Solid-phase synthesis of FKBP12 inhibitors: N-sulfonyl and N-carbamoylprolyl/pipecolyl amides.
In parallel with our work on solution-phase parallel synthesis of ligands for the rotamase enzyme FKBP12, we herein report a methodology for the solid-phase synthesis of two classes of inhibitor, N-sulfonyl and N-carbamoylprolyl and pipecolyl amides along with their in vitro/in vivo biological results.
Wei
Ling
L
Guilford Pharmaceuticals Inc., Research Department, 6611 Tributary Street, 21224, Baltimore, MD, USA
Wu
Yon- Qian
Y
Wilkinson
Douglas E
DE
Chen
Yi
Y
Soni
Raj
R
Scott
Chad
C
Ross
Douglas T
DT
Guo
Hong
H
Howorth
Pamela
P
Valentine
Heather
H
Liang
Shi
S
Spicer
Dawn
D
Fuller
Mike
M
Steiner
Joseph
J
Hamilton
Gregory S
GS
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000201:enzymology; D010875:Pipecolic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins / Q000037:antagonists & inhibitors*
D002219:Carbamates; D004791:Enzyme Inhibitors; D010875:Pipecolic Acids; D013451:Sulfonic Acids; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D022021:Tacrolimus Binding Proteins