920022-47-5Relevant articles and documents
Discovery of highly selective brain-penetrant vasopressin 1a antagonists for the potential treatment of autism via a chemogenomic and scaffold hopping approach
Ratni, Hasane,Rogers-Evans, Mark,Bissantz, Caterina,Grundschober, Christophe,Moreau, Jean-Luc,Schuler, Franz,Fischer, Holger,Alvarez Sanchez, Ruben,Schnider, Patrick
, p. 2275 - 2289 (2015/03/30)
From a micromolar high throughput screening hit 7, the successful complementary application of a chemogenomic approach and of a scaffold hopping exercise rapidly led to a low single digit nanomolar human vasopressin 1a (hV1a) receptor antagonist 38. Initial optimization of the mouse V1a activities delivered suitable tool compounds which demonstrated a V1a mediated central in vivo effect. This novel series was further optimized through parallel synthesis with a focus on balancing lipophilicity to achieve robust aqueous solubility while avoiding P-gp mediated efflux. These efforts led to the discovery of the highly potent and selective brain-penetrant hV1a antagonist RO5028442 (8) suitable for human clinical studies in people with autism.
INDOL-3-YL-CARBONYL-SPIRO-PIPERIDINE DERIVATIVES AS V1A RECEPTOR ANTAGONISTS
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Page/Page column 94, (2008/06/13)
The invention relates to indol-3-yl-carbonyl-spiro-piperidine derivatives which act as V1a receptor antagonists and which are represented by Formula I: wherein the spiro-piperidine head group A and the residues R1, R2 and R3 are as defined herein. The invention further relates to pharmaceutical compositions containing such compounds, methods for preparing the compounds and pharmaceutical compositions, and their use in the treatment of dysmenorrhea, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, obsessive compulsive disorder, anxious and depressive disorders.
