Lead optimization of methionine aminopeptidase-2 (MetAP2) inhibitors containing sulfonamides of 5,6-disubstituted anthranilic acids.
Article Details
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Wang GT, Mantei RA, Kawai M, Tedrow JS, Barnes DM, Wang J, Zhang Q, Lou P, Garcia LA, Bouska J, Yates M, Park C, Judge RA, Lesniewski R, Sheppard GS, Bell RL
Lead optimization of methionine aminopeptidase-2 (MetAP2) inhibitors containing sulfonamides of 5,6-disubstituted anthranilic acids.
Bioorg Med Chem Lett. 2007 May 15;17(10):2817-22. Epub 2007 Feb 25.
- PubMed ID
- 17350258 [ View in PubMed]
- Abstract
A series of aryl sulfonamides of 5,6-disubstituted anthranilic acids were identified as potent inhibitors of methionine aminopeptidase-2 (MetAP2). Small alkyl groups and 3-furyl were tolerated at the 5-position of anthranilic acid, while -OCH(3), CH(3), and Cl were found optimal for the 6-position. Placement of 2-aminoethoxy group at the 6-position enabled interaction with the second Mn(2+) but did not result in enhancement in potency. Introduction of a tertiary amino moiety at the ortho-position of the sulfonyl phenyl ring gave reduced protein binding and improved cellular activity, but led to lower oral bioavailability.
DrugBank Data that Cites this Article
- Polypeptides
Name UniProt ID Methionine aminopeptidase 2 P50579 Details - Binding Properties
Drug Target Property Measurement pH Temperature (°C) 3-ETHYL-6-{[(4-FLUOROPHENYL)SULFONYL]AMINO}-2-METHYLBENZOIC ACID Methionine aminopeptidase 2 IC 50 (nM) 16 7.4 22 Details