Abstract
On the basis of the pyrrolopyrimidine core structure that was previously discovered, cathepsin K inhibitors having a spiro amine at the P3 have been explored to enhance the target, bone marrow, tissue distribution. Several spiro structures were identified with improved distribution toward bone marrow. The representative inhibitor 7 of this series revealed in vivo reduction in C-terminal telopeptide of type I collagen in rats and monkeys.
MeSH terms
-
Animals
-
Bone Marrow / metabolism
-
Bone Resorption / drug therapy*
-
Cathepsin K
-
Cathepsins / antagonists & inhibitors*
-
Collagen Type I / metabolism
-
Cysteine Proteinase Inhibitors / chemistry*
-
Cysteine Proteinase Inhibitors / pharmacokinetics*
-
Haplorhini
-
Pyrimidines / chemistry
-
Pyrimidines / pharmacology
-
Pyrroles / chemistry
-
Pyrroles / pharmacology
-
Rats
-
Spiro Compounds
-
Tissue Distribution
Substances
-
Collagen Type I
-
Cysteine Proteinase Inhibitors
-
Pyrimidines
-
Pyrroles
-
Spiro Compounds
-
pyrrolopyrimidine
-
Cathepsins
-
Cathepsin K
-
Ctsk protein, rat