3-[2-(N-phenylacetamide)]-1,5-benzodiazepines: orally active, binding selective CCK-A agonists.
A series of modifications were made to the C-3 substituent of the 1,5-benzodiazepine CCK-A agonist 1. Replacement of the inner urea NH and addition of a methyl group to generate a C-3 quaternary carbon resulted in acetamide 6, which showed CCK-A receptor binding selectivity and sub-micromolar agonist activity in vitro. Benzodiazepine 6 was active in an in vivo mouse gallbladder emptying assay and represents a novel orally active, binding selective CCK-A agonist.
Willson
T M
TM
Glaxo Wellcome Research and Development, Research Triangle Park, North Carolina 27709, USA. willsontm@glaxo.com
Henke
B R
BR
Momtahen
T M
TM
Myers
P L
PL
Sugg
E E
EE
Unwalla
R J
RJ
Croom
D K
DK
Dougherty
R W
RW
Grizzle
M K
MK
Johnson
M F
MF
Queen
K L
KL
Rimele
T J
TJ
Yingling
J D
JD
James
M K
MK
D000083:Acetanilides; D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D002766:Cholecystokinin / Q000819:agonists*; D005704:Gallbladder / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D051379:Mice; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D011949:Receptors, Cholecystokinin / Q000378:metabolism
C100739:2-(2,4-dioxo-5-phenyl-3-methyl-3-((phenylcarbamoyl)methyl)-2,3,4,5-tetrahydrobenzo(b)(1,5)diazepin-1-yl)-N-isopropyl-N-phenylacetamide; D000083:Acetanilides; D001381:Azepines; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin