Small molecule biaryl FSH receptor agonists. Part 1: Lead discovery via encoded combinatorial synthesis.
High-throughput screening of two million compounds in 37 distinct encoded combinatorial libraries using FSH receptor transfected cells provided small molecule agonists such as 1 (EC(50)=3 microM) and 2 (EC(50)=3.9 microM), based on which a focused combinatorial library with a total of 31372 compounds was designed, synthesized, and screened to reveal 72 novel biaryl FSH receptor agonists such as 8a-c as well as a unique combinatorial SAR.
Guo
Tao
T
Pharmacopeia, Inc, PO Box 5350, Princeton, NJ 08543-5350, USA.tguo@pharmcop.com
Adang
Anton E P
AE
Dolle
Roland E
RE
Dong
Guizhen
G
Fitzpatrick
Dan
D
Geng
Peng
P
Ho
Koc-Kan
KK
Kultgen
Steven G
SG
Liu
Ruiyan
R
McDonald
Edward
E
McGuinness
Brian F
BF
Saionz
Kurt W
KW
Valenzano
Kenneth J
KJ
van Straten
Nicole C R
NC
Xie
Dan
D
Webb
Maria L
ML
D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D011962:Receptors, FSH / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism
D011962:Receptors, FSH