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N-Benzoyl amino acids as ICAM/LFA-1 inhibitors. Part 2: Structure–activity relationship of the benzoyl moiety
- Source :
-
Bioorganic & Medicinal Chemistry Letters . May2004, Vol. 14 Issue 9, p2055. 5p. - Publication Year :
- 2004
-
Abstract
- o-Bromobenzoyl l-tryptophan 1 inhibits the association of LFA-1 with ICAM-1 with an IC50 of 1.7 μM. Evaluation of the structure–activity relationship of the benzoyl moiety shows that 2,6-di-substitutions greatly enhance potency of this class of inhibitors. Electronegative substitutions that favor a 90° angle between the benzoyl ring and the amide bond yield the most potent compounds. There is a strong correlation between the potency of the compounds and the difference between the ab initio energy at 90° and the global minima energy for given compounds. Combining the favored benzoyl substitutions with l-histidine and l-asparagine resulted in a 15-fold increase in potency over compound 1. [Copyright &y& Elsevier]
- Subjects :
- *TRYPTOPHAN
*AMINO acids
*ENZYME inhibitors
*AMIDES
Subjects
Details
- Language :
- English
- ISSN :
- 0960894X
- Volume :
- 14
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Publication Type :
- Academic Journal
- Accession number :
- 12776499
- Full Text :
- https://doi.org/10.1016/j.bmcl.2004.02.046