329041-19-2

Upstream product

• 6456-74-2 Glycine tert-butyl ester 
• 87001-32-9 p-benzyloxybenzenesulfonyl chloride 
• 27532-96-3 glycine tert-butyl ester hydrochloride 

Downstream Products

• 950888-11-6 [(4-benzyloxy-benzenesulfonyl)-(4-oxo-hexyl)-amino]-acetic acid tert-butyl ester 
• 329041-21-6 [(4-benzyloxy-benzenesulfonyl)-(4-oxo-pentyl)-amino]-acetic acid tert-butyl ester 
• 950888-15-0 [(4-benzyloxy-benzenesulfonyl)-(4-oxo-octyl)-amino]-acetic acid tert-butyl ester 
• 329041-20-5 [(4-benzyloxy-benzenesulfonyl)-pent-4-enyl-amino]-acetic acid tert-butyl ester 

Relevant academic research and scientific papers

Selective inhibition of aggrecanase in osteoarthritis treatment

This invention relates to a method of treatment for osteoarthritis involving inhibitors of aggrecanase that demonstrate IC50s of less than 20 nM and demonstrate differential potency against matrix metalloproteinases (MMPs) and a disintegrin and

Discovery of 3-OH-3-methylpipecolic hydroxamates: Potent orally active inhibitors of aggrecanase and MMP-13

A series of 3-hydroxy-3-methylpipecolic hydroxamate inhibitors of MMP-13 and aggrecanase was designed based on the observation of increased aggrecanase activity with substitution at the 3-position of the piperidine ring. Potency versus aggrecanase was optimized by modification of the benzyloxyarylsulfonamide group that binds in the S1′ pocket. These compounds also possess markedly improved bioavailability and lower metabolic clearance compared to analogous 3,3-dimethyl-5-hydroxypipecolic hydroxamates. These improvements are attributed to lowered lipophilicity proximal to the metabolically labile hydroxamic acid. Synthesis, structure activity relationships, and in vivo efficacy data are described.

Selective inhibitors of aggrecanase in osteoarthritis treatment

This invention relates to a method of treatment for osteoarthritis involving inhibitors of aggrecanase that demonstrate IC50s of less than 20 nM and demonstrate differential potency against matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs or reprolysins). This invention also relates to compounds, methods of treatment and composition of Formula I: or a therapeutically acceptable salt thereof, whereinX is carbon or nitrogen;R1 and R2 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, wherein at least one of R1 and R2 is methyl;R3 and R4 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, or R3 and R4 may be taken together to form a carbonyl group; andR5 and R6 are independent substituents in the ortho, meta, or para positions and are independently selected from the group consisting of hydrogen, halogen, cyano, methyl, and ethyl;with the provisos:when X is carbon, then R7 and R8 are both hydrogen and at least one of R1, R2, R3, and R4 is hydroxy;when X is carbon and R5 is para-halo, then at least one of R6, R3, and R4 is not hydrogen;when X is nitrogen, then R8 is not present and R7 is hydrogen or a group of the formula:wherein, Y is -CH2-NH2 or -NH-CH3; andwhen X is nitrogen and R7 is H, then R3 and R4 are taken together to form a carbonyl group.