| Structural highlights
Publication Abstract from PubMed
The synthesis, evaluation, and structure-activity relationships of a class of gamma-lactam 1,3-diaminopropan-2-ol transition-state isostere inhibitors of BACE are discussed. Two strategies for optimizing lead compound 1a are presented. Reducing the overall size of the inhibitors resulted in the identification of gamma-lactam 1i, whereas the introduction of conformational constraint on the prime-side of the inhibitor generated compounds such as the 3-hydroxypyrrolidine inhibitor 28n. The full in vivo profile of 1i in rats and 28n in Tg 2576 mice is presented.
Monosubstituted gamma-lactam and conformationally constrained 1,3-diaminopropan-2-ol transition-state isostere inhibitors of beta-secretase (BACE).,Boy KM, Guernon JM, Shi J, Toyn JH, Meredith JE, Barten DM, Burton CR, Albright CF, Marcinkeviciene J, Good AC, Tebben AJ, Muckelbauer JK, Camac DM, Lentz KA, Bronson JJ, Olson RE, Macor JE, Thompson LA 3rd Bioorg Med Chem Lett. 2011 Jun 30. PMID:21782431[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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References
- ↑ Boy KM, Guernon JM, Shi J, Toyn JH, Meredith JE, Barten DM, Burton CR, Albright CF, Marcinkeviciene J, Good AC, Tebben AJ, Muckelbauer JK, Camac DM, Lentz KA, Bronson JJ, Olson RE, Macor JE, Thompson LA 3rd. Monosubstituted gamma-lactam and conformationally constrained 1,3-diaminopropan-2-ol transition-state isostere inhibitors of beta-secretase (BACE). Bioorg Med Chem Lett. 2011 Jun 30. PMID:21782431 doi:10.1016/j.bmcl.2011.06.109
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