Potent, orally bioavailable somatostatin agonists: good absorption achieved by urea backbone cyclization.
Backbone cyclization of urea-based somatostatin agonists resulted in novel, orally bioavailable agonists. Binding assays confirmed that the resulting conformationally constrained cyclic ureas retained the potency of their acyclic counterparts. SAR studies subsequently led to highly potent analogs, selective for receptor subtype 2, and having good oral bioavailability.
Pasternak
A
A
Department of Medicinal Chemistry, and Biochemistry & Physiology, Merck Research Laboratories, Rahway, NJ 07065, USA.
Pan
Y
Y
Marino
D
D
Sanderson
P E
PE
Mosley
R
R
Rohrer
S P
SP
Birzin
E T
ET
Huskey
S E
SE
Jacks
T
T
Schleim
K D
KD
Cheng
K
K
Schaeffer
J M
JM
Patchett
A A
AA
Yang
L
L
D000284:Administration, Oral; D000818:Animals; D001562:Benzimidazoles; D001682:Biological Availability; D004285:Dogs; D007211:Indoles; D013004:Somatostatin / Q000819:agonists* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014508:Urea / Q000737:chemistry*
D001562:Benzimidazoles; D007211:Indoles; C114420:L 054522; D013004:Somatostatin; D014508:Urea