

Research output: Contribution to journalArticleResearchpeer-review

Fürst, Rita ; Choi, Jun Yong ; Knapinska, Anna M. ; Smith, Lyndsay ; Cameron, Michael D. ; Ruiz, Claudia ; Fields, Gregg B. ; Roush, William R. . / Development of matrix metalloproteinase-13 inhibitors – A structure activity/structure-property relationship study. In: Bioorganic & Medicinal Chemistry. 2018 ; Vol. 26, No. 18.
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