1.
Bioorg Med Chem Lett
; 19(20): 5898-901, 2009 Oct 15.
Article
in English
| MEDLINE
| ID: mdl-19733066
ABSTRACT
A pharmacophore mapping approach, derived from previous experience of PIKK family enzymes, was used to identify a hit series of selective inhibitors of the mammalian target of rapamycin (mTOR). Subsequent refinement of the SAR around this hit series based on a tri-substituted triazine scaffold has led to the discovery of potent and selective inhibitors of mTOR.
Subject(s)
Antineoplastic Agents/chemistry , Morpholines/chemistry , Protein Kinase Inhibitors/chemistry , Protein Kinases/chemistry , Pyrimidines/chemistry , Triazines/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Humans , Morpholines/chemical synthesis , Morpholines/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Phosphoinositide-3 Kinase Inhibitors , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/pharmacology , Protein Kinases/metabolism , Pyrimidines/chemical synthesis , Pyrimidines/pharmacology , Structure-Activity Relationship , TOR Serine-Threonine Kinases , Triazines/chemical synthesis , Triazines/pharmacology
2.
Bioorg Med Chem Lett
; 18(14): 3942-5, 2008 Jul 15.
Article
in English
| MEDLINE
| ID: mdl-18579376
ABSTRACT
We have previously described poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors based on a substituted benzyl-phthalazinone scaffold. As an alternative chemical template, a novel series of alkoxybenzamides were developed with restricted conformation through intramolecular hydrogen bond formation; the compounds exhibit low nM enzyme and cellular activity as PARP-1 inhibitors.
