Discovery of a spiroindane based compound as a potent, selective, orally bioavailable melanocortin subtype-4 receptor agonist.
We report the design, synthesis and properties of spiroindane based compound 1, a potent, selective, orally bioavailable, non-peptide melanocortin subtype-4 receptor agonist. Compound 1 shows excellent erectogenic activity in the rodent models.
He
Shuwen
S
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065-0900, USA. shuwen_he@merck.com
Ye
Zhixiong
Z
Dobbelaar
Peter H
PH
Sebhat
Iyassu K
IK
Guo
Liangqin
L
Liu
Jian
J
Jian
Tianying
T
Lai
Yingjie
Y
Franklin
Christopher L
CL
Bakshi
Raman K
RK
Dellureficio
James P
JP
Hong
Qingmei
Q
Tsou
Nancy N
NN
Ball
Richard G
RG
Cashen
Doreen E
DE
Martin
William J
WJ
Weinberg
David H
DH
Macneil
Tanya
T
Tang
Rui
R
Tamvakopoulos
Constantin
C
Peng
Qianping
Q
Miller
Randy R
RR
Stearns
Ralph A
RA
Chen
Howard Y
HY
Chen
Airu S
AS
Strack
Alison M
AM
Fong
Tung M
TM
Macintyre
D Euan
DE
Wyvratt
Matthew J
MJ
Nargund
Ravi P
RP
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D007172:Erectile Dysfunction / Q000188:drug therapy*; D000882:Haplorhini; D006801:Humans; D007189:Indans / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D015394:Molecular Structure; D011485:Protein Binding; D051381:Rats; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists* / Q000378:metabolism*; D013141:Spiro Compounds / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
D007189:Indans; D044105:Receptor, Melanocortin, Type 4; D013141:Spiro Compounds