The design, synthesis and physical chemical properties of novel human vasopressin V2-receptor antagonists optimized for parenteral delivery.
Ionizable groups were introduced onto the 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine scaffold of the vasopressin V2-antagonist WAY-VPA-985 in the search for molecules optimized for parenteral formulation. The synthesis and structure activity relationships (SAR) are presented together with solubility data in a model parenteral system. The amine, WAY-140288 (4f), was chosen for further development. p6
Ashwell
M A
MA
Wyeth-Ayerst Research, Princeton, NJ 08543, USA. ashwellm@war.wyeth.com
Bagli
J F
JF
Caggiano
T J
TJ
Chan
P S
PS
Molinari
A J
AJ
Palka
C
C
Park
C H
CH
Rogers
J F
JF
Sherman
M
M
Trybulski
E J
EJ
Williams
D K
DK
D065092:Antidiuretic Hormone Receptor Antagonists; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry*; D001569:Benzodiazepines / Q000737:chemistry*; D006801:Humans; D007263:Infusions, Parenteral; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship
D065092:Antidiuretic Hormone Receptor Antagonists; D001549:Benzamides; D011758:Pyrroles; D001569:Benzodiazepines; C409452:lixivaptan