Studies towards the synthesis of methionine aminopeptidase inhibitors

Diversification utilizing a ROMP-derived coupling reagent

Punitha Vedantham, Mianji Zhang, Parul J. Gor, Min Huang, Gunda I. Georg, Gerald H. Lushington, Lester A. Mitscher, Qizhuang Ye, Paul R. Hanson

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Efforts to synthesize potential methionine aminopeptidase inhibitors is described. Preliminary SAR and docking studies served as a guide to design the compound libraries. "Chromatography-free" synthesis of various heterocyclic amides was realized by using a high-load, soluble coupling reagent derived via ringopening metathesis polymerization (ROMP). Subsequent microwave-assisted Suzuki reactions with orthosubstituted arylboronic acids, followed by chromatographic purification afforded a 55-member library in high yields and purities. While the biological testing was not satisfactory, concurrent X-ray crystallography studies revealed key structural features essential for inhibition of methionine aminopeptidase, which directed fruitful results reported in the accompanying manuscript. In addition, in silico Lipinksi profiles and ADME properties of the library are also reported.

Original languageEnglish
Pages (from-to)195-203
Number of pages9
JournalJournal of Combinatorial Chemistry
Volume10
Issue number2
DOIs
StatePublished - Mar 2008

Fingerprint

Aminopeptidases
Diversification
Polymerization
Methionine
Inhibitor
Libraries
Synthesis
Manuscripts
Docking
X ray crystallography
X Ray Crystallography
Microwaves
Chromatography
Purification
Amides
Computer Simulation
Microwave
Concurrent
Testing
Acids

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Discrete Mathematics and Combinatorics

Cite this

Studies towards the synthesis of methionine aminopeptidase inhibitors : Diversification utilizing a ROMP-derived coupling reagent. / Vedantham, Punitha; Zhang, Mianji; Gor, Parul J.; Huang, Min; Georg, Gunda I.; Lushington, Gerald H.; Mitscher, Lester A.; Ye, Qizhuang; Hanson, Paul R.

In: Journal of Combinatorial Chemistry, Vol. 10, No. 2, 03.2008, p. 195-203.

Research output: Contribution to journalArticle

Vedantham, P, Zhang, M, Gor, PJ, Huang, M, Georg, GI, Lushington, GH, Mitscher, LA, Ye, Q & Hanson, PR 2008, 'Studies towards the synthesis of methionine aminopeptidase inhibitors: Diversification utilizing a ROMP-derived coupling reagent', Journal of Combinatorial Chemistry, vol. 10, no. 2, pp. 195-203. https://doi.org/10.1021/cc7000869
Vedantham, Punitha ; Zhang, Mianji ; Gor, Parul J. ; Huang, Min ; Georg, Gunda I. ; Lushington, Gerald H. ; Mitscher, Lester A. ; Ye, Qizhuang ; Hanson, Paul R. / Studies towards the synthesis of methionine aminopeptidase inhibitors : Diversification utilizing a ROMP-derived coupling reagent. In: Journal of Combinatorial Chemistry. 2008 ; Vol. 10, No. 2. pp. 195-203.
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