Piperidine-renin inhibitors compounds with improved physicochemical properties.
Piperidine renin inhibitors with heterocyclic core modifications or hydrophilic attachments show improved physical properties (lower lipophilicity, improved solubility). Tetrahydroquinoline derivative rac-30 with a molecular weight of 517 and a log D(pH 7.4) of 1.9 displays potent and long lasting blood pressure lowering effects after oral administration to sodium depleted conscious marmosets.
Güller
R
R
Pharma Research Department, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Binggeli
A
A
Breu
V
V
Bur
D
D
Fischli
W
W
Hirth
G
G
Jenny
C
C
Kansy
M
M
Montavon
F
F
Müller
M
M
Oefner
C
C
Stadler
H
H
Vieira
E
E
Wilhelm
M
M
Wostl
W
W
Märki
H P
HP
D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry* / Q000494:pharmacology; D002144:Callithrix; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D000092502:Renin Inhibitors
D000959:Antihypertensive Agents; D010880:Piperidines; D011994:Recombinant Proteins; D000092502:Renin Inhibitors